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Abstract In recent years, human anatomy education has faced challenges with traditional donor dissection, leading to the emergence of virtual dissection as an alternative. This study aims to investigate the academic performance and satisfaction of medical students by comparing the virtual and donor dissections. An open-labeled crossover randomized controlled trial was conducted with 154 first-year medical students in Human Anatomy and Neuroanatomy laboratories, which were divided into three classes. Students were randomly assigned to either the virtual (virtual dissection followed by donor dissection) or donor (donor dissection followed by virtual dissection) groups in each class. A curriculum, incorporating head-mounted displays (HMDs), a life-sized touchscreen, and tablets, was developed. Data was evaluated through quizzes and surveys. In the Human Anatomy laboratory, each class of the donor group conducted heart extraction, dissection and observation. In observation class, the virtual group had a significantly higher mean quiz score than the donor group (p

Abstract Nicotinamide adenine dinucleotide (NAD)+ serves as a crucial coenzyme in numerous essential biological reactions, and its cellular availability relies on the activity of the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed salvage pathway. Here we show that treatment with saturated fatty acids activates the NAD+ salvage pathway in hypothalamic astrocytes. Furthermore, inhibition of this pathway mitigates hypothalamic inflammation and attenuates the development of obesity in male mice fed a high-fat diet (HFD). Mechanistically, CD38 functions downstream of the NAD+ salvage pathway in hypothalamic astrocytes burdened with excess fat. The activation of the astrocytic NAMPT–NAD+–CD38 axis in response to fat overload induces proinflammatory responses in the hypothalamus. It also leads to aberrantly activated basal Ca2+ signals and compromised Ca2+ responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes. Our findings highlight the significant contribution of the hypothalamic astrocytic NAD+ salvage pathway, along with its downstream CD38, to HFD-induced obesity.

Abstract Response to digital healthcare lifestyle modifications is highly divergent. This study aimed to examine the association between single nucleotide polymorphism (SNP) genotypes and clinical efficacy of a digital healthcare lifestyle modification. We genotyped 97 obesity-related SNPs from 45 participants aged 18–39 years, who underwent lifestyle modification via digital cognitive behavioral therapy for obesity for 8 weeks. Anthropometric, eating behavior phenotypes, and psychological measures were analyzed before and after the intervention to identify their clinical efficacy. CETP (rs9939224) SNP significantly predict “super-responders” with greater body mass index (BMI) reduction (p = 0.028; GG − 2.91%, GT − 9.94%), while APOA2 (rs5082) appeared to have some potential for predicting “poor-responders” with lower BMI reduction (p = 0.005; AA − 6.17%, AG + 2.05%, and GG + 5.11%). These SNPs was also associated with significant differences in eating behavior changes, healthy diet proportions, health diet diversity, emotional and restrained eating behavior changes. Furthermore, classification using gene–gene interactions between rs9939224 and rs5082 significantly predicted the best response, with a greater decrease in BMI (p = 0.038; − 11.45% for the best response group (CEPT GT/TT × APOA2 AA) vs. + 2.62% for the worst response group (CEPT GG × APOA2 AG/GG)). CETP and APOA2 SNPs can be used as candidate markers to predict the efficacy of digital healthcare lifestyle modifications based on genotype-based precision medicine. Trial registration: NCT03465306, ClinicalTrials.gov. Registered March, 2018.

Abstract Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.

Purpose: Although eating is imperative for survival, few comprehensive methods have been developed to assess freely moving nonhuman primates' eating behavior. In the current study, we distinguished eating behavior into appetitive and consummatory phases and developed nine indices to study them using manual and deep learning-based (DeepLabCut) techniques. Method: The indices were utilized to three rhesus macaques by different palatability and hunger levels to validate their utility. To execute the experiment, we designed the eating behavior cage and manufactured the artificial food. The total number of trials was 3, with 1 trial conducted using natural food and 2 trials using artificial food. Result: As a result, the indices of highest utility for hunger effect were approach frequency and consummatory duration. Appetitive composite score and consummatory duration showed the highest utility for palatability effect. To elucidate the effects of hunger and palatability, we developed 2D visualization plots based on manual indices. These 2D visualization methods could intuitively depict the palatability perception and hunger internal state. Furthermore, the developed deep learning-based analysis proved accurate and comparable with manual analysis. When comparing the time required for analysis, deep learning-based analysis was 24-times faster than manual analysis. Moreover, temporal and spatial dynamics were visualized via manual and deep learning-based analysis. Based on temporal dynamics analysis, the patterns were classified into four categories: early decline, steady decline, mid-peak with early incline, and late decline. Heatmap of spatial dynamics and trajectory-related visualization could elucidate a consumption posture and a higher spatial occupancy of food zone in hunger and with palatable food. Discussion: Collectively, this study describes a newly developed and validated multi-phase method for assessing freely moving nonhuman primate eating behavior using manual and deep learning-based analyses. These effective tools will prove valuable in food reward (palatability effect) and homeostasis (hunger effect) research.

Eating behviours consist of seeking and consummatory phases. Here, authors show that two distinct lateral hypothalamic leptin receptor neurons orchestrate seeking and consummatory phases of eating behaviour via hunger signal, Neuropeptide Y.

Abstract The human facial skeleton consists of multiple segments and causes difficulty during analytic processes. We developed image analysis software to quantify the amount of injury and validate the smooth curvature of the surface after facial bone reduction surgery. Three-dimensional computed tomography images of facial bone were obtained from 40 patients who had undergone open reduction surgery to treat unilateral zygomaticomaxillary fractures. Analytic software was developed based on the discrete curvature of a triangular mesh model. The discrete curvature values were compared before and after surgery using two regions of interest. For the inferior orbital rim, the weighted average of curvature changed from 0.543 ± 0.034 to 0.458 ± 0.042. For the anterior maxilla, the weighted average of curvature changed from 0.596 ± 0.02 to 0.481 ± 0.031, showing a significant decrement (P

Abstract Human voice recognition techniques have remarkable potential for clinical applications because information from acoustic signals can reflect human body conditions. This paper reports the fabrication of Ag nanocrystal (NC)-based multiaxial wearable strain gauge sensors by ink-lithography for voice recognition systems. Benefiting from the one-step-device-fabrication strategy of ink-lithography, which can yield Ag NC patterns with specific dimensions and endow physical properties, the Ag NC-based multiaxial strain sensors can be fabricated on an ultrathin substrate (~ 6 μm). Additionally, the coffee-ring effect can be induced onto the Ag NC patterns to realize high sensitivity and angle dependence (gauge factors $${G}_{0^\circ }$$ G 0 ∘ = 11.7 ± 1.2 and $${G}_{90^\circ }$$ G 90 ∘ = 105.5 ± 20.1); moreover, the voice onset time for voice recognition can be detected by the sensors. These features assist in distinguishing between voiced and voiceless plosive contrasts via measurements of contact-based voice onset time differences and can act as a cornerstone for further advancements in wearable sensors as well as voice recognition and analysis. Graphical Abstract

ObjectiveThe hypothalamus regulates energy homeostasis, and its damage results in severe obesity. We aimed to investigate the multifaceted characteristics of hypothalamic obesity.MethodsWe performed multidimensional analyses of brain structure/function and psychological and behavioral phenotypes in 29 patients with hypothalamic damage (HD) (craniopharyngioma) and 31 controls (non-functional pituitary adenoma). Patients underwent structural and functional magnetic resonance imaging and completed self-reports and cognitive tasks.ResultsPatients with HD showed significantly higher postoperative weight gain than controls. The HD group also showed significant hypothalamic damage and lower neural activation in the left caudate nucleus in response to food images. The HD group had significantly higher food inattention, lower satiety, and higher restrained eating behavior. Within the HD group, higher restrained eating behavior was significantly associated with lower activation in the bilateral fusiform gyrus.ConclusionThese results suggest that hypothalamic damage contributes to weight gain by altering the brain response, attention, satiety, and eating behaviors. The present study proposes novel neuro-psycho-behavioral mechanisms targeted for patients with hypothalamic obesity.

Abstract Suicide is a leading cause of death worldwide, presenting a serious public health problem. We aimed to investigate the biological basis of suicide completion using proteomics on postmortem brain tissue. Thirty-six postmortem brain samples (23 suicide completers and 13 controls) were collected. We evaluated the proteomic profile in the prefrontal cortex (Broadmann area 9, 10) using tandem mass tag-based quantification with liquid chromatography–tandem mass spectrometry. Bioinformatics tools were used to elucidate the biological mechanisms related to suicide. Subgroup analysis was conducted to identify common differentially expressed proteins among clinically different groups. Of 9801 proteins identified, 295 were differentially expressed between groups. Suicide completion samples were mostly enriched in the endocannabinoid and apoptotic pathways (CAPNS1, CSNK2B, PTP4A2). Among the differentially expressed proteins, GSTT1 was identified as a potential biomarker among suicide completers with psychiatric disorders. Our findings suggest that the previously under-recognized endocannabinoid system and apoptotic processes are highly involved in suicide.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) (PETFDG) image can visualize neuronal injury of the brain in Alzheimer’s disease. Early-phase amyloid PET image is reported to be similar to PETFDG image. This study aimed to generate PETFDG images from 18F-florbetaben PET (PETFBB) images using a generative adversarial network (GAN) and compare the generated PETFDG (PETGE-FDG) with real PETFDG (PETRE-FDG) images using the structural similarity index measure (SSIM) and the peak signal-to-noise ratio (PSNR). Materials and Methods: Using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, 110 participants with both PETFDG and PETFBB images at baseline were included. The paired PETFDG and PETFBB images included six and four subset images, respectively. Each subset image had a 5 min acquisition time. These subsets were randomly sampled and divided into 249 paired PETFDG and PETFBB subset images for the training datasets and 95 paired subset images for the validation datasets during the deep-learning process. The deep learning model used in this study is composed of a GAN with a U-Net. The differences in the SSIM and PSNR values between the PETGE-FDG and PETRE-FDG images in the cycleGAN and pix2pix models were evaluated using the independent Student’s t-test. Statistical significance was set at p ≤ 0.05. Results: The participant demographics (age, sex, or diagnosis) showed no statistically significant differences between the training (82 participants) and validation (28 participants) groups. The mean SSIM between the PETGE-FDG and PETRE-FDG images was 0.768 ± 0.135 for the cycleGAN model and 0.745 ± 0.143 for the pix2pix model. The mean PSNR was 32.4 ± 9.5 and 30.7 ± 8.0. The PETGE-FDG images of the cycleGAN model showed statistically higher mean SSIM than those of the pix2pix model (p < 0.001). The mean PSNR was also higher in the PETGE-FDG images of the cycleGAN model than those of pix2pix model (p < 0.001). Conclusions: We generated PETFDG images from PETFBB images using deep learning. The cycleGAN model generated PETGE-FDG images with a higher SSIM and PSNR values than the pix2pix model. Image-to-image translation using deep learning may be useful for generating PETFDG images. These may provide additional information for the management of Alzheimer’s disease without extra image acquisition and the consequent increase in radiation exposure, inconvenience, or expenses.

In recent years, digital technologies have rapidly advanced and are being applied to remedy medical problems. These technologies allow us to monitor and manage our physical and mental health in our daily lives. Since lifestyle modification is the cornerstone of the management of obesity and eating behavior problems, digital therapeutics (DTx) represent a powerful and easily accessible treatment modality. This review discusses the critical issues to consider for enhancing the efficacy of DTx in future development initiatives. To competently adapt and expand public access to DTx, it is important for various stakeholders, including health professionals, patients, and guardians, to collaborate with other industry partners and policy-makers in the ecosystem.

Background and Objectives: The optimal assessment of cognitive function, including the impact of education, is crucial in managing Alzheimer’s disease (AD). This study aimed to evaluate the role of cognitive reserve (CR), represented by the metabolic status of regions of the cerebral cortex, to evaluate cognitive decline considering the educational attainment of patients with AD. Materials and Methods: We used data from the Alzheimer’s Disease Neuroimaging Initiative database, and selected 124 patients who underwent both baseline F-18 fluorodeoxyglucose (FDG) and F-18 florbetaben (FBB) positron emission tomography (PET) scans. Demographics, cognitive function variables (Clinical Dementia Rating—Sum of Boxes [CDR]; AD Assessment Scale 11/13 [ADAS11/13] Mini-Mental State Examination [MMSE]), and the average standardized uptake value ratio (SUVR) of cerebral cortex regions to those of the cerebellum were obtained from the data. The participants’ education level was divided into low and high education subgroups using four cut-offs of 12, 14, 16, and 18 years of educational attainment (G12, G14, G16, and G18, respectively). Demographic and cognitive function variables were compared between the two subgroups in each of the four groups, and their correlations with the SUVRs were evaluated. Results: There was no significant difference between the high and low education subgroups in each of the four groups, except for ADAS11/13 and MMSE in G14 and age in G16. The SUVRs of FDG PET (FDGSUVR) were significantly correlated with CDR, ADAS11/13, and MMSE scores. FDGSUVR showed different trajectories of neurodegeneration between the low and high education groups. Conclusions: FDGSUVR correlated moderately but significantly with neuropsychological test results, without being influenced by education level. Therefore, FDG PET may reflect CR independent of education level, and therefore could be a reliable tool to evaluate cognitive decline in AD.

BackgroundTo investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues.MethodsIn a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum buffet.ResultsObese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic substantially undermined medical education and healthcare systems. Owing to the pandemic in South Korea, most medical schools needed to be flexible when conducting online and offline classes, but the guidelines did not reflect the specificity of medical schools. This study described the impact of modified anatomy education schedules at the Seoul National University College of Medicine (SNUCM) on students' academic performance and satisfaction.MethodsAnatomy education in SNUCM is divided into three regional units (the upper and lower limbs, trunk, and head and neck). Owing to the COVID-19 pandemic, the schedule was mixed with simultaneous and rotating schedules. The authors conducted exceptions for online lectures, cadaver dissections, and written and practical examinations in three classes of approximately 50 students each. Furthermore, the authors assessed students' performance using three sets of written and practical examinations, and students completed a questionnaire regarding modified anatomy laboratory schedules.ResultsDespite the pandemic events in Seoul and South Korea during the laboratory sessions, all sessions were completed without any confirmed COVID-19 cases among the students, faculty, and staff. Most of the scores on the written and practical examinations significantly decreased in 2020 compared to those in 2019. However, in the trunk session that used the virtual anatomy application, the score on the practical examination in 2020 was significantly higher than that in 2019. Over 70% (79 and 77 out of 105 respondents on the upper and lower limbs and trunk, respectively) and 53% (55/105) students reported that there were no significant difficulties in studying anatomy in a face-to-face laboratory.ConclusionsIn conclusion, an adequate education program for cadaver dissection should be developed and provided to overcome the pandemic restrictions. The study findings could serve as a reference for anatomy education during the COVID-19 pandemic.

ObjectiveSeveral attempts have been done to capture damaged hypothalamus (HT) using volumetric measurements to predict the development of hypothalamic obesity in patients with craniopharyngioma (CP). This study was to develop a novel method of HT volume measurement and examine the associations between postoperative HT volume and clinical parameters in patients with CP.MethodsWe included 78 patients with adult-onset CP who underwent surgical resection. Postoperative HT volume was measured using T1- and T2-weighted magnetic resonance imaging (MRI) with a slice thickness of 3 mm, and corrected for temporal lobe volume. We collected data on pre- and postoperative body weights, which were measured at the time of HT volume measurements.ResultsThe corrected postoperative HT volume measured using T1- and T2-weighted images was significantly correlated (r=0.51 [95% confidence interval (CI) 0.32 to 0.67], P

Obtaining a histological fingerprint from the in-vivo brain has been a long-standing target of magnetic resonance imaging (MRI). In particular, non-invasive imaging of iron and myelin, which are involved in normal brain functions and are histopathological hallmarks in neurodegenerative diseases, has practical utilities in neuroscience and medicine. Here, we propose a biophysical model that describes the individual contribution of paramagnetic (e.g., iron) and diamagnetic (e.g., myelin) susceptibility sources to the frequency shift and transverse relaxation of MRI signals. Using this model, we develop a method, χ-separation, that generates the voxel-wise distributions of the two sources. The method is validated using computer simulation and phantom experiments, and applied to ex-vivo and in-vivo brains. The results delineate the well-known histological features of iron and myelin in the specimen, healthy volunteers, and multiple sclerosis patients. This new technology may serve as a practical tool for exploring the microstructural information of the brain.

BackgroundThe digital health care community has been urged to enhance engagement and clinical outcomes by analyzing multidimensional digital phenotypes. ObjectiveThis study aims to use a machine learning approach to investigate the performance of multivariate phenotypes in predicting the engagement rate and health outcomes of digital cognitive behavioral therapy. MethodsWe leveraged both conventional phenotypes assessed by validated psychological questionnaires and multidimensional digital phenotypes within time-series data from a mobile app of 45 participants undergoing digital cognitive behavioral therapy for 8 weeks. We conducted a machine learning analysis to discriminate the important characteristics. ResultsA higher engagement rate was associated with higher weight loss at 8 weeks (r=−0.59; P

What drives us to eat? It is one of the most fundamental questions in the obesity research field which have been investigated for centuries. Numerous novel in vivo technologies in the neuroscience field allows us to reevaluate the multiple components and phases of food-related behaviors. Focused on the cognitive, executive, behavioral and temporal aspects, food-related behaviors can be distinguished into appetitive phase (food craving→food seeking) and consummatory phase (food consumption). Food craving phase is an internal state or stage in which the animal has the motivation to eat the food but there is no actual food specific behaviors or actions. Food seeking phase entails repeated behaviors with a food searching purpose until the animal discovers the food (or food-related cue) and the approach behavior stage after the discovery of food. Food consumption phase is the step that the animal grabs, chews and intake the food. This review will specifically focus on characteristics and evaluation methods for each phase of food-related behavior in rodent, non-human primates and human.

Background and Objectives: Unstable thoracolumbar burst fractures require surgical management as they can result in neurological deficits if left untreated. This study aimed to evaluate whether a new bone scan scoring system could accurately assess instability in thoracolumbar burst fractures. Materials and Methods: Fifty-two patients with thoracolumbar burst fractures who underwent bone scans and magnetic resonance imaging prior to surgery between January 2015 and August 2017 at Ulsan University Hospital were selected for inclusion. Instability was determined by clinical assessment and imaging, and the Thoracolumbar Injury Classification and Severity score was determined. Bone scans were visually evaluated using a new bone scan scoring system. Bone scan findings of vertebral body (BB) and posterior column (BP) were scored separately and were summed to produce BTS {BTS (total score) = BB (body score, 5 points) + BP (posterior score, 2 points)}. The diagnostic performance of the scoring system for identifying unstable then thoracolumbar burst fractures were assessed. Results: Of the 52 thoracolumbar burst fractures, 34 (65.4%) were unstable and 31 (59.6%) had a Thoracolumbar Injury Classification and Severity score ≥ 5. The diagnostic performance of using BTS ≥ 4 to identify unstable thoracolumbar burst fractures and those with a Thoracolumbar Injury Classification and Severity score ≥ 5 was as follows: sensitivity, 61.8% and 58.1%; specificity, 94.4% and 81.0%; positive predictive value, 95.5% and 81.8%; and negative predictive value, 56.7% and 56.7%, respectively. Conclusions: The proposed bone scan scoring system has a high specificity and positive predictive value for identifying thoracolumbar burst fractures that are unstable or have a Thoracolumbar Injury Classification and Severity score ≥ 5. This scoring system may help to inform decisions regarding surgical management.

Objectives To identify optimum sample conditions for human brains, we compared the clearing efficiency, antibody staining efficiency, and artifacts between fresh and cadaver samples. Methods Fresh and cadaver samples were cleared using X-CLARITY™. Clearing efficiency and artifact levels were calculated using ImageJ, and antibody staining efficiency was evaluated after confocal microscopy imaging. Three staining methods were compared: 4-day staining (4DS), 11-day staining (11DS), and 4-day staining with a commercial kit (4DS-C). The optimum staining method was then selected by evaluating staining time, depth, method complexity, contamination, and cost. Results Fresh samples outperformed cadaver samples in terms of the time and quality of clearing, artifacts, and 4′,6-diamidino-2-phenylindole (DAPI) staining efficiency, but had a glial fibrillary acidic protein (GFAP) staining efficiency that was similar to that of cadaver samples. The penetration depth and DAPI staining improved in fresh samples as the incubation period lengthened. 4DS-C was the best method, with the deepest penetration. Human brain images containing blood vessels, cell nuclei, and astrocytes were visualized three-dimensionally. The chemical dye staining depth reached 800 µm and immunostaining depth exceeded 200 µm in 4 days. Conclusions We present optimized sample preparation and staining protocols for the visualization of three-dimensional macrostructure in the human brain.

Eating disorders, like binge eating, have a strong association with schizophrenia. Illness characteristics like disordered eating, cognition, and behavior can lead to eating disorders. Previous research highlighted the neurobiological structural similarity and the role of hormonal factors, like hypocretin, in the etiology of eating disorders in schizophrenia. Modifying the obesogenic environment by adapting healthy eating styles has been effective in reducing binging episodes. Antipsychotic medications also have a role in altering eating patterns that result in binge eating disorder. Adolescents with psychosis have a higher incidence of eating disorders. Here, we present an elderly female with schizophrenia who had obesogenic behaviors along with binge eating disorder. Interestingly, the patient had atypical age of onset and presentation and no psychopathological symptoms as a reason for binging.

Glucagon-like peptide-1 (GLP-1), whose agonists are widely prescribed, is a peptide proven effective in reducing obesity. Similarly, oxytocin (OXT) is a peptide known to increase satiety and help reduce body weight. In the present study, we aimed to examine the metabolic effects of co-administration of GLP-1 and OXT in diet-induced obesity (DIO) mice to elucidate their functions and interactions in the central nervous system. To this end, 40 DIO mice were subjected to stereotaxic surgery for the installation of an osmotic minipump and intracerebroventricular administration of GLP-1, OXT, or both. Initially, it was anticipated that co-administration of these anorexigenic peptides would be as effective as, if not more than, either GLP-1 or OXT alone in providing metabolic benefits to the obese mice. Interestingly, co-administration of OXT and GLP-1 offset the reductions in body weight and food intake promoted by either peptide alone. Co-administration also negated the decrease in fat and increase in lean mass produced by either peptide alone. Moreover, co-administration showed an equivalent calorimetric benefit as either peptide alone. Therefore, these results suggest antagonistic, rather than synergistic or additive, effects of centrally administered GLP-1 and OXT that attenuate the metabolic benefits of either peptide.

Phosphate overload contributes to mineral bone disorders that are associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and of negligible nutritional value in humans. However, the mechanism and adverse effects of high-phytate intake on Ca2+ and phosphate absorption and homeostasis are unknown. Here, we show that excessive intake of phytate along with a low-Ca2+ diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca2+ supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca2+-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca2+ bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca2+ diet and is a risk factor for phosphate overloading and for the development of crystal nephropathies and bone disease.

Diabetic retinopathy (DR) is a common complication of diabetes, and it is the consequence of microvascular retinal changes due to high glucose levels over a long time. Metabolomics profiling is a rapidly evolving method used to identify the metabolites in biological fluids and investigate disease progression. In this study, we used a targeted metabolomics approach to quantify the serum metabolites in type 2 diabetes (T2D) patients. Diabetes patients were divided into three groups based on the status of their complications: non-DR (NDR, n = 143), non-proliferative DR (NPDR, n = 123), and proliferative DR (PDR, n = 51) groups. Multiple logistic regression analysis and multiple testing corrections were performed to identify the significant differences in the metabolomics profiles of the different analysis groups. The concentrations of 62 metabolites of the NDR versus DR group, 53 metabolites of the NDR versus NPDR group, and 30 metabolites of the NDR versus PDR group were found to be significantly different. Finally, sixteen metabolites were selected as specific metabolites common to NPDR and PDR. Among them, three metabolites including total DMA, tryptophan, and kynurenine were potential makers of DR progression in T2D patients. Additionally, several metabolites such as carnitines, several amino acids, and phosphatidylcholines also showed a marker potential. The metabolite signatures identified in this study will provide insight into the mechanisms underlying DR development and progression in T2D patients in future studies.

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Abstract Background Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant hereditary disorder characterized by the presence of endocrine tumors affecting the parathyroid, pancreas, and pituitary. A heterozygous germline inactivating mutation in the MEN1 gene (first hit) may be followed by somatic loss of the remaining normal copy or somatic mutations in the MEN1 gene (second hit). Whole-exome sequencing has been successfully used to elucidate the mutations associated with the different types of tumors. Case presentation We performed whole-exome sequencing (WES) on three parathyroid tumors, one pancreatic insulinoma, and a blood sample taken from the same patient with MEN1 to study tumor heterogeneity in MEN1 originating from different tumors. We identified a novel frame-shift deletion (c.1382_1383delAG, p.E461GfsX69) in the MEN1 gene using WES, which was confirmed by Sanger sequencing. WES and the SNP array revealed somatic LOH on chromosome 11 in parathyroid tumors (left upper, left lower, and right upper parathyroid). However, we did not detect a somatic MEN1 gene mutation or LOH in the pancreatic insulinoma. WES revealed two somatic functional variants outside the MEN1 gene in the pancreatic insulinoma. Conclusions This study revealed heterogeneity among tumors in the same patient with MEN1, suggesting that different tumor-specific tumorigenic mechanisms may contribute to the pathogenesis of MEN1 tumors. The present study supports the clinical applicability of the WES strategy to research on multiple tumor samples and blood.

Abstract The relative contribution of lean mass and fat mass on bone health is inconclusive. We investigated the relative contributions of lean and fat masses on fragility fracture risk in Korean men and women. This was an ongoing prospective community-dwelling cohort study at Ansung beginning in 2001, which included 2,189 men and 2,625 women over 40 years old. Study subjects were classified into the following four groups according to lean mass (LM)/height2 and percentage fat mass (PF). Clinical fragility fracture events were assessed at baseline and biennially using self-reported questionnaires. During a median follow-up of 9.4 years, 77 (3.5%) men and 203 (7.7%) women experienced at least one incident fracture. In Cox proportional hazard models, men with low LM under normal and high PF had a 2.16 and 2.59- fold higher risk for fragility fractures than normal ones even after adjusting for covariates. However, in women, low LM or high FM was not associated with fracture risk. We demonstrated sex-based differences in the association of body composition and incident fracture risk in Koreans aged over 40 years during a 10-year follow-up duration. Maintaining muscle mass in men is vital to maintaining bone health and preventing fragility fractures in Koreans.

Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Glycated hemoglobin (HbA1c) is an indicator of the average blood glucose concentration. Failing to control HbA1c levels can accelerate the development of complications in patients with diabetes. Although metabolite profiles associated with HbA1c level in diabetes patients have been characterized using different platforms, more studies using high-throughput technology will be helpful to identify additional metabolites related to diabetes. Type 2 diabetes (T2D) patients were divided into two groups based on the HbA1c level: normal (HbA1c ≤6%) and high (HbA1c ≥9%) in both discovery and replication sets. A targeted metabolomics approach was used to quantify serum metabolites and multivariate logistic regression was used to identify significant differences between groups. The concentrations of 22 metabolites differed significantly between the two groups in the discovery set. In the replication set, the levels of 21 metabolites, including 16 metabolites identified in the discovery set, differed between groups. Among these, concentrations of eleven amino acids and one phosphatidylcholine (PC), lysoPC a C16:1, were higher and four metabolites, including three PCs (PC ae C36:1, PC aa C26:0, PC aa C34:2) and hexose, were lower in the group with normal HbA1c group than in the group with high HbA1c. Metabolites with high concentrations in the normal HbA1c group, such as glycine, valine, and PCs, may contribute to reducing HbA1c levels in patients with T2D. The metabolite signatures identified in this study provide insight into the mechanisms underlying changes in HbA1c levels in T2D.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

BackgroundType 2 diabetes is one of the most common diseases with devastating complications. However, genetic susceptibility of diabetic complications has not been clarified. The vitamin D endocrine system is related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes and cardiovascular disease. Recent studies reported that single nucleotide polymorphisms of vitamin D receptor (VDR) gene were associated with diabetic complications.MethodsIn present study, we evaluated the association of BsmI polymorphism of VDR with diabetic complications in Korean diabetes patients. Total of 537 type 2 diabetic subjects from the Endocrinology Clinic of Chungbuk National University Hospital were investigated. Polymerase chain reaction-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI (rs1544410; BB, Bb, bb) polymorphisms.ResultsMean age was 62.44±10.64 years and mean disease duration was 13.65±7.39 years. Patients with B allele (BB or Bb) was significantly associated with lower risk of diabetic retinopathy (severe non-proliferative diabetic retinopathy or proliferative retinopathy; 7.4%, 5/68) compared with patients without B allele (bb; 17.3%, 81/469; P=0.035). This association was also significant after adjusting for hemoglobin A1c level, body mass index, age, sex, and diabetes mellitus duration, concurrent dyslipidemia and hypertension (odds ratio, 2.99; 95% confidence interval, 1.08 to 8.29; P=0.035) in logistic regression analysis.ConclusionOur findings suggest that B allele of Bsm1 polymorphism in VDR gene is associated with lower risk of diabetic retinopathy in type 2 diabetic patients. Bsm1 genotype could be used as a susceptibility marker to predict the risk of diabetes complication.

Introduction Low bone mass is prevalent in HIV‐positive patients. However, compared to Western countries, less is known about HIV‐associated osteopenia in Asian populations. Methods We performed a cross‐sectional survey in Seoul National University Hospital from December 2011 to May 2012. We measured bone mineral density using central dual energy X‐ray absorptiometry, with consent, in male HIV‐positive patients, aged 40 years and older. Diagnosis of low bone mass was made using International Society for Clinical Densitometry Z‐score criteria in the 40–49 years age group and World Health Organization T‐score criteria in the >50‐year age group. The data were compared with those of a community‐based cohort in Korea. Results Eighty‐four HIV‐positive male patients were included in this study. Median age was 49 (interquartile range [IQR], 45–56) years, and median body mass index (BMI) was 22.6 (IQR, 20.9–24.4). Viral suppression was achieved in 75 (89.3%) patients and median duration of antiretroviral therapy was 71 (IQR, 36–120) months. The overall prevalence of low bone mass was 16.7% in the 40–49 years age group and 54.8% in the>50 years age group. Our cohort had significantly lower bone mass at the femur neck and total hip than HIV‐negative Koreans in the 40–49 years age group. Low bone mass was significantly associated with low BMI, and a high level of serum carboxy‐terminal collagen crosslinks, but was not associated with antiretroviral regimen or duration of antiretroviral therapy. Conclusions Low bone mass is prevalent in Korean HIV‐positive males undergoing antiretroviral therapy, and may be associated with increased bone resorption.

Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days). Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed), and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.