Influenza a H5N1 detection

We developed a sensitive and rapid real-time reverse transcription- polymerase chain reaction (RT-PCR) assay to detect influenza A H5N1 virus in clinical samples. This assay was evaluated with samples from H5N1-infected patients and demonstrated greater sensitivity and faster turnaround time than nested RT-PCR.published_or_final_versio

The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review

Hypoglycemia is a major barrier impeding glycemic control in persons with type 2 diabetes mellitus and creates a substantial burden on the healthcare system. Certain populations that require special attention, such as older adults and individuals with renal impairment, a longer duration of diabetes or those who have experienced prior hypoglycemia, may be at a higher risk of hypoglycemia, particularly with insulin treatment. Second-generation basal insulin analogues (insulin glargine 300 U/mL and degludec) have demonstrated reductions in hypoglycemia compared with insulin glargine 100 U/mL although evidence of this benefit across specific populations is less clear. In this review we summarize the literature with respect to the efficacy and safety data for second-generation basal insulin analogues in adults with type 2 diabetes mellitus who are at risk of hypoglycemia or who require special attention. Randomized controlled trials, meta-analyses and real-world evidence demonstrate that the use of second-generation basal insulin analogues is associated with less hypoglycemia compared with insulin glargine 100 U/mL without compromising glycated hemoglobin control. A reduced risk of hypoglycemia with second-generation basal insulin analogues was evident in older adults and in individuals with obesity, renal impairment, a history of cardiovascular disease or a long duration of insulin use. Further studies are needed in other populations, including those with more severe renal impairment or hepatic dysfunction, the hospitalized population and those with cognitive impairment. Overall, less hypoglycemia associated with second-generation basal insulin analogues may help reduce barriers for insulin use, improve adherence and offset the costs of hypoglycemia-related healthcare resource utilization

Critical role for Transglutaminase 2 in scleroderma skin fibrosis and in the development of dermal sclerosis in a mouse model of scleroderma

Objective Scleroderma is a life-threatening autoimmune disease characterized by inflammation, tissue remodelling, and fibrosis. This study aimed to investigate the expression and function of transglutaminase 2 (TGM2) in scleroderma skin and experimentally-induced dermal fibrosis to determine its potential role and therapeutic implications. Methods We performed immunohistochemistry on skin sections to assess TGM2 expression and localisation, and protein biochemistry of both SSc-derived and healthy control dermal fibroblasts to assess TGM2 expression, function and ECM deposition in the presence of a TGM2 and TGFβ neutralizing antibodies and a small molecule inhibitor of the TGFβRI kinase. Mice with a complete deficiency of TGM2 (Tgm2-/-) were investigated in the bleomycin-induced model of skin fibrosis. Results TGM2 was found to be widely expressed in both control and scleroderma skin samples, as well as in cultured fibroblasts. Scleroderma fibroblasts exhibited elevated TGM2 expression, which correlated with increased expression of fibrosis markers (collagen type 1, αSMA and CCN2). Inhibition of TGM2 using a neutralizing antibody reduced the expression of key markers of fibrosis. The effects of TGM2 inhibition were similar to those observed with TGFβ neutralization, suggesting a potential cross-talk between TGM2 and TGFβ signalling. Moreover, TGM2 knock-out mice showed significantly reduced dermal fibrosis compared to wild-type mice. In vitro experiments with TGM2-deleted fibroblasts demonstrated impaired cell migration and collagen matrix contraction, which could be partially restored by exogenous TGFβ. Conclusion TGM2 can regulate several key pro-fibrotic activities of TGFβ suggesting that attenuating TGM2 function may be of benefit in severe forms of connective tissue disease with skin fibrosis

Priming conditions shape breadth of neutralizing antibody responses to sarbecoviruses.

Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VoC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. To define the magnitude and breadth of cross-neutralization in individuals with different exposure to SARS-CoV-2 infection and vaccination, we here use a multiplex surrogate neutralization assay based on virus spike receptor binding domains of multiple SARS-CoV-2 VoC, as well as related bat and pangolin viruses. We include sera from cohorts of individuals vaccinated with two or three doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (Coronavac or Sinopharm) vaccines with or without a history of previous SARS-CoV-2 or SARS-CoV-1 infection. SARS-CoV-2 or SARS-CoV-1 infection followed by BNT162b2 vaccine, Omicron BA.2 breakthrough infection following BNT162b2 vaccine or a third dose of BNT162b2 following two doses of BNT162b2 or Coronavac elicit the highest and broadest neutralization across VoCs. For both breadth and magnitude of neutralization across all sarbecoviruses, those infected with SARS-CoV-1 immunized with BNT162b2 outperform all other combinations of infection and/or vaccination. These data may inform vaccine design strategies for generating broadly neutralizing antibodies to SARS-CoV-2 variants or across the sarbecovirus subgenus

Delaying initiation of dialysis till symptomatic uraemia - Is it too late?

Background. The optimal timing of initiating renal replacement therapy in patients with chronic renal failure remains uncertain. The primary objective of our study is to determine whether delaying dialysis initiation as a result of patients' choice may have any impact on survival in subjects with end-stage renal disease. Methods. We prospectively studied the clinical outcome during the first year of all consecutive patients (n=233) deemed suitable for peritoneal dialysis (PD) after pre-dialysis counselling over a 2-year period from 2002 to 2004. All patients who were offered dialysis were included in the analysis from the day of initial counselling regardless of whether or not they were eventually established on PD. Results. There were 151 'elective starters' (50.3% male, mean±SD age=57.7±13.9 years, 39.7% diabetic) who were electively initiated on dialysis when glomerular filtration rate reached 10 ml/min/ 1.73m 2 or below. The remaining 82 subjects (53.7% male, mean±SD age=58.4±11.3 years, 46.3% diabetic, P=0.33 vs elective starters) declined dialysis initially (initial refusers). On follow-up, 45 (55%) initial refusers developed a uraemic emergency and agreed to undergo dialysis, and 39 (48%) were eventually established on maintenance PD (late starters). Kaplan-Meier analysis of 1-year survival showed a significantly higher rate of all-cause (18.3% vs 6.6%, P=0.004, log-rank test) and cardiovascular (9.8% vs 2.6%, P=0.014) mortality among the initial refusers. Conclusion. Patients who refuse timely start of dialysis have worse overall outcome at one year after the offer of dialysis, compared with elective starters. © The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.link_to_OA_fulltex

Acceptance and Perception of Artificial Intelligence Usability in Eye Care (APPRAISE) for Ophthalmologists: A Multinational Perspective

BACKGROUND: Many artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract. METHODS: This was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning. RESULTS: One thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10-12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63-0.83. CONCLUSION: Ophthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology

Adaptation and conservation insights from the koala genome

The koala, the only extant species of the marsupial family Phascolarctidae, is classified as ‘vulnerable’ due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala’s ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala’s survival in the wild