Association of CD209 (DC-SIGN) rs735240 SNV with paucibacillary leprosy in the Brazilian population and its functional effects.

BACKGROUND: Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M. leprae involves the DC-SIGN receptor, which is present on the dendritic cells (DCs) and participates in immune activation. OBJECTIVES: To evaluate the association of polymorphisms in the promoter region of the gene encoding DC-SIGN (CD209) and the clinical form of leprosy, and to investigate its functional effects. METHODS: The study population included 406 leprosy patients from an endemic area in Brazil [310 multibacillary (MB); 96 paucibacillary (PB)]. A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed. RESULTS: The GA genotype and the presence of the A allele of rs735240 (-939G>A) were associated with PB leprosy [OR: 2.09 (1.18-3.69) and 1.84 (1.07-3.14), respectively]. Carriers of the A allele showed reduced expression of CD209 and TGF-ß1 in leprosy lesions in comparison with individuals with GG genotype, in addition to a higher response to the Mitsuda test. CONCLUSION: These data suggest that rs735240 influences the immune response against M. leprae and clinical presentation of leprosy.

Polymorphisms in the TGFB1 and IL2RA genes are associated with clinical forms of leprosy in Brazilian population.

BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae, and compromises the skin and peripheral nerves. This disease has been classified as multibacillary (MB) or paucibacillary (PB) depending on the host immune response. Genetic epidemiology studies in leprosy have shown the influence of human genetic components on the disease outcomes. OBJECTIVES We conducted an association study for IL2RA and TGFB1 genes with clinical forms of leprosy based on two case-control samples. These genes encode important molecules for the immunosuppressive activity of Treg cells and present differential expressions according to the clinical forms of leprosy. Furthermore, IL2RA is a positional candidate gene because it is located near the 10p13 chromosome region, presenting a linkage peak for PB leprosy. METHODS A total of 885 leprosy cases were included in the study; 406 cases from Rondonópolis County (start population), a hyperendemic region for leprosy in Brazil, and 479 cases from São Paulo state (replication population), which has lower epidemiological indexes for the disease. We tested 11 polymorphisms in the IL2RA gene and the missense variant rs1800470 in the TGFB1 gene. FINDINGS The AA genotype of rs2386841 in IL2RA was associated with the PB form in the start population. The AA genotype of rs1800470 in TGFB1 was associated with the MB form in the start population, and this association was confirmed for the replication population. MAIN CONCLUSIONS We demonstrated, for the first time, an association data with the PB form for a gene located on chromosome 10. In addition, we reported the association of TGFB1 gene with the MB form. Our results place these genes as candidates for validation and replication studies in leprosy polarisation.

Amniotic Fluid-Soluble Form of Triggering Receptors Expressed on Myeloid Cells: A Physiologic Constituent at Term.

BACKGROUND: Triggering receptors expressed on myeloid cells-1 (TREM-1) are innate immune receptors that mediate inflammatory response. In recent times, the role of these receptors has become the focus of several studies in the gestational context. Evaluation of soluble TREM-1 concentration in normal pregnancy is scarce, and no data are available on the levels of this receptor in the last weeks of normal pregnancy. METHOD: Amniotic fluid (AF) samples were obtained from 77 patients in the last weeks of normal pregnancy during cesarean section, and the soluble form of TREM-1 (sTREM-1) levels determined using specific sandwich enzyme-linked immunosorbent assay kit. RESULTS: sTREM-1 was detectable in all AF samples, and its levels did not vary in the last weeks of third trimester pregnancy. There was no correlation between sTREM-1 levels in AF and advancing gestational age. CONCLUSION: sTREM-1 is a physiologic constituent of AF and its levels are not temporally regulated in pregnancies at term.

Accountable care organizations: financial advantages of larger hospital organizations.

Accountable care organizations (ACOs) are groups of providers who agree to accept the responsibility for elevating the health status of a defined group of patients, with the goal of enabling people to take charge of their health and enroll in shared decision making with providers. The large initial investment required (estimated at $1.8 million) to develop an ACO implies that the participation of large health care organizations, especially hospitals and health systems, is required for success. Findings of this study suggest that ACOs based in a larger hospital organization are more likely to meet Centers for Medicare and Medicaid Services criteria for formation because of financial and structural assets of those entities.

Brazilians have different views on when abortion should be legal, but most do not agree with imprisoning women for abortion.

Unsafe abortions remain a major public health problem in countries with very restrictive abortion laws. In Brazil, parliamentarians - who have the power to change the law - are influenced by "public opinion", often obtained through surveys and opinion polls. This paper presents the findings from two studies. One was carried out in February-December 2010 among 1,660 public servants and the other in February-July 2011 with 874 medical students from three medical schools, both in São Paulo State, Brazil. Both groups of respondents were asked two sets of questions to obtain their opinion about abortion: 1) under which circumstances abortion should be permitted by law, and 2) whether or not women in general and women they knew who had had an abortion should be punished with prison, as Brazilian law mandates. The differences in their answers were enormous: the majority of respondents were against putting women who have had abortions in prison. Almost 60% of civil servants and 25% of medical students knew at least one woman who had had an illegal abortion; 85% of medical students and 83% of civil servants thought this person(s) should not be jailed. Brazilian parliamentarians who are currently reviewing a reform in the Penal Code need to have this information urgently.

Estimation of preterm birth rate, associated factors and maternal morbidity from a demographic and health survey in Brazil.

To determine the prevalence of preterm birth from self-reports by Brazilian women, to assess complications, interventions and outcomes, to identify factors associated with preterm birth, and to improve the preterm birth rates estimates. This is a secondary analysis of data from a Demographic Health Survey. It interviewed a sample of 4,743 Brazilian women who had 6,113 live births from 2001 to 2007. Estimates of preterm birth rates were obtained per region and per year according to self-reported gestational age. The prevalence rate and 95 % confidence interval (CI) for preterm was determined according to the characteristics of mothers and offspring. Odds ratios and 95 % CI were estimated for complications such as severe maternal morbidity. The preterm birth rate was 9.9 %, with regional variations. Preterm birth was more likely to be associated with neonatal death, low birth weight, and longer hospital stay. Maternal factors associated with preterm birth were: white ethnicity, living in an urban area, history of hypertension or heart disease, twin gestation, non-elective Cesarean section, medical insurance for delivery, low number of antenatal visits, and severe morbidity. A self-report survey has indicated that the preterm birth rate in Brazil is higher than official data suggest, with an increasing trend in more developed areas, and is associated with poor neonatal and maternal outcomes.

From planning to practice: building the national network for the Surveillance of Severe Maternal Morbidity.

BACKGROUND: Improving maternal health is one of the Millennium Development Goals for 2015. Recently some progress has been achieved in reducing mortality. On the other hand, in developed regions, maternal death is a relatively rare event compared to the number of cases of morbidity; hence studying maternal morbidity has become more relevant. Electronic surveillance systems may improve research by facilitating complete data reporting and reducing the time required for data collection and analysis. Therefore the purpose of this study was to describe the methods used in elaborating and implementing the National Network for the Surveillance of Severe Maternal Morbidity in Brazil. METHODS: The project consisted of a multicenter, cross-sectional study for the surveillance of severe maternal morbidity including near-miss, in Brazil. RESULTS: Following the development of a conceptual framework, centers were selected for inclusion in the network, consensus meetings were held among the centers, an electronic data collection system was identified, specific software and hardware tools were developed, research material was prepared, and the implementation process was initiated and analyzed. CONCLUSION: The conceptual framework developed for this network was based on the experience acquired in various studies carried out in the area over recent years and encompasses maternal and perinatal health. It is innovative especially in the context of a developing country. The implementation of the project represents the first step towards this planned management. The system online elaborated for this surveillance network may be used in further studies in reproductive and perinatal health.

Effect of anesthetic technique on the quality of anesthesia recovery for abdominal histerectomy: a cross-observational study.

INTRODUCTION: Spinal anesthesia combined with sedation and general anesthesia combined with epidural are two techniques often used for patients undergoing abdominal hysterectomy. There is no consensus that one of these techniques is superior regarding the perception of patients towards the quality of postoperative recovery. This observational cross-sectional study aimed to assess the quality of postoperative recovery in women undergoing open abdominal hysterectomy by comparing both anesthetic techniques. METHOD: We recruited 162 women aged between 30 and 74 years to be submitted to abdominal hysterectomy. The anesthetic technique used followed the preference of the attending anesthesiologist without interference of the investigators. After applying the exclusion criteria, 80 patients underwent spinal anesthesia combined with sedation (Group 1) and 62 women underwent epidural anesthesia combined with general anesthesia (Group 2). The quality of postoperative recovery was evaluated using the questionnaire Quality of Recovery-40 (QoR-40) completed 24 hours after the end of the surgery. RESULTS: Eighty patients in Group 1 answered the QoR-40 questionnaire with an average rating of 179.4 points, median of 186.5, standard deviation of 17.4 and a confidence interval of 3.8. The 60 patients in Group 2 answered the QoR-40 with an average of 174.9 points, median of 178 points, standard deviation of 16 points and a confidence interval of 4.0 (p = 0.024). CONCLUSION: Women who received spinal anesthesia combined with sedation considered quality of postoperative recovery better.

Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection.

Leprosy is a disease with a clinical spectrum of presentations that is also manifested in diverse histological features. At one pole, lepromatous lesions (L-pole) have phagocytic foamy macrophages heavily parasitized with freely multiplying intracellular Mycobacterium leprae. At the other pole, the presence of epithelioid giant cells and granulomatous formation in tuberculoid lesions (T-pole) lead to the control of M. leprae replication and the containment of its spread. The mechanism that triggers this polarization is unknown, but macrophages are central in this process. Over the past few years, leprosy has been studied using large scale techniques to shed light on the basic pathways that, upon infection, rewire the host cellular metabolism and gene expression. M. leprae is particularly peculiar as it invades Schwann cells in the nerves, reprogramming their gene expression leading to a stem-like cell phenotype. This modulatory behavior exerted by M. leprae is also observed in skin macrophages. Here, we used live M. leprae to infect (10:1 multiplicity of infection) monocyte-derived macrophages (MDMs) for 48 h and analyzed the whole gene expression profile using microarrays. In this model, we observe an intense upregulation of genes consistent with a cellular immune response, with enriched pathways including peptide and protein secretion, leukocyte activation, inflammation, and cellular divalent inorganic cation homeostasis. Among the most differentially expressed genes (DEGs) are CCL5/RANTES and CYP27B1, and several members of the metallothionein and metalloproteinase families. This is consistent with a proinflammatory state that would resemble macrophage rewiring toward granulomatous formation observed at the T-pole. Furthermore, a comparison with a dataset retrieved from the Gene Expression Omnibus of M. leprae-infected Schwann cells (MOI 100:1) showed that the patterns among the DEGs are highly distinct, as the Schwann cells under these conditions had a scavenging and phagocytic gene profile similar to M2-like macrophages, with enriched pathways rearrangements in the cytoskeleton, lipid and cholesterol metabolism and upregulated genes including MVK, MSMO1, and LACC1/FAMIN. In summary, macrophages may have a central role in defining the paradigmatic cellular (T-pole) vs. humoral (L-pole) responses and it is likely that the multiplicity of infection and genetic polymorphisms in key genes are gearing this polarization.

HLA-DPB1 and HLA-C alleles are associated with leprosy in a Brazilian population.

Despite intense efforts, the number of new cases of leprosy has remained significantly high over the past 20 years. Host genetic background is strongly linked to the pathogenesis of this disease, which is caused by Mycobacterium leprae (M. leprae), and there is a consensus that the most significant genetic association with leprosy is attributed to the major histocompatibility complex (MHC). Here, we investigated the association of human leukocyte antigen (HLA) class I and II genes with leprosy in a Brazilian population encompassing 826 individuals from a hyperendemic area of Brazil; HLA typing of class I (-A, -B, -C) and class II (-DRB1, -DQA1, -DQB1, -DPA1, and -DPB1) loci was conducted. Initially, the associations were tested using the chi-square test, with p-values adjusted using the false discovery rate (FDR) method. Next, statistically significant signals of the associations were submitted to logistic regression analyses to adjust for sex and molecular ancestry data. The results showed that HLA-C*08, -DPB1*04, and -DPB1*18 were associated with protective effects, while HLA-C*12 and -DPB1*105 were associated with susceptibility to leprosy. Thus, our findings reveal new associations between leprosy and the HLA-DPB1 locus and confirm previous associations between the HLA-C locus and leprosy.

Rationale for a long-term evaluation of the consequences of potentially life-threatening maternal conditions and maternal "near-miss" incidents using a multidimensional approach.

Recent advances in health care mean that women survive severe conditions and events related to pregnancy that would previously have resulted in death. Therefore, a greater number of women will experience significant maternal morbidity with significant consequences. Little is known, however, about these long-term consequences. Some investigators have evaluated the repercussions of severe biological or traumatic events, and have reported that survivors are at an increased risk of death in the five years after the event. In addition, they continue to experience both organic and emotional problems such as clinical, cardiac, respiratory, and neurological complications, as well as anxiety and depression, following discharge from hospital. Following a maternal "near-miss" incident, various life domains may be affected (organic, mental, cognitive, and social function), and these must be evaluated in addition to the related economic issues and quality of life. However, because of the diversity of methods and instruments used to evaluate possible repercussions, comparisons between the few studies available on the subject are difficult. An in-depth debate should be initiated to discuss the methodological aspects of such investigation. We propose a conceptual and methodological discussion on the long-term repercussions of severe maternal morbidity based on the evaluation of the following variables: reproductive health, quality of life, posttraumatic stress syndrome, sexual function, postpartum depression, daily functioning, and the physical, neurological, and psychomotor development of the children born after a complicated pregnancy.

Development and validation of a questionnaire to identify severe maternal morbidity in epidemiological surveys.

OBJECTIVE: to develop and validate a questionnaire on severe maternal morbidity and to evaluate the maternal recall of complications related to pregnancy and childbirth. DESIGN: validity of a questionnaire as diagnostic instrument. SETTING: a third level referral maternity in Campinas, Brazil. POPULATION: 386 survivors of severe maternal complications and 123 women that delivered without major complications between 2002 and 2007. METHODS: eligible women were traced and interviewed by telephone on the occurrence of obstetric complications and events related to their treatment. Their answers were compared with their medical records as gold standard. Sensitivity, specificity and likelihood ratios plus their correspondent 95% confidence intervals were used as main estimators of accuracy. MAIN OUTCOMES: diagnosis of severe maternal morbidity associated with past pregnancies, including hemorrhage, eclampsia, infections, jaundice and related procedures (hysterectomy, admission to ICU, blood transfusion, laparotomy, inter-hospital transfer, mechanical ventilation and post partum stay above seven days). RESULTS: Women did not recall accurately the occurrence of obstetric complications, especially hemorrhage and infection. The likelihood ratios were < 5 for hemorrhage and infection, while for eclampsia it almost reached 10. The information recalled by women regarding hysterectomy, intensive care unit admission and blood transfusion were found to be highly correlated with finding evidence of the event in the medical records (likelihood ratios ranging from 12.7-240). The higher length of time between delivery and interview was associated with poor recall. CONCLUSION: Process indicators are better recalled by women than obstetric complication and should be considered when applying a questionnaire on severe maternal morbidity.

General anesthesia technique and perception of quality of postoperative recovery in women undergoing cholecystectomy: A randomized, double-blinded clinical trial.

BACKGROUND: The two most common general anesthesia techniques are total intravenous anesthesia (TIVA) and venous/inhalation balanced general anesthesia (BGA). It is unclear whether any of these two techniques affect patient perception of the quality of recovery. The aim of this randomized, double-blinded clinical trial was to assess the quality of postoperative recovery of women undergoing laparoscopic cholecystectomy under general anesthesia. We compared patients who received TIVA with those who received BGA. We also evaluated the factors that may decrease patient-perceived quality of postoperative recovery. METHODS: We prospectively recruited 121 women aged 18-65 years who were scheduled for elective laparoscopic cholecystectomy due to cholelithiasis. These patients were randomized to receive TIVA (target-controlled infusion of propofol and remifentanil) or BGA (continuous remifentanil infusion and sevoflurane inhalation). To measure the quality of postanesthetic and postoperative recovery, we administered the Quality of Recovery-40 (QoR-40) questionnaire 24 hours after the patient awoke from anesthesia. RESULTS: All 60 patients in the TIVA group responded to QoR-40 (median, 188 points; minimum 128; maximum 200). Sixty-one patients in the BGA group had a mean QoR-40 score of 186 points (median, 188 points; minimum 146; maximum 200). There was no significant difference in the QoR-40 score between the two groups (p = 0.577). The patients who presented postoperative nausea and vomiting (PONV) and pain had worse perception of the quality of postoperative recovery. CONCLUSIONS: Both TIVA and BGA had a similar effect on the perception of the quality of postoperative recovery in women undergoing elective laparoscopic cholecystectomy. PONV and pain may negatively affect patient perception of the quality of postoperative recovery.

Brazilian network for the surveillance of maternal potentially life threatening morbidity and maternal near-miss and a multidimensional evaluation of their long term consequences.

BACKGROUND: It has been suggested that the study of women who survive life-threatening complications related to pregnancy (maternal near-miss cases) may represent a practical alternative to surveillance of maternal morbidity/mortality since the number of cases is higher and the woman herself is able to provide information on the difficulties she faced and the long-term repercussions of the event. These repercussions, which may include sexual dysfunction, postpartum depression and posttraumatic stress disorder, may persist for prolonged periods of time, affecting women's quality of life and resulting in adverse effects to them and their babies. OBJECTIVE: The aims of the present study are to create a nationwide network of scientific cooperation to carry out surveillance and estimate the frequency of maternal near-miss cases, to perform a multicenter investigation into the quality of care for women with severe complications of pregnancy, and to carry out a multidimensional evaluation of these women up to six months. METHODS/DESIGN: This project has two components: a multicenter, cross-sectional study to be implemented in 27 referral obstetric units in different geographical regions of Brazil, and a concurrent cohort study of multidimensional analysis. Over 12 months, investigators will perform prospective surveillance to identify all maternal complications. The population of the cross-sectional component will consist of all women surviving potentially life-threatening conditions (severe maternal complications) or life-threatening conditions (the maternal near miss criteria) and maternal deaths according to the new WHO definition and criteria. Data analysis will be performed in case subgroups according to the moment of occurrence and determining cause. Frequencies of near-miss and other severe maternal morbidity and the association between organ dysfunction and maternal death will be estimated. A proportion of cases identified in the cross-sectional study will comprise the cohort of women for the multidimensional analysis. Various aspects of the lives of women surviving severe maternal complications will be evaluated 3 and 6 months after the event and compared to a group of women who suffered no severe complications in pregnancy. Previously validated questionnaires will be used in the interviews to assess reproductive function, posttraumatic stress, functional capacity, quality of life, sexual function, postpartum depression and infant development.

Psychological preparation reduces preoperative anxiety in children. Randomized and double-blind trial.

OBJECTIVE: To verify the effect of psychological preparation on the relief of preoperative anxiety in children and to correlate parents' and children's levels of anxiety. METHOD: After the approval of the institutional Research Ethics Committee and written consent of the children's parents or guardians, 118 children of both genders were prospectively selected, aged between 2 and 8 years, physical condition classification ASA I, who were treated in the pre-anesthetic evaluation ambulatory of the University Hospital and who underwent ambulatory surgeries at the same hospital. Two controlled groups of 59 children were randomized: control group basic preparation and psychological preparation group. On the day of surgery, all selected children were evaluated regarding their level of anxiety using the modified Yale Preoperative Anxiety Scale and their parents were evaluated regarding their level of anxiety through the Visual Analog Scale. The evaluator was blinded to which study group the child and family member belonged to. RESULTS: Nine children and their family members were excluded per group when the results were analyzed. Children from the prepared group showed significant reductions in their level of anxiety in relation to the control group (p=0.04). There was no correlation between the level of anxiety of children and their parents' levels (p=0.78). CONCLUSION: The psychological preparation was effective in reducing the level of anxiety of children. However, there was no relation between the level of anxiety of children and their parents' level.

Diuretic or sodium-restricted diet for obstructive sleep apnea-a randomized trial.

Study Objectives: Interventions that decrease leg fluid retention reduce obstructive sleep apnea (OSA) severity in nonrandomized experiments. We aimed to investigate in a randomized trial the effect of interventions that reduce fluid volume on OSA severity. Methods: Men diagnosed with severe OSA were randomized to receive daily spironolactone 100 mg + furosemide 20 mg or nutritional counseling to sodium-restricted diet plus placebo pill or placebo pill. All participants underwent home sleep apnea testing at baseline and after 1 week follow-up. The change in apnea-hypopnea index (AHI) was the primary outcome. Results: The study included 54 participants and all were assessed at follow-up. The average baseline value of the AHI was similar among groups and from baseline to follow-up the AHI reduced 14.4 per cent (δ value -7.3 events per hour; 95% confidence interval, -13.8 to -0.9) in the diuretic group, 22.3 per cent (-10.7; 95% CI, -15.6 to -5.7) in the diet group, and 0.8 per cent (0.4; 95% CI, -2.5 to 3.2) in the placebo group (p = .001 for time × group interaction). None of the patients had their AHI returned to normal. The reduction in the total body water was 2.2 ± 2.2 L in the diuretic group (p < .001) and 1.0 ± 1.6 l in the low salt diet group (p = .002). Sleepiness and neck circumference were significantly reduced only in the diet group (p = .007 and p < .001 for the time × group interactions, respectively). Conclusions: Interventions to reduce bodily fluid content in men with severe OSA promoted a limited decrease of apnea frequency. This finding suggests that rostral fluid displacement affects only partially the OSA severity and/or that other factors prevail in determining pharyngeal collapsibility. Clinical Trial: Sodium-Restricted Diet and Diuretic in the Treatment of Severe Sleep Apnea (DESALT), https://clinicaltrials.gov/ct2/show/NCT01945801 ClinicalTrials.gov number: NCT01945801.

Phenotypical characteristics of group B streptococcus in parturients.

Colonization by Group B Streptococcus (GBS) is highly prevalent among pregnant women, with prevalence rates ranging between 4% and 30%. The infection may be transmitted vertically and may result in serious neonatal consequences. In the period from November 2003 to May 2004, a cross-sectional study was carried out among 316 parturients at the Jundiaí Teaching Hospital to establish the prevalence of genital GBS colonization, to identify the factors associated with colonization and the characteristic phenotypes of these streptococci. Samples from rectal and vaginal areas were collected for selective culture in Todd-Hewitt broth. Susceptibility to 7 antimicrobial agents was tested using the antibiotic diffusion disk technique, and the isolated strains were classified using specific antisera. The prevalence of GBS colonization was 14.6%. No strain was resistant to penicillin, ampicillin, erythromycin or nitrofurantoin. The majority of strains were sensitive to cephalothin. Greatest resistance was to gentamicin (76.1%), followed by clindamycin (17.4%). The most frequent serotype was Ib (23.9%), followed by serotypes II and Ia (19.6% and 17.4%, respectively). There was no correlation between serotype and greater antimicrobial resistance. In conclusion, the prevalence of GBS in parturients was high and penicillin continues to be the drug of choice for intrapartum prophylaxis. The most frequent serotype (Ib) found in this study differs from those found in the majority of studies carried out in other countries, revealing the need to identify prevalent serotypes in each region so that specific vaccines can be designed.

Disrupted day-night pattern of cardiovascular death in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) patients who suffer sudden cardiac death die predominantly during the night. We aimed to investigate whether all cardiovascular-related deaths display the same night-time peak as sudden cardiac death. METHODS: Data from a large cohort of adults who underwent full-night polysomnography between 1985 and 2015 in a university-affiliated sleep clinic were analyzed. Time and cause of death of these patients and of persons from the general population were identified in death certificates from the State Health Secretariat. The day-night pattern of cardiovascular death was compared among groups of non-OSA, OSA (apnea-hypopnea index, AHI ≥5), CPAP users, and persons from the general population. RESULTS: Among 619 certificates, 160 cardiovascular-related deaths were identified. The time of death of the 142 persons with OSA was uniformly distributed over 24 h, with neither an identifiable peak nor a circadian pattern (Rayleigh test; P = 0.8); the same flat distribution was seen in those with purported CPAP use (n = 49). Non-OSA individuals presented a morning peak and a night nadir of deaths, clearer when analyzed in eight-hour intervals. The same pattern was observed in 92 836 certificates from the State general population, with cardiovascular deaths showing the expected morning peak, night nadir, and a significant circadian pattern (Rayleigh test; P < 0.001). CONCLUSIONS: In OSA patients, the distribution of cardiovascular-related deaths throughout the 24-h period is virtually flat, in contrast with the described nighttime peak of sudden cardiac death. OSA-related phenomena during nighttime might be blunting the mechanisms, arrhythmic or not, behind the morning peak of cardiovascular-related deaths.

Association of CD209 (DC-SIGN) rs735240 SNV with paucibacillary leprosy in the Brazilian population and its functional effects

BACKGROUND Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M. leprae involves the DC-SIGN receptor, which is present on the dendritic cells (DCs) and participates in immune activation. OBJECTIVES To evaluate the association of polymorphisms in the promoter region of the gene encoding DC-SIGN (CD209) and the clinical form of leprosy, and to investigate its functional effects. METHODS The study population included 406 leprosy patients from an endemic area in Brazil [310 multibacillary (MB); 96 paucibacillary (PB)]. A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed. RESULTS The GA genotype and the presence of the A allele of rs735240 (-939G>A) were associated with PB leprosy [OR: 2.09 (1.18-3.69) and 1.84 (1.07-3.14), respectively]. Carriers of the A allele showed reduced expression of CD209 and TGF-β1 in leprosy lesions in comparison with individuals with GG genotype, in addition to a higher response to the Mitsuda test. CONCLUSION These data suggest that rs735240 influences the immune response against M. leprae and clinical presentation of leprosy.

A cohort study of functioning and disability among women after severe maternal morbidity.

OBJECTIVE: To assess functioning and disability related to severe maternal morbidity (SMM) via the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). METHODS: In a retrospective cohort study, women with or without a history of SMM who delivered at a tertiary public hospital in Brazil between July 2008 and June 2012, completed the WHODAS 2.0 questionnaire by individual interview between August 2012 and November 2013. General WHODAS scores were evaluated by maternal and neonatal characteristics, and specific domain scores according to SMM event. RESULTS: Overall, 638 women were enrolled (315 with SMM and 323 without SMM). The mean general WHODAS score was higher among women with SMM (19.04±16.18) than among women without SMM (15.77±14.46; P=0.015). Domain scores were also higher in the SMM group for mobility (16.00±20.22 vs 11.63±17.51; P=0.003), household activities (26.79±30.16 vs 20.09±26.08; P=0.005), participation (23.55±21.72 vs 17.27±19.17; P<0.001), and work/school activities for women currently studying or working (20.52±26.64 vs 11.66±19.67; P=0.001). Excluding SMM, a parity of two or more was the only factor significantly associated with higher scores overall (P=0.013) and for domain 4 (getting along with people; P=0.017). CONCLUSION: By comparison with women without childbirth complications, SMM impaired self-reported functioning among women 1-5years after delivery.