HSF1 induces RNA polymerase II synthesis of ribosomal RNA in S. cerevisiae during nitrogen deprivation.

The resource intensive process of accurate ribosome synthesis is essential for cell viability in all organisms. Ribosome synthesis regulation centers on RNA polymerase I (pol I) transcription of a 35S rRNA precursor that is processed into the mature 18S, 5.8S and 25S rRNAs. During nutrient deprivation or stress, pol I synthesis of rRNA is dramatically reduced. Conversely, chronic stress such as mitochondrial dysfunction induces RNA polymerase II (pol II) to transcribe functional rRNA using an evolutionarily conserved cryptic pol II rDNA promoter suggesting a universal phenomenon. However, this polymerase switches and its role in regulation of rRNA synthesis remain unclear. In this paper, we demonstrate that extended nitrogen deprivation induces the polymerase switch via components of the environmental stress response. We further show that the switch is repressed by Sch9 and activated by the stress kinase Rim15. Like stress-induced genes, the switch requires not only pol II transcription machinery, including the mediator, but also requires the HDAC, Rpd3 and stress transcription factor Hsf1. The current work shows that the constitutive allele, Hsf1PO4* displays elevated levels of induction in non-stress conditions while binding to a conserved site in the pol II rDNA promoter upstream of the pol I promoter. Whether the polymerase switch serves to provide rRNA when pol I transcription is inhibited or fine-tunes pol I initiation via RNA interactions is yet to be determined. Identifying the underlying mechanism for this evolutionary conserved phenomenon will help understand the mechanism of pol II rRNA synthesis and its role in stress adaptation.

Prevalence and determinants of symptomatic COVID-19 infection among children and adolescents in Qatar: a cross-sectional analysis of 11 445 individuals.

There is a paucity of evidence about the prevalence and risk factors for symptomatic infection among children. This study aimed to describe the prevalence of symptomatic coronavirus disease 2019 (COVID-19) and its risk factors in children and adolescents aged 0-18 years in Qatar. We conducted a cross-sectional study of all children aged 0-18 years diagnosed with COVID-19 using polymerase chain reaction in Qatar during the period 1st March to 31st July 2020. A generalised linear model with a binomial family and identity link was used to assess the association between selected factors and the prevalence of symptomatic infection. A total of 11 445 children with a median age of 8 years (interquartile range (IQR) 3-13 years) were included in this study. The prevalence of symptomatic COVID-19 was 36.6% (95% confidence interval (CI) 35.7-37.5), and it was similar between children aged <5 years (37.8%), 5-9 years (34.3%) and 10 + years (37.3%). The most frequently reported symptoms among the symptomatic group were fever (73.5%), cough (34.8%), headache (23.2%) and sore throat (23.2%). Fever (82.8%) was more common in symptomatic children aged <5 years, while cough (38.7%) was more prevalent in those aged 10 years or older, compared to other age groups. Variables associated with an increased risk of symptomatic infection were; contact with confirmed cases (RD 0.21; 95% CI 0.20-0.23; P = 0.001), having visited a health care facility (RD 0.54; 95% CI 0.45-0.62; P = 0.001), and children aged under 5 years (RD 0.05; 95% CI 0.02-0.07; P = 0.001) or aged 10 years or older (RD 0.04; 95% CI 0.02-0.06; P = 0.001). A third of the children with COVID-19 were symptomatic with a higher proportion of fever in very young children and a higher proportion of cough in those between 10 and 18 years of age.

Pre-symptomatic and asymptomatic transmission of COVID-19: Implications for control measures in Qatar.

Public health control measures for communicable diseases are often based on the identification of symptomatic cases. However, emerging epidemiological evidence demonstrates the role of pre-symptomatic and asymptomatic transmissions of coronavirus disease 2019 (COVID-19). Understanding high-risk settings where transmissions can occur from infected individuals without symptoms has become critical for improving the response to the pandemic. In this review, we discussed the evidence on the transmission of severe acute respiratory syndrome coronavirus-2, its effect on control strategies, and lessons that can be applied in Qatar. Although Qatar has a small population, it has a distinct setting for COVID-19 control. It has a largely young population and is mostly composed of expatriates particularly from the Middle East and Asia that reside in Qatar for work. Further key considerations for Qatar and travel include population movement during extended religious holiday periods, screening and tracing of visitors and residents at entry points into the country, and expatriates living and working in high-density settings. We also consider how its international airport serves as a major transit destination for the region, as Qatar is expected to experience a rapid expansion of visitors while preparing to host the FIFA World Cup in 2022.

A retrospective epidemiological study on the incidence of salmonellosis in the State of Qatar during 2004-2012.

BACKGROUND: Salmonella is a food- and water-borne pathogen that can be easily spread in a population, leading to the outbreak of salmonellosis that is caused by ingestion of mixed salads contaminated by the pathogen. Most cases occur in the late spring months and can be seen as single cases, clusters, or episodes. OBJECTIVE: The aim of this study was to describe the incidence and epidemiological characteristics of salmonellosis in the State of Qatar. METHODS: This was a retrospective, descriptive study carried out in laboratory-confirmed cases of salmonellosis during 2004-2012 from all Salmonella surveillance centers. Therapeutic records of patients who were clinically suspected of having Salmonella diseases were analyzed. Initially, cases with typhoid fever were investigated in the laboratory by means of Widal agglutination tests, while non-typhoidal Salmonella diseases were determined based on culture technique. RESULTS: The annual incident of salmonellosis cases were 12.3, 23.0, 30.3, 19.4, 15.3, 18.0, 22.7, 18.5, and 18.1 per 100,000 population in 2006-2011 and 2012, respectively. The number of salmonellosis cases was high among less than 2-year-old females and 3-year-old males. In addition, one-fourth of patients (27.7%) were Qatari when compared to other nationalities. A significant difference in age was found between Qatari (6.08 ± 12.28 years) and non-Qatari (15.04 ± 19.56 years) patients. Of the reported cases, 79.8% included the onset date of the first symptoms. Contact phone numbers were available for 94% of the cases but addresses were available for only 50.4% of cases. The time difference between onset of symptoms and diagnosis was 5.4 ± 5.7 days. The most frequent serotype reported were type b (41.9%), type d (26.9%), and type c1 (12.2%). CONCLUSION: The present surveillance data showed a high incidence of salmonellosis in Qatar that poses a serious public health problem. Special intervention and health awareness programs are required for early screening, detection, and treatment as well as for strengthening the surveillance system of salmonellosis, with special emphasis on the laboratory study of cases.

Characterizing the Qatar advanced-phase SARS-CoV-2 epidemic.

The overarching objective of this study was to provide the descriptive epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Qatar by addressing specific research questions through a series of national epidemiologic studies. Sources of data were the centralized and standardized national databases for SARS-CoV-2 infection. By July 10, 2020, 397,577 individuals had been tested for SARS-CoV-2 using polymerase-chain-reaction (PCR), of whom 110,986 were positive, a positivity cumulative rate of 27.9% (95% CI 27.8-28.1%). As of July 5, case severity rate, based on World Health Organization (WHO) severity classification, was 3.4% and case fatality rate was 1.4 per 1,000 persons. Age was by far the strongest predictor of severe, critical, or fatal infection. PCR positivity of nasopharyngeal/oropharyngeal swabs in a national community survey (May 6-7) including 1,307 participants was 14.9% (95% CI 11.5-19.0%); 58.5% of those testing positive were asymptomatic. Across 448 ad-hoc testing campaigns in workplaces and residential areas including 26,715 individuals, pooled mean PCR positivity was 15.6% (95% CI 13.7-17.7%). SARS-CoV-2 antibody prevalence was 24.0% (95% CI 23.3-24.6%) in 32,970 residual clinical blood specimens. Antibody prevalence was only 47.3% (95% CI 46.2-48.5%) in those who had at least one PCR positive result, but 91.3% (95% CI 89.5-92.9%) among those who were PCR positive > 3 weeks before serology testing. Qatar has experienced a large SARS-CoV-2 epidemic that is rapidly declining, apparently due to growing immunity levels in the population.

Evaluating the Knowledge of Endotracheal Cuff Pressure Monitoring Among Critical Care Providers by Palpation of Pilot Balloon and By Endotracheal Tube Cuff Manometer.

Introduction Mishandled endotracheal cuff pressure may either make ventilation difficult or cause damage to the airway. Therefore, the aim of this audit was to assess the knowledge about endotracheal cuff pressure monitoring with a manometer and manual palpation of pilot balloon among critical care providers. Methods This audit includes 150 critical care providers having experience of handling endotracheal tube (ETT) cuff at critical care area of National Institute of Cardiovascular Diseases (NICVD), Karachi from April 2017 to June 2017. Knowledge about endotracheal cuff pressure monitoring with the manometer and deleterious effects of mishandled ETT cuff was assessed using a self-reported questionnaire. Enrolled healthcare providers were asked to palpate the patient and cuff pressure was recorded and categorized. Results Out of 150 participants, 66 (44.0%) were doctors. Only 46 (30.67%) participants had prior knowledge about ETT cuff manometer and 110 (73.33%) had never used a manometer. Similarly only 42 (28.0%) had knowledge of hazardous effects of mishandled ETT cuff. Kappa coefficient of 0.155 with p=0.015 showed significant yet low agreement between participant prediction and the actual amount of air in cuff balloon. Agreement level was comparatively higher for staff as compared to doctors with a Kappa coefficient of 0.210 (p=0.018) vs. 0.133 (p=0.099). Conclusion In this study of knowledge and practice of ETT tube cuff pressure monitoring, we observed low levels of knowledge (30.67%), poor adherence to standard practice (73.33%) and were able to demonstrate poor agreement (Kappa coefficient 0.155; p=0.015) between the palpation method and cuff manometer measurements for assessing cuff pressure.

Development of cataract and associated risk factors: the Visual Impairment Project.

OBJECTIVE: To evaluate risk factors for the development of cataract in Australian residents. METHODS: A total of 3721 participants from 9 randomly selected urban districts within Victoria were recruited and invited to attend comprehensive standardized interviews and ophthalmic examinations at baseline and then 5-year follow-up. Lens opacities were graded clinically and on photographs according to the Wilmer cataract grading system. The development of cortical, nuclear, and posterior subcapsular cataract were assessed separately for associated risk factors. Risk exposure at baseline was used as the predictor for cataract development, which included various sociodemographic, dietary, familial, medical, and ocular characteristics of the participants. Risk factor analyses were performed by univariate and multivariate logistic regression. RESULTS: Increased age was a risk factor for development of all types of cataract with an increasing risk trend throughout life for nuclear cataract. Female sex, a laborer's occupation, and myopia were independent risk factors for development of cortical cataract. For development of nuclear cataract, the independent risk factors were having a birthplace outside Australia and New Zealand, current cigarette smoking, and having a history of arthritis. Diabetes mellitus and having taken calcium channel blockers for longer than 5 years were independent risk factors for posterior subcapsular cataract. CONCLUSIONS: The trend of increasing incidence of cataract with increased age is a major public health concern with an aging population in Australia and the world. Among the risk factors identified, cigarette smoking is a factor that is readily modifiable and preventable. The other risk factors identified require further support or clarification of underlying mechanisms to find modifiable features.

Recent migrants' perspectives on antibiotic use and prescribing in primary care: a qualitative study.

BACKGROUND: Currently there is great interest in antibiotic prescribing practices in the UK, but little is known about the experiences of the increasing numbers of recent migrants (those present in the UK for >1 year but <5 years) registered at GP practices. Qualitative research has suggested that reasons for not prescribing antibiotics may not be clearly communicated to migrants. AIM: This study aimed to explore the factors that shape migrants' experiences of and attitudes to antibiotics, and to suggest ways to improve effective communication around their use. DESIGN AND SETTING: A qualitative study on recent migrants' health beliefs, values, and experiences in a community setting in primary care. METHOD: Twenty-three recent migrants were interviewed in their preferred language by trained community researchers. The research team conducted a thematic analysis, focusing on health beliefs, engaging with health services, transnational medicine, and concepts of fairness. Experiences around antibiotics were a strong emerging theme. RESULTS: Three reasons were identified for antibiotics seeking: first, holding an 'infectious model' of illness implying that antibiotics are required quickly to avoid illness becoming worse or spreading to others; second, reasoning that other medications will be less effective for people 'used to' antibiotics'; and third, perceiving antibiotic prescription as a sign of being taken seriously. Some participants obtained antibiotics from their country of origin or migrant networks in the UK; others changed their mind and accepted alternatives. CONCLUSION: Primary care professionals should aim to understand migrants' perspectives to improve communication with patients. Further research is needed to identify different strategies needed to respond to the varying understandings of antibiotics held by migrants.

The macular xanthophylls.

The macular pigments are predominantly composed of three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. These carotenoids are concentrated and distributed in a selective manner. The properties of these pigments are further explored along with their methods of uptake, stabilization, and storage. The dual nature of these pigments as filters and antioxidants are elaborated upon in relation to their protective effects upon the macula, specifically in age-related macular degeneration. Evidence suggests that increased levels of macular pigment are correlated with a decreased risk of age-related macular degeneration. Many have sought to exploit this therapeutic relation. Studies reveal that oral supplementation with lutein and zeaxanthin can increase the levels of macular pigments in the retina and plasma. The effects of such supplementation on actual ocular function have yet to be fully addressed. New and standardized methods of assessing macular pigment density are discussed and future areas of research to further our understanding of macular xanthophylls as they pertain to age-related macular degeneration are highlighted.

Primary total hip arthroplasty with a flanged, cemented all-polyethylene acetabular component: evaluation at a minimum of 20 years.

One hundred twenty-three consecutive primary total hip arthroplasties in 107 patients were performed with the insertion of a cemented, all polyethylene, flanged acetabular component. At a minimum of 20 years, 66 patients had died (75 hips) and 8 patients (8 hips) were lost to follow-up evaluation, leaving 40 hips in 33 patients. At a mean of 21.1 years, 2 cups had been revised for aseptic loosening, one well-fixed cup was revised at the time of femoral component revision, and 4 additional cups had definite evidence of radiographic loosening. Survivorship analysis revealed a 77.3% survivorship for the component at 21 years, with revision or definite loosening as an endpoint (95% confidence interval, 67.8%-86.8%).

Successful treatment of refractory low grade duodenal lymphoma with rituximab, an anti-CD20 monoclonal antibody.

Duodenal lymphoma accounts for a small percentage of gastrointestinal tumors and has a very poor prognosis. The majority of patients have little or no cure with limited time of remission. Median survival is 5 to 10 years, and most patients die of lymphoma, its complications, or complications of therapy. We report a patient with lymphoma refractory to treatment with cyclophosphamide, vincristine, and prednisone, who was successfully treated with rituximab, a CD-20 monoclonal antibody.