Long-lasting stress, quantitative changes in nitric oxide concentration and functional state of brain mitochondria

We have studied biochemical changes occurring in brain cell mitochondria of white rats on the background of stress induced by 30-day isolation and disruption of circadian rhythms. It was ascertained that due to long-lasting stress, there occurs activation of oxidative processes in mitochondria as well as inhibition of anti-oxidant system activity, causing development of energy deficiency in brain cells. The above-mentioned biochemical processes become the reason for activation and opening of the mitochondrial permeability transition pore (MPTP), which, in its turn, signals the start of neuroapoptosis and various neurodegenerative processes.     

Breastfeeding practices of Cameroonian mothers determined by dietary recall since birth and the dose-to-the-mother deuterium-oxide turnover technique

Exclusive breastfeeding during the first 6 months of infant's life is a public health recommendation and important factor for the promotion of optimal growth, health and behavioural development of each child. The accuracy of the mothers' self-reported past infant-feeding events was examined and compared with the isotopic dilution technique. Breastfeeding practices were assessed in a sample of 44 Cameroonian mother-infant pairs using dietary recall since birth. Intakes of breast milk and non-breast milk water were measured in the same sample using the dose-to-the-mother deuterium-oxide turnover technique and compared with questionnaire. Results showed that mothers' self-reported behaviour overestimates the exclusive breastfeeding rate. Seventy-five per cent of the mothers who claimed to be exclusively breastfeeding were found to be predominantly or partially breastfeeding by the dose-to-the-mother deuterium-oxide turnover technique. Only 11% of the infants were exclusively breastfed, and the breast milk output was not significantly affected (P ≤ 0.05) by the mother's body composition. Mean intakes of breast milk and non-breast milk water were 701 mL day(-1) and 268 mL day(-1), respectively. Introduction of non-breast milk foods is associated with a reduction in the level of breast milk intake, but the difference in breast milk intake was not significant between exclusively and predominantly breastfed infants. In conclusion, the dose-to-the-mother deuterium-oxide turnover technique can be applied to validate the mother's reports of infant-feeding practices, but non-breast milk water intake by breastfeeding category still needs to be normalized.     

Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC)

Objectives

Lymphadenectomy as a part of the staging for EC patients is controversial. Sentinel lymph node detection has been introduced to determine which patients would benefit from adjuvant therapy and to limit morbidities associated with a full pelvic nodal dissection. The purpose of this study is to evaluate diagnostic accuracy and detection rate of robotic sentinel lymph node detection (RSLND) as a part of the surgical staging for EC.

Methods

A retrospective database of all patients who underwent intraoperative lymphatic mapping using cervical injection methylene blue followed by RSLND as a part of their procedure was reviewed. Sentinel lymph node (SLN) was initially examined by routine Hematoxylin and Eosin (H&E) and ultrastaging by immunohistochemistry (IHC).

Results

Between 4/2011 and 6/2013, 120 patients with endometrial cancer underwent RSLND. The median age was 62 years (25–87); median BMI was 32 (18–76). Out of 120 patients, only one patient underwent RSLND with fertility preservation; and 119 patients underwent robotic hysterectomy and surgical staging with RSLND. None of the cases was converted to an open procedure. At least 1 SLN was detected in 86% (103/120) of the patients. Bilateral SLNs were detected in 52% (62/120). Positive nodes were identified in 8% (10/120) of the patients. Of those with SLN (+), 50% (5/10) were by ultrastaging (IHC) alone. No patients had positive regional nodes without SLN (+).

Conclusions

RSLND using methylene blue cervical injection can identify SLN in most patients with EC. IHC ultrastaging improves the detection of node positive disease when compared to traditional pathological evaluation.     

Severe malnutrition and metabolic complications of HIV-infected children in the antiretroviral era: clinical care and management in resource-limited settings

More than 2 million children globally are living with HIV infection and >90% of these reside in sub-Saharan Africa. Severe acute malnutrition (SAM) remains a major problem for HIV-infected children who live in resource-limited settings (RLS), and SAM is an important risk factor for mortality. SAM in HIV-infected children is associated with complications including electrolyte disorders, micronutrient deficiencies, and severe infections, which contribute to the high mortality. Access to antiretroviral therapy (ART) has significantly improved the survival of HIV-infected children, although the response to ART of children with SAM remains undocumented in the literature. Immune and virologic responses to ART in RLS are similar to those of infected children in resource-rich settings, but delays in initiation of therapy have led to a high early mortality. Antiretroviral drug toxicities have been described in children who receive therapy and may affect their quality of life and long-term survival. Metabolic complications of ART include lipodystrophy, dyslipidemia, lactic acidosis, insulin resistance, and osteopenia. These complications have been well described in adults and children from developed countries, but data from RLS are limited, and these complications may be compounded by SAM. In this article we review the epidemiology, clinical presentation, and complications of SAM in HIV-infected children and the metabolic complications of HIV-infected children in the era of ART, and discuss future research priorities for RLS.     

Acute toxicity studies of Croton membranaceus root extract

Aim of the study

Croton membranaceus root and leaf extracts are used in the Bahamas to aromatize tobacco, in Nigeria to improve digestion, and in Ghana, for benign prostate hyperplasia. Despite claims of success there is paucity of information on its toxicity. The aim of this study was to determine if Croton membranaceus has acute toxicity properties.

Materials and methods

Roots were air-dried in a solar dryer for one week before milling. The powder was extracted with 96% ethanol, freeze-dried and re-extracted with distilled water and freeze-dried. 15 male Sprague-Dawley rats (180-200 g) were divided equally into 2 treatment groups [low dose (LD) and high dose (HD)], plus a control group (C). LD and HD received 1500 and 3000 mg/kg b.wt. Croton membranaceus aqueous extract, respectively, one time and observed for 14 days. Haematological [Full Blood Count and haemoglobin (Hb)], biochemical [bilirubin, alanine aminotransferase (ALA), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatise (ALP), γ-glutamyltranspetidase (GGT), urea, creatinine, creatinine kinase - Muscle and Brain (CK-MB), creatinine kinase - Total (CK-R)] examinations were performed.

Results

Control group's CK-MB (5444 ± 534 U/L) and LD group CK-MB (4014 ± 1016 U/L) were significantly different (p < 0.05). Control and the HD group CK-MB (3955 ± 1135 U/L) were significantly different (p < 0.05). Both LD and HD CK-R levels (697 ± 197 U/L and 732 ± 203 U/L, respectively), were lower than the control (1139 ± 220 U/L) at 48 h and 14 days (p < 0.05, p < 0.05, respectively). γ-GT levels of the HD group was 4.8 ± 0.4 U/L compared to the Control group value of 0.9 ± 0.2 U/L (p < 0.05).

Conclusions

Taking all factors into consideration, Croton membranaceus ingestion does not produce general acute toxicity. However, its creatinine kinase lowering ability could be explored.     

Alcohol Consumption During Pregnancy and Risk of Placental Abruption and Placenta Previa

The purpose of this study was to examine the association between prenatal alcohol consumption and the occurrence of placental abruption and placenta previa in a population-based sample. We used linked birth data files to conduct a retrospective cohort study of singleton deliveries in the state of Missouri during the period 1989 through 2005 (n = 1,221,310). The main outcomes of interest were placenta previa, placental abruption and a composite outcome defined as the occurrence of either or both lesions. Multivariate logistic regression was used to generate adjusted odd ratios, with non-drinking mothers as the referent category. Women who consumed alcohol during pregnancy had a 33% greater likelihood for placental abruption during pregnancy (adjusted odds ratio (OR), 95% confidence interval (CI) = 1.33 [1.16–1.54]). No association was observed between prenatal alcohol use and the risk of placenta previa. Alcohol consumption in pregnancy was positively related to the occurrence of either or both placental conditions (adjusted OR [95% CI] = 1.29 [1.14–1.45]). Mothers who consumed alcohol during pregnancy were at elevated risk of experiencing placental abruption, but not placenta previa. Our findings underscore the need for screening and behavioral counseling interventions to combat alcohol use by pregnant women and women of childbearing age.     

Using research to influence sexual and reproductive health practice and implementation in Sub-Saharan Africa: a case-study analysis

Background

Research institutions and donor organizations are giving growing attention to how research evidence is communicated to influence policy. In the area of sexual and reproductive health (SRH) and HIV there is less weight given to understanding how evidence is successfully translated into practice. Policy issues in SRH can be controversial, influenced by political factors and shaped by context such as religion, ethnicity, gender and sexuality.

Methods

The case-studies presented in this paper analyse findings from SRH/HIV research programmes in sub-Saharan Africa: 1) Maternal syphilis screening in Ghana, 2) Legislative change for sexual violence survivors In Ghana, 3) Male circumcision policy in South Africa, and 4) Male circumcision policy in Tanzania. Our analysis draws on two frameworks, Sumner et al’s synthesis approach and Nutley’s research use continuum.

Results

The analysis emphasises the relationships and communications involved in using research to influence policy and practice and recognises a distinction whereby practice is not necessarily influenced as a result of policy change – especially in SRH – where there are complex interactions between policy actors.

Conclusion

Both frameworks demonstrate how policy networks, partnership and advocacy are critical in shaping the extent to which research is used and the importance of on-going and continuous links between a range of actors to maximize research impact on policy uptake and implementation. The case-studies illustrate the importance of long-term engagement between researchers and policy makers and how to use evidence to develop policies which are sensitive to context: political, cultural and practical.

     

Monoclonal antibody targeting MUC1 and increasing sensitivity to docetaxel as a novel strategy in treating human epithelial ovarian cancer

The purpose of this study was to investigate the in vitro effect of anti-MUC1 monoclonal antibody (MAb) C595 alone and in combination with docetaxel, on the growth and survival of different epithelial ovarian cancer (EOC) cell lines. MUC1 expression was assessed on EOC cell lines (OVCAR-3, IGROV-1, A2780, CAOV-3, TOV-21G, TOV-112D, SKOV-3 and OV-90) using immunofluorescence labeling and flow cytometry. The effect of MAb C595 alone or in combination with docetaxel on the cell lines was studied by proliferation, colony and TUNEL assays. Our results indicate that all primary and metastatic EOC cell lines tested were positive to MAb C595 (MUC1); MAb C595 inhibited EOC cell proliferation in a MUC1- and dose-dependent manner; low-dose MAb C595 (1/2 of IC₅₀) combined with docetaxel greatly improved efficiency of cell killing in EOC cells and induced apoptosis; the additive effect of MAb C595 was further confirmed in colony forming assays; and cell death following single or combined treatments was associated with the release of cytochrome c and increased caspase-3 activity. These results suggest that MAb C595 used either alone, or combined with docetaxel, is an attractive strategy for targeting human EOC.     

Increasing the priority of mental health in Africa: findings from qualitative research in Ghana, South Africa, Uganda and Zambia

Despite the high prevalence of mental illness, mental health remains a low priority in Africa. There has been no investigation of the views of stakeholders in Africa on why this is and what can be done. This paper reports a comparison of the views of stakeholders in Ghana, South Africa, Uganda and Zambia, focusing on the priority given to mental health by the government at the national and regional/province levels. We conducted semi-structured interviews with key stakeholders and used a two-stage approach to analysis: firstly framework analysis in each study country, followed by comparative analysis of the country data. Mental health was largely considered a low priority at national and regional/provincial levels in all four countries. We identified nine factors affecting the priority of mental health, which were grouped into three categories: legitimacy of the problem, feasibility of response and support for response. Respondents put forward a range of experiences and suggestions for increasing the priority given to mental health. We conclude with broad suggestions to raise the priority of mental health. These suggestions are particularly relevant as mental health increases in priority on the international agenda, in order to inform advocacy for increased priority for mental health in Africa.