Diagnosis of cystic fibrosis: a high heterogeneity of symptoms and genotypes in a Brazil population.

INTRODUCTION: In highly multiracial populations with inadequate newborn screening, knowledge of the various phenotypic presentations of Cystic Fibrosis (CF) can help reach an early diagnosis. This study aims to describe phenotypes and genotypes at the time of CF diagnosis in a state in the Northeast Region of Brazil. METHODS: Retrospective cross-sectional study. Clinical data were extracted from the medical records of CF patients. Clinical, laboratory, and genotypic characteristics were described for patients admitted to a tertiary referral center between 2007 and 2021. RESULTS: Fifty-eight (58) patients were included in the study, 53.5% of whom were diagnosed through clinical suspicion. The median age at diagnosis was 4.7 months (IQR: 1.5-14.8 months). Five patients had false-negative results in the newborn screening. Faltering growth was the most frequent clinical manifestation. Bronchiectasis and a history of pneumonia predominated in those older than ten, while thinness, underweight, and electrolyte imbalances were more frequent in children under two. Sequencing of the CFTR gene identified 27 genotypes, with at least one class I-III variant in all patients, and nine variants that are rare, previously undescribed, or have uncertain significance (619delA, T12991, K162Q, 3195del6, 1678del > T, 124del123bp, 3121-3113 A > T). The most frequent alleles were p.Phe508del, p.Gly542*, p.Arg334Trp, and p.Ser549Arg. CONCLUSIONS: Malnutrition and electrolyte imbalances were the most frequent phenotypes for children < 2 years and were associated with genotypes including 2 class I-III variants. Rare and previously undescribed variants were identified. The p.Gly542*, p.Arg334Trp, and p.Ser549Arg alleles were among the most frequent variants in this population.

Whey Protein, Vitamins C and E Decrease Interleukin-10 in Chronic Hemodialysis Patients: A Pioneer, Randomized, Double-Blind Pilot Trial.

OBJECTIVE: To evaluate the effects of supplementation with whey protein combined with vitamins C and E on inflammatory markers in hemodialysis (HD) patients. DESIGN AND METHODS: This was a pioneer, randomized and double-blinded study. Patients were randomized into two groups and stratified by HD frequency. The supplementation group received 20 g of whey protein, 250 mg of vitamin C, and 600 IU of vitamin E; the placebo group, 20 g of rice flour, and microcrystalline cellulose capsules. The interventions were given after HD, 3 times a week, for 8 weeks. The inflammatory markers were assessed: interleukin (IL) IL-12p70, IL-10, IL-6, IL-8, and tumor necrosis factor alpha. For statistical analysis, the χ2 test, Student's t-test, Mann-Whitney test, analysis of variance for repeated two-way measurements, paired t test, and Wilcoxon test were performed. P < .05 was considered statistically significant. RESULTS: Twenty-three patients completed the study. No significant differences were found in inflammatory markers when comparing the groups postintervention. In the intragroup was a decrease in IL-10 in the supplementation group after 8 weeks (P = .0382). IL-6 tended to decrease by 810.95% in the supplementation group and increased by 732.8% (nonsignificant) in the placebo group. CONCLUSION: Whey protein combined with vitamins C and E significantly reduced IL-10 in the supplementation group and could be beneficial to reduce IL-6 in HD patients. Future studies are suggested with a larger sample size, different supplementation doses, and longer interventions.

COVID-19 recurrence is related to disease-early profile T cells while detection of anti-S1 IgG is related to multifunctional T cells.

COVID-19 is caused by SARS-CoV-2 infection and leads from asymptomatic to severe outcomes. The recurrence of the COVID-19 has been described, however, mechanisms involved remains unclear. Thus, the work aimed to investigate the role of multifunctional T cells in patients with recurrent COVID-19. We evaluated clinical characteristics, presence of anti-S1 and anti-Nucleocapsid IgG in patients' sera, and multifunctional T cells (for IFN-γ, IL-2, and TNF-α) in patients with multiple episodes of COVID-19 and controls. Data demonstrate that patients with recurrent COVID-19 have a T cell pattern predominantly related to IFN-γ production. Also, patients with COVID-19 history and absence of anti-S1 IgG had lower levels of CD4+ IFN + IL-2 + TNF + T cells independently of number of disease episodes. Complementary, vaccination changed the patterns of T cells phenotypes and induced IgG seroconversion, despite not induce higher levels of multifunctional T cells in all patients. In conclusion, the data suggest that recurrent disease is related to early-disease T cell profile and absence of anti-S1 IgG is related to lower multifunctional CD4 T cell response, what suggests possibility of new episodes of COVID-19 in these patients.

Sexual assault and vulnerability to sexually transmitted infections among homeless Brazilian women: a cross sectional qualitative study.

BACKGROUND: Homeless women have complex life conditions and are often exposed to violence, sexual exploitation, rape, prostitution, reproductive disorders, survival sex trading, unintended pregnancies and sexually transmitted infections (STIs). The aim was to explore the existence of sexual aggression and vulnerability to STIs among homeless Brazilian women. METHODS: Fifteen interviews were conducted with homeless women who were admitted to a women's shelter in a large city in Brazil. Data were collected through semi-structured interviews, audiorecorded and complemented with notes of the researcher in field diary, subjected to inductive thematic analysis and analyzed in light of the social relations of gender. RESULTS: Two themes were constructed: "Being a woman on the streets: a look at gender inequalities" and "Pain and the raped body: the scars of homeless women". The transgression of women's rights was observed with reports of sexual abuse interspersed with physical violence. Unprotected sexual practices were part of the daily lives of these women, with repercussions for their exposure to sexually transmitted infections. Dependence on psychoactive substances was mentioned, and transactional sex was used as a source of income to maintain such dependence, as well as to promote the women's livelihood. CONCLUSION: Homeless women experience complex situations on the streets involving exposure to different types of violence, the use of transactional sex as a survival strategy and unprotected sexual practices. Furthermore, the way in which women have been exposed to sexual assault and their coping mechanisms to those require attention. Interventions are need to improve the healthcare assistance of homeless women victims of sexual assault, considering the vulnerability of this population.

Offerings and User Demands of eHealth Services in Spain: National Survey.

BACKGROUND: The accelerated development of information and communication technologies has made health care one of the pioneering fields in the incorporation of these tools. As new technologies have been applied, existing technologies have been sophisticated and improved and the concept of eHealth has expanded. However, these advances and expansion of eHealth do not seem to have served to adapt the supply of services to users' demands; rather, supply seems to be governed by other variables. OBJECTIVE: The main objective of this work was to review the existing differences between user demands and the supply of eHealth services in Spain and their causes. The aim is to provide information on the level of use of the services and the causes of the variation in demand for these services, which can be useful in correcting existing differences and adapting them to the needs of users. METHODS: A survey, "Use and Attitudes Toward eHealth in Spain," was applied by telephone to a sample of 1695 people aged 18 years and over, taking into account sociodemographic profile characteristics (sex, age, habitat, educational level). The confidence level was set at 95% and the margin of error was ±2.45 for the whole sample. RESULTS: The survey results showed that the online doctor's appointment service is the most frequently used eHealth service by users: 72.48% of respondents used this service at some point and 21.28% stated that they use it regularly. The other services showed significantly lower percentages of use, including "managing health cards" (28.04%), "consulting medical history" (20.37%), "managing test results" (20.22%), "communicating with health professionals" (17.80%), and "requesting a change of doctor" (13.76%). Despite this low usage, a large majority of respondents (80.00%) attach great importance to all the services offered. Overall, 16.52% of the users surveyed were willing to make new service requests to the regional websites, with 9.33% of them highlighting services such as "the availability of a complaints and claims mailbox," "the possibility of consulting medical records," and "the availability of more detailed information on medical centers (location, medical directory, waiting lists, etc)." Other outstanding requests (8.00%) were to simplify the procedures for using certain existing services. CONCLUSIONS: The data from the survey show that eHealth services are widely known and highly valued by users, but not all services are used with the same frequency or intensity. It appears that users find it difficult to suggest new services that might be useful to them in terms of demand for new services that do not currently exist. It would be useful to use qualitative studies to gain a deeper understanding of currently unmet needs and the possibilities of eHealth. The lack of access to and use of these services and the unmet needs particularly affect more vulnerable populations who have the greatest difficulty in meeting their needs through alternative means to eHealth.

Effects of a Novel Infant Formula on the Fecal Microbiota in the First Six Months of Life: The INNOVA 2020 Study.

Exclusive breastfeeding is highly recommended for infants for at least the first six months of life. However, for some mothers, it may be difficult or even impossible to do so. This can lead to disturbances in the gut microbiota, which in turn may be related to a higher incidence of acute infectious diseases. Here, we aimed to evaluate whether a novel starting formula versus a standard formula provides a gut microbiota composition more similar to that of breastfed infants in the first 6 months of life. Two hundred and ten infants (70/group) were enrolled in the study and completed the intervention until 12 months of age. For the intervention period, infants were divided into three groups: Group 1 received formula 1 (INN) with a lower amount of protein, a proportion of casein to whey protein ratio of about 70/30 by increasing the content of α-lactalbumin, and with double the amount of docosahexaenoic acid/arachidonic acid than the standard formula; INN also contained a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis). Group 2 received the standard formula (STD) and the third group was exclusively breastfed (BF) for exploratory analysis. During the study, visits were made at 21 days, 2, 4, and 6 months of age, with ±3 days for the visit at 21 days of age, ±1 week for the visit at 2 months, and ±2 weeks for the others. Here, we reveal how consuming the INN formula promotes a similar gut microbiota composition to those infants that were breastfed in terms of richness and diversity, genera, such as Bacteroides, Bifidobacterium, Clostridium, and Lactobacillus, and calprotectin and short-chain fatty acid levels at 21 days, 2 and 6 months. Furthermore, we observed that the major bacteria metabolic pathways were more alike between the INN formula and BF groups compared to the STD formula group. Therefore, we assume that consumption of the novel INN formula might improve gut microbiota composition, promoting a healthier intestinal microbiota more similar to that of an infant who receives exclusively human milk.

Innova 2020: A Follow-Up Study of the Fecal Microbiota of Infants Using a Novel Infant Formula between 6 Months and 12 Months of Age.

The World Health Organization recommends exclusive breastfeeding on demand until at least the sixth month of life. Breast milk or infant formula is the infant's primary food source until the age of one year, followed by the gradual introduction of other foods. During weaning, the intestinal microbiota evolves to a profile close to that of the adult, and its disruption can result in an increased incidence of acute infectious diseases. We aimed to determine whether a novel starting formula (INN) provides gut microbiota compositions more similar to those of breastfed (BF) infants from 6 to 12 months of age compared to a standard formula (STD). This study included 210 infants (70 per group) who completed the intervention until they reached the age of 12 months. In the intervention period, infants were divided into three groups. Group 1 received an INN formula with a lower protein content, a casein to whey protein ratio of approximately 70/30, twice as much docosahexaenoic acid as the STD formula, a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis, BPL1TM HT), and twice as much arachidonic acid as the STD formula contained. The second group received the STD formula, while the third group was exclusively BF for exploratory purposes. In the course of the study, visits were conducted at 6 months and 12 months of age. Compared to the BF and STD groups, the Bacillota phylum levels in the INN group were significantly reduced after 6 months. At the end of 6 months, the alpha diversity indices of the BF and INN groups differed significantly from those of the STD group. At 12 months, the Verrucomicrobiota phylum levels in the STD group were significantly lower than those in the BF and INN groups. Based on the comparison between 6 and 12 months, the Bacteroidota phylum levels in the BF group were significantly higher than those in the INN and STD groups. When comparing the INN group with the BF and STD groups, Clostridium sensu stricto 1 was significantly higher in the INN group. The STD group had higher levels of calprotectin than the INN and BF groups at 6 months. The immunoglobulin A levels in the STD group were significantly lower than those in the INN and BF groups after 6 months. Both formulas had significantly higher levels of propionic acid than the BF group at 6 months. At 6 months, the STD group showed a higher quantification of all metabolic pathways than the BF group. The INN formula group exhibited similar behavior to the BF group, except for the superpathway of phospholipid biosynthesis (E. coli). We hypothesize that the novel INN formula may promote an intestinal microbiota that is more similar to the microbiota of an infant who consumes only human milk before the weaning period.

Ergot Alkaloids on Cereals and Seeds: Analytical Methods, Occurrence, and Future Perspectives.

Ergot alkaloids are secondary metabolites resulting from fungi of the genus Claviceps that have proven to be highly toxic. These mycotoxins commonly infect cereal crops such as wheat, rye, barley, and oats. Due to the increase worldwide consumption of cereal and cereal-based products, the presence of ergot alkaloids in food presents a concern for human safety. For this reason, it is essential to develop several analytical methods that allow the detection of these toxic compounds. This review compiles and discusses the most relevant studies and methods used in the detection and quantification of ergot alkaloids. Moreover, the decontamination techniques are also addressed, with special attention to sorting, cleaning, frying, baking, peeling, and ammonization methods, as they are the only ones already applied to ergot alkaloids.

Prevalence and Medication Treatment of Opioid Use Disorder Among Primary Care Patients with Hepatitis C and HIV.

BACKGROUND: Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. OBJECTIVE: To describe the prevalence of documented OUD, as well as receipt of office-based medication treatment, among primary care patients with HCV or HIV. DESIGN: Retrospective observational cohort study using electronic health record and insurance data. PARTICIPANTS: Adults ≥ 18 years with ≥ 2 visits to primary care during the study (2014-2016) at 6 healthcare systems across five states (CO, CA, OR, WA, and MN). MAIN MEASURES: The primary outcome was the diagnosis of OUD; the secondary outcome was OUD treatment with buprenorphine or oral/injectable naltrexone. Prevalence of OUD and OUD treatment was calculated across four groups: HCV only; HIV only; HCV and HIV; and neither HCV nor HIV. In addition, adjusted odds ratios (AOR) of OUD treatment associated with HCV and HIV (separately) were estimated, adjusting for age, gender, race/ethnicity, and site. KEY RESULTS: The sample included 1,368,604 persons, of whom 10,042 had HCV, 5821 HIV, and 422 both. The prevalence of diagnosed OUD varied across groups: 11.9% (95% CI: 11.3%, 12.5%) for those with HCV; 1.6% (1.3%, 2.0%) for those with HIV; 8.8% (6.2%, 11.9%) for those with both; and 0.92% (0.91%, 0.94%) among those with neither. Among those with diagnosed OUD, the prevalence of OUD medication treatment was 20.9%, 16.0%, 10.8%, and 22.3%, for those with HCV, HIV, both, and neither, respectively. HCV was not associated with OUD treatment (AOR = 1.03; 0.88, 1.21), whereas patients with HIV had a lower probability of OUD treatment (AOR = 0.43; 0.26, 0.72). CONCLUSIONS: Among patients receiving primary care, those diagnosed with HCV and HIV were more likely to have documented OUD than those without. Patients with HIV were less likely to have documented medication treatment for OUD.

Exercise Training in Patients With Heart Failure With Preserved Ejection Fraction: A Community Hospital Pilot Study.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) experience poor exercise tolerance and quality of life. Little is known about the feasibility or effects of HFpEF exercise training (ET) in a community hospital setting. OBJECTIVE: The aim of this study was to examine the feasibility and pilot data of a community-based HFpEF ET intervention. METHODS: This was a single-group (n = 16), pretest-posttest, 9-week ET intervention. The Minnesota Living With Heart Failure Questionnaire, Patient Health Questionnaire-9, cardiopulmonary exercise test (peak VO2), and 6-minute walk test were used for evaluation. RESULTS: Participants (n = 16) attended 88% of prescribed ET sessions and 94% completed all pretest-posttest assessments. Significant improvements in Minnesota Living With Heart Failure Questionnaire (P = .01), Patient Health Questionnaire-9 (P ≤ .01), exercise test time (P = .01) and 6-minute walk test (P = .001), but not in peak VO2 (P = .16), were found. CONCLUSIONS: The ET intervention was feasible and safe, and findings support improved quality of life, depressive symptoms, and exercise tolerance. Larger controlled trials are warranted.

Reducing childhood malnutrition in Bangladesh: the importance of addressing socio-economic inequalities.

OBJECTIVE: To obtain projections of the prevalence of childhood malnutrition indicators up to 2030 and to analyse the changes of wealth-based inequality in malnutrition indicators and the degree of contribution of socio-economic determinants to the inequities in malnutrition indicators in Bangladesh. Additionally, to identify the risk factors of childhood malnutrition. DESIGN: Cross-sectional study. A Bayesian linear regression model was used to estimate trends and projections of malnutrition. For equity analysis, slope index, relative index and decomposition in concentration index were used. Multilevel logistic models were used to identify risk factors of malnutrition. SETTING: Household surveys in Bangladesh from 1996 to 2014. PARTICIPANTS: Children under the age of 5 years. RESULTS: A decreasing trend was observed for all malnutrition indices. In 1990, predicted prevalence of stunting, wasting and underweight was 55·0, 15·9 and 61·8 %, respectively. By 2030, prevalence is projected to reduce to 28·8 % for stunting, 12·3 % for wasting and 17·4 % for underweight. Prevalence of stunting, wasting and underweight were 34·3, 6·9 and 32·8 percentage points lower in the richest households than the poorest households. Contribution of the wealth index to child malnutrition increased over time and the largest contribution of pro-poor inequity was explained by wealth index. Being an underweight mother, parents with a lower level of education and poorer households were the key risk factors for stunting and underweight. CONCLUSIONS: Our findings show an evidence-based need for targeted interventions to improve education and household income-generating activities among poor households to reduce inequalities and reduce the burden of child malnutrition in Bangladesh.

Time trends and social security burden of temporary work disability due to chronic venous disease in Brazil.

BACKGROUND: Chronic venous disease (CVD) and disability are worldwide problems and have significant socioeconomic implications. This study aims to analyze the time trends and social security burden of temporary work disability due to CVD in Brazil. METHODS: An ecological time series study using the Brazilian Social Security System database was performed from 2005 to 2014. Data from all benefits granted to workers with temporary disability due to CVD were analyzed. The cases were identified using diagnosis codes I83-I83.9 of the International Classification of Diseases 10th Revision (ICD-10). The time trend analyses were performed by the Joinpoint Regression Model, with sex, age, regions, income, and category of affiliation as variables. Crude and age-standardized rates were calculated. RESULTS: A total of 429,438 benefits were granted for temporary work disability due to CVD from 2005 to 2014, with a growing trend and an age-standardized annual percent change (APC) of 3.4 (95% CI: 2.6-4.2) (p < 0.05). Social security expense increased 3.5-fold, and the number of days in benefit doubled from 2005 to 2014. In total, 27,017,818 working days were lost. The average duration of benefits was 55.3 days. The majority of workers were women (68.2%) (p < 0.001), between 30 and 59 years old, employed, had a monthly income ≤2 minimum wages (MW) (83.2%), and lived in the regions southeast (53.6%) and south (29.3%). Significantly higher APCs were observed for women than for men (APC: 4.9, 95% CI: 4.0-5.7 versus APC: 1.2, 95% CI: 0.1-2.4). All regions in Brazil had a significant growing trend, except in the north. No significant growth was observed in the age group of 60-69 years. A decreasing trend was observed in workers with monthly incomes above 2 MW (p < 0.05). CONCLUSIONS: Temporary work disability due to CVD and social security burden showed increasing trends with millions of working days lost, particularly among women and low-income workers. Preventing disability is challenging, and public policies are needed to reduce the social and economic impact of disability. Therefore, measures for promoting health at the workplace should be encouraged.

Nursing case management for people with hypertension in primary health care: A randomized controlled trial.

INTRODUCTION: Hypertension is a chronic disease that requires continuous and long-term care to prevent or delay the development of associated complications. Although various interventions for hypertension exist, case management in Brazil's primary healthcare is understudied. We examined nursing case management effectiveness for controlling blood pressure among Brazilian adults with hypertension in the public healthcare system. METHOD: A randomized controlled trial with a 12-month follow-up was conducted at a primary healthcare clinic in southern Brazil. Adult patients with hypertension were randomly allocated to intervention (n = 47) and usual care groups (n = 47). The nursing case management model includes nursing consultations, telephone contact, home visits, health education, and appropriate referrals. Patient outcomes (blood pressure, body mass index, waist circumference, quality of life, treatment adherence) were assessed at baseline and 6- and 12-month follow-up for the intervention group and at baseline and 12-month follow-up for the usual care group. Data were collected from only the intervention group at T6 to avoid contact between the researcher and the usual care group, and to check the care plan and modify it if necessary. RESULTS: After the intervention, the intervention group's blood pressure decreased significantly compared to the usual care group. The differences in systolic and diastolic blood pressure between the groups was -8.3 (intervention)/1.1 (usual care) mmHg (p = .004) and -7.4/-0.6 mmHg (p = .007), respectively. The intervention group had significantly greater improvement in waist circumference (-2.0/1.2 cm), body mass index (- 0.4/0.3), and treatment adherence (4.8/-1.1) than the usual care group (all p < .05). CONCLUSION: Nursing case management in primary healthcare may be effective for improving outcomes among patients with hypertension.

Association Between Zika Virus Microcephaly in Newborns With the rs3775291 Variant in Toll-Like Receptor 3 and rs1799964 Variant at Tumor Necrosis Factor-α Gene.

Congenital Zika syndrome (CZS) is a cluster of malformation, and the mechanisms that lead it are still unclear. Using hypothesis-driven candidate genes and their function in viral infections, single-nucleotide polymorphisms (SNPs) were genotyped by quantitative polymerase chain reaction in a sample population from Sergipe State, Brazil. This study shows that rs3775291 SNP at Toll-like receptor 3, which triggers type I interferon antiviral responses in mothers infected by Zika virus during pregnancy, is associated with CZS occurrence (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.158-4.148). Moreover, rs1799964 SNP at tumor necrosis factor-α gene in CZS babies is associated with severe microcephaly (OR, 2.63; 95% CI, 1.13-6.21).

Non-Leishmania Parasite in Fatal Visceral Leishmaniasis-Like Disease, Brazil.

Through whole-genome sequencing analysis, we identified non-Leishmania parasites isolated from a man with a fatal visceral leishmaniasis-like illness in Brazil. The parasites infected mice and reproduced the patient's clinical manifestations. Molecular epidemiologic studies are needed to ascertain whether a new infectious disease is emerging that can be confused with leishmaniasis.

Regional Overview on Maternal Nutrition and Examples of Health System Programme and Policy Responses: Asia and the Pacific.

BACKGROUND: The double burden of malnutrition in Asia and the Pacific is driving a renewed focus on maternal malnutrition. SUMMARY: Though adverse consequences of maternal malnutrition have been long recognized, there is slow progress in addressing nutritional problems of women/adolescent girls. Coverage and quality of current maternal nutrition interventions, mostly delivered through antenatal care programmes vary across countries, and are often sub-optimum. Further, despite a marked increase in overweight and obesity in women of reproductive age, at present, most programmes are focused on under-nutrition and micronutrient deficiencies. Key Messages: The recent antenatal care recommendations released by World Health Organization provide a benchmark for countries to evaluate their programmes and identify gaps and challenges to improving maternal nutrition. Asian and Pacific countries need to address all forms of maternal malnutrition. For countries that historically focused on maternal under-nutrition, expanding their programmes to incorporate interventions to address overweight and obesity will be challenging. Innovative methods for nutrition counselling, both in terms of content and using novel channels of communication, are needed. Protocols and guidance on managing excessive weight gain as well as determining appropriate pregnancy weight gains are needed, while managing micronutrient deficiencies, particularly in settings where inherited disorders of red blood cells exist.

Measles outbreak: preliminary report on a case series of the first 8,070 suspected cases, Manaus, Amazonas state, Brazil, February to November 2018.

We report an ongoing measles outbreak in Manaus, Amazonas state, Brazil. As at 3 November 2018, 1,631 cases were confirmed corresponding to an incidence of 75.3 per 100,000 inhabitants; all five sanitary districts presented confirmed cases. Reintroduction of measles virus in Manaus is likely related to the current outbreak in Venezuela and due to recent decline in measles vaccine coverage. Given the current scenario, prevention and control measures should target individuals aged 15-29 years.

Perceptions of health managers and professionals about mental health and primary care integration in Rio de Janeiro: a mixed methods study.

BACKGROUND: Community-based primary mental health care is recommended in low and middle-income countries. The Brazilian Health System has been restructuring primary care by expanding its Family Health Strategy. Due to mental health problems, psychosocial vulnerability and accessibility, Matrix Support teams are being set up to broaden the professional scope of primary care. This paper aims to analyse the perceptions of health professionals and managers about the integration of primary care and mental health. METHOD: In this mixed-method study 18 health managers and 24 professionals were interviewed from different primary and mental health care services in Rio de Janeiro. A semi-structured survey was conducted with 185 closed questions ranging from 1 to 5 and one open-ended question, to evaluate: access, gateway, trust, family focus, primary mental health interventions, mental health records, mental health problems, team collaboration, integration with community resources and primary mental health education. Two comparisons were made: health managers and professionals' (Mann-Whitney non-parametric test) and health managers' perceptions (Kruskall-Wallis non parametric-test) in 4 service designs (General Traditional Outpatients, Mental Health Specialised Outpatients, Psychosocial Community Centre and Family Health Strategy)(SPSS version 17.0). Qualitative data were subjected to Framework Analysis. RESULTS: Firstly, health managers and professionals' perceptions converged in all components, except the health record system. Secondly, managers' perceptions in traditional services contrasted with managers' perceptions in community-based services in components such as mental health interventions and team collaboration, and converged in gateway, trust, record system and primary mental health education. Qualitative data revealed an acceptance of mental health and primary care integration, but a lack of communication between institutions. The Mixed Method demonstrated that interviewees consider mental health and primary care integration as a requirement of the system, while their perceptions and the model of work produced by the institutional culture are inextricably linked. CONCLUSION: There is a gap between health managers' and professionals' understanding of community-based primary mental health care. The integration of different processes of work entails both rethinking workforce actions and institutional support to help make changes.

Cross-resistance of Leishmania infantum isolates to nitric oxide from patients refractory to antimony treatment, and greater tolerance to antileishmanial responses by macrophages.

Visceral leishmaniasis is a life-threatening disease characterized by intense parasitism of the spleen, liver, and bone marrow. Antimonials have served as front-line antileishmanial therapeutics for decades, but the increasing failure rates under antimonial treatment have challenged the continued use of these drugs. Pentavalent antimonials are known to reinforce the killing mechanisms of macrophages, although the associated mechanism remains unclear. Here, for the first time, we determined whether Leishmania infantum strains isolated from patients refractory to antimony treatment (relapse cases) were cross-resistant to antimonials, liposomal amphotericin B, and/or nitric oxide, and also whether these strains modulate macrophage infection. We selected four clinical isolates from relapse cases and two clinical isolates from antimony-responsive patients (control group) for the present study. The L. infantum promastigotes from all four relapse cases were resistant to trivalent antimonial treatment and nitric oxide, while only one isolate was resistant to liposomal amphotericin B. We evaluated whether the resistant strains from relapse cases showed enhanced infectivity and amastigote survival in macrophages, or macrophage-killing mechanisms in macrophages activated by lipopolysaccharide plus interferon gamma. Infection indexes calculated using macrophages infected with isolates from relapse were higher than those observed with control strains that were stimulated independently. Macrophage infection was higher with L. infantum isolates from relapse cases and correlated with enhanced interleukin 1-ß production but showed similar nitrite production. Our results demonstrate that L. infantum field isolates from relapse cases were resistant to antimonials and nitric oxide and that these parasites stimulated inflammatory cytokines and were resistant to macrophage-killing mechanisms, factors that may contribute to disease severity.