Mckennayu8605

The objective of this review is to evaluate the effectiveness of physical rehabilitation versus non-rehabilitation control in improving physical functioning and quality of life in long-term care residents with dementia.

Many long-term-care residents live with dementia and have impaired physical function and poor quality of life. Physical rehabilitation can improve physical function and quality of life for people living with dementia, yet many long-term-care residents with dementia do not receive this intervention, and health care providers are unsure of which rehabilitation interventions are effective. Studies synthesizing effective rehabilitation programs are needed to guide practice in the long-term-care sector where many residents live with dementia. Previous studies have focused broadly on long-term care, specific professions, interventions or outcomes, or people with dementia in the community. Our review will focus on long-term-care residents living with dementia and a broader definition of physical rehabilitation.

This review will include studies that evaluate physical rehabilitation in comparison with non-rehabilitation controls among long-term-care residents with any severity of dementia. We will include studies that measure the effect on performance-based physical functioning and self- or proxy-reported quality of life.

Searches will be conducted in APA PsycINFO (EBSCO), CINAHL (EBSCO), MEDLINE (Ovid), Embase, Scopus, and the Cochrane CENTRAL database with no date or language limitations. Two independent reviewers will conduct a critical appraisal of eligible studies, assess methodological quality, and extract the data. Where possible, studies will be pooled in a statistical meta-analysis.

PROSPERO CRD42022308444.

PROSPERO CRD42022308444.Clinically identified genetic variants in ion channels can be benign or cause disease by increasing or decreasing the protein function. Consequently, therapeutic decision-making is challenging without molecular testing of each variant. Our biophysical knowledge of ion channel structures and function is just emerging, and it is currently not well understood which amino acid residues cause disease when mutated. check details We sought to systematically identify biological properties associated with variant pathogenicity across all major voltage and ligand-gated ion channel families. We collected and curated 3,049 pathogenic variants from hundreds of neurodevelopmental and other disorders and 12,546 population variants for 30 ion channel or channel subunits for which a high-quality protein structure was available. Using a wide range of bioinformatics approaches, we computed 163 structural features and tested them for pathogenic variant enrichment. We developed a novel 3D spatial distance scoring approach that enables comparis and 679 electrophysiological experiments, we show that pore axis distance is associated with seizure age of onset and cognitive performance as well as differential gain vs. loss-of-channel function. In summary, we identified biological properties associated with ion-channel malfunction and show that these are correlated with in vitro functional read-outs and clinical phenotypes in patients with neurodevelopmental disorders. Our results suggest that clinical decision support algorithms that predict variant pathogenicity and function are feasible in the future.Dominant framings of intimate partner violence (IPV) construct the experience as one where a cisgender man enacts violence against a cisgender woman. While often the case, this framing obfuscates the experiences of people who identify as lesbian, gay, bisexual, transgender diverse, or queer (LGBTQ) and may challenge their ability to conceive of their relationship-based experiences as abusive or violent. The extent to which hostile experiences from family of origin violence (FOV) members are conceived or named as violence is also unclear. A large, online, national survey of LGBTQ adults separately assessed experiences of IPV and FOV in two ways a direct question relating to abuse from a partner/s or family member/s, and a second question (asked irrespective of the previous answer) which sought to establish experience of a nuanced list of abusive acts that can constitute violence (including emotional abuse, LGBTQ-specific forms of violence, and enforced social isolation). Following comparison of responses, multiple regression analyses were performed to assess variation by demographic characteristics. Among the full sample of 6,835 individuals, when asked directly, 30.93% (n = 2,108) of participants indicated that they had ever experienced FOV and 41.73% (n = 2,846) indicated that they had ever experienced IPV. However, when asked about experiences of FOV using the second nuanced question, 43.18% (n = 2,675) responded in ways that indicated that they had ever experienced FOV and 60.71% (n = 3,716) with respect to IPV. The recognition of violence, as indicated by responses to the direct question varied by numerous characteristics, including age, gender, and educational attainment. These findings indicate some LGBTQ people may struggle to recognize or name their family or relationship experiences as abusive or violent, which may complicate their ability or willingness to access professional support. More expansive framings, policies, and responses to IPV and FOV are required.The intestinal L-cell incretin, glucagon-like peptide-1 (GLP-1), exhibits a circadian pattern of secretion, thereby entraining diurnal insulin release. Secretagogin (Scgn), an actin-binding regulatory protein, is essential for the temporal peak of GLP-1 secretion in vitro. To interrogate the role of Scgn in diurnal GLP-1 secretion in vivo, peak and trough GLP-1 release were evaluated in knockout mice (Scgn-/-, Gcg-CreERT2/+; Scgnfl/fl and Vil-CreERT2/+; Scgnfl/fl), and RNA sequencing (RNA-Seq) was conducted in Scgn knockdown L-cells. All 3 knockout models demonstrated loss of the diurnal rhythm of GLP-1 secretion in response to oral glucose. Gcg-CreERT2/+; Scgnfl/fl mice also lost the normal pattern in glucagon secretion, while Scgn-/- and Vil-CreERT2/+; Scgnfl/fl animals demonstrated impaired diurnal secretion of the related incretin, glucose-dependent insulinotrophic polypeptide. RNA-Seq of mGLUTag L-cells showed decreased pathways regulating vesicle transport, transport and binding, and protein-protein interaction at synapse, as well as pathways related to proteasome-mediated degradation including chaperone-mediated protein complex assembly following Scgn knockdown. Scgn is therefore essential for diurnal L-cell GLP-1 secretion in vivo, likely mediated through effects on secretory granule dynamics.

Temporal changes in the structural connectivity of major language tracts after stroke and their contribution to aphasia recovery are unclear.

To investigate longitudinal arcuate fasciculus (AF) integrity changes and their relationship with post-stroke aphasia recovery using diffusion tensor imaging (DTI).

Thirty-five patients with aphasia due to first-ever left hemispheric stroke underwent the Korean version of the Western Aphasia Battery and DTI at 1- and 6-month post stroke onset. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of both AF tracts were analyzed to evaluate the temporal changes in tract integrity and determine the correlation between changes (Δ; follow-up - initial) in DTI parameters and language scores.

At 6 months post-stroke, the mean FA decreased, and mean MD and RD increased in both hemispheres; however, compared with mean AD observed after 1 month, the mean observed at 6 months increased only in the left hemisphere (

 < .05). ΔFA of the left AF and proportional change in the aphasia quotient showed a significant positive correlation (

 = 0.365,

 = .031). No correlation was found between changes in the right AF parameters and language score. The group with increased FA in the left AF showed more significant language improvement than the group with decreased FA.

During the subacute stage, the integrity of AF decreased in both hemispheres in patients with aphasia, and the change in structural connectivity of the left AF was associated with language improvement.

During the subacute stage, the integrity of AF decreased in both hemispheres in patients with aphasia, and the change in structural connectivity of the left AF was associated with language improvement.Hepatic fibrosis occurs in response to prolonged tissue injury in the liver, which results in abnormal accumulation of extracellular matrix. Hepatic stellate cells (HSCs) have been suggested to play a major role in liver fibrosis. However, the molecular mechanisms remain incompletely understood. Sirtuin 6 (SIRT6), an NAD+ -dependent deacetylase, has been previously implicated in the regulation of the transforming growth factor β (TGFβ)-SMAD3 pathway that plays a significant role in liver fibrosis. In this work, we aimed to identify other important players during hepatic fibrogenesis, which are modulated by SIRT6. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ or WWTR1), key players in the Hippo pathway, have been implicated in the promotion of hepatic fibrosis. Our data show that HSC-specific Sirt6 knockout mice are more susceptible to high-fat-cholesterol-cholate diet-induced hepatic fibrosis than their wildtype counterparts. Our signaling analyses suggest that in addition to the TGFβ-SMAD3 pathway, YAP and TAZ are also highly activated in the SIRT6-deficient HSCs. As it is not clear how SIRT6 might regulate YAP and TAZ, we have decided to elucidate the mechanism underlying the regulation of YAP and TAZ by SIRT6 in HSCs. Overexpression or knockdown of SIRT6 corroborates the role of SIRT6 in the negative regulation of YAP and TAZ. Further biochemical analyses reveal that SIRT6 deacetylates YAP and TAZ and reprograms the composition of the TEA domain transcription factor complex to suppress their downstream target genes, particularly those involved in hepatic fibrosis. In conclusion, our data suggest that SIRT6 plays a critical role in the regulation of the Hippo pathway to protect against hepatic fibrosis.Economic hardship may lead to a wide range of negative outcomes, including violence. However, existing literature on economic hardship and violence is limited by reliance on official reports of violence and conflation of different measures of economic hardship. The goals of this study are to measure how violence-related injuries are associated with five measures of county-level economic shocks unemployment rate, male mass layoffs, female mass layoffs, foreclosure rate, and unemployment rate change, measured cross-sectionally and by a 1-year lag. This study measures three subtypes of violence outcomes (child abuse, elder abuse, and intimate partner violence). Yearly county-level data were obtained on violence-related injuries and economic measures from 2005 to 2012 for all 87 counties in Minnesota. Negative binomial models were run regressing the case counts of each violence outcome at the county-year level on each economic indicator modeled individually, with population denominator offsets to yield incidence rate ratios.