Genetics of schizophrenia in the South African Xhosa.

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide.

Surveillance in the field: Over-identification of Ebola suspect cases and its contributing factors in West African at-risk contexts.

During an Ebola outbreak, the WHO recommends that health professionals consider people as suspect cases (SCs) when they show key signs such as the sudden onset of high fever or specific symptoms after having had contact with a suspect or confirmed Ebola case. SCs should then get care, be isolated and be reported to health authorities until the Ebola virus disease is confirmed through a lab test. This exploratory study aims to understand this identification process in the field based on a qualitative analysis of the diagnosis and therapeutic itineraries of 19 SCs in Cote d'Ivoire and Senegal (2014-2015). Results indicate that the main criteria for SC identification at the field level were fever (understood broadly) and provenance from a highly affected country (applied indiscriminately). WHO criteria were not followed in at least 9 of the 19 cases. Several medical, social and cultural factors favour over-identification of people as SCs, including relativism in defining 'high fever', placism, humanitarian or securitarian bias, issues in categorising SC's contact cases, and the context of fear. To avoid undue categorisation and its possible harmful social effects, the WHO definition should be implemented more carefully in various contexts and with greater consideration for ethical issues, while prioritising diagnosis strategies with higher specificity.

The prevalence and predictors of intimate partner violence among pregnant women attending a midwife and obstetrics unit in the Western Cape.

BACKGROUND: Intimate partner violence (IPV) during pregnancy is prevalent across the world, but more so in low- and middle-income countries. It is associated with various adverse outcomes for mothers and infants. This study sought to determine the prevalence and predictors of IPV among pregnant women attending one midwife and obstetrics unit (MOU) in the Western Cape, South Africa. METHODS: A convenience sample of 150 pregnant women was recruited to participate in the study. Data were collected using several self-report measures concerning the history of childhood trauma, exposure to community violence, depression and alcohol use. Multivariable logistic models were developed, the first model was based on whether any IPV occurred, the remaining models investigated for physical-, sexual- and emotional abuse. RESULTS: Lifetime and 12-month prevalence rates for any IPV were 44%. The 12-month IPV rates were 32% for emotional and controlling behaviours, 29% physical and 20% sexual abuse. The adjusted model predicting physical IPV found women who were at risk for depression were more likely to experience physical IPV [odds ratios (ORs) 4.42, 95% confidence intervals (CIs) 1.88-10.41], and the model predicting sexual IPV found that women who reported experiencing community violence were more likely to report 12-month sexual IPV (OR 3.85, CI 1.14-13.08). CONCLUSION: This is the first study, which illustrates high prevalence rates of IPV among pregnant woman at Mitchells Plain MOU. A significant association was found between 12-month IPV and unintended pregnancy. Further prospective studies in different centres are needed to address generalisability and the effect of IPV on maternal and child outcomes.

Heavy metals in the irrigation water, soils and vegetables in the Philippi horticultural area in the Western Cape Province of South Africa.

The aims of this study were to investigate the extent of heavy metal contamination in the Philippi horticultural area in the Western Cape Province, South Africa. Concentrations of Cd, Cr, Cu, Mn, Ni, Pb and Zn were determined in the irrigation water, soils and vegetables in both winter and summer cropping seasons with an ICP-AES and tested against certified standards. Differences were found in heavy metal concentrations between the winter and summer cropping seasons in the irrigation water, soils and vegetables. Certain heavy metals exceeded the maximum permissible concentrations in the irrigation water, soils and vegetables produced in South Africa. These toxic concentrations were predominantly found in the summer cropping season for the soils and in the crops produced in winter. It is thus suggested that further studies are carried out in the Philippi horticultural area to determine the sources of the heavy metals to try and mitigate the inputs thereof and therefore reduce the amount of heavy metals entering the human food chain.

Fibrin network structure. Changes in characteristics in response to physical activity in combination with a pre-exercise meal.

The metabolic environment determines the characteristics of fibrin network structure (FNS) in plasma. Physical activity or changes in the diet (e.g., high and low glycemic index meals) can initiate these changes. The FNS were measured by means of mass-length ratio, turbidity, and compaction of the plasma obtained from male subjects. Samples were taken before and after the introduction of the different diets and physical activity. The results indicate that changes in the FNS do occur, but further investigation is required to obtain conclusive results.

Analysis of endoplasmic reticulum trafficking signals by combinatorial screening in mammalian cells.

To improve the accuracy of predicting membrane protein sorting signals, we developed a general methodology for defining trafficking signal consensus sequences in the environment of the living cell. Our approach uses retroviral gene transfer to create combinatorial expression libraries of trafficking signal variants in mammalian cells, flow cytometry to sort cells based on trafficking phenotype, and quantitative trafficking assays to measure the efficacy of individual signals. Using this strategy to analyze arginine- and lysine-based endoplasmic reticulum localization signals, we demonstrate that small changes in the local sequence context dramatically alter signal strength, generating a broad spectrum of trafficking phenotypes. Finally, using sequences from our screen, we found that the potency of di-lysine, but not di-arginine, mediated endoplasmic reticulum localization was correlated with the strength of interaction with alpha-COP.

Haplogroup-associated differences in neonatal death and incidence of low birth weight at elevation: a preliminary assessment.

OBJECTIVE: We sought to assess reproductive fitness differences between mitochondrial deoxyribonucleic acid haplogroups at high altitude. STUDY DESIGN: This study considers differences in outcomes of conception, birth weight, and neonatal mortality rates for 62 women classified according to haplogroups (B or non-B). RESULTS: The number of low-weight births (<2500 g) for the non-B group was significant (P =.019). Mothers in the non-B group reported more spontaneous abortions (P =.171) and stillbirths (P =.301). The difference in conceptions per woman between groups was significant (P =.036). However, no difference in infants alive at 1 month of age was evident. Neonatal death was significant (P =.017). The odds of an unsuccessful outcome among mothers in the B group was compared with mothers in the non-B group and was significant (P =.029). The chance of an adverse outcome, that is, fetal or infant death before 1 month, for mothers in the B group was between 11.1% and 88.7% lower than for mothers in the non-B group. CONCLUSIONS: The neonatal mortality rate for the non-B group was significantly elevated relative to the B group. The molecular basis for these observations is not clear.

HIV-1 survival kinetics in peritoneal dialysis effluent.

Viable and potentially infectious HIV-1 has been recovered from the peritoneal dialysis effluent (PDE) of patients with end-stage renal disease (ESRD) who are infected with the human immunodeficiency virus (HIV). No information had previously been available as to how long HIV-1 could survive in this environment, and no data were available as to how long HIV-1 could survive on peritoneal dialysis exchange tubing (PDET). Therefore, this study was designed to answer these questions. HIV-1 Mn was added to PDE and allowed to incubate at room temperature for 0 to 14 days. Following centrifugation, the cellular component of the PDE mixture was placed in co-culture with peripheral blood mononuclear cells (PBMC) from HIV negative donors. Aliquots from the co-cultures were removed after 14 days and assayed for the HIV-1-P24 antigen. High levels of HIV P24 antigen were recovered up to and including seven days of room temperature incubation. HIV could not be recovered from PDE that had been incubated at room temperature for 10 to 14 days. Ten milliters of HIV-PDE mixture was placed within PDET and incubated at room temperature for 10 minutes. The solution was then removed by gravity drainage. After drying times of 0 to 168 hours, the tubing was flushed with HIV culture medium and placed in co-culture with PBMCs from HIV negative donors. The culture supernatant was assayed for the HIV-1 P24 antigen as a marker of viral replication. High levels of HIV-1 P24 antigen were recovered from the PDET wash for up to and including 48 hours of drying time. No viable virus could be detected for drying times of between 72 and 168 hours. To determine if common disinfectants found in the dialysis unit could inactivate HIV, dilutions of Amukin 50% and household bleach were prepared at final concentrations ranging from 1:32 to 1:2048. These disinfectant solutions were incubated with PDE containing HIV for 10 minutes. The cellular fraction of the PDE was isolated by centrifugation, washed, and placed in co-cultures with peripheral blood mononuclear cells. HIV P24 antigen levels were assayed every three days for 28 days. Amukin 50% and a 10% household bleach solution were effective in killing HIV in PDE at dilutions up to and including 1:512. These results indicate that HIV can survive in PDE at room temperature for up to seven days. HIV can survive on peritoneal dialysis exchange tubing for up to 48 hours. Final dilutions of 1:512 Amukin 50% and 10% household bleach, after 10 minutes of exposure, are effective viricidal agents in disinfecting PDE.

Disposal of dialysate in HIV-positive patients: an update.

One of the concerns with the use of peritoneal dialysis in human immunodeficiency virus (HIV)-positive patients is disposal of the peritoneal effluents. This article reviews survival characteristics of HIV in dialysate effluents and current disinfectant strategies.

Recovery of human immunodeficiency virus from peritoneal dialysis effluent.

Increasing numbers of HIV-infected patients who have ESRD are being treated with continuous ambulatory peritoneal dialysis (CAPD). To investigate the potential infectious nature of peritoneal dialysate (PD), the peritoneal dialysis effluent was studied in 14 patients on CAPD who were known to be HIV antibody positive. Peripheral blood mononuclear cells and the sediment of PD were obtained from each patient and subjected to a qualitative microculture assay using a coculture of patient cells or PD fluid with peripheral blood mononuclear cells from non-HIV-infected individuals. Samples from the coculture were collected twice weekly for HIV P24 antigen determination as a marker of viral replication. PD, white blood cell and red blood cell counts, and peripheral blood CD4 lymphocyte counts were also measured. All 14 patients developed a positive blood culture by Day 3. Twelve of the 14 patients developed a positive PD fluid culture. The mean CD4 count was 310 cells/mm3. No patient had clinical or cellular evidence of peritonitis at the time of fluid sampling. These data indicate that peritoneal dialysis effluent from patients who are HIV antibody positive is potentially infectious.

The effect of ischaemia-reperfusion on [3H]inositol phosphates and ins(1,4,5)P3 levels in cardiac atria and ventricles--a comparative study.

In this study incorporation of [3H]inositol into inositol phosphates and phosphoinositides as well as tissue Ins(1,4,5)P3 levels of the atria and ventricles of isolated, perfused rat hearts were compared. Although the incorporation of [3H]inositol into the phosphoinositides of atria and ventricles was similar, significantly higher (2-3 fold) incorporation rates into inositol phosphates were observed in atrial tissue. Using a D-myo-[3H]Ins(1,4,5)P3 assay system, the Ins(1,4,5)P3 levels observed in atria from perfused rat hearts were also significantly higher than those obtained under the same experimental circumstances in the ventricles. Since previous studies on whole hearts showed inhibition of the phosphatidylinositol (PI) pathway during ischaemia with an immediate significant stimulation upon reperfusion [12, 20], the effects of ischaemia and 1 min postischaemic reperfusion were also examined separately in atria and ventricles. The results showed that 20 min of global ischaemia significantly depressed Ins(1,4,5)P3 levels as well as incorporation of [3H]inositol into ventricular InsP2 and InsP3. Reperfusion caused an immediate (within 1 min) increase in Ins(1,4,5)P3 levels and also [3H]inositol incorporation into all three cytosolic inositol phosphates in the ventricles. However, the effect of ischaemia and reperfusion on Ins(1,4,5)P3 levels as well as the incorporation of [3H]inositol into the inositol phosphates were less prominent in the atria. It therefore appears that the differential responses of the atria and the ventricles to an oxygen deficiency [41] are also reflected in the differences in PI metabolism during ischaemia-reperfusion.

Anaesthetic considerations in idiopathic orthostatic hypotension and the Shy-Drager syndrome.

Orthostatic hypotension due to autonomic failure may occur secondary to systemic disease states (notably diabetes) or as a disease entity in its own right with a variable degree of neurological involvement that has resulted in a confused classification. The diagnosis, classification and treatment of these latter forms of orthostatic hypotension is reviewed. The pathology is in the central and efferent autonomic pathway, resulting in a disordered baro-receptor reflex, postural hypotension, abnormal responses to tilting and the Valsalva manoeuvre, an inappropriately fixed heart rate and other autonomic features. Anaesthesia may be associated with profound hypotension and some of the signs of anaesthesia may be absent. The response to cardiac depressant drugs and reduction of circulating blood volume may be exaggerated due to absence of compensatory mechanisms. The response to vasoactive agents is unpredictable. The importance of preoperative evaluation, monitoring during operation and the careful selection of anaesthetic agents and techniques is discussed.