Mild-photothermal and nanocatalytic therapy for obesity and associated diseases.

Background: Current anti-obesity medications suffer from limited efficacy and side-effects because they act indirectly on either the central nervous system or gastrointestinal system. Herein, this work aims to introduce a transdermal photothermal and nanocatalytic therapy enabled by Prussian blue nanoparticles, which directly act on obese subcutaneous white adipose tissue (sWAT) to induce its beneficial remodeling including stimulation of browning, lipolysis, secretion of adiponectin, as well as reduction of oxidative stress, hypoxia, and inflammation. Methods: Prussian blue nanoparticles were synthesized and incorporated into silk fibroin hydrogel for sustained retention. The efficacy of mild photothermal (808 nm, 0.4 W/cm2, 5 min) and nanocatalytic therapy (mPTT-NCT) was assessed both in vitro (3T3-L1 adipocytes) and in vivo (obese mice). The underlying signaling pathways are carefully revealed. Additionally, biosafety studies were conducted to further validate the potential of this therapy for practical application. Results: On 3T3-L1 adipocytes, mPTT-NCT was able to induce browning, enhance lipolysis, and alleviate oxidative stress. On obese mice model, the synergistic treatment led to not only large mass reduction of the targeted sWAT (53.95%) but also significant improvement of whole-body metabolism as evidenced by the substantial decrease of visceral fat (65.37%), body weight (9.78%), hyperlipidemia, and systemic inflammation, as well as total relief of type 2 diabetes. Conclusions: By directly targeting obese sWAT to induce its beneficial remodeling, this synergistic therapy leads to significant improvements in whole-body metabolism and the alleviation of obesity-related conditions, including type 2 diabetes. The elucidation of underlying signaling pathways provides fundamental insights and shall inspire new strategies to combat obesity and its associated diseases.

The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis.

In clinical endocrinology, it is often assumed that the results of thyroid hormone function tests (TFTs) before total thyroidectomy are considered euthyroid when the circulating concentrations of thyrotropin [TSH] and free thyroxine [FT4] are within the normal reference ranges. Postoperative thyroid replacement therapy with levothyroxine. The aim of L-T4 is to reproduce the preoperative euthyroid condition. Currently, intra-individual changes in the euthyroid set point before and after total thyroidectomy are only partly understood. After total thyroidectomy, a greater postoperative [FT4] than preoperative [FT4] for equivalent euthyroid [TSH] was found, with differences ranging from 3 to 8 pmol/L. This unexplained difference can be explained by the use of a mathematical model of the hypothalamus-pituitary-thyroid (HPT) axis set point theory. In this article, the postoperative HPT euthyroid set point was calculated using a dataset of total thyroidectomized patients with at least three distinguishable postoperative TFTs. The postoperative [TSH] set point was used as a homeostatic reference for the comparison of preoperative TFTs. The preoperative [FT4] value was equal to the postoperative [FT4] value in 50% of the patients, divided by a factor of ~ 1.25 (within +/- 10%). The factor of 1.25 stems from the lack of postoperative use of thyroidal triiodothyronine (T3). Furthermore, approximately 25% of the patients presented a greater preoperative [FT4] difference than postoperative [FT4]/1.25 combined with a normal [TSH] difference. Based on these observations, the effect of T3 on the value of the [FT4] set point was analyzed and explained from a control theory perspective.

Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.

Diabetes mellitus is a chronic disease that impairs metabolism, and its prevalence has reached an epidemic proportion globally. Most people affected are with type 2 diabetes mellitus (T2DM), which is caused by a decline in the numbers or functioning of pancreatic endocrine islet cells, specifically the ß-cells that release insulin in sufficient quantity to overcome any insulin resistance of the metabolic tissues. Genetic and epigenetic factors have been implicated as the main contributors to the T2DM. Epigenetic modifiers, histone deacetylases (HDACs), are enzymes that remove acetyl groups from histones and play an important role in a variety of molecular processes, including pancreatic cell destiny, insulin release, insulin production, insulin signalling, and glucose metabolism. HDACs also govern other regulatory processes related to diabetes, such as oxidative stress, inflammation, apoptosis, and fibrosis, revealed by network and functional analysis. This review explains the current understanding of the function of HDACs in diabetic pathophysiology, the inhibitory role of various HDAC inhibitors (HDACi), and their functional importance as biomarkers and possible therapeutic targets for T2DM. While their role in T2DM is still emerging, a better understanding of the role of HDACi may be relevant in improving insulin sensitivity, protecting ß-cells and reducing T2DM-associated complications, among others.

Association of Acylcarnitines With Maternal Cardiometabolic Risk Factors Is Defined by Chain Length: The S-PRESTO Study.

CONTEXT: Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate, and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers. OBJECTIVE: To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors. METHODS: Liquid chromatography tandem mass spectrometry-based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26 to 28 weeks' pregnancy, and 3 months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. RESULTS: Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared with preconception and postpartum. Renal clearance of carnitine increased with an increase in prepregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration than mothers with normal glucose metabolism at preconception. CONCLUSION: This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes.

Contrast-specific propensity scores for causal inference with multiple interventions.

Existing methods that use propensity scores for heterogeneous treatment effect estimation on non-experimental data do not readily extend to the case of more than two treatment options. In this work, we develop a new propensity score-based method for heterogeneous treatment effect estimation when there are three or more treatment options, and prove that it generates unbiased estimates. We demonstrate our method on a real patient registry of patients in Singapore with diabetic dyslipidemia. On this dataset, our method generates heterogeneous treatment recommendations for patients among three options: Statins, fibrates, and non-pharmacological treatment to control patients' lipid ratios (total cholesterol divided by high-density lipoprotein level). In our numerical study, our proposed method generated more stable estimates compared to a benchmark method based on a multi-dimensional propensity score.

Clinical and imaging features of women with polygenic partial lipodystrophy: a case series.

BACKGROUND: Familial partial lipodystrophy (FPLD) is an inherited disorder of white adipose tissue that causes premature cardiometabolic disease. There is no clear diagnostic criteria for FPLD, and this may explain the under-detection of this condition. AIM: This pilot study aimed to describe the clinical features of women with FPLD and to explore the value of adipose tissue measurements that could be useful in diagnosis. METHODS: In 8 women with FPLD and 4 controls, skinfold measurements, DXA and whole-body MRI were undertaken. RESULTS: Whole genome sequencing was negative for monogenic metabolic causes, but polygenic scores for partial lipodystrophy were elevated in keeping with FPLD type 1. The mean age of diagnosis of DM was 31 years in the FPLD group. Compared with controls, the FPLD group had increased HOMA-IR (10.3 vs 2.9, p = 0.028) and lower mean thigh skinfold thickness (19.5 mm vs 48.2 mm, p = 0.008). The FPLD group had lower percentage of leg fat and an increased ratio of trunk to leg fat percentage on DXA. By MRI, the FPLD group had decreased subcutaneous adipose tissue (SAT) volume in the femoral and calf regions (p < 0.01); abdominal SAT, visceral adipose tissue, and femoral and calf muscle volumes were not different from controls. CONCLUSION: Women with FPLD1 in Singapore have significant loss of adipose but not muscle tissue in lower limbs and have early onset of diabetes. Reduced thigh skinfold, and increased ratio of trunk to leg fat percentage on DXA are potentially clinically useful markers to identify FPLD1.

Platform for the interdisciplinary study of cardiovascular, metabolic and neurovascular diseases (PICMAN) protocol.

Through extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21-72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, 'multi-omics analyses' and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study.

A fully convolutional neural network for comprehensive compartmentalization of abdominal adipose tissue compartments in MRI.

BACKGROUND: Existing literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PURPOSE: To implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. MATERIAL AND METHODS: MRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). RESULTS: The proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. CONCLUSION: Convolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.

Alterations in SAMD9, AHSG, FRG2C, and FGFR4 Genes in a Case of Late-Onset Massive Tumoral Calcinosis.

Background/Objective: Tumoral calcinosis (TC) is a rare, arcane, and debilitating disorder of phosphate metabolism manifesting as hard masses in soft tissues. Primary hyperphosphatemic TC has been shown to be caused by pathogenic variants in the genes encoding FGF23, GALNT3, and KLOTHO. We report a case of massive TC mechanistically associated with phosphatonin resistance associated with heterozygous alterations in the sterile alfa motif domain-containing protein-9 gene (SAMD9), alfa 2-Heremans-Schmid glycoprotein gene (AHSG), FSHD region gene 2-family member-C gene (FRG2C), and fibroblast growth factor receptor-4 gene (FGFR4). Case Report: A middle-aged Malay woman with systemic sclerosis presented with painful hard lumps of her axillae, lower limbs, and external genitalia. She was eucalcemic with mild hyperphosphatemia associated with reduced urinary phosphate excretion. Magnetic resonance imaging revealed calcified soft tissue masses. Paradoxically, the serum intact FGF23 level increased to 89.6 pg/mL, corroborated by Western blots, which also showed overexpression of sFRP4 and MEPE, consistent with phosphatonin resistance. Discussion: Whole genome sequencing identified 2 heterozygous alterations (p.A454T and p.T479M) in SAMD9, 2 heterozygous alterations (p.M248T and p.S256T) in AHSG, a frameshift alteration (p.Arg156fs) in FRG2C, and a heterozygous alteration (p.G388R) in FGFR4, all of which are associated with calcinosis. Nonsynonymous alterations of FRP4 and MEPE were also detected. Conclusion: This highlights that the simultaneous occurrence of alterations in several genes critical in phosphate homeostasis may trigger massive TC despite their heterozygosity. These findings should prompt functional studies in cell and animal models to reveal mechanistic insights in the pathogenesis of such crippling mineralization disorders.

Effects of Medications on Heat Loss Capacity in Chronic Disease Patients: Health Implications Amidst Global Warming.

Pharmacological agents used to treat or manage diseases can modify the level of heat strain experienced by chronically ill and elderly patients via different mechanistic pathways. Human thermoregulation is a crucial homeostatic process that maintains body temperature within a narrow range during heat stress through dry (i.e., increasing skin blood flow) and evaporative (i.e., sweating) heat loss, as well as active inhibition of thermogenesis, which is crucial to avoid overheating. Medications can independently and synergistically interact with aging and chronic disease to alter homeostatic responses to rising body temperature during heat stress. This review focuses on the physiologic changes, with specific emphasis on thermolytic processes, associated with medication use during heat stress. The review begins by providing readers with a background of the global chronic disease burden. Human thermoregulation and aging effects are then summarized to give an understanding of the unique physiologic changes faced by older adults. The effects of common chronic diseases on temperature regulation are outlined in the main sections. Physiologic impacts of common medications used to treat these diseases are reviewed in detail, with emphasis on the mechanisms by which these medications alter thermolysis during heat stress. The review concludes by providing perspectives on the need to understand the effects of medication use in hot environments, as well as a summary table of all clinical considerations and research needs of the medications included in this review. SIGNIFICANCE STATEMENT: Long-term medications modulate thermoregulatory function, resulting in excess physiological strain and predisposing patients to adverse health outcomes during prolonged exposures to extreme heat during rest and physical work (e.g., exercise). Understanding the medication-specific mechanisms of altered thermoregulation has importance in both clinical and research settings, paving the way for work toward refining current medication prescription recommendations and formulating mitigation strategies for adverse drug effects in the heat in chronically ill patients.

Multidimensional conservation analysis decodes the expression of conserved long noncoding RNAs.

Although long noncoding RNAs (lncRNAs) experience weaker evolutionary constraints and exhibit lower sequence conservation than coding genes, they can still conserve their features in various aspects. Here, we used multiple approaches to systemically evaluate the conservation between human and mouse lncRNAs from various dimensions including sequences, promoter, global synteny, and local synteny, which led to the identification of 1,731 conserved lncRNAs with 427 high-confidence ones meeting multiple criteria. Conserved lncRNAs, compared with non-conserved ones, generally have longer gene bodies, more exons and transcripts, stronger connections with human diseases, and are more abundant and widespread across different tissues. Transcription factor (TF) profile analysis revealed a significant enrichment of TF types and numbers in the promoters of conserved lncRNAs. We further identified a set of TFs that preferentially bind to conserved lncRNAs and exert stronger regulation on conserved than non-conserved lncRNAs. Our study has reconciled some discrepant interpretations of lncRNA conservation and revealed a new set of transcriptional factors ruling the expression of conserved lncRNAs.

Endothelial Damage Arising From High Salt Hypertension Is Elucidated by Vascular Bed Systematic Profiling.

BACKGROUND: Considerable evidence links dietary salt intake with the development of hypertension, left ventricular hypertrophy, and increased risk of stroke and coronary heart disease. Despite extensive epidemiological and basic science interrogation of the relationship between high salt (HS) intake and blood pressure, it remains unclear how HS impacts endothelial cell (EC) and vascular structure in vivo. This study aims to elucidate HS-induced vascular pathology using a differential systemic decellularization in vivo approach. METHODS: We performed systematic molecular characterization of the endothelial glycocalyx and EC proteomes in mice with HS (8%) diet-induced hypertension versus healthy control animals. Isolation of eGC and EC compartments was achieved using differential systemic decellularization in vivo methodology. Altered protein expression in hypertensive compared to normal mice was characterized by liquid chromatography tandem mass spectrometry. Proteomic results were validated using functional assays, microscopic imaging, and histopathologic evaluation. RESULTS: Proteomic analysis revealed a significant downregulation of eGC and associated proteins in HS diet-induced hypertensive mice (among 1696 proteins identified in this group, 723 were markedly decreased in abundance, while only 168 were increased in abundance. Bioinformatic analysis indicated substantial derangement of the eGC layer, which was subsequently confirmed by fluorescent and electron microscopy assessment of vessel damage ex vivo. In the EC fraction, HS-induced hypertension significantly altered protein mediators of contractility, metabolism, mechanotransduction, renal function, and the coagulation cascade. In particular, we observed dysregulation of integrin subunits α2, α2b, and α5, which was associated with arterial wall inflammation and substantial infiltration of CD68+ monocyte-macrophages. Consequently, HS-induced hypertensive mice also displayed reduced vascular integrity of multiple organs including lungs, kidneys, and heart. CONCLUSIONS: These findings provide novel molecular insight into HS-induced structural changes in eGC and EC composition that may increase cardiovascular risk and potentially guide the development of new diagnostics and therapeutic interventions.

Prediction of subclinical atherosclerosis in low Framingham risk score individuals by using the metabolic syndrome criteria and insulin sensitivity index.

Background: Subclinical atherosclerosis can be present in individuals with an optimal cardiovascular risk factor profile. Traditional risk scores such as the Framingham risk score do not adequately capture risk stratification in low-risk individuals. The aim of this study was to determine if markers of metabolic syndrome and insulin resistance can better stratify low-risk individuals. Methods: A cross-sectional study of 101 healthy participants with a low Framingham risk score and no prior morbidities was performed to assess prevalence of subclinical atherosclerosis using computed tomography (CT) and ultrasound. Participants were compared between groups based on Metabolic Syndrome (MetS) and Insulin-Sensitivity Index (ISI-cal) scores. Results: Twenty three individuals (23%) had subclinical atherosclerosis with elevated CT Agatston score ≥1. Presence of both insulin resistance (ISI-cal <9.23) and fulfillment of at least one metabolic syndrome criterion denoted high risk, resulting in significantly improved AUC (0.706 95%CI 0.588-0.822) over the Framingham risk score in predicting elevated CT Agatston score ≥1, with net reclassification index of 50.9 ± 23.7%. High-risk patients by the new classification also exhibited significantly increased carotid intima thickness. Conclusions: The overlap of insulin resistance and presence of ≥1 criterion for metabolic syndrome may play an instrumental role in identifying traditionally low-risk individuals predisposed to future risk of atherosclerosis and its sequelae.

Gender differences in fasting and postprandial metabolic traits predictive of subclinical atherosclerosis in an asymptomatic Chinese population.

The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score.Clinical Trial Registration: The trial was registered at clinicaltrials.gov as NCT03531879.

Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence.

It is well established that thyroid dysfunction is linked to an increased risk of cardiovascular morbidity and mortality. The pleiotropic action of thyroid hormones strongly impacts the cardiovascular system and affects both the generation of the normal heart rhythm and arrhythmia. A meta-analysis of published evidence suggests a positive association of FT4 concentration with major adverse cardiovascular end points (MACE), but this association only partially extends to TSH. The risk for cardiovascular death is increased in both subclinical hypothyroidism and subclinical thyrotoxicosis. Several published studies found associations of TSH and FT4 concentrations, respectively, with major cardiovascular endpoints. Both reduced and elevated TSH concentrations predict the cardiovascular risk, and this association extends to TSH gradients within the reference range. Likewise, increased FT4 concentrations, but high-normal FT4 within its reference range as well, herald a poor outcome. These observations translate to a monotonic and sensitive effect of FT4 and a U-shaped relationship between TSH and cardiovascular risk. Up to now, the pathophysiological mechanism of this complex pattern of association is poorly understood. Integrating the available evidence suggests a dual etiology of elevated FT4 concentration, comprising both ensuing primary hypothyroidism and a raised set point of thyroid function, e. g. in the context of psychiatric disease, chronic stress and type 2 allostatic load. Addressing the association between thyroid homeostasis and cardiovascular diseases from a systems perspective could pave the way to new directions of research and a more personalized approach to the treatment of patients with cardiovascular risk.

Brown adipose tissue influences adiponectin and thyroid hormone changes during Graves' disease therapy.

Thyroid hormones (TH), adiponectin and brown adipose tissue (BAT) are regulators of energy homoeostasis. Influence of BAT activity on the relationship between TH and adiponectin remains unexplored. The aim of the study was to identify the relationship between TH and adiponectin and to clarify the impact of active BAT on the metabolic effects of adiponectin before and after the correction of thyrotoxicosis. Twenty-one patients with newly diagnosed hyperthyroidism from Graves' disease were recruited. A titration dosing regimen of thionamide anti-thyroid drug (ATD) was used to establish euthyroidism over 12-24 weeks. Anthropometric, biochemical and adipocytokine parameters were measured before and after control of hyperthyroidism. BAT activity was quantified by fusion 18 F-fluorodeoxyglucose (18 F-FDG) PET/MR imaging, and patients were grouped based on BAT status. Plasma adiponectin level was significantly increased following correction of hyperthyroidism in the overall sample. Free thyroxine (FT4) was also identified as a predictor of adiponectin level in thyroid dysfunction. However, significant changes in adiponectin level and correlations involving adiponectin were absent in BAT-positive patients but maintained in BAT-negative patients. BAT activity diminishes the correlative relationship with body composition and abolishes TH and adiponectin relationships when transitioning from a hyperthyroid to euthyroid state.

Feasibility analysis of a prevention programme for patients with early chronic disease using A mathematical model.

The increasing prevalence of the chronic disease is of considerable concern to health-care organisations. Prevention programmes to patients with early chronic disease have the potential to improve individual health and quality of life through disease avoidance or delay and to save the medical cost of the health care system. Due to the limited budget in healthcare this study seeks to analyse the feasibility of a programme prior to implementation. A mathematical model is developed to determine incidence reduction rate at which the underlying cost break-even can be achieved; consequently, the programme would be feasible. We show the existence and uniqueness of the underlying incidence reduction and establish the feasibility frontier concerning the trade-offs between intervention effective period and incidence reduction rate. We use a diabetes prevention programme to demonstrate the efficiency and advantage of the model. The proposed model would inform decision-makers scientific principles in determining an intervention for implementation.

Increased Consumption of Unsaturated Fatty Acids Improves Body Composition in a Hypercholesterolemic Chinese Population.

While an increase in fat intake and the resulting excess calorie intake are implicated in weight gain, different fat types exert variable effects on body composition, with unsaturated fats showing favorable effects on body composition in Western population. Whether and to what extent these associations apply to Asian population have not been established. We investigated the effects of two separate Asian-based oil blends, rich in unsaturated fats, made from refined rice bran, sesame, and flaxseed oils, in comparison with refined olive oil, on body composition using dual-energy X-ray absorptiometry (DXA), from an 8-week, parallel design, randomized trial in 66 men (58.7 ± 5.71 years old, 23.0 ± 2.38 kg/m2) and 69 postmenopausal women (59.1 ± 5.34 years old, 21.7 ± 2.52 kg/m2), with borderline hypercholesterolemia. Despite increases in mean daily intakes of total energy (approximately +400 kcal/day, female, and approximately +240 kcal/day, male), as well as increases in percentage of calories from fats and proteins and decreases in percentage of calories from carbohydrates during the dietary intervention period, there were no significant changes in total body fat mass in both genders and also in all treatment groups. While total body weight increased slightly (0.36 ± 0.12 kg, p = 0.005) in women during intervention, this was mainly due to gain in lean mass (0.38 ± 0.081 kg, p < 0.0001). Correspondingly, there were reductions in total body fat (%), android fat (%), and gynoid fat (%) in women. No significant differences between the 3 intervention oil types were found in any of the measured parameters in either gender. Increasing relative intakes of unsaturated fats may prevent fat mass gain and circumvent muscle mass loss associated with menopause in older Asian women. Long-term studies are needed to confirm findings. This study had been registered on clinicaltrials.gov (Identifier No.: NCT03964857, https://www.clinicaltrials.gov/ct2/show/NCT03964857).