The spectrum of side effects associated with COVID-19 vaccines in patients with inborn errors of immunity.

OBJECTIVE: COVID-19 immunization was implemented with emergency-use authorization. We had concerns/lack of information on mRNA vaccine side effects in different inborn errors of immunity (IEI) types. METHODS: We enrolled 141 patients (IEIP) and 151 healthy controls(HC) who received SARS-CoV-2 vaccine/s(Sinovac and/or Pfizer-BioNTech(mRNA vaccine), one to five doses), questioned them for side-effects, evaluated in three groups according to the vaccine/s they received; only Sinovac, only Pfizer-BioNTech, and both vaccines. RESULTS: Arm pain, generalized weakness, myalgia, and fever were common side effects in IEI-P and HC groups. Generalized weakness/fatigue, fever, and palpitation were significantly frequent in IEI-P who experienced COVID-19 compared to those who did not (p = 0.021, p = 0.047, and p = 0.024, respectively). Severe symptoms after vaccination, new-onset splenomegaly and pancytopenia, urticaria, herpes simplex virus (HSV), and varicella zoster virus (VZV) reactivation were seen in four IEI-P (2.8%). CONCLUSION: IEI-P mRNA vaccination is relatively safe compared to the conventional vaccine. Individuals who experience uncommon side effects should undergo immunological screening.

Management of Osteoporosis, Fracture and Falls in People with Multiple Sclerosis: Systematic Review of Guidelines.

People with multiple sclerosis (MS) have a higher prevalence of osteoporosis, falls and fractures. Guidelines for MS populations targeting the management of osteoporosis, fracture and falls risk may help reduce the burden of musculoskeletal disease in this population. We aimed to systematically review current guidelines regarding osteoporosis prevention, screening, diagnosis and management in people with MS. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, a systematic review of scientific databases (MEDLINE, CINAHL, Embase and Scopus) was performed (n = 208). In addition, websites from MS organisations and societies were screened for clinical guidelines (n = 28). Following duplicate removal, screening and exclusions (n = 230), in total six guidelines were included in this review. Three of the identified guidelines were specific to managing osteoporosis in MS, while two linked vitamin D to bone health and one was focused on the effect of acute glucocorticoid use for MS exacerbations on bone health. All guidelines were found to contain inadequate recommendations for osteoporosis screening, management and treatment in people with MS given the evidence of higher prevalence of osteoporosis at an earlier age and compounding risk factors in this population. Early diagnosis and treatment of osteoporosis in people with MS is necessary as fractures lead to significant morbidity and mortality. Development of structured clinical guidelines directed at specific healthcare services will ensure screening, appropriate management, and care of bone health in people with MS.

Risk factors for incident cardiovascular events and their population attributable fractions in rural India: The Rishi Valley Prospective Cohort Study.

OBJECTIVE: We prospectively determined incident cardiovascular events and their association with risk factors in rural India. METHODS: We followed up with 7935 adults from the Rishi Valley Prospective Cohort Study to identify incident cardiovascular events. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) with 95% confidence intervals (95% CI) for associations between potential risk factors and cardiovascular events. Population attributable fractions (PAFs) for risk factors were estimated using R ('averisk' package). RESULTS: Of the 4809 participants without prior cardiovascular disease, 57.7% were women and baseline mean age was 45.3 years. At follow-up (median of 4.9 years, 23,180 person-years [PYs]), 202 participants developed cardiovascular events, equating to an incidence of 8.7 cardiovascular events/1000 PYs. Incidence was greater in those with hypertension (hazard ratio [HR] [95% CI] 1.73 [1.21-2.49], adjusted PAF 18%), diabetes (1.96 [1.15-3.36], 4%) or central obesity (1.77 [1.23, 2.54], 9%) which together accounted for 31% of the PAF. Non-traditional risk factors such as night sleeping hours and number of children accounted for 16% of the PAF. CONCLUSIONS: Both traditional and non-traditional cardiovascular risk factors are important contributors to incident cardiovascular events in rural India. Interventions targeted to these factors could assist in reducing the incidence of cardiovascular events.

The burden of rheumatologic disease in Aboriginal and Torres Strait Islander Australians.

The objective of this article is to summarise the current knowledge regarding the prevalence of six rheumatological conditions in indigenous Australians - rheumatoid arthritis (RA), osteoarthritis (OA), osteoporosis (OSP), systemic lupus erythematosus (SLE), gout and musculoskeletal (MSK) pain. Online medical literature databases were searched for 'indigenous', 'Aboriginal' and 'Torres Strait Islander', as well as the names of the six conditions. Other included search terms were 'crystal', 'urate', 'arthritis' and 'arthropathy'. No limitations were placed on publication data or language. Forty-five articles examining the prevalence of the six conditions were identified. Based on the published literature, SLE appears to have a higher prevalence, while RA appears to have a lower prevalence in indigenous Australians compared to the non-indigenous community. MSK pain is prevalent, has a significant impact on indigenous people and is perceived as an important area of need. There is a paucity of data regarding these conditions in indigenous Australians. This may be impacted by the uncertainty of case ascertainment by self-report, differences in disease phenotypes and prevalence between the metropolitan compared to the rural or remote indigenous population, and difficulty with access to healthcare. Further studies in conjunction with local indigenous communities are needed to accurately determine the burden of rheumatological disease in the indigenous population. This will assist with resource and workforce planning to deliver culturally appropriate interventions. Strategies for future clinical work and research include the development and dissemination of culturally safe rheumatology resources, rheumatology training of Aboriginal Health Workers and wider integration of rheumatology clinics into community-controlled Aboriginal Health Services.

Cross-Calibration of iDXA and pQCT Scanners at Rural and Urban Research Sites in The Gambia, West Africa.

Between-scanner differences in measures of bone and body composition can obscure or exaggerate physiological differences in multi-site studies or the magnitude of changes in longitudinal studies. We conducted a cross-calibration study at two bone imaging centres in The Gambia, West Africa where DXA (dual-energy X-ray absorptiometry) and pQCT (peripheral Quantitative-Computed Tomography) are routinely used. Repeat scans were obtained from 64 Gambian adults (58% Male) aged Mean(SD) 30.9 (13.5) years with Mean(SD) body mass index (BMI) 21.7 (4.0) kg/m2, using DXA (GE Lunar iDXA, whole body [WB], total hip [TH], lumbar spine [LS]) and pQCT (Stratec XCT2000L/XCT2000, tibia 4%, 50% sites). Between-scanner differences were tested using paired t tests (p < 0.05). Between-scanner correlation was explored with linear regression, and cross-calibration equations derived. Bland-Altman analysis investigated machine trend/bias. When differences were detected (p < 0.05), cross-calibration equations were applied to urban values, with t tests and Bland Altman analysis repeated. Between-scanner differences exceeded the predefined level of statistical significance (p < 0.05) for WB aBMD and BA; all pQCT measures vBMD, BMC, cortical cross-sectional area (CSA) and stress-strain index (SSI). Between-scanner correlation was high (R2:0.92-0.99), except pQCT Mu.Den (R2 = 0.51). Bland Altman plots indicated bias increased with increasing BMD. Cross-calibration equations attenuated all between-scanner differences and systematic bias. Cross-calibration, particularly of pQCT scanners, is an important consideration in multi-site studies particularly where between population comparisons are intended. Our experiences and findings may be generalisable to other resource-limited settings where the logistics of sourcing parts and in-country repair may result in lengthy scanner downtime.

Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial.

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.

Sex Differences in Bone Health Among Indian Older Adults with Obesity, Sarcopenia, and Sarcopenic Obesity.

Age-related changes in fat and lean mass contribute to bone health, but these associations may be influenced by sex and ethnicity. This study investigated sex-specific associations of obesity and sarcopenia with bone mineral density (BMD) and bone mineral apparent density (BMAD) among Indian older adults. 1057 adults aged ≥ 50 years were included. Dual-energy X-ray absorptiometry (DXA) measured BMD at the hip, spine and whole-body, and BMAD was calculated as BMD/√bone area. Obesity was defined by body fat percentage (cut points; > 25% for men and > 35% for women), and sarcopenia was defined using the revised Asian Working Group for Sarcopenia classification with low hand grip strength (< 28 kg for men and < 18 kg for women) and appendicular lean mass index (< 7.0 kg/m2 for men and < 5.4 kg/m2 for women). Participants were classified into four groups: controls (no obesity or sarcopenia), obesity, sarcopenia, or sarcopenic obesity. Linear regression (ß-coefficients and 95%CI) analyses were performed with adjustments for age, smoking status, protein intake, and socioeconomic status. Prevalence of sarcopenia (37%) and sarcopenic obesity (6%) were higher in men than women (17% and 4%, respectively). Compared with controls, men with obesity had lower whole-body BMD and BMAD, but women with obesity had higher hip and spine BMD and BMAD (all p < 0.05). Men, but not women, with sarcopenic obesity, had lower hip and whole-body BMD and BMAD (all p < 0.05) than controls. Men with sarcopenia had lower BMD and BMAD at the hip only, whereas women had lower BMD at all three sites and had lower BMAD at the hip and spine (all p < 0.05), compared with controls. Obesity, sarcopenia, and sarcopenic obesity have sex-specific associations with BMD and BMAD in Indian older adults. With the aging population in India, it is important to understand how body composition contributes to poor bone health among older adults.

Osteoporosis management and falls prevention in patients with haemophilia: Review of haemophilia guidelines.

INTRODUCTION: Patients with haemophilia (PWH) have a high prevalence of osteoporosis, falls and fractures at all ages. The role of haemophilia itself may contribute to low bone mineral density (BMD) due to coagulation factor deficiency. Guidelines for the management of osteoporosis, fracture and fall risk may help to reduce fracture and fall risk, and delay osteoporosis onset. AIM: We aim to review current haemophilia guidelines regarding osteoporosis prevention, screening, diagnosis and management, and fall prevention. METHOD: A database search (Ovid MEDLINE) revealed two haemophilia guidelines (World and British) published within the last ten years. Local Australian haemophilia guidelines were identified through a manual search. RESULTS: All haemophilia guidelines were found to contain inadequate recommendations for osteoporosis management and fall prevention due to a lack of evidence in the literature. CONCLUSION: Further studies are required to assess the trajectory of bone health in PWH, the mechanism of bone loss in PWH, and the effectiveness of weight-bearing exercises, interventions for fall prevention, screening programmes, and use of anti-osteoporosis medications in PWH across the lifecourse.

Risk factors for incident cardiovascular events among adults in low- and middle-income countries: A systematic review and meta-analysis of prospective cohort studies.

The relative contributions of risk factors for cardiovascular events at a population level has received little attention in low- and middle-income countries (LMICs). We estimated the population attributable fraction (PAF) of risk factors associated with incident cardiovascular events in LMICs. We searched six databases for relevant articles, supplemented with a manual search of reference lists. Articles included in the meta-analyses were those based on prospective community-based cohorts and incorporating adjusted hazard ratios (HR) or relative risks with 95% confidence intervals (95% CI) for associations between risk factors and a composite cardiovascular and/or stroke endpoint. Pooled HRs and 95% CI were calculated using the random effects model. We assessed heterogeneity using the I2 test and study quality using the Newcastle-Ottawa Scale. We calculated the PAF of each associated risk factor. The protocol was registered in PROSPERO (CRD42019122741). We identified 18 cohorts from LMICs with 1,125,846 participants, 77,045 composite cardiovascular events and 42,216 strokes. Substantial proportions of incident cardiovascular events were attributable to hypertension (HR [95% CI], 2.23 [2.01-2.48], PAF = 28%); current smoking (1.44 [1.31-1.58], PAF = 10%); and diabetes mellitus (1.93 [1.67-2.23], PAF = 8%). Other risk factors identified included number of children, depression, bone mineral density, and air pollution. A substantial proportion of incident cardiovascular events were linked to traditional metabolic and behavioural modifiable risk factors. However, other novel risk factors also appear to contribute. Targeting of these established and novel risk factors has the potential to reduce the burden of CVD in LMICs.

Prevalence of Sarcopenia and Relationships Between Muscle and Bone in Indian Men and Women.

Both ethnicity and age are important determinants of musculoskeletal health. We aimed to determine the prevalence of sarcopenia, assess the suitability of current diagnostic guidelines, and explore muscle-bone relationships in adults from India. A total of 1009 young (20-35 years) and 1755 older (> 40 years) men and women from existing studies were collated and pooled for the analysis. Dual-energy x-ray absorptiometry measured areal bone mineral density (aBMD) at the hip and spine, and fat and lean mass; hand dynamometer measured hand grip strength (HGS). Indian-specific cut-points for appendicular lean mass (ALM), ALM index (ALMI) and HGS were calculated from young Indian (-2SD mean) populations. Sarcopenia was defined using cut-points from The Foundations for the National Institutes of Health (FNIH), revised European Working Group on Sarcopenia in Older People (EWGSOP2), Asian Working Group for Sarcopenia (AWGS), and Indian-specific cut-points. Low lean mass cut-points were then compared for their predictive ability in identifying low HGS. The relationship between muscle variables (ALM, ALMI, HGS) and aBMD was explored, and sex differences were tested. Indian-specific cut-points (men-HGS:22.93 kg, ALM:15.41 kg, ALMI:6.03 kg/m2; women-HGS:10.76 kg, ALM:9.95 kg, ALMI:4.64 kg/m2) were lower than existing definitions. The Indian-specific definition had the lowest, while EWGSOP2 ALMI had the highest predictive ability in detecting low HGS (men:AUC = 0.686, women:AUC = 0.641). There were sex differences in associations between aBMD and all muscle variables, with greater positive associations in women than in men. The use of appropriate cut-points for diagnosing low lean mass and physical function is necessary in ethnic populations for accurate sarcopenia assessment. Muscle-bone relationships are more tightly coupled during ageing in Indian women than men.

Evaluation of the pharyngeal recess with cone-beam computed tomography.

PURPOSE: To evaluate the radiological anatomy of the pharyngeal recess (PR) by gender and age. METHODS: Images of patients who underwent cone-beam computed tomography (CBCT) were analyzed retrospectively. A total of 600 PRs (140 male, 160 female) were examined. PR depths, distances between the posterior nasal spine (PNS) and the posterior wall of the pharynx, right and left torus levatorius lengths, and distances between the right and left torus levatorius were measured on the axial plane passing through the PNS-basion point. RESULTS: PR depths differed significantly between age groups (right p = 0.030, left p = 0.047). The PR depths of individuals under 35 years of age were significantly higher than those of individuals aged 35 and over. Further, the distances between the PNS and the posterior wall of the pharynx differed significantly between age groups and between gender groups. The distances between the PNS and the posterior wall of the pharynx were shorter in patients under 35 years of age (p = 0.000). In terms of gender, these distances were significantly longer in males (p = 0.014). The distances between the right and left torus levatorius were also significantly longer in males (p = 0.029). CONCLUSION: The PR is the region in which nasopharyngeal carcinoma originates most frequently and is very important for early diagnosis. The present results indicated that this region can be examined with CBCT.

Sex-specific associations between insulin resistance and bone parameters in overweight and obese older adults.

OBJECTIVES: To determine sex-specific associations between insulin resistance and bone parameters measured by peripheral quantitative computed tomography in overweight and obese community-dwelling older adults. STUDY DESIGN: Cross-sectional study of 79 community-dwelling overweight and obese adults (mean ± SD age 62.8 ± 7.9 years; body mass index 32.3 ± 6.1 kg/m2 ; 58% women). MAIN OUTCOME MEASURES: Peripheral quantitative computed tomography assessed distal radius and tibia trabecular volumetric bone mineral density (vBMD) and proximal radius and tibia cortical vBMD, periosteal circumference, endosteal circumference and stress-strain index. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated from fasting glucose and insulin values. Lean mass was assessed using dual-energy X-ray absorptiometry. Total minutes of moderate and vigorous physical activity (MVPA) were calculated using the Active Australia Survey. RESULTS: Men and women in this cohort had no significant differences in fasting glucose and insulin concentrations, HOMA-IR values and diabetes prevalence (all P > 0.05). In women, HOMA-IR was positively correlated with proximal radius periosteal and endosteal circumference (r = 0.331; P = 0.034 and r = 0.325; P = 0.038, respectively). These associations became nonsignificant in multivariable regression analyses; however, HOMA-IR was negatively associated with proximal radius cortical vBMD (B = -4.79; 95% CI -8.66, -0.92) after adjusting for age, lean mass and MVPA. All associations between HOMA-IR and bone parameters became nonsignificant in a sensitivity analysis excluding individuals with diabetes, or self-reported use of glucose-lowering medications. There were no associations between HOMA-IR and bone parameters in men. CONCLUSIONS: Homeostatic Model Assessment of Insulin Resistance was negatively associated with radial cortical vBMD in overweight and obese older women, but not in men. Further studies are needed to clarify sex-specific associations between insulin resistance and bone health in overweight and obese older adults.

Low-carbohydrate, high-fat diets have sex-specific effects on bone health in rats.

PURPOSE: Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC-HF) could be detrimental for growth and bone health. In young male rats, LC-HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC-HF diets on bone health exist. METHODS: Twelve-week-old male and female Wistar rats were isoenergetically pair-fed either a control diet (CD), "Atkins-style" protein-matched diet (LC-HF-1), or ketogenic low-protein diet (LC-HF-2) for 4 weeks. In females, microcomputed tomography and histomorphometry analyses were performed on the distal femur. Sex hormones were analysed with liquid chromatography-tandem mass spectrometry, and endocrine parameters including GH and IGF-I were measured by immunoassay. RESULTS: Trabecular bone volume, serum IGF-I and the bone formation marker P1NP were lower in male rats fed both LC-HF diets versus CD. LC-HF diets did not impair bone health in female rats, with no change in trabecular or cortical bone volume nor in serum markers of bone turnover between CD versus both LC-HF diet groups. Pituitary GH secretion was lower in female rats fed LC-HF diet, with no difference in circulating IGF-I. Circulating sex hormone concentrations remained unchanged in male and female rats fed LC-HF diets. CONCLUSION: A 4-week consumption of LC-HF diets has sex-specific effects on bone health-with no effects in adult female rats yet negative effects in adult male rats. This response seems to be driven by a sex-specific effect of LC-HF diets on the GH/IGF system.

Evaluation of simulated periodontal defects via various radiographic methods.

OBJECTIVES: The aim of this study was to compare the diagnostic accuracy of conventional films and direct digital radiographs (DDR), in the determination of the depth and type of simulated periodontal intrabony defects. MATERIALS AND METHODS: Three types of periodontal intrabony defects (one, two, and three walled) were artificially created in dry mandibles. Standard radiographic images were taken with Ultraspeed, Ektaspeed, Insight films, and DDR. The radiographic images were evaluated by three oral radiologists to identify the type and depth of these defects on the radiographs. RESULTS: The average measured depth of the defects on the dry mandibles was 7.85 mm. The average depth of the type 1 defect on the radiographs was 7.19 mm, type 2 was 7.18 mm, and type 3 was 7.15 mm. The average depth of the defects via the Ultraspeed film was 7.15 mm, Ektaspeed film was 7.17 mm, Insight film was 7.19 mm, and DDR was 7.20 mm. Type 1, type 2, and type 3 defect depth measurements showed 8.9, 9.7, and 16.3% understated, respectively (p < 0.01). The accurate estimation rates of type 1, type 2, and type 3 defects were 93.8, 53, and 25.4%, respectively. CONCLUSIONS: Both radiographic techniques have the same diagnostic value and display the minor destructive changes in the bone. As the number of osseous walls increases, it becomes difficult to determine the defect type and morphology. Further research is needed to monitor the intrabony defects, with less radiation exposure. CLINICAL RELEVANCE: The accurate identification of defect type and depth depends on the number of walls, not the imaging methods.

Comparison of the performance of cardiovascular risk prediction tools in rural India: the Rishi Valley Prospective Cohort Study.

AIMS: We compared the performance of cardiovascular risk prediction tools in rural India. METHODS AND RESULTS: We applied the World Health Organization Risk Score (WHO-RS) tools, Australian Risk Score (ARS), and Global risk (Globorisk) prediction tools to participants aged 40-74 years, without prior cardiovascular disease, in the Rishi Valley Prospective Cohort Study, Andhra Pradesh, India. Cardiovascular events during the 5-year follow-up period were identified by verbal autopsy (fatal events) or self-report (non-fatal events). The predictive performance of each tool was assessed by discrimination and calibration. Sensitivity and specificity of each tool for identifying high-risk individuals were assessed using a risk score cut-off of 10% alone or this 10% cut-off plus clinical risk criteria of diabetes in those aged >60 years, high blood pressure, or high cholesterol. Among 2333 participants (10 731 person-years of follow-up), 102 participants developed a cardiovascular event. The 5-year observed risk was 4.4% (95% confidence interval: 3.6-5.3). The WHO-RS tools underestimated cardiovascular risk but the ARS overestimated risk, particularly in men. Both the laboratory-based (C-statistic: 0.68 and χ2: 26.5, P = 0.003) and non-laboratory-based (C-statistic: 0.69 and χ2: 20.29, P = 0.003) Globorisk tools showed relatively good discrimination and agreement. Addition of clinical criteria to a 10% risk score cut-off improved the diagnostic accuracy of all tools. CONCLUSION: Cardiovascular risk prediction tools performed disparately in a setting of disadvantage in rural India, with the Globorisk performing best. Addition of clinical criteria to a 10% risk score cut-off aids assessment of risk of a cardiovascular event in rural India. LAY SUMMARY: In a cohort of people without prior cardiovascular disease, tools used to predict the risk of cardiovascular events varied widely in their ability to accurately predict who would develop a cardiovascular event.The Globorisk, and to a lesser extent the ARS, tools could be appropriate for this setting in rural India.Adding clinical criteria, such as sustained high blood pressure, to a cut-off of 10% risk of a cardiovascular event within 5 years could improve identification of individuals who should be monitored closely and provided with appropriate preventive medications.

Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic ß-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.

Detection and characteristics of the gubernacular tract in supernumerary teeth on cone beam computed tomography.

OBJECTIVES: The aim of this study was to evaluate the prevalence and visualization of supernumerary teeth (ST) and imaging characteristics of their gubernacular tract (GT) using cone beam computed tomography (CBCT). METHODS: Presence and visualization of ST were retrospectively evaluated using 960 CBCT images. The imaging characteristics of GT were analyzed to determine various presentations of GT according to type, shape, and orientation of ST. RESULTS: ST were radiographically detected in 93 patients, for a prevalence of 9.7%. Premolar shaped ST were more common (p = 0.003). GT was detected in 104 (77.2%) of impacted ST and mostly found straight in shape (49.0%). It was most frequently observed in peridens (n = 51, 49.0%) followed by mesiodens (n = 41, 39.4%) and more frequently seen in premolar-like ST (n = 44, 42.3%). The mean length of the GT in mandible was 2.8 mm, the mean length of the GT in maxilla was 1.0 mm (p < 0.001). The mean angle of the GT in mandible was 17.0, and the mean angle of the GT in maxilla was 43.0 (p = 0.004). CONCLUSIONS: CBCT can be used for evaluations in dental practice to provide comprehensive information about ST and their GT characteristics. Clinicians should be able to identify the characteristics of GTs on CBCT for dental treatments, especially traction and extraction of ST.

Sex-specific associations between markers of arterial stiffness and bone mineral density in Indian men and women.

BACKGROUND: Osteoporosis and cardiovascular disease (CVD) share common risk factors, yet both are usually underdiagnosed in the absence of major complications. We investigated associations between arterial stiffness, cardiac workload, carotid intima media thickness (CIMT) and areal bone mineral density (aBMD) in Indian adults. METHODS: Men and women aged >45 years from the Andhra Pradesh Children and Parents Study (APCAPS) were included for cross-sectional analysis (521 women and 696 men). Dual energy x-ray absorptiometry (DXA) measured aBMD at the whole body, total hip and lumbar spine. Supine blood pressure and heart rate were measured and used to calculate rate pressure product and pulse pressure; augmentation index, pulse wave velocity and CIMT were measured. Sex-interactions were tested (denoted as p-int); adjustments were made for confounders. Data were expressed as SD differences with 95 % confidence intervals. RESULTS: There were significant negative associations between pulse pressure and aBMD at all sites in women only. In unadjusted analyses, for every 1SD increase in pulse pressure, women had greater negative differences in aBMD at the whole body (-0.13 vs 0.007), total hip (-0.20 vs -0.05) and lumbar spine (-0.12 vs 0.05) compared with men. After adjustments, sex differences remained. Similar negative associations were seen between pulse wave velocity and augmentation index with aBMD in women only. There were no sex differences between CIMT and rate pressure product with aBMD. CONCLUSIONS: Markers of arterial stiffness are associated with poorer bone health in Indian women, but not in men. There is a need to identify the shared risk factors and markers of arterial stiffness and poor bone health to detect those who require co-management of these diseases to prevent cardiovascular events and fractures.

Medication and bone health in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications incur decreases in areal bone mineral density (aBMD) and higher fracture risk in this population. OBJECTIVE: To investigate the effects of commonly used medications on aBMD and fracture risk among people with MS. METHODS: MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from their inception until February 5, 2023. We included randomized controlled trials as well as cross-sectional, retrospective, and prospective studies investigating whether glucocorticoids, immunomodulators, antidepressants, anticonvulsants, anxiolytics, opioids, or antipsychotics influenced aBMD or fracture risk in people with MS. Data were pooled using random effects meta-analyses to determine hazard ratios (HRs) and 95% CIs. RESULTS: We included 22 studies (n = 18,193). Six studies were included in the meta-analyses of glucocorticoid use and aBMD, whereas 2 studies were included in the medication use and fracture risk meta-analyses. No studies assessed the effect of antidepressants, anxiolytics, anticonvulsants, opioids, and antipsychotics on aBMD, and no studies assessed the effect of immunomodulators on fracture risk. Glucocorticoid use was significantly negatively associated with femoral neck aBMD (correlation = -0.21 [95% CI = -0.29 to -0.13]), but not with lumbar spine aBMD (correlation = -0.21 [95% CI = -0.50 to 0.12]). There were no differences in fracture risk between users of glucocorticoids (HR = 1.71 [95% CI = 0.04 to 76.47]), antidepressants (HR = 1.84 [95% CI = 0.09 to 38.49]), or anxiolytics (HR = 2.01 [95% CI = 0.06 to 64.22]), compared with nonusers. CONCLUSIONS: The available evidence is insufficient to support a relationship between greater fracture risk for people with MS taking glucocorticoid, antidepressant, or anxiolytic medication, compared with nonusers, and it is unclear whether these medications are associated with bone loss in people with MS, beyond that in the general population. Additional high-quality studies with homogenous methodology exploring how medications influence aBMD and fracture risk in people with MS are required.

Sustainability of a 12-month lifestyle intervention delivered by community health workers in reducing blood pressure in Nepal: 5-year follow-up of the COBIN open-label, cluster randomised trial.

BACKGROUND: The sustainability and scalability of limited-duration interventions in low-income and middle-income countries remain unclear. We aimed to investigate the sustainability in reduction of blood pressure through a 12-month lifestyle intervention led by community health workers to reduce blood pressure in Nepal, 4 years after the intervention ceased. METHODS: The Community-Based Intervention for Control of Hypertension in Nepal (COBIN) trial was a non-blinded, cluster-randomised trial done in Kaski, Nepal. Adults aged 25-65 years were eligible. People were excluded if they declined consent, were severely ill, unlikely to be in the community throughout the intervention, or pregnant. During the 12-month intervention, female community health volunteers (FCHVs) visited participants in the intervention groups and provided lifestyle counselling and blood pressure measurement every 4 months. At the end of the 12-month intervention, systolic blood pressure was significantly lower in the intervention group than in the usual care group in all cohorts, ranging from -2·3 mm Hg (95% CI -3·8 to -0·8) lower in those with normal blood pressure to -4·9 mm Hg (-7·8 to -2·0) in the hypertensive cohort. The primary outcome for this follow-up study was a mean change in systolic blood pressure from baseline to follow-up at 60 months. We did an intention-to-treat analysis. FINDINGS: Between April 1, 2015, and Dec 31, 2015, 1638 participants were recruited in COBIN (939 [57·3%] assigned to intervention and 699 [42·7%] assigned to usual care). Of the 1468 (89·6%) who completed the 12-month assessments, we followed up 1352 (92·1%) participants at 60 months, between Oct 11, 2020, and May 5, 2022. 964 (71·3%) participants were women and 388 (28·7%) were men. From baseline to 60 months, the mean systolic blood pressure increased by 10·4 mm Hg (95% CI 9·1-11·6) in the intervention group and 6·0 mm Hg (4·6-7·5) in the usual care group (adjusted mean difference 4·1 mm Hg [2·2 to 5·8]). INTERPRETATION: Lifestyle counselling and blood pressure monitoring by community health workers is effective in substantially reducing blood pressure while adults are being monitored in a trial but, following cessation of the intervention, this benefit is not maintained in the long term, with potential for harm. This finding could have important implications for funders and research communities to regularly target participants for education and follow-up at an optimal timepoint to reduce any likelihood of harm. FUNDING: Monash University (Melbourne, VIC, Australia) and the Jayanti Memorial Trust (Kathmandu, Nepal). TRANSLATION: For the Nepali translation of the abstract see Supplementary Materials section.