Management of Patients on Nonsteroidal Anti-inflammatory Drugs: A Clinical Practice Recommendation From the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72218/1/j.1572-0241.2008.02200.x.pd

Lower gut abundance of Eubacterium rectale is linked to COVID-19 mortality

IntroductionEmerging preclinical and clinical studies suggest that altered gut microbiome composition and functions are associated with coronavirus 2019 (COVID- 19) severity and its long-term complications. We hypothesize that COVID-19 outcome is associated with gut microbiome status in population-based settings.MethodsGut metagenomic data of the adult population consisting of 2871 subjects from 16 countries were obtained from ExperimentHub through R, while the dynamic death data of COVID-19 patients between January 22, 2020 and December 8, 2020 in each country was acquired from Johns Hopkins Coronavirus Resource Center. An adjusted stable mortality rate (SMR) was used to represent these countries’ mortality and correlated with the mean relative abundance (mRA) of healthy adult gut microbiome species.ResultsAfter excluding bacterial species with low prevalence (prevalence <0.2 in the included countries), the β-diversity was significantly higher in the countries with high SMR when compared with those with median or low SMR (p <0.001). We then identified the mRA of two butyrate producers, Eubacterium rectale and Roseburia intestinalis, that were negatively correlated with SMR during the study period. And the reduction of these species was associated with severer COVID-19 manifestation.ConclusionPopulation-based microbiome signatures with the stable mortality rate of COVID-19 in different countries suggest that altered gut microbiome composition and functions are associated with mortality of COVID-19

Happiness matters : exploring the linkages between personality, personal happiness, and work-related psychological health among priests and sisters in Italy

This study responds to the challenge posed by Rossetti’s work to explore the antecedents and consequences of individual differences in happiness among priests and religious sisters. The Oxford Happiness Questionnaire was completed together with measures of personality and work-related psychological health by 95 priests and 61 religious sisters. Overall the data demonstrated high levels of personal happiness among priests and religious sisters, but also significant signs of vulnerability. Personality provided significant prediction of individual differences in both personal happiness and work-related psychological health. However, personal happiness provided additional protection against work-related emotional exhaustion and additional enhancement of work-related satisfaction. These findings suggest that acknowledging and affirming personal happiness may enhance the work-related psychological health of Catholic priests and religious sisters

Lack of benefits for prevention of cardiovascular disease with aspirin therapy in type 2 diabetic patients - a longitudinal observational study

<p>Abstract</p> <p>Background</p> <p>The risk-benefit ratio of aspirin therapy in prevention of cardiovascular disease (CVD) remains contentious, especially in type 2 diabetes. This study examined the benefit and harm of low-dose aspirin (daily dose < 300 mg) in patients with type 2 diabetes.</p> <p>Methods</p> <p>This is a longitudinal observational study with primary and secondary prevention cohorts based on history of CVD at enrolment. We compared the occurrence of primary composite (non-fatal myocardial infarction or stroke and vascular death) and secondary endpoints (upper GI bleeding and haemorrhagic stroke) between aspirin users and non-users between January 1995 and July 2005.</p> <p>Results</p> <p>Of the 6,454 patients (mean follow-up: median [IQR]: 4.7 [4.4] years), usage of aspirin was 18% (n = 1,034) in the primary prevention cohort (n = 5731) and 81% (n = 585) in the secondary prevention cohort (n = 723). After adjustment for covariates, in the primary prevention cohort, aspirin use was associated with a hazard-ratio of 2.07 (95% CI: 1.66, 2.59, p < 0.001) for primary endpoint. There was no difference in CVD event rate in the secondary prevention cohort. Overall, aspirin use was associated with a hazard-ratio of 2.2 (1.53, 3.15, p < 0.001) of GI bleeding and 1.71 (1.00, 2.95, p = 0.051) of haemorrhagic stroke. The absolute risk of aspirin-related GI bleeding was 10.7 events per 1,000 person-years of treatment.</p> <p>Conclusion</p> <p>In Chinese type 2 diabetic patients, low dose aspirin was associated with a paradoxical increase in CVD risk in primary prevention and did not confer benefits in secondary prevention. In addition, the risk of GI bleeding in aspirin users was rather high.</p

The astrin–kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignment

Kinastrin is identified as a major interacting partner for astrin in mitotic cells, and is required for astrin targeting to microtubule plus ends

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

Demodex Blepharitis: A Comprehensive Review of the Disease, Current Management, and Emerging Therapies

Demodex blepharitis is a common disease of the eyelid, affecting approximately 25 million Americans. This article reviews what is known about the mechanisms and impact of Demodex blepharitis, risk factors, signs and symptoms, diagnostic techniques, current management options, and emerging treatments. Demodex mites contribute to blepharitis in several ways: direct mechanical damage, as a vector for bacteria, and by inducing hypersensitivity and inflammation. Risk factors for Demodex blepharitis include increasing age, rosacea, and diabetes. The costs, symptom burden, and psychosocial effects of Demodex blepharitis are considerable. The presence of collarettes is pathognomonic for Demodex blepharitis. Redness, dryness, discomfort, foreign body sensation, lash anomalies, and itching are also hallmarks of the disease. Although a number of oral, topical, eyelid hygiene and device-based options have been used clinically and evaluated in studies for the management of Demodex blepharitis, none have been FDA approved to treat the disease. Recent randomized controlled clinical trials suggest that lotilaner ophthalmic solution, 0.25%, is a topical treatment with the potential to eradicate Demodex mites and eliminate collarettes and eyelid redness for an extended period

Radiotherapy after mastectomy for screen-detected ductal carcinoma in situ

Background. A role for radiotherapy after mastectomy for ductal carcinoma in situ (DCIS) is unclear. Using a prospective audit of DCIS detected through the NHS Breast Screening Programme we sought to determine a rationale for the use of postmastectomy radiotherapy for DCIS. Methods. Over a nine year period, from 9,972 patients with screen-detected DCIS and complete surgical, pathology, radiotherapy and follow up data, 2,944 women underwent mastectomy for DCIS of whom 33 (1.12%) received radiotherapy. Results. Use of post mastectomy radiotherapy was significantly associated with a close (<1mm) pathology margin, particularly (χ2(1) 95.81; p<0.00001), DCIS size (χ2 (3) 16.96; p<0.001) and the presence of microinvasion (χ2(1) 3.92; p<0.05). At median follow up 61 months, no woman who received radiotherapy had an ipsilateral further event, and only 1/33 women (3.0%) had a contralateral event. Of the women known not to have had radiotherapy post mastectomy, 45/2,894 (1.6%) had an ipsilateral further event and 83 (2.9%) had a contralateral event. Conclusion: For DCIS treated by mastectomy, a close (<1mm) margin, large tumour size and microinvasion, may merit radiotherapy to reduce ipsilateral recurrence