Clade-specific forebrain cytoarchitectures of the extinct Tasmanian tiger.

The thylacine, or Tasmanian tiger, is the largest of modern-day carnivorous marsupials and was hunted to extinction by European settlers in Australia. Its physical resemblance to eutherian wolves is a striking example of evolutionary convergence to similar ecological niches. However, whether the neuroanatomical organization of the thylacine brain resembles that of canids and how it compares with other mammals remain unknown due to the scarcity of available samples. Here, we gained access to a century-old hematoxylin-stained histological series of a thylacine brain, digitalized it at high resolution, and compared its forebrain cellular architecture with 34 extant species of monotremes, marsupials, and eutherians. Phylogenetically informed comparisons of cortical folding, regional volumes, and cell sizes and densities across cortical areas and layers provide evidence against brain convergences with canids, instead demonstrating features typical of marsupials, and more specifically Dasyuridae, along with traits that scale similarly with brain size across mammals. Enlarged olfactory, limbic, and neocortical areas suggest a small-prey predator and/or scavenging lifestyle, similar to extant quolls and Tasmanian devils. These findings are consistent with a nonuniformity of trait convergences, with brain traits clustering more with phylogeny and head/body traits with lifestyle. By making this resource publicly available as rapid web-accessible, hierarchically organized, multiresolution images for perpetuity, we anticipate that additional comparative insights might arise from detailed studies of the thylacine brain and encourage researchers and curators to share, annotate, and preserve understudied material of outstanding biological relevance.

Early administration of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: High-intensity statin therapy is currently recommended initial guideline therapy in ACS treatment. However, only a minority of patients are achieving LDL-C attainment goal at 6 months. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are on recommended guideline therapy post-ACS if LDL-C goal attainment is not achieved after high-intensity statin (4-6 weeks) and after the addition of ezetimibe if guideline goal attainment is not achieved after an additional 4-6 weeks. Thus, it has been recommended that PCSK9 inhibitors be considered earlier post-ACS. However, the efficacy of early PCSK9 inhibitors initiation in ACS patients remains uncertain. METHODS: This systematic review and meta-analysis was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) and observational studies involving ACS patients who received PCSK9 inhibitors within 48 h of hospitalization were included. Common and random effects models were used to evaluate the pooled effect of early PCSK9 inhibitor administration. Nine RCTs and three cohort studies were included. RESULTS: Early PCSK9 inhibitor administration reduced the incidence of MI, ACS hospitalization, and revascularization at 6-18 months post-ACS. Although there was a drift towards reduced stroke, all-cause mortality, and cardiovascular death, no statistically significant reduction was observed. Additionally, PCSK9 inhibitors significantly enhanced lipid control at 4-12 weeks after index hospitalization. CONCLUSION: Early PCSK9 inhibitors initiation in ACS patients reduces MACE and improves lipid profiles. While the results propose promising benefits in terms of stroke and mortality, further research with longer follow-up is required for more decisive evidence.

Triglyceride-glucose index as a predictor of cardiac adverse events in acute coronary syndrome patients undergoing percutaneous coronary intervention: role of diabetes.

BACKGROUND: Triglyceride-glucose index (TyG), a surrogate marker of insulin resistance (IR), could be a potential prognostic marker in patients with acute coronary syndromes (ACS). We evaluated the effect of the TyG index on major adverse cardiac and cerebrovascular events (MACCE) in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: This registry-based cohort study was conducted at Tehran Heart Center from 2015 to 2021 and the median follow-up duration was 378 days. The primary outcome was MACCE and the secondary outcomes were MACCE components: all-cause mortality, myocardial infarction, stroke, target vessel revascularization, target lesion revascularization, and coronary artery bypass grafting. For comparison among TyG quartiles (Q), the log-rank test was used. Unadjusted and adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to describe the association between TyG quartiles and MACCE. A subgroup of euglycemic patients was also evaluated. RESULTS: A total of 13,542 patients were included. Patients in the fourth TyG quartile (Q4) were younger, had higher mean BMI, and higher prevalence of hypertension, diabetes, and dyslipidemia. The adjusted Cox model showed that a 1-unit increment of the TyG index was associated with a significantly higher risk of MACCE (aHR 1.18, 95% CI 1.08 to 1.30, p < 0.001). Among TyG quartiles, there was a higher MACCE incidence in Q4 compared to Q1 (aHR 1.29, 95% CI 1.08 to 1.53, p = 0.005). In the euglycemic subgroup of the population, there was no significant association between MACCE incidence and a 1-unit increase in TyG or among TyG quartiles. CONCLUSION: Based on our findings, while higher TyG levels and quartiles were associated with higher rates of MACCE in ACS, there was no such effect in the euglycemic population. If confirmed in future studies, these results can be beneficial for clinicians to risk stratify these patients with an easy-to-use index and determine clinical plans based on their risk.

Current clinical evidence is insufficient to support HMME-PDT as the first choice of treatment for young children with port wine birthmarks.

BACKGROUND: Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades. AIM: To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities. METHOD: PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality. RESULT: A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults. CONCLUSION: PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

Researching the future: scenarios to explore the future of human genome editing.

BACKGROUND: Forward-looking, democratically oriented governance is needed to ensure that human genome editing serves rather than undercuts public values. Scientific, policy, and ethics communities have recognized this necessity but have demonstrated limited understanding of how to fulfill it. The field of bioethics has long attempted to grapple with the unintended consequences of emerging technologies, but too often such foresight has lacked adequate scientific grounding, overemphasized regulation to the exclusion of examining underlying values, and failed to adequately engage the public. METHODS: This research investigates the application of scenario planning, a tool developed in the high-stakes, uncertainty-ridden world of corporate strategy, for the equally high-stakes and uncertain world of the governance of emerging technologies. The scenario planning methodology is non-predictive, looking instead at a spread of plausible futures which diverge in their implications for different communities' needs, cares, and desires. RESULTS: In this article we share how the scenario development process can further understandings of the complex and dynamic systems which generate and shape new biomedical technologies and provide opportunities to re-examine and re-think questions of governance, ethics and values. We detail the results of a year-long scenario planning study that engaged experts from the biological sciences, bioethics, social sciences, law, policy, private industry, and civic organizations to articulate alternative futures of human genome editing. CONCLUSIONS: Through sharing and critiquing our methodological approach and results of this study, we advance understandings of anticipatory methods deployed in bioethics, demonstrating how this approach provides unique insights and helps to derive better research questions and policy strategies.

The Healthcare Environment Survey: A multicountry psychometric evaluation of nurses' job satisfaction.

AIM: To evaluate the properties of a reduced-item Healthcare Environment Survey measuring nurses' job satisfaction across eight countries. BACKGROUND: There is currently no rigorously tested international measure of nurses' job satisfaction that can be used internationally to improve the nurse work environment. METHODS: Nursing staff from 11 hospitals in eight countries participated in this study. The original 57-item, 11-facet Healthcare Environment Survey was evaluated for reliability, validity, and measurement invariance: Cronbach's alpha was used to test for reliability; construct, discriminate, and convergent testing were used to test validity; and invariance testing including configural, metric, and scalar tests were used to study measurement invariance between the countries. RESULTS: 2,046 nursing staff completed the survey. Reliability was established for all six subscales and the combined composite score. Both validity and measurement invariance were supported in every test conducted. An excellent model fit was found for the final 19-item, 6-facet Healthcare Environment Survey that explained 82% of the variance of nurses' job satisfaction. CONCLUSIONS: Findings suggest the instrument is an efficient measure of nurses' job satisfaction across multiple countries. Longitudinal testing for invariance will be needed to ensure the model remains a good fit. Testing more countries will also verify model fit. IMPLICATIONS FOR NURSING: The instrument can be used to measure nurse job satisfaction globally. IMPLICATIONS FOR NURSING POLICY: The instrument can be used to assess interventions to improve the social (patient, unit manager, and coworker) and technical (professional rewards, autonomy, and professional growth) aspects of nurse job satisfaction.

Quantifying the impact of COVID-19 on travel behavior in different socio-economic segments.

The COVID-19 pandemic has resulted in substantial negative impacts on social equity. To investigate transport inequities in communities with varying medical resources and COVID controlling measures during the COVID pandemic and to develop transport-related policies for the post-COVID-19 world, it is necessary to evaluate how the pandemic has affected travel behavior patterns in different socio-economic segments (SES). We first analyze the travel behavior change percentage due to COVID, e.g., increased working from home (WFH), decreased in-person shopping trips, decreased public transit trips, and canceled overnight trips of individuals with varying age, gender, education levels, and household income, based on the most recent US Household Pulse Survey census data during Aug 2020 âˆ¼ Dec 2021. We then quantify the impact of COVID-19 on travel behavior of different socio-economic segments, using integrated mobile device location data in the USA over the period 1 Jan 2020-20 Apr 2021. Fixed-effect panel regression models are proposed to statistically estimate the impact of COVID monitoring measures and medical resources on travel behavior such as nonwork/work trips, travel miles, out-of-state trips, and the incidence of WFH for low SES and high SES. We find that as exposure to COVID increases, the number of trips, traveling miles, and overnight trips started to bounce back to pre-COVID levels, while the incidence of WFH remained relatively stable and did not tend to return to pre-COVID level. We find that the increase in new COVID cases has a significant impact on the number of work trips in the low SES but has little impact on the number of work trips in the high SES. We find that the fewer medical resources there are, the fewer mobility behavior changes that individuals in the low SES will undertake. The findings have implications for understanding the heterogeneous mobility response of individuals in different SES to various COVID waves and thus provide insights into the equitable transport governance and resiliency of the transport system in the "post-COVID" era.

Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial.

AIMS: Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients. METHODS AND RESULTS: A total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053). CONCLUSIONS: Icosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.

Public transport trends in Australia during the COVID-19 pandemic: An investigation of the influence of bio-security concerns on trip behaviour.

This paper draws on findings from an Australia-wide survey with data collected in three waves throughout 2020 to explore the impact of COVID-19 on public transport trends in metropolitan areas of Australia. Following consideration of the public transport sector response to the pandemic and the emerging literature context, we explore three principal questions: (i) How has weekly travel composition changed across the waves? (ii) How has level of concern with using public transport changed over the course of the pandemic given new bio-security concerns? and (iii) How has attitudes to risk been associated with the changes in PT use? A key finding is that concerns over bio-security issues around public transport are enduring, that concern about hygiene is significantly negatively related to public transport use and that those with higher concern about the hygiene of public transport also held higher concern about COVID-19 at work. Even as COVID-19 restrictions are eased, both concern about crowds and hygiene have a significant and negative correlation with public transport use. Concluding remarks are offered on what might need to happen for public transport patronage to start returning.

Revealing hidden genetic diagnoses in the ocular anterior segment disorders.

PURPOSE: Ocular anterior segment disorders (ASDs) are clinically and genetically heterogeneous, and genetic diagnosis often remains elusive. In this study, we demonstrate the value of a combined analysis protocol using phenotypic, genomic, and pedigree structure data to achieve a genetic conclusion. METHODS: We utilized a combination of chromosome microarray, exome sequencing, and genome sequencing with structural variant and trio analysis to investigate a cohort of 41 predominantly sporadic cases. RESULTS: We identified likely causative variants in 54% (22/41) of cases, including 51% (19/37) of sporadic cases and 75% (3/4) of cases initially referred as familial ASD. Two-thirds of sporadic cases were found to have heterozygous variants, which in most cases were de novo. Approximately one-third (7/22) of genetic diagnoses were found in rarely reported or recently identified ASD genes including PXDN, GJA8, COL4A1, ITPR1, CPAMD8, as well as the new phenotypic association of Axenfeld-Rieger anomaly with a homozygous ADAMTS17 variant. The remainder of the variants were in key ASD genes including FOXC1, PITX2, CYP1B1, FOXE3, and PAX6. CONCLUSIONS: We demonstrate the benefit of detailed phenotypic, genomic, variant, and segregation analysis to uncover some of the previously "hidden" heritable answers in several rarely reported and newly identified ocular ASD-related disease genes.

The Impact of Interprofessional Shared Governance and a Caring Professional Practice Model on Staff's Self-report of Caring, Workplace Engagement, and Workplace Empowerment Over Time.

OBJECTIVE: To describe the impact of the implementation of interprofessional shared governance and a caring professional practice model (Relationship-Based Care [RBC]) on the staff's self-report of caring, work engagement, and workplace empowerment over a 4-year time frame. BACKGROUND: Shared or interprofessional governance has moved mainstream within healthcare settings, particularly within agencies seeking to sustain high reliability in the offering of quality patient care services and/or interest in meeting Magnet standards or embarking upon the Pathway to Excellence. Nurse leaders report that organizations having implemented shared governance thrive, citing professional governance as key to workplace engagement and empowerment, particularly related to quality care initiatives. Transition to interprofessional shared governance structures typically takes 2 to 3 years. It is unknown whether related outcome variables are sustainable over time. METHODS: Utilizing Watson's theory of human caring and appreciative inquiry as underlying frameworks, a longitudinal, quantitative study design was employed. Interprofessional focus groups and introductory sessions were offered to inform and engage all personnel within the medical center. Motivated units were identified, professional shared governance council members elected, and unit-specific education provided. Quality improvement initiatives were facilitated within unit councils, and formal leadership programs to enhance project guidance and to support staff empowerment skills for the managers of the units that were up-and-running were provided. Preimplementation and postimplementation measurements of staff's caring, workplace engagement and work empowerment were assessed, compared, and trended across units over time. RESULTS: Only work empowerment scores among staff working within RBC units were sustainable and increased progressively and significantly over time. Work engagement levels initially rose and then stabilized over time. Caring levels remained stable despite the implementation of a caring professional practice model. Statistically significant correlations were noted between work engagement and empowerment, followed by the relationship between work engagement and caring, followed by the relationship between empowerment and caring. CONCLUSIONS: The sustainability of work empowerment is likely related to the periodic provision of education for leaders regarding leading within an empowered work environment. A stronger focus on staff caring, particularly within quality improvement initiatives, with leadership guidance, will be paramount moving forward.

Activation of RhoA, Smad2, c-Src, PKC-ßII/δ and JNK in atopic dermatitis.

Atopic dermatitis is a multifactorial skin disease characterised by chronic and relapsing inflammation whose pathogenesis is incompletely understood. We found that the expression of TGFßR1 and the activation of SMAD2, RhoA, JNK, PKC-ßII/δ and c-Src were upregulated in the infiltrated inflammatory cells, fibroblasts and vasculatures in the dermis and epidermis. In addition, increases in the expression of TGFßR1 and phosphorylation levels of JNK and c-Src were positively correlated with the inflammatory progression of atopic dermatitis severity.

Evaluating the Clinical Practice Model's Strengths and Improvement Opportunities Using the Professional Practice Framework Assessment Survey: One Integrated Healthcare System's Experience.

OBJECTIVES: The aims of this study are (1) to describe the division, organizational strengths, and improvement opportunities of self-reported behaviors indicative of the multidimensional construct of professional practice and (2) to understand demographic characteristics that contributed to these strengths and improvement opportunities. BACKGROUND: Prior to implementing a system-wide interdisciplinary shared governance structure, ProHealth Care measured staff attitudes toward the multidimensional construct of professional practice as proposed within the Clinical Practice Model framework using the Professional Practice Framework Assessment Survey (PPFA-S). METHODS: Clinical and support staff were invited to share their views toward professional practice using the previously validated, reliable tool, the PPFA-S. RESULTS: Partnering relationships, scope of practice, and shared purpose were strengths. Strategies were initiated to strengthen networking councils, integrated competency, evidence-based practice, transformative capacity, and clinical tools. CONCLUSIONS: The survey identified professional practice strengths and improvement opportunities across the organization as well as factors contributing to these strengths and opportunities. These findings were useful to help guide system integration.

Predictors of Caring in the Context of Relationship-Based Care.

The caring connection between patients and health-care staff members is important to both patients and staff. This connection is amplified in organizations implementing Relationship-Based Care (RBC), a patient care delivery model that has relationships with self and others as its central concept. A secondary analysis of data from 542 health-care workers in a health-care system in the northeastern United States was performed to identify a profile of staff factors that predict a caring connection as perceived by staff. Specifically, staff self-care, clarity (of self, role, and system), dimensions of job satisfaction, and demographics were examined in relationship to caring for patients. The study demonstrated that constructs within RBC do relate to the creation of a caring connection between health-care staff members and patients, including caring for self, having a direct relationship with the patient using concepts of Primary Nursing, clarity of role, and being a direct care provider.

Synthesis of a Nonracemic C2-Symmetric Tetrahydro-1,4-azaborine and Evaluation of Hydroboration Enantioselectivity.

Tetrahydro-1,4-azaborines were accessed by hydroboration of N,N-diprenyltoluenesulfonamide 4. Conversion to the methylborinates 11 and 12 followed by heating with l-alanine and crystallization afforded (R,R,S)-13 (27%). Reduction of borinic acid (R,R)-18 with Soderquist's KH* gave (R,R)-19, and hydride abstraction by TMSCl in the presence of alkenes resulted in hydroboration, 84-86% ee for (Z)-alkenes, but (E)-alkenes or 1,1-disubstituted alkenes gave <5% ee.

Light and energy based therapeutics for genitourinary syndrome of menopause: Consensus and controversies.

Gynecologist and plastic surgeons pioneered the application of lasers in medicine and surgery almost 5 decades ago, initially used to treat cervical and vaginal pathologies. Ever since, energy-based devices have been deployed to treat pelvic pathologies and improve fertility. Recent technological developments triggered an unprecedented wave of publications, assessing the efficacy of fractional laser, and radiofrequency on the vaginal wall in reversing natural aging processes. Studies have shown that a certain degree of thermal energy deposited on the vaginal wall stimulates proliferation of the glycogen-enriched epithelium, neovascularization, and collagen formation in the lamina propria, and improves natural lubrication and control of urination. This review aimed to review such data and to guide future research. A unique assembly of experts from around the globe, compiled and edited this manuscript based on a thorough literature review and personal experience. Lasers Surg. Med. 49:137-159, 2017. © 2017 Wiley Periodicals, Inc.

Content validity, face validity and internal consistency of the Slovene version of Caring Factor Survey for care providers, caring for co-workers and caring of managers.

BACKGROUND: Caring relationships are important for developing a caring culture. It is important that care provider's relationships with patients, co-workers and managers are caring relationships. However, in the Slovene language, there is a lack of psychometrically sound instruments to measure these caring relationships. AIM: To explore the psychometric properties of the Slovenian version of the Caring Factor Survey (CFS) for care providers, the care given by co-workers and managers as judged by the providers, by evaluating its content validity, face validity and internal consistency. METHODS: In the process of our instrument, we used translation and back translation and validation based on experts' agreement. Content validity was quantified by the content validity index (CVI) and a modified Cohen's kappa index. Face validity was evaluated by ten nurses who reviewed the instruments. In the process of psychometric testing based on survey data, we used a cross-sectional research design with a convenience sample of 91 caregivers working in internal or surgical wards in two health care institutions. Cronbach's alpha and corrected item-total correlations were used to test internal consistency. RESULTS: All items in all three versions of the CFS had a CVI score higher than 0.78 and excellent modified Cohen's kappa index, showing excellent content validity. The average content validity indices were 0.990, 0.975 and 0.963. The face validity was good with no major remarks given. Cronbach's alpha was 0.941, 0.962 and 0.970. The item-total correlations reached a criterion of 0.2 < r < 0.3 for all items. CONCLUSION: All three versions of the CFS showed an acceptable content validity, face validity and internal consistency; however, due to some methodological shortcomings, results should be interpreted with caution. Further psychometric testing is needed.