Palestinian children's experiences of drug abuse in the home in the Occupied Territories of Palestine: A scoping review of extant literature

The Occupied Territories of Palestine (OtP) consists of the non-contiguous West Bank including East Jerusalem, and the Gaza Strip. Its dense population with political and economic tensions is affected by a rise in drug trafficking, abuse and addiction. A scoping review mapped what is known about Palestinian children's experiences of drug abuse in the home. Following application of exclusion measures, six records remained. Charting and analysis resulted in three themes; The consequences of being a child with a drug using parent; Causal factors of drug use in Palestinian families; and Prevalence rates of parental drug use are unknown. The review paints a concerning picture of stigma, family dysfunction, school drop-out, child and family isolation and maladaptive child development. Exposure to drugs, trauma and abuse contributes to strong potential for Palestinian child drug use, sexual exploitation, overdose, psychiatric illness, and infectious diseases acquisition. The review will inform the urgent strategic response

Internet sourcing and UK end consumer trend interest in the controlled medicines (opioids, sedatives and GABA drugs) in pre and post COVID-19 timeframes.

Sourcing and self-medication of medicinal pharmaceuticals including those containing opioids obtained from non-regulated online suppliers is a serious public health issue. The main concerns include a lack of quality control, drug side effects, drug interactions, diversion and possible pathway to drug dependence. The internet offers increased availability and accessibility of these medicines through both legal routes obtaining pharmaceuticals on prescription and illegal routes via websites on both the surface and Dark Web. The impact of the current severe acute respiratory syndrome coronavirus 2 (SARSCoV-2 or COVID-19) pandemic reduced face-to face access for non-COVID-19 related health conditions and to drug treatment services. This study provides an overview of the extent of online sourcing of UK controlled medicines (opioids, sedatives and GABA drugs) from unregulated suppliers and estimates of customer interest, in particular focusing on the COVID-19 lockdown period in the UK, where access to some healthcare services was limited. Whilst it was not possible to identify an increase for online searches for controlled medicines over the past five years, or during the COVID-19 period, searches remained plentiful, in particular for oxycodone, morphine and diazepam. This study highlights the need for enhanced pharmacovigilance of non-regulated online suppliers and the imperatives of continued health messaging around the potential abuse of these controlled drugs and the dangers of using sites purporting to be regulated pharmacies

A Poorly Known High-Latitude Parasitoid Wasp Community: Unexpected Diversity and Dramatic Changes through Time

Climate change will have profound and unanticipated effects on species distributions. The pace and nature of this change is largely unstudied, especially for the most diverse elements of terrestrial communities – the arthropods – here we have only limited knowledge concerning the taxonomy and the ecology of these groups. Because Arctic ecosystems have already experienced significant increases in temperature over the past half century, shifts in community structure may already be in progress. Here we utilise collections of a particularly hyperdiverse insect group – parasitoid wasps (Hymenoptera; Braconidae; Microgastrinae) – at Churchill, Manitoba, Canada in the early and mid-twentieth century to compare the composition of the contemporary community to that present 50–70 years ago. Morphological and DNA barcoding results revealed the presence of 79 species of microgastrine wasps in collections from Churchill, but we estimate that 20% of the local fauna awaits detection. Species composition and diversity between the two time periods differ significantly; species that were most common in historic collections were not found in contemporary collections and vice versa. Using barcodes we compared these collections to others from across North America; contemporary Churchill species are most affiliated with more south-western collections, while historic collections were more affiliated with eastern collections. The past five decades has clearly seen a dramatic change of species composition within the area studied coincident with rising temperature

Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

Wolbachia and DNA barcoding insects: patterns, potential and problems

Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein – wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor – for which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells

Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure

Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins

The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI)