Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30–50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype–genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.

We conducted a controlled before-and-after trial to evaluate the impact of an onsite urban sanitation intervention on the prevalence of enteric infection, soil transmitted helminth re-infection, and diarrhea among children in Maputo, Mozambique. A non-governmental organization replaced existing poor-quality latrines with pour-flush toilets with septic tanks serving household clusters. We enrolled children aged 1-48 months at baseline and measured outcomes before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. Despite nearly exclusive use, we found no evidence that intervention affected the prevalence of any measured outcome after 12 or 24 months of exposure. Among children born into study sites after intervention, we observed a reduced prevalence of Trichuris and Shigella infection relative to the same age group at baseline (<2 years old). Protection from birth may be important to reduce exposure to and infection with enteric pathogens in this setting.

Summary Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size, but selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy.

Background. Onsite sanitation serves more than 740 million people in urban areas, primarily in low-income countries. Although this critical infrastructure may play an important role in controlling enteric infections in high-burden settings, its health impacts have never been evaluated in a controlled trial. Methods. We conducted a controlled before and after trial to evaluate the impact an onsite urban sanitation intervention on the prevalence of bacterial and protozoan infection (primary outcome), soil transmitted helminth (STH) re-infection, and seven-day period prevalence of diarrhoea among children living in informal neighborhoods of Maputo, Mozambique. A non-governmental organization replaced existing shared latrines in poor condition with engineered pour-flush toilets with septic tanks serving household clusters. We enrolled children aged 1-48 months at baseline and measured outcomes before the intervention and at 12 and 24 months following intervention. We measured outcomes concurrently among children served by the sanitation improvements and those in a comparable control arm served by existing poor sanitation. The trial was registered at ClinicalTrials.gov, number NCT02362932. Findings. At baseline, we enrolled 454 children from 208 intervention clusters and 533 children from 287 control clusters. We enrolled or re-visited 462 intervention and 477 control children 12 months 60 after intervention and 502 intervention and 499 control children 24 months after intervention. Despite nearly exclusive use of the intervention, we found no evidence that engineered onsite sanitation affected the overall prevalence of any measured bacterial or protozoan infection (12-month adjusted prevalence ratio 1.05, 95% CI [0.95-1.16]; 24-month adjusted prevalence ratio 0.99, 95% CI [0.91-1.09]), any STH re-infection (1.11 [0.89-1.38]; 0.95 [0.77-1.17]), or diarrhoea (1.69 [0.89-3.21]; 0.84 [0.47-1.51]) after 12 or 24 months of exposure. Among children born into study sites after the intervention and measured at the 24-month visit, we observed a reduced prevalence of any STH re-infection of 49% (adjusted prevalence ratio 0.51 [95% confidence interval 0.27 - 0.95]), Trichuris of 76% (0.24 [0.10 - 0.60]), and Shigella infection by 51% (0.49 [0.28-0.85]) relative to the same age group at baseline. Interpretation. The intervention did not reduce the overall prevalence of enteric infection and diarrhoea among all enrolled children but may have substantially reduced the prevalence of STHs and Shigella among children born into clusters with sanitary improvements.

Background The declaration of COVID-19 a pandemic by the World Health Organization on 11 March 2020 marked the beginning of a global health crisis of an unprecedented nature and scale. The approach taken by countries across the world varied widely, however, the delivery of frontline healthcare was consistently recognised as being central to the pandemic response. This study aimed to identify and explore the issues currently facing pharmacy teams across Commonwealth countries during the COVID-19 pandemic. The study also evaluates pharmacy professionals’ understanding of key knowledge areas from the COVID-19 webinar hosted by the Commonwealth Pharmacists’ Association (CPA). Method A quantitative survey-based approach was adopted, using a 32-item questionnaire developed from the literature on pharmacy and pandemic response. The survey was hosted on Survey Monkey and pilot tested. The final survey was disseminated by CPA member organisations. A 6-item online questionnaire was sent via email to all attendees of CPA's COVID-19 webinar. Descriptive statistics on frequency distributions and percentages were used to analyse the responses. Data were analysed using Microsoft® Excel (2010). Results There were 545 responses from pharmacy professionals across 31/54 Commonwealth countries in Africa, Asia, the Americas, Europe and the Pacific. Majority of the respondents reported being at least somewhat worried (90%) and more than 65% were very worried or extremely about the impact of COVID-19 on them personally and professionally. Nearly two-thirds of respondents stated finding it somewhat difficult or very difficult to work effectively during the pandemic. Challenges mostly faced by pharmacy professionals working remotely included; general anxiety about the impact of COVID-19 on their lives (12%), and difficulties in communicating with their co-workers (12%). Most pharmacy professionals had not previously been actively involved in a global health emergency (82%) nor obtained training on global/public health emergency preparedness (62%). Between 45 and 97% of the COVID-19 webinar attendees provided the correct answers to post-webinar questions, suggesting some improvement in knowledge. Conclusion Our study confirms pharmacy professionals’ concerns about practice during a pandemic and provides preliminary data on the challenges and learning needs of the profession. The CPA has since acted on these findings, providing ongoing opportunities to develop and refine resources for the profession as the pandemic evolves. Pharmacy professionals have also demonstrated improved knowledge on the management of COVID-19 and resources available for professionals.