Exploring the Use of a Restoration Step to Detect Mosaic Chromosomal Alterations in Prostate Samples

Department of Epidemiologyhttps://openworks.mdanderson.org/sumexp22/1044/thumbnail.jp

Spiny Mice (\u3cem\u3eAcomys\u3c/em\u3e) Exhibit Attenuated Hallmarks of Aging and Rapid Cell Turnover after UV Exposure in the Skin Epidermis

The study of long-lived and regenerative animal models has revealed diverse protective responses to stressors such as aging and tissue injury. Spiny mice (Acomys) are a unique mammalian model of skin wound regeneration, but their response to other types of physiological skin damage has not been investigated. In this study, we examine how spiny mouse skin responds to acute UVB damage or chronological aging compared to non-regenerative C57Bl/6 mice (M. musculus). We find that, compared to M. musculus, the skin epidermis in A. cahirinus experiences a similar UVB-induced increase in basal cell proliferation but exhibits increased epidermal turnover. Notably, A. cahirinus uniquely form a suprabasal layer co-expressing Keratin 14 and Keratin 10 after UVB exposure concomitant with reduced epidermal inflammatory signaling and reduced markers of DNA damage. In the context of aging, old M. musculus animals exhibit typical hallmarks including epidermal thinning, increased inflammatory signaling and senescence. However, these age-related changes are absent in old A. cahirinus skin. Overall, we find that A. cahirinus have evolved novel responses to skin damage that reveals new aspects of its regenerative phenotype

Interstitial lung abnormality is prevalent and associated with worse outcome in patients undergoing transcatheter aortic valve replacement

BackgroundInterstitial lung abnormality (ILA) is found in 5-10% of the general population and is associated with increased mortality risk. Risk factors for ILA, including advanced age and smoking history also increase the risk for aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become an increasingly utilized intervention for patients with severe AS, and requires a high-resolution computed tomography (HRCT) of the chest to assess aortic valve dimensions.ObjectivesTo determine the prevalence and clinical significance of ILA on HRCT performed in patients referred for TAVR.MethodsConsecutive pre-TAVR HRCTs performed over a 5-year period were reviewed. ILA was defined as bilateral, nondependent reticular opacities. All-cause mortality among TAVR recipients was compared between ILA cases and non-ILA controls matched 2:1 by age and gender using Cox proportional hazards regression and the Kaplan Meier estimator.ResultsOf 623 HRCTs screened, ILA was detected in 92 (14.7%), including 62 patients that underwent TAVR. Among ILA cases, 17 (27.4%) had a typical or probable usual interstitial pneumonia pattern, suggesting a diagnosis of idiopathic pulmonary fibrosis. Survival was worse in ILA cases compared to non-ILA controls (p = 0.008) and ILA was an independent predictor of mortality after multivariable adjustment (HR 3.29, 95% CI 1.34-8.08; p = 0.009).ConclusionsILA is a common finding among patients with severe AS and is associated with increased mortality in those undergoing TAVR. Further research is needed to elucidate the biology underpinning this observation and determine whether ILA evaluation and risk stratification modulates this mortality risk

Filling the Gaps in the Pharmacy Workforce in Post-Conflict Areas: Experience from Four Countries in Sub-Saharan Africa

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-28, pub-electronic 2021-07-31Publication status: PublishedFunder: World Health Organization; Grant(s): WHO Kobe Centre – WKC: K18009Background: While the pharmacy workforce is the third largest professional healthcare group worldwide, the pharmacy workforce landscape remains unclear in post-conflict areas in sub-Saharan Africa. Method: Key informants were selected for semi-structured interviews due to their role in providing pharmacy services in the selected country: the Central African Republic (CAR), the Democratic Republic of Congo (DRC), Ethiopia, and South Sudan. Transcripts from the interviews were anonymized, coded, and analyzed. Results: Nine participants were recruited (CAR: 2; DRC: 2; Ethiopia: 2; South Sudan: 3), and all except two were pharmacists. Conflict-specific challenges in pharmacy service delivery were identified as the following: unpredictable health needs and/or mismatched pharmaceutical supply, transport difficulties due to insecure roads, and shortage of pharmacy workforce due to brain drain or interrupted schooling. Barriers to health workforce retention and growth were identified to be brain drain as a result of suboptimal living and working conditions or remuneration, the perception of an unsafe work environment, and a career pathway or commitment duration that does not fit the diaspora or expatriate staff. Conclusion: To tackle the barriers of pharmacy health workforce retention and growth, policy solutions will be required and efforts that can bring about long-term improvement should be prioritized. This is essential to achieve universal health coverage and the targets of the sustainable development goals for conflict affected areas, as well as to “leave no one behind”

MERLIon CCS Challenge: A English-Mandarin code-switching child-directed speech corpus for language identification and diarization

To enhance the reliability and robustness of language identification (LID) and language diarization (LD) systems for heterogeneous populations and scenarios, there is a need for speech processing models to be trained on datasets that feature diverse language registers and speech patterns. We present the MERLIon CCS challenge, featuring a first-of-its-kind Zoom video call dataset of parent-child shared book reading, of over 30 hours with over 300 recordings, annotated by multilingual transcribers using a high-fidelity linguistic transcription protocol. The audio corpus features spontaneous and in-the-wild English-Mandarin code-switching, child-directed speech in non-standard accents with diverse language-mixing patterns recorded in a variety of home environments. This report describes the corpus, as well as LID and LD results for our baseline and several systems submitted to the MERLIon CCS challenge using the corpus.Comment: Accepted by Interspeech 2023, 5 pages, 2 figures, 3 table

Treatment of pathophysiologic propagation outside of the pulmonary veins in retreatment of atrial fibrillation patients:RECOVER AF study

Aims RECOVER AF evaluated the performance of whole-chamber non-contact charge-density mapping to guide the ablation of non-pulmonary vein (PV) targets in persistent atrial fibrillation (AF) patients following either a first or second failed procedure. Methods RECOVER AF was a prospective, non-randomized trial that enrolled patients scheduled for a first or second ablation re- and results treatment for recurrent AF. The PVs were assessed and re-isolated if necessary. The AF maps were used to guide the ablation of non-PV targets through elimination of pathologic conduction patterns (PCPs). Primary endpoint was freedom from AF on or off antiarrhythmic drugs (AADs) at 12 months. Patients undergoing retreatment with the AcQMap System (n = 103) were 76% AF-free at 12 months [67% after single procedure (SP)] on or off AADs (80% free from AF on AADs). Patients who had only received a pulmonary vein isolation (PVI) prior to study treatment of non-PV targets with the AcQMap System were 91% AF-free at 12 months (83% SP). No major adverse events were reported. Conclusion Non-contact mapping can be used to target and guide the ablation of PCPs beyond the PVs in persistent AF patients returning for a first or second retreatment with 76% freedom from AF at 12 months. The AF freedom was particularly high, 91% (43/47), for patients enrolled having only a prior de novo PVI, and freedom from all atrial arrhythmias for this cohort was 74% (35/47). These early results are encouraging and suggest that guiding individualized targeted ablation of PCPs may therefore be advantageous to target at the earliest opportunity in patients with persistent AF.</p

Assessing the outcomes of participatory research: protocol for identifying, selecting, appraising and synthesizing the literature for realist review

<p>Abstract</p> <p>Background</p> <p>Participatory Research (PR) entails the co-governance of research by academic researchers and end-users. End-users are those who are affected by issues under study (<it>e.g.</it>, community groups or populations affected by illness), or those positioned to act on the knowledge generated by research (<it>e.g.</it>, clinicians, community leaders, health managers, patients, and policy makers). Systematic reviews assessing the generalizable benefits of PR must address: the diversity of research topics, methods, and intervention designs that involve a PR approach; varying degrees of end-user involvement in research co-governance, both within and between projects; and the complexity of outcomes arising from long-term partnerships.</p> <p>Methods</p> <p>We addressed the above mentioned challenges by adapting realist review methodology to PR assessment, specifically by developing inductively-driven identification, selection, appraisal, and synthesis procedures. This approach allowed us to address the non-uniformity and complexity of the PR literature. Each stage of the review involved two independent reviewers and followed a reproducible, systematic coding and retention procedure. Retained studies were completed participatory health interventions, demonstrated high levels of participation by non-academic stakeholders (<it>i.e.</it>, excluding studies in which end-users were not involved in co-governing throughout the stages of research) and contained detailed descriptions of the participatory process and context. Retained sets are being mapped and analyzed using realist review methods.</p> <p>Results</p> <p>The librarian-guided search string yielded 7,167 citations. A total of 594 citations were retained after the identification process. Eighty-three papers remained after selection. Principle Investigators (PIs) were contacted to solicit all companion papers. Twenty-three sets of papers (23 PR studies), comprising 276 publications, passed appraisal and are being synthesized using realist review methods.</p> <p>Discussion</p> <p>The systematic and stage-based procedure addressed challenges to PR assessment and generated our robust understanding of complex and heterogeneous PR practices. To date, realist reviews have focussed on evaluations of relatively uniform interventions. In contrast our PR search yielded a wide diversity of partnerships and research topics. We therefore developed tools to achieve conceptual clarity on the PR field, as a beneficial precursor to our theoretically-driven synthesis using realist methods. Findings from the ongoing review will be provided in forthcoming publications.</p

CowN Sustains Nitrogenase Turnover in the Presence of the Inhibitor Carbon Monoxide

Nitrogenase is the only enzyme capable of catalyzing nitrogen fixation, the reduction of dinitrogen gas (N2) to ammonia (NH3). Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Nitrogen-fixing bacteria rely on the protein CowN to grow in the presence of CO. However, the mechanism by which CowN operates is unknown. Here, we present the biochemical characterization of CowN and examine how CowN protects nitrogenase from CO. We determine that CowN interacts directly with nitrogenase and that CowN protection observes hyperbolic kinetics with respect to CowN concentration. At a CO concentration of 0.001 atm, CowN restores nearly full nitrogenase activity. Our results further indicate that CowN’s protection mechanism involves decreasing the binding affinity of CO to nitrogenase’s active site approximately tenfold without interrupting substrate turnover. Taken together, our work suggests CowN is an important auxiliary protein in nitrogen fixation that engenders CO tolerance to nitrogenase