Sex differences in treatments and outcomes of patients with cardiogenic shock: a systematic review and epidemiological meta-analysis.

BACKGROUND: Women are at higher risk of mortality from many acute cardiovascular conditions, but studies have demonstrated differing findings regarding the mortality of cardiogenic shock in women and men. To examine differences in 30-day mortality and mechanical circulatory support use by sex in patients with cardiogenic shock. MAIN BODY: Cochrane Central, PubMed, MEDLINE and EMBASE were searched in April 2024. Studies were included if they were randomised controlled trials or observational studies, included adult patients with cardiogenic shock, and reported at least one of the following outcomes by sex: raw mortality, adjusted mortality (odds ratio) or use of mechanical circulatory support. Out of 4448 studies identified, 81 met inclusion criteria, pooling a total of 656,754 women and 1,018,036 men. In the unadjusted analysis for female sex and combined in-hospital and 30-day mortality, women had higher odds of mortality (Odds Ratio (OR) 1.35, 95% confidence interval (CI) 1.26-1.44, p < 0.001). Pooled unadjusted mortality was 35.9% in men and 40.8% in women (p < 0.001). When only studies reporting adjusted ORs were included, combined in-hospital/30-day mortality remained higher in women (OR 1.10, 95% CI 1.06-1.15, p < 0.001). These effects remained consistent across subgroups of acute myocardial infarction- and heart failure- related cardiogenic shock. Overall, women were less likely to receive mechanical support than men (OR = 0.67, 95% CI 0.57-0.79, p < 0.001); specifically, they were less likely to be treated with intra-aortic balloon pump (OR = 0.79, 95% CI 0.71-0.89, p < 0.001) or extracorporeal membrane oxygenation (OR = 0.84, 95% 0.71-0.99, p = 0.045). No significant difference was seen with use of percutaneous ventricular assist devices (OR = 0.82, 95% CI 0.51-1.33, p = 0.42). CONCLUSION: Even when adjusted for confounders, mortality for cardiogenic shock in women is approximately 10% higher than men. This effect is seen in both acute myocardial infarction and heart failure cardiogenic shock. Women with cardiogenic shock are less likely to be treated with mechanical circulatory support than men. Clinicians should make immediate efforts to ensure the prompt diagnosis and aggressive treatment of cardiogenic shock in women.

PLCδ1 Plays Central Roles in the Osmotic Activation of ΔN-TRPV1 Channels in Mouse Supraoptic Neurons and in Murine Osmoregulation.

The magnocellular neurosecretory cells (MNCs) of the hypothalamus play a vital role in osmoregulation, but the mechanisms underlying MNC osmosensitivity are not fully understood. We showed previously that high osmolality activates phospholipase C (PLC) in rat MNCs in a Ca2+-dependent manner and that PLC activation is necessary for full osmotic activation of an N-terminal variant of the TRPV1 (ΔN-TRPV1) channel. We therefore hypothesized that the Ca2+-dependent δ1 isoform of PLC contributes to ΔN-TRPV1 activation and tested whether MNC function is defective in a transgenic PLCδ1 KO mouse. Water deprivation for 24 h caused greater increases in serum osmolality and losses in body weight in PLCδ1 KO mice than it did in control mice. Action potentials and ΔN-TRPV1 currents were measured in acutely isolated mouse MNCs using whole-cell patch clamp before and after exposure to hypertonic solutions. This treatment elicited a significant activation of ΔN-TRPV1 currents and an increase in firing rate in MNCs isolated from control mice, but not from PLCδ1 KO mice. Submembranous filamentous actin was measured in isolated MNCs before and after treatment with angiotensin II and hypertonic solution. Both treatments caused an increase in filamentous actin fluorescence in MNCs isolated from control mice, but both responses were significantly attenuated in MNCs from PLCδ1 KO mice. Our data demonstrate that the PLCδ1 isoform plays a key role in the activation of ΔN-TRPV1 channels and in osmosensory transduction in MNCs. This study advances our understanding of the molecular mechanisms underlying mammalian osmoregulation.SIGNIFICANCE STATEMENT Magnocellular neurosecretory cells (MNCs) of the hypothalamus play a central role in osmoregulation. We have identified a key role for the PLCδ1 isoform in the activation of ΔN-TRPV1 channels and osmosensory transduction in MNCs. The data indicate that the PLCδ1 isoform is activated by the Ca2+ influx occurring during MNC action potentials and exerts a positive feedback on ΔN-TRPV1 channels to enhance MNC excitability. This study provides evidence that PLCδ1 is a key molecule underlying osmosensory transduction, the regulation of VP release, and osmoregulation.

Routine postoperative noninvasive respiratory support and pneumonia after elective surgery: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Postoperative pulmonary complications, including pneumonia, are a substantial cause of morbidity. We hypothesised that routine noninvasive respiratory support was associated with a lower incidence of pneumonia after surgery. METHODS: Systematic review and meta-analysis of RCTs comparing the routine use of continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or high-flow nasal oxygen (HFNO) against standard postoperative care in the adult population. We searched MEDLINE (PubMed), EMBASE, and CENTRAL from the start of indexing to July 27, 2021. Articles were reviewed and data extracted in duplicate, with discrepancies resolved by a senior investigator. The primary outcome was pneumonia, and the secondary outcome was postoperative pulmonary complications. We calculated risk difference (RD) with 95% confidence intervals using DerSimonian and Laird random effects models. We assessed risk of bias using the Cochrane risk of bias tool. RESULTS: From 18 513 records, we included 38 trials consisting of 9782 patients. Pneumonia occurred in 214/4403 (4.9%) patients receiving noninvasive respiratory support compared with 216/3937 (5.5%) receiving standard care (RD -0.01 [95% confidence interval: -0.02 to 0.00]; I2=8%; P=0.23). Postoperative pulmonary complications occurred in 393/1379 (28%) patients receiving noninvasive respiratory support compared with 280/902 (31%) receiving standard care (RD -0.11 [-0.23 to 0.01]; I2=79%; P=0.07). Subgroup analyses did not identify a benefit of CPAP, NIV, or HFNO in preventing pneumonia. Tests for publication bias suggest six unreported trials. CONCLUSION: The results of this evidence synthesis do not support the routine use of postoperative CPAP, NIV, or HFNO to prevent pneumonia after surgery in adults. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42019156741.

Client buy-in: An essential consideration for graded motor imagery in hand therapy.

STUDY DESIGN: This is a cross-sectional survey research. INTRODUCTION: Current evidence provides efficacy of graded motor imagery (GMI) in chronic pain conditions but also reveals barriers to its implementation. PURPOSE OF THE STUDY: The purpose of this study was to describe current utilization of GMI in hand therapy practice. METHODS: Survey tool, informed by literature and Revised Neurophysiology of Pain Questionnaire (NPQ) was electronically distributed to members of the American Society of Hand Therapists. RESULTS: 132 therapists completed the survey. 65.2% reported they would always or very likely use GMI in clients with central sensitization, but no relationship between the likelihood of therapists using GMI to score achieved on the NPQ was found. Lack of patient buy-in, was the main barrier cited. "Sell it well" with pain neuroscience education the most cited strategy. DISCUSSION: GMI is frequently used in clients with central sensitization but requires client buy-in. CONCLUSIONS: Understanding and explaining pain mechanism is essential for implementing GMI.

Enantioselective Catalyst Systems from Copper(II) Triflate and BINOL-Silanediol.

Silanediol and copper catalysis are merged, for the first time, to create an enhanced Lewis acid catalyst system for enantioselective heterocycle functionalization. The promise of this silanediol and copper catalyst combination is demonstrated in the enantioselective addition of indoles to alkylidene malonates to give rise to the desirable adducts in excellent yield and high enantiomeric excess. From these studies, 1,1'-bi-2-naphthol (BINOL)-based silanediols emerge as one-of-a-kind cocatalysts. Their potential role in the reaction pathway is also discussed.

Stream Nitrogen, Phosphorus, and Sediment Concentrations Show Contrasting Long-term Trends Associated with Agricultural Change.

Stream water quality can be greatly influenced by changes in agricultural practices, but studies of long-term dynamics are scarce. Here we describe trends over 21 yr (1994-2014) in nutrients and suspended sediments in three streams in a Midwestern US agricultural watershed. During this time, the watershed experienced substantial changes in agricultural practices, most importantly a pronounced shift from conventional to conservation tillage. In the 1990s and early 2000s, NH, soluble reactive P, and suspended sediment concentrations (standardized for discharge and season) each declined significantly (>4-12% per year) in at least two of the three streams ( < 0.01), whereas NO changed relatively little. However, since the early 2000s, declines in NH and sediment concentrations have slowed, soluble reactive P concentrations have not declined and may actually have increased, and NO concentrations have declined sharply. The more recent lack of decline in soluble reactive P coincides with a plateau in the prevalence of conservation tillage and may be because of increased soil P stratification due to long-term reduced tillage. The more recent decline in NO may be due to improved efficiency of N fertilizer use, increased soil denitrification, and/or declines in atmospheric N deposition. Our study shows that stream concentrations of N, P, and sediment can respond in contrasting ways to changes in agriculture, and that temporal trends can moderate, accelerate, or reverse over decadal timescales. Management strategies must consider contrasting temporal responses of water quality indicators and may need to be adaptively adjusted at scales of years to decades.

Justifying Rehabilitation Intensity Through Functional Performance Measures in Postacute Care.

The Centers for Medicare and Medicaid Services (CMS) has scrutinized the provision of rehabilitation services in skilled nursing facilities (SNFs) for some time. Little research guidance exists on appropriate dosage or rehabilitation intensity (RI) among SNF patients or patients in other postacute care (PAC) settings. CMS developed a PAC assessment, the Continuity Assessment Record and Evaluation (CARE) Tool, in response to questions about what issues drive placement in various PAC settings under Medicare. The ability to adequately assess functional outcomes and correlate them to the RI provided by using the CARE Tool is promising. However, further research, policy advocacy, and practice analysis must be undertaken to promote and protect adequate access to occupational therapy and physical therapy in SNFs and other PAC settings. Individual practitioners must participate in data gathering to ensure that the data for analysis are fully informed by the occupational therapy perspective.

Role of Occupational Therapy in Preventing Work-Related Musculoskeletal Disorders With Recycling Workers: A Pilot Study.

Little is known about injury prevention in recycling workers; therefore, in this study, I aimed to identify physical and psychosocial risk factors for employees involved in single-stream recycling and to explore strategies for prevention and wellness. Fifteen participants who were either recycling workers or supervisors located throughout seven locations on an urban university campus participated. A mixed-methods research design was used to obtain data through a variety of standardized work environment and health questionnaires and semistructured interviews. Approximately 80% of participants expressed satisfaction with their jobs; 50% reported having a musculoskeletal injury; and 33% reported a lack of support from coworkers or supervisors, which created stress and anxiety. Additional risk factors included poor body mechanics, equipment issues, poor social interactions, and lack of supervisor knowledge for prevention. Occupational therapy practitioners are well situated to support preventive interventions that address the combined physical and psychosocial needs of recycling workers.

Role of Occupational Therapy in Case Management and Care Coordination for Clients With Complex Conditions.

Specific aspects of the profession of occupational therapy support a distinct value for its practitioners participating fully in the development of case management and care coordination systems. The expectation in the 21st century is that the U.S. health care system must be transformed from one that promotes volume of service to one that promotes value of care. Case management and care coordination will be critical components of that transformation. Occupational therapy's principles, education, practice, approach, and perspective offer much to benefit this increased attention to case management and care coordination. Occupational therapy practitioners should promote themselves and their profession as these system changes develop.

Osmotic activation of phospholipase C triggers structural adaptation in osmosensitive rat supraoptic neurons.

The magnocellular neurosecretory cells of the hypothalamus (MNCs) synthesize and secrete vasopressin or oxytocin. A stretch-inactivated cation current mediated by TRPV1 channels rapidly transduces increases in external osmolality into a depolarization of the MNCs leading to an increase in action potential firing and thus hormone release. Prolonged increases in external osmolality, however, trigger a reversible structural and functional adaptation that may enable the MNCs to sustain high levels of hormone release. One poorly understood aspect of this adaptation is somatic hypertrophy. We demonstrate that hypertrophy can be evoked in acutely isolated rat MNCs by exposure to hypertonic solutions lasting tens of minutes. Osmotically evoked hypertrophy requires activation of the stretch-inactivated cation channel, action potential firing, and the influx of Ca(2+). Hypertrophy is prevented by pretreatment with a cell-permeant inhibitor of exocytotic fusion and is associated with an increase in total membrane capacitance. Recovery is disrupted by an inhibitor of dynamin function, suggesting that it requires endocytosis. We also demonstrate that hypertonic solutions cause a decrease in phosphatidylinositol 4,5-bisphosphate in the plasma membranes of MNCs that is prevented by an inhibitor of phospholipase C (PLC). Inhibitors of PLC or protein kinase C (PKC) prevent osmotically evoked hypertrophy, and treatment with a PKC-activating phorbol ester can elicit hypertrophy in the absence of changes in osmolality. These studies suggest that increases in osmolality cause fusion of internal membranes with the plasma membrane of the MNCs and that this process is mediated by activity-dependent activation of PLC and PKC.

Relationship between touch sensation of the affected hand and performance of valued activities in individuals with chronic stroke.

OBJECTIVE: To investigate the association between touch sensation of the affected hand and performance and satisfaction with performance of valued activities in individuals with chronic stroke. METHODS: Using a cross-sectional study design, this study correlated factors related to hand sensation and activity performance in individuals with chronic stroke. The Touch Test Evaluators and Canadian Occupational Performance Measure (COPM) were used. Correlations were used to determine the relationships between touch sensation of the affected hand and individuals' performance and satisfaction with performance of valued activities. RESULTS: There was a good to excellent relationship between sensation and performance and satisfaction with performance of valued activities for individuals with intact touch sensation of the affected hand who scored higher on the COPM. There was little to no relationship between touch sensation of the affected hand and performance of valued activities for individuals with impaired sensation. CONCLUSION: This is the first study to relate touch sensation of the affected hand and performance and satisfaction with performance of valued activities in individuals with stroke. The findings suggest that rehabilitation therapists need to continue to address sensory function in evaluation and intervention as it relates to performance in valued activities. This study serves as a foundation for future research in sensation and performance of valued activities in individuals with chronic stroke.

Bootstrapping a powerful mixed portmanteau test for time series.

A new portmanteau test statistic is proposed for detecting nonlinearity in time series data. The new portmanteau statistic is calculated from the log of the determinant of a matrix comprised of the autocorrelations and cross-correlations of the residuals and squared residuals of a fitted time series. The asymptotic distribution of the proposed test statistic is derived as a linear combination of chi-square distributed random variables and can be approximated by a gamma distribution. A bootstrapping approach is shown to be robust when distributional assumptions are relaxed. The efficacy of the statistic is studied against linear and nonlinear dependency structures of some stationary time series models. It is shown that the new test can provide higher power than other tests in many situations. We demonstrate the advantages of the proposed test by investigating linear and nonlinear effects in an economic series and two environmental time series.

Design and Synthesis of a New Class of Twin-Chain Amphiphiles for Self-Assembled Monolayer-based Electrochemical Biosensor Applications.

A new class of twin-chain hydroxyalkylthiols (mercaptoalkanols) featuring a nearly constant cross-section and the potential for modification of one or both termini are available with complete regioselectivity through Pd-mediated couplings of benzene diiododitriflate, including an example of a previously unreported coupling to generate an ortho-substituted arene bis acetic acid. Self-assembled monolayers (SAMs) prepared from the new amphiphiles demonstrate improved stability in an electrochemical sensor system compared with monolayers prepared from analogous single chain thiols.

Primate follicular development and oocyte maturation in vitro.

The factors and processes involved in primate follicular development are complex and not fully understood. An encapsulated three-dimensional (3D) follicle culture system could be a valuable in vitro model to study the dynamics and regulation of folliculogenesis in intact individual follicles in primates. Besides the research relevance, in vitro follicle maturation (IFM) is emerging as a promising approach to offer options for fertility preservation in female patients with cancer. This review summarizes the current published data on in vitro follicular development from the preantral to small antral stage in nonhuman primates, including follicle survival and growth, endocrine (ovarian steroid hormone) and paracrine/autocrine (local factor) function, as well as oocyte maturation and fertilization. Future directions include major challenges and strategies to further improve follicular growth and differentiation with oocytes competent for in vitro fertilization and subsequent embryonic development, as well as opportunities to investigate primate folliculogenesis by utilizing this 3D culture system. The information may be valuable in identifying optimal conditions for human follicle culture, with the ultimate goal of translating the experimental results and products to patients, thereby facilitating diagnostic and therapeutic approaches for female fertility.

Chiral silanediols in anion-binding catalysis.

A perfect pair: Silanediols are effective catalysts for the addition of silyl ketene acetals to N-acylisoquinolinium ions. Importantly, this is the first example of a silanediol plausibly participating in anion-binding catalysis, a relatively new direction in the field of hydrogen-bond-donor catalysis. The chiral, enantiopure C2 -symmetric silanediol 1 catalyzes enantioselective transformations.

Re2O7-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles.

Re(VII) oxides catalyze the acetalization, monoperoxyacetalization, monothioacetalization and allylation of hemiacetals. The reactions, which take place under mild conditions and at low catalyst loadings, can be conducted using hemiacetals, the corresponding O-silyl ethers, and, in some cases, the acetal dimers. Aldehydes react under similar conditions to furnish good yields of dithioacetals. Reactions of hemiacetals with nitrogen nucleophiles are unsuccessful. 1,2-Dioxolan-3-ols (peroxyhemiacetals) undergo Re(VII)-promoted etherification but not allylation. Hydroperoxyacetals (1-alkoxyhydroperoxides) undergo selective exchange of the alkoxide group in the presence of either Re2O7 or a Brønsted acid.

Protocol to visualize ion channel trafficking in acutely isolated rodent neurons using live-cell immunocytochemistry.

Here, we present a protocol for live-cell immunocytochemistry to demonstrate reversible translocation of ion channels to the neuronal cell surface. We describe steps for cell preparation and isolation, experimental treatment, antibody binding prior to fixation, specific pipetting techniques, troubleshooting, and expected outcomes of correct use of the protocol. This protocol will be useful to study regulated translocation of ion channels and other membrane proteins. For complete details on the use and execution of this protocol, please refer to Haan et al.1.

Specialist hybrid models with asymmetric training for malaria prevalence prediction.

Malaria is a common and serious disease that primarily affects developing countries and its spread is influenced by a variety of environmental and human behavioral factors; therefore, accurate prevalence prediction has been identified as a critical component of the Global Technical Strategy for Malaria from 2016 to 2030. While traditional differential equation models can perform basic forecasting, supervised machine learning algorithms provide more accurate predictions, as demonstrated by a recent study using an elastic net model (REMPS). Nevertheless, current short-term prediction systems do not achieve the required accuracy levels for routine clinical practice. To improve in this direction, stacked hybrid models have been proposed, in which the outputs of several machine learning models are aggregated by using a meta-learner predictive model. In this paper, we propose an alternative specialist hybrid approach that combines a linear predictive model that specializes in the linear component of the malaria prevalence signal and a recurrent neural network predictive model that specializes in the non-linear residuals of the linear prediction, trained with a novel asymmetric loss. Our findings show that the specialist hybrid approach outperforms the current state-of-the-art stacked models on an open-source dataset containing 22 years of malaria prevalence data from the city of Ibadan in southwest Nigeria. The specialist hybrid approach is a promising alternative to current prediction methods, as well as a tool to improve decision-making and resource allocation for malaria control in high-risk countries.

Osmotically evoked PLCδ1-dependent translocation of ΔN-TRPV1 channels in rat supraoptic neurons.

Osmoregulation is an essential homeostatic process that requires constant release of vasopressin during sustained increases in plasma osmolality. The magnocellular neurosecretory cells (MNCs) respond to increases in external osmolality through increases in the activity of ΔN-TRPV1 channels, which leads to increased action potential firing and vasopressin release. We show that sustained exposure of acutely isolated rat and mouse MNCs to hypertonic solutions (90 min) causes a reversible translocation of ΔN-TRPV1 channels from internal stores to the plasma membrane that depends on the activation of phospholipase C and on SNARE-dependent exocytosis. ΔN-TRPV1 channel translocation is absent in MNCs isolated from transgenic mice lacking the PLCδ1 isoform, suggesting that PLCδ1 is essential for triggering this process. The translocation of ΔN-TRPV1 channels to the cell surface could contribute to the maintenance of MNC excitability during sustained increases in osmolality. Our data therefore have important implications for the mechanisms underlying mammalian osmoregulation.

A comparative study of model-centric and data-centric approaches in the development of cardiovascular disease risk prediction models in the UK Biobank.

Aims: A diverse set of factors influence cardiovascular diseases (CVDs), but a systematic investigation of the interplay between these determinants and the contribution of each to CVD incidence prediction is largely missing from the literature. In this study, we leverage one of the most comprehensive biobanks worldwide, the UK Biobank, to investigate the contribution of different risk factor categories to more accurate incidence predictions in the overall population, by sex, different age groups, and ethnicity. Methods and results: The investigated categories include the history of medical events, behavioural factors, socioeconomic factors, environmental factors, and measurements. We included data from a cohort of 405 257 participants aged 37-73 years and trained various machine learning and deep learning models on different subsets of risk factors to predict CVD incidence. Each of the models was trained on the complete set of predictors and subsets where each category was excluded. The results were benchmarked against QRISK3. The findings highlight that (i) leveraging a more comprehensive medical history substantially improves model performance. Relative to QRISK3, the best performing models improved the discrimination by 3.78% and improved precision by 1.80%. (ii) Both model- and data-centric approaches are necessary to improve predictive performance. The benefits of using a comprehensive history of diseases were far more pronounced when a neural sequence model, BEHRT, was used. This highlights the importance of the temporality of medical events that existing clinical risk models fail to capture. (iii) Besides the history of diseases, socioeconomic factors and measurements had small but significant independent contributions to the predictive performance. Conclusion: These findings emphasize the need for considering broad determinants and novel modelling approaches to enhance CVD incidence prediction.