A cluster-randomised trial comparing home-based primary health care and usual clinic care for epilepsy in a resource-limited country

OBJECTIVE: To ascertain whether home-based care with community and primary healthcare workers' support improves adherence to antiseizure medications, seizure control, and quality of life over routine clinic-based care in community samples of people with epilepsy in a resource-poor country. METHODS: Participants included consenting individuals with active epilepsy identified in a population survey in impoverished communities. The intervention included antiseizure medication provision, adherence reinforcement and epilepsy self- and stigma management guidance provided by a primary health care-equivalent worker. We compared the intervention group to a routine clinic-based care group in a cluster-randomised trial lasting 24 months. The primary outcome was antiseizure medication adherence, appraised from monthly pill counts. Seizure outcomes were assessed by monthly seizure aggregates and time to first seizure and impact by the Personal Impact of Epilepsy scale. RESULTS: Enrollment began on 25.09.2017 and was complete by 24.07.2018. Twenty-four clusters, each comprising ten people with epilepsy, were randomised to either home- or clinic-care. Home-care recepients were more likely to have used up their monthly-dispensed epilepsy medicine stock (Regression Coefficient: 0.585; 95% Confidence Intervals, 0.289 to 0.881; P=0.001) and had fewer seizures (Regression coefficient: -2.060; 95%CI, -3.335 to -0.785; P=0.002). More people from clinic-care (n=44; 37%) than home-care (n=23; 19%) exited the trial (P=0.003). The time to first seizure, adverse effects and the personal impact of epilepsy were similar in the two arms. SIGNIFICANCE: Home care for epilepsy compared to clinic care in resource-limited communities improves medication adherence and seizure outcomes and reduces the secondary epilepsy treatment gap

HnRNPK maintains single strand RNA through controlling double-strand RNA in mammalian cells

Although antisense transcription is a widespread event in the mammalian genome, double-stranded RNA (dsRNA) formation between sense and antisense transcripts is very rare and mechanisms that control dsRNA remain unknown. By characterizing the FGF-2 regulated transcriptome in normal and cancer cells, we identified sense and antisense transcripts IER3 and IER3-AS1 that play a critical role in FGF-2 controlled oncogenic pathways. We show that IER3 and IER3-AS1 regulate each other\u27s transcription through HnRNPK-mediated post-transcriptional regulation. HnRNPK controls the mRNA stability and colocalization of IER3 and IER3-AS1. HnRNPK interaction with IER3 and IER3-AS1 determines their oncogenic functions by maintaining them in a single-stranded form. hnRNPK depletion neutralizes their oncogenic functions through promoting dsRNA formation and cytoplasmic accumulation. Intriguingly, hnRNPK loss-of-function and gain-of-function experiments reveal its role in maintaining global single- and double-stranded RNA. Thus, our data unveil the critical role of HnRNPK in maintaining single-stranded RNAs and their physiological functions by blocking RNA-RNA interactions

Alcohol use by men is a risk factor for the acquisition of sexually transmitted infections and human immunodeficiency virus from female sex workers in Mumbai, India

OBJECTIVE: We investigated whether men who were under the influence of alcohol when visiting female sex workers (FSW) were at greater risk for sexually transmitted infections (STI) and human immunodeficiency virus (HIV). STUDY: A cross-sectional analysis using baseline data from a randomized controlled trial of an HIV prevention intervention for high-risk men in Mumbai, India. RESULTS: The overall HIV prevalence among 1741 men sampled was 14%; 64% had either a confirmed STI or HIV; 92% reported sex with an FSW, of whom 66% reported having sex while under the influence of alcohol (SUI). SUI was associated with unprotected sex (odds ratio [OR]: 3.1; 95% confidence interval [CI], 2.3–4.1), anal sex (OR: 1.5; 1.1–2.0), and more than10 FSW partners (OR: 2.2; 1.8–2.7). SUI was independently associated with having either an STI or HIV (OR: 1.5; 1.2–1.9). CONCLUSION: Men who drink alcohol when visiting FSWs engage in riskier behavior and are more likely to have HIV and STIs. Prevention programs in India need to raise awareness of this relationship

Noncoding RNA Ginir functions as an oncogene by associating with centrosomal proteins.

Long noncoding RNAs constitute a major fraction of the eukaryotic transcriptome, and together with proteins, they intricately fine-tune various growth regulatory signals to control cellular homeostasis. Here, we describe the functional characterisation of a novel pair of long intergenic noncoding RNAs (lincRNAs) comprised of complementary, fully overlapping sense and antisense transcripts Genomic Instability Inducing RNA (Ginir) and antisense RNA of Ginir (Giniras), respectively, from mouse cells. This transcript pair is expressed in a spatiotemporal manner during embryonic development. The individual levels of the sense and antisense transcripts are finely balanced during embryonic growth and in adult tissues. Functional studies of the individual transcripts performed using overexpression and knock-down strategies in mouse cells has led to the discovery that Ginir RNA is a regulator of cellular proliferation and can act as an oncogene having a preeminent role in malignant transformation. Mechanistically, we demonstrate that the oncogenic function of Ginir is mediated by its interaction with centrosomal protein 112 (Cep112). Additionally, we establish here a specific interaction between Cep112 with breast cancer type 1 susceptibility protein (Brca1), another centrosome-associated protein. Next, we prove that the mutual interaction between Cep112 with Brca1 is significant for mitotic regulation and maintenance of genomic stability. Furthermore, we demonstrate that the Cep112 protein interaction with Brca1 protein is impaired when an elevated level of Ginir RNA is present in the cells, resulting in severe deregulation and abnormality in mitosis, leading to malignant transformation. Inhibiting the Ginir RNA function in transformed cells attenuates transformation and restores genomic stability. Together, these findings unravel, to our knowledge, a hitherto-unknown mechanism of oncogenesis mediated by a long noncoding RNA and establishes a unique role of Cep112-Brca1 interaction being modulated by Ginir RNA in maintaining mitotic fidelity