Knowledge, attitude, and practice study among healthcare workers, during COVID-19 pandemic in an aspiring district of Uttar Pradesh

Background: COVID-19 (coronavirus disease 2019) declared pandemic by WHO on 30th January 2020. Till date there is no antiviral treatment or vaccine has been developed for COVID-19. Primary preventive measures include regular hand washing, social distancing and respiratory etiquettes are only proven methods till date.Methods: A type of questionnaire based cross sectional study was conducted among the healthcare workers (HCWs) of Maharaja Suheldev Autonomous State Medical College, Bahraich.Results: In this predominantly uneducated and socially backward area, majority of participants had knowledge about COVID-19 precautionary measures and most of them are confident of winning over the disease; 77.5% were confident of successfully controlling the disease, yet maximum healthcare workers took seriously the precautionary measures.Conclusions: Good COVID-19 knowledge is associated with optimistic attitudes and appropriate practices towards COVID-19, suggesting that health education programs aimed at improving COVID-19 knowledge are helpful for encouraging an optimistic attitude and maintaining safe practices

Contemporary spatial association of genetic diversity determinants in Asian Dipterocarps: a systematic review

Considering the research gaps and areas to be prioritized specifically in the forestry research sector with stress given on conservation genetics and tree improvement, we make an effort to understand the spatial patterns and identify the key determinants, which produce major effects on genetic diversity of Asian Dipterocarps. This review focuses on identifying patterns and establishing relationships between genecological parameters derived on the basis of molecular markers with factors, such as geographical range, vertical profile and IUCN categories along with recognizing research gaps pertaining to operational forestry and terrestrial ecosystems. Corresponding to 47 research papers, meta-analysis of 50 species under subfamily Dipterocarpoideae revealed significant differences in genetic parameters, namely expected heterozygosity (HE) and number of alleles per locus (NA), for most genera and factors. These parameters showed significant correlations with vertical strata (rk=-0.241; p<0.05) and altitude (rs=0.283; p<0.01). However, on the basis of co-dominant and dominant markers, the parameters exhibited contrasting results for the species’ characteristics. Further, pollen exchange and seed dispersal predominantly explained the genetic variations among the contributing factors, generally believed to be correlated with vertical strata and geographical range of the species. Conclusively, two major clusters were formed through principal component analysis (PCA), where HE and NA were the main deciding factors. Anthropogenic interferences, viz. forest fragmentation and deforestation found to be subsidising major impacts, which increase inbreeding and genetic drift, causing the loss of rare alleles and consequently, decreasing genetic variation. The study emphasizes the importance of genecological conservation and access to diverse genetic resources information, which will ensure global forest conservation and climate change mitigation network for sustainable development

Unexpected origins of the enhanced pairing affinity of 2 \u27-fluoro-modified RNA

Various chemical modifications are currently being evaluated for improving the efficacy of short interfering RNA (siRNA) duplexes as antisense agents for gene silencing in vivo. Among the 2\u27-ribose modifications assessed to date, 2\u27deoxy-2\u27-fluoro-RNA (2\u27-F-RNA) has unique properties for RNA interference (RNAi) applications. Thus, 2\u27-F-modified nucleotides are well tolerated in the guide (antisense) and passenger (sense) siRNA strands and the corresponding duplexes lack immunostimulatory effects, enhance nuclease resistance and display improved efficacy in vitro and in vivo compared with unmodified siRNAs. To identify potential origins of the distinct behaviors of RNA and 2\u27-F-RNA we carried out thermodynamic and X-ray crystallographic analyses of fully and partially 2\u27-F-modified RNAs. Surprisingly, we found that the increased pairing affinity of 2\u27-F-RNA relative to RNA is not, as commonly assumed, the result of a favorable entropic contribution (\u27conformational preorganization\u27), but instead primarily based on enthalpy. Crystal structures at high resolution and osmotic stress demonstrate that the 2\u27-F-RNA duplex is less hydrated than the RNA duplex. The enthalpy-driven, higher stability of the former hints at the possibility that the 2\u27-substituent, in addition to its important function in sculpting RNA conformation, plays an underappreciated role in modulating Watson-Crick base pairing strength and potentially pi-pi stacking interactions

In vivo silencing of alpha-synuclein using naked siRNA

<p>Abstract</p> <p>Background</p> <p>Overexpression of α-synuclein (SNCA) in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease <it>post-mortem</it>. Genetic variability in <it>SNCA </it>contributes to risk of idiopathic Parkinson's disease (PD), possibly as a result of overexpression. <it>SNCA </it>downregulation is therefore a valid therapeutic target for PD.</p> <p>Results</p> <p>We have identified human and murine-specific siRNA molecules which reduce <it>SNCA in vitro</it>. As a proof of concept, we demonstrate that direct infusion of chemically modified (naked), murine-specific siRNA into the hippocampus significantly reduces <it>SNCA </it>levels. Reduction of <it>SNCA </it>in the hippocampus and cortex persists for a minimum of 1 week post-infusion with recovery nearing control levels by 3 weeks post-infusion.</p> <p>Conclusion</p> <p>We have developed naked gene-specific siRNAs that silence expression of <it>SNCA in vivo</it>. This approach may prove beneficial toward our understanding of the endogenous functional equilibrium of <it>SNCA</it>, its role in disease, and eventually as a therapeutic strategy for α-synucleinopathies resulting from <it>SNCA </it>overexpression.</p

Observation of epitaxially ordered twinned zinc aluminate “nanoblades” on c-capphire

We report the observation of a novel nanostructured growth mode of the ceramic spinel zinc aluminate grown on c-sapphire in the form of epitaxially ordered twinned crystallites with pronounced vertically aligned “nanoblades” on top of these crystallites. The nanostructures are formed on bare c-sapphire substrates using a vapour phase transport method. Electron microscopy images reveal the nanostructure morphology and dimensions and allow direct and indirect observation of the twin boundary location in a number of samples. The nanoblade structure with sharply rising sidewalls gives rise to a distinctive bright contrast in secondary electron images in scanning electron microscopy measurements

A Community-Based Prospective Cohort Study of Exclusive Breastfeeding in Central Nepal

Background: Existing information on breastfeeding in low income countries such as Nepal has been largely derived from cross-sectional demographic health surveys. This study investigated exclusive breastfeeding rates, and compared the duration of exclusive breastfeeding between rural and urban mothers in central Nepal using an alternate cohort methodology. Methods: A community-based prospective cohort study was conducted among 639 recently delivered mothers representative of the Kaski district of Nepal. Breastfeeding information was obtained at birth (n = 639), 4 weeks (n = 639), 12 weeks (n = 615; 96.2%) and 22 weeks (n = 515; 80.6%) through repeated interviews using validated questionnaires. Risk of cessation of exclusive breastfeeding was assessed by Cox regression analysis. Results: The great majority of women received breastfeeding information (74%) and were encouraged to breastfeed by health personnel or family members (81%). Although nearly all mothers (98%) breastfed up to six months, the reported exclusive breastfeeding rate declined rapidly from 90.9% at birth to 29.7% at 22 weeks. Urban women experienced significantly shorter (p = 0.02) exclusive breastfeeding duration (mean 104.5, 95% CI 95.8 to113.1 days) and were more likely to cease exclusive breastfeeding (hazard ratio (HR) 1.28, 95% CI 1.03 to 1.60) than their rural counterparts (mean 144.7, 95% CI 132.3 to 157.1 days). Breastfeeding problem (HR 2.07, 95% CI 1.66 to2.57) and caesarean delivery (HR 1.88, 95% CI 1.36 to 2.62) were also significantly associated with exclusive breastfeeding cessation.Conclusions: Despite the almost universal practice of breastfeeding, the reported exclusive breastfeeding rates declined substantially over time. Exclusive breastfeeding up to six months was more common in rural than urban areas of central Nepal. Urban mothers also exclusively breastfed shorter than rural mothers

Unexpected origins of the enhanced pairing affinity of 2′-fluoro-modified RNA

Various chemical modifications are currently being evaluated for improving the efficacy of short interfering RNA (siRNA) duplexes as antisense agents for gene silencing in vivo. Among the 2′-ribose modifications assessed to date, 2′deoxy-2′-fluoro-RNA (2′-F-RNA) has unique properties for RNA interference (RNAi) applications. Thus, 2′-F-modified nucleotides are well tolerated in the guide (antisense) and passenger (sense) siRNA strands and the corresponding duplexes lack immunostimulatory effects, enhance nuclease resistance and display improved efficacy in vitro and in vivo compared with unmodified siRNAs. To identify potential origins of the distinct behaviors of RNA and 2′-F-RNA we carried out thermodynamic and X-ray crystallographic analyses of fully and partially 2′-F-modified RNAs. Surprisingly, we found that the increased pairing affinity of 2′-F-RNA relative to RNA is not, as commonly assumed, the result of a favorable entropic contribution (‘conformational preorganization’), but instead primarily based on enthalpy. Crystal structures at high resolution and osmotic stress demonstrate that the 2′-F-RNA duplex is less hydrated than the RNA duplex. The enthalpy-driven, higher stability of the former hints at the possibility that the 2′-substituent, in addition to its important function in sculpting RNA conformation, plays an underappreciated role in modulating Watson–Crick base pairing strength and potentially π–π stacking interactions

The Genetic Signatures of Noncoding RNAs

The majority of the genome in animals and plants is transcribed in a developmentally regulated manner to produce large numbers of non–protein-coding RNAs (ncRNAs), whose incidence increases with developmental complexity. There is growing evidence that these transcripts are functional, particularly in the regulation of epigenetic processes, leading to the suggestion that they compose a hitherto hidden layer of genomic programming in humans and other complex organisms. However, to date, very few have been identified in genetic screens. Here I show that this is explicable by an historic emphasis, both phenotypically and technically, on mutations in protein-coding sequences, and by presumptions about the nature of regulatory mutations. Most variations in regulatory sequences produce relatively subtle phenotypic changes, in contrast to mutations in protein-coding sequences that frequently cause catastrophic component failure. Until recently, most mapping projects have focused on protein-coding sequences, and the limited number of identified regulatory mutations have been interpreted as affecting conventional cis-acting promoter and enhancer elements, although these regions are often themselves transcribed. Moreover, ncRNA-directed regulatory circuits underpin most, if not all, complex genetic phenomena in eukaryotes, including RNA interference-related processes such as transcriptional and post-transcriptional gene silencing, position effect variegation, hybrid dysgenesis, chromosome dosage compensation, parental imprinting and allelic exclusion, paramutation, and possibly transvection and transinduction. The next frontier is the identification and functional characterization of the myriad sequence variations that influence quantitative traits, disease susceptibility, and other complex characteristics, which are being shown by genome-wide association studies to lie mostly in noncoding, presumably regulatory, regions. There is every possibility that many of these variations will alter the interactions between regulatory RNAs and their targets, a prospect that should be borne in mind in future functional analyses

Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021

Background Osteoarthritis is the most common form of arthritis in adults, characterised by chronic pain and loss of mobility. Osteoarthritis most frequently occurs after age 40 years and prevalence increases steeply with age. WHO has designated 2021–30 the decade of healthy ageing, which highlights the need to address diseases such as osteoarthritis, which strongly affect functional ability and quality of life. Osteoarthritis can coexist with, and negatively effect, other chronic conditions. Here we estimate the burden of hand, hip, knee, and other sites of osteoarthritis across geographies, age, sex, and time, with forecasts of prevalence to 2050. Methods In this systematic analysis for the Global Burden of Disease Study, osteoarthritis prevalence in 204 countries and territories from 1990 to 2020 was estimated using data from population-based surveys from 26 countries for knee osteoarthritis, 23 countries for hip osteoarthritis, 42 countries for hand osteoarthritis, and US insurance claims for all of the osteoarthritis sites, including the other types of osteoarthritis category. The reference case definition was symptomatic, radiographically confirmed osteoarthritis. Studies using alternative definitions from the reference case definition (for example self-reported osteoarthritis) were adjusted to reference using regression models. Osteoarthritis severity distribution was obtained from a pooled meta-analysis of sources using the Western Ontario and McMaster Universities Arthritis Index. Final prevalence estimates were multiplied by disability weights to calculate years lived with disability (YLDs). Prevalence was forecast to 2050 using a mixed-effects model. Findings Globally, 595 million (95% uncertainty interval 535–656) people had osteoarthritis in 2020, equal to 7·6% (95% UI 6·8–8·4) of the global population, and an increase of 132·2% (130·3–134·1) in total cases since 1990. Compared with 2020, cases of osteoarthritis are projected to increase 74·9% (59·4–89·9) for knee, 48·6% (35·9–67·1) for hand, 78·6% (57·7–105·3) for hip, and 95·1% (68·1–135·0) for other types of osteoarthritis by 2050. The global age-standardised rate of YLDs for total osteoarthritis was 255·0 YLDs (119·7–557·2) per 100 000 in 2020, a 9·5% (8·6–10·1) increase from 1990 (233·0 YLDs per 100 000, 109·3–510·8). For adults aged 70 years and older, osteoarthritis was the seventh ranked cause of YLDs. Age-standardised prevalence in 2020 was more than 5·5% in all world regions, ranging from 5677·4 (5029·8–6318·1) per 100 000 in southeast Asia to 8632·7 (7852·0–9469·1) per 100 000 in high-income Asia Pacific. Knee was the most common site for osteoarthritis. High BMI contributed to 20·4% (95% UI –1·7 to 36·6) of osteoarthritis. Potentially modifiable risk factors for osteoarthritis such as recreational injury prevention and occupational hazards have not yet been explored in GBD modelling. Interpretation Age-standardised YLDs attributable to osteoarthritis are continuing to rise and will lead to substantial increases in case numbers because of population growth and ageing, and because there is no effective cure for osteoarthritis. The demand on health systems for care of patients with osteoarthritis, including joint replacements, which are highly effective for late stage osteoarthritis in hips and knees, will rise in all regions, but might be out of reach and lead to further health inequity for individuals and countries unable to afford them. Much more can and should be done to prevent people getting to that late stage