Long-term care facilities' response to the COVID-19 pandemic: An international, cross-sectional survey.

AIMS: To (i) assess the adherence of long-term care (LTC) facilities to the COVID-19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. DESIGN: Cross-sectional survey. METHODS: Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID-19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. RESULTS: The adherence was significantly higher among facilities with more pre-pandemic in-service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work-life imbalance. CONCLUSIONS: Pre-pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. IMPACT: This is the first study to comprehensively examine the adherence of LTC facilities to COVID-19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre-pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Evaluating Functional Performance Tests in those with Non-arthritic Intra-articular Hip Pain: An International Consensus Statement.

Background: Non-arthritic intra-articular hip pain, caused by various pathologies, leads to impairments in range of motion, strength, balance, and neuromuscular control. Although functional performance tests offer valuable insights in evaluating these patients, no clear consensus exists regarding the optimal tests for this patient population. Purpose: This study aimed to establish expert consensus on the application and selection of functional performance tests in individuals presenting with non-arthritic intra-articular hip pain. Study Design: A modified Delphi technique was used with fourteen physical therapy experts, all members of the International Society for Hip Arthroscopy (ISHA). The panelists participated in three rounds of questions and related discussions to reach full consensus on the application and selection of functional performance tests. Results: The panel agreed that functional performance tests should be utilized at initial evaluation, re-evaluations, and discharge, as well as criterion for assessing readiness for returning to sports. Tests should be as part of a multimodal assessment of neuromuscular control, strength, range of motion, and balance, applied in a graded fashion depending on the patient's characteristics. Clinicians should select functional performance tests with objective scoring criteria and prioritize the use of tests with supporting psychometric evidence. A list of recommended functional performance tests with varying intensity levels is provided. Low-intensity functional performance tests encompass controlled speed in a single plane with no impact. Medium-intensity functional performance tests involve controlled speed in multiple planes with low impact. High-intensity functional performance tests include higher speeds in multiple planes with higher impact and agility requirements. Sport-specific movement tests should mimic the patient's particular activity or sport. Conclusion: This international consensus statement provides recommendations for clinicians regarding selection and utilization of functional performance tests for those with non-arthritic intra-articular hip pain. These recommendations will encourage greater consistency and standardization among clinicians during a physical therapy assessment.

The 2022 International Society for Hip Preservation (ISHA) physiotherapy agreement on assessment and treatment of greater trochanteric pain syndrome (GTPS): an international consensus statement.

The 2022 International Society of Hip Preservation (ISHA) physiotherapy agreement on assessment and treatment of greater trochanteric pain syndrome (GTPS) was intended to present a physiotherapy consensus on the assessment and surgical and non-surgical physiotherapy management of patients with GTPS. The panel consisted of 15 physiotherapists and eight orthopaedic surgeons. Currently, there is a lack of high-quality literature supporting non-operative and operative physiotherapy management. Therefore, a group of physiotherapists who specialize in the treatment of non-arthritic hip pathology created this consensus statement regarding physiotherapy management of GTPS. The consensus was conducted using a modified Delphi technique to guide physiotherapy-related decisions according to the current knowledge and expertise regarding the following: (i) evaluation of GTPS, (ii) non-surgical physiotherapy management, (iii) use of corticosteroids and orthobiologics and (iv) surgical indications and post-operative physiotherapy management.

The value of dynamic elastomeric fabric orthoses in the management of a complex hypermobile Ehlers-Danlos syndrome patient: A case report.

The use of dynamic elastomeric fabric orthoses is examined in a young woman with hypermobile Ehlers-Danlos syndrome (hEDS) referred for physiotherapy with hip dysplasia, prior to a right periacetabular osteotomy. Dynamic elastomeric fabric orthoses plus rigorous subjective examination, therapists' listening skills, and patient-centered goals were useful for this hEDS patient.

The 2019 International Society of Hip Preservation (ISHA) physiotherapy agreement on assessment and treatment of femoroacetabular impingement syndrome (FAIS): an international consensus statement.

The 2019 International Society of Hip Preservation (ISHA) physiotherapy agreement on femoroacetabular impingement syndrome (FAIS) was intended to build an international physiotherapy consensus on the assessment, non-surgical physiotherapy treatment, pre-/post-operative management, and return to sport decisions for those patients with FAIS. The panel consisted of 11 physiotherapists and 8 orthopaedic surgeons. There is limited evidence regarding the use of physiotherapy in the overall management of those with FAIS. Therefore, a group of ISHA member physiotherapists, who treat large numbers of FAIS patients and have extensive experience in this area, constructed a consensus statement to guide physiotherapy-related decisions in the overall management of those with FAIS. The consensus was conducted using a modified Delphi technique. Six major topics were the focus of the consensus statement: (i) hip assessment, (ii) non-surgical physiotherapy management, (iii) pre-habilitation prior to hip arthroscopy, (iv) post-operative physiotherapy rehabilitation, (v) stages of post-operative rehabilitation and (vi) return to sports criteria/guidelines after surgery.

Erratum to: The 2019 International Society of Hip Preservation (ISHA) physiotherapy agreement on assessment and treatment of femoroacetabular impingement syndrome (FAIS): an international consensus statement.

[This corrects the article DOI: 10.1093/jhps/hnaa043.].

Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice.

The effects of methionine restriction (MR) in rodents are well established; it leads to decreased body and fat mass, improved glucose homeostasis and extended lifespan, despite increased energy intake. Leucine restriction (LR) replicates some, but not all, of these effects of MR. To determine any differences in metabolic effects between MR and LR, this study compared 8 weeks of MR (80% restriction), LR (80% restriction) and control diet in 10-month-old C57BL/6J male mice. Body composition, food intake and glucose homeostasis were measured throughout the study and biochemical analyses of white adipose tissue (WAT) and liver were performed. MR and LR decreased body and fat mass, increased food intake, elevated lipid cycling in WAT and improved whole-body glucose metabolism and hepatic insulin sensitivity in comparison to the control diet. MR produced more substantial effects than LR on body mass and glucose homeostasis and reduced hepatic lipogenic gene expression, which was absent with the LR diet. This could be a result of amino acid-specific pathways in the liver responsible for FGF21 stimulation (causing varied levels of FGF21 induction) and Akt activation. In summary, LR is effective at improving metabolic health; however, MR produces stronger effects, suggesting they activate distinct signalling pathways.

Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR-/- mouse model of atherosclerosis.

Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with type 1 or type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance, due to impaired insulin receptor (IR) signalling. Here, we demonstrate that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR prevents and reverses atherosclerotic plaque formation in an LDLR-/- mouse model of atherosclerosis. Acute (single dose) or chronic PTP1B inhibitor (trodusquemine) treatment of LDLR-/- mice decreased weight gain and adiposity, improved glucose homeostasis and attenuated atherosclerotic plaque formation. This was accompanied by a reduction in both, circulating total cholesterol and triglycerides, a decrease in aortic monocyte chemoattractant protein-1 (MCP-1) expression levels and hyperphosphorylation of aortic Akt/PKB and AMPKα. Our findings are the first to demonstrate that PTP1B inhibitors could be used in prevention and reversal of atherosclerosis development and reduction in CVD risk.

The HAPI 'Hip Arthroscopy Pre-habilitation Intervention' study: does pre-habilitation affect outcomes in patients undergoing hip arthroscopy for femoro-acetabular impingement?

The purpose of this randomized prospective comparative controlled pilot study was to determine whether specific patient exercises done pre-hip arthroscopy surgery for femoro-acetabular impingement affected post-operative recovery. Between October 2013 and June 2014, 6 males and twelve females over the age of eighteen, who were listed for hip arthroscopy for femoro-acetabular impingement, were randomized into two groups. A hip-specific, 8-week home exercise programme was given to the experimental group before their surgery. The control group was given no instruction on exercise before surgery. All participants followed the same rehabilitation programme after surgery. Outcome measures were assessed at set time intervals. Hand held dynamometry was used to assess muscle strength, and the EQ-5D-5 L Score and the Non-Arthritic Hip Score were utilized. Sixteen participants completed the study (eight controls: mean age 41.75 years and eight intervention: mean age 37.5 years). A mixed ANCOVA analysis compared the treatment groups taking baseline values into account. A statistically significant difference was found between the treatment groups for knee extension strength on both operative (P = 0.05) and non-operative sides (P = 0.002), hip flexor strength operative side (P = 0.02) and for EQ-5D-5 L health (P = 0.03), in favour of the intervention group. There was no significant difference between the treatment groups for the other measures, although some tended towards significance. This small pilot study has been designed to aid the further research and the differences between the groups found in these results may inform future larger scale studies.

Methionine restriction improves renal insulin signalling in aged kidneys.

Dietary methionine restriction (MR) leads to loss of adiposity, improved insulin sensitivity and lifespan extension. The possibility that dietary MR can protect the kidney from age-associated deterioration has not been addressed. Aged (10-month old) male and female mice were placed on a MR (0.172% methionine) or control diet (0.86% methionine) for 8-weeks and blood glucose, renal insulin signalling, and gene expression were assessed. Methionine restriction lead to decreased blood glucose levels compared to control-fed mice, and enhanced insulin-stimulated phosphorylation of PKB/Akt and S6 in kidneys, indicative of improved glucose homeostasis. Increased expression of lipogenic genes and downregulation of PEPCK were observed, suggesting that kidneys from MR-fed animals are more insulin sensitive. Interestingly, renal gene expression of the mitochondrial uncoupling protein UCP1 was upregulated in MR-fed animals, as were the anti-ageing and renoprotective genes Sirt1, FGF21, klotho, and ß-klotho. This was associated with alterations in renal histology trending towards reduced frequency of proximal tubule intersections containing vacuoles in mice that had been on dietary MR for 190days compared to control-fed mice, which exhibited a pre-diabetic status. Our results indicate that dietary MR may offer therapeutic potential in ameliorating the renal functional decline related to ageing and other disorders associated with metabolic dysfunction by enhancing renal insulin sensitivity and renoprotective gene expression.

Randomised controlled trial of GP-led in-hospital management of homeless people ('Pathway').

Homeless people have complex problems. GP enhanced care (Pathway) has shown benefits. We performed a randomised, -parallel arm trial at two large inner city hospitals. Inpatient homeless adults were randomly allocated to either standard care (all management by the hospital-based clinical team) or enhanced care with input from a homeless care team. The hospital data system provided healthcare usage information, and we used questionnaires to assess quality of life. 206 patients were allocated to enhanced care and 204 to usual care. Length of stay (up to 90 days after admission) did not differ between groups (standard care 14.0 days, enhanced care 13.3 days). Average reattendance at the emergency department within a year was 5.8 visits in the standard care group and 4.8 visits with enhanced care, but this decrease was not significant. -Quality of life scores after discharge (in 108 patients) improved with enhanced care (EQ-5D-5L score increased by 0.12 [95% CI 0.032 to 0.22] compared wtih 0.03 [-0.1 to 0.15; p=0.076] with standard care). The proportion of people sleeping on the streets after discharge was 14.6% in the standard care arm and 3.8% in the enhanced care arm (p=0.034). The quality-of-life cost per quality-adjusted life-year was £26,000. The Pathway approach doesn't alter length of stay but improves quality of life and reduces street -homelessness.

Fenretinide mediated retinoic acid receptor signalling and inhibition of ceramide biosynthesis regulates adipogenesis, lipid accumulation, mitochondrial function and nutrient stress signalling in adipocytes and adipose tissue.

Fenretinide (FEN) is a synthetic retinoid that inhibits obesity and insulin resistance in high-fat diet (HFD)-fed mice and completely prevents 3T3-L1 pre-adipocyte differentiation. The aim of this study was to determine the mechanism(s) of FEN action in 3T3-L1 adipocytes and in mice. We used the 3T3-L1 model of adipogenesis, fully differentiated 3T3-L1 adipocytes and adipose tissue from HFD-induced obese mice to investigate the mechanisms of FEN action. We measured expression of adipogenic and retinoid genes by qPCR and activation of nutrient-signalling pathways by western blotting. Global lipid and metabolite analysis was performed and specific ceramide lipid species measured by liquid chromatography-mass spectrometry. We provide direct evidence that FEN inhibits 3T3-L1 adipogenesis via RA-receptor (RAR)-dependent signaling. However, RARα antagonism did not prevent FEN-induced decreases in lipid levels in mature 3T3-L1 adipocytes, suggesting an RAR-independent mechanism. Lipidomics analysis revealed that FEN increased dihydroceramide lipid species 5- to 16-fold in adipocytes, indicating an inhibition of the final step of ceramide biosynthesis. A similar blockade in adipose tissue from FEN-treated obese mice was associated with a complete normalisation of impaired mitochondrial ß-oxidation and tricarboxylic acid cycle flux. The FEN catabolite, 4-oxo-N-(4-hydroxyphenyl)retinamide (4-OXO), also decreased lipid accumulation without affecting adipogenesis. FEN and 4-OXO (but not RA) treatment additionally led to the activation of p38-MAPK, peIF2α and autophagy markers in adipocytes. Overall our data reveals FEN utilises both RAR-dependent and -independent pathways to regulate adipocyte biology, both of which may be required for FEN to prevent obesity and insulin resistance in vivo.

A key role for PTP1B in dendritic cell maturation, migration, and T cell activation.

Dendritic cells (DC) are the major antigen-presenting cells bridging innate and adaptive immunity, a function they perform by converting quiescent DC to active, mature DC with the capacity to activate naïve T cells. They do this by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here, we demonstrate that myeloid cell-specific genetic deletion of PTP1B (LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derived DC (BMDC) activation associated with increased levels of phosphorylated Stat3. We show that myeloid cell-specific PTP1B deletion also causes decreased migratory capacity of epidermal DC, as well as reduced CCR7 expression and chemotaxis to CCL19 by BMDC. PTP1B deficiency in BMDC also impairs their migration in vivo. Further, immature LysM PTP1B BMDC display fewer podosomes, increased levels of phosphorylated Src at tyrosine 527, and loss of Src localization to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysM PTP1B BMDC fail to present antigen to T cells as efficiently as control BMDC. These data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.

Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.

Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h. Food intake and whole-body physiology were assessed and serum/tissues analyzed biochemically. Methionine restriction in 12-month-old mice completely reversed age-induced alterations in body weight, adiposity, physical activity, and glucose tolerance to the levels measured in healthy 2-month-old control-fed mice. This was despite a significant increase in food intake in 12-month-old MR-fed mice. Methionine restriction decreased hepatic lipogenic gene expression and caused a remodeling of lipid metabolism in white adipose tissue, alongside increased insulin-induced phosphorylation of the insulin receptor (IR) and Akt in peripheral tissues. Mice restricted of methionine exhibited increased circulating and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and expression of ATF4, with a concomitant decrease in IRE1α phosphorylation. Short-term 48-h MR treatment increased hepatic FGF21 expression/secretion and insulin signaling and improved whole-body glucose homeostasis without affecting body weight. Our findings suggest that MR feeding can reverse the negative effects of aging on body mass, adiposity, and insulin resistance through an FGF21 mechanism. These findings implicate MR dietary intervention as a viable therapy for age-induced metabolic syndrome in adult humans.

Myeloid-cell protein tyrosine phosphatase-1B deficiency in mice protects against high-fat diet and lipopolysaccharide-induced inflammation, hyperinsulinemia, and endotoxemia through an IL-10 STAT3-dependent mechanism.

Protein tyrosine phosphatase-1B (PTP1B) negatively regulates insulin and leptin signaling, rendering it an attractive drug target for treatment of obesity-induced insulin resistance. However, some studies suggest caution when targeting macrophage PTP1B, due to its potential anti-inflammatory role. We assessed the role of macrophage PTP1B in inflammation and whole-body metabolism using myeloid-cell (LysM) PTP1B knockout mice (LysM PTP1B). LysM PTP1B mice were protected against lipopolysaccharide (LPS)-induced endotoxemia and hepatic damage associated with decreased proinflammatory cytokine secretion in vivo. In vitro, LPS-treated LysM PTP1B bone marrow-derived macrophages (BMDMs) displayed increased interleukin (IL)-10 mRNA expression, with a concomitant decrease in TNF-α mRNA levels. These anti-inflammatory effects were associated with increased LPS- and IL-10-induced STAT3 phosphorylation in LysM PTP1B BMDMs. Chronic inflammation induced by high-fat (HF) feeding led to equally beneficial effects of macrophage PTP1B deficiency; LysM PTP1B mice exhibited improved glucose and insulin tolerance, protection against LPS-induced hyperinsulinemia, decreased macrophage infiltration into adipose tissue, and decreased liver damage. HF-fed LysM PTP1B mice had increased basal and LPS-induced IL-10 levels, associated with elevated STAT3 phosphorylation in splenic cells, IL-10 mRNA expression, and expansion of cells expressing myeloid markers. These increased IL-10 levels negatively correlated with circulating insulin and alanine transferase levels. Our studies implicate myeloid PTP1B in negative regulation of STAT3/IL-10-mediated signaling, highlighting its inhibition as a potential anti-inflammatory and antidiabetic target in obesity.

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis.

Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of leptin and insulin signaling, is positively correlated with adiposity and contributes to insulin resistance. Global PTP1B deletion improves diet-induced obesity and glucose homeostasis via enhanced leptin signaling in the brain and increased insulin signaling in liver and muscle. However, the role of PTP1B in adipocytes is unclear, with studies demonstrating beneficial, detrimental or no effect(s) of adipose-PTP1B-deficiency on body mass and insulin resistance. To definitively establish the role of adipocyte-PTP1B in body mass regulation and glucose homeostasis, adipocyte-specific-PTP1B knockout mice (adip-crePTP1B(-/-)) were generated using the adiponectin-promoter to drive Cre-recombinase expression. Chow-fed adip-crePTP1B(-/-) mice display enlarged adipocytes, despite having similar body weight/adiposity and glucose homeostasis compared to controls. High-fat diet (HFD)-fed adip-crePTP1B(-/-) mice display no differences in body weight/adiposity but exhibit larger adipocytes, increased circulating glucose and leptin levels, reduced leptin sensitivity and increased basal lipogenesis compared to controls. This is associated with decreased insulin receptor (IR) and Akt/PKB phosphorylation, increased lipogenic gene expression and increased hypoxia-induced factor-1-alpha (Hif-1α) expression. Adipocyte-specific PTP1B deletion does not beneficially manipulate signaling pathways regulating glucose homeostasis, lipid metabolism or adipokine secretion in adipocytes. Moreover, PTP1B does not appear to be the major negative regulator of the IR in adipocytes.

Depletion of intracellular zinc inhibits the ubiquitin ligase activity of viral regulatory protein ICP0 and restricts herpes simplex virus 1 replication in cell culture.

The viral ubiquitin ligase ICP0 stimulates the onset of HSV-1 lytic infection and productive reactivation of viral genomes from latency. In order to mediate these processes, it requires its C3HC4 RING finger domain, a tertiary structural fold that is coordinated by the binding of two zinc (Zn(2+)) atoms. Here we formally demonstrate that Zn(2+) binding and intracellular Zn(2+) levels are critical for ICP0's biochemical activity and that depletion of intracellular Zn(2+) severely attenuates HSV-1 replication.

Synaptic integration of newly generated neurons in rat dissociated hippocampal cultures.

In the dentate gyrus of the hippocampus new neurons are born from precursor cells throughout development and into adulthood. These newborn neurons hold significant potential for self-repair of brain damage caused by neurodegenerative disease. However, the mechanism by which newborn neurons integrate into the brain is not understood due to a lack of knowledge of the molecular and functional characteristics of the synapses formed by newborn neurons. Here we report that dissociated hippocampal cultures continue to produce new granule cells in vitro that fire action potentials and become synaptically integrated into the existing network of mature hippocampal neurons. Quantification of the expression of synaptic proteins at newborn and mature granule cell synapses revealed synapse development onto newborn neurons occurs sequentially with initial synaptic contacts evident from 6 days after cell birth. These data also showed that the dendrites of newborn neurons have a high density of Piccolo and Bassoon puncta on them and therefore have a high potential to be integrated into the neuronal network through new synaptic connections. Electrophysiological recordings from newborn neurons reveal these synapses are functional within 10 days of cell birth. GABAergic input synapses were found to mature faster in newborn neurons than glutamatergic synapses where sequential recruitment of postsynaptic glutamate receptors occurred. Group I metabotropic glutamate receptors (mGluR1/5) were present at higher levels compared with ionotropic glutamate receptors (NMDA and AMPA receptors), suggesting that metabotropic and ionotropic receptors play differential roles at glutamatergic synapses in the integration and the maturation of newborn neurons. These data show that dissociated hippocampal cultures can provide a useful model system in which to study the integration of newborn neurons into existing neuronal circuits to increase our understanding of how the function of newborn neuron synapses could contribute to restoring damaged neuronal networks.