The role of stroke care infrastructure on the effectiveness of a hub-and-spoke telestroke model in South Carolina.

OBJECTIVE: To examine the relationship between stroke care infrastructure and stroke quality-of-care outcomes at 29 spoke hospitals participating in the Medical University of South Carolina (MUSC) hub-and-spoke telestroke network. MATERIALS AND METHODS: Encounter-level data from MUSC's telestroke patient registry were filtered to include encounters during 2015-2022 for patients aged 18 and above with a clinical diagnosis of acute ischemic stroke, and who received intravenous tissue plasminogen activator. Unadjusted and adjusted generalized estimating equations assessed associations between time-related stroke quality-of-care metrics captured during the encounter and the existence of the two components of stroke care infrastructure-stroke coordinators and stroke center certifications-across all hospitals and within hospital subgroups defined by size and rurality. RESULTS: Telestroke encounters at spoke hospitals with stroke coordinators and stroke center certifications were associated with shorter door-to-needle (DTN) times (60.9 min for hospitals with both components and 57.3 min for hospitals with one, vs. 81.2 min for hospitals with neither component, p <.001). Similar patterns were observed for the percentage of encounters with DTN time of ≤60 min (63.8% and 68.9% vs. 32.0%, p <.001) and ≤45 min (34.0% and 38.4% vs. 8.42%, p <.001). Associations were similar for other metrics (e.g., door-to-registration time), and were stronger for smaller (vs. larger) hospitals and rural (vs. urban) hospitals. CONCLUSIONS: Stroke coordinators or stroke center certifications may be important for stroke quality of care, especially at spoke hospitals with limited resources or in rural areas.

Rapid Evaluations of Telehealth Strategies to Address Hypertension: A Mixed-Methods Exploration at Two US Health Systems During the COVID-19 Pandemic.

Telehealth is a promising intervention for hypertension management and control and was rapidly adopted by health systems to ensure continuity of care during the COVID-19 pandemic. Rapid evaluations of telehealth strategies at 2 US health systems explored how telehealth affected health care access and blood pressure outcomes among populations disproportionately affected by hypertension. Both health systems implemented telehealth strategies to maintain continuity of health care services during the COVID-19 pandemic. The evaluations used a mixed-method approach; qualitative interviews were conducted with key staff, and quantitative analyses were performed on patient electronic health record data. Both health systems exhibited similar trends in telehealth use, which allowed for continued access to health care for some patients but hindered other patients who had limited access to the internet or the equipment needed. Telehealth provides opportunities for blood pressure control and management. Further evaluation is needed to understand the role of broadband internet access as a social determinant of health and its impact on equitable patient access to health care.

PI(3,5)P2 controls vacuole potassium transport to support cellular osmoregulation.

Lysosomes are dynamic organelles with critical roles in cellular physiology. The lysosomal signaling lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is a key regulator that has been implicated to control lysosome ion homeostasis, but the scope of ion transporters targeted by PI(3,5)P2 and the purpose of this regulation is not well understood. Through an unbiased screen in Saccharomyces cerevisiae, we identified loss-of-function mutations in the vacuolar H+-ATPase (V-ATPase) and in Vnx1, a vacuolar monovalent cation/proton antiporter, as suppressor mutations that relieve the growth defects and osmotic swelling of vacuoles (lysosomes) in yeast lacking PI(3,5)P2. We observed that depletion of PI(3,5)P2 synthesis in yeast causes a robust accumulation of multiple cations, most notably an ∼85 mM increase in the cellular concentration of potassium, a critical ion used by cells to regulate osmolarity. The accumulation of potassium and other cations in PI(3,5)P2-deficient yeast is relieved by mutations that inactivate Vnx1 or inactivate the V-ATPase and by mutations that increase the activity of a vacuolar cation export channel, Yvc1. Collectively, our data demonstrate that PI(3,5)P2 signaling orchestrates vacuole/lysosome cation transport to aid cellular osmoregulation.

The acceptability, feasibility, and possible benefits of a neurobiologically-informed 5-day multifamily treatment for adults with anorexia nervosa.

OBJECTIVE: Novel treatments for adults with anorexia nervosa (AN) are lacking. Recent scientific advances have identified neurobiologically-driven temperament contributors to AN symptoms that may guide development of more effective treatments. This preliminary study evaluates the acceptability, feasibility and possible benefits of a multicenter open trial of an intensive 5-day neurobiologically-informed multifamily treatment for adults with AN and their supports (SU). The temperament-focused treatment combines psychoeducation of AN neurobiology and SU involvement to develop skills to manage traits contributing to disease chronicity. METHOD: Fifty-four adults with AN and at least one SU (n = 73) received the 5-day treatment. Acceptability, feasibility, and attrition were measured post-treatment. Clinical outcome (BMI, eating disorder psychopathology, family function) was assessed post-treatment and at >3-month follow-up. RESULTS: The treatment had low attrition, with only one drop-out. Patients and SU rated the intervention as highly acceptable, and clinicians reported good feasibility. At post-treatment, patients demonstrated significantly increased BMI, reduced eating disorder psychopathology, and improved family function. Benefits were maintained in the 39 patients who completed follow-up assessment, with 62% reporting full or partial remission. DISCUSSION: Preliminary results are promising and suggest this novel treatment is feasible and acceptable. To establish treatment efficacy, fully-powered randomized controlled trials are necessary.

The Influence of Polyploidy on the Evolution of Yeast Grown in a Sub-Optimal Carbon Source.

Polyploidization events have occurred during the evolution of many fungi, plant, and animal species and are thought to contribute to speciation and tumorigenesis, however little is known about how ploidy level contributes to adaptation at the molecular level. Here we integrate whole genome sequencing, RNA expression analysis, and relative fitness of ∼100 evolved clones at three ploidy levels. Independent haploid, diploid, and tetraploid populations were grown in a low carbon environment for 250 generations. We demonstrate that the key adaptive mutation in the evolved clones is predicted by a gene expression signature of just five genes. All of the adaptive mutations identified encompass a narrow set of genes, however the tetraploid clones gain a broader spectrum of adaptive mutations than haploid or diploid clones. While many of the adaptive mutations occur in genes that encode proteins with known roles in glucose sensing and transport, we discover mutations in genes with no canonical role in carbon utilization (IPT1 and MOT3), as well as identify novel dominant mutations in glucose signal transducers thought to only accumulate recessive mutations in carbon limited environments (MTH1 and RGT1). We conclude that polyploid cells explore more genotypic and phenotypic space than lower ploidy cells. Our study provides strong evidence for the beneficial role of polyploidization events that occur during the evolution of many species and during tumorigenesis.

Reactive dissociative experiences in response to acute increases in shame feelings.

Studies have not examined if a direct causal relationship exists between shame and dissociation. The current research examined whether increases in dissociation were evident following exposure to acute shame feelings induced via narrative scripts of shame-evoking situations. Following Gilbert's (1998) differentiation between external and internal shame, participants heard shame-inducing or emotionally neutral stories in conditions designed to heighten (1) external shame, (2) internal shame or (3) general shame. In study 1, using a student sample (N = 78), dissociation as measured by the Modified Peritraumatic Dissociation Questionnaire was elevated during the shame script compared to the neutral script regardless of the type of shame participants were exposed to. A strong correlation was found between trait shame and trait dissociation. In study 2, using a treatment-attending sample (N = 33) and assessing intrusions in the two days following the script exposure, participants again demonstrated an increase in acute dissociative experiences during the shame script compared to the neutral script regardless of the type of shame evoked. Intrusions were present for the shame narrative with the distress they caused related to acute (peri-experimental) dissociation. Elevations in shame feelings produced a reactive response in dissociative experiences, which may heighten the distress associated with shame-filled intrusions.