Drivers of Microbial Risk for Direct Potable Reuse and de Facto Reuse Treatment Schemes: The Impacts of Source Water Quality and Blending.

Although reclaimed water for potable applications has many potential benefits, it poses concerns for chemical and microbial risks to consumers. We present a quantitative microbial risk assessment (QMRA) Monte Carlo framework to compare a de facto water reuse scenario (treated wastewater-impacted surface water) with four hypothetical Direct Potable Reuse (DPR) scenarios for Norovirus, Cryptosporidium, and Salmonella. Consumer microbial risks of surface source water quality (impacted by 0-100% treated wastewater effluent) were assessed. Additionally, we assessed risks for different blending ratios (0-100% surface water blended into advanced-treated DPR water) when source surface water consisted of 50% wastewater effluent. De facto reuse risks exceeded the yearly 10-4 infections risk benchmark while all modeled DPR risks were significantly lower. Contamination with 1% or more wastewater effluent in the source water, and blending 1% or more wastewater-impacted surface water into the advanced-treated DPR water drove the risk closer to the 10-4 benchmark. We demonstrate that de facto reuse by itself, or as an input into DPR, drives microbial risks more so than the advanced-treated DPR water. When applied using location-specific inputs, this framework can contribute to project design and public awareness campaigns to build legitimacy for DPR

Alternative splicing and protein diversity: plants versus animals

Plants, unlike animals, exhibit a very high degree of plasticity in their growth and development and employ diverse strategies to cope with the variations during diurnal cycles and stressful conditions. Plants and animals, despite their remarkable morphological and physiological differences, share many basic cellular processes and regulatory mechanisms. Alternative splicing (AS) is one such gene regulatory mechanism that modulates gene expression in multiple ways. It is now well established that AS is prevalent in all multicellular eukaryotes including plants and humans. Emerging evidence indicates that in plants, as in animals, transcription and splicing are coupled. Here, we reviewed recent evidence in support of co-transcriptional splicing in plants and highlighted similarities and differences between plants and humans. An unsettled question in the field of AS is the extent to which splice isoforms contribute to protein diversity. To take a critical look at this question, we presented a comprehensive summary of the current status of research in this area in both plants and humans, discussed limitations with the currently used approaches and suggested improvements to current methods and alternative approaches. We end with a discussion on the potential role of epigenetic modifications and chromatin state in splicing memory in plants primed with stresses

Phenotypic and genotypic analysis of benzimidazole resistance in reciprocal genetic crosses of Haemonchus contortus

Haemonchus contortus is arguably one of the most economically important and ubiquitous parasites of livestock globally and commonly involved in cases of anthelmintic resistance. Here, we performed reciprocal genetic crosses using susceptible (MHco3(ISE)) and multiple anthelmintic resistant (MHco18(UGA2004)) H. contortus isolates. Resultant admixed populations were designated MHco3/18 or MHco18/3, where the lead isolate reflects the origin of the females. Three independent filial generations were generated for each cross, which were subjected to bioassays, molecular approaches and population genetic analyses to investigate the phenotypic and genotypic inheritance of benzimidazole (BZ) resistance at each stage. A panel of microsatellite markers confirmed the success of the genetic cross as markers from both parents were seen in the F(1) crosses. Egg hatch tests revealed a stark difference between the two F(1) crosses with ED(50) estimates for MHco18/3 being 9 times greater than those for MHco3/18. Resistance factors based on ED(50) estimates ranged from 6 to 57 fold in the filial progeny compared to MHco3(ISE) parents. Molecular analysis of the F167Y and F200Y SNP markers associated with BZ resistance were analysed by pyrosequencing and MiSeq deep amplicon sequencing, which showed that MHco3/18.F(1) and MHco18/3.F(1) both had similar frequencies of the F200Y resistant allele (45.3% and 44.3%, respectively), whereas for F167Y, MHco18/3.F(1) had a two-fold greater frequency of the resistant-allele compared to MHco3/18.F(1) (18.2% and 8.8%, respectively). Comparison between pyrosequencing and MiSeq amplicon sequencing revealed that the allele frequencies derived from both methods were concordant at codon 200 (r(c) = 0.97), but were less comparable for codon 167 (r(c) = 0.55). The use of controlled reciprocal genetic crosses have revealed a potential difference in BZ resistance phenotype dependent on whether the resistant allele is paternally or maternally inherited. These findings provide new insight and prompt further investigation into the inheritance of BZ resistance in H. contortus

The Ontario Pharmacy Evidence Network Atlas of Smoking Cessation Services

Introduction Tobacco smoking is a significant public health concern. It is estimated that more than 40,000 deaths and $6.5 billion in direct health care costs are attributable to tobacco smoking in Canada each year. Individuals who smoke tobacco or who are exposed to second-hand smoke are at increased risk of respiratory disease, cardiovascular disease and cancer. It is well known that quitting smoking can improve immediate and long-term health, yet nicotine dependence is a significant barrier to smoking cessation. Multimodal approaches that include medication and counselling services promote successful smoking cessation

Not Managing Expectations: A Grounded Theory of Intimate Partner Violence From the Perspective of Pakistani People

Intimate partner violence (IPV) is a major social and public health problem affecting people from different cultures and societies. Much research has been undertaken to understand the phenomenon, its determinants, and its consequences in numerous countries. However, there is a paucity of research on IPV in many areas of the world including Pakistan. The present study aimed to develop a theory of the meaning and process of IPV from the perspective of Pakistani men and women living in and outside Pakistan

Functional analysis of germline <em>VANGL2</em> variants using rescue assays of <em>vangl2</em> knockout zebrafish

\ua9 The Author(s) 2023. Published by Oxford University Press. Developmental studies have shown that the evolutionarily conserved Wnt Planar Cell Polarity (PCP) pathway is essential for the development of a diverse range of tissues and organs including the brain, spinal cord, heart and sensory organs, as well as establishment of the left-right body axis. Germline mutations in the highly conserved PCP gene VANGL2 in humans have only been associated with central nervous system malformations, and functional testing to understand variant impact has not been performed. Here we report three new families with missense variants in VANGL2 associated with heterotaxy and congenital heart disease p.(Arg169His), non-syndromic hearing loss p.(Glu465Ala) and congenital heart disease with brain defects p.(Arg135Trp). To test the in vivo impact of these and previously described variants, we have established clinically-relevant assays using mRNA rescue of the vangl2 mutant zebrafish. We show that all variants disrupt Vangl2 function, although to different extents and depending on the developmental process. We also begin to identify that different VANGL2 missense variants may be haploinsufficient and discuss evidence in support of pathogenicity. Together, this study demonstrates that zebrafish present a suitable pipeline to investigate variants of unknown significance and suggests new avenues for investigation of the different developmental contexts of VANGL2 function that are clinically meaningful

Saccharomyces cerevisiae-based system for studying clustered DNA damages

DNA-damaging agents can induce clustered lesions or multiply damaged sites (MDSs) on the same or opposing DNA strands. In the latter, attempts to repair MDS can generate closely opposed single-strand break intermediates that may convert non-lethal or mutagenic base damage into double-strand breaks (DSBs). We constructed a diploid S. cerevisiae yeast strain with a chromosomal context targeted by integrative DNA fragments carrying different damages to determine whether closely opposed base damages are converted to DSBs following the outcomes of the homologous recombination repair pathway. As a model of MDS, we studied clustered uracil DNA damages with a known location and a defined distance separating the lesions. The system we describe might well be extended to assessing the repair of MDSs with different compositions, and to most of the complex DNA lesions induced by physical and chemical agents