Screening of Fracture Risk and Osteoporosis Among Older Long-term Care Residents: A Prospective Study.

This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs.

Immature bovine cartilage wear is due to fatigue failure from repetitive compressive forces and not reciprocating frictional forces.

OBJECTIVE: Wear of articular cartilage is not well understood. We hypothesize that cartilage wears due to fatigue failure in repetitive compression instead of reciprocating friction. DESIGN: This study compares reciprocating sliding of immature bovine articular cartilage against glass in two testing configurations: (1) a stationary contact area configuration (SCA), which results in static compression, interstitial fluid depressurization, and increasing friction coefficient during reciprocating sliding, and (2) a migrating contact area configuration (MCA), which maintains pressurization and low friction while producing repetitive compressive loading in addition to reciprocating sliding. Contact pressure, sliding duration, and sliding distance were controlled to be similar between test groups. RESULTS: SCA tests exhibited an average friction coefficient of µ=0.084±0.032, while MCA tests exhibited a lower average friction coefficient of µ=0.020±0.008 (p<10-4). Despite the lower friction, MCA cartilage samples exhibited clear surface damage with a significantly greater average surface deviation from a fitted plane after wear testing (Rq=0.125±0.095 mm) than cartilage samples slid in a SCA configuration (Rq=0.044±0.017 mm, p=0.002), which showed minimal signs of wear. Polarized light microscopy confirmed that delamination damage occurred between the superficial and middle zones of the articular cartilage in MCA samples. CONCLUSIONS: The greatest wear was observed in the group with lowest friction coefficient, subjected to cyclical instead of static compression, implying that friction is not the primary driver of cartilage wear. Delamination between superficial and middle zones implies the main mode of wear is fatigue failure under cyclical compression, not fatigue or abrasion due to reciprocating frictional sliding.

Reliability Evaluation of Board-Level Flip-Chip Package under Coupled Mechanical Compression and Thermal Cycling Test Conditions.

Flip Chip Ball Grid Array (FCBGA) packages, together with many other heterogeneous integration packages, are widely used in high I/O (Input/Output) density and high-performance computing applications. The thermal dissipation efficiency of such packages is often improved through the use of an external heat sink. However, the heat sink increases the solder joint inelastic strain energy density, and thus reduces the board-level thermal cycling test reliability. The present study constructs a three-dimensional (3D) numerical model to investigate the solder joint reliability of a lidless on-board FCBGA package with heat sink effects under thermal cycling testing, in accordance with JEDEC standard test condition G (a thermal range of -40 to 125 °C and a dwell/ramp time of 15/15 min). The validity of the numerical model is confirmed by comparing the predicted warpage of the FCBGA package with the experimental measurements obtained using a shadow moiré system. The effects of the heat sink and loading distance on the solder joint reliability performance are then examined. It is shown that the addition of the heat sink and a longer loading distance increase the solder ball creep strain energy density (CSED) and degrade the package reliability performance accordingly.

Microfibers in laundry wastewater: Problem and solution.

Data corroborated in this study highlights laundry wastewater as a primary source of microfibers (MFs) in the aquatic environment. MFs can negatively impact the aquatic ecosystem via five possible pathways, namely, acting as carriers of other contaminats, physical damage to digestive systems of aquatic organisms, blocking the digestive tract, releasing toxic chemicals, and harbouring invasive and noxious plankton and bacteria. This review shows that small devices to capture MFs during household laundry activities are simple to use and affordable at household level in developed countries. However, these low cost and small devices are unrealiable and can only achieve up to 40 % MF removal efficiency. In line filtration devices can achieve higher removal efficiency under well maintained condition but their performance is still limited compared to over 98 % MF removal by large scale centralized wastewater treatment. These results infer that effort to increase sanitation coverage to ensure adequate wastewater treatment prior to environmental discharge is likely to be more cost effective than those small devices for capturing MFs. This review also shows that natural fabrics would entail significantly less environmental consequences than synthetic materials. Contribution from the fashion industry to increase the share of natural frabics in the current textile market can also reduce the loading of plastic MFs in the environment.

Peri-discharge complex interventions for reducing 30-day hospital readmissions among heart failure patients: overview of systematic reviews and network meta-analysis.

AIMS: An overview of systematic reviews (SRs) and network meta-analysis (NMA) was conducted to synthesize evidence of comparative effectiveness of different peri-discharge complex interventions for reducing 30-day hospital readmissions among heart failure (HF) patients. METHODS: We searched five databases for SRs from their inception to August 2019 and conducted additional search for randomized controlled trials (RCTs) published between 2003 and 2020. We used random-effect pairwise meta-analysis with pooled risk ratios (RRs) and 95% confidence intervals (CIs) to quantify the effect of complex interventions, and NMA to evaluate comparative effectiveness among complex interventions. Primary outcome was 30-day all-cause hospital readmissions, while secondary outcomes were 30-day HF-related hospital readmissions, 30-day mortality, and 30-day emergency department visits. RESULTS: From 20 SRs and additional RCT search, 21 eligible RCTs (n = 5362) assessing eight different peri-discharge complex interventions were included. Pairwise meta-analysis showed no significant difference between peri-discharge complex interventions and controls on all outcomes, except that peri-discharge complex interventions were significantly more effective than controls in reducing 30-day mortality (pooled RR = 0.68, 95% CI: 0.49-0.95, 5 RCTs). NMA indicated that for reducing 30-day all-cause hospital readmissions, supportive-educative intervention had the highest probability to be the best intervention, followed by disease management; while for reducing 30-day HF-related hospital readmissions, disease management is likely to be the best intervention. CONCLUSIONS: Our results suggest that disease management has the best potential to reduce 30-day all-cause and HF-related hospital readmissions. Benefits of the interventions may vary across health system contexts. Evidence-based complex interventions require local adaptation prior to implementation.

A descriptive analysis of 2020 California Occupational Safety and Health Administration COVID-19-related complaints

COVID-19 mortality disproportionately affected specific occupations and industries. The Occupational Safety and Health Administration (OSHA) protects the health and safety of workers by setting and enforcing standards for working conditions. Workers may file OSHA complaints about unsafe conditions. Complaints may indicate poor workplace safety during the pandemic. We evaluated COVID-19-related complaints filed with California (Cal)/OSHA between January 1, 2020 and December 14, 2020 across seven industries. To assess whether workers in occupations with high COVID-19-related mortality were also most likely to file Cal/OSHA complaints, we compared industry-specific per-capita COVID-19 confirmed deaths from the California Department of Public Health with COVID-19-related complaints. Although 7,820 COVID-19-related complaints were deemed valid by Cal/OSHA, only 627 onsite inspections occurred and 32 citations were issued. Agricultural workers had the highest per-capita COVID-19 death rates (402 per 100,000 workers) but were least represented among workplace complaints (44 per 100,000 workers). Health Care workers had the highest complaint rates (81 per 100,000 workers) but the second lowest COVID-19 death rate (81 per 100,000 workers). Industries with the highest inspection rates also had high COVID-19 mortality. Our findings suggest complaints are not proportional to COVID-19 risk. Instead, higher complaint rates may reflect worker groups with greater empowerment, resources, or capacity to advocate for better protections. This capacity to advocate for safe workplaces may account for relatively low mortality rates in potentially high-risk occupations. Future research should examine factors determining worker complaints and complaint systems to promote participation of those with the greatest need of protection.

Mucin 5AC is significantly upregulated in exosomes from the nasal lavage fluid and may promote the expression of COX-2, VEGF and MMP-9: an implication in nasal polyp pathogenesis.

BACKGROUND: Exosomes are critical mediators of intercellular communication and could be involved in many human diseases; however, little is known about the role of exosomes in nasal polyps (NP). METHODS: Exosomes in nasal lavage fluids (NLF) were isolated by ultracentrifugation. Exosome identity was validated by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and specific exosomal markers. The exosome proteome was revealed by LC-MS/MS, and the expression of the candidate exosomal protein, mucin 5AC, was confirmed by Western blot analysis and immunohistochemistry (IHC). Cellular uptake of the exosomes was monitored by fluorescence confocal microscopy and the ensuing effects on COX-2, VEGF and MMP-2/MMP-9 were determined by Western blotting, ELISA and gelatin zymography, respectively. RESULTS: Mass spectrometry analysis and subsequent verification by Western blotting identified that mucin 5AC was significantly upregulated in exosomes from NLFs of NP patients. Moreover, the expression of mucin 5AC was increased in the tissue specimens of the NP patients. Functional assays suggest that the mucin 5 AC-enriched exosomes could be effectively taken up by chronic rhinosinusitis without NP (CRSsNP)-derived fibroblasts, the control cells, resulting in a significant increase in the expression of COX-2, VEGF and MMP-9. CONCLUSIONS: Mucin 5AC, the major airway mucin, cannot only be carried and transferred by nasal exosomes, but may also promote tissue remodeling and angiogenesis and thus could be a potential therapeutic target of NP.

Monitoring the Assembly and Aggregation of Polypeptide Materials by Time-Resolved Emission Spectra.

Polypeptide assembly and aggregation are the common forms of its physiological and pathological activity, and monitoring them on a molecular level is critical for resolving numerous medical (e.g., onset of neurodegenerative diseases) or biological problems. Sensitivity of the intrinsic fluorescence of protein to its assembly, aggregation, or complexation offers a noninvasive methodology for identifying and determining different stages of these processes. In this protocol, we present the approach based on the time-resolved emission spectra (TRES), which reveals the number of fluorescent residues, the presence of dielectric relaxation, and the changes in fluorescence kinetics during aggregation.

Author Correction: mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mercury distribution and speciation in two lagoons with different pollution and eutrophication conditions in Taiwan.

This study explored biogeochemical processes controlling the distribution of mercury (Hg) species in two lagoons with different pollution and eutrophication conditions in southwestern Taiwan. The eutrophication and pollution levels were higher in the Dapeng Bay than in the Chiku Lagoon, engendering a higher particulate Hg concentration and enrichment factor in the Dapeng Bay. The concentration range of total dissolved Hg (HgTD) and reactive Hg (HgR) was comparable between the lagoons, but the concentration of particulate Hg (HgP) was higher in the Dapeng Bay. HgR and HgTD abundance was primarily controlled by the availability of dissolved oxygen (DO) and biological absorption. In addition to pollution (which elevated HgP concentration), biological absorption and/or adsorption rather than lithogenic processes more likely regulated the HgP concentration. The effect of Hg pollution may superimpose on that of DO on the distributions of HgR and HgTD and may enhance HgP formation in the Dapeng Bay.

Colistin and tylosin enhances disaccharidase activities, and improves morphology and permeability of the intestine of broilers.

1. The present study focused on the potential effects of antibiotics on intestinal digestion and integrity in broilers in terms of disaccharidase activity, electrophysiological properties and morphology. 2. One-day-old Arbour Acres birds were randomly allocated to one of four treatment groups for 42 days; control, colistin (20 mg/kg), tylosin (55 mg/kg) or chlortetracycline (CTC, 55 mg/kg) groups. Colistin and tylosin supplementation, but not CTC supplementation, caused an increase in body weight gain. 3. Colistin and tylosin elevated the activities of maltase and sucrase in the mucosa of the jejunum on d 42. Age caused a gradual decrease in the short-circuit current (Isc) and conductance (Gt) of the ileum, as a measure of permeability. The Isc and Gt of the ileum were higher in the colistin-supplemented broilers than in the control birds on d 42. Tylosin- and CTC-supplemented birds displayed Isc and Gt values similar to those of the control birds. 4. Colistin supplementation increased the villus area in the jejunum and thinned the muscularis mucosae in the ileum compared with the control group. Tylosin supplementation decreased the thickness of the muscularis mucosae and the depth of crypt in the jejunum. CTC thickened the muscularis mucosae in the jejunum and ileum. 5. Colistin and tylosin exhibited a beneficial effect on intestinal digestion and integrity by enhancing disaccharidase activities and improving gut morphology and permeability.

Ascending-Dose Study of Controlled-Release Ketamine Tablets in Healthy Volunteers: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability.

Parenteral ketamine has fast-onset antidepressant and antianxiety effects; however, it causes dissociation, hypertension, and tachycardia shortly after dosing. Ketamine's antidepressant effects may be due to active metabolites rather than to ketamine itself. We hypothesized that oral controlled-release ketamine tablets would improve safety and tolerability compared with injected ketamine by reducing peak ketamine exposures compared with dosing by injection. In this randomized, placebo-controlled ascending-dose study, ketamine doses of 60, 120, or 240 mg or matching placebo (single dose followed by every-12-hours dosing for 5 doses) were given to 24 healthy volunteers. Pharmacokinetics, pharmacodynamics (brain-derived neurotropic factor), adverse events, and vital signs were assessed up to 72 hours. Drug release occurred over ∼10 hours, with most drug substance present as norketamine (∼90%). Area under the concentration-time curve and peak concentration were dose proportional. Elimination half-life was prolonged (7-9 hours) compared with published data from immediate-release oral formulations. There were no changes in blood pressure or heart rate after any dose. Mild dissociation was reported after 240 mg but not lower doses; mean dissociation ratings in this group were minimal (1-2/76). There were no clinically significant changes in ECGs or safety laboratory tests at any time. Compared with injected ketamine, oral controlled-release ketamine tablets did not increase blood pressure or heart rate, and only at doses of 240 mg was dissociation of mild intensity reported. Reducing and delaying ketamine peak concentration by oral dosing with controlled-release ketamine tablets improve this drug's tolerability for patients with depression/anxiety.

mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis.

mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.

Tracking Insulin Glycation in Real Time by Time-Resolved Emission Spectroscopy.

The application of time-resolved fluorescence sensing to the study of heterogenic biomolecular systems remains challenging because of the complexity of the resulting photophysics. Measuring the time-resolved emission spectroscopy (TRES) spectra can provide a more informative alternative to the modeling of the fluorescence decay that is currently employed. Here, we demonstrate this approach by monitoring real-time changes in intrinsic insulin fluorescence by TRES as a straightforward probe to directly measure kinetics of insulin aggregation and glycation. Our findings hold promise for monitoring the storage of insulin and its application in the control of diabetes and may support the development of more effective therapeutics against amyloidosis.

DNA Damage Repair in Huntington's Disease and Other Neurodegenerative Diseases.

Recent genome-wide association studies of Huntington's disease (HD) primarily highlighted genes involved in DNA damage repair mechanisms as modifiers of age at onset and disease severity, consistent with evidence that more DNA repair genes are being implicated in late age-onset neurodegenerative diseases. This provides an exciting opportunity to advance therapeutic development in HD, as these pathways have already been under intense investigation in cancer research. Also emerging are the roles of other polyglutamine disease proteins in DNA damage repair mechanisms. A potential universal trigger of oxidative DNA damage shared in these late age-onset diseases is the increase of reactive oxygen species (ROS) in human aging, defining an age-related mechanism that has defied other hypotheses of neurodegeneration. We discuss the potential commonality of DNA damage repair pathways in HD and other neurodegenerative diseases. Potential targets for therapy that may prove beneficial across many of these diseases are also identified, defining nodes in the ataxia telangiectasia-mutated (ATM) complex, mismatch repair, and poly ADP-ribose polymerases (PARPs).

A novel application of membrane distillation to facilitate nickel recovery from electroplating wastewater.

In many years, the nickel electroplating technique has been applied to coat nickel on other materials for their increased properties. Nickel electroplating has played a vital role in our modern society but also caused considerable environmental concerns due to the mass discharge of its wastewater (i.e. containing nickel and other heavy metals) to the environment. Thus, there is a growing need for treating nickel electroplating wastewater to protect the environment and, in tandem, recover nickel for beneficial use. This study explores a novel application of membrane distillation (MD) for the treatment of nickel electroplating wastewater for a dual purpose: facilitating the nickel recovery and obtaining fresh water. The experimental results demonstrate the technical capability of MD to pre-concentrate nickel in the wastewater (i.e. hence pave the way for subsequent nickel recovery via chemical precipitation or electrodeposition) and extract fresh water. At a low operating feed temperature of 60 °C, the MD process increased the nickel content in the wastewater by more than 100-fold from 0.31 to 33 g/L with only a 20% reduction in the process water flux and obtained pure fresh water. At such high concentration factors, the membrane surface was slightly fouled by inorganic precipitates; however, membrane pore wetting was not evident, confirmed by the purity of the obtained fresh water. The fouled membrane was effectively cleaned using a 3% HCl solution to restore its surface morphology. Finally, the preliminary thermal energy analysis of the combined MD-chemical precipitation/electrodeposition process reveals a considerable reduction in energy consumption of the nickel recovery process.

Secondary dentition characteristics in an ethnic Chinese orthodontic population: A retrospective cross-sectional study.

AIM: To determine the prevalence of dental anomalies and its association with gender. METHODS: This retrospective cross-sectional study was conducted using radiographs, photographs and clinical records of patients who attended the Department of Orthodontics at the National Dental Centre Singapore. Records of 2508 ethnic Chinese orthodontic patients aged 14-25 years were examined for the prevalence of dental anomalies in the permanent dentition, excluding third molars. Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc.). Logistic regression was used to determine the association between gender and the occurrence of various dental anomalies. Kappa coefficients were calculated to test for intra-examiner reproducibility. Statistical significance was set at P < 0.05. RESULTS: Prevalence of dental anomalies was 5.7% hyperdontia, 11.1% hypodontia, 5.5% peg-shaped upper lateral incisors, 21.9% impacted teeth, 1.3% transposition and 0.4% double teeth. There was no significant gender difference in the occurrence of the anomalies except hyperdontia, with males having significantly higher odds of hyperdontia compared with females (odds ratio, 1.488; 95% confidence interval, 1.062-2.085; P = 0.021). CONCLUSION: Occurrence of hyperdontia is greater in males than females, while no significant gender differences were noted for hypodontia, peg-shaped upper lateral incisors, impacted teeth, transposition and double teeth.

Protein fibrillogenesis model tracked by its intrinsic time-resolved emission spectra.

The excited-state kinetics of the fluorescence of tyrosine in a de novo protein fibrillogenesis model was investigated as a potential tool for monitoring protein fibre formation and complexation with glucose (glycation). In stark contrast to insulin the time-resolved emission spectra (TRES) recorded over the period of 700 hours in buffered solutions of the model with and without glucose revealed no apparent changes in Tyr fluorescence responses. This indicates the stability of the model and provides a measurement-supported basis for its use as a reference material in fluorescence studies of protein aggregation.

Continuous and bolus intraventricular topotecan prolong survival in a mouse model of leptomeningeal medulloblastoma.

Leptomeningeal metastasis remains a difficult clinical challenge. Some success has been achieved by direct administration of therapeutics into the cerebrospinal fluid (CSF) circumventing limitations imposed by the blood brain barrier. Here we investigated continuous infusion versus bolus injection of therapy into the CSF in a preclinical model of human Group 3 medulloblastoma, the molecular subgroup with the highest incidence of leptomeningeal disease. Initial tests of selected Group 3 human medulloblastoma cell lines in culture showed that D283 Med and D425 Med were resistant to cytosine arabinoside and methotrexate. D283 Med cells were also resistant to topotecan, whereas 1 µM topotecan killed over 99% of D425 Med cells. We therefore introduced D425 Med cells, modified to express firefly luciferase, into the CSF of immunodeficient mice. Mice were then treated with topotecan or saline in five groups: continuous intraventricular (IVT) topotecan via osmotic pump (5.28 µg/day), daily bolus IVT topotecan injections with a similar daily dose (6 µg/day), systemic intraperitoneal injections of a higher daily dose of topotecan (15 µg/day), daily IVT pumped saline and daily intraperitoneal injections of saline. Bioluminescence analyses revealed that both IVT topotecan treatments effectively slowed leptomeningeal tumor growth in the brains. Histological analysis showed that they were associated with localized brain necrosis, possibly due to backtracking of topotecan around the catheter. In the spines, bolus IVT topotecan showed a trend towards slower tumor growth compared to continuous (pump) IVT topotecan, as measured by bioluminescence. Both continuous and bolus topotecan IVT showed longer survival compared to other groups. Thus, both direct IVT topotecan CSF delivery methods produced better anti-medulloblastoma effect compared to systemic therapy at the dosages used here.