Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) results from degeneration of the sinonasal mucosa. The prevalence in the general population varies from 1 to 4%, but in Brazil there is a lack of statistics. It is a complex disease with a wide spectrum of phenotypes. Pathological anatomy (PA) of the polyp is the reference method indicated for analyzing eosinophils. Nasal lavage cytology (LN) is a less widespread and less invasive test.
Objectives: The main objective is to compare eosinophilia between the AP and LN methods in CRSwNP. Secondarily, evaluate the association of tissue eosinophilia with disease control; the severity of asthma; awareness of aeroallergens; endoscopic and tomographic findings; Total IgE and peripheral eosinophilia.
Methods: cross-sectional study, which compared: the degree of agreement for detecting eosinophilia between AP and LN methods; and peripheral eosinophilia with tissue, in relation to the diagnosis of the Type 2 endotype in CRSwNP. In addition to analyzing clinical and Conclusions: epidemiological factors associated with tissue eosinophilia, the following were performed: SNOT22, asthma control assessment, Prick test, laboratory tests, nasal endoscopy and tomography.
Result: 30 patients were captured. The average age was 52 years. All were characterized as eosinophilic by one of three methods: peripheral eosinophilia, AP or total IgE. Eosinophils were altered by: 70% in the periphery if the cutoff point was above 250 cells/mm 3 and 83.3% when considering above 150 cells/mm 3; 86.6% in AP and 30% in LN. Total IgE was altered by 63.3%. Eosinophilic LN is statistically associated with elevated tissue eosinophilia.
Peripheral eosinophilia with a cutoff point of 150 cells/mm 3 was the test that came closest to the gold standard, AP. LN is a non-invasive and easy to perform method, however it has been shown to be inferior to peripheral eosinophilia and total IgE.

Introduction: Severe asthma is a complex heterogeneous disease that can be complicated by several comorbidities, especially those related to the upper airways, such as chronic rhinosinusitis and allergic rhinitis, which play a key role in the management of these patients, considering the concept of a 'Unified Airway'. The aim of this study was to evaluate upper airway comorbidities (UAC) in patients in the ProAR cohort and their association with asthma control. Methods: Retrospective evaluation of the first visit of the cohort, between 2013 and 2015, of the aeroallergic sensitization profile; and prospective evaluation of a sample of patients at the second visit of the cohort, between March⁄2018 and February⁄2020, of UAC. In both studies, clinical and laboratory evaluations and complementary asthma tests were performed. In the prospective study, otorhinolaryngological evaluation, questionnaires to evaluate CRS and other comorbidities of UA, in addition to nasopharyngolaryngoscopy video, were added. Results: A narrative review of the literature was conducted to identify the main asthma-related comorbidities of AV and their control, as well as to systematize an otorhinolaryngological evaluation of these comorbidities in asthmatic patients. The main ones were: Allergic Rhinitis, CRS, AERD, GERD, CVD and OSAHS; The systematization was presented through clinical cases and multiple-choice questions. The results of the retrospective study of the first visit of the cohort involved 1066 participants, with a higher prevalence of aeroallergic sensitization in individuals with asthma, compared to those with chronic rhinitis alone (70.4% vs 47%, p=0.000), high sensitization to mites, cockroaches, animal dander, grasses and fungi in the presence of asthma, which is also associated with polysensitization, in addition to a sensitization profile different from that observed in individuals with chronic rhinitis alone. In the prospective study, referring to the second visit of the cohort, 428 patients with asthma were evaluated, 76.2% of those with mild asthma had CRS, and 60.8% with moderate to severe asthma. The diagnosis of CRS, regardless of asthma severity, was associated with poor asthma control (GINA and ACQ-6), asthma exacerbation and poorer asthma quality of life in more than 50% of these patients; GERD symptoms and daytime sleepiness were also highly prevalent in the presence of CRS. Nasal polyposis has been shown to be a marker of moderate to severe asthma, and the diagnosis of AERD was exclusive to this group. Conclusions: Comorbidities of UA are common in patients with asthma, regardless of their severity. Aeroallergic sensitization differs from chronic rhinitis alone in comparison with its association with asthma, endorsing the hypothesis that allergic rhinitis presents a different phenotype when associated with asthma. CRS is also commonly associated with asthma, contributing to its poor control. Adequate investigation and treatment of upper airways comorbidities in asthmatic patients is recommended, especially in those in whom there is partial or no asthma control, and a systematized evaluation of these comorbidities facilitates the clinical care trajectory of these patients.

Background: HTLV-1 is a globally distributed pathogen that affects approximately 5 to 10 million people. It is estimated that Brazil has about 800,000 people living with the virus, which characterizes it as one of the countries with the highest absolute number of cases. In Brazil, the North and Northeast regions are the most affected by HTLV-1, with emphasis on the city of Salvador, capital of Bahia, which has a prevalence of 1.7%. HTLV-1 infection can lead to the development of diseases such as ATLL, HAM/TSP and IDH. The HTLV-1 genome has structural genes and a region responsible for encoding accessory and regulatory proteins, important for the establishment, dissemination, and action of the virus. The sequencing of this genome can elucidate factors of this virus that influence the spread and development of clinical manifestations associated with HTLV-1. The main objective of this work is to evaluate the role of mutations in the HTLV-1 genome and its possible association with the development of HTLV-1-associated diseases, describing the importance of sequencing techniques in studies of the viral genome. Methods: Samples of infected individuals were collected, DNA was extracted and sequenced for further identification of mutations in the LTR and hbz regions of HTLV-1. Systematic reviews were performed following PRISMA instructions. Results: Two mutations, V15M and R119Q, were observed in the hbz region, with V15M observed exclusively in HAM/TSP patients, while R119Q appears to be a protective factor for the development of the disease. In LTR, mutations were found that led to both the emergence and deletion of transcription sites. In addition, four works were found that related mutations in env and ORF-1 with the development of some clinical form. The Sanger methodology, despite the evolution of sequencing technologies, remains the most used for the study of HTLV-1. Conclusions: It was possible to observe that due to the difficulty of obtaining a large “n” and the lack of clinical and epidemiological information available along with the sequences in the database, it is difficult to establish and relate factors that influence the development of clinical manifestations associated with HTLV -1. In addition, it is possible to verify the lack of investments in HTLV-1 studies, due to the low number of sequences and studies available when compared to other pathogens, such as HIV.

Falls Behavioural Scale (FAB) has not yet been validated in the population after stroke. Objectives: Validate the behavioral scale of falls (FAB-Brazil) for individuals after stroke.
Methods: This is a cross -sectional study conducted with individuals after stroke, recruited at the teaching clinic - care of a public hospital in the city of Salvador, Bahia. Individuals over 18 years old were included with clinical-radiological diagnosis of ischemic or hemorrhagic stroke, regardless of the number of events that had independent march. Individuals with cognitive impairment determined by the mini examination of the mental state were excluded. People with severe visual or auditory sensory deprivation were also excluded, vestibulopathies and other neurological or orthopedic diseases that could affect balance and mobility, as well as those unable to stand independently. An evaluation record was prepared by the researchers, containing information on the sociodemographic, clinical and functional characteristics of the study participants, as well as fall numbers in the last 12 months. Community mobility was evaluated according to the number of times individuals left home per week. Then the following scales were used: the National Institutes of Health Stroke Scale (NIHSS), the modified barthel index (IBM), FAB-Brazil, Activities-Specific Balance Confidence (ABC), Euroquol 5-D, the TimeD Up and Go (TUG) and the Stroke Self Effficacy Questionnaire (Sseq) questionnaire. All instruments are validated for Brazilian populous. Data from 80 patients between August 2018 and October 2022 were collected. Results: It was observed that most individuals were male (53.8%), with an average age of 57.68 years (13.2) and a median of 9 year education (5 - 12). Of these, 62.5% had companions and most (60%) did not return to work after stroke. Regarding clinical aspects, it was observed that the average stroke time was 7 months (4 - 13) and the median of gravity, measured through the NIHSS was 1 (0 - 3). Most individuals had ischemic stroke (88.2%), the right brain hemisphere being the most affected (50.6%). According to the IBM median, the evaluated individuals were functionally independent 49.5 (45 - 50), had moderate confidence in the measured balance through ABC 56.29 (27.09), did not have episodes of fall (70.5%) and TUG of 13.01 (10.20 - 17.35). The SSEQ presented an average of 30.53 (6.47) and FAB-Brazil 3.03 (0.47). FAB-Brazil inter-examiners agreement was good (intraclass correlation index = 0,865, p < 0,001). FAB-Brazil for individuals after stroke showed significant correlations with stroke severity, functional capacity, confidence in balance, quality of life, functional mobility, how many times left home last week and with the dimensions of FAB-Brazil itself (P <0.05 for all comparisons). Conclusion: FAB-Brazil for individuals after stroke showed good internal reliability and interseximinators; and good correlation with several other functional dimensions after stroke.

Background: Epidemiological studies suggest a higher prevalence of systemic arterial hypertension (HTN) and other cardiovascular diseases in patients with psoriasis. The underlying mechanism remains unclear, but may involve activation of the renin-angiotensin-aldosterone system (RAAS). This study aimed to compare renin and aldosterone levels between psoriasis patients and non-psoriasis individuals.

 Methods: A prospective, cross-sectional study enrolled consecutive patients from a university hospital’s dermatology outpatient clinic. Clinical evaluation was followed by blood collection for renin and aldosterone measurement, allowing for comparison between psoriasis and non-psoriasis patients. Subgroup analyses stratified participants based on HTN presence. Multiple linear regression analyses identified independent predictors of higher renin and aldosterone levels.

Results: The study included 17 patients (mean age: 55 ± 13 years, 50.6% men, 85.9% non-white), with 57,6% having psoriasis and 44.1% with HTN. Mean plasma renin levels were similar in psoriasis and non-psoriasis patients (26.3 ± 51.4 versus 23.9 ± 48.7 µUI/ml, respectively, p = 0.764). However, psoriasis patients showed significantly higher mean serum aldosterone levels (25.3 ± 49.4 versus 11.7 ± 10.7 ng/dl, p = 0.009). Stratification revealed that only psoriasis patients with HTN had significantly higher aldosterone levels compared to other subgroups. In multiple linear regression analyses, psoriasis was only associated with higher levels of aldosterone in hypertensive patients.

Conclusions: This study indicates elevated serum aldosterone levels in patients with both psoriasis and HTN. Further investigation is necessary to understand the potential impact of this finding on cardiovascular morbidity and mortality in psoriasis patients. 

Introduction: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. About 30-40% of patients develop sudden and acute inflammatory episodes, the so-called leprosy reactions. Previous studies have shown a series of miRNAs associated with leprosy phenotypes, evidencing the role of this epigenetic mechanism in the pathogenesis of the disease. Objective: This study aimed to evaluate the correlation of miRNAs previously associated with leprosy with genes linked to apoptosis and autophagy in lesions of patients with leprosy, compare the expression pattern of genes in biopsies of patients with and without reactions and describe the clinical profile and epidemiological analysis of patients with leprosy treated at reference centers in the state of Bahia, HUPES-AMN and ICOM. Methods: Biopsies of 28 patients with and without leprosy reactions, with different clinical forms of leprosy were recruited. For analysis purposes, these patients were allocated according to the WHO classification as paucibacillary (PB) or multibacillary (MB), and separated into patients with or without reactions. RNA samples contained in our biorepository were used, extracted by the method using TRIzol® Reagent (Ambion®). Obtaining complementary DNA (cDNA) was performed using the commercially available High Capacity kit (ThermoFisher). The genes were chosen because they are important in cell death processes and are regulated by the miRNAs previously analyzed by the group. Gene expression by real-time qPCR method by TaqMan® was performed and the data analyzed by comparing the threshold cycle (Ct) between groups of samples. Correlation analysis between genes and miRNAs was performed using the Spearman Correlation test, using GraphPad Prism8. Differences were considered significant when the p-value was below 0.05 (p ˂ 0.05). The patients' clinical-epidemiological database was analyzed using the R program for Windows, version 4.2.3 and the data presented in tables. Results: The expression of the genes ATG12, TNFRSF10A, PARK2, BCL2, CFLAR and STX7 was evaluated by qPCR and the expression between patients without reaction (PB + MB) and patients with reaction (RR and ENH) was compared and there was no statistically significant association in this comparison. Our results showed a correlation between miRNAs and ATG12 (miR-125a-3p), TNFRSF10A (miR-146b-5p), PARK2, CFLAR and STX7 (miR-132-5p) genes. In the epidemiological analysis, we observed that the MB form is more prevalent in males and that disease forms within this spectrum are more prone to the development of reactions, as well as affecting patients with lower educational and economic levels. Conclusion: We reinforce a role for these miRNAs in the pathogenesis of leprosy, influencing mechanisms such as apoptosis and autophagy in the skin; The MB form of the disease occurs within a social context of greater social vulnerability compared to PB patients.

Introduction: Burnout Syndrome (BS) is recognized as a three-dimensional occupational phenomenon: Emotional Exhaustion (EE), Depersonalization (DP) and Low Personal Accomplishment (RRP). The literature addresses the possible relationship between burnout and changes in the Hypothalamic-Pituitary-Adrenal (HHA) axis with the release of pro-inflammatory mediators such as c-reactive protein (CRP). Objective: To estimate the association between Burnout and Creactive Protein Levels in Primary Health Care Nurses in the state of Bahia. Methodology: A cross-sectional, analytical, confirmatory population study was carried out, integrated into a multicentric research, entitled “Burnout Syndrome and Metabolic Syndrome in Nursing Workers in Primary Health Care – (PHC)”, such research was conducted in 43 municipalities, covering the 7 mesoregions of Bahia, Brazil, with 273 nurses. Used the Maslach Burnout Inventory to identify Burnout. CRP levels had a cutoff point of ≥ 0.50 mg/dL. Descriptive, bivariate and logistic regression analyzes were performed. Results: hsCRP levels ranged from 0 to 4.2mg/dL (average 0.68 ±0.73), being altered in 43.6% of the samples evaluated. The average was 0.85mg/dL (SD=0.62) in the group diagnosed with BS and 0.62mg/dL (SD=0.75) in the absence of diagnosis. The difference between the groups was statistically significant (p=0.02). The final logistic model showed that the occurrence of BS was 2.37 times higher (95%CI 2.04 – 3.23 p<0.001) in individuals with altered hsCRP levels. Conclusion: Strategies are necessary to identify, treat and prevent Burnout. New studies with more robust methodologies are necessary for the implementation of occupational health programs as an alternative for controlling stress, and consequently its complications such as Burnout and its health problems.

Introduction: Cutaneous leishmaniasis (CL) and toxoplasmosis represent two neglected diseases and are characterized as a relevant public health problem. CL caused by L. braziliensis usually presents as one or more ulcers with raised, well-defined borders. Protection against Leishmania infection is associated with the production of IFN-γ, a cytokine involved in macrophage activation and subsequent destruction of the parasite. This Th1 response is important for controlling the multiplication of leishmania. However, the overproduction of inflammatory cytokines as observed in CL caused by L. braziliensis has been associated with tissue damage, development of skin lesions and poor response to therapy. In this study, we evaluated whether chronic T. gondii infection modulates the inflammatory response of patients with CL, influencing the clinical presentation or therapeutic outcome. Material and Methods: A prospective cohort of 122 patients with active CL was performed to assess clinical presentation and therapeutic response. Additionally, a cross-sectional study was performed to assess the immune response. Serology was performed to determine the positive and negative IgG groups for T.gondii Levels of cytokines and chemokines in response to Leishmania antigen from Peripheral Blood Mononuclear Cells (PBMC) and in cultured biopsies without challenge were analyzed by ELISA prior to initiating therapy. All patients were treated with pentavalent antimony and the complete healing of the lesion 90 days after treatment was considered as a cure criterion. Results: In our study, 71.3% of patients with CL were seropositive for T. gondii. A higher cure rate and shorter wound healing time were observed in patients with CL and IgG+ for T. gondii. There was a decrease in the levels of CXCL9, CXCL10 and IL-17 in SLA-stimulated PBMC supernatants from patients with CL and positive serology for T. gondii. Patients with positive serology who were cured by therapy showed high levels of IL-10, while in individuals negative for T. gondii, we found an increase in IL-1β production in the treatment failure group. An increase in the production of CXCL9 and IFN-y and a decrease in IL-17 and IL-1β was observed in the lesions of LC patients with positive IgG for T.gondii Conclusion: Thus, this work shows that chronic infection by T. gondii modulates the immune response of patients with CL, contributing to therapeutic cure.

Tegumentary leishmaniasis, caused by Leishmania braziliensis, is the most important form of tegumentary leishmaniasis in Latin America. Although the role of dogs as reservoirs of Leishmania infantum and the clinical features of canine visceral leishmaniasis are well described, little is known about the role of dogs with tegumentary leishmaniasis in the L.braziliensis transmission cycle. Reports of systemic and local treatment for cutaneous leishmaniasis in dogs with pentavalent antimonials are scarce. The objectives of this study were to determine the prevalence and incidence of canine leishmaniasis (CTL) in an area of transmission of Leishmania braziliensis and its role in human tegumentary leishmaniasis and to evaluate the effectiveness of intralesional treatment with meglumine antimoniate in dogs with CTL in an area of transmission of L.braziliensis. The incidence of canine infection by L. braziliensis and CTL were determined by identifying infected dogs and sick dogs over a period of one year in the village of Corte de Pedra. The diagnosis for detection of canine infection was performed by Polymerase Chain Reaction (PCR) and by serological test through enzyme immunoassay (ELISA). The second objective was to determine the frequency of human tegumentary leishmaniasis in households with dogs with and without evidence of disease or infection by L.braziliensis. The third study was a randomized controlled clinical trial with the objective of evaluating the efficacy and effectiveness of intralesional Glucantime compared with the use of intralesional sodium chloride solution (placebo) in dogs with CTL caused by L. braziliensis. Of a total of 214 animals studied, 142 animals were positive for infection by L. braziliensis and after one year the incidence of CTL was 9.3% and of asymptomatic infection was 4.6%. People living in homes with dogs with CTL or with asymptomatic infection were 4 times more likely to develop CL than people living in homes without dogs or with negative dogs. To carry out the randomized and controlled clinical trial to evaluate the effectiveness of intralesional meglumine antimoniate in dogs with CTL, 32 animals were selected, 16 allocated to the treatment group and 16 to the placebo group. After evaluation on day 90, cure was observed in 87.5% of the animals in the treatment group versus 12.5% in the placebo group. In an area of transmission of Leishmania braziliensis, the prevalence of infection in dogs is high, as is the incidence, suggesting that the dog can participate in the chain of transmission of this parasite. The use of intralesional Glucantime is an effective therapeutic strategy in the treatment of CTL.

Background: Virtually all patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) have some degree of erectile dysfunction (ED) but ED is also found in a large percentage of HTLV-1 carriers.
Aim: To evaluate the evolution of ED in HTLV-1 infected individuals followed for up
to 15 years.
Methods: Prospective cohort study of HTLV-1 infected men with ED, aged 18 to 70 years, followed from January 2004 to December 2019. We used the International Abbreviated Index of Erectile Function 5 (IIEF-5), the Expanded Disability Status Scale (EDSS) and the Osame Motor Disability Scale, and the Overactive Bladder Symptom Score (OABSS) to define and stratify ED, neurologic and bladder dysfunction, respectively.
Outcomes: Time to development of severe ED.
Results: We studied 90 men with ED, mean age 52.8 ± 9.78 years. At baseline, 42 were carriers, 16 had probable HAM/TSP and 32 had definite HAM/TSP. IIEF-5 was highest among carriers and lowest in patients with definite HAM/TSP whereas OABSS was lowest in carriers and highest in definite HAM/TSP patients. Median follow-up was 8.50 [3.00 – 12.00] years. IIEF-5 fell significantly from baseline to last follow-up among carriers, probable HAM/TSP and definite HAM/TSP patients. There was an inverse correlation between the IIEF-5 and the OABSS at last follow-up (r = -0.62, P < 0.001). In survival analysis, the time to development of severe ED was significantly shorter in patients with definite HAM/TSP when compared to carriers (P = 0.001) and probable HAM/TSP (P = 0.014). The presence of definite HAM/TSP at baseline was independently associated with the development of severe ED, after adjustment for
baseline age and proviral load (HR 6.74; P = 0.008). Clinical implication: Formal assessment of erectile function should be part of the routine clinical assessment of HTLV-1-infected individuals; worsening erectile function should alert clinicians to the possibility of neurologic deterioration. Strengths and limitations: This is the first prospective cohort study to describe the course of ED in HTLV-1-infected individuals. The small sample size and absence of seronegative controls are limitations.
Conclusion: ED is a slowly progressive clinical manifestation of HTLV-1 infection and the degree of neurologic compromise at baseline is the main predictor of time to progression to severe ED.

Objective: To compare the effectiveness of meglumine antimoniate (Sbv) (Glucantime™, 20mg/kg/day intravenously for 20 days) associated with G-CSF and the use of Sbv (same scheme) plus placebo in the treatment of cutaneous leishmaniasis (CL).
Methods: Thirty-two patients aged between 18 and 50 years with localized ulcerated LC (up to 3 lesions) with positive PCR for L. braziliensis were included in the study. G-CSF or placebo (0.9% saline solution) was applied by
intralesional infiltration of 0.1 mL at 4 equidistant points on the edge of the largest ulcer on day 0 and day 15. Cytokine levels (IL-1 β, TNF, IFN-γ and IL-10) were determined in culture supernatant of mononuclear cells stimulated with soluble Leishmania antigen at a concentration of 5 μg/ml.m. on days 0 and 15 (during treatment). Healing was defined as complete healing without elevation of the ulcer edges by day 90 after initiation of therapy. Failure was defined by the presence of an active ulcer or scar with raised edges at day 90.
Results: Males predominated in the G-CSF group (59%), while the control group had a higher frequency of females (53.3%). Most of the lesions were located in the lower limbs. The study showed no differences in therapeutic outcome between the two groups. The cure rate in the G-CSF group was 53% and in the placebo group it was 47%, however at the final evaluation on day 180 there was an increase in cure in the G-CSF group compared to the placebo group (65% versus 47%), but it was not significant.
Conclusion: The association of G-CSF and Sbv in the treatment of CL was not able to significantly change the cure rate when compared to the control group, probably due to insufficient sample size. The continuation of this study in a larger number of patients may be necessary to prove the effectiveness of the association of G-CSF in the treatment of CL.

Objetives:
i) determine whether modification of the neurologic compononent of SOFA outperforms the
unmodified score, ii) develop novel age calibrated score iii) determine whether a pneumonia specific
score outperforms common ICU and pneumonia severity scores and evaluate the performance of this
score in a multi
center COVID 19 ICU cohort.
Methods:
Prospective cohort studies of adult ICU patients hospitalized at Hospital de Cidade in Salvador,
Bahia, Brazil followed by a multi
center prospective cohort study of adults hospitalized in the ICU of
COVID treatment centers in Bahia.
Results:
Modification of the neurologic component SOFA with either a novel score for defining
neurologic system deficits, Full Outline of UnResponsiveness (FOUR) or Richmond Agitation
Sedation
Score (RASS) did not improve prediction of ICU mortality (SOFA
GCS AUC = 0.74 vs SOFA RASS AUC =
0.71 and SOFA
FOUR AUC = 0.67). A novel Age Calibrated ICU Score (ACIS) outperformed the SAPS3
score in prediction of mortality in our ICU cohort (AUC = 0.80 vs 0.72). The pneumonia shock score
score in prediction of mortality in our ICU cohort (AUC = 0.80 vs 0.72). The pneumonia shock score
demonstrated signficant performance improvement (AUC = 0.80) over existing ICU and pneumonia
demonstrated signficant performance improvement (AUC = 0.80) over existing ICU and pneumonia
severity scores including SAPS 3, qSOFA, CURB
severity scores including SAPS 3, qSOFA, CURB--65, and CRB65, and CRB--65 (AUC = 0.74, 0.64, 0.65, and 0.63,65 (AUC = 0.74, 0.64, 0.65, and 0.63,
respectively). Th
respectively). The calibrated e calibrated score subsequently performed well in those admitted to the ICU with SARSscore subsequently performed well in those admitted to the ICU with SARS--CoVCoV--22 infection (AUC = 0.80).infection (AUC = 0.80).
Conclusion:
Conclusion: Given the advanced age of our cohort and likelihood of an increasingy elderly ICUGiven the advanced age of our cohort and likelihood of an increasingy elderly ICU
population worldwide, we demonstrated that the novel age calibrated severity score outperformed
population worldwide, we demonstrated that the novel age calibrated severity score outperformed
SAPS3, offering a tool that may serve to help triage limited resources to those most likely to survive their
SAPS3, offering a tool that may serve to help triage limited resources to those most likely to survive their
critical illness. The calibrated pneumonia shock score accurately idenitifed those at risk for ICU mortality
critical illness. The calibrated pneumonia shock score accurately idenitifed those at risk for ICU mortality
from pneumonia in both pre
from pneumonia in both pre-- and postand post--COVID cohorts. This offers another simple bedside tool to helpCOVID cohorts. This offers another simple bedside tool to help
accurately assign individuals based on severity in subsequent clinical trials.
accurately assign individuals based on severity in subsequent clinical trials.

Exosomes are 30-100nm organelles secreted by various cell types. They occur when the
endosomal membrane invaginates into multivesicular bodies (MVB) and are secreted through
the melding of MVBs with the plasma membrane (PM). Leishmania exosomes are composed
by several proteins such as heat shock proteins, annexins, GP63, proteins with signaling
activity and also contain mRNAs and miRNA. Over the past 10 years it has been reported that
these vesicles are actively manipulating host signaling and immune cell functions, due to the
enrichment by Leishmania exosomes of virulence factors such as GP63. Studies demonstrate
that Leishmania donovani exosomes activate tyrosine-phosphatases, downregulating IFN-γ
and inhibiting the expression of microbicidal molecules such as TNF and NO, which creates a
microenvironment that favors parasite proliferation. Despite of not having immunological
memory, studies suggest that after a first stimuli mononuclear phagocytes can get “trained”,
passing through epigenetic changes and responding more effectively against a second stimuli,
that way, the sensitization of macrophages with L. braziliensis exosomes, prior to its infection
by this pathogen, may be associated with higher inflamatory cytokines production as well as
inflammasome activation, once the pathways involved in this process would already be
activated. Methods and Results: Healthy subjects’ macrophages were sensitized for 24
hours with L. braziliensis exosomes. Afterwards, these cells were infected with L. braziliensis
and cultured for 24 hours. We observed higher levels of IL-1β and IL-6 in cultures that were
sensitized before infection than in cells only infected. Furthermore, stimulation with L.
braziliensis exosomes induced production of IL-1β, IL-6, IL-10 & TNF by macrophages. We
inhibited the secretion of exosomes by L. braziliensis prior to macrophage infection and
observed that cells infected with those parasites induced less production of IL-1β, IL-6, IL-10
& TNF and cultures presented lower infection rate than cells that were infected with regular
Leishmania. Exosome stimulation also induced the consumption of NLRP3 inflammasome in
macrophages and the blocked of these receptors resulted in lower levels of IL-6, TNF and IL-
1β. Our results suggest that L. braziliensis exosomes stimulate macrophages leading to
inflammation and those effects might be NLRP3 dependent.

Introduction: Neurogenic dysfunction of the lower urinary tract in adults can manifest in the storage or emptying phase. Dysfunctions for bladder storage are widely studied, unlike changes in bladder emptying. The voiding dysfunctions tend to worsen with the evolution of the underlying pathology, which may result in damage to the upper urinary tract. Objective: To evaluate the role of physiotherapeutic approaches in the treatment of bladder emptying dysfunction secondary to neurological disorders. Methods: Systematic review of randomized clinical trials, including adults with neurogenic bladder emptying dysfunction. Search performed in Pubmed, Lilacs, PEDro and Embase databases. Results: 8 were included, totaling 369 participants aged between 34 and 52 years. The physiotherapeutic resources used were sacral, tibial, anal/vaginal intracavitary and acupuncture. The pathologies studied were multiple sclerosis, spinal cord injury and traumatic brain injury. The maximum amount of intervention applied to patients was 12 sessions. The outcomes analyzed were: post-void bladder residue, voided volume, maximum flow rate and detrusor pressure. 2 studies demonstrated a benefit with statistical significance in more than one analyzed outcome. In the assessment of methodological quality using the PEDro scale, the score ranged from 4 to 10 points (low to high quality rating), with an average of 6.6 (SD 2.4). Conclusion: The role of physical therapy in the management of patients with bladder emptying dysfunction of neurogenic origin is still uncertain. New randomized clinical trials are needed to establish the role of physical therapy approaches in the treatment of this population. Prosperous registration CRD42021243087.

Fundamentals: Individuals&#39; self-perception on their health, work and lifestyle is work ability, which is a concept of several dimensions, featuring a multidimensional and versatile construct as it encompasses physical, mental, and social preconditions.
Objectives: estimating the factors associated with work ability among health professionals in primary health care. Methods: Cross-sectional study from March to December, 2019, comprised of 107 professionals and a response rate of 75.3%, within 8 Family Health Units (USF - Unidades de Saúde da Família) and 25 teams. Results: Response rate of 75.35%. 29.9% were nursing technicians aged less than 38 years (52.3%, predominantly female (83.2%). 24.3% of inadequate WA. Conclusion: it is concluded that factors associated with inadequate work ability among primary care health professionals are physical activity and depersonalization.

Background: Chagas Disease (CD) is caused by the protozoan parasite
Trypanosoma cruzi and is a frequent cause of heart failure (HF) in Latin
America. Although cognitive impairment is commonly reported, whether it is a
direct result of CD or a nonspecific symptom of HF is unknown. We therefore
aimed to compare cognitive function of HF patients with or without CD.
Objective: to evaluate the cognitive aspects of chagasic cardiomyopathy.
Material and Methods: we performed a cross-sectional study from a cohort of
HF (according to the Framingham clinical criteria), separetad by groups of
chagasic or non-chagasic etiologies from four Brazilian centers. For cognitive
assessment, HF blind investigators, applied a series of cognitive instruments:
Mini Mental State Examination (MMSE), Nitrini’s Brief Cognitive Screening
Battery (BCSB), Rey Complex Figure Test (RCFT), Digit Span subtest and
Luria's fist-edge-palm test. It was evaluated the global cognition and specific
domains of memory, executive and visuospatial function, expressed as mean Z
scores of each test. Linear regression was used to determine the association
between CD and each cognitive domain after adjustment for age, sex,
educational level and left ventricular ejection fraction. Results: we recruited 496
patients between 2007 and 2021, 240 (48.3%) with CD. Patients with CD were
older (57+11 vs 54±11 years), more likely female and had lower educational
level. Global cognitive function was worse in CD vs non-CD patients (-0.90 vs.
0.61, respectively, p=0.001), mostly due to visuospatial function (-1.22 vs -0.45, 

respectively, p<0.001). The pattern for visuospatial domain impairment was
maintained in the multivariable analysis (effect of CD = -0.52, 95% confidence
interval = -0.88 to -0.16). Conclusions: Chagas disease is associated with
cognitive impairment independently of heart failure severity. A significant
association was observed between Chagas disease and visuospatial
dysfunction. The results obtained suggest that other mechanisms beside
cardioembolism or hypoperfusion contribute to this impairment.

Objective: To evaluate the presence of olfactory disorders according to the University of Pennsylvania Olfactory Test (UPSIT), in patients with Asthma. Methods: Cross-sectional study, part of a prospective cohort, through the evaluation of 93 patients diagnosed with Asthma from March 2019 to February 2020, at the Center for Excellence in Asthma - NEA/ProAR in Salvador, Bahia. All patients underwent the UPSIT smell test and otorhinolaryngological evaluation. Results: Among the 93 asthmatic individuals studied (63 with severe asthma and 30 with mild to moderate asthma), 89 (95.7%) had diagnosed olfactory disorders and only 4 (4.3%) had normosmia. Individuals with moderate, severe hyposmia or anosmia were older, with a mean of 56.5 years, while individuals with normosmia or mild hyposmia were younger, with a mean of 49.4 years (p0.029); 78.7% of individuals with moderate, severe hyposmia or anosmia had severe asthma, while 21.3% of these individuals had mild to moderate asthma(p0,002); 67 asthmatic individuals (72%) were diagnosed with chronic rhinosinusitis (CRS), of which only 5.9% had nasal polyps. No statistical significance was found in the analysis of CRS and olfactory disorders. Among the patients diagnosed with anosmia, 100% (7 patients) did not have the criteria for allergic rhinitis. On the other hand, 100% of the individuals with normosmia (2 patients) presented criteria for allergic rhinitis. (p 0.035) The use of oral steroids in the last year or
injectable steroids in the last 6 months was evaluated and the data revealed that 86.9% of the individuals with moderate, severe hyposmia or anosmia had used these medications. Among the individuals with normosmia or mild hyposmia, 64.5% had used oral or injectable corticosteroids in the same period. (p0.012)
Considering the entire sample studied, only 14 patients did not have a diagnosis of allergic rhinitis or CRS. Of these patients without diagnosed nasal pathologies, 100% had olfactory disorders diagnosed through the UPSIT with the following distribution: 6 moderate hyposmia, 5 severe hyposmia and 3 anosmia.
Conclusion: The results of this study lead to the conclusion that olfactory disorders are frequent in asthma, observing a direct correlation between the severity of the olfactory disorder and the severity of asthma.
Key

Parkinson's disease (PD) is associated with increased motor disability and decreased quality of life (QoL). However evidence demonstrating the value of multidisciplinary care to improve QoL remains scarce. Objective: The aim of the present study was to evaluate the effect of multidisciplinary rehabilitation to improve QoL of patients with PD. Methods: This single institution prospective observational longitudinal study enrolled patients with clinical diagnosis of PD and without severe cognitive impairment or comorbidity. Patients were followed into an inpatient rehabilitation program five times per week for four weeks and completed the The Parkinson's Disease Quality of Life Questionnaire (PDQ-39) on admission (T0), day 30 (T1), and day 90 after discharge (T2). The primary outcomes were the improvement of PDQ-39 total score and its dimensions on T1 and T2 compared to baseline. Secondary outcomes included changes in motor functioning and balance: MDS-UPDRS parts II and III, 10 Meter Walk Test, MiniBest, Timed Up Go (TUG). Results: Eighty-five of 88 recruited subjects completed follow-up. There was a significant improvement between T0 and T1 in the PDQ-39 total score with a mean drop of 13.2±13.6 points (95% CI =10.3-16.2; P<0.001) that was sustained after 90 days (T2), 17.1±12.1 points ( 95% CI=14.5-29.7; P<0.001). In addition, the secondary endpoints were met with improvement in MDS-UPDRS parts II and III, 10 Meter Walk Test, MiniBest and TUG (P<0.05 for all comparisons). Conclusions: An inpatient multidisciplinary rehabilitation program improves quality of life of patients with PD. The benefit was durable and sustained at the 3-month follow-up period.

Introduction: Falls in individuals with Parkinson's disease (PD) are frequent and often recurrent (≥ 2 falls), being an important source of disability in this population. Two predictive scales were recently developed and showed moderate to high accuracy for predicting recurrent falls in the next 12 months. The first tool composed of 3 predictors (AUC = 0.84; 95% CI 0.78–0.90) includes history of ≥ 2 falls in the last year, motor fluctuations and disability (Unified Parkinson's Disease Rating Scale, section on activities of daily living (UPDRS ADL) > 12 points or Movement Disorders Society (MDS) UPDRS, section on motor aspects of experiences of daily living (M-EVD) >14 points) and the tool consisting of 5 predictors (AUC = 0.86; 95% CI 0.81–0.92) includes these three predictors plus the levodopa equivalent dose  (LED) > 700 mg / day and Berg balance scale ≤ 49 points. Both scales need to be externally validated to ensure their generalizability, accuracy and clinical utility. Objective: Externally validate two tools predictive of recurrent falls in the next 12 months in people with PD. Material and Methods: 156 participants with PD were included and followed for 12 months to check the occurrence of recurrent falls. Demographic and clinical data, including a history of ≥ 2 falls in the previous year, symptoms of PD, and current medications, including LED, were recorded. Participants were assessed by UPDRS ADL, MDSUPDRS M-EVD and Berg balance scale. Multivariate logistic regression analyzes were performed and the accuracy of the predictive scales was determined by area under the receiver-operating characteristic curve (AUC). Results: 46 (29.5%) participants reported ≥ 2 falls during the 12-month follow-up. When considering the UPDRS ADL as a predictive variable, the multivariate models showed that only a history of ≥ 2 falls in the last year and motor fluctuations were independent predictors of recurrent falls in both tools. When considering the MDS-UPDRS M-EVD, the variable history of ≥ 2 falls in the last year was an independent predictor of recurrent falls in both tools and motor fluctuations was an independent predictor of recurrent falls only in the scale with 3predictor. The 3-predictor tool had an AUC = 0.71; 95% CI 0.63-0.79. The 5-predictor tool had an AUC = 0.69; 95% CI 0.60-0.77. Replacing the UPDRS AVD with the MDS-UPDRS M-EVD, the scale with 3 predictors had an AUC = 0.74; 95% CI 0.650.82. Scale 2 with 5 predictors had an AUC = 0.71; 95% CI 0.63-0.80. Conclusion: Both tools had moderate accuracy for predicting recurrent falls in the next 12 months in people with PD. 

aim: To compare clinical features and outcome of children with severe acute lower respiratory infection (ALRI) with or without SARS-CoV-2 infection admitted to Paediatric Intensive Care Unit (PICU). Methods: For this retrospective cohort study, all children aged<17 years admitted with severe ALRI at a PICU, in Salvador, Brazil were evaluated. Investigation of SARS-CoV-2 infection was performed by real-time reverse-transcription PCR. Clinical data, physical findings upon admission and outcome were registered. Patients were categorized by with or without SARS-Cov-2 infection. Outcomes were death and invasive mechanical ventilation (IMV). Results: We enrolled 210 patients, whose median age was 2.8 years (IQR: 7.1 months–6.2 years). IMV was used in 33 (15.7%; 95%CI 11.3%-21.1%) patients. Eight (3.8%; 95%CI 1.8%-7.1%) cases died. 62 patients (29.5%) tested positive for SARS-CoV-2. Male gender (67.7% vs. 52.7%, P=0.045) and sickle cell disease (6.5% vs. 0%, P=0.007) were associated with SARS-CoV-2 infection. Wheezing upon admission was more common in patients without SARS-CoV-2 infection (38.5% vs. 21.0%, P=0.01). IMV was more frequent among patients with SARS-CoV-2 infection (25.8% vs. 11.5%, P=0.009) as well as death (8.1% vs. 2.0%, P=0.05). Conclusion: Children with severe ALRI infection with SARS-CoV-2 need IMV more frequently than those without it.

Introduction: Stroke is the second cause of death and a major cause of disability in the world, and about 13.5–38.9% of ischemic strokes occur during sleep. Obstructive Sleep Apnea (OSA) is a highly prevalent and independent risk factor for stroke, associated with recurrence and mortality, but its relevance for functional outcomes is lacking. Aims: To determine if sleep apnea risk scores are associated with stroke recurrence and functional outcome in stroke patients. Methods: Prospective cohort, where consecutive patients with imaging-confirmed ischemic stroke were recruited from a public hospital in Salvador-Brazil. Demographic and cerebrovascular risk factor data and sleep apnea risk score were collected at baseline. We used STOP-Bang questionnaire (0 to 8) and SOS score (0-34) to quantify risk of OSA; higher scores indicating higher risk. Patients were followed for 90 days. Stroke recurrence data was colected and functional outcome was assessed by modified Rankin Scale (mRS). Poor outcome was defined as mRS = 3 to 6. Results: We enrolled 383 patients with ischemic stroke between October, 2018 and November, 2019. After 90 days, 216 (56.4%) had poor outcome. Patients with poor outcome were older [66 (±13) vs. 60 (±12) years; p=0.000], more often female [119 (55.1%) vs. 71 (42.5%); p=0.018] and had higher NIHSS on admission [14 (interquartile range – IQR 9-19) vs. 5 (IQR 3-8); p<0.001]. Median STOP-Bang score was significantly higher in patients with poor
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outcome [4 (IQR 3-5) vs. 3 (IQR 2-5); p = 0.001]. Median SOS score was not difference between groups [11 (IQR 7-16) vs. 12 (IQR 7-17); p=0.632]. In multivariable analysis, STOP-Bang score was independently associated with poor prognosis after adjustment for confounding variables (OR 1.68, 95% CI 1.05 to 2.72, p=0.032). When STOP-BANG score was stratified by OSA risk, patients with low, moderate and high OSA risk reached poor outcomes in 37.7%, 58.9% and 63.2% of cases, respectively (p=0.003). In contrast, we did not find association between SOS score and functional outcome, even in non-adjusted analysis (OR 1.06, 95% CI 0.78-1.43, p=0.717). Eighty-eight patients (23%) woke-up with stroke, with no difference between groups [36 (21.6%) vs. 52 (24%); p=0.626]. There was no association between sleep apnea scores and wake-up stroke in the univariate analysis [(SOS OR 1.1; 95% CI 0.76-1.52; p=0.68); (STOP-Bang OR 1.1; 95% CI 0.78-1.5; p=0.59)]. Stroke recurred in a small proportion of patients (1.6%) and thus, our study was not powered to detect predictors of stroke recurrence. Conclusion: A simple sleep apnea score (STOP-Bang) is independently associated with poor functional outcome in ischemic stroke patients, even after adjustment for confounding variables. A longer time of observation is necessary to evaluate its association with stroke recurrence.

The incidence of congenital syphilis (SC) has increased in Brazil in recent years and in 2014 to 2016 there was a shortage of penicillin for the treatment of newborns (NBs), worsening this situation. Objective: To describe the clinical and laboratory evolution of newborns treated for SC with ceftriaxone and cefotaxime at Maternidade Tsylla Balbino, Salvador, Bahia. Study design: descriptive study, with a retrospective assessment of the newborn at birth and clinical and laboratory reassessment at 3 years of age. Results: The review of 5500 medical records resulted in 170 pregnant women with a positive non-treponemal test (VDRL) at the time of admission and 95 newborns diagnosed with SC. Due to the shortage of penicillin, two treatment groups were formed: ceftriaxone (N = 25) and cefotaxime (N = 11). In this sample, 55.6% of mothers had high school education, 86.1% underwent prenatal care and 38.9% received a diagnosis upon admission to the maternity hospital. Only 30.6% of pregnant women were adequately treated, while 94.4% of sexual partners did not undergo treatment. It is observed that the VDRL values of the newborns were equal to or less than those of the mother in the maternity ward. Only 2 children in the ceftriaxone group had positive FTAABS and all VDRL were negative in the reevaluation. There was a loss of important follow-up demonstrating the vulnerability of this population that needs public health strategies for the growth and development of children, avoiding the sequelae of SC. Conclusion: This study contributes to the epidemiological and empirical record of the treatment of CS and points to the possibility of listing ceftriaxone and cefotaxime for treatment in newborns in case of shortage of penicillin.

Background: Chagas disease (CD) is an important cause of cardiomyopathy and stroke in our country. The relationship between CD and cognitive dysfunction is less known and the mechanism of this dysfunction is unknown. Objective: to study the relationship between the density of silent vascular lesions and cognitive dysfunction (by cognitive domains) in patients without clinical experience and/or history of stroke. It is intended to verify whether the burden of cerebral infarctions is the main mechanism of cognitive dysfunction in patients with CD. Material and Methods: a sample of 500 patients with heart failure (HF) according to Framingham criteria, separated into the group of Chagas etiology (cases) and other etiologies (controls), was evaluated. After analysis and signing of the consent form, all participating patients underwent cognitive analysis using the Mini Mental State Examination (MMSE); Brief Cognitive Screening Battery (Nitrini et al.); Rey's Complex Figure test and Clock Drawing test. Brain MRI scans (1.5T GE equipment) and preliminary analysis of 274 patients described here were performed using FLAIR/T1 sequences to detect the load of vascular lesions (lacunar and territorial). Complementary analysis was performed to study cerebral, cerebellar and white matter lesion volumetry, as well as spectroscopy markers. Results: patients with CD showed worse performance in visuospatial function (p<0.001), when compared to the control group. Individuals with CD had a lower frequency of lacunar infarcts compared to individuals without CD (p=0.047); and a similar frequency of territorial infarctions (p= 0.732). In the volumetric analysis, we noticed a greater degree of brain atrophy (p= 0.006) in CD compared to controls. Conclusions: data analysis suggests that Chagas disease is associated with greater cognitive impairment, especially in the visuospatial domain. Silent brain lesions do not seem to be determinant for cognitive deficit in chagasic patients without a clinical history of stroke and cognitive impairment may be associated with the greater degree of brain atrophy identified in this group.

Background: Falls are related to PD and behavioral factors may be associated with the risk of falling. The Fall Behavior Scale (FaB) assesses these factors, however it‟s use is not validated for people with PD in the Portuguese language (FaB-Brasil). Objective: To test the psychometric properties of the Fall Behavioral Scale (FaB-Brazil) for people with PD. Methods: Sociodemographic, clinical and functional data, community mobility and scales were collected: MDS-UPDRS (Part II and III), modified H&Y, S&E, ABC, PDQ-8, TUG and FaB-Brasil. Internal consistency was assessed by Cronbach's alpha coefficient and test-retest and inter-examiner reliability by ICC. The convergent validity between the FAB-Brasil and the study variables was assessed using Spearman's correlation. Discriminant validity was assessed using the student t-test. Results: 96 people with PD were evaluated, 52.1% were male, with a mean age of 65.1 (9.58) years. The scale's internal consistency was 0.77; the inter-examiner ICC was 0.88 and the test-retest was 0.90. The correlation between FaB-Brasil and the study variables was weak, except between FaB-Brasil and ABC, which was moderate, all of them were significant. Men had less secure behavior than women and fallers had more secure behavior than non-fallers. Conclusions: The FaB-Brasil for people with PD had good internal consistency, test-retest and inter-examiner reliability, and good construct validity.

Introduction: Leprosy is a chronic infectious and dermatological disease caused by the bacillus Mycobacterium leprae and still constitutes a public health challenge in many countries, including Brazil. Although the immunopathological mechanisms by which the bacillus continues to be persistent, causing the complex clinical forms of the disease and reaction episodes are not fully understood, the participation of Toll-like receptors (TLRs) in mediating the inflammatory response is widely recognized. In this context, we evaluated the expression of miRNAs participating in the post-transcriptional control of TLRs pathways in individuals with leprosy. Materials and Methods: We selected miRNAs in public domain softwares (TargetScanHuman and miRBase); we performed gene expression by real time PCR using 11 miR assays (146a-5p, 146b-5p, 147a, 155-5p, 9-3p, 125a-3p, 132-5p, 21-3p, let-7a-3p , 511-3p, 103a-3p) and U6snRNA (nucleolar RNA) in 38 samples, 28 biopsies (14 individuals without reaction (SR) and 14 reaction individuals) and 10 cell samples (4 individuals (before and after Reverse Reaction (RR)) and 6 individuals (before and after leprous nodular erythema (ENL)); protein dosing was performed using the sandwich ELISA technique; after normalization of gene expression using endogenous genes by the RefFinder program, the statistical data referring to biopsies were generated by the Welch t test and in the cells by the Wilcoxon test; in the analysis of cytokines / chemokines and the bacillary index, the Spearman Correlation test, through the GraphPad Prism8. Results: In biopsies there was a significant increase in the expression of miR-125a-3p in individuals PB and ENL, in the comparisons (PB vs MB and vs RR; ENH vs MB) and a correlation (+) between this miR and the BI in reactive patients. For miR-147a, there was a (+) correlation with IL-8, CXCL-10, and BI in SR individuals; also,in the SR there was a correlation between miR-155-5p and CXCL-9 and a correlation (-) between miR-21-3p and IL-1β. We also observed correlations (+) between miRs 146b-5p and 132-5p and BI in reactive individuals (RR + ENL). Conclusions: In addition to being associated with clinical forms, miRNAs are also correlated with immunological and clinical markers. MiRs 125a-3p and 147a appear to have a more prominent role in pathogenesis.Introduction: Leprosy is a chronic infectious and dermatological disease caused by the bacillus Mycobacterium leprae and still constitutes a public health challenge in many countries, including Brazil. Although the immunopathological mechanisms by which the bacillus continues to be persistent, causing the complex clinical forms of the disease and reaction episodes are not fully understood, the participation of Toll-like receptors (TLRs) in mediating the inflammatory response is widely recognized. In this context, we evaluated the expression of miRNAs participating in the post-transcriptional control of TLRs pathways in individuals with leprosy. Materials and Methods: We selected miRNAs in public domain softwares (TargetScanHuman and miRBase); we performed gene expression by real time PCR using 11 miR assays (146a-5p, 146b-5p, 147a, 155-5p, 9-3p, 125a-3p, 132-5p, 21-3p, let-7a-3p , 511-3p, 103a-3p) and U6snRNA (nucleolar RNA) in 38 samples, 28 biopsies (14 individuals without reaction (SR) and 14 reaction individuals) and 10 cell samples (4 individuals (before and after Reverse Reaction (RR)) and 6 individuals (before and after leprous nodular erythema (ENL)); protein dosing was performed using the sandwich ELISA technique; after normalization of gene expression using endogenous genes by the RefFinder program, the statistical data referring to biopsies were generated by the Welch t test and in the cells by the Wilcoxon test; in the analysis of cytokines / chemokines and the bacillary index, the Spearman Correlation test, through the GraphPad Prism8. Results: In biopsies there was a significant increase in the expression of miR-125a-3p in individuals PB and ENL, in the comparisons (PB vs MB and vs RR; ENH vs MB) and a correlation (+) between this miR and the BI in reactive patients. For miR-147a, there was a (+) correlation with IL-8, CXCL-10, and BI in SR individuals; also,in the SR there was a correlation between miR-155-5p and CXCL-9 and a correlation (-) between miR-21-3p and IL-1β. We also observed correlations (+) between miRs 146b-5p and 132-5p and BI in reactive individuals (RR + ENL). Conclusions: In addition to being associated with clinical forms, miRNAs are also correlated with immunological and clinical markers. MiRs 125a-3p and 147a appear to have a more prominent role in pathogenesis.

Acute liver failure (ALF) is characterized by sudden damage to liver cells, leading to coagulopathy and changes such as hepatic encephalopathy. ALF is the most serious form of manifestation of DILI (Drug Induced Liver Injury). For the most part, ALF DILI tends to be an idiosyncratic reaction and can occur within six months of starting treatment using the medication. In Latin American countries, frequencies of 6% and 15% were found in Uruguay and Argentina, respectively. In Brazil, little is known about the epidemiology of ALF by DILI and the xenobiotics involved. OBJECTIVE: To know the frequency of acute liver failure cases caused by allopathic drugs, phytotherapeutics, plant ingredients and food supplements in Brazil. METHOD: Multicenter retrospective observational study. An e-mail invitation was sent to each Center. For those who accepted to participate, an on-site visit was carried out to collect data from the medical records of patients with suspected ALF DILI. Information was collected on: demographic data, clinical characteristics, laboratory tests, imaging tests during the episode and/or histological summary, if liver biopsy, serology of acute hepatitis caused by virus or other suggestive liver diseases with the clinical picture presented by the patient. The entire drug history was verified, taking into account the use of vegetables, herbal medicines and food supplements. RESULTS: Of the 60 invited centers, only 12 Liver Transplant Centers agreed to participate. Of the 325 individuals identified with IHF, 34% were of idiopathic etiology, DILI (27%) and AIH (18%). The re-evaluation of 89 cases of DILI, using causality criteria, revealed that in only 42 individuals DILI could be confirmed as a cause of ALF. Toxicity of acetaminophen (APAP) (n = 3) or DILI due to herbal and dietary supplements (n = 2) were not commonly found. The most frequent therapeutic classes found were: tuberculostatics (Anti-TB) 9 (21%), non-steroidal anti-inflammatory drugs  (NSAIDs) 9 (21%), and antibiotics 7 (19%). Regarding the resolution of the picture of ALF DILI, all underwent transplantation, of which 45% (19/42) survived more than one year after transplantation. CONCLUSION: Idiopathic etiology and DILI are the main causes of ALF in Brazil. ALF DILI affects women considerably, it is most often caused by Anti-TB, NSAIDs and antimicrobials, to a lesser degree, by antiepileptics, antimetabolites, and herbal products. Paracetamol is not an expressive cause of ALF in the studied population.

Background: Falls are common in people with Parkinson’s disease (PD) and have detrimental effects which can lower the quality of life.

Objectives: To compare the circumstances of falls in people with with PD based on fall frequency and to identify predictors of falls with injuries.

Methods: Prospective cohort with individuals from a PD outpatient clinic, Salvador-Bahia. Participants with PD (n=229) and independent gait ability were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), activities of daily living (ADL) and motor sections, modified Hoehn and Yahr Scale, Activities-specific Balance Confidence Scale (ABC), Falls Efficacy Scale-International (FES-I), Berg Balance Scale (BBS), Functional Reach Test, Timed Up and Go Test (TUG) and Dynamic Gait Index (DGI), and followed-up for 12 months with a diary to identify falls, their circumstances (time, location of fall, activity was doing the fall, cause of the fall and if it had any injurious falls. Predictors with p<0,05 in univariate were chosen for entry into the multivariate model.

Results: 805 falls were reported by 111 (48%) participants. Outdoor falls were more common among single (1)/non-frequent (1-4 falls) fallers, while indoor falls among recurrent (≥2)/frequent (≥5 falls) fallers (p<0.001). Tripping was one of the major perceived cause of falls among single/non-frequent fallers and freezing of gait among recurrent/frequent fallers (p<0.001). Disease duration (Odds Ratio [OR]=0.92; 95% confidence interval [CI] 0.86-0.97;),), Dynamic Gait Index (OR=1.24; 95% CI 1.10-1.38), Activities-specific Balance Confidence Scale (OR=0.98; 95% CI 0.96-0.99), outdoor falls (OR=2.17; 95% CI 1.27-3.72) and falls related to extrinsic factors (OR=3.13; 95% IC 1.70-5.74) (p<0.05) were predictors of falls with injuries.

Conclusions: Circumstances of falls differ between single/non-frequent and recurrent/frequent falls. Outdoor falls caused by tripping and slipping were more common among single / non-frequent fallers, while indoor falls caused by freezing of gait and reduced balance among recurrent / frequent falls. Better balance during gait, falls in the external environment caused by extrinsic factors and better balance during gait were predictors of falls with adverse consequences. Longer PD duration and better confidence in balance were protective factors for falls with adverse consequences.

Leishmaniasis is an infectious disease of significant clinical and epidemiological diversity, with a wide geographical distribution in the world. Bahia is one of the most affected Brazilian states for tegumentary and visceral leishmaniases. In the present work, we consolidated secondary data from several complementary databases that allowed us to record the sandfly species identified for overlayed the geographical distribution data onto maps of vegetational aspects. In addition it was carried out the prospective characterization of the phlebotomine fauna found around and near residences of newly diagnosed Cutaneous Leishmaniasis (LC) and Disseminated Leishmaniasis (LD) in the region of Corte de Pedra, Bahia southeastern. This prospective study that intends to analyze the rates of natural infection of sandfly species by L. (V.) braziliensis in this households. Overall, 21.602 records of phlebotomine occurrence between 1949-2016 were analyzed, encompassing 85% of Bahia’s municipalities. Eghty sand fly species under seventeen genera were enlisted. Among described species, fourteen were proven or putative Leishmania spp vectors and three were considered exclusively endemic in the state. Lutzomyia longipalpis, Nyssomyia intermedia and Nyssomyia whitmani were found in 74%, 29% and 27% of municipalities, respectively. Salvador, the state capital and major city with over 2.5 million inhabitants presented records for twenty different sand fly species, including known vectors for leishmaniasis. In particular, a wide distribution of Evandromyia sallesi was detected for this city. In the prospective study 619 specimens of sandflies were captured: 273 males (44%) and 346 females (56%), totaling 20 species from may/2018 to july/2019. The species Ny. whitmani was the most representative, at 62.2%, followed by Ny. intermedia (9.2%), Ev. bahiensis (6.3%), Trichophoromyia viannamartinsi (4.5%), the latter two endemic to Bahia. It was sent 94% of the total collected females for the detection of natural infection by L. (V.) braziliensis, divided into pools per month, clinical form, species and ecotope. Of the 97 pools of sandflies analyzed, seven were positive for L. (V.) braziliensis: three for Ny. whitmani, two from Th. viannamartinsi and, only one positive pool for Psychodopygus davisi and Trichopygomyia longispina. The global minimum infection rate (MIR) found was 2.2% and, for the mentioned species, 1.94%, 10%, 33% and 50%, respectively. These results open a prerogative for entomological monitoring works for a seasonal the natural infection evaluation of diferente sandflies species proven or putative ATL vectors by the different forms of L. (V.) braziliensis circulating in the Corte de Pedra (BA) endemic area.

Background and Objectives: Salvador, Brazil was the epicenter of microcephaly (MC) related to congenital zika syndrome . Although a severe development delay of these children is expected, studies have showen a heterogeneous profile that even included, in some cases, mild delays. Our aim was to identify predictive factors for developmental disorders in children with MC related to congenital zika syndrome (CZS).
Methods: Prospective cohort of newborns at Hospital Geral Roberto Santos (HGRS) in Salvador, BA, Brazil. Children with MC associated with CZS, born from September 2015 to April 2016 were included in this cohort and followed until the third year of life. They were examined by a multiprofessional staff at HGRS outpatient clinic which prospectively assessed clinical, anthropometric and neurodevelopmental outcomes (using composite Bayley III score). Neonatal head CT scan analysis was also performed by two blinded investigators for detection of brain abnormalities and the degree of ventricle enlargement, measured by Evans’ Index (EI).
Results: Of all clinical, anthropometric and radiological parameters evaluated in the study, EI was the only variable associated with developmental delay and remained significant after adjustment for head circumference (Intergrowth Z-score). A 0.1 point increase in the EI was associated with a delay of 2.8 months in cognitive (p = 0.038), 2.5 months in receptive language (p =0.047) and 2.5 months in fine motor (p = 0.048) domains.
Conclusions: Evans’ Index predicted developmental delay in composite Bayley score in the cognitive, receptive and fine motor domains in children with MC associated with CZS.

Objective: To estimate the association between Occupational Stress and Abdominal Adiposity (AA) in primary healthcare (PHC) nursing professionals. Case selection and method: A confirmatory, descriptive, cross-sectional and multicenter study carried out with 194 participants from the nursing team of the Family Health Units of the Municipality of Vitória da Conquista, BA, Brazil. Socio-demographic, labor and health condition data were collected using the Work Stress Scale (WSS) proposed by Paschoal and Tamayo (2004) for verifying Occupational Stress (independent variable) and waist-circumference for AA measurement (dependent variable). The SPSS 22.0 software for Windows was used for statistical analysis. Accordingly, the descriptive analysis of the data was expressed through central tendency measures. The associations between the variables occurred through the Pearson Chi-square, Fisher Exact and Mann-Whitney tests. The variables with possible associations (p-value<0.1) were included in a multivariate logistic regression model and using the Odds Ratio with its respective 95% confidence interval (CI). Results: The observed prevalence of high occupational stress corresponded to 63 (32.5%) and AA to 75 (38.7%); there was an association between occupational stress and abdominal adiposity (p-value=0.000), whereby 56 (74.7%) of the participants presenting AA also had high stress levels. In relation to the socio-demographic and labor variables, there was a predominance of women 167 (86.1%), doing night-shifts 139 (71.6%), nursing technicians 155 (79.%), considering their quality of life as good 154 (79.4%). In logistic regression only the variable race/color presenting a statistical significance was observed (p=0.006), where 68.5% of the participants with adiposity were self-declared as having brown skin, with 4.7 higher chances of having AA. Participants with a high level of occupational stress had 58.7 times greater probability of having AA when compared to participants with low levels of occupational stress, with Nursing technicians having presented a greater percentage of high occupational stress and AA. Conclusion: Greater prevalence of high stress and AA was observed. There was a statistically significant association between high occupational stress and AA among nursing professionals in the studied sample.

Objective: To correlate the frequency of eosinophils in the induced sputum with severity of Chronic Obstructive Pulmonary Disease (COPD) Methods: This is a cross-sectional study comparing the clinic profile, pulmonary function, the cellularity of the sputum and cytokine levels in 35 patients with asthma/COPD (ACO) with 35 patients with only COPD. The cellularity in the sputum was determined by microscopy after citocentrifugation, the PRICK-test was performed and serum cytokines were determined by ELISA. Results: Patients with ACO had the PRICK-Test more positive (p < 0.001), had an increasing in the frequency of eosinophils in the sputum (p < 0.001), a reduction in the forced expiratory volume (FEV1), than patients with COPD. Moreover there was an inverse correlation between the frequency of eosinophis in the sputum with the FEV1 (R2=0,61; p˂0.05) and patients with ACO had more admissions in emergency rooms. The concentration of eotaxin was similar in the 2 groups and higher than that observed in healthy subjects (p <0.001). Conclusions: The eosinophilic inflammatory component is a marker of severity of COPD and in addition to play a key role in the pathogenesis of ACO. It is also participate in the pathogenesis of COPD.

CHARACTERIZATION OF CLINICAL MANIFESTATIONS, AND RESPONSE TO TREATMENT IN CHILDREN WITH CUTANEOUS LEISHMANIASIS. Cutaneous leishmaniasis (LC) caused by Leishmania braziliensis is characterized by a well limited ulcer with raised borders. The disease occurs predominantly in young male adults and there are a limited number of studies on CL in the pediatric population. The aim of the present study was to compare the clinical presentation and response to antimonial therapy in children versus adult population. The participants were 571 patients diagnosed with CL at the Health Clinic of Corte de Pedra, Brazil, in 2016 and divided into 3 groups: 1. Age between 0-12 years, children (129 cases - 22.6%); 2. Age between 13 and 18 years, adolescents (83 cases - 14.6%); 3. Age greater ≥ 19 years, adults (359 cases -62.8%). The children had a shorter duration of disease, a higher incidence of head injuries and smaller lesions, when compared to the adults group (P <0.05). Cure was defined by complete healing of the ulcer in the absence of raised borders 90 days after initiation of therapy and failure by the presence of active ulcer or a scar with raised edges at day 90. The therapeutic failure was associated with lower age, lower duration of disease, more than one lesion and larger lesion size. After multivariate analysis, all these variables remained significant. Although the greater risk of failure due to multivariate analysis has been associated with lower age, in general, the cure rate between children (43%), adolescent (40%) and adult (48%) is similar. In conclusion, we observed that there was a significant increase in the number of children with CL compared to previous studies in the same endemic area, but with the exception of the site of the lesions, the LC presentation as well as the response to antimony therapy was similar in children and adults.

Introduction. The human T cell lymphotropic virus type 1 (HTLV-1) associated myelopathy (HAM) is the main neurologic disease caused by HTLV-1 but other neurologic and clinic manifestations associated to the virus are documented in more than 50% of infected subjects. A high proviral load (PVL) is recognized as a risk factor for HAM but there is a lack of prospective studies evaluating if HTLV-1 carriers with high PVL are at risk to develop HAM or other HTLV-1 related diseases. In this study we compare the incidence of clinic manifestations and the cytokine levels in HTLV-1 carries with high and low proviral load. Methods. Participants were 30 HTLV-1 high PVL carriers (> 50,000 copies/106PBMC) and equal number of subjects with PVL lower than 50,000 copies/106PBMC. They were followed by 3 to 16 years (median of 11 years). The PVL was measured by real time PCR and IFN-γ, TNF and IL-10 levels were quantified by Elisa in supernatants of unstimulated mononuclear cells at entry and at the end of the follow-up. Abnormalities in the neurologic examination, development of HAM, urinary dysfunction, erectile dysfunction, periodontal disease and the occurrence of sicca syndrome were recorded annually. Results. Among the self-reported symptoms in the initial evaluation, only the presence of paresthesia on hands was more frequent in the group with high PVL (p .04). The production of IFN-γ was higher in the group with high PVL group (median 1308 versus 686pg/ml, p<.011) when compared to the control group in the first assessment. During the follow-up there was a decreasing in the proviral load only among the cases. Moreover, there was no difference in the occurrence of urinary or erectile dysfunction, periodontal disease, sicca syndrome, neurologic signs between the two groups and non-patients developed HAM. Conclusion. HTLV-1 carries with high proviral load and with exaggerated inflammatory response may not progressed to HAM/TSP, indicating that other factors in addition to the proviral load are involved in the passage of HTLV-1 infected cells from the blood to the central nervous system.

Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus identified. It is estimated that the number of people infected by HTLV-1 is around 10 to 20 million worldwide. In addition to adult T-cell leukemia / lymphoma (ATLL) and HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/ TSP), several other diseases or clinical manifestations have been associated with HTLV-1 infection, such as overactive bladder, dry syndrome, polymyositis, periodontitis, arthropathy and erectile dysfunction. The occurrence of arthritis in patients infected with HTLV-1 has been reported, but to date, there is no definition about joint manifestations in patients with HTLV-1 associated arthropathy (HAAP), the radiographic aspects of joint involvement in these patients are unknown, and there are no diagnostic criteria for HAAP. Objective: To describe the radiographic aspects in individuals infected by HTLV-1 that present joint pain. Methods: This is a controlled cross-sectional study with the participation of HTLV-1 infected individuals that had joint chronic pain complaint in activity at last year, with age range from 18 to 75 years old, both genders and a control group composed of HTLV-1 seronegative individuals with hip, knee and/or ankle osteoarthritis. All subjects with HTLV-1 and controls were evaluated by a rheumatologist, all answered a questionnaire and made conventional X-rays from the hips, knees and ankle/feet. Results: Eighty-one HTLV-1 infected patients and 30 subjects with osteoarthritis diagnosis have taken part of the study. There was no difference between groups related to age and gender (p > 0.05). The prevailing standard of the joint involvement in the HTLV-1 positive group was polyarticular and symmetrical while in the control group it was oligoarticular and asymmetrical (p < 0.0001). While osteophytes and the joint space narrowing were predominant findings in patients with osteoarthritis (p < 0.0001), in HTLV-1 infected patients the frequency of enthesophytes was greater than in control group (p < 0.03). In reference to the presence of enthesophytes and the presence of joint space narrowing and/or osteophyte, enthesophyte without space reduction and without osteophyte was only observed in HTLV-1 infected individuals (p = 0.001). Conclusions: The HTLV-1 associated arthropathy is clinically characterized by a symmetrical polyarthralgia being the main radiological finding the occurrence of enthesophytes in the absence of osteophytes and joint space narrowing. The occurrence of signs of synovitis is very low in individuals infected with HTLV-1 with joint complaints, and arthralgia is a relevant joint manifestation in this population. There was no difference between the clinical forms of HTLV-1 infection and radiographic findings.

Introduction: Disseminated Leishmaniasis (DL) caused by Leishmania braziliensis is characterized by the presence of 10 or more papular, acneiform and ulcerated lesions. Some studies have shown that evidence of polymorphism of leishmania parasites and L.braziliensis isolated from patients with DL, cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) are polymorphic,presenting a genetic diversity that is associated with clinical forms of ATL. The soluble antigen obtained from L.braziliensis isolates from DL patients induced a greater inflammatory response when compared to antigen obtained from isolates of patients with CL in cells of patients with CL and DL. Studies have shown that monocytes / macrophages from patients with CL and ML behave differently against infection with L.braziliensis when compared to cells from healthy controls (HS). There are no studies about the behavior of monocytes in DL. Objective: To evaluate the role of monocytes and isolates of Leishmania braziliensis genotypically different in the inflammatory response in DL. Methods: Monocytes from patients with DL (n=12) and from patients with CL (n=12) were infected with L. braziliensis isolates from patients with DL and isolated from patients with CL at a ratio of 5:1. The evaluation of the degree of infection and the parasite load was evaluated after cytospin preparations by optical microscopy. To analyze the survival of different L. braziliensis isolates in monocytes from DL and CL patients, the number of viable promastigotes was quantified on the culture supernatant by optical microscopy. The evaluation of oxidative radical production was performed by oxidation of Dihydrorhodamine 123 (DHR-123) and analyzed by flow cytometry. Expression of TLRs and cytokines / chemokines was assessed by flow cytometry. Results: The monocyte frequency of DL patients infected with DL isolate and parasite load was higher than that observed in monocytes infected with the CL isolate after 48 hours of infection. The same was observed in the cells of patients with CL. The number of viable promastigotes in the monocyte supernatant infected with the DL isolate was higher when compared to the CL isolate in both groups. The same was observed in CL monocytes. Oxidative burst production by DL monocytes and CL monocytes infected with DL isolate was higher when compared to CL isolates in DL monocytes and CL monocytes. TLR2 expression was higher in DL monocytes after infection with DL isolate when compared to CL isolate. The production of CXCL9 was higher after infection with the DL isolate when compared to the CL isolate. Conclusions: These results suggest that the genotypic differences of L.braziliensis causing DL and CL can influence the behavior of this parasite in human monocytes and contribute to the pathogenesis of the disease.

Background: American Cutaneous Leishmaniasis is an infectious disease caused by several protozoan species of the genus Leishmania. Leishmania (Viannia) braziliensis is the species that causes a broad spectrum of different clinical manifestations, the most common being cutaneous leishmaniasis (CL). Analyzes of lesions fragments of patients with CL present an intense inflammatory process with high frequency of lymphocytes and macrophages, with few parasites being observed. Inflammatory cytokines are important for the increase in leishmanicidal activity of mononuclear phagocytes, but high TNF and IL-1β production contribute to tissue damage and ulcer emergence. Recently, increased attention has been given to the polyunsaturated fatty acids of the omega-3 family, EPA and DHA, due to their anti-inflammatory properties. However, the role of these fatty acids in leishmaniasis, especially in cutaneous form caused by L. braziliensis has not been investigated. Objective: To evaluate the immunoregulatory effects of EPA and DHA polyunsaturated fatty acids on the inflammatory response of patients with CL caused by L. braziliensis Methods: Lesions fragments were obtained from patients with CL and skin from healthy individuals for analysis of genetic expression by the RNAseq technique. Serum were obtained from patients with CL and healthy individuals for measurement of total omega 3, cytokines TNF, IL6, IL1β and eicosanoids PGE2 and LTB4 by the ELISA technique. Peripheral blood mononuclear cells were obtained from patients with LC and cultured for 72 hours in the presence or absence of SLA, LPS, Pam3Cys, EPA, DHA or EPA + DHA. In addition, monocytes from CL patients were cultured for 7 days for differentiation into macrophages and infected with L. braziliensis (5: 1), after infection the cells were cultured in the presence or absence of EPA, DHA or EPA + DHA for 2, 48 and 72 hours. Supernatants from the PBMC and macrophages cultures were used to quantify the cytokines TNF, IL-6, IL-1β and eicosanoids PGE2 and LTB4 by the ELISA technique. Results: An increase in the expression of the genes NF-κβ, IL-6, TNF, IL-1β, COX2, ALOX5 and PGE2 and LTB4 receptors was observed. Regarding the genes involved in the regulation of inflammation PPARG, RXRA, ALOX12 and ALOX15 were repressed in the lesion of patients with CL when compared to IS skin. We found that patients with CL exhibit high circulating levels of TNF, IL-6, IL-1β, PGE2 and LTB4 compared to IS. The addition of EPA and DHA to SLA stimulated PBMC cultures modulated the production of IL-6 and IL-1β and the association of these PUFAs was potentiated in the regulation of TNF, IL-6 and IL-1β cytokine production. We also observed that DHA and EPA + DHA induced the production of LTB4 in SLA-stimulated PBMC. We have also found that PPAR-γ is directly involved in the synthesis of PGE2 and LTB4 and the effects of EPA and DHA on cytokine modulation are nuclear receptor dependent. In addition DHA boosted the production of LTB4 in the absence of PPAR-γ; finally, we found that exogenous EPA and DHA contribute to the destruction of Leishmania by macrophages, through the production of LTB4. Conclusion: Our results suggest that in vitro supplementation with EPA and DHA have beneficial effects in the resolution of LC inflammation and infection, opening new perspectives for the adjuvant treatment of this disease.

Introduction: HTLV-1 is associated with the occurrence of periodontitis. The reason
why individuals infected by HTLV-1 develop periodontal disease is not known.
Objectives: To evaluate the association between proviral load and inflammatory
cytokines and periodontal disease in HTLV-1 infection. Methods: Cross-sectional study
realized in the HTLV-1 Multidisciplinary Ambulatory of Professor Edgard Santos
University Hospital Complex Immunology Service (Com-HUPES). The patients
periodontium was evaluated by probing and we used the cytokine dosage and the latest
proviral load registered in the database available in the Immunology Service
Multidisciplinary Ambulatory (COM-HUPES. Results: Eighty HTLV-1 infected
subjects were included in this study and 40 patients presented periodontal disease and
40 subjects without periodontal disease. The median proviral load and interquartile
range in subjects without and with periodontal disease were 14915.0 (IQ 1333.750-
47195.900) and 18863.5 (IQ 1348.750-68631.250), respectively, p>0.5. The production
of TNF in controls without periodontal disease was 17.0 pg and in patients with
periodontal disease was 43.0 pg with p>0.5. The production of IFN was 362.5 pg and
885.0 pg respectively p>0.5. There hasn’t also been difference related to the production
of IL-10 and the occurrence of periodontal disease, p>0.5. It hasn’t been observed
difference between proviral load, IFN, TNF and IL-10 in relation to the periodontal
disease gravity.Conclusion: The lack of relationship between inflammatory response or
proviral load with periodontal disease associated with HTLV-1 indicates that other
factors in addition to pro-viral load and immune response are involved in the migration
of HTLV-1 to the periodontium.

The Zika virus infection (ZIKV) appered at the Basil in 2015, causing an unprecedented epidemic outbreak with severe brain disorders in fetuses. Objective: to describe the clinical, neuroimaging and neurophysiological findings of children with microcephaly associated with congenital ZIKV infection (CZS) Study design: retrospective, descriptive, cross-sectional study. Methods: review of electronic records of children diagnosed with microcephaly at birth, and probable CZS, admitted to a child rehabilitation center in the city of Salvador, Brazil. The chil-dren were evaluated following standardized procedures and were submitted to neuroimaging and neurophysiological studies during follow-up with an interdisciplinary team. Results: In the 102 children in this study the most mothers (81%) reported symptoms of ZIKV during the first trimester of pregnancy. Microcephaly was severe in 54.9% of the cases. Cerebral atrophy (92.1%), ventriculomegaly (92.1%), malformation of cortical development (85.1%) and cor-tico-subcortical calcifications (80.2%) were observed in all children. Abnormalities in neuro-logical examinations were found in 97.0% of the cases, and neurophysiological findings evi-denced epileptogenic activity in 56.3% of auditory deficit in 17.3% and visual impairment in 14.1% related to this infection during pregnancy. Arthrogryposis was found in 10.8% of chil-dren. Conclusion: This group of children presented clinical and radiological criteria for CZS. High frequency of brain abnormalities and signs of early neurological disorders were found, epileptogenic activity and signs of sensorineural changes were common. This suggests that mi-crocephaly may be associated with a worse spectrum of neurological manifestations related to this infection during pregnancy.

BACKGROUND: Current research indicates that the Zika virus (ZIKV) congenital
infection can lead to cerebral palsy (CP). OBJECTIVE: To assess the gross motor
development of children at risk for ZIKV infection during gestation, over the first 2 years of
their lives. METHODS: Seventy-seven children were assessed at the median ages of 11, 18
and 24 months, using the evaluative instrument Gross Motor Function Measure (GMFM-
66). At the third assessment, the children with diagnoses of CP were classified by severity
through the Gross Motor Function Classification System (GMFCS) and the motor
development potential was estimated based on GMFM-66 scores. RESULTS: At 2 years of
age, all children had the diagnosis of CP. Seventy-four (96.1%) presented gross motor skills
similar to those of children aged 4 months or less according to the World Health
Organization’s standard. They were classified in GMFCS level V according to the median
GMFM-66 score. The majority of children was quadriplegic and GMFM-66 showed
significant change scores between 11 and 18 months (P=0.001) and between 11 and 24
months (P<0.001). No significant difference (P=0.076) was found between 18 and 24
months. CONCLUSIONS: Despite showing some gross motor development during the
initial 18 months of life, children at risk of ZIKV infection during gestation and with
diagnosis of CP experienced severe motor skill impairment and presented low GMFM-66
scores at 2 years of age. We observed a tendency of children with lower motor development
potential to reach their limit more quickly than children with higher potential.

Introduction: Leishmania (Viannia) braziliensis is the main cause of American Cutaneous Leishmaniasis (ACL) in Brazil. Corte de Pedra (CP) in Bahia L. (V.) braziliensis causes the three clinical forms of leishmaniasis: cutaneous leishmaniasis (LC), mucosal leishmaniasis (LM) and disseminated leishmaniasis (LD). Leishmanolysin, or GP63, is an important leishmania surface protease capable of hydrolyzing a wide variety of substrates both in the parasite and in the host. Its products are involved in the adhesion and internalization of these parasites in the host macrophages and have been related to the resistance of the parasite to the lysis by the complement system and the increase of the virulence of L. (V.) braziliensis. Goal. To evaluate the effects of conserved GP63 segments on the interaction of Leishmania (V.) braziliensis with host macrophages and their immunogenicity. Methods: Forty-five alleles of gp63 were identified in the endemic area for LTA of Corte de Pedra, Bahia. The conserved SRYD, PAVGNIPA, HEVAH and KAREQYGC segments of the GP63 molecule have been found to interact with the host cell. Based on the sequence of these segments, four peptides were synthesized. Macrophages from healthy donors were used in the in vitro evaluation of the ability of these peptides to stimulate the host cell and to inhibit the internalization of L. (V.) braziliensis by these cells. Macrophages were incubated with medium, peptides, Leishmania and Leishmania + peptides in parallel for 4 hours at a ratio of 2: 1 (Leishmania: macrophages). The percentage and number of amastigotes per cell was evaluated by microscopy. An enzyme-linked immunosorbent assay (ELISA) was performed to investigate antibodies in LTA patients for the conserved segments and inhibition assays for analysis of gene expression by RNAseq. Results: Stimulations with synthetic peptides with human macrophages showed that the segments inhibited the internalization of Leishmania in host cells with a p˂0.0001. The ELISA assays showed presence of antibodies against the conserved segments in all clinical forms. And the more severe forms were more associated with antibodies against the segments. Conclusion: Preserved segments of GP63 are naturally immunogenic in populations infected with L. (V.) braziliensis and synthetic peptides (PAVGNIPA, SRYD, HEMAH, and KAREQYGC) of GP63 protein; inhibit the internalization of L. (V.) braziliensis in MDM.

Introduction: The Zika virus is a flavivirus belonging to the family Flaviviridae, transmitted by Aedes mosquitoes. Its circulation was restricted to the African and Asian continents for six decades, where it caused small outbreaks with mild clinical presentations, similar to dengue. After migrating to the Pacific and the Americas, Zika virus infection became remarkable and caused major epidemics with burgeoning clinical manifestations, which required a better understanding of the changes that occurred over time. Objective: To describe the dynamics of the Zika virus from 1947 to 2018 and to analyze its prevalence in the metropolitan region of Salvador/Bahia during and up to two years after the epidemic phase. Methods: This thesis is divided into three chapters, the first presents a literature review focusing on the evidence of transmission and dispersion of the Zika virus from 1947 to 2018; the second chapter is an analysis of prevalence among various populations in the metropolitan region of Salvador/Bahia/Brazil and a retrospective analysis of cryopreserved sera from an HIV-infected population within this region. The third chapter presents the results of a new serology for the Zika virus from three subpopulations, seen in the previous chapter, carried out 1,5 to 2 years after the epidemic. Results: Since its first identification in 1947 in the Zika forest region, in Uganda, the virus has migrated to the Asian continent where it has caused mild clinical manifestations similar to dengue. Sixty years later, it reached the Pacific islands, the 

Zika virus became more aggressive and rapidly spread among local populations, which reached high prevalence rates, such as Mali (52%) and Yap Islands (73%). In addition, it was noted that the Zika virus caused devastating clinical consequences, probably due to genetic mutations occurred between 2000 and 2005. Later, in 2013, Zika reached the Americas, including the metropolitan region of Salvador, where a prevalence of 63% was recorded in the examined population. Although there were no major risk factors for the infection of the disease, a higher prevalence was observed among people from lower socioeconomic strata. Two years after the epidemic peak, the same individuals were reassessed. A significant decrease in antibody levels was observed, with up to one third of these individuals presenting negative serology, without seroconversion.
Conclusion: The expansion of the Zika virus had two phases. The first presented slow expansion, without clinical severity, and the second had rapid expansion, with serious clinical consequences, such as microcephaly, probably as a result of virus mutations. After the peak of the epidemic, some regions, including the metropolitan region of Salvador, reached a high prevalence in the population and had the transmission cycle blocked. The levels of antibodies recorded in this area declined significantly after two years and the consequences of this reduction are still unknown.

INTRODUCTION: Leishmaniasis is a stigmatizing disease, considered a serious
public health problem. It presents three classic clinical forms, among them Cutaneous
and Mucosa forms. The former affects upper and lower limbs, with ulcerated lesions,
which may be multiple or unique. Second, it reaches the upper respiratory tract, with
destructive lesions, which can affect the voice, swallowing and breathing of the
patients. OBJECTIVES: To characterize the voice and verify the vocal response to
speech therapy intervention. METHODS: The vocal emission / a: of 22 participants
from each group (total of 44 cases) was collected for the computerized analysis of the
voice through the Kay PENTAX® Real Time Spectrogram and the Multi Dimensional
Voice Program Advanced and for perceptualaudit analysis through of the RASATI
scale. RESULTS: Before the speech therapy, participants with Mucosa Leishmaniasis
had a statistically significant result, where 5 (27.7%) participants presented asthenic
vocal quality, and altered parameters of frequency measurements, frequency
disturbance, noise and sub-harmonic measurements. Of the participants with
Cutaneous Leishmaniasis, 8 (36.4%) presented grade 1 vocal instability. After the
speech therapy, patients with Cutaneous Leishmaniasis showed a reduction in the
degree of roughness and an improvement in acoustic parameters of frequency
disturbance. The group with sequelae of Leishmaniasis Mucosa presented reduction of
the measurements of sub-harmonic segments. Only the sequelae group of Cutaneous
Leishmaniasis had statistically significant results regarding spectrography, with
improvement of the following parameters: color intensity of the trace, presence of
noise, substitution of harmonics for noise, definition and regularity of harmonics,
regularity of low frequencies and the whole spectrogram and for anti-resonance. There
was no statistically significant difference in the Voice Behavior Profile.
CONCLUSION: Both groups presented vocal alterations in different degrees before
vocal therapy, and patients with Mucosal Leishmaniasis presented more severe
degrees. After speech therapy intervention, participants with Cutaneous Leishmaniasis
sequela had more vocal benefits after performing the technique, possibly because they
did not present lesions in the vocal tract.

Introduction: Co-infections interfere in disease progression. They could emerge a latent infections and accelerate a pathology, like HIV and visceral leishmaniasis co-infection, or induce protection, such as HBV and Plasmodium sp.. In this research, we evaluated the prevalence between Leishmania sp., HIV, HTLV and intestinal parasites co-infections and the co-infection influence on Tegumentary Leishmaniasis (TL). Methodology: Were followed 2102 individuals (507 countryside and 1595 urban) in an endemic area for TL and schistosomiasis (Jiquiriçá/BA). The study had three stages: First, were realized educational activities, mapping, socioeconomic and epidemiological survey, stool/blood obtaining, and Montenegro antigen skin test (MAST); Second, infections diagnosis (serology and confirmatory test) and immune profile evaluation for infected and co-infected with CBA; Third, data processing, results dispensation, monitoring of infected and carriers. Results: One (1) HIV-infected and others 6 (six) HLTV-infected were found in the study. In countryside individuals, previous diagnosed with TL (PDTL) were 35.8% and positive MAST were 34.0%. These variables correlation show that 8.2% individuals had negative PDTL and positive MAST. With these results, we sought immune response profile changes with CBA. Th1, Th2 and Th17 cytokines levels were not statistically significant. Eleven distinct gastrointestinal parasites were detected, characteristics of rural areas or areas with poor sanitation, which totaled 63.9% of participants. The highlighted intestinal parasites were Schistosoma mansoni (27.7%), Ascaris lumbricoides (17.9%) and Trichuris trichiura (14.9%). For those infected with any kind of intestinal parasites, 35.8% had co-infections (from 1 to 3 simultaneously). The major medical co-infection was TL and schistosomiasis with 9.1% of individuals. Thus, we sought immune responses profile changes in co-infected individuals with TL and schistosomiasis. The CBA showed that Th1, Th2 and Th17 cytokines levels were not statistically significant. This is a subproject of “MOLECULAR MARKERS AND COINFECTIONS IN INFECTOPARASITY DISEASES IN MAN” approved by FAPESB PRONEX 2010.

Introduction: American Cutaneous Leishmania sis (LTA) is a parasitic infectious disease caused by protozoa of the genus Leishmania and is among the endemic diseases with the greatest impact on public health due to its globalized distribution and limitations in diagnosis, treatment and control in endemic areas. Pentavalent antimonial (Sbv) administered intravenously or intramuscularly has been the drug of first choice for the treatment of the disease, with increasing reports of increased resistance to this drug at different endemic sites. In recent years, polymorphisms in genes associated with wound healing and tissue repair have been shown to be risk factors for LC caused by Leishmania braziliensis. Objective: To evaluate whether polymorphisms in genes related to lesion healing and tissue repair, previously associated with the development of LC, would also be biomarkers of the response to treatment of the disease. Methods: A case-control study was performed to test the association of single nucleotide polymorphism (SNP) markers in the FLI1, COL1A1, CTGF, IL-22 and SMAD2 genes and cure or therapeutic failure in patients from the endemic area of Corte de Pedra -BA. Participating patients were allocated as refractory to Sbv (cases) or responders to Sbv (controls). After extracting the DNA with proteinase K by the salting-out method, the SNPs were genotyped by the real time qPCR technique using TaqMan assays (ThermoFisher) and analyzed by logistic regression using the STATA™ program. In addition, complementary analysis between the SNPs and parameters of medical records such as treatment, area of the Montenegro test, size and number of lesions were performed by the program GraphPad Prism5. We also tested associations between these same parameters and response to treatment in the cohort. Results: We did not observe associations between the markers tested and cure or therapeutic failure in CL in the population-based genetic study (p >0.05). However, we observed a strong association between the COL1A1 gene (p = 0.0009) and the treatment parameter, with a majority of responders carrying genotypes containing the A allele (AA and AG), as well as an association (p = 0.0170) between the FLI1 CC genotype and the size of the lesions of the patients. In addition, in the comparison between responders and refractory patients with Sbv with different clinical parameters, we observed a strong association between the area of skin test induration (IDRM) and treatment, with the test area significantly higher in patients responding to pentavalent antimonial ( p = 0.0003). Conclusions: The COL1A1 gene is linked to the treatment response in CL by mechanisms that hypothetically involve collagen deposition at the lesion site and could help to contain the parasites and / or optimize the cicatricial process in patients responding to Sbv treatment; the FLI1 gene polymorphism, previously associated with LC, was shown to be marker of increased lesion for C allele carriers ;Patients with greater area of the Montenegro Test develop a better cellular response at the onset of the disease, which controls better the infectious process and is reflected in a better therapeutic response.

BACKGROUND: The Human T Cell Lymphotropic Virus Type 1 (HTLV-1) is the causal agent of HTLV-1 associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and it infects almost 20 million people around the world. It is well known that the urinary symptoms are associated with damage to the neurological system. However, few studies characterize the type of urologic dysfunction, its clinical course and the association with inflammatory cytokines and pro viral load. OBJECTIVE: To analyze the clinical evolution of vesical dysfunction associated with HTLV-1 infection. METHODS: HTLV-1 infected subjects were followed up since April 2011 till November 2018. The diagnosis of HTLV-1 infection was made by ELISA and confirmed with Western Blot. The patients were stratified in two groups: probable HAM/TSP and definite HAM/TSP. They were evaluated by the overactive bladder symptoms score (OABSS) and bladder diary every 6 months, and by at least two urodynamic studies over time. All patients received had anticholinergic drugs prescribed. The progression of the disease was defined by a composite model: need for additional non-conservative treatment (physiotherapy, onabotulinum toxin), loss of vesical complacency (<20cmH2O/mL), increase in more than 30% in OABSS, persistence of OABSS > 10 one year to another, presence of ureterohydronephrosis and the need for self-intermittent catheterization or permanent catheter (Foley) to promote bladder emptying. RESULTS: 175 HTLV-1 infected patients with urinary complaints were analyzed. Of these patients, 85 had definite HAM/TSP. The mean of the age of the patients was 51.4 + 11.9 years in probable HAM/TSP group and 51.2 + 12.9 years in
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definite HAM/TSP group (P>0,05). Gender, scholarship, marital status and length of follow up were not statistically different between the two groups. The main urodynamic finding was detrusor hyperactivity (63.9% in probable HAM/TSP group versus 74.1% in definite HAM/TSP group, P>0.05). After a mean follow-up of 5 years, there was a significant reduction in urgency episodes and an increase in daytime voiding, while nocturia episodes and OABSS did not vary statistically significantly over the time. The frequency of clean self-intermittent catheterization to promote bladder emptying increased from 13% to 19% over the cohort period in the definite HAM/TSP group. Regarding progression of urinary dysfunction, 40.7% of the patients in both groups had the urologic disease progressed as defined by the composite model. In a regression model, proviral load and inflammatory cytokines were not associated with urologic disease progression. CONCLUSIONS: Overactive bladder is the main clinical manifestations of urinary dysfunction in HTLV-1. It was present even in patients that did not meet the criteria for HAM/TSP. Inflammatory cytokines and proviral load were not associated with progression of urinary dysfunction. The severity of the disease is more pronounced in patients with definite HAM/TSP.

Cutaneous leishmaniasis (CL) due to infection by Leishmania braziliensis is characterized by high levels of TNF, IFN and cell infiltrate composed by macrophages, monocytes, dendritic cells, CD4+T and CD8+T cells. In addition to these cells, the metalloproteinases, with its ability to degrade extracellular matrix components, can participate in the formation of the lesion. The activity of MMPs is extremely regulated, and its action is controlled by the inhibitor TIMP. To evaluate the production of MMP-1 and MMP-3 and the effects of TNF, IL-6, IL-1β, IFN on the production of them in patients with CL. Peripheral blood mononuclear cells were obtained from healthy subjects and patients with CL to determine the frequency of CD4+, CD8+ cells and subsets of monocytes and the expression of MMPs and CD147 inducer. Cell culture was performed in the presence or absence of SLA, anti-IFN-γ, anti-TNF, anti-IL-6 and anti-IL-1β and, levels of MMP-1 and MMP-3 were determined by ELISA. Production of MMP-3 was higher in cultures stimulated with SLA from CL patients compared to healthy subjects, although no difference was observed in the production of MMP-1 between these groups. PBMC cultured from patients with CL in the presence of anti-IFN- produces more MMP-1 compared to healthy individuals and, an increase of MMP-1 and TIMP-1 in biopsies from patients with CL. After neutralization of TNF, IL-6 and IL-1β the level of MMP-1 was increased in patients with CL, however no increase of MMP-3 was observed when we neutralize those cytokines. Meanwhile, CD147 is more expressed in CD8+T cells from CL patients compared to healthy subjects. These observations suggest that these MMPs can participate in the process of tissue remodeling in lesions from patients with L. braziliensis infection.

Pneumonia is among the leading causes of childhood mortality worldwide. Bacterial pathogens are important causative agents of this disease and the identification of bacterial infection is key to pneumonia control. The diagnosis of bacterial pneumonia is challenging in children and serological assays have been playing an important role in the identification of bacterial infection in childhood pneumonia in epidemiological studies. Although broadly used, these tests are not fully validated and there are factors related to the child immunity and to the assay itself that need further clarification.
We evaluated if combining different numbers of pneumococcal antigens on the serological assay, pre-existing antibody levels, sampling interval, age, and duration of illness influenced the detection of antibody responses against protein antigens from Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in children with pneumonia. We found that serological assays using combinations of different pneumococcal proteins detect a higher rate of antibody responses against S. pneumoniae compared to assays using a single pneumococcal protein. We also found that pre-existing antibody levels and sampling interval influence the detection of antibody responses against pneumococcal and H. influenzae proteins by serological assays.
We then investigated the natural development during the first 13 years of life of antibodies against proteins from S. pneumoniae, H. influenzae, and M. catarrhalis in a cohort of healthy children. We demonstrated that the maturation of immune responses against different pneumococcal proteins shares similarities, especially among CbpA, PcpA, and PhtD. Also, it was shown that antibody production against H. influenzae and M. catarrhalis proteins starts early in life and reaches peak levels earlier than antibody production against the pneumococcal proteins.
We evaluated the seasonal distribution and the association of meteorological factors with the frequency of infection caused by S. pneumoniae, H. influenzae, and M. catarrhalis in children with pneumonia in a tropical region. We showed that M. catarrhalis pneumonia is more frequent during fall-winter and that the frequency of M. catarrhalis pneumonia is positively associated with relative humidity and negatively associated with air temperature and sunshine.
Finally, we compared the results of serological assays using pneumococcal proteins, C-polysaccharide, or pneumococcal capsular polysaccharides for the investigation of pneumococcal infection in children hospitalized with pneumonia. We showed that the serological assay using pneumococcal proteins are more sensitive for the detection of pneumococcal infection than assays using pneumococcal polysaccharides.
In conclusion, serological assays using protein antigens are suitable diagnostic methods for the investigation of infection caused by S. pneumoniae, H. influenzae, or M. catarrhalis in children with pneumonia.

Sand fly
saliva contains a variety of pharmacologic agents, such as anticoagulants, vasodilators,
immunomodulatory and anti-inflammatory molecules. Differently from others parasite/vectors
interactions, prior immunization with the Lu. intermedia saliva, the main vector of Leishmania
braziliensis in Brazil, enhancement Leishmania infection. In addition, patients with active ulcers
displayed higher levels of anti-Lu. intermedia saliva antibodies when compared with individuals
with sub-clinical L. braziliensis infection, suggesting that exposure to sand flies saliva influences
the outcome of L. braziliensis infection. In the first part of the present study we characterize the
immune response against Lu. intermedia salivary proteins in residents of L. braziliensis
transmission area. Participants in the present study included 264 individuals living in Corte de
Pedra, Bahia, and were evaluated regarding humoral and cellular immune response to Lu.
intermedia saliva. Anti-Lu. intermedia saliva antibodies were found in 150 (56.8%) subjects and
a positive serology was associated with home arrival after 16 pm (p=0.01). Moreover, there was
a predominance of IgG1 and IgG4 Immunoglobulin subclass in sera. Individuals with positive
serology to Lu. intermedia saliva displayed higher concentrations of IL-10, IL-13 and IFN-γ
compared to controls whereas TNF levels were similar in both groups. In addition, subjects with
positive serology to Lu. intermedia saliva also displayed high levels CXCL9 and CCL2 than
controls. Furthermore, the main sources of IL-10-secreting cells were CD4+, including CD25+
and Foxp3+ subsets and the neutralization of IL-10 in vitro was able to reverse the increased
parasite load in macrophages induced by saliva. In the second part of the study, we identified the
salivary proteins that act as vector exposure makers in residents from an endemic area. For this,
we produced the most abundant proteins and evaluated the seroconversion in residents from a
CL endemic area. We found a strong correlation among antibodies against LinB-13 and IgG to
total saliva. By evaluating a cohort of households contacts of patients with active disease, we
confirmed that LinB-13 is a marker of exposure to Lu. intermedia. Moreover, we showed a
dissociation between humoral response to LinB-13 and DTH to Leishmania. Finally, the
presence of antibodies anti-LinB-13 is a risk factor for cutaneous leishmaniasis (CL)
development, confirming our previous results that showed an increased risk of CL development
after natural exposure to Lu. intermedia saliva. The exposure to Lu. intermedia saliva modulates
an immune response of exposed subjects, facilitating parasite survival in vitro, and increasing
the risk of developing disease.