One solution to the arsenic problem: a return to surface (improved dug) wells

Arsenic contamination in drinking-water in Bangladesh is a major catastrophe, the consequences of which exceed most other man-made disasters. The national policy encourages the use of surface water as much as possible without encountering the problems of sanitation that led to the use of groundwater in the first place. This paper describes the success of the Dhaka Community Hospital (DCH) team and the procedure in implementing sanitary, arsenic-free, dugwells. The capital cost for running water is US$ 5-6 per person. Sixty-six sanitary dugwells were installed in phases between 2000 and 2004 in Pabna district of Bangladesh where there was a great need of safe water because, in some villages, 90% of tubewells were highly contaminated with arsenic. In total, 1,549 families now have access to safe arsenic-free dugwell water. Some of them have a water-pipe up to their kitchen. All of these were implemented with active participation of community members. They also pay for water-use and are themselves responsible for the maintenance and water quality. The DCH helped the community with installation and maintenance protocol and also with monitoring water quality. The bacteria levels are low but not always zero, and studies are in progress to reduce bacteria by chlorination.     

Inhibition of acetaldehyde metabolism decreases acetylcholine release in medial frontal cortex of freely moving rats

The effect of high acetaldehyde (ACe) on acetylcholine (ACh) release was studied in vivo in the medial frontal cortex (mfc) of freely moving rats using brain microdialysis coupled with high performance liquid chromatography and an electrochemical detector. Ethanol (EtOH) and ACe concentrations were quantified simultaneously in the mfc of awake rats by in vivo microdialysis followed by head-space gas chromatography. Rats were treated intraperitoneally with saline, EtOH (1 and 2 g/kg) or cyanamide (CY, 50 mg/kg, a potent aldehyde dehydrogenase inhibitor) plus EtOH (1 and 2 g/kg). No significant effect on ACh levels was observed in saline groups, as compared to baseline value. The basal level of ACh in the dialysate was about 0.30 +/- 0.04 pmol/20 microl, and this value was reduced significantly in the EtOH (1 and 2 g/kg) and CY + EtOH (1 and 2 g/kg) groups for 240 min after EtOH administration. The time courses of ACh release continued to decrease significantly after EtOH administration in the CY + EtOH (1 and 2 g/kg) groups compared to the values in the saline and EtOH (1 and 2 g/kg) groups. A significant decrease in ACh release was observed from 140 to 240 min after EtOH dosing in the EtOH (1 and 2 g/kg) groups, as compared to saline groups. EtOH and ACe concentrations in the mfc were first determined at 15 min after a dose of EtOH, reached a peak at 30 min and then gradually decreased in the CY + EtOH (1 and 2 g/kg) groups. The present study suggests that both EtOH and ACe concentration in the brain can decrease in vivo ACh release in the mfc of free-moving rats, and the ACe-induced decrease in ACh levels was significantly higher than EtOH.     

Severe malnutrition in infants aged <6 months—Outcomes and risk factors in Bangladesh: A prospective cohort study

Severe acute malnutrition (SAM) affects ~4 million infants under 6 months (u6m) worldwide, but evidence underpinning their care is “very low” quality. To inform future research and policy, the objectives of our study were to identify risk factors for infant u6m SAM and describe the clinical and anthropometric outcomes of treatment with current management strategies. We conducted a prospective cohort study in infants u6m in Barisal district, Bangladesh. One group of 77 infants had SAM (weight‐for‐length Z‐score [WLZ] <?3 and/or bipedal oedema); 77 others were “non‐SAM” (WLZ ≥?2 to <+2, no oedema, mid‐upper‐arm circumference ≥125 mm). All were enrolled at 4–8 weeks of age and followed up at 6 months. Maternal education and satisfaction with breastfeeding were among factors associated with SAM. Duration of exclusive breastfeeding was shorter at enrolment (3·9 ± 2.1 vs. 5.7 ± 2.2 weeks, P < 0.0001) and at age 6 months (13.2 ± 8.9 vs. 17.4 ± 7.9 weeks; P = 0.003) among SAM infants. Despite referral, only 13 (17%) reported for inpatient care, and at 6 months, 18 (23%) infants with SAM still had SAM, and 3 (3.9%) died. In the non‐SAM group, one child developed SAM, and none died. We conclude that current treatment strategies have limited practical effectiveness: poor uptake of inpatient referral being the main reason. World Health Organization recommendations and other intervention strategies of outpatient‐focused care for malnourished but clinically stable infants u6m need to be tested. Breastfeeding support is likely central to future treatment strategies but may be insufficient alone. Better case definitions of nutritionally at‐risk infants are also needed.     

Association between Non-Typhoidal Salmonella Infection and Growth in Children under 5 Years of Age: Analyzing Data from the Global Enteric Multicenter Study

Non-typhoidal Salmonella (NTS) is one of the less focused on infections and is often associated with faulty child nutrition in the developing world. This study aimed to evaluate the association of NTS infection with growth faltering among children under the age of five. We analyzed data from 378 fecal NTS positive children with both moderate-to-severe diarrhea (MSD) and asymptomatic infection from the seven countries of South Asia and sub-Saharan Africa during enrolment and on day 60 follow up in the Global Enteric Multicenter Study (GEMS) for the period of December 2007 to March 2011. Children not associated with fecal NTS (n = 1134) were randomly selected from the same dataset (1:3 ratio) as a comparison group. The association between an explanatory variable and the outcome variable was longitudinally tested using generalized estimating equations (GEE), where the dependent variables were height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z-score, and the independent variable was the presence of fecal NTS. The GEE multivariable model identified a negative association between fecal NTS and WAZ (coefficient: −0.19; 95% CI (confidence interval): −0.33, −0.04, and p value = 0.010), WHZ (coef: −0.19; 95% CI: −0.34, −0.05, and p value = 0.007), and HAZ (coef: −0.13; 95% CI: −0.27, −0.01, and p value = 0.073) after adjusting for age, gender, diarrhea, breastfeeding status, mothers’ education, number of children under the age of five, household size by the number of people regularly sleep at the home, handwashing practice, source of drinking water, wealth index, presence of co-pathogens, comorbidity, and study sites. In the GEMS, where children were followed during 50–90 days of enrolment, the presence of fecal NTS harmed the child’s anthropometric outcomes. Minimizing potential exposure to NTS is needed to curb worsening child undernutrition.     

Protein kinase C stabilizes X‐linked inhibitor of apoptosis protein (XIAP) through phosphorylation at Ser87 to suppress apoptotic cell death

Background: Multiple protein kinases have been shown to be involved in the apoptotic neuronal loss of Alzheimer's disease (AD). Although some studies support the role of protein kinase C (PKC) in amyloid precursor protein processing as well as in tau phosphorylation, a direct role for PKC in apoptotic neuronal death remains to be clarified. In the present study, we report on the possible role of PKC in cell survival during conditions of stress through phosphorylation of the X‐linked inhibitor of apoptosis protein (XIAP). Methods: Phosphorylation of XIAP at Ser87 was confirmed by western blot analysis employing phosphorylation dependent anti‐XIAP antibody after incubation of recombinant XIAP with active PKC in vitro. And increased phosphorylation of XIAP at the site was also confirmed in SH‐SY5Y cells treated with PKC activator, phorbol 12‐myristate 13‐acetate (PMA). A mutant XIAP construct in which Ser87 was substituted by Ala, was prepared, and transfected to cells. After the transfection of wild or mutant XIAP, cells viability was evaluated by counting living and dead cells treated with PMA during etoposide‐induced apoptosis. Results: Recombinant XIAP was phosphorylated at Ser⁸⁷ by PKC in vitro and treatment of XIAP‐transfected SH‐SY5Y cells with a PKC activator, phorbol 12‐myristate 13‐acetate (PMA) induced phosphorylation of XIAP at Ser⁸⁷. Pulse chase experiments revealed that, when phosphorylated at Ser⁸⁷, wild‐type XIAP is more stable than XIAP with a Ser87Ala substitution, which is degraded faster. Importantly, the phosphorylation of XIAP at the site by PKC significantly increased cell survival up to approximately 2.5 times under the condition of apoptosis induced by 25 µg/ml etoposide. Conclusion: The findings of the present study indicate a role for PKC, through phosphorylation of XIAP at Ser⁸⁷ and its stabilization, in cell survival under conditions of stress and lend strength to the idea that PKC is crucial in regulating neuronal homeostasis, which may be impaired in AD.     

Characterization of astrocyte reactivity and gene expression on biomaterials for neural electrodes

Neural electrode devices hold great promise to help people with the restoration of lost functions. However, research is lacking in the biomaterial design of a stable, long-term device. Glial scarring is initiated when a device is inserted into brain tissue and an inflammatory response ensues. Astrocytes become hypertrophic, hyperplastic, and upregulate glial-fibrillary acidic protein. This study was designed to investigate the astrocyte proliferation, viability, morphology, and gene expression to assess the reactive state of the cells on different material surfaces. Although platinum and silicon have been extensively characterized both in vivo and in vitro for their biocompatibility with neuronal cells, this study used the novel usage of PMMA and SU-8 in neural electrodes by comparative analysis of materials' biocompatibility. This study has shown evidence of noncytotoxicity of SU-8. We have also confirmed the biocompatibility of PMMA with astrocytes. Moreover, we have established sound guidelines of which neural implant materials should meet to be depicted biocompatible.     

High ethanol and acetaldehyde impair spatial memory in mouse models: opposite effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory

Aldehyde dehydrogenase 2 deficiency may directly contribute to excess acetaldehyde (AcH) accumulation after ethanol (EtOH) drinking and AcH mediates some of the behavioral effects of EtOH. Apolipoprotein E has been suggested to be involved in the alteration of attention and memory. We have chosen Aldh2-knockout (Aldh2-KO), ApoE-KO, and their wild-type (WT) control mice to examine the effects of EtOH and AcH on spatial memory and to compare the possible relationship between genetic deficiency and memory using two behavioral assessments. Mice were trained for 4 days, with EtOH (0.5, 1.0, 2.0 g/kg) being given intraperitoneally on day 4. A probe trial was given on day 5 in the non-EtOH state in the Morris water maze (MWM). The results showed that 2.0 g/kg EtOH increased errors, indicating memory impairment on the eight-arm radial maze (RAM) for all the mice studied. One gram per kilogram EtOH impaired the performance of Aldh2-KO and ApoE-KO mice, but not WT mice. We found similar effects of EtOH on the MWM performance, with 2.0 g/kg EtOH increasing the latencies. One gram per kilogram EtOH increased the latencies of Aldh2-KO and WT mice, but not ApoE-KO mice. The 2.0 g/kg EtOH-induced memory impairment in Aldh2-KO mice was greater, suggesting an AcH effect. Furthermore, time spent on the probe trial was shorter in mice that had previously received 2.0 g/kg EtOH. ApoE-KO mice learned more slowly, while Aldh2-KO mice learned more quickly. Both the RAM and MWM results suggest that high EtOH and AcH impair spatial memory in mice, while lower doses do not have consistent memory effects. In addition, we conclude that genetic differences might underlie some of EtOH's effects on memory.     

Findings for current marks: Histopathological examination and energy-dispersive X-ray spectroscopy of three cases

We describe herein three cases of electrocution. As most deaths caused by electricity are due to cardiac arrhythmia or paralysis of the respiratory muscles, autopsy findings in electrocution cases are generally non-specific, with the exception of the presence of current marks. We detected metallization by histological examination and energy-dispersive X-ray spectroscopy (EDX) analysis in tissues of typical or atypical current marks. In addition, myofiber break-up was observed in one case. One patient was hospitalized before death and revealed patchy contraction band necrosis, along with infiltration of leucocytes and vacuolation in the diaphragm. The presence of current marks is the hallmark for forensic diagnosis of electrocution. Although specific findings are lacking at autopsy in cases of electrocution, detailed histological examination and EDX analysis provide useful information for forensic diagnosis.