Search Results (201)

Background/Objectives: This study is an investigation of the occurrence, remission and recurrence of major depressive disorders (MDDs) in adults with type 2 diabetes (T2DM). Methods: Interviews were conducted with individuals (N = 176) who met the criteria for MDD using the Structured Clinical Interview for the DSM-IV-TR (SCID). Results: N = 176 T2DM adults, with a mean (SD) age of 55.5 (10.4) years, 74% of whom were female and 62% were white, completed the Structured Clinical Interview for the DSM-IV-TR (SCID). A mean (SD) number of 1.8 (0.9) episodes of major depression (MDD) were recorded from birth to the date of interview, with a mean (SD) onset age of the first episode of 40.4 (15.9) years. Median (IQR) MDD episode duration was 13.9 (5.6–31.9) months and the median (IQR) cumulative lifetime exposure duration to MDD was 33 (12.9–63.1) months. Kaplan–Meier survival analysis along with the frailty model, to account for the correlation among multiple recurrences or remissions within a subject, indicated that the median first episode duration was shorter than the median second episode duration (14 vs. 37.9 months, p < 0.0001). Of those who had at least three episodes, the median second episode duration was shorter than the median third-episode duration (13.0 vs. 28.0 months, p = 0.006). The median recurrence time following first remission was significantly longer than the median recurrence time following second remission (138.0 vs. 80.6 months, p = 0.02). Conclusions: These results document that clinical depression is recurrent in adults with T2DM. Moreover, depressive episodes in individuals with T2DM are persistent well beyond episode durations observed in the general population. Full article

Reproductive health literacy (RHL) is essential to women’s ability to make informed reproductive health (RH) decisions and is a key determinant of RH outcomes. Resettled refugee women often experience poorer RH outcomes, yet there is limited research on their RHL and its influence on RH decision-making. This scoping review aims to (1) to evaluate existing methods for measuring RHL among resettled refugee women and (2) to characterize the relationship between RHL, RH decision-making, behavior, and outcomes among refugee women residing in high-income countries. A search of peer-reviewed literature published in English found limited direct measurement of RHL. Measurement methods were primarily qualitative or based on unvalidated survey instruments, limiting comparability and generalizability. The current methodologies do not adequately capture RH knowledge or RHL proficiency. A range of additional factors were found to influence RH decision-making and behavior, supporting the need for a means to accurately measure RHL. Further quantitative research is needed to clarify the extent to which RHL and knowledge influence RH behavior and outcomes. The development of a culturally relevant, validated RHL instrument that integrates knowledge and contextual influences would support healthcare providers and public health agents in serving and designing effective interventions for refugee women post-resettlement. Full article

Historical cross-sectional approaches examining cognitive aging consistently reveal a pattern of steady decline on nonverbal problem-solving, speeded tasks, and maintenance on verbal tasks. However, as measures developed and broadened the factor structure to align with Cattell–Horn–Carroll (CHC) theory, and age ranges were extended from 75 to 90 years, a more nuanced approach to cognitive aging emerged. The present study, using the Wechsler Adult Intelligence Scale, Fifth Edition (WAIS-5), examined the cognitive aging process through a cross-sectional approach. WAIS-5 normative sample data (aligned with the 2022 U.S. census) were obtained from the test publisher. The sample included adult participants aged 20–24 through 85–90 (n = 1660), which were mapped into 11 age groups. Using post-stratification weighting to control for educational attainment, cognitive decline was observed throughout aging; verbal skills were maintained longer than other abilities, while processing speed declined steadily and rapidly from young adulthood to old age. Working memory was vulnerable to the aging process but demonstrated slower patterns of decline than the other vulnerable abilities. Fluid reasoning and visual spatial skills (although aligning with separate CHC broad abilities theoretically) were strikingly similar in their pattern of decline across a person’s lifespan. Results are highly consistent with the large body of cross-sectional research conducted during the previous generation by Salthouse and his colleagues, as well as other teams of researchers. Full article

Metastatic breast cancer (BC) is a major cause of cancer-related deaths among women. Its progression is influenced by extracellular vesicles (EVs) released by BC cells, which modulate distant tissue environments to promote metastasis. We previously identified the oncogenic protein Kindlin-2 (K2) as a key driver of BC metastasis, including its role in the nucleus in regulating cell senescence. Here, we investigated whether K2-containing EVs facilitate both autologous (cancer-to-cancer) and heterologous (cancer-to-stroma) communication to promote metastasis. We found that 10–15% of EVs from metastatic BC cells contained K2, while this subpopulation was nearly absent in the EVs from K2-knockout (KO) cells, indicating selective packaging. These EVs transferred K2 to recipient K2-KO cells, where they accumulated in the nucleus. Using a 3D tumorsphere assay, we showed that K2+ EVs enhanced cancer cell invasiveness. Moreover, K2+ EVs activated fibroblasts into a cancer-associated phenotype, increasing α-SMA and FAP expression. Conditioned media from these activated fibroblasts further boosted cancer cell invasion. These results show that EV-associated K2 is actively transferred to recipient cells and regulates metastasis through nuclear signaling, suggesting K2+ EVs are critical mediators of BC progression and potential targets for therapy. Full article

The COVID-19 pandemic sparked changes globally, as leaders scrambled to protect wellbeing and safety. With many U.S. students sent away from their campuses, undergraduate students still grappled with the time-old question: “what will I do after college,” except during an unprecedented time in history rife with heightened career uncertainty. This qualitative study presents the results of a survey administered as part of a mind–body health project conducted in the wake of the pandemic, speaking directly to undergraduate college students’ health-related career aspirations. Two open-ended survey questions—(1) what is your intended career, and (2) how (if at all) has the COVID-19 pandemic changed your perspective about your future career—were administered with thematic analysis conducted. Qualitative analysis using hybrid data and theory-driven approaches revealed several themes around an increased desire to work within health-related fields, decreased desire to work in healthcare, non-medical to medical career shift, and additional undecidedness. Connecting theory to practice, Super’s Life-Space, Life-Span Career Theory and Krumboltz’s Social Learning Theory of Career Decision-Making guide practical implications and grander discussion around career development during periods of crisis. Full article

Phase-separated membraneless biomolecular condensates in the cytoplasm and nucleus are now recognized to play a major role in modulating diverse functions in mammalian cells, and contribute to cancer pathogenesis through dysregulated function of condensates of transcription factors such as STAT3 and fusion oncoproteins. Oral cancer, the sixth most prevalent malignancy worldwide, in the absence of overt causes such as tobacco or alcohol, most frequently occurs in a U-shaped zone (floor of mouth, side of tongue, anterior fauces and retromolar region) reflecting the path of liquid transit through the mouth. The cellular basis for this “high-risk” zone and the biochemical mechanisms used by oral cells to combat repetitive tonicity and temperature stresses are incompletely understood. We had previously observed that at 37 °C, in OECM1 oral carcinoma cells, cytoplasmic condensates of antiviral human GFP-MxA GTPase disassembled within 1–2 min of exposure of cells to saliva-like one-third hypotonicity, and underwent “spontaneous” reassembly in the next 5–7 min. Moreover, hypotonic beverages (water, tea, coffee), investigated at 37 °C, triggered this condensate cycling. In the present studies we investigated whether this process was temperature sensitive, representative of cold vs. warm drinks. We observed a slowing of this cycle at 5 °C, and speeding up at 50 °C. The involvement in this disassembly/reassembly process of WNK-SPAK/OSR1 serine-threonine kinase pathway, best studied for regulation of water and Na, K and Cl influx and efflux in kidney tubule cells, was evaluated by us in oral cells using pathway inhibitors WNK463, WNK-IN-11 and closantel. The pan-WNK inhibitor WNK463 inhibited hypotonicity-driven condensate disassembly, while the SPAK/OSR1 inhibitor closantel markedly slowed reassembly. Unexpectedly, the WNK1-selective inhibitor (WNK-IN-11), triggered a dramatic and rapid (within 1 h) spheroid to fibril transition of GFP-MxA condensates in live cells, but without affecting MxA antiviral function. The new data suggest a novel hypothesis for the anatomic localization of oral cancer in the U-shaped “high-risk” zone in the mouth: dysfunction of biomolecular condensates in oral cells along the beverage transit pathway through the mouth due to repetitive tonicity and temperature stresses that might underlie a prooncogenic progression. Full article

Endosomal dysfunction is one of the earliest cellular signs in Alzheimer’s disease. Tumor susceptibility gene 101 protein (TSG101) is a component of the endosomal sorting complex required for transport (ESCRT)-I, which plays a key role in sorting ubiquitinated cell surface proteins and lipids onto intraluminal vesicles of multivesicular bodies for trafficking to lysosomes or autophagosomes for degradation, or to the plasma membrane for exosomal secretion. TSG101-dependent trafficking has been implicated in the propagation and spread of misfolded proteins associated with neurodegenerative diseases. We used transgenesis mice to study the in vivo consequences of disrupting TSG101-dependent trafficking in adult neurons. Mice lacking Tsg101 in forebrain neurons (Tsg101^ck2-null) showed rapid loss of hippocampal neurons and progressive forebrain atrophy. Astrogliosis was apparent in the dentate gyrus within 1 week of deleting Tsg101, followed by apoptosis of hippocampal CA3 neurons and accumulation of the autophagy adapter P62/SQSTM1 and ubiquitinated proteins. Failure to detect lipidated LC3 indicated autophagy was impaired rather than upregulated. Endosomal markers (RAB5 and RAB7) and amyloid protein also accumulated in hippocampal neurons of Tsg101^ck2-null mice. Our data establish a critical role for TSG101 in neuronal survival and demonstrate the importance of the in vivo assessment of gene and protein functions. Full article

Biochemical alterations linked to metabolic syndrome (MetS), type 2 diabetes (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD) may be brought on by the Western diet. Based on research conducted over the past decade, fructose is one of the main culprits. Over 80% of ingested fructose is metabolized by the liver at first pass, where it stimulates de novo lipogenesis (DNL) to drive hepatic triglyceride (TG) synthesis, which contributes to MASLD, hepatic insulin resistance (IR), and dyslipidemia. Fructose reduction produces quick and significant amelioration in these metabolic disturbances. We hereby propose potential overarching processes that can link these pathways to signaling disruption by the critical metabolic sensor AMP-activated protein kinase (AMPK). We proffer that when large amounts of fructose and glucose enter the liver, triose fluxes may be sufficient to produce transient increases in methylglyoxal (MG), allowing steady-state concentrations between its production and catabolism by glyoxalases to be high enough to modify AMPK-sensitive functional amino acid residues. These reactions would transiently interfere with AMPK activation by both AMP and aldolase. Such a sequence of events would boost the well-documented lipogenic impact of fructose. Given that MG adducts are irreversible, modified AMPK molecules would be less effective in metabolite sensing until they were replaced by synthesis. If proven, this mechanism provides another avenue of possibilities to tackle the problem of fructose in our diet. We additionally discuss potential multimodal treatments and future research avenues for this apparent hepatic AMPK malfunction. Full article

The liver’s crucial role in methylglyoxal (MG) metabolism is frequently overlooked in the literature. We present a perspective that enhances the current understanding of the role of methylglyoxal (MG) and the glyoxalase cycle in the pathogenesis of insulin resistance and obesity, ultimately leading to type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). Fructose may be a significant substrate contributing, particularly in contemporary times, to the flux of trioses in the liver, accounting for a substantial portion of MG production. The steady-state concentration of MG—and the subsequent modification of proteins—would then be determined by the flux of trioses, their utilization in lipogenesis, and their decomposition into MG, which is further converted into D-lactate by glyoxalase enzymes GLO1 and GLO2. Consequently, enhancing the activity and/or expression of GLO1 could potentially mitigate the adverse effects of fructose in the liver. Additional research and validation are required to confirm these biological pathways. These arguments are in favor of further research into safe and efficient ways to activate the glyoxalase pathway to lessen the negative effects of fructose metabolism that lead to insulin resistance (IR) and its related repercussions. Full article

Background: Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for severe aortic stenosis in high- and intermediate-risk patients, with expanding indications for lower-risk populations. However, post-procedural complications, such as stroke, conduction disturbances, and heart failure readmissions, remain concerns. The aim of our study is to analyze the national trends in TAVR procedures, in-hospital outcomes, major readmission causes, and the association of risk factors for readmissions following TAVR. Methods: We analyzed NIS data (2018–2022) to assess TAVR utilization trends, patient demographics, and in-hospital outcomes. The NRD (2021–2022) was used to evaluate 60-day readmission rates for stroke, complete heart block, and heart failure. Multivariate regression models were employed to identify risk factors having significant association with major readmission causes. Results: TAVR utilization increased from 10,788 cases in 2018 to 17,784 in 2022, with a concurrent decrease in in-hospital mortality (1.33% to 0.90%) and length of stay (3.88 to 2.97 days). Of 123,376 TAVR index admissions in 2021, 28,654 patients had 66,100 readmission events (53.57%) in the 60 days following discharge. Heart failure (17,566 cases, 26.57% of readmissions) was the most common readmission cause, followed by complete heart block (1760 cases, 2.66% of readmissions) and stroke (284 cases, 0.42% of readmissions). Predictors of post-TAVR stroke included uncontrolled hypertension (OR 2.29, p < 0.001) and chronic heart failure (OR 2.73, p < 0.001). Left bundle branch block (LBBB) was strongly associated with complete heart block (OR 12.89, p < 0.001) and heart failure readmissions (OR 7.65, p < 0.001). Conclusions: TAVR utilization has increased with improving perioperative outcomes, but post-TAVR readmissions remain significant, particularly for heart failure, stroke, and conduction disturbances. Pre-procedural uncontrolled hypertension, hyperlipidemia, congestive heart failure, and atrial fibrillation were risk factors with significant association with stroke in the 60 days following TAVR. The presence of documented pre-procedural LBB, RBB, as well as BFB were risk factors with significant association with complete heart block following TAVR placements. Pre-procedural LBB, RBB, BFB, and atrial fibrillation were risk factors having significant association with heart failure readmissions in the 60 days following TAVR. Full article

Background: Aim of the study is to analyze the trends and outcomes in Left Ventricular Assist Device (LVAD) placements between the years 2016 and 2022 using the National Inpatient Sample (NIS). Methods: Using the NIS for the years 2016–2022, we identified the total number of LVAD placements using the PCS 10 code 02HA0QZ. In-hospital outcomes and healthcare resource utilization burden were assessed. Stratification of outcomes with Extracorporeal Membrane Oxygenation (ECMO) support were performed for the years 2018–2022. Outcome analysis variance in admissions requiring ECMO support was performed using multivariate regression analysis. A two tailed p-value < 0.05 was used to determine statistical significance. Results: A general decreasing trend was observed in the total number of LVAD placements, with 852 total admissions requiring LVAD placements identified in 2016 compared to 665 in 2022. The admissions for LVAD placements requiring ECMO support had an increasing trend, with 2.21% of admissions needing ECMO support in 2018 compared to 12.18% in 2018. After multivariate regression analysis, the association between all-cause mortality during the hospital stay for LVAD placements and requirement of ECMO was found to be significant, with an odds ratio of 2.34 (1.83–4.42, p-value: 0.001). Conclusions: A general decreasing trend in LVAD placements was observed between 2016 and 2022. All-cause mortality and hospital charges during the admission had a stable trend over the years. The requirement of ECMO support had an increasing trend from 2018 to 2022. Requirement of ECMO support during the admissions for LVAD placements had a statistically significant association with all-cause mortality during the admission. A 11.50% readmission rate was observed in the 30 days following discharge, with heart failure being the major cause of readmission. Full article

Background: Advances in pediatric perioperative care have supported the safe provision of increasingly complex surgical care to patients with complicated diseases and abnormal physiology. This has led to the possible misalignment of the impact of potential surgical outcomes and goals of care. Methods / Objectives: We describe the development of a novel process that leverages the combination of longitudinal engagement of pediatric palliative care consultants and multidisciplinary care planning to ensure that perioperative care remains patient-centered and goal-directed for all children, especially children with complex baseline disease. Conclusions: Our novel process should be considered a solution to a crictial gap in pediatric perioperative care. Full article

In this article, the authors examine the history, development, and current state of K-12 online learning, challenging the assertions that COVID-19-era distance education was unprecedented. Drawing on historical examples, the authors demonstrate how educational systems have repeatedly leveraged various technologies for remote instruction during disruptions, from correspondence courses to radio broadcasts to modern digital platforms. The analysis reveals persistent challenges in implementing effective online learning, including inadequate teacher preparation, inconsistent terminology, and limited theoretical frameworks. While K-12 online learning has shown promise for expanding educational access and flexibility, adoption remains relatively low globally. The article concludes that realizing the potential of K-12 online learning requires addressing fundamental issues in research, practice, and policy while learning from past experiences rather than treating each implementation as novel. Full article

Aging has been thought to be factual, inherited, and obligatory. However, aging can be divided into primary (i.e., inevitable physiological changes) and secondary (i.e., age-associated changes driven by life choices, environment, and society) aging. The impact of social norms and life choices is why no two 70-year-olds look the same. The life choice that appears to have the strongest impact on aging is physical activity. Research continues to highlight the power of mitigating age-related losses via physical activity and debunking the notion that age-related changes such as falls, frailty, and functional decline are inevitable. Physiotherapists are the healthcare professionals who reverse or slow down age-related changes and prevent secondary aging from occurring. Physiotherapists are the health profession’s experts in movement science, whose interventions primarily center around physical activity as medicine. Thus, physiotherapists function as pharmacists of physical activity and are well-positioned to prescribe the dosages needed for wellness promotion as well as disease prevention and management. This paper provides guidance from the perspective of the physiotherapist on exercise prescription most optimal and consumable for an older population. Full article