Haploinsufficiency of the mouse Tshz3 gene leads to kidney defects.

Renal tract defects and autism spectrum disorder (ASD) deficits represent the phenotypic core of the 19q12 deletion syndrome caused by the loss of one copy of the TSHZ3 gene. Although a proportion of Tshz3 heterozygous (Tshz3+/lacZ) mice display ureteral defects, no kidney defects have been reported in these mice. The purpose of this study was to characterize the expression of Tshz3 in adult kidney as well as the renal consequences of embryonic haploinsufficiency of Tshz3 by analyzing the morphology and function of Tshz3 heterozygous adult kidney. Here, we described Tshz3 expression in the smooth muscle and stromal cells lining the renal pelvis, the papilla and glomerular endothelial cells (GEnCs) of the adult kidney as well as in the proximal nephron tubules in neonatal mice. Histological analysis showed that Tshz3+/lacZ adult kidney had an average of 29% fewer glomeruli than wild-type kidney. Transmission electron microscopy of Tshz3+/lacZ glomeruli revealed a reduced thickness of the glomerular basement membrane and a larger foot process width. Compared to wild type, Tshz3+/lacZ mice showed lower blood urea, phosphates, magnesium and potassium at 2 months of age. At the molecular level, transcriptome analysis identified differentially expressed genes related to inflammatory processes in Tshz3+/lacZ compare to wild-type (control) adult kidneys. Lastly, analysis of the urinary peptidome revealed 33 peptides associated with Tshz3+/lacZ adult mice. These results provide the first evidence that in the mouse Tshz3 haploinsufficiency leads to cellular, molecular and functional abnormalities in the adult mouse kidney.

Vasorelaxant effects of ellagitannins isolated from Cuphea carthagenensis.

Cuphea carthagenensis (Jacq.) J. F. Macbr. is a popular plant in Brazilian folk medicine owing to its hypotensive and central nervous system depressant effects. This study aimed to validate the hypotensive effect of the plant's aqueous extract (AE) in rats and examine the vascular actions of three hydrolyzable tannins, oenothein B, woodfordin C, and eucalbanin B, isolated from AE. Systolic blood pressure in unanesthetized rats was determined using the non-invasive tail-cuff method. Oral treatment of normotensive rats with 0.5 and 1.0 g/kg/day AE induced a dose-related hypotensive effect after 1 week. In rat aortic rings pre-contracted with noradrenaline, all ellagitannins (20 - 180 µM) induced a concentration-related vasorelaxation. This effect was blocked by either removing the endothelium or pre-incubating with NG-nitro-l-arginine methyl ester (10 µM), an inhibitor of nitric oxide (NO) synthase. In KCl-depolarized rat portal vein preparations, the investigated compounds did not affect significantly the maximal contractile responses and pD2 values of the concentration-response curves to CaCl2. Our results demonstrated the hypotensive effect of C. carthagenensis AE in unanesthetized rats. All isolated ellagitannins induced vasorelaxation in vitro via activating NO synthesis/NO release from endothelial cells, without altering the Ca2+ influx in vascular smooth muscle preparations. Considering the low oral bioavailability of ellagitannins, the determined in vitro actions of these compounds are unlikely to account for the hypotensive effect of AE in vivo. It remains to be determined the role of the bioactive ellagitannin-derived metabolites in the hypotensive effect observed after oral treatment of unanesthetized rats with the plant extract.

"Addressing the core trait of bipolar disorder": A concept analysis of mood-stabilizing drugs.

OBJECTIVE: The term "mood stabilizer" is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning. METHODS: We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta-analyses and other sources for drugs used in the treatment of bipolar disorder. RESULTS: Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: "not worsening," "acute effects," "prophylactic effects," and "advanced effects." "Prophylactic effects" were often considered the core aspect of a legitimate mood stabilizer. CONCLUSION: The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long-term outcomes and illness trajectory, instead of simply approaching symptom clusters.

Acute Recovery after a Fatigue Protocol Using a Recovery Sports Legging: An Experimental Study.

Enhancing recovery is a fundamental component of high-performance sports training since it enables practitioners to potentiate physical performance and minimise the risk of injuries. Using a new sports legging embedded with an intelligent system for electrostimulation, localised heating and compression (completely embodied into the textile structures), we aimed to analyse acute recovery following a fatigue protocol. Surface electromyography- and torque-related variables were recorded on eight recreational athletes. A fatigue protocol conducted in an isokinetic dynamometer allowed us to examine isometric torque and consequent post-exercise acute recovery after using the sports legging. Regarding peak torque, no differences were found between post-fatigue and post-recovery assessments in any variable; however, pre-fatigue registered a 16% greater peak torque when compared with post-fatigue for localised heating and compression recovery methods. Our data are supported by recent meta-analyses indicating that individual recovery methods, such as localised heating, electrostimulation and compression, are not effective to recover from a fatiguing exercise. In fact, none of the recovery methods available through the sports legging tested was effective in acutely recovering the torque values produced isometrically.

A Qualitative Study on Traumatic Experiences of Suicide Survivors.

The suicide of a loved one can be a traumatic experience. The objective of this study was to investigate trauma-related experiences of suicide survivors. This is a qualitative study with people who had recently lost a family member or a close one to suicide, conducted at least two months after the event. Forty-one participants agreed to take part in the study and were interviewed. The interviewees' perception was that suicide brought harm, symptoms, and suffering. Traumatic experiences can begin immediately after the event, with many reporting symptoms lasting many months and persistent impact, both personal and to the family. Postvention models after suicide should incorporate such findings, and investigate trauma consistently.

Detection of SARS-CoV-2 in different human biofluids using the loop-mediated isothermal amplification assay: A prospective diagnostic study in Fortaleza, Brazil.

We adopted the reverse-transcriptase-loop-mediated isothermal amplification (RT-LAMP) to detect severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in patient samples. Two primer sets for genes N and Orf1ab were designed to detect SARS-CoV-2, and one primer set was designed to detect the human gene Actin. We collected prospective 138 nasopharyngeal swabs, 70 oropharyngeal swabs, 69 salivae, and 68 mouth saline wash samples from patients suspected to have severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 to test the RT-LAMP in comparison with the gold standard technique reverse-transcription quantitative polymerase chain reaction  (RT-qPCR). The accuracy of diagnosis using both primers, N5 and Orf9, was evaluated. Sensitivity and specificity for diagnosis were 96% (95% confidence interval [CI]: 87-99) and 85% (95% CI: 76-91) in 138 samples, respectively. Accurate diagnosis results were obtained only in nasopharyngeal swabs processed via extraction kit. Accurate and rapid diagnosis could aid coronavirus disease 2019 (COVID-19) pandemic management by identifying, isolating, and treating patients rapidly.

BR-bombesin: a novel bombesin-related peptide from the skin secretion of the Chaco tree frog (Boana raniceps) with physiological gastric effects.

Bombesin mediates several biological activities in the gastrointestinal (GI) tract and central nervous system in mammals, including smooth muscle contraction, secretion of GI hormones and regulation of homeostatic mechanisms. Here, we report a novel bombesin-like peptide isolated from Boana raniceps. Its amino acid sequence, GGNQWAIGHFM-NH2, was identified and structurally confirmed by HPLC, MS/MS and 454-pyrosequencing; the peptide was named BR-bombesin. The effect of BR-bombesin on smooth muscle contraction was assessed in ileum and esophagus, and its anti-secretory activity was investigated in the stomach. BR-bombesin exerted significant contractile activity with a concentration-response curve similar to that of commercially available bombesin in ileum strips of Wistar rats. In esophageal strips, BR-bombesin acted as an agonist, as many other bombesin-related peptides act, although with different behavior compared to the muscarinic agonist carbachol. Moreover, BR-bombesin inhibited stomach secretion by approximately 50% compared to the untreated control group. This novel peptide has 80% and 70% similarity with the 10-residue C-terminal domain of human neuromedin B (NMB) and human gastrin releasing peptide (GRP10), respectively. Molecular docking analysis revealed that the GRP receptor had a binding energy equal to - 7.3 kcal.mol-1 and - 8.5 kcal.mol-1 when interacting with bombesin and BR-bombesin, respectively. Taken together, our data open an avenue to investigate BR-bombesin in disorders that involve gastrointestinal tract motility and acid gastric secretion.

Optimization of an in Silico Protocol Using Probe Permeabilities to Identify Membrane Pan-Assay Interference Compounds.

Membrane pan-assay interference compounds (PAINS) are a class of molecules that interact nonspecifically with lipid bilayers and alter their physicochemical properties. An early identification of these compounds avoids chasing false leads and the needless waste of time and resources in drug discovery campaigns. In this work, we optimized an in silico protocol on the basis of umbrella sampling (US)/molecular dynamics (MD) simulations to discriminate between compounds with different membrane PAINS behavior. We showed that the method is quite sensitive to membrane thickness fluctuations, which was mitigated by changing the US reference position to the phosphate atoms of the closest interacting monolayer. The computational efficiency was improved further by decreasing the number of umbrellas and adjusting their strength and position in our US scheme. The inhomogeneous solubility-diffusion model (ISDM) used to calculate the membrane permeability coefficients confirmed that resveratrol and curcumin have distinct membrane PAINS characteristics and indicated a misclassification of nothofagin in a previous work. Overall, we have presented here a promising in silico protocol that can be adopted as a future reference method to identify membrane PAINS.

Electrocardiographic findings in pregnant women in Angola.

BACKGROUND: Studies on the electrocardiogram findings in African pregnant women are limited. There is no information available in the literature on the electrocardiographic parameters of pregnant Angolan women. OBJECTIVES: The aim of this study was to describe electrocardiographic findings in women with normal pregnancies in Bengo Province, Angola. METHODS: This is a community-based study with a cross-sectional design conducted between September 2013 and March 2014 in Bengo. The study involved 114 black pregnant women, compared with a paired control group comprising of 120 black non-pregnant women, aged 15 to 42 years. A 12-lead electrocardiogram and a rhythm strip were recorded for all participants. RESULTS: In this study, the mean age was 26.2 ± 7.3 years. Comparing pregnant women vs. non-pregnant, we found the following mean values: Heart rate (83 bpm vs. 74 bpm, p < .001), PR interval (146 ms vs. 151 ms, p = .034), QT interval (360 ms vs. 378 ms, p < .001), QTIc Fridericia (398 ms vs. 403, p = .017), QTIc Framingham (399 ms vs. 404 ms, p = .013) and T-wave axis (340 vs. 410 , p = .001).The main electrocardiographic changes found were: Sinus tachycardia (4.4% vs. 2.5%), T-wave inversion (14.9% vs. 1.7%), Minor ST segment depression (4.5% vs. 0%) and left ventricular hypertrophy (11.4% vs. 11.7%, p = .726). CONCLUSIONS: Pregnant Angolan women compared with controls, had several significantly higher values for heart rate, and significantly lower values of systolic blood pressure and diastolic blood pressure, PR interval, QT interval, QTc interval by Fridericia and Framingham and T-wave axis. Sinus tachycardia, T-wave inversion, and left ventricular hypertrophy, were the main electrocardiographic changes found.

Prediction of body fat in adolescents: validity of the methods relative fat mass, body adiposity index and body fat index.

OBJECTIVE: To verify the validity of anthropometric methods body adiposity index (BAI), relative fat mass (RFM) and body fat index (BFI) to estimate body fat percentage (%BF) in adolescents. METHODS: A cross-sectional study was carried out with 420 Brazilian adolescents aged 15-19 years, stratified by age (< 18 years, n = 356; ≥ 18 years, n = 64) and sex (boys, n = 216; girls, n = 204). The Anthropometric measurements height, body weight, hip circumference and waist circumference were collected to calculate the %BF by BAI, RFM, BFI methods. Subsequently, %BF was measured by dual emission X-ray absorptiometry (DXA), adopted as a reference method. In the statistical analysis of the data, the Pearson correlation test and the paired t test between %BF obtained by the equations and by the DXA were performed. The method validation criterion was that 68% of individuals should be within an acceptable error range of ± 3.5% of BF and Cohen's Kappa index ≥ 0.61. Additionally, the Bland-Altman graphical analysis was performed. RESULTS: All methods showed a high correlation with DXA. For the Kappa index, only the RFM reached the criterion in the total sample (0.67) and in the sample < 18 years (0.68). None of the methods reached the criterion of 68% of the sample within the error range of ± 3.5% of BF. CONCLUSION: The BAI, RFM and BFI equations were not valid for predicting BF in the studied sample according to the criteria adopted regardless of sex or age. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Latent structure and factor reliability of the National Health Service Community Mental Health Service User Questionnaire.

BACKGROUND: National Health Service use the Community Mental Health Service User Questionnaire (NHS-CMH) to assess care quality. However, its reliability and internal validity is uncertain. AIMS: To test the NHS-CMH structure, reliability and item-level characteristics. METHODS: We used data from 11,373 participants who answered the 2017 NHS-CMH survey. First, we estimated the NHS-CMH structure using Exploratory Factor Analysis (EFA) in half of the dataset. Second, we tested the best EFA-derived model with Confirmatory Factor Analysis (CFA). We tested the internal validity, construct reliability (omega - ω), explained common variance of each factor (ECV), and item thresholds. RESULTS: EFA suggested a 4-factor solution. The structure derived from the EFA was confirmed, demonstrating good reliability for the four correlated dimensions: "Relationship with Staff" (ω = 0.952, ECV = 40.1%), "Organizing Care" (ω = 0.855, ECV = 21.4%), "Medication and Treatments" (ω = 0.837, ECV = 13.3%), and "Support and Well-being" (ω = 0.928, ECV = 25.3%). A second-order model with a high-order domain of "Quality of Care" is also supported. CONCLUSIONS: The NHS-CMH can be used to reliably assess four user-informed dimensions of mental health care quality. This model offers an alternative for its current use (item-level and untested sum scores analysis).

Urinary peptidome and diabetic retinopathy in the DIRECT-Protect 1 and 2 trials.

BACKGROUND: Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively. METHODS: Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT-Protect 1 and 2, respectively. End points were two-step (RET2) and three-step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT-Protect 1. The identified peptides were then validated cross-sectionally in the remaining 1/3 from DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts and significant peptides were tested longitudinally. RESULTS: Follow-up ranged 4.0-4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: -.223, p < 0.001 and Rho: -.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types. CONCLUSIONS: We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR.

The urinary proteomics classifier chronic kidney disease 273 predicts cardiovascular outcome in patients with chronic kidney disease.

BACKGROUND: The urinary proteomic classifier chronic kidney disease 273 (CKD273) is predictive for the development and progression of chronic kidney disease (CKD) and/or albuminuria in type 2 diabetes. This study evaluates its role in the prediction of cardiovascular (CV) events in patients with CKD Stages G1-G5. METHODS: We applied the CKD273 classifier in a cohort of 451 patients with CKD Stages G1-G5 followed prospectively for a median of 5.5 years. Primary endpoints were all-cause mortality, CV mortality and the composite of non-fatal and fatal CV events (CVEs). RESULTS: In multivariate Cox regression models adjusting for age, sex, prevalent diabetes and CV history, the CKD273 classifier at baseline was significantly associated with total mortality and time to fatal or non-fatal CVE, but not CV mortality. Because of a significant interaction between CKD273 and CV history (P = 0.018) and CKD stages (P = 0.002), a stratified analysis was performed. In the fully adjusted models, CKD273 classifier was a strong and independent predictor of fatal or non-fatal CVE only in the subgroup of patients with CKD Stages G1-G3b and without a history of CV disease. In those patients, the highest tertile of CKD273 was associated with a >10-fold increased risk as compared with the lowest tertile. CONCLUSIONS: The urinary CKD273 classifier provides additional independent information regarding the CV risk in patients with early CKD stage and a blank CV history. Determination of CKD273 scores on a random urine sample may improve the efficacy of intensified surveillance and preventive strategies by selecting patients who potentially will benefit most from early risk management.

New avenues in molecular genetics for the diagnosis and application of therapeutics to the epilepsies.

Genetic epidemiology studies have shown that most epilepsies involve some genetic cause. In addition, twin studies have helped strengthen the hypothesis that in most patients with epilepsy, a complex inheritance is involved. More recently, with the development of high-density single-nucleotide polymorphism (SNP) microarrays and next-generation sequencing (NGS) technologies, the discovery of genes related to the epilepsies has accelerated tremendously. Especially, the use of whole exome sequencing (WES) has had a considerable impact on the identification of rare genetic variants with large effect sizes, including inherited or de novo mutations in severe forms of childhood epilepsies. The identification of pathogenic variants in patients with these childhood epilepsies provides many benefits for patients and families, such as the confirmation of the genetic nature of the diseases. This process will allow for better genetic counseling, more accurate therapy decisions, and a significant positive emotional impact. However, to study the genetic component of the more common forms of epilepsy, the use of high-density SNP arrays in genome-wide association studies (GWAS) seems to be the strategy of choice. As such, researchers can identify loci containing genetic variants associated with the common forms of epilepsy. The knowledge generated over the past two decades about the effects of the mutations that cause the monogenic epilepsy is tremendous; however, the scientific community is just starting to apply this information in order to generate better target treatments.

Vasodilatory action of trans-4-methoxy-ß-nitrostyrene in rat isolated pulmonary artery.

Trans-4-methoxy-ß-nitrostyrene (T4MN) induced more potent vasorelaxant effects in resistance arteries from hypertensive rats than its parent drug, ß-nitrostyrene 1-nitro-2-phenylethene (NPe). To better understand the influence of insertion of the electron-releasing methoxy group in the aromatic ring of NPe, we investigated vasorelaxant effects of T4MN in isolated pulmonary artery and compared them with those of NPe in view of the potential interest of T4MN in pulmonary arterial hypertension. T4MN and NPe both caused concentration-dependent vasorelaxation in pulmonary artery rings pre-contracted with either phenylephrine (1 µmol/L) or KCl (60 mmol/L), an effect unaffected by endothelium removal. In endothelium-intact preparations pre-contracted with phenylephrine, the vasorelaxant effect of T4MN was more potent than that of NPe. However, unlike NPe, this effect was significantly reduced following pretreatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 µmol/L, a guanylate cyclase inhibitor) or tetraethylammonium (5 mmol/L, a potassium channel blocker). T4MN abolished the CaCl2 -induced contractions in pulmonary artery preparations stimulated with phenylephrine (PHE) under Ca2+ -free conditions in the presence of verapamil, to preferentially activate receptor-operated calcium channels. From these findings, we propose that T4MN evokes endothelium-independent vasorelaxant effects in isolated rat pulmonary artery, partially by inhibiting Ca2+ influx through L-type Ca2+ channels, as well as by activating soluble guanylate cyclase and potassium channels. The present results suggest the therapeutic potential of T4MN in treating pulmonary arterial hypertension.

Factors Associated With Seizure Adequacy Along the Course of Electroconvulsive Therapy.

OBJECTIVES: Eliciting a generalized seizure is essential to electroconvulsive therapy (ECT), but there is still a need to understand how patient and session variables interact to generate a seizure of adequate quality. Here, we investigate factors associated with motor seizure length as a measure of quality in a large database of patients who underwent ECT. METHODS: This is a retrospective cohort including data from all adult inpatients who underwent ECT at a university hospital in Brazil from 2009 to 2015. We used linear mixed models to investigate the effects of patient, session, and medication on seizure length. RESULTS: Session information was available for 387 patients, a total of 3544 sessions and 4167 individual stimulations. Multiple stimulations were necessary in 12.4% of sessions. Median seizure length was 30 seconds. Seizure length was directly correlated with stimulus dosage and inversely correlated with the session number, patient age, prescription of anticonvulsants in the day before and ß-blockers during the session, and the thiopental dose. Use of benzodiazepines was not associated with a shorter seizure duration, irrespective of dose. CONCLUSIONS: We demonstrate here how motor seizure length evolves during a course of ECT. With a large number of sessions, we are able to integrate a host of factors in a prediction model. Seizure quality was influenced by a number of the studied factors, many of which are potentially modifiable and could be assessed before initiating and handled during treatment.

Characteristics of suicides of young people in Porto Alegre, Southern Brazil, from 2010 to 2016.

The purpose of this study was to describe demographic, toxicological, criminal, and medicolegal characteristics of suicides of young people aged up to 24 years examined by the Porto Alegre Medicolegal Office, from 2010 to 2016. This cross-sectional study collected data from the Porto Alegre Medicolegal Office and the Rio Grande do Sul State Police Department. The information was obtained from death certificates, toxicological analyses and police reports. Rates were calculated according to sex and age range (under 15 years old, 15 to 19 years old, and 20 to 24 years old) for comparing local with national data. There were 143 people who died by suicide in the period, 120 males and 23 females. Hanging was the most frequently used method, but in the range of 10 to 14 years old, firearm use was the predominant method. Fifty percent of male victims and 30% of female victims had some criminal history. Suicide rates in the study groups generally followed national trends. The relative frequency of suicide by firearm in this study diverged from international findings, as it was relatively more frequent in children under 15 years old and less frequent in older ranges. If confirmed, the finding draws attention to access to firearms in this age range. In older age ranges, adolescents and young adults were frequently involved in the criminal system. This finding may be useful for planning interventions involving both mental health education and screening for problems that may be associated with criminal involvement.

Decrease in Hospital Admissions for Transient Ischemic Attack, Mild, and Moderate Stroke During the COVID-19 Era.

BACKGROUND AND PURPOSE: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, doctors and public authorities have demonstrated concern about the reduction in quality of care for other health conditions due to social restrictions and lack of resources. Using a population-based stroke registry, we investigated the impact of the onset of the COVID-19 pandemic in stroke admissions in Joinville, Brazil. METHODS: Patients admitted after the onset of COVID-19 restrictions in the city (defined as March 17, 2020) were compared with those admitted in 2019. We analyzed differences between stroke incidence, types, severity, reperfusion therapies, and time from stroke onset to admission. Statistical tests were also performed to compare the 30 days before and after COVID-19 to the same period in 2019. RESULTS: We observed a decrease in total stroke admissions from an average of 12.9/100 000 per month in 2019 to 8.3 after COVID-19 (P=0.0029). When compared with the same period in 2019, there was a 36.4% reduction in stroke admissions. There was no difference in admissions for severe stroke (National Institutes of Health Stroke Scale score >8), intraparenchymal hemorrhage, and subarachnoid hemorrhage. CONCLUSIONS: The onset of COVID-19 was correlated with a reduction in admissions for transient, mild, and moderate strokes. Given the need to prevent the worsening of symptoms and the occurrence of medical complications in these groups, a reorganization of the stroke-care networks is necessary to reduce collateral damage caused by COVID-19.

Normal limits of the electrocardiogram in Angolans.

INTRODUCTION: Studies on the normal electrocardiogram limits in African populations are limited, especially in sub-Saharan Africa. There is no literature describing normal ECG limits in Angolans. OBJECTIVES: The aim of this study is to establish the normal ECG limits for adult Angolans, without established heart disease, stratified by gender and age. METHODS: A cross-sectional study was performed, involving 2179 participants from a population in northern Angola, without established heart disease, aged between 15 and 74 years. A 12­lead ECG and a rhythm strip were recorded for all participants and analysed and processed by the University of Glasgow software and encoded by the Minnesota Code. The normal range of the electrocardiographic parameters were established as the 2nd and 98th percentiles of the measurement distribution per age group and gender. Mann-Whitney and Kruskal-Wallis tests were used for two independent groups and Bonferroni adjustments were used for multiple testing. GAMLSS models were used to obtain the continuous age-dependent percentile curves. RESULTS: The normal range of the ECG differed between men and women: heart rate 49 to 100 bpm vs. 55 to 108 bpm, P wave duration 81 to 130 ms vs. 84 to 130 ms, PR interval 119 to 210 ms vs. 120 to 202 ms, QRS duration 74 to 110 ms vs. 70 to 104 ms, QT interval 324 to 441 ms vs. 314 and 438 ms, P-wave axis - 29 to 850 vs. -18 to 810, QRS-wave axis - 13 to 850 vs. -180 and 820, T-wave axis 0 to 720 vs. -8 to 730, Sokolow-Lyon index 2.13 to 6.21 mV vs. 1.60 to 4.87 mV, Cornell index 0.17 to 6.24 mV vs. 0.14 mV to 4.35 mV. CONCLUSIONS: The values described for the electrocardiographic measurements above can act as a reference framework for Angolan adults without established heart disease. Our study suggests that the normal range of most ECG parameters vary according to age and sex and the ECG diagnostic criteria must therefore be specific for these demographic measures.

Case report on the multiple pathways to posttraumatic stress disorder following suicide.

Trauma pathology is not only a sum of risk factors, but emerges as a result of complex causal interaction. The case presented here illustrates the pathway from suicide exposure to the development of fully-fledged treatment-resistant posttraumatic stress disorder (PTSD), demonstrating how recognized risk factors can act in tandem to generate a difficult to treat syndrome. From a clinical perspective, bottom-up approaches that take into account real coping experiences of people bereaved by suicide are more effective to facilitate recovery and prevent adverse outcomes. Finally, even though treatment is often implemented, the diagnosis can be missed further complicating coping and treatment.