Rising level of arsenic in water and fodder: a growing threat to livestock and human populations in Pakistan

Arsenic (As) is considered to be one of the top environmental contaminants of concern worldwide. In many regions in Pakistan, there are reports of increased levels of As in the environment, and this metalloid remains a major source of contamination of soil, water and fodder. This pathway of exposure has emerged as a new threat for both wildlife and the surrounding human communities because of the mobilization and accumulation of As via the food chain. The objective of this critical review is to synthesize historical information about As levels in the environmental resources of Pakistan to better characterize the risk to livestock and humans in the region. The South Punjab and Sindh are the dominant areas which are reported to contain the highest As contamination compared to other regions. This is a concern as millions of animals as well as the human population are facing significant health issues due to As. For example, some of the population of Sindh province are potentially faced with As levels ～10–50?μg/L in drinking water, which is well above safe drinking limits of 10?μg/L outlined by the World Health Organization. These collective data on As are anticipated to be a useful source of information for decisions by the environmental protection agency in Pakistan regarding the adoption of preventive measures against its adverse impacts and toxicity.     

A Closer Look at Racism and Heterosexism in Medical Students’ Clinical Decision-Making Related to HIV Pre-Exposure Prophylaxis (PrEP): Implications for PrEP Education

Social biases among healthcare providers could limit PrEP access. In this survey study of 115 US medical students, we examined associations between biases (racism and heterosexism) and PrEP clinical decision-making and explored prior PrEP education as a potential buffer. After viewing a vignette about a PrEP-seeking MSM patient, participants reported anticipated patient behavior (condomless sex, extra-relational sex, and adherence), intention to prescribe PrEP to the patient, biases, and background characteristics. Minimal evidence for racism affecting clinical decision-making emerged. In unadjusted analyses, heterosexism indirectly affected prescribing intention via all anticipated behaviors, tested as parallel mediators. Participants expressing greater heterosexism more strongly anticipated increased risk behavior and adherence problems, which were associated with lower prescribing intention. The indirect effect via condomless sex remained significant adjusting for background characteristics. Prior PrEP education did not buffer any indirect effects. Heterosexism may compromise PrEP provision to MSM and should be addressed in PrEP-related medical education.     

Soft palate reconstruction after radionecrosis: Combined anterolateral thigh adipofascial and nasoseptal flaps

Although radiation-based treatment for nasopharyngeal cancer may achieve excellent long term oncologic results, late effects of therapy may lead to soft tissue radionecrosis and velopharyngeal insufficiency (VPI). Repair of these oro- and nasopharyngeal defects presents a complex reconstructive challenge. We present a case of a long-term survivor treated with chemoradiotherapy for nasopharyngeal cancer who developed progressive dysphagia, velopharyngeal insufficiency, and radionecrosis of the nasopharynx and soft palate, leading to tracheostomy and gastrostomy tube dependence. A staged reconstruction was performed, initially with a tubed nasoseptal flap for a creation of a mucosal-lined nasopharyngeal port. An adipofascial anterolateral thigh free flap was subsequently performed for soft palate reconstruction. Within 2 months, the oropharyngeal reconstruction had remucosalized and she was decannulated, taking an oral diet. Her speech was intelligible and she had good nasal breathing without symptoms of velopharyngeal insufficiency.     

Migrant care workers as protective factor against caregiver burden: results from a longitudinal analysis of the EUROFAMCARE study in Italy

Objective: The aim of the analysis is to assess the impact of privately employed migrant care workers (MCWs) on the burden of Italian family members who care for a disabled older person.

Methods: EUROFAMCARE is a one-year prospective survey carried out to provide evidence on the availability and use of support services by family carers of older people in Europe. In Italy, 990 family caregivers were enrolled and successful follow-ups were completed for 863 subjects. The survey also assessed the level of caregiver burden using the COPE index, which has three sub-sections: ‘Positive Value’ (PV), ‘Quality of Support’ (QS) and ‘Negative Impact’ (NI). We used the one-year change of the COPE-NI as dependent variable and we realised multilevel regression models to estimate the longitudinal predictors of caregivers’ burden increase.

Results: At a cross-sectional level, most burdened caregivers are those caring for a demented relative (COPE-NI = 13.6), with no educational title (14.5) and looking after their own spouses (15.1). Longitudinally those employing an MCW are significantly protected against burden increase (regression coefficient: ?1.52; p < 0.01) while those who cannot rely on the support of other family members are exposed to the risk of burden increase (0.991; p < 0.05). Other formal services do not have any protective effect.

Conclusion: Our study suggests that employing an MCW, rather than using formal services, is associated with a reduction of caregiving burden. Further research should assess whether the shift in care responsibilities to the MCWs also implies a transfer of care burden, and understand how these workers can be better supported by existing formal services.     

Determinants of Postoperative Outcomes of Female Genital Fistula Repair Surgery

OBJECTIVE:: To determine predictors of fistula repair outcomes 3 months postsurgery. METHODS:: We conducted a multicountry prospective cohort study between 2007 and 2010. Outcomes, measured 3 months postsurgery, included fistula closure and residual incontinence in women with a closed fistula. Potential predictors included patient and fistula characteristics and context of repair. Multivariable generalized estimating equation models were used to generate adjusted risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS:: Women who returned for follow-up 3-month postsurgery were included in predictors of closure analyses (n=1,274). Small bladder size (adjusted RR 1.57, 95% CI 1.39-1.79), prior repair (adjusted RR 1.40, 95% CI 1.11-1.76), severe vaginal scarring (adjusted RR 1.56, 95% CI 1.20-2.04), partial urethral involvement (adjusted RR 1.36, 95% CI 1.11-1.66), and complete urethral destruction or circumferential defect (adjusted RR 1.72, 95% CI 1.33-2.23) predicted failed fistula closure. Women with a closed fistula at 3-month follow-up were included in predictors of residual incontinence analyses (n=1,041). Prior repair (adjusted RR 1.37, 95% CI 1.13-1.65), severe vaginal scarring (adjusted RR 1.35, 95% CI 1.10-1.67), partial urethral involvement (adjusted RR 1.78, 95% CI 1.27-2.48), and complete urethral destruction or circumferential defect (adjusted RR 2.06, 95% CI 1.51-2.81) were significantly associated with residual incontinence. CONCLUSION:: The prognosis for genital fistula closure is related to preoperative bladder size, previous repair, vaginal scarring, and urethral involvement. LEVEL OF EVIDENCE:: II.     

GLI inhibitor GANT-61 diminishes embryonal and alveolar rhabdomyosarcoma growth by inhibiting Shh/AKT-mTOR axis

Rhabdomyosarcoma (RMS) typically arises from skeletal muscle. Currently, RMS in patients with recurrent and metastatic disease have no successful treatment. The molecular pathogenesis of RMS varies based on cancer sub-types. Some embryonal RMS but not other sub-types are driven by sonic hedgehog (Shh) signaling pathway. However, Shh pathway inhibitors particularly smoothened inhibitors are not highly effective in animals. Here, we show that Shh pathway effectors GLI1 and/or GLI2 are over-expressed in the majority of RMS cells and that GANT-61, a specific GLI1/2 inhibitor dampens the proliferation of both embryonal and alveolar RMS cells-derived xenograft tumors thereby blocking their growth. As compared to vehicle-treated control, about 50% tumor growth inhibition occurs in mice receiving GANT-61 treatment. The proliferation inhibition was associated with slowing of cell cycle progression which was mediated by the reduced expression of cyclins D1/2/3 & E and the concomitant induction of p21. GANT-61 not only reduced expression of GLI1/2 in these RMS but also significantly diminished AKT/mTOR signaling. The therapeutic action of GANT-61 was significantly augmented when combined with chemotherapeutic agents employed for RMS therapy such as temsirolimus or vincristine. Finally, reduced expression of proteins driving epithelial mesenchymal transition (EMT) characterized the residual tumors.