Weight gain and the risk of total hip replacement a population-based prospective cohort study of 265,725 individuals

SummaryObjectiveTo study the association between change in the body mass index (BMI) at different ages and the risk of a later total hip replacement (THR) due to primary osteoarthritis (OA).DesignA total of 265,725 individuals who had two repeated measurements of weight and height were included from national health screenings. These individuals were followed prospectively. The data were matched with the Norwegian Arthroplasty Register and 4,442 of these individuals were identified as having received a THR for primary OA. Cox proportional hazard regression was used to calculate sex-specific relative risks for having a THR according to age at screening and BMI change.ResultsMen and women aged 20 years or younger at the first screening in the quartile with the greatest BMI change per year had more than twice the risk of later having a THR compared with those in the quartile with the smallest BMI change per year. For men older than 30 years at the first screening, there was no relationship between BMI gain, or weight gain, and later risk of THR. For older women, BMI gain was associated with risk of THR, but to a lesser degree than in younger women.ConclusionThere was a clear relationship between change in BMI and the risk of later THR in young men and women, whereas the association was absent in older men and weaker in older women. It is important to focus on weight control to prevent future OA, and the preventive strategy should be focused on the young population

Hoarding disorder: A new obsessive-compulsive related disorder in DSM-5

Obsessive-compulsive disorder (OCD) and related disorders have been the subject of significant revisions in the fifth edition of the Diagnostic and Statistical Manual (DSM-5). One of these major changes has been the removal of OCD from the \u2018Anxi- ety Disorders\u2019 section and its instalment in a new and distinct Obsessive-Compulsive and Related Disorders (OCRDs) chap- ter. However, it is the instatement of Hoarding Disorder (HD) as a new OCRD that marks the most significant change. Previously considered a symptom of OCPD, and subsequently linked to OCD, it is now acknowledged that hoarding can emerge inde- pendently from any alternative condition. The present paper provides an updated review of recent investigations supporting the status of HD as an independent nosological entity. Specifi- cally, we will present the new DSM-5 diagnostic criteria and examine the literature pertaining to the psychopathological and phenomenological aspects of the disorder, with particular atten- tion to practical strategies that can help clinicians to recognise and differentiate HD from OCD. Finally, the available assess- ment and treatment strategies for HD are summarised

MicroBundleCompute: Automated segmentation, tracking, and analysis of subdomain deformation in cardiac microbundles

Advancing human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) technology will lead to significant progress ranging from disease modeling, to drug discovery, to regenerative tissue engineering. Yet, alongside these potential opportunities comes a critical challenge: attaining mature hiPSC-CM tissues. At present, there are multiple techniques to promote maturity of hiPSC-CMs including physical platforms and cell culture protocols. However, when it comes to making quantitative comparisons of functional behavior, there are limited options for reliably and reproducibly computing functional metrics that are suitable for direct cross-system comparison. In addition, the current standard functional metrics obtained from time-lapse images of cardiac microbundle contraction reported in the field (i.e., post forces, average tissue stress) do not take full advantage of the available information present in these data (i.e., full-field tissue displacements and strains). Thus, we present "MicroBundleCompute," a computational framework for automatic quantification of morphology-based mechanical metrics from movies of cardiac microbundles. Briefly, this computational framework offers tools for automatic tissue segmentation, tracking, and analysis of brightfield and phase contrast movies of beating cardiac microbundles. It is straightforward to implement, requires little to no parameter tuning, and runs quickly on a personal computer. In this paper, we describe the methods underlying this computational framework, show the results of our extensive validation studies, and demonstrate the utility of exploring heterogeneous tissue deformations and strains as functional metrics. With this manuscript, we disseminate "MicroBundleCompute" as an open-source computational tool with the aim of making automated quantitative analysis of beating cardiac microbundles more accessible to the community.Comment: 16 main pages, 7 main figures, Supplementary Information included as appendice

Weight gain and the risk of total hip replacement a population-based prospective cohort study of 265,725 individuals

s u m m a r y Objective: To study the association between change in the body mass index (BMI) at different ages and the risk of a later total hip replacement (THR) due to primary osteoarthritis (OA). Design: A total of 265,725 individuals who had two repeated measurements of weight and height were included from national health screenings. These individuals were followed prospectively. The data were matched with the Norwegian Arthroplasty Register and 4,442 of these individuals were identified as having received a THR for primary OA. Cox proportional hazard regression was used to calculate sexspecific relative risks for having a THR according to age at screening and BMI change. Results: Men and women aged 20 years or younger at the first screening in the quartile with the greatest BMI change per year had more than twice the risk of later having a THR compared with those in the quartile with the smallest BMI change per year. For men older than 30 years at the first screening, there was no relationship between BMI gain, or weight gain, and later risk of THR. For older women, BMI gain was associated with risk of THR, but to a lesser degree than in younger women. Conclusion: There was a clear relationship between change in BMI and the risk of later THR in young men and women, whereas the association was absent in older men and weaker in older women. It is important to focus on weight control to prevent future OA, and the preventive strategy should be focused on the young population. Ó , as is previous joint injury Weight reduction has proven effective in relieving pain in symptomatic knee OA 15 , and it has been associated with lower risk of knee OA later in life 17 . An increase in BMI in early adult life was associated more strongly with later knee OA than an increase in BMI in middle age Health Study included 93,442 female nurses and found a moderate effect of weight gain from the age of 18 years until the date of THR, and no effect of weight loss 20 . A third study investigated the effect of weight change between ages 20 and 49 years on self-reported hip OA in 1,180 male physicians 18 . This study found no effect of weight change, but with only 26 men reporting hip OA, the power to detect an association was limited. In the Nurses' Health Study, the recalled BMI at 18 years was highly associated with later THR, more than BMI close to the date of TH

Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone

<p>Abstract</p> <p>Background</p> <p>All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO) and the PPARγ agonist pioglitazone (PIO) on bone in intact female rats.</p> <p>Methods</p> <p>Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied.</p> <p>Results</p> <p>The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1.</p> <p>Conclusion</p> <p>We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation.</p

Multiphysics computational modeling in <i>C</i>Heart

From basic science to translation, modern biomedical research demands computational models which integrate several interacting physical systems. This paper describes the infrastructural framework for generic multiphysics integration implemented in the software $\boldsymbol{\mathcal{C}}\mathbf{Heart}$, a finite-element code for biomedical research. To generalize the coupling of physics systems, we introduce a framework in which the geometric and operator relationships between the constituent systems are rigorously defined. We then introduce the notion of topological interfaces and define specific operators encompassing many common model coupling requirements. These interfaces enable the evaluation of weak form integrals between mesh subregions of arbitrary finite-element bases' orders, types, and spatial dimensions. Equation maps are introduced which provide abstract representations of the individual physics systems that can be automatically combined to permit a monolithic matrix assembly. Flexible solution strategies for the resulting coupled systems are implemented, permitting fine-tuning of solution updates during fixed point iterations, and subgrouping where several problems are being solved together. Partitioning of coupled mesh domains for optimal load balancing is also supported, taking into account the per-processor cost of the entire coupled problem within the graph problem. The demonstration of the performance is illustrated through important real-world multiphysics problems relevant to cardiac physiology

Effect of combined treatment with alendronate and calcitriol on femoral neck strength in osteopenic rats

<p>Abstract</p> <p>Background</p> <p>Hip fracture is associated with pronounced morbidity and excess mortality in elderly women with postmenopausal osteoporosis. Many drugs have been developed to treat osteoporosis and to reduce the risk of osteoporotic fractures. We investigated the effects of combined alendronate and vitamin D₃treatment on bone mass and fracture load at the femoral neck in ovariectomized (OVX) rats, and evaluated the relationship between bone mass parameters and femoral neck strength.</p> <p>Methods</p> <p>Thirty 12-week-old female rats underwent either a sham-operation (n = 6) or OVX (n = 24). Twenty weeks later, OVX rats were further divided into four groups and received daily doses of either saline alone, 0.1 mg/kg alendronate, 0.1 μg/kg calcitriol, or a combination of both two drugs by continuous infusion via Alzet mini-osmotic pumps. The sham-control group received saline alone. After 12 weeks of treatment, femoral necks were examined using peripheral quantitative computed tomography (pQCT) densitometry and mechanical testing.</p> <p>Results</p> <p>Saline-treated OVX rats showed significant decreases in total bone mineral content (BMC) (by 28.1%), total bone mineral density (BMD) (by 9.5%), cortical BMC (by 26.3%), cancellous BMC (by 66.3%), cancellous BMD (by 29.0%) and total cross-sectional bone area (by 30.4%) compared with the sham-control group. The combined alendronate and calcitriol treatments improved bone loss owing to estrogen deficiency. On mechanical testing, although OVX significantly reduced bone strength of the femoral neck (by 29.3%) compared with the sham-control group, only the combined treatment significantly improved the fracture load at the femoral neck in OVX rats to the level of the sham-controls. The correlation of total BMC to fracture load was significant, but that of total BMD was not.</p> <p>Conclusion</p> <p>Our results showed that the combined treatment with alendronate and calcitriol significantly improved bone fragility of the femoral neck in OVX osteopenic rats.</p