Body Weight Monitoring Research Articles

Clinical Factors Affecting Daily Dosage of Desmopressin Orally Disintegrating Tablets in Arginine Vasopressin Deficiency.

Desmopressin orally disintegrating tablets (ODTs) are widely used to treat arginine vasopressin deficiency (AVP-D). However, limited information is available on the dosage regimen; the dosage for each patient is selected based on their response to the initiation dose. To investigate the relationships between clinical characteristics and the daily dose of ODTs and to identify factors that affect ODT dosages. This retrospective study included 209 adult patients with AVP-D. Patients were administered ODTs sublingually and instructed to restrict eating and drinking for 30 minutes after taking ODTs using a patient leaflet. ODT dose titration was conducted during hospitalization with close monitoring of urine output, body weight, and serum sodium levels. Multivariable linear regression models were applied to identify clinical factors associated with the daily dose of ODTs at discharge. We also evaluated the dosage at 1 year in 134 patients who were followed up in our hospital. The median daily dose of ODTs at discharge was 90 µg (IQR 60-120 µg). Multivariable linear regression models identified sex, age, and estimated creatinine clearance (eCCr) as significant factors associated with the daily dose of ODTs, with eCCr having the strongest effect. After excluding patients recovering from AVP-D, 71% of those followed up at our hospital took the same daily dose at 1 year after discharge. To achieve the safe and stable treatment of AVP-D, the daily dose of ODT needs to be selected based on a patient's sex, age, and eCCr under appropriate sublingual administration by patient education.

Abstract 13242: Annual Body Weight Change and Subsequent Prognosis in Heart Failure With Preserved Ejection Fraction: Insights From the PURSUIT-HFpEF Registry

Introduction: Maintaining optimal body weight is important in heart failure management. Weight gain (WG) may signal excessive caloric intake and fluid retention, whereas weight loss (WL) would imply cachexia. Both conditions could affect the prognosis of heart failure with reduced ejection fraction. However, the significance of WG and WL in patients with heart failure and preserved ejection fraction (HFpEF) has not been well established. Methods: An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. Of 1231 patients who enrolled in the registry, we enrolled 662 patients (age, 82±9 years; females, 54.1%; body mass index, 22.3±4.3kg/m 2 ; atrial fibrillation, 38.3%) whose weight at discharge and one year later were both available. WG and WL were defined as a gain or loss of ≥5% weight between baseline and 1 year, respectively. Other patients who did not demonstrate a significant change in weight were categorized as having a stable weight (SW). All-cause mortality was the primary endpoint. Results: During 1-year, the median body weight slightly increased from 52.1 (interquartile range [IQR]: 45.1-61.9) to 53.0 kg (IQR 45.0-63.0) kg (p <0.001), with a median change of 0.6 kg (IQR: -1.8-2.8). A total of 182 (27%), 125 (19%), and 355 (54%) patients experienced WG, WL, and SW, respectively. During a follow-up of 603 days (IQR: 329-982), 149 patients died. The mortality rate was highest in patients experiencing WL, followed by those experiencing WG and SW (30.2% vs. 21.5% vs. 18.0%, respectively; log-rank p = 0.006). After adjusting for potential confounders, Cox regression analysis revealed that WL, not WG, was independently associated with higher mortality (hazard ratio 2.44 [95% CI 1.51-3.95], p <0.001). Conclusions: Significant number of patients with HFpEF experienced WG and WL within a year. Patients who experienced WL had a higher risk of mortality compared to those who experienced WG and SW. These results highlight the importance of monitoring body weight changes in the management of HFpEF.

151 Depth Video Data-Enabled Predictions of Longitudinal Dairy Cow Body Weight Using Thresholding and Mask R-Cnn Algorithms

Abstract Cow body weight monitoring is critical in farm management because it is associated with the growth, nutritional status, and health of dairy cows. Regularly collecting body weight records often requires human labor or expensive equipment. Recently, a low-cost 3D depth sensor camera-enabled computer vision analysis has been proposed to address the body weight prediction challenges. Cow body weight is a repeated trait; however, past body weight prediction research only used data collected at a single time point. Furthermore, the utility of deep learning on body weight predictions remains unanswered. Therefore, the objectives of this study were to predict cow body weight from repeatedly measured video data and compare the performance of thresholding and Mask R-CNN deep learning approaches. We set up an Intel Realsense D435 camera at the Virginia Tech Kentland farm to collect top-view videos for 10 Holstein and 2 Jersey cows for 28 days, twice per day. Real body weight records were also collected by a walk-over-weighing system simultaneously. A total of 40,405 depth images and depth map files were obtained. We explored three approaches to segment the cow body from the background, including single thresholding, adaptive thresholding, and Mask R-CNN. Four image-derived biometric measurements, length, width, height, and volume, were estimated from segmented images and fitted in ordinary least squares. Two cross-validation designs, forecasting and leave-several-cow-out, were used to evaluate prediction performance. The correlation between image-derived biometric measurements and body weight ranged from 0.84 to 0.95. On average, the Mask-RCNN approach resulted in the best prediction coefficient of determination and mean absolute percentage error of 0.96 and 3.54% in the forecasting cross-validation, respectively. The predictive performance of the single and adaptive thresholding approaches was similar. The Mask-RCNN approach was also the best in the leave-several-cow-out cross-validation, followed by adaptive and single thresholding. The prediction coefficients of determination of Mask-RCNN for leave-one-cow-out, leave-two-cow-out, leave-three-cow-out, leave-four-cow-out were 0.05, 0.69, 0.85, and 0.90, respectively, while mean absolute percentage errors were 4.51%, 4.51%, and 4.59%, 4.70% respectively. Our results suggest predicting cow body weight from depth video data using deep learning is feasible.

28 On-Farm Rapid Test to Assess Immunological Health of Young Pigs

Abstract Immunological competence is important for young pig survivability. A rapid on-farm test of immunological status may be a tool to help with early identification of sick animals. A new immunological test uses gold nanoparticle technology (D2Dx) to detect changes in serum proteins, particularly IgG and was evaluated as a potential on-farm measure of immunological health of pigs born during a farm level Porcine Respiratory Reproductive Syndrome (PRRS) outbreak. Up to three piglets from each litter in 2 farrowing groups (28 days apart) were selected for serial blood sampling and monitoring of body weight. Group 1 (n = 13 sows) experienced the PRRS outbreak approximately 14 days before farrowing and Group 2 (n = 15) approximately 40 days before farrowing. Attempts were made to select one piglet from each of 3 general categories [small (< 1.0 kg), average (1.1 – 1.6 kg), heavy (>1.6 kg)] from each litter. Serum samples were collected at day 2 and 15 of age from each piglet and serum IgG concentration and D2Dx ratio were assessed. Serum immunocrit at day 2 was also completed. Daily animal care of piglets and sows followed standard barn protocols. No creep feed was provided, sows were fed ad libitum, and cross-fostering was limited. Stillborn rate and preweaning death loss was approximately 70% in Group 1 and 35% in Group 2. Birth weight was similar between Group 1 and 2 litters (1.4 ± 0.3 kg). However, body weight gain to day 15 was 1.7 ± 0.95 kg and 2.7 ± 1.1 kg for piglets from Group 1 and 2, respectively, which may be due to timing of the PRRS outbreak. The D2Dx ratio declined from day 2 to 15 (0.029 vs -0.002) in both groups and was significantly reduced in Group 2 pigs (P < 0.001). A lower ratio suggests a stronger type 2 immune response and has been associated with decreased overall immunity in cattle, humans, and rodents. The D2Dx ratio was negatively correlated (r = -0.58) with BW gain in Group 1 pigs and positively correlated (r = 0.36) with gain in Group 2 pigs. Both immunocrit (day 2) and IgG (d15) were greater in Group 1 pigs than Group 2 (P < 0.01). There was a no relationship between birth weight and day 2 serum immunocrit (R2 = 0.06) or day 2 D2Dx (R2 = 0.01). There was no relationship between serum IgG and D2Dx at d15. The PRRS disease activity impacts immunocrit and serum IgG measures in the neonatal pig. The D2Dx ratio was not strongly related to piglet immunological status under disease conditions; however, the stronger type 2 immune response may be reflective of positive changes in piglet immune function and the response to maternal PRRS antibodies in milk.

Protective effect of benzaldehyde combined with albendazole against brain injury induced by Angiostrongylus cantonensis infection in mice

Angiostrongylus cantonensis, which is also known as rat lungworm, is an important food-borne zoonotic parasite that causes severe neuropathological damage and symptoms, including eosinophilic meningitis and eosinophilic meningoencephalitis, in humans. At present, the therapeutic strategy for cerebral angiostrongyliasis remains controversial. Benzaldehyde, an important bioactive constituent of Gastrodia elata (Tianma) reduces oxidative stress by inhibiting ROS production. This study aimed to evaluate the therapeutic effect of benzaldehyde in combination with albendazole on angiostrongyliasis in animal models. First, the data from body weight monitoring and behavioural analyses demonstrated that benzaldehyde improve body weight and cognitive function changes after A. cantonensis infection. Next, blood‒brain barrier breakdown and pathological changes were reduced after benzaldehyde and albendazole treatment in A. cantonensis-infected BALB/c mice. Subsequently, we established four RNA-seq datasets from different treatment mouse brains, including the normal, infection, infection+albendazole, and infection+albendazole+3-HBA groups. Ultimately, we found that benzaldehyde regulates cell apoptosis, oxidative stress, and sonic hedgehog signalling in A. cantonensis-infected mouse brains. This study evaluated the therapeutic effect of benzaldehyde on angiostrongyliasis and provided a potential therapeutic strategy for human angiostrongyliasis in the clinic. Moreover, we elucidated the molecular mechanism of benzaldehyde in A. cantonensis-infected mouse brains.

Acetylcorynoline relieves 2, 4, 6-trinitrobenesulfonic acid-induced Crohn's disease-like colitis in mice by regulating intestinal epithelial cell apoptosis

To explore the effect of acetylcorynoline for relieving 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD)-like colitis in mice and explore the underlying mechanism. Male C57BL/6 mice were subjected to TNBS treatment to establish models of TNBS-induced CD-like colitis, followed by treatment with saline or 10, 20, or 40 mg/kg acetylcorynoline by gavage. The protective effect of acetylcorynoline against colitis was evaluated by monitoring body weight changes, measurement of DAI and colon length, and histological examination. The colon tissues and cultured colon organoids treated with LPS and acetylcorynoline were examined for expressions of tight junction proteins and apoptosis-related proteins using immunofluorescence assay, Western blotting, and TUNEL staining. The mechanism of acetylcorynoline-induced inhibition of intestinal epithelial cell apoptosis was predicted by network pharmacology and verified by Western blotting. Acetylcorynoline treatment significantly alleviated weight loss and colon length shortening and reduced DAI score and inflammation score in TNBS mice (P < 0.05). Claudin-1 was significantly upregulated in the colon tissue of acetylcorynolinetreated mice (P < 0.05), where the protein levels of claudin-1, ZO-1, and Bcl-2 were increased and C-caspase3 and Bax were reduced (P < 0.05) and the number of apoptotic intestinal epithelial cells decreased (P < 0.05). In cultured colon organoids, acetylcorynoline significantly increased ZO-1, claudin-1 and Bcl-2 expressions and decreased C-caspase3 and Bax expressions (P < 0.05). KEGG pathway enrichment analysis suggested that the PI3K- AKT signaling pathway was correlated with acetylcorynoline treatment for CD, and the expressions of p-AKT and p-PI3K decreased significantly after the treatment in both the in vivo and in vitro models (P < 0.05). The PI3K-AKT activator (740Y-P) significantly promoted the expressions of p-PI3K, p-AKT, C-caspase3 and Bax and inhibited Bcl-2 in the colon organoids (P < 0.05). Acetylcorynoline protects against TNBS-induced CDlike colitis in mice possibly by suppressing the activation of the PI3K/AKT signaling pathway, thereby inhibiting apoptosis of the intestinal epithelial cells.

Probing the Biosafety of Implantable Artificial Secretory Granules for the Sustained Release of Bioactive Proteins.

Among bio-inspired protein materials, secretory protein microparticles are of clinical interest as self-contained, slow protein delivery platforms that mimic secretory granules of the human endocrine system, in which the protein is both the drug and the scaffold. Upon subcutaneous injection, their progressive disintegration results in the sustained release of the building block polypeptides, which reach the bloodstream for systemic distribution and subsequent biological effects. Such entities are easily fabricated in vitro by Zn-assisted cross-molecular coordination of histidine residues. Using cationic Zn for the assembly of selected pure protein species and in the absence of any heterologous holding material, these granules are expected to be nontoxic and therefore adequate for different clinical uses. However, such presumed biosafety has not been so far confirmed and the potential protein dosage threshold not probed yet. By selecting the receptor binding domain (RBD) from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein as a model protein and using a mouse lab model, we have explored the toxicity of RBD-made secretory granules at increasing doses up to ∼100 mg/kg of animal weight. By monitoring body weight and biochemical blood markers and through the histological scrutiny of main tissues and organs, we have not observed systemic toxicity. Otherwise, the bioavailability of the material was demonstrated by the induction of specific antibody responses. The presented data confirm the intrinsic biosafety of artificial secretory granules made by recombinant proteins and prompt their further clinical development as self-contained and dynamic protein reservoirs.

Gambaran Penanganan Kejadian Stunting pada Balita di Wilayah Kerja Puskesmas Jagir Kota Surabaya

One of the nutritional problems that is currently a concern of the government is stunting. In 2020 the prevalence of stunting in the world is reported to reach 149.2 million children (22%). Based on World Bank data for 2020, the incidence of stunting in Indonesia ranks 115th out of 151 countries in the world and 3rd in the Southeast Asia Region. The purpose of this study is to find out the description of the handling of stunting in toddlers in the Working Area of the Jagir Health Center, Surabaya. The analysis used was univariate analysis by looking at the distribution of the frequency of stunting under five. The results of research on the nutritional status of toddlers based on the percentage of height for age showed that as many as 0.6% (15 toddlers) were found to be stunted, which was divided into two categories, namely short and very short in the Working Area of the Jagir Health Center, Surabaya, spread across 3 urban villages. Based on the percentages for December 2022 - February 2023, there was a decrease in stunting toddlers who were found. Treatment carried out to reduce stunting rates at the Jagir Health Center are monitoring body weight and height through home visits, providing stunting food in the form of animal protein assisted by KSH to deliver stunting food and monitoring the food until it is consumed, providing KIE to family members, as well as coordination with cross-sectors if there are obstacles related to non-health problems.

Enhancing knowledge of Diabetes self-management and quality of life in people with Diabetes Mellitus by using Guru Diabetes Apps-based health coaching.

Virtual diabetes coaching through applications has the potential to improve self-management in people with Type 2 Diabetes Mellitus. However, applications designed for Asian's diabetic have never been studied. Therefore, our study aimed to identify the effect of Guru Diabetes Apps-Based Health Coaching on the level of glycemic hemoglobin, knowledge, and quality of life in Indonesians, as one of Asian ethnicities. This study used an experimental design. Participants with T2DM were recruited from three primary care health centers. The intervention included 3 months of virtual health coaching through the Guru Diabetes application. The daily monitoring of glycemic blood glucose, blood pressure, body weight, nutrition intake, and activity provided were used as baseline to conduct virtual in-person coaching. The glycemic hemoglobin level, knowledge level, and quality of life were assessed at baseline and post-enrollment. A multilevel modeling approach was used for statistical analysis. A total of 66 respondents were enrolled, and 62 respondents (93.93%) remained in the study at 3 months. After completing the intervention, the HbA1c level decreased in all groups, however it did not differ among the groups. On the other hand, the results indicate significant improvement in the average diabetes self-management knowledge score (pre = 14.97 vs post = 19.07, p < 0.05) and quality of life score (pre = 54.34 vs post = 60.28, p < 0.05), with significant difference among the groups (p < 0.05). Participants in the Android Application-Based Health Coaching experienced a significant improvement in diabetes self-management knowledge and quality of life scores at 3 months. In conclusion, the Guru Diabetes Apps-Based Health Coaching has the potential to support people with T2DM in performing diabetes self-management at home.

The role of natural compounds in rat mammary cancer: the beneficial effects of Santolina chamaecyparissus L. aqueous extract

Breast cancer is the most diagnosed cancer among women, and a leading cause of death worldwide. Santolina chamaecyparissus L. is a plant with multiple health benefits, including anticancer and anti-diabetic properties. This study aimed to assess the chemopreventive effects of S. chamaecyparissus aqueous extract (SCE) in an animal model of mammary cancer. A total of 28 four-week-old female Wistar rats were divided into four groups: control, MNU-induced (IND), SCE-supplemented (SCE), and SCE+IND. SCE was added to drinking water (12.72 mg/kg body weight) ad libitum. MNU was administered via the intraperitoneal route at 50 days of age. Weekly monitoring of body weight, food/drink intake, humane endpoints, and number of mammary tumours were recorded. Twenty weeks after MNU administration, animals were sacrificed by anaesthetic overdose and a necropsy was performed. Blood samples were used to determine blood count and serum biochemistry analysis, while kidney and liver samples were analysed for oxidative stress. Tumour samples were collected for gene expression and histology studies. SCE chemical composition was analysed by LC-MS and contained 19 phenolic compounds, with the most abundant being myricetin-O-glucuronide and 1,3-O-dicaffeoylquinic acid. Two animals in the IND group were sacrificed due to exceeding the humane endpoint limits. SCE supplementation delayed mammary tumour development, reducing its volume and weight. SCE had a positive impact on haematological parameters, particularly the neutrophil-lymphocyte ratio (P=0.026). No significant differences were observed in serum biochemistry, except for creatinine kinase MB, or in oxidative stress markers. Gene expression analysis showed significantly reduced VEGF expression levels (P=0.0158) in tumours from SCE+IND. These findings suggest that SCE is deserving of further study to identify the individual compounds and to understand its influence on animal models during cancer development.

Longitudinal body weight dynamics in relation to cognitive decline over 18 years: A prospective cohort study

AbstractBackgroundWeight loss and body weight variability have been related to cognitive decline in old adults, respectively. However, the long‐term and independent associations of the two measures of body weight dynamics with cognitive decline remain unclear.MethodIn the Health and Retirement Study (HRS), we included 10,258 participants (58.4% women; mean age ± standard deviation (SD), 68.0 ± 9.8 years) free from memory‐related diseases in 1998. Body weight was reported biennially from 1993/1994 to 2016. Linear regression of the longitudinal body mass index for each individual was used to estimate body weight change (BWC, slope, kg/m2·year) and body weight variability (BWV, root mean squared error, kg/m2). Both measures were categorized by tertiles, with participants being classified as stable weight, weight loss, and weight gain (median = 0.0, ‐0.3, and 0.2 kg/m2·year, respectively), and small, moderate, and large BWV (median = 0.5, 1.1, and 2.0 kg/m2, respectively). Cognitive function was measured biennially from 1998 to 2016 using the Telephone Interview for Cognitive Status (TICS). We investigated the associations of BWC and BWV with annual rate of cognitive decline using linear mixed models.ResultDuring a median (IQR) follow‐up of 12 (4‐18) years, the average rate of cognitive decline was ‐0.052 z‐score/year. When adjusted for basic demographics, average BMI, and major lifestyle factors, we observed no significant associations of weight gain and moderate BWV with cognitive decline, whereas both weight loss and large BWV were associated with faster cognitive decline in the same model. Compared to those with stable weight, participants with weight loss experienced faster cognitive decline by ‐0.012 (95%CI, ‐0.015, ‐0.009) z‐score/year. Large BWV was also related to faster cognitive decline (β = ‐0.003, 95% CI: ‐0.006, ‐0.001) compared with small BWV. The associations were similar for both episodic memory and working memory, and across prespecified study subgroups.ConclusionWeight loss and large body weight variability were associated with faster cognitive decline in old adults. Our findings suggest the importance of dynamic body weight monitoring and management as a potential strategy to prevent age‐related cognitive decline.

Retrospective analysis of 102 neonatal cases hospitalized with diagnosis of the ongoing phenomenon of neonatal period: hypernatremic dehydration

Aim: The aim of this study was to examine the prevalence of hypernatremic dehydration (HD) among term neonates admitted to a tertiary care unit over a three-year period and to identify mother and neonate related risk factors associated with HD.&#x0D; Material and Method: Medical records of 102 term babies and their mothers were analyzed retrospectively. The gender, weight at birth, type of birth, postnatal day of diagnosis, weight and weight loss percentage at diagnosis, season and presenting complaint upon admission, feeding with human milk/formula/mixed, laboratory findings, usage of antibiotics as well as maternal age, parity, residence, level of education and presence of smoking were recorded. Serum sodium (Na) levels, severity of dehydration, age on admission, and length of stay in the neonatal intensive care unit (NICU) were recorded along with any significant effect of maternal demographic properties, residence, season, gender, and type of birth.&#x0D; Results: The average Na levels were found to be 152.1±4.2 mEq/L (max:166 mEq/L). Mild, moderate and severe hypernatremia were found in 34 (33%), 62 (61%) and 6 (6%) patients, respectively. More weight loss was observed in neonates born via cesarean section vs. vaginal delivery (12.8±3.0% vs. 11.6±3.5%, p=0.01). Higher serum Na levels (153.9±4.86 mEq/L vs. 151±2.34 mEq/L, p=0.008) and a greater median age at admission (4.5 [IQR4-6]) days vs. 3 [IQR3-4]) days, p=0.03) were reported for neonates born to mothers residing in rural/suburban vs. urban areas. Serum Na levels were not different based on the mother's level of education or parity (p=0.96 and p=0.29, respectively). There was no difference in serum Na levels (p=0.05) but the percentage of weight loss was higher when the mother smoked (14.3±3.8% vs. 11.7±3.1%, p=0.003). Serum Na and glucose levels were lower, antibiotics usage rates, and prevalence of mixed feedings were higher in early term infants (p=0.01, p=0.002, p=0.04 and p=0.04, respectively). Males had higher creatinine levels (0.89±0.27 mg/dl vs. 0.78±0.28 mg/dl, p=0.005), but there was no difference between the sexes in terms of day of admission, percentage of weight loss, or length of stay in NICU.&#x0D; Conclusion: Hypernatremic dehydration is a significant and increasingly prevalent problem of neonatal period. Serum Na levels and severity of dehydration in neonates may be affected by the type of birth, mother's smoking status, residence and early term birth. Counseling on breastfeeding, education of health professionals and caregivers on the signs and symptoms of dehydration, and monitoring of body weight are essential for the prevention, diagnosis, and treatment of HD.

Androgen receptor coordinates muscle metabolic and contractile functions.

Androgens are anabolic steroid hormones that exert their function by binding to the androgen receptor (AR). We have previously established that AR deficiency in limb muscles impairs sarcomere myofibrillar organization and decreases muscle strength in male mice. However, despite numerous studies performed in men and rodents, the signalling pathways controlled by androgens via their receptor in skeletal muscles remain poorly understood. Male ARskm-/y (n=7-12) and female ARskm-/- mice (n=9), in which AR is selectively ablated in myofibres of musculoskeletal tissue, and male AR(i)skm-/y , in which AR is selectively ablated in post-mitotic skeletal muscle myofibres (n=6), were generated. Longitudinal monitoring of body weight, blood glucose, insulin, lipids and lipoproteins was performed, alongside metabolomic analyses. Glucose metabolism was evaluated in C2C12 cells treated with 5α-dihydrotestosterone (DHT) and the anti-androgen flutamide (n=6). Histological analyses on macroscopic and ultrastructural levels of longitudinal and transversal muscle sections were conducted. The transcriptome of gastrocnemius muscles from control and ARskm-/y mice was analysed at the age of 9weeks (P<0.05, 2138 differentially expressed genes) and validated by RT-qPCR analysis. The AR (4691 peaks with false discovery rate [FDR]<0.1) and H3K4me2 (47225 peaks with FDR<0.05) cistromes in limb muscles were determined in 11-week-old wild-type mice. We show that disrupting the androgen/AR axis impairs in vivo glycolytic activity and fastens the development of type 2 diabetes in male, but not in female mice. In agreement, treatment with DHT increases glycolysis in C2C12 myotubes by 30%, whereas flutamide has an opposite effect. Fatty acids are less efficiently metabolized in skeletal muscles of ARskm-/y mice and accumulate in cytoplasm, despite increased transcript levels of genes encoding key enzymes of beta-oxidation and mitochondrial content. Impaired glucose and fatty acid metabolism in AR-deficient muscle fibres is associated with 30% increased lysine and branched-chain amino acid catabolism, decreased polyamine biosynthesis and disrupted glutamate transamination. This metabolic switch generates ammonia (2-fold increase) and oxidative stress (30% increased H2 O2 levels), which impacts mitochondrial functions and causes necrosis in <1% fibres. We unravel that AR directly activates the transcription of genes involved in glycolysis, oxidative metabolism and muscle contraction. Our study provides important insights into diseases caused by impaired AR function in musculoskeletal system and delivers a deeper understanding of skeletal muscle pathophysiological dynamics that is instrumental to develop effective treatment for muscle disorders.

A Capacitive Pressure Sensor with Linearity and High Sensitivity over a Wide Pressure Range using Thermoplastic Microspheres

AbstractA flexible pressure sensor with a linear response over a wide pressure range with high sensitivity is extremely desirable for high‐pressure applications, such as monitoring body weight and plantar pressure distributions. As a promising candidate to achieve the high sensitivity, a porous structure in capacitive pressure sensors is essential. However, this structure invokes the early saturation of sensitivity owing to a low compression modulus. In this study, thermoplastic microspheres (TPM) as porous materials are utilized, and demonstrate a solution‐processed simple structure that is highly sensitive (3.1 × 10−3 kPa−1) over a wide pressure range (1 MPa) with linearity (R2 = 0.996). The TPM‐containing pressure sensor responds within 100 ms and can withstand a 10 000 times cyclic test under 150 kPa. The linearity may be attributed to the rigid characteristics of the TPM‐containing membrane. These results show that the TPM‐containing pressure sensor has sufficient sensitivity and linearity to reduce the need for complex system calibrations and has potential applications in pressure distribution and weight monitoring.

Lifestyle Intervention Guided by Group and Internet-Based Counseling in the T2D-GENE Trial Supports Its Applicability and Feasibility.

Type 2 diabetes (T2D) can be prevented or postponed by lifestyle modifications as shown by previous intervention studies. In most of these studies, participants have received resource-demanding individual counseling. In the 3-year T2D-GENE trial with lifestyle intervention, we investigated whether a less resource-demanding form of group and internet-based counseling is feasible and effective in preventing T2D in people with an increased risk for T2D. Altogether, 628 middle-aged to elderly men either with a high number or low number of T2D risk alleles were recruited. Five to seven group sessions were organized during the intervention, in addition to information and activities delivered via the web portal, and weekly monitoring of body weight and physical activity. Four-day food records with personal feedback were documented five times during the study. Of the 549 participants completing the study, over 90% participated in the group sessions and kept the food records. The four self-feedback tasks delivered during the second and the third years of the study were completed by 80-89% of the participants. In conclusion, a group and web portal-based lifestyle intervention is applicable for middle-aged to elderly men as a lifestyle modification aiming to prevent T2D.

Electroacupuncture alleviated depression-like behaviors in ventromedial prefrontal cortex of chronic unpredictable mild stress-induced rats: Increasing synaptic transmission and phosphorylating dopamine transporter.

Electroacupuncture (EA) shows advantages in both clinical practice and depression animal models. Dopaminergic-related dysfunction in the prefrontal cortex (PFC) may be a hidden antidepressant mechanism of EA, where dopamine transporter (DAT) plays an essential role. This study aimed to investigate the synaptic transmission and DAT-related changes of EA in depression. Male Sprague-Dawley rats were subjected to 3-week chronic unpredictable mild stress (CUMS). The successfully modeled rats were then randomly and equally assigned to CUMS, selective serotonin reuptake inhibitor (SSRI), and EA or SSRI + EA groups, followed by a 2-week treatment respectively. After monitoring body weight and behavioral tests of all rats, the ventromedial PFC (vmPFC) tissue was collected for electrophysiology and the expression detection of DAT, phosphorylated DAT (p-DAT), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and trace amine-associated receptor 1 (TAAR1). Depressive-like behaviors induced by CUMS were alleviated by EA, SSRI, and SSRI + EA treatments through behavioral tests. Compared with CUMS group, EA improved synaptic transmission in vmPFC by upregulating spontaneous excitatory postsynaptic currents amplitude. Molecularly, EA reversed the increased total DAT and p-DAT expression as well as the decreased ratio of p-DAT/total DAT along with the activation of TAAR1, cAMP, and PKA in vmPFC. We speculated that the antidepressant effect of EA was associated with enhanced synaptic transmission in vmPFC, and the upregulated phosphorylation of DAT relevant to TAAR1, cAMP, and PKA may be the potential mechanism.

A202 INVESTIGATION OF THE DIRECT EFFECT OF HEMIN-HEMOPEXIN AND HAPTOGLOBIN STIMULATION IN INFLAMMATORY BOWEL DISEASE

Abstract Background Inflammatory bowel disease (IBD) is a global health issue defined by persistent intestinal epithelial inflammation resulting in bleeding, and it is one of the major risk factors of colorectal cancer (CRC). Hemin is an activator of heme-oxygenase and has anti-inflammatory, cytoprotective, and antiapoptotic properties by stimulating hemopexin and haptoglobin production. Hemopexin and haptoglobin are scavenging proteins with high affinity for hemin and hemoglobin, and are activated by interleukin (IL)-22. Purpose To evaluate the protective role of hemin through the stimulation of hemopexin and haptoglobin in experimental acute colitis. Method Mice were preconditioned with hemin by intraperitoneal injection with 5mg/kg body weight of hemin for three days while control mice were treated with PBS. Colitis was induced by giving 2.5-3% dextran sulfate sodium (DSS) in drinking water for 12 days. The disease activity index (DAI) was determined by daily monitoring of body weight, fecal bleeding and stool consistency. At the end of the experiment, liver, feces, serum and colon samples were harvested for the evaluation of fecal levels of hemopexin, fecal haptoglobin, IL-22, IL-22BP, IL-6 and TNF-α. Fecal microbiota composition will be determined using 16S rRNA sequencing. Result(s) We found that hemin treatment resulted in the presence of hemopexin and haptoglobin in fecal samples, where they may exert a protective role and influence the growth of pathobionts able to acquire iron using heme and hemoglobin as sources. Conclusion(s) The findings from this study will contribute to the understanding of the possible protective role of hemopexin and haptoglobin in ulcerative colitis. Please acknowledge all funding agencies by checking the applicable boxes below CIHR Disclosure of Interest None Declared

Longitudinal body weight dynamics in relation to cognitive decline over two decades: A prospective cohort study.

The aim of this study was to investigate the associations of body weight change (BWC) and body weight variability (BWV) with changes in cognitive function. In 10,340 Health and Retirement Study participants (mean age: 68.0 years), body weight was reported biennially from 1993/1994 to 2016, and cognitive function was measured biennially from 1998 to 2016. We calculated BWC and BWV as the slope and root-mean-square error by regressing body weight on time for each individual. BWC was categorized by quintiles (Q): stable weight (Q2 to Q4), weight loss (Q1), and weight gain (Q5). BWV was categorized by tertiles. We used linear mixed regression models to assess associations with cognitive change. Compared with stable weight (median: 0kg/y), weight loss (median: -1.3kg/y) predicted faster cognitive decline as demonstrated by mean difference of -0.023 (95% CI: -0.027 to -0.019) in cognitive change z score per year, whereas weight gain (median: 1kg/y) was related to slower cognitive decline (β=0.006; 95% CI: 0.003 to 0.009). Larger BWV was also associated with faster cognitive decline (β comparing the top with bottom tertile=-0.003; 95% CI: -0.006 to -0.0002). Similar associations were observed for episodic and working memory. Weight loss and large BWV over a long time independently predicted faster cognitive decline in middle-aged and older adults, underscoring the importance of long-term dynamic body weight monitoring.

Treatment of Orthotopic U251 Human Glioblastoma Multiforme Tumors in NRG Mice by Convection-Enhanced Delivery of Gold Nanoparticles Labeled with the β-Particle-Emitting Radionuclide, 177Lu.

In this study, we investigated convection-enhanced delivery (CED) of 23 ± 3 nm gold nanoparticles (AuNPs) labeled with the β-particle-emitting radionuclide 177Lu (177Lu-AuNPs) for treatment of orthotopic U251-Luc human glioblastoma multiforme (GBM) tumors in NRG mice. The cytotoxicity in vitro of 177Lu-AuNPs (0.0-2.0 MBq, 4 × 1011 AuNPs) on U251-Luc cells was also studied by a clonogenic survival assay, and DNA double-strand breaks (DSBs) caused by β-particle emissions of 177Lu were measured by confocal immunofluorescence microscopy for γH2AX. NRG mice with U251-Luc tumors in the right cerebral hemisphere of the brain were treated by CED of 1.1 ± 0.2 MBq of 177Lu-AuNPs (4 × 1011 AuNPs). Control mice received unlabeled AuNPs or normal saline. Tumor retention of 177Lu-AuNPs was assessed by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and biodistribution studies. Radiation doses were estimated for the tumor, brain, and other organs. The effectiveness for treating GBM tumors was determined by bioluminescence imaging (BLI) and T2-weighted magnetic resonance imaging (MRI) and by Kaplan-Meier median survival. Normal tissue toxicity was assessed by monitoring body weight and hematology and blood biochemistry analyses at 14 d post-treatment. 177Lu-AuNPs (2.0 MBq, 4 × 1011 AuNPs) decreased the clonogenic survival of U251-Luc cells to 0.005 ± 0.002 and increased DNA DSBs by 14.3-fold compared to cells treated with unlabeled AuNPs or normal saline. A high proportion of 177Lu-AuNPs was retained in the U251-Luc tumor in NRG mice up to 21 d with minimal re-distribution to the brain or other organs. The radiation dose in the tumor was high (599 Gy). The dose in the normal right cerebral hemisphere of the brain excluding the tumor was 93-fold lower (6.4 Gy), and 2000-3000-fold lower doses were calculated for the contralateral left cerebral hemisphere (0.3 Gy) or cerebellum (0.2 Gy). The doses in peripheral organs were <0.1 Gy. BLI revealed almost complete tumor growth arrest in mice treated with 177Lu-AuNPs, while tumors grew rapidly in control mice. MRI at 28 d post-treatment and histological staining showed no visible tumor in mice treated with 177Lu-AuNPs but large GBM tumors in control mice. All control mice reached a humane endpoint requiring sacrifice within 39 d (normal saline) or 45 d post-treatment (unlabeled AuNPs), while 5/8 mice treated with 177Lu-AuNPs survived up to 150 d. No normal tissue toxicity was observed in mice treated with 177Lu-AuNPs. We conclude that CED of 177Lu-AuNPs was highly effective for treating U251-Luc human GBM tumors in the brain in NRG mice at amounts that were non-toxic to normal tissues. These 177Lu-AuNPs administered by CED hold promise for treating patients with GBM to prevent recurrence and improve long-term outcome.

Therapeutic effect of Baimai Ointment on peripheral sensitization of chronic inflammatory pain in mice

Chronic inflammatory pain is mainly manifested by peripheral sensitization. Baimai Ointment(BMO), a classical Tibetan medicine for external use, has good clinical efficacy in the treatment of chronic inflammatory pain, while its pharmacodynamics and mechanism for relieving peripheral sensitization remain unclear. This study established an animal model of chronic inflammatory pain induced by complete Freund's adjuvant to explore the mechanism of BMO in the treatment of chronic inflammatory pain by behavioral test, side effect assessment, network analysis, and experimental verification. The pharmacodynamics experiment showed that BMO increased the thresholds of mechanical pain sensitivity and thermal radiation pain sensitivity of chronic inflammatory pain mice in a dose-dependent manner, and had inhibitory effect on foot swelling, inflammatory mediator, and the expression of transient receptor potential vanilloid-1(TRPV1) and transient receptor potential A1(TRPA1). The results of body weight monitoring, pain sensitivity threshold detection in normal mice, rotarod performance test, and forced swimming test showed that BMO had no obvious toxic or side effect. The network analysis of 51 candidate active molecules selected according to the efficacy of BMO, content of main components, and ADME parameters showed that the inhibitory effect of BMO on chronic inflammatory pain was associated with the core regulatory elements of tumor necrosis factor(TNF) and T cell receptor signaling pathways. BMO down-regulated the protein levels of mitogen-activated protein kinase 14(MAPK14), MAPK1, and prostaglandin-endoperoxide synthase 2(PTGS2), and up-regulated the phosphorylation le-vel of glycogen synthase kinase 3 beta(GSK3 B) in the plantar tissue of mice. In conclusion, BMO can effectively relieve peripheral sensitization of chronic inflammatory pain without inducing tolerance and obvious toxic and side effects. The relevant mechanism may be related to the regulation of BMO on core regulatory elements of TNF and T cell receptor signaling pathways in surrounding tissues.