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Betaine is the major water-soluble component of Lycium chinensis. Although there are reports of a protective effect of betaine on fatty liver disease, the underlying mechanisms are unclear. We investigated the effects of betaine on forkhead box O6 (FoxO6) and peroxisome proliferator-activated receptor gamma (PPARγ) expression, which are associated with hepatic lipid accumulation. In this study, we attempted to elucidate the molecular regulation of betaine on hyperglycemia-induced lipid accumulation via FoxO6 activation. HepG2 cells and liver tissue isolated from db/db mice treated with betaine at a dose of 50 mg/kg/day for 3 weeks were used. In the present study, we investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO6/PPARγ signaling in liver cells. Interestingly, betaine notably decreased lipid accumulation in FoxO6-induced mRNA expression of lipogenesis-related genes. In addition, hepatic insulin signaling was decreased; and activation of FoxO6, which is negatively regulated by Akt, was reduced by betaine treatment. Furthermore, betaine inhibited the FoxO6 interaction with PPARγ and cellular triglycerides in high-glucose- or FoxO6-overexpression-treated liver cells. In addition, we confirmed that betaine administration via oral gavage significantly ameliorated hepatic steatosis in db/db mice. The protein level of PPARγ, a lipogenic transcription factor, was decreased in the livers of db/db mice. Therefore, it has previously been shown to induce hepatic steatosis. We conclude that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the interaction between FoxO6 and PPARγ, thereby suppressing lipogenic gene transcription.

ImportanceUndertreatment of older adults with atrial fibrillation with anticoagulation therapy is an important practice gap. It has been posited that the availability of direct oral anticoagulants (DOACs) would improve oral anticoagulant (OAC) initiation in older adults with atrial fibrillation given their superior safety profile compared with warfarin.ObjectivesTo systematically examine trends in OAC initiation and nonadherence in older adults with atrial fibrillation and coexisting geriatric conditions.Design, Setting, and ParticipantsThis retrospective cohort study uses administrative claims data from Optum’s Clinformatics Data Mart from January 1, 2010, to December 31, 2020. Participants included beneficiaries of Medicare Advantage plans aged 65 years and older with atrial fibrillation and elevated risk of ischemic stroke. Data analysis was performed from October 2021 to October 2022.ExposuresCoexisting dementia, frailty, and anemia.Main Outcomes and MeasuresThe primary outcomes were OAC initiation within 12 months after the first diagnosis of atrial fibrillation per year and nonadherence with OAC per year (defined as ResultsThere were 21 603 to 51 236 patients per year (total for 2010-2020, 381 488 patients) in the OAC-eligible incident AF cohort (mean [SD] age, 77.2 [6.1] to 77.4 [6.8] years; 13 871 [51.8%] to 22 901 [49.8%] women). OAC initiation within 12 months after incident AF increased from 20.2% (5405 of 26 782 patients) in 2010 to 32.9% (7111 of 21 603 patients) in 2020. DOAC uptake increased from 1.1% (291 of 26 782 patients) to 30.9% (6678 of 21 603 patients), and warfarin initiation decreased from 19.1% (5114 of 26 782 patients) to 2.0% (436 of 21 603 patients). Older age (odds ratio [OR], 0.98; 95% CI, 0.98-0.98), dementia (OR, 0.57; 95% CI, 0.55-0.58), frailty (OR, 0.74; 95% CI, 0.72-0.76), and anemia (OR, 0.75; 95% CI, 0.74-0.77) were associated with lower odds of OAC initiation. During the study period, the median (IQR) proportion of days covered increased from 77.6% (41.0%-96.4%) to 90.2% (57.4%-98.6%), and OAC nonadherence decreased from 52.2% (2290 of 4389 patients) to 39.0% (3434 of 8798 patients).Conclusions and RelevanceSince the introduction of DOACs, OAC initiation in older adults with has improved but remained suboptimal in 2020. Additional strategies are needed to improve stroke prophylaxis in all older adults with atrial fibrillation including those with coexisting dementia, frailty, and anemia.

Previously, we reported that Sargassum horneri (Turner) C. Agardh (S. horneri) is a brown algae species that exerts anti-inflammatory activity toward murine macrophages. However, the anti-neuroinflammatory effects and the mechanism of S. horneri on microglia cells are still unknown. We investigated the anti-neuroinflammatory effects of S. horneri extract on microglia in vitro and in vivo. In the present study, we found that S. horneri was not cytotoxic to BV-2 microglia cells and it significantly decreased lipopolysaccharide (LPS)-induced NO production. Moreover, S. horneri also diminished the protein expression of iNOS, COX-2, and cytokine production, including IL-1β, TNF-α, and IL-6, on LPS-stimulated microglia activation. S. horneri elicited anti-neuroinflammatory effects by inhibiting phosphorylation of p38 MAPK and NF-κB. In addition, S. horneri inhibited astrocytes and microglia activation in LPS-challenged mice brain. Therefore, these results suggested that S. horneri exerted anti-neuroinflammatory effects on LPS-stimulated microglia cell activation by inhibiting neuroinflammatory factors and NF-κB signaling.

Background We showed that the activation of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome by the forkhead box O6 (FoxO6) transcription factor through binding of the thioredoxin-interacting protein (TXNIP) under inflammatory conditions might lead to hepatic steatosis. Although the role of the FoxO6 in mediating lipid accumulation and the chronic inflammatory process underlying the pathophysiology of hepatic steatosis are well explored, the precise mechanisms of the involvement of FoxO6 have not fully been delineated to date. Methods NLRP3 inflammasome and lipogenesis were monitored in mice overexpressed with constitutively active (CA)-FoxO6 allele, and FoxO6-null mice. In vitro study, liver cells overexpressing CA-FoxO6 were treated with palmitate, and then alterations in lipid metabolism were measured. Results The focus of our investigation was to apply palmitate treatment to elucidate the mechanisms underlying the role of FoxO6 in the activation of the cytokine IL-1β through the NLRP3 inflammasome. Initial experiments revealed that palmitate-induced FoxO6 activity was caused by its dephosphorylation, which induced its transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adapter protein ASC, and pro-caspase-1. Furthermore, TXNIP, a key regulator of cellular redox state in the upstream NLRP3 inflammasome, was induced by FoxO6 in liver and HepG2 cells. Conclusion The main contribution of the current study is the identification of FoxO6 as a key signaling element upstream of TXNIP in the regulation of the hepatic NLRP3 inflammasome of the molecular mechanisms involved in hepatic lipogenesis.

Treatment effect is typically summarized in terms of relative risk reduction or number needed to treat ("conventional effect summary"). Restricted mean survival time (RMST) summarizes treatment effect in terms of a gain or loss in event-free days. Older adults' preference between the two effect summary measures has not been studied.We conducted a mixed methods study using a quantitative survey and qualitative semi-structured interviews. For the survey, we enrolled 102 residents with hypertension at five senior housing facilities (mean age 81.3 years, 82 female, 95 white race). We randomly assigned respondents to either RMST-based (n = 49) or conventional decision aid (n = 53) about the benefits and harms of intensive versus standard blood pressure-lowering strategies and compared decision conflict scale (DCS) responses (range: 0 [no conflict] to 100 [maximum conflict];25 is associated with implementing decisions). We used a purposive sample of 23 survey respondents stratified by both their random assignment and DCS from the survey. Inductive qualitative thematic analysis explored complementary perspectives on preferred ways of summarizing treatment effects.The mean (standard deviation) total DCS was 22.0 (14.3) for the conventional decision aid group and 16.7 (14.1) for the RMST-based decision aid group (p = 0.06), but the proportion of participants with a DCS25 was higher in the RMST-based group (26 [49.1%] vs 34 [69.4%]; p = 0.04). Qualitative interviews suggested that, regardless of effect summary measure, older individuals' preference depended on their ability to clearly comprehend quantitative information, clarity of presentation in the visual aid, and inclusion of desired information.When choosing a blood pressure-lowering strategy, older adults' perceived uncertainty may be reduced with a time-based effect summary, although our study was underpowered to detect a statistically significant difference. Given highly variable individual preferences, it may be useful to present both conventional and RMST-based information in decision aids.

Inflammation exacerbates systemic pathophysiological conditions and chronic inflammation is a sustained and systemic phenomenon that aggravates aging that can lead to chronic age-related diseases. These inflammatory phenomena have recently been redefined and delineated at the molecular, cellular, and systemic levels. Many transcription factors that are activated in response to tumor metabolic state have been reported to be regulated by a class of histone deacetylase called sirtuins (SIRTs). Sirtuins play a pivotal role in the regulation of tumor cell metabolism, proliferation, and angiogenesis, including oxidative stress and inflammation. The SIRT1-mediated signaling pathway in diabetes and cancer is the SIRT1/forkhead-box class O (FoxO)/nuclear factor-kappa B (NF-κB) pathway. In this review, we describe the accumulation of SIRT1-, NF-κB-, and FoxO-mediated inflammatory processes and cellular proinflammatory signaling pathways. We also describe the proinflammatory mechanisms underlying metabolic molecular pathways in various diseases such as liver cancer and diabetes. Finally, the regulation of cancer and diabetes through the anti-inflammatory effects of natural compounds is highlighted. Evidence from inflammation studies strongly suggests that cells may be a major source of cytokines secreted during various diseases. A better understanding of the mechanisms that underpin the inflammatory response and palliative role of natural compounds will provide insights into the molecular mechanisms of inflammation and various diseases for potential intervention.

Medical management of heart failure (HF) has evolved and has achieved significant survival benefits, resulting in highly complex medication regimens. Complex medication regimens create challenges for older adults, including nonadherence and increased adverse drug events, especially associated with cognitive impairment, physical limitations, or lack of social support. However, the association between medication complexity and patients' health outcomes among older adults with HF is unclear. The purpose of this review is to address how the complexity of HF medications has been assessed in the literature and what clinical outcomes are associated with medication regimen complexity in HF. Further, we aimed to explore how older adults were represented in those studies. The Medication Regimen Complexity Index was the most commonly used tool for assessment of medication regimen complexity. Rehospitalization was most frequently assessed as the clinical outcome, and other studies used medication adherence, quality of life, healthcare utilization, healthcare cost, or side effect. However, the studies showed inconsistent results in the association between the medication regimen complexity and clinical outcomes. We also identified an extremely small number of studies that focused on older adults. Notably, current medication regimen complexity tools did not consider a complicated clinical condition of an older adult with multimorbidity, therapeutic competition, drug interactions, or altered tolerance to the usual dose strength of the medications. Furthermore, the outcomes that studies assessed were rarely comprehensive or patient centered. More studies are required to fill the knowledge gap identifying more comprehensive and accurate medication regimen complexity tools and more patient-centered outcome assessment.

Forkhead box O transcription factors (FoxOs) play an important role in maintaining normal cell physiology by regulating survival, apoptosis, autophagy, oxidative stress, the development and maturation of T and B lymphocytes, and the secretion of inflammatory cytokines. Cell types whose functions are regulated by FoxOs include keratinocytes, mucosal dermis, neutrophils, macrophages, dendritic cells, tumor-infiltrating activated regulatory T (Tregs) cells, B cells, and natural killer (NK) cells. FoxOs plays a crucial role in physiological and pathological immune responses. FoxOs control the development and function of Foxp3+ Tregs. Treg cells and Th17 cells are subsets of CD4+ T cells, which play an essential role in immune homeostasis and infection. Dysregulation of the Th17/Treg cell balance has been implicated in the development and progression of several disorders, such as autoimmune diseases, inflammatory diseases, and cancer. In addition, FoxOs are stimulated by the mitogen-activated protein (MAP) kinase pathway and inhibited by the PI3 kinase/AKT pathway. Downstream target genes of FoxOs include pro-inflammatory signaling molecules (toll-like receptor (TLR) 2, TLR4, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α), chemokine receptors (CCR7 and CXCR2), B-cell regulators (APRIL and BLYS), T-regulatory modulators (Foxp3 and CTLA-4), and DNA repair enzymes (GADD45α). Here, we review the recent progress in our understanding of FoxOs as the key molecules involved in immune cell differentiation and its role in the initiation of autoimmune diseases caused by dysregulation of immune cell balance. Additionally, in various diseases, FoxOs act as a cancer repressor, and reviving the activity of FoxOs forces Tregs to egress from various tissues. However, FoxOs regulate the cytotoxicity of both CD8+ T and NK cells against tumor cells, aiding in the restoration of redox and inflammatory homeostasis, repair of the damaged tissue, and activation of immune cells. A better understanding of FoxOs regulation may help develop novel potential therapeutics for treating immune/oxidative stress-related diseases.

Background: Circadian rhythm is associated with the aging process and sex differences; however, how age and sex can change circadian regulation systems remains unclear. Thus, we aimed to evaluate age- and sex-related changes in gene expression and identify sex-specific target molecules that can regulate aging. Methods: Rat livers were categorized into four groups, namely, young male, old male, young female, and old female, and the expression of several genes involved in the regulation of the circadian rhythm was confirmed by in silico and in vitro studies. Results: Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the expression of genes related to circadian rhythms changed more in males than in females during liver aging. In addition, differentially expressed gene analysis and quantitative real-time polymerase chain reaction/western blotting analysis revealed that Nr1d1 and Nr1d2 expression was upregulated in males during liver aging. Furthermore, the expression of other circadian genes, such as Arntl, Clock, Cry1/2, Per1/2, and Rora/c, decreased in males during liver aging; however, these genes showed various gene expression patterns in females during liver aging. Conclusions: Age-related elevation of Nr1d1/2 downregulates the expression of other circadian genes in males, but not females, during liver aging. Consequently, age-related upregulation of Nr1d1/2 may play a more crucial role in the change in circadian rhythms in males than in females during liver aging.

Introduction Multicomponent interventions improve physical function and frailty in older adults, but their long-term benefit remains uncertain. Methods This prospective non-randomised study was conducted in 383 older Koreans (mean age, 76.8 years; female 72.3%) who were living alone or receiving medical aid. Of these, 187 individuals chose to receive a 24-week intervention that consisted of group exercise, nutritional supplements, depression management, deprescribing and home hazard reduction. The remaining 196 individuals received usual care. We compared the short physical performance battery (SPPB) score (0–12 points), frailty phenotype scale (0–5 points) and deficit-accumulation frailty index (0–1) at baseline, 6, 18 and 30 months. Results After 1:1 propensity score matching (n = 117 per group), the mean SPPB scores for the intervention and comparison groups were 7.6 versus 7.6 at baseline, 10.7 versus 7.1 at 6 months (mean difference, 3.5; 95% confidence interval [CI], 2.8–4.2), 9.1 versus 7.8 at 18 months (1.3; 95% CI, 0.6–2.0) and 8.6 versus 7.5 at 30 months (1.1; 95% CI, 0.4–1.8). The intervention group had lower frailty phenotype scale (1.1 versus 1.8; difference, −0.7; 95% CI −1.0 to −0.3) and frailty index (0.22 versus 0.27; difference, −0.04; −0.06 to −0.02) at 6 months, but similar scores at 18 and 30 months. The 30-month mean institutionalisation-free survival time was 28.5 months in the intervention group versus 23.3 months in the comparison group (difference, 5.2 months; 95% CI, 3.1–7.4). Conclusions The 24-week multicomponent intervention showed sustained improvement in physical function, temporary reduction in frailty and longer institutionalisation-free survival over 30 months.

BackgroundNo study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel–aspirin) versus clopidogrel–aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke.MethodsWe identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel–aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months.ResultsAmong 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel–aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel–aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel–aspirin group than in the other combination group (weighted HR: 0.82 (0.59–1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76–1.44)) or other combination group and the 3-month primary outcome.ConclusionOther combined antiplatelet treatment, compared with aspirin alone or clopidogrel–aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel–aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed.

Background Electronic frailty indices (eFIs) are increasingly used to identify patients at risk for morbidity and mortality. Whether eFIs capture the spectrum of frailty change, including decline, stability, and improvement, is unknown. Methods In a nationwide retrospective birth cohort of U.S. Veterans, a validated eFI, including 31 health deficits, was calculated annually using medical record and insurance claims data (2002–2012). K-means clustering was used to assign patients into frailty trajectories measured 5 years prior to death. Results There were 214 250 veterans born between 1927 and 1934 (mean [SD] age at death = 79.4 [2.8] years, 99.2% male, 90.3% White) with an annual eFI in the 5 years before death. Nine frailty trajectories were identified. Those starting at nonfrail or prefrail had 2 stable trajectories (nonfrail to prefrail, n = 29 786 and stable prefrail, n = 28 499) and 2 rapidly increasing trajectories (prefrail to moderately frail, n = 28 244 and prefrail to severely frail, n = 22 596). Those who were mildly frail at baseline included 1 gradually increasing trajectory (mildly to moderately frail, n = 33 806) and 1 rapidly increasing trajectory (mildly to severely frail, n = 15 253). Trajectories that started at moderately or severely frail included 2 gradually increasing trajectories (moderately to severely frail, n = 27 662 and progressing severely frail, n = 14 478) and 1 recovering trajectory (moderately frail to mildly frail, n = 13 926). Conclusions Nine frailty trajectories, including 1 recovering trajectory, were identified in this cohort of older U.S. Veterans. Future work is needed to understand whether prevention and treatment strategies can improve frailty trajectories and contribute to compression of morbidity toward the end of life.

The effect of solidification rate on micro-segregation in investment casting of IN738LC superalloy was studied. In Ni-based superalloys, the micro-segregation of solute atoms is formed due to limited diffusion during cast and solidification. The microstructure of cast Ni-based superalloys is largely divided into dendrite core of initial solidification and interdendrite of final solidification. In particular, mosaic shaped eutectic γ/γ’ and carbides are formed in the interdendrite of the final solidification region in some cases. The micro-segregation phenomena formed in regions of dendrite core and interdendrite including eutectic γ/γ’ and carbides were analyzed using OM, SEM/EDS and micro Vickers hardness. As a result of analysis, the lack of (Cr, W) and the accumulation of Ti were measured in the eutectic γ/γ’, and the accumulation of (Cr, Mo) and the lack of Ti were measured in the interdendrite between dendrite and eutectic. Carbides formed in interdendritic region were composed of (Ti, W, Mo, C). The segregation applied to each microstructure is mainly due to the formation of γ’ with Ni3(Al,Ti) composition. The Ni accumulation accompanied by Cr depletion, and the Ti accumulated in the eutectic region as a γ’ forming elements. The Mo tends to diffuse out from the dendrite core to the interdendrite, and the W diffuse out from the interdendrite to the dendrite core. Therefore, the accumulation of Mo in the interdendrite and the deficiency of W occur in the eutectic region located in the interdendrite. Heat treatment makes the degree of the micro-segregation decrease due to the diffusion during solid solution. This study could be applied to the heat treatment technology for the micro-segregation control in cast Ni-based superalloys.

In this letter, we propose a comprehensive benchmarking method to simultaneously address mobility enhancement and density-of-states bottleneck in advanced field-effect-transistors (FETs) with novel high-mobility (high- $\mu$ ) channel materials, where we focused on conventional covalent bonding semiconductors with pure and partially ionic character. This method relies only on the measured extrinsic transconductance of a long-channel FET in the saturation regime together with the source resistance, yielding the product of the effective mobility ( $\mu _{{eff}}$ ) and effective gate capacitance ( ${C}_{g\_{}{{eff}}}$ ). We tested this method in In x Ga1– x As quantum-well high-electron-mobility transistors (HEMTs) with various indium mole fractions, such as 0.53, 0.7, 0.8 and 1, as well as in Si n-FETs. We found that the In x Ga1– x As HEMTs with $\mu _{{eff}}$ over 10,000 cm2/ $\text{V}\cdot \text{s}$ at 300 K provided more than 20 times greater $\mu _{{eff}} \times {C}_{g\_{}{{eff}}}$ than Si n-FETs. More specifically, the product initially improved as ${x}$ increased, then showed a peak value of $10,300\,\,\mu \text{F}\cdot \text{V}^{-1}\cdot \text{s}^{-1}$ at ${x}$ of around 0.8, and degraded slightly beyond that composition. To verify the validness of the proposed method, we separately measured and analyzed ${C}_{g\_{}{{eff}}}$ and $\mu _{{eff}}$ using the split-CV technique, showing excellent agreement with the ones from the proposed method.

Given the role of comorbid conditions in the pathophysiology of HFpEF, we aimed to identify and rank the importance of comorbid conditions associated with post-hospitalization outcomes of older adults hospitalized for HFpEF. We examined data from 4605 Medicare beneficiaries hospitalized in 2007–2014 for HFpEF based on ICD-9-CM codes for acute diastolic heart failure (428.31 or 428.33). To identify characteristics with high importance for prediction of mortality, all-cause rehospitalization, rehospitalization for heart failure, and composite outcome of mortality or all-cause rehospitalization up to 1 year, we developed boosted decision tree ensembles for each outcome, separately. For interpretability, we estimated hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional hazards models. Age and frailty were the most important characteristics for prediction of mortality. Frailty was the most important characteristic for prediction of rehospitalization, rehospitalization for heart failure, and the composite outcome of mortality or all-cause rehospitalization. In Cox proportional hazards models, a 1-SD higher frailty score (0.1 on theoretical range of 0–1) was associated with a HR of 1.27 (1.06–1.52) for mortality, 1.16 (1.07–1.25) for all-cause rehospitalization, 1.24 (1.14–1.35) for HF rehospitalization, and 1.15 (1.07–1.25) for the composite outcome of mortality or all-cause rehospitalization. In conclusion, frailty is an important predictor of mortality and rehospitalization in adults aged [Formula: see text] 66 years with HFpEF.

Diaphragmatic hernias have been reported in 0.8%–1.6% of patients who experience blunt chest trauma. The hernia is assumed to form as a result of direct diaphragmatic violation or significant intraabdominal or intrathoracic pressure caused by the trauma. Some reports have described cases of delayed diaphragmatic hernia and subsequent stomach perforation that occurred a few days to several years after an accident. We report an extremely rare case of diaphragmatic herniation in which the process from initial blunt trauma to visceral organ perforation took only 2 days, without any evidence of herniation on the initial X-ray or computed tomography. Delayed diaphragmatic herniation and subsequent visceral organ perforation should not be missed during the period immediately after blunt chest trauma.

In this paper, we report the fabrication and characterization of Lg = 50 nm Gate-All-Around (GAA) In0.53Ga0.47As nanosheet (NS) metal-oxide-semiconductor field-effect transistors (MOSFETs) with sub-20 nm nanosheet thickness that were fabricated through an S/D regrowth process. The fabricated GAA In0.53Ga0.47As NS MOSFETs feature a bi-layer high-k dielectric layer of Al2O3/HfO2, together with an ALD-grown TiN metal-gate in a cross-coupled manner. The device with Lg = 50 nm, WNS = 200 nm and tNS = 10 nm exhibited an excellent combination of subthreshold-swing behavior (S < 80 mV/dec.) and carrier transport properties (gm_max = 1.86 mS/μm and ION = 0.4 mA/μm) at VDS = 0.5 V. To the best of our knowledge, this is the first demonstration of InxGa1-xAs GAA NS MOSFETs that would be directly applicable for their use in future multi-bridged channel (MBC) devices.

The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated.In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed.Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months.END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

Frailty is common in older adults with fractures. Osteoporosis medications reduce subsequent fracture, but limited data exist on medication efficacy in frail individuals. Our objective was to determine whether medications reduce the risk of subsequent fracture in frail, older adults. A retrospective cohort of Medicare fee-for-service beneficiaries was conducted (2014-2016). We included adults aged ≥65 years who were hospitalized with fractures without osteoporosis treatment. Pre-fracture frailty was defined using claims-based frailty index (≥0.2 = frail). Exposure to any osteoporosis treatment (oral or intravenous bisphosphonates, denosumab, and teriparatide) was ascertained using Part B and D claims and categorized according to the cumulative duration of exposure: none, 1-90 days, and 90 days. Subsequent fractures were ascertained from Part A or B claims. Cause-specific hazard models with time-varying exposure were fit to examine the association between treatment and fracture outcomes, controlling for relevant covariates. Among 29,904 patients hospitalized with fractures, 15,345 (51.3%) were frail, and 2148 (7.2%) received osteoporosis treatment (median treatment duration 183.0 days). Patients who received treatment were younger (80.2 versus 82.2 years), female (86.5% versus 73.0%), and less frail (0.20 versus 0.22) than patients without treatment. During follow-up, 5079 (17.0%) patients experienced a subsequent fracture. Treatment with osteoporosis medications for90 days compared with no treatment reduced the risk of fracture (hazard ratio [HR] = 0.82; 95% confidence interval [CI] 0.68-1.00) overall. Results were similar in frail (HR = 0.85; 95% CI 0.65-1.12) and non-frail (HR = 0.80; 95% CI 0.61-1.04) patients but not significant. In conclusion, osteoporosis treatment90 days was associated with similar trends in reduced risk of subsequent fracture in frail and non-frail persons. Treatment rates were very low, particularly among the frail. When weighing treatment options in frail older adults with hospitalized fractures, clinicians should be aware that drug therapy does not appear to lose its efficacy. © 2022 American Society for Bone and Mineral Research (ASBMR).

The expected growth of stroke burden in Korea in early 2000s led to the initiation of a government-funded clinical research project with the goal of development and implementation of national stroke guidelines. The CRCS-K (Clinical Research Collaboration for Stroke in Korea) began as a part of this project. For stroke epidemiology and quality of care research, the CRCS-K developed a multicenter, prospective, stroke registry and began collection of data in 2008. Now, about 100 000 cases have been registered at 17 university hospitals or regional stroke centers and about 200 articles have been published based on the registry experience. The analysis of the 10-year secular trends showed overall improvement of stroke care and outcomes and areas for improvement. This large-scale, high-quality dataset provides opportunities to explore and compare treatment disparities using the comparative effectiveness research methods, design and conduct a registry-based randomized clinical trial, connect the registry data with other data sources including the national claims data and neuroimaging or genetic data, and collaborate with other international researchers. An international stroke registry consortium may be a viable future direction.

Functional status and quality of life are not routinely assessed after skilled nursing facility (SNF) discharge. We determined feasibility of measuring frailty among adults ≥65 years admitted to SNF after hospitalization, and post-discharge outcomes. We calculated a frailty index (non-frail [≤0.25], mild frailty [0.26–0.35], moderate [0.36–0.45], and severe [>0.45]). After SNF discharge, we conducted serial telephone interviews measuring ability to perform functional activities and Patient Reported Outcome Measurement Information System (PROMIS) scores. Overall of 68 screened patients, 42 were eligible, and 24 (57.1%) eligible patients were enrolled. Of these, 5 (20.8%) were admitted after elective hospitalizations, 17 (70.8%) were female, and 11 (45.8%) had moderate-to-severe frailty. Frailty was measured in all participants in a mean 32.1 minutes. At 90 days, a total of three participants died, and two were lost to follow-up. Post-discharge functional status varied by frailty, with moderate-to-severe frailty having persistent impairment and lower PROMIS scores (worse quality of life) compared to those with no or mild frailty (38.2 [13.7] vs. 47.3 [8.1] p = .04). Measuring frailty and quality of life in older patients admitted to SNF is feasible. Furthermore, measuring frailty may help identify those at particularly high risk of poor recovery and lower quality of life after discharge.

Poor compliance with medications is a growing concern in geriatric care and is increasingly more relevant among people living with HIV (PLWH) as they age. Our goal was to understand geriatric conditions associated with antiretroviral therapy (ART) nonadherence in a Medicare population of older PLWH. We analyzed Medicare data from PLWH aged 50 years or older who were continuously enrolled in fee-for-service Medicare from January 1, 2014 to June 30, 2015. Prevalent geriatric conditions (dementia, depression, falls, hip fracture, sensory deficits, osteoporosis, orthostatic hypotension, urinary incontinence, frailty) were identified in January 1, 2014–December 31, 2014. ART nonadherence was defined as 70% were males. In adjusted models, age was not associated with nonadherence, frailty status was the only geriatric condition associated with nonadherence [robust: reference, prefrail odds ratio (OR): 0.97, confidence interval (95% CI) 0.86–1.10, frail OR: 1.34 95% CI 1.11–1.61], and odds of nonadherence were lower for polypharmacy [OR: 0.48 (0.43–0.54)]. Our findings suggest that patient-centered care plans aimed at improving ART adherence among older PLWH would benefit from long-term surveillance; a deeper understanding of the role of frailty and polypharmacy, even at chronologically younger ages in PLWH.

A 2.5-kg castrated male Maltese dog, suspected to be older than 10 y, was presented with a prolapsed mass at the anus. This had occurred on 2 previous occasions within the last 4 mo and had been managed with manual reduction and purse-string sutures. The rectal prolapse had viable tissue and was reducible but resulted in straining and fecal accumulation. Colopexy (with intracorporeal sutures) was performed laparoscopically using 3 ports; the distal colon was retracted cranially and attached to the abdominal wall with 3 simple interrupted sutures in a single row. The dog recovered uneventfully, had good appetite and normal activity, did not strain, and defecated without issues. There were no wound-healing complications and at 12-month post-operative examination, the patient was in good condition without clinical signs. Based on this case report, laparoscopic colopexy is clinically practical for management of rectal prolapse in small-breed dogs.

Residency specialty choice, a complex decision-making process, is often influenced by confidence level built upon knowledge, experience, and fit with the specialty. Despite the need for physiatrists with population growth, especially people with disability and older patients, limited growth in the number of residency positions and delayed exposure to the field of physical medicine and rehabilitation potentially contribute to a lack of confidence in pursuing physical medicine and rehabilitation. Early introduction to a specialty has been shown to impact specialty selection. Thus, this study aims to explore the impact of timing of exposure to physiatry on the confidence level of physical medicine and rehabilitation residents in their specialty choice. A survey for current physical medicine and rehabilitation residents was developed and distributed to residency program directors with a request to forward it to all residents. The response rate was low at 13%; however, the results provide a window into the experience of today's medical and premedical students. Interestingly, of the 175 respondents, a similar number reported first exposure to physiatry during third year and before medical school. In addition, earlier exposure was associated with higher confidence levels in specialty choice, the most powerful factor being the exposure to the specialty before starting medical school or during the preclinical years in medical school. These findings highlight opportunities to improve the physiatry workforce by providing earlier exposure to the specialty, even before medical school. Based on the results of the survey and ongoing discussions among medical students, residents, and faculty leaders, the authors review current recruitment efforts and new ideas.