Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p≪0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system. © 2014 Whitcomb et al

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Literary review of Yava (Barley)

According to Upanishadas, food is Brahman, the Divine reality. The physical body itself is born of and lives by food. Right diet is the essence of disease prevention and the foundation of a healthy and happy life. A properly selected diet and diet plan plays a critical importance in the management of any disease. Only a well-balanced diet can cure numerous diseases, sometimes even good medicines are unable to cure certain diseases without balanced diet, that’s why food is said to be most important medicine. Today there is increasing public awareness of the importance of diet for the maintenance and promotion of health. An Ayurvedic text entails the uses of Yava in religious ceremony, dietary and medicinal preparations. Yava is used for Lekhana Karma. The present paper deals with literary review of Yava

Panel 4 : Report of the Microbiology Panel

Objective. To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions. Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice. (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.Peer reviewe

Was there any change in tobacco smoking among adults in Bangladesh during 2009-2017? Insights from two nationally representative cross-sectional surveys.

OBJECTIVE: This study assessed the changes in prevalence and associated factors of tobacco smoking among Bangladeshi adults over time. DESIGN: Nationally representative cross-sectional surveys. SETTING: Two most recent Global Adults Tobacco Survey (GATS) data from Bangladesh, carried out in 2009 and 2017. PARTICIPANTS: Adult population aged 15 and above (n=9629 in 2009; n=12 783 in 2017). OUTCOME MEASURES: Current use of tobacco smoke, including cigarettes, bidi, hukkah, cigars or pipes, which was dichotomised ('yes'/'no'). METHODS: We analysed data from two recent rounds of GATS (2009 and 2017). Multivariate logistic regression analysis was used. RESULTS: The overall prevalence of tobacco smoking among Bangladeshi adults was noted (23.00%, 95% CI 22.98 to 23.00 in 2009; 16.44%, 95% CI 16.43 to 16.45 in 2017). Being male (adjusted OR (AOR)=59.72, CI 40.56 to 87.93 for 2009; AOR=71.17, CI 41.08 to 123.32 for 2017), age between 25 and 64 years (all AORs >2 and p<0.05), smoking permissible at home (AOR=7.08, CI 5.88 to 8.52 for 2009; AOR=5.90, CI 5.34 to 6.95 for 2017), and watching tobacco smoking product use in movie/drama scenes (AOR=1.26, CI 1.11 to 1.44 for 2009; AOR=1.34, CI 1.17 to 1.54 for 2017) were found to be significantly associated with increased tobacco smoking among adults both in 2009 and in 2017. However, being offered free tobacco sample products (AOR=0.66, CI 0.57 to 0.77 for 2009; AOR=0.87, CI 0.76 to 0.99 for 2017) and having primary, secondary or higher education (all AORs <1 and p<0.05) as well as being a student (AOR=0.16, CI 0.09 to 0.29 for 2009; AOR=0.32, CI 0.19 to 0.53) were associated with lower odds of tobacco smoking in both surveys. CONCLUSIONS: Although the prevalence of tobacco smoking has declined over the period, it is still high among those who were relatively older, men, less educated and exposed to a movie/drama where tobacco smoking is promoted. Therefore, appropriate interventions are required to stop tobacco smoking among the Bangladeshi population

Stigma toward people with COVID-19 among Bangladeshi older adults.

The onset of the coronavirus disease (COVID-19) pandemic and its overwhelming physical and mental health burden can result in stigmatization toward the disease and those affected. This study aimed to measure the prevalence of COVID-19-related stigma and its associated factors among older people in Bangladesh. This cross-sectional study was conducted among 1,045 Bangladeshi older adults aged 60 years and above through telephone interviews in September 2021. The outcome was measured using an eight-point Stigma Scale, adapted to the Bengali language. Level of stigma was indicated by the cumulative score of the eight-items, ranging from 0 to 8, with a higher score indicating a higher level of stigma. On average, participants had stigmas on three of the eight items, and 62.6% had a high stigma score. The most prevalent stigmas were as follows: COVID-19 is a punishment from God (79.3%), patients with previous COVID-19 must be isolated (67.3%), and people infected with COVID-19 did not meet hygiene standards (63.9%). Participants who lived in rural areas (β: 0.67, 95% CI: 0.39 to 0.95) and who perceived needing additional care during the pandemic (β: 0.35, 95% CI: 0.09 to 0.60) had a higher average stigma score, whereas stigma scores were lower among unemployed/retired participants (β: -0.22, 95% CI: -0.45 to 0.00). The study findings suggest implementing interventions to raise awareness through appropriate health literacy interventions and mass media campaigns

Critical mutation rate has an exponential dependence on population size for eukaryotic-length genomes with crossover

The critical mutation rate (CMR) determines the shift between survival-of-the-fittest and survival of individuals with greater mutational robustness (“flattest”). We identify an inverse relationship between CMR and sequence length in an in silico system with a two-peak fitness landscape; CMR decreases to no more than five orders of magnitude above estimates of eukaryotic per base mutation rate. We confirm the CMR reduces exponentially at low population sizes, irrespective of peak radius and distance, and increases with the number of genetic crossovers. We also identify an inverse relationship between CMR and the number of genes, confirming that, for a similar number of genes to that for the plant Arabidopsis thaliana (25,000), the CMR is close to its known wild-type mutation rate; mutation rates for additional organisms were also found to be within one order of magnitude of the CMR. This is the first time such a simulation model has been assigned input and produced output within range for a given biological organism. The decrease in CMR with population size previously observed is maintained; there is potential for the model to influence understanding of populations undergoing bottleneck, stress, and conservation strategy for populations near extinction

Agrobacterium-mediated transformation systems of Primula vulgaris

Background: Genetic transformation is a valuable tool and an important procedure in plant functional genomics contributing to gene discovery, allowing powerful insights into gene function and genetically controlled characteristics. Primulaceae species provide one of the best-known examples of heteromorphic flower development, a breeding system which has attracted considerable attention, including that of Charles Darwin. Molecular approaches, including plant transformation give the best opportunity to define and understand the role of genes involved in floral heteromorphy in the common primrose, Primula vulgaris, along with other Primula species. Results: Two transformation systems have been developed in P. vulgaris. The first system, Agrobacterium-mediated vacuum infiltration of seedlings, enables the rapid testing of transgenes, transiently in planta. GUS expression was observed in the cotyledons, true leaves, and roots of Primula seedlings. The second system is based on Agrobacterium tumefaciens infection of pedicel explants with an average transformation efficiency of 4.6%. This transformation system, based on regeneration and selection of transformants within in vitro culture, demonstrates stable transgene integration and transmission to the next generation. Conclusion: The two transformation systems reported here will aid fundamental research into important traits in Primula. Although, stable integration of transgenes is the ultimate goal for such analyses, transient gene expression via Agrobacterium-mediated DNA transfer, offers a simple and fast method to analyse transgene functions. The second system describes, for the first time, stable Agrobacterium-mediated transformation of Primula vulgaris, which will be key to characterising the genes responsible for the control of floral heteromorphy

COVID-19 related anxiety and its associated factors: a cross-sectional study on older adults in Bangladesh.

BACKGROUND: The COVID-19 pandemic has resulted in serious mental health conditions, particularly among older adults. This research explored the prevalence of COVID-19-related anxiety and its associated factors among older adults residing in Bangladesh. METHODS: This cross-sectional study was conducted among 1,045 older Bangladeshi adults aged ≥ 60 years through telephone interviews in September 2021. A semi-structured interview schedule was used to collect data on participants' characteristics and COVID-19-related anxiety. The anxiety level was measured using the Bengali version of the five-point Coronavirus Anxiety Scale (CAS). A linear regression model explored the factors associated with COVID-19-related anxiety. RESULTS: Overall, the prevalence of COVID-19-related anxiety was 23.2%. The regression analysis revealed that the average COVID-19-related anxiety score was significantly higher among females (β: 0.43, 95% CI: 0.05 to 0.81), and among those who faced difficulty getting medicine (β: 0.57, 95% CI: 0.16 to 0.97), felt isolated (β: 0.60, 95% CI: 0.24 to 0.95), and felt requiring additional care during the pandemic (β: 0.53, 95% CI: 0.16 to 0.91). Alternatively, the average COVID-19-related anxiety score was significantly lower among those who were widowed (β: -0.46, 95% CI: -0.87 to -0.04) and living distant from the health centre (β: -0.48, 95% CI: -0.79 to -0.17). CONCLUSION: The findings of the present study suggest providing immediate psychosocial support package to the older adults, particularly females and those who are vulnerable to receive health and social care support during the COVID-19 pandemic in Bangladesh

Gut Microbiota, Probiotics and Diabetes

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes