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1.
Vaccine ; 42(15): 3445-3454, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38631956

ABSTRACT

Major histocompatibility complex class II (MHC-II) molecules are involved in immune responses against pathogens and vaccine candidates' immunogenicity. Immunopeptidomics for identifying cancer and infection-related antigens and epitopes have benefited from advances in immunopurification methods and mass spectrometry analysis. The mouse anti-MHC-II-DR monoclonal antibody L243 (mAb-L243) has been effective in recognising MHC-II-DR in both human and non-human primates. It has also been shown to cross-react with other animal species, although it has not been tested in livestock. This study used mAb-L243 to identify Staphylococcus aureus and Salmonella enterica serovar Typhimurium peptides binding to cattle and swine macrophage MHC-II-DR molecules using flow cytometry, mass spectrometry and two immunopurification techniques. Antibody cross-reactivity led to identifying expressed MHC-II-DR molecules, together with 10 Staphylococcus aureus peptides in cattle and 13 S. enterica serovar Typhimurium peptides in swine. Such data demonstrates that MHC-II-DR expression and immunocapture approaches using L243 mAb represents a viable strategy for flow cytometry and immunopeptidomics analysis of bovine and swine antigen-presenting cells.


Subject(s)
Antibodies, Monoclonal , Macrophages , Salmonella typhimurium , Staphylococcus aureus , Animals , Cattle , Swine/immunology , Staphylococcus aureus/immunology , Antibodies, Monoclonal/immunology , Macrophages/immunology , Salmonella typhimurium/immunology , Histocompatibility Antigens Class II/immunology , Cross Reactions/immunology , Flow Cytometry , Mass Spectrometry , Mice
2.
Front Microbiol ; 15: 1339569, 2024.
Article in English | MEDLINE | ID: mdl-38455070

ABSTRACT

Background: Respiratory Syncytial Virus (RSV) presents a significant health threat, especially to young children. In-depth understanding of RSV entry mechanisms is essential for effective antiviral development. This study introduces an innovative RSV variant, featuring the fusion of the beta-lactamase (BlaM) enzyme with the RSV-P phosphoprotein, providing a versatile tool for dissecting viral entry dynamics. Methods: Using the AlphaFold2 algorithm, we modeled the tertiary structure of the P-BlaM chimera, revealing structural similarities with both RSV-P and BlaM. Functional assessments, utilizing flow cytometry, quantified beta-lactamase activity and GFP expression in infected bronchial epithelial cells. Western blot analysis confirmed the integrity of P-BlaM within virions. Results: The modeled P-BlaM chimera exhibited structural parallels with RSV-P and BlaM. Functional assays demonstrated robust beta-lactamase activity in recombinant virions, confirming successful P-BlaM incorporation as a structural protein. Quercetin, known for its antiviral properties, impeded viral entry by affecting virion fusion. Additionally, Ulixertinib, an ERK-1/2 inhibitor, significantly curtailed viral entry, implicating ERK-1/2 pathway signaling. Conclusions: Our engineered RSV-P-BlaM chimera emerges as a valuable tool, illuminating RSV entry mechanisms. Structural and functional analyses unveil potential therapeutic targets. Quercetin and Ulixertinib, identified as distinct stage inhibitors, show promise for targeted antiviral strategies. Time-of-addition assays pinpoint quercetin's specific interference stage, advancing our comprehension of RSV entry and guiding future antiviral developments.

3.
Article in English | MEDLINE | ID: mdl-38236058

ABSTRACT

BACKGROUND: Despite notable progress over time, broad insight into the scientific landscape of orthopaedic oncology is lacking. We conducted a bibliometric analysis of the 500 most cited papers in the field. METHODS: We searched the Science Citation Index Expanded database of the Web of Science Core Collection to find the 500 most cited articles in the field. RESULTS: Citation count ranged from 81 to 1,808. Articles were published from 1965 to 2018. Over half of all articles were published in the United States (53.6%). The 2000s was the most productive decade with 170 (34%) articles. All articles were written in English and were published across 29 journals. Female participation as first authors significantly increased from the 1960s to the 2010s (0% vs 14.6%, P = 0.0434). Similarly, female involvement as senior authors grew from the 1960s to the 2010s (0% vs 12.2%, P = 0.0607). Primary bone sarcomas were the most cited topic among articles from the 1970s to the 1980s. From studies produced in the 1990s up until the 2010s, reconstruction procedures were the most cited topic. CONCLUSION: Trends over the years have resulted in an emphasis on a surgical technique. Notable progress has been made regarding gender diversity, yet disparities still exist.


Subject(s)
Orthopedics , Female , Humans , United States , Bibliometrics , Publications , Databases, Factual , Writing
4.
Vaccine ; 41(48): 7067-7071, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37858448

ABSTRACT

Distribution and administration strategy are critical to successful population immunization efforts. Agent-based modeling (ABM) can reflect the complexity of real-world populations and can experimentally evaluate vaccine strategy and policy. However, ABMs historically have been limited in their time-to-development, long runtime, and difficulty calibrating. Our team had several technical advances in the development of our GradABMs: a novel class of scalable, fast and differentiable simulations. GradABMs can simulate million-size populations in a few seconds on commodity hardware, integrate with deep neural networks and ingest heterogeneous sources. This allows for rapid and real-world sensitivity analyses. Our first epidemiological GradABM (EpiABMv1) enabled simulation interventions over real million-scale populations and was used in vaccine strategy and policy during the COVID-19 pandemic. Literature suggests decisions aided by evidence from these models saved thousands of lives. Our most recent model (EpiABMv2) extends EpiABMv1 to allow improved regional calibration using deep neural networks to incorporate local population data, and in some cases different policy recommendations versus our prior models. This is an important advance for our model to be more effective at vaccine strategy and policy decisions at the local public health level.


Subject(s)
Pandemics , Vaccines , Humans , Pandemics/prevention & control , Computer Simulation , Neural Networks, Computer , Policy
5.
J Bone Miner Res ; 38(11): 1679-1688, 2023 11.
Article in English | MEDLINE | ID: mdl-37681243

ABSTRACT

Bisphosphonates are first-line treatments for several bone and mineral disorders. Studies have reported an increased incidence of serious atrial fibrillation in patients receiving bisphosphonates; however, uncertainty remains as to whether electrical disturbances are precipitated by bisphosphonates. We aimed to review the literature for studies reporting electrocardiogram (ECG) findings in patients receiving intravenous bisphosphonates for any indication. We searched MEDLINE and EMBASE from inception until January 14, 2023, for studies reporting ECG parameters after intravenous bisphosphonate infusion. We excluded studies that only reported atrial fibrillation. Study quality was assessed using the Newcastle-Ottawa scale. Continuous data were meta-analyzed if reported in at least two studies. Random-effects models were fitted and reported as standardized mean difference (SMD) with 95% confidence intervals (95% CIs). We found 1083 unique records, of which 11 met our inclusion and exclusion criteria. Studies had a low to low/moderate risk of bias. Six prospective cohort studies were included in the meta-analysis. Five studies used zoledronic acid, whereas one study used pamidronate. Most studies (n = 4) were conducted in postmenopausal women with osteoporosis, one study was conducted in patients with bone metastases, and one study in children with osteoporosis secondary to cerebral palsy. Study populations ranged from n = 15 to n = 116. Heart rate-corrected QT (QTc) was significantly longer post-infusion (SMD = 0.46 ms [95% CI 0.80 to 0.11]; n = 67 patients, k = 2 studies, τ2 = 0). There were no differences in heart rate, P wave (maximum), P wave (minimum), P wave dispersion, PR interval, QRS duration, QTc, QTc (maximum), QTc (minimum), and QTc dispersion. The correlation between pre- and post-infusion QTc was not significant (p = 0.93). Overall, there is a weak association between intravenous bisphosphonate infusion and a QTc interval prolongation. However, there is insufficient evidence to support an association between intravenous bisphosphonate and any ECG variable changes, which may precipitate atrial fibrillation. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Atrial Fibrillation , Bone Density Conservation Agents , Osteoporosis , Child , Humans , Female , Diphosphonates/adverse effects , Bone Density Conservation Agents/adverse effects , Prospective Studies , Osteoporosis/chemically induced , Osteoporosis/drug therapy , Electrocardiography , Minerals
6.
Cureus ; 15(7): e42765, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37663980

ABSTRACT

Intraoperative seizures under general anesthesia are infrequent. However, seizure activity under general anesthesia confirmed by contemporaneous EEG has been reported. We describe the case of a 39-year-old female undergoing right frontal brain tumor resection who experienced an intraoperative seizure. Intraoperative neuromonitoring was utilized and included four channels of EEG, somatosensory evoked potentials (SSEP), and transcranial motor evoked potentials (MEP). During this operation, characteristic motor manifestations of a seizure occurred. However, the EEG did not demonstrate seizure activity due to limitations in EEG lead placement. Post-operatively in the ICU, motor manifestations of seizure activity continued, and subsequent EEG recordings demonstrated classic seizure activity. Due to the previous hemicraniectomy, corkscrew EEG electrodes were not placed over the right skull defect, thereby failing to detect the intraoperative seizure. Anesthesiologists should be aware that limitations with EEG electrode placement can fail to detect intraoperative seizures, and treatment to extinguish the seizure should proceed in an emergent fashion.

7.
Mol Microbiol ; 120(3): 341-350, 2023 09.
Article in English | MEDLINE | ID: mdl-37537859

ABSTRACT

Respiratory syncytial virus (RSV) is a virus that causes acute respiratory infections in neonates and older adults. To infect host cells, the attachment glycoprotein (G) interacts with a cell surface receptor. This interaction determines the specific cell types that are susceptible to infection. RSV possesses a type I fusion protein F. Type I fusion proteins are metastable when rearrangement of the prefusion F occurs; the fusion peptide is exposed transforming the protein into postfusion form. The transition between the prefusion form and its postfusion form facilitates the viral envelope and the host cell membrane to fuse, enabling the virus to enter the host cell. Understanding the entry mechanism employed by RSV is crucial for developing effective antiviral therapies. In this review, we will discuss the various types of viral fusion proteins and explore the potential entry mechanisms utilized by RSV. A deeper understanding of these mechanisms will provide valuable insights for the development of novel approaches to treat RSV infections.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Infant, Newborn , Humans , Aged , Antibodies, Neutralizing , Respiratory Syncytial Virus, Human/metabolism , Viral Fusion Proteins/metabolism
8.
Heart ; 110(2): 108-114, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37536758

ABSTRACT

OBJECTIVE: To examine the association between high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, muscle function decline and 14.5-year fall-related hospitalisation risk in women aged over 70 years. METHODS: 1179 ambulatory community-dwelling women aged over 70 years with subclinical levels of hs-cTnI (ie, <15.6 ng/L), who were followed up for 14.5 years, were included. Samples for hs-cTnI were obtained in 1998. Fall-related hospitalisations were retrieved from linked health records. Muscle function measures, including handgrip strength and the Timed-Up-and-Go (TUG) test, were assessed in 1998 and 2003. RESULTS: Mean±SD age was 75.2±2.7 years. Over 14.5 years of follow-up, 40.4% (476 of 1179) experienced fall-related hospitalisation. Participants were categorised into four approximate hs-cTnI quartiles: quartile 1 (<3.6 ng/L), quartile 2 (3.6-4.4 ng/L), quartile 3 (4.5-5.8 ng/L) and quartile 4 (≥5.9 ng/L). Compared with those in Q1, women in Q4 were likely to experience fall-related hospitalisation (36.0% vs 42.8%). In a multivariable-adjusted model that accounted for CVD and fall risk factors, compared with women in Q1, those in Q4 had a 46% higher risk of fall-related hospitalisation (HR 1.46, 95% CI 1.08 to 1.98). Additionally, women in Q4 had slower TUG performance compared with those in Q1 (10.3 s vs 9.5 s, p=0.032). CONCLUSION: Elevated level of hs-cTnI was associated with slower TUG performance and increased fall-related hospitalisation risk. This indicates subclinical level of hs-cTnI can identify clinically relevant falls, emphasising the need to consider cardiac health during fall assessment in women aged over 70 years. TRIAL REGISTRATION NUMBER: ACTRN12617000640303.


Subject(s)
Hand Strength , Troponin I , Humans , Female , Aged , Aged, 80 and over , Biomarkers , Hospitalization , Troponin T
10.
Sci Rep ; 13(1): 6752, 2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37185779

ABSTRACT

We report on the synthesis and characterization of V2O5 nanoparticles grown using a sol-gel method at different calcination temperatures. We observed a surprising reduction in the optical band gap from 2.20 to 1.18 eV with increasing calcination temperature from 400 to 500 °C. Raman and X-Ray diffraction measurements indicated slight changes in the lattice parameters induced by the growth process. However, density functional theory calculations of the Rietveld-refined and pristine structures revealed that the observed optical gap reduction could not be explained by structural changes alone. By introducing oxygen vacancies to the refined structures, we could reproduce the reduction of the band gap. Our calculations also showed that the inclusion of oxygen vacancies at the vanadyl position creates a spin-polarized interband state that reduces the electronic band gap and promotes a magnetic response due to unpaired electrons. This prediction was confirmed by our magnetometry measurements, which exhibited a ferromagnetic-like behavior. Our findings suggest that oxygen vacancies play a crucial role in band gap reduction and the promotion of a ferromagnetic-like response in an otherwise paramagnetic material. This provides a promising route to engineer novel devices.

12.
Arch Gerontol Geriatr ; 107: 104911, 2023 04.
Article in English | MEDLINE | ID: mdl-36587454

ABSTRACT

BACKGROUND: A few cross-sectional studies have highlighted inconsistent associations between cardiovascular disease (CVD) and musculoskeletal conditions. We sought to investigate the relationship between clinical CVD including subtypes, compromised muscle function, as well as incident self-reported and injurious falls in older women. MATERIALS AND METHODS: 1431 community-dwelling older women (mean age ± SD; 75.2 ± 2.7 years) were included in over 14.5 years of a prospective study, the Perth Longitudinal Study of Ageing in Women. CVD (up to 18-years prior to the baseline visit) and injurious fall hospitalizations over 14.5 years were obtained from linked health records. Self-reported falls for five years were obtained via a written adverse event diary posted every four months. Timed-Up-and-Go (TUG) test and hand grip strength were used to assess mobility and muscle strength, respectively. Mobility impairment was defined as TUG performance >10.2 sec and muscle weakness characterized as grip strength <22 kg. RESULTS: Over 5-years, 411 (28.7%) women reported a falls, while 567 (39.6%) were hospitalized due to an injurious fall over 14.5 years. Prior CVD events were associated with 32% (HR 1.32 95%CI, 1.06-1.64) and 29% (HR 1.29 95%CI, 1.07-1.56) increased risk of self-reported and injurious falls, respectively, in multivariable-adjusted models. When considering subtypes of CVD, only cerebrovascular disease was related to self-reported (HR 1.77; 95%CI, 1.15-2.72) and injurious falls requiring hospitalization (HR 1.51; 95%CI, 1.00-2.27). CVD was also associated with cross-sectional and prospective mobility impairments. However, no evidence for such relationships was observed for muscle weakness. CONCLUSIONS: Prevalent CVD events, particularly cerebrovascular disease, are related to an increased risk of long-term falls. These findings highlight the need to recognize increased falls risk in patients with CVD. Further, there is a need to understand whether incorporating prevalent CVD into falls screening tools improves risk stratification or affects model calibration.


Subject(s)
Cardiovascular Diseases , Hand Strength , Humans , Female , Aged , Male , Longitudinal Studies , Prospective Studies , Hand Strength/physiology , Accidental Falls , Cross-Sectional Studies , Risk Factors , Aging , Muscle Weakness , Muscles
13.
Bone ; 168: 116647, 2023 03.
Article in English | MEDLINE | ID: mdl-36543300

ABSTRACT

BACKGROUND: Cardiovascular effects of osteoporosis medications have recently been highlighted. Although oral and intravenous bisphosphonates are assumed to have similar cardiovascular safety, few head-to-head comparisons exist. The cardiovascular safety of teriparatide is unknown. Aim We conducted a pharmacovigilance safety study of cardiac events using real-life adverse event reports from alendronate, zoledronic acid and teriparatide users. METHODS: Adverse drug reactions were obtained from Vigibase, a WHO database of individual case safety reports (ICSRs) from 130 countries (1967-2020). ISCRs for atrial fibrillation (AF), angina pectoris, arteriosclerosis coronary artery (ACA), cardiac arrhythmias, coronary artery disease (CAD), thromboembolic events (TE), ischaemic heart disease (IHD), torsade de pointes/QT prolongation (TDP) associated with alendronate, zoledronic acid and teriparatide use were extracted. Data were included in a disproportionality analysis where the lower end of the 95 % credibility interval for the information component (IC025), showing a statistical association when >0. Head-to-head comparisons of ISCRs were estimated by age-adjusted odds ratios and 95 % confidence intervals. RESULTS: 465 episodes of angina, 287 ACA, 13,385 arrhythmias, 792 CAD, 6743 TE, 3264 IHD, 1037 myocardial infarcts, and 3714 TDP events were recorded across 50,365 alendronate, 52,436 zoledronic acid and 137,629 teriparatide users. There was a significant association between alendronate and zoledronate with all outcomes except MI. Teriparatide use was associated with AF, arrythmias and angina only. In head-to-head comparisons, teriparatide use was associated with fewer ACA and CAD events than alendronate and fewer ACA than zoledronic acid. DISCUSSION: Osteoporosis medication use is associated with adverse cardiac events, except for MI, and these appear to be more common with oral and intravenous bisphosphonates than teriparatide. Our data do not support differential effects of oral and intravenous bisphosphonates on cardiac events. Mechanisms whereby teriparatide may be cardio-protective warrant further investigation.


Subject(s)
Bone Density Conservation Agents , Coronary Artery Disease , Osteoporosis , Humans , Diphosphonates/adverse effects , Teriparatide/adverse effects , Alendronate/adverse effects , Bone Density Conservation Agents/adverse effects , Zoledronic Acid/therapeutic use , Pharmacovigilance , Osteoporosis/drug therapy , Osteoporosis/chemically induced , DNA-Binding Proteins
14.
Nutr Metab Cardiovasc Dis ; 33(1): 95-104, 2023 01.
Article in English | MEDLINE | ID: mdl-36411216

ABSTRACT

BACKGROUND AND AIMS: We and others have identified links between cardiovascular conditions and poor musculoskeletal health. However, the relationship between measures of carotid atherosclerosis such as focal carotid plaque and common carotid intima media thickness (CCA-IMT) and falls remains understudied. This study examined the association between measures of carotid atherosclerosis and fall-related hospitalization over 11.5 years in community dwelling older women. METHODS AND RESULTS: 1116 older women recruited in 1998 to a five-year randomized controlled trial to examine the effect of calcium supplementation in preventing fracture and who had undertaken B-mode ultrasound in 2001 (three years after the baseline clinical visit) were included in this study. The participants were followed for over 11.5 years as Perth Longitudinal Study of Ageing Women (PLSAW). Over the follow up period, 428 (38.4%) women experienced a fall-related hospitalization. Older women with carotid plaque had 44% a higher relative hazard for fall-related hospitalization (HR 1.44; 95%CI, 1.18 to 1.76) compared to those without carotid plaque. The association persisted after adjustment for established falls risk factors such as measures of muscle strength and physical function.Each SD increase in the mean and maximum CCA-IMT was also associated with a higher risk of fall-related hospitalizations (HR 1.10; 95%CI, 1.00 to 1.21 and HR 1.11; 95%CI, 1.01 to 1.22, respectively). CONCLUSIONS: Measures of carotid atherosclerosis are associated with a higher risk of fall-related hospitalization independent of established falls risk factors. These findings suggest the importance of vascular health when considering falls risk.


Subject(s)
Carotid Artery Diseases , Plaque, Atherosclerotic , Humans , Female , Aged , Male , Longitudinal Studies , Accidental Falls/prevention & control , Carotid Intima-Media Thickness , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Risk Factors , Aging , Hospitalization , Carotid Artery, Common/diagnostic imaging
15.
J Gerontol A Biol Sci Med Sci ; 78(7): 1147-1154, 2023 Jul 08.
Article in English | MEDLINE | ID: mdl-36000920

ABSTRACT

BACKGROUND: Abdominal aortic calcification (AAC) has been inconsistently associated with skeletal health. We aimed to investigate the association of AAC with bone mineral density (BMD) and fracture risk by pooling the findings of observational studies. METHODS: MEDLINE, EMBASE, Web of Science, and Google Scholar were searched (August 2021). All clinical studies that assessed the association between AAC and BMD or fracture were included. AAC was categorized into any/advanced (all higher reported groups) versus no/less advanced (lowest reported group). Pooled standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CI) were determined for BMD and fracture, respectively, using random-effects models. RESULTS: Of 2 192 articles screened, 86 (61 553 participants) were included in the review, while 42 provided data for meta-analysis. AAC was associated with lower BMD at the total hip (SMD = -1.05 [95%CI: -1.47 to -0.63]; 16 studies), femoral neck (-0.25 [-0.46 to-0.04]; 10), and lumbar spine (-0.67 [-1.21 to -0.12]; 20). AAC was associated with a greater risk of any fracture (RR = 1.73 [95%CI: 1.48-2.02]; 27). AAC was also associated with vertebral, non-vertebral, and hip fractures. In dose-response analysis, the highest AAC group had greater risks of any, vertebral and non-vertebral fractures. CONCLUSIONS: AAC is associated with lower BMD and increased fracture risk at multiple sites, underscoring the potential importance of vascular disease on skeletal health. Detection of AAC at the time of BMD testing may provide clinicians with prognostic information about bone health to enhance osteoporosis screening programs and fracture risk prediction.


Subject(s)
Fractures, Bone , Hip Fractures , Vascular Diseases , Humans , Bone Density/physiology , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Lumbar Vertebrae/diagnostic imaging
16.
Bone ; 167: 116610, 2023 02.
Article in English | MEDLINE | ID: mdl-36372197

ABSTRACT

Osteoporosis medications have been reported to have beneficial and harmful cardiovascular effects. Much of this evidence stems from single reports and as such, a comprehensive examination of the evidence is needed. We conducted a network meta-analysis (NMA) of cardiovascular adverse event (CAE) data from randomized trials of osteoporosis medications in postmenopausal women. Trials were identified from recent NMAs of osteoporosis treatment for fracture reduction with an updated literature search (December 2020). Included studies were randomized, included over 100 participants, and reported skeletal primary outcomes. We investigated three-point major adverse cardiovascular events (MACE3), four- (MACE4) and five-point MACE (MACE5), as well as myocardial infarction (MI) and stroke. Data were synthesized in a random-effects network meta-analysis using Bayesian modelling. Probabilistic ranking of treatment safety was performed. Relative to placebo, point estimates for the odds ratios (OR) with 95 % credible intervals (CrI) were also generated. We identified 75 trials (n = 136,940 women), of which 27 (68,699 women, nine arms) reported CAEs. In women randomized to placebo, the overall event rate for the MACE3 outcome was 2.58 % compared with 1.99 % in those randomized to all other active comparators. Probabilistic ranking found abaloparatide, oral bisphosphonates, teriparatide, and menopausal hormone therapy were less likely to have increased risk of CAEs than placebo, while romosozumab ranked more likely to have increased risk of CAEs than placebo for all outcomes. Compared with placebo, abaloparatide (one trial, n = 1642) was associated with a reduced odds for MACE3 (OR = 0·31; 95%CrI: 0·06 to 0·99), MACE4 (0·28; 0·06 to 0·88) and MACE5 (0·25; 0·06 to 0·79). When all PTH analogues were grouped together, magnitude and direction of effects were consistent but no longer statistically significant. We did not find pooled direct and indirect evidence that osteoporosis treatments significantly increased the risk of adverse cardiovascular events relative to placebo. (PROSPERO: CRD42020178702).


Subject(s)
Cardiovascular Diseases , Osteoporosis, Postmenopausal , Osteoporosis , Humans , Female , Postmenopause , Network Meta-Analysis , Bayes Theorem , Randomized Controlled Trials as Topic , Cardiovascular Diseases/drug therapy , Osteoporosis, Postmenopausal/drug therapy
17.
Eur J Nutr ; 62(2): 951-964, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36333495

ABSTRACT

PURPOSE: Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency. METHODS: Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups. RESULTS: Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes. CONCLUSION: Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.


Subject(s)
Overweight , Vitamin D Deficiency , Humans , Aged , Middle Aged , Pilot Projects , Dietary Supplements , Obesity , Vitamin D , Vitamins , Cholecalciferol , Body Composition , Double-Blind Method
18.
J Shoulder Elbow Surg ; 32(2): 374-382, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36206982

ABSTRACT

INTRODUCTION: Glenoid reconstruction is indicated for recurrent glenohumeral instability with significant glenoid bone deficiency. Coracoid autograft (Latarjet) and distal tibial osteochondral allograft (DTA) reconstructions have been used to successfully restore glenohumeral stability. Relative advantages and disadvantages associated with each reconstruction technique have been described. However, direct comparisons of functional glenohumeral biomechanics associated with Latarjet vs. DTA reconstruction are lacking. This study was designed to compare these 2 glenoid reconstruction techniques with respect to joint kinematics and cartilage pressure mapping using a robotic testing system. METHODS: In accordance with institutional review board policies, human cadaveric shoulders (n = 8) were cyclically tested in the neutral position and 90° of external rotation with 60° and 90° of abduction under a 45-N joint-compression load to measure clinically relevant translations, loads, and torques. Joint contact pressure maps were obtained under a 120-N joint-compression load using pressure mapping sensors. After confirming that a 25% anterior glenoid defect resulted in glenohumeral dislocation, testing was performed to compare 3 conditions: native intact glenoid, 25% anterior glenoid defect with Latarjet reconstruction, and 25% anterior glenoid defect with DTA reconstruction. Analyses of variance and t tests were used to analyze data with statistical significance set at P < .05. RESULTS: Significant differences in anterior translation, inferior drawer, anterior drawer, compression loads, horizontal abduction, negative elevation (adduction), and external rotation torques during cyclical testing in 90° of external rotation with 60° and/or 90° of abduction were noted when comparing the 2 different glenoid bone reconstruction techniques to native, intact shoulders. The only significant difference between Latarjet and DTA reconstructions for measured translations, loads, and torques was a significantly higher absolute maximum compressive load for Latarjet compared to DTA at 60° of abduction. CONCLUSION: Latarjet coracoid osseous autograft and distal tibial osteochondral allograft reconstructions of large (25%) glenoid bone defects prevent failure (dislocation) and are associated with significant glenohumeral kinematic differences that largely confer less translation, load, and torque on the joint in abduction when compared to the native state. These findings suggest that these 2 surgical techniques exhibit similar glenohumeral kinematics such that each provides adequate functional stability following anterior glenoid bone reconstruction. Joint compression load and articular contact pressure distribution may favor distal tibial osteochondral allograft reconstruction for treatment of large (25%) anterior glenoid bone defects associated with shoulder instability.


Subject(s)
Joint Instability , Shoulder Dislocation , Shoulder Joint , Humans , Shoulder Joint/surgery , Joint Instability/surgery , Bone Transplantation/methods , Cadaver , Shoulder Dislocation/surgery , Biomechanical Phenomena , Allografts
19.
medRxiv ; 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38168429

ABSTRACT

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. Forecasting teams were asked to provide national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one through four weeks ahead for the 2021-22 and 2022-23 influenza seasons. Across both seasons, 26 teams submitted forecasts, with the submitting teams varying between seasons. Forecast skill was evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperformed the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble was the 2nd most accurate model measured by WIS in 2021-22 and the 5th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degraded over longer forecast horizons and during periods of rapid change. Current influenza forecasting efforts help inform situational awareness, but research is needed to address limitations, including decreased performance during periods of changing epidemic dynamics.

20.
JBMR Plus ; 6(6): e10628, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35720664

ABSTRACT

[This corrects the article DOI: 10.1002/jbm4.10522.].

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