Overview of growth differentiation factor 15 in metabolic syndrome.

Growth and differentiation factor 15 (GDF15) is a member of the transforming growth factor-ß (TGF-ß) superfamily. GDF15 has been linked with several metabolic syndrome pathologies such as obesity and cardiovascular diseases. GDF15 is considered to be a metabolic regulator, although its precise mechanisms of action remain to be determined. Glial cell-derived neurotrophic factor family receptor alpha-like (GRAL), located in the hindbrain, has been identified as the receptor for GDF15 and signals through the coreceptor receptor tyrosine kinase (RET). Administration of GDF15 analogues in preclinical studies using various animal models has consistently been shown to induce weight loss through a reduction in food intake. GDF15, therefore, represents an attractive target to combat the current global obesity epidemic. In this article, we review current knowledge on GDF15 and its involvement in metabolic syndrome.

Panels of circulating microRNAs as potential diagnostic biomarkers for breast cancer: a systematic review and meta-analysis.

PURPOSE: Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC. METHODS: Analyses across databases were performed to identify potential BC-related circulating miRNAs. Next, a comprehensive meta-analysis was conducted for each miRNA following the PRISMA guidelines. An electronic and manual search for relevant literature was carried out by two reviewers through PubMed, ScienceDirect, Biomed Central, and Google Scholar. The quality of the included studies was assessed using the QUADAS-2, and the statistical analyses were performed using R software 4.1.1. Finally, the accurate biomarkers confirmed through meta-analyses were combined into diagnostic models for BC. RESULTS: Twenty-seven circulating miRNAs were identified as BC-related by bioinformatic tools. After screening, only 10 miRNAs presented in 45 studies were eligible for meta-analyses. By assessing pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, 8 miRNAs (miR-21, miR-30b, miR-125b, miR-145, miR221 miR-222, and miR-335) were revealed as promising BC diagnostic biomarkers. Two panels constructed from these miRNAs showed excellent diagnostic accuracy for BC, with areas under the SROC curve of 0.917 and 0.944. CONCLUSION: We identified 8 potential circulating miRNAs and 2 diagnostic models that are useful for diagnosing BC. However, the established miRNA panels have not been tested in any experimental studies and thus should be validated in large case-control studies for clinical use.

A new diffractometer for diffuse scattering studies on the ID28 beamline at the ESRF.

A new diffractometer is now available to the general user community at the ESRF. The new diffractometer is a side station of the high-resolution inelastic X-ray scattering spectrometer on beamline ID28 and is located in the same experimental hutch. Both instruments can be operated simultaneously. The new diffractometer combines a fast and low-noise hybrid pixel detector with a variable diffraction geometry. The beam spot on the sample is 50 µm × 50 µm, where focusing is achieved by a combination of Be lenses and a KB mirror. Wavelengths from 0.5 to 0.8 Šcan be used for the diffraction experiments. The setup is compatible with a variety of sample environments, allowing studies under non-ambient conditions. The diffractometer is optimized to allow a rapid survey of reciprocal space and diffuse scattering for the identification of regions of interest for subsequent inelastic scattering studies, but can also be employed as a fully independent station for structural studies from both powder and single-crystal diffraction experiments. Several software packages for the transformation and visualization of diffraction data are available. An analysis of data collected with the new diffractometer shows that the ID28 side station is a state-of-the-art instrument for structural investigations using diffraction and diffuse scattering experiments.

Comparison of different dosage regimes of epsilon aminocaproic acid on blood loss in children undergoing craniosynostosis surgery.

BACKGROUND: Open cranial vault reconstruction is frequently performed for craniosynostosis. These procedures often involve high volume blood loss that requires blood transfusion. Antifibrinolytics have been shown to decrease blood loss during these procedures but the optimal dose that maximizes benefits is not known. AIMS: The primary aim was to evaluate the differences in calculated blood loss between a high infusion rate (40 mg/kg/h) and a low infusion rate (≤30 mg/kg/h) of epsilon aminocaproic acid after a 100 mg/kg loading dose. Secondary aims were to determine if a high infusion rate of epsilon aminocaproic acid was associated with decreased packed red cell transfusion volume and to determine the factors associated with blood loss. METHODS: This was a retrospective study of children who underwent open cranial vault reconstruction. Using an electronic medical record, we identified patients that fit the inclusion criteria. Demographic, laboratory, transfusion, and perioperative data were collected and statistical analysis was performed. RESULTS: Fifty-three patients were included into the study with twenty-three receiving higher infusion rate (40 mg/kg/h) epsilon aminocaproic acid. There was a 14.3 mL/kg (95% CI 6.6-23.9) decrease in calculated blood loss in the high-dose cohort. CONCLUSION: An EACA bolus of 100 mg/kg followed by an infusion of 40 mg/kg was associated with a lower calculated blood loss compared to the group who received 100 mg/kg EACA and ≤ 30 mg/kg infusion.

Dilutional coagulopathy in pediatric scoliosis surgery: A single center report.

BACKGROUND: Children undergoing posterior spinal fusion experience high blood loss often necessitating transfusion. An appropriately activated coagulation system provides hemostasis during surgery, but pathologic dysregulation can cause progressive bleeding and increased transfusions. Despite receiving antifibrinolytics for clot stabilization, many patients still require transfusions. AIMS: We sought to examine the association of dilutional coagulopathy with blood loss and blood transfusion in posterior spinal fusion for pediatric scoliosis patients. METHODS: A retrospective, single institution study of children undergoing posterior spinal fusion >6 levels with a standardized, prospective anesthetic protocol utilizing antifibrinolytics. Blood loss was evaluated using a hematocrit-based calculation. To evaluate transfusions, a normalized Blood Product Transfusion calculation was developed. Factors associated with blood loss and blood transfusions were determined by univariate analysis and multivariate regression modeling with multicollinearity and mediation analysis. RESULTS: Patients received 73.7 mL/kg (standard deviation ±30.8) of fluid poor in coagulation factors. Estimated blood loss was 42.6 mL/kg (standard deviation ±18.0). There was a significant association between estimated blood loss and total fluids delivered (Spearman's rho = 0.51, 95% confidence interval 0.33-0.65, P < 0.001). Factors significantly associated with normalized Blood Product Transfusion in this cohort included age, weight, scoliosis type, levels fused, total osteotomies, pelvic fixation, total fluid, maximum prothrombin time, and minimum fibrinogen. Regression modeling showed the best combination of variables for modeling normalized Blood Product Transfusion included patient weight, number of levels fused, total fluid administered, and maximum prothrombin time. CONCLUSION: Blood product transfusion remains a frustrating problem in pediatric scoliosis. Identifying and controlling dilutional coagulopathy in these patients may reduce blood loss and the need for blood transfusion.

Perioperative Outcomes and Management in Pediatric Complex Cranial Vault Reconstruction: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND: The Pediatric Craniofacial Collaborative Group established the Pediatric Craniofacial Surgery Perioperative Registry to elucidate practices and outcomes in children with craniosynostosis undergoing complex cranial vault reconstruction and inform quality improvement efforts. The aim of this study is to determine perioperative management, outcomes, and complications in children undergoing complex cranial vault reconstruction across North America and to delineate salient features of current practices. METHODS: Thirty-one institutions contributed data from June 2012 to September 2015. Data extracted included demographics, perioperative management, length of stay, laboratory results, and blood management techniques employed. Complications and outlier events were described. Outcomes analyzed included total blood donor exposures, intraoperative and perioperative transfusion volumes, and length of stay outcomes. RESULTS: One thousand two hundred twenty-three cases were analyzed: 935 children aged less than or equal to 24 months and 288 children aged more than 24 months. Ninety-five percent of children aged less than or equal to 24 months and 79% of children aged more than 24 months received at least one transfusion. There were no deaths. Notable complications included cardiac arrest, postoperative seizures, unplanned postoperative mechanical ventilation, large-volume transfusion, and unplanned second surgeries. Utilization of blood conservation techniques was highly variable. CONCLUSIONS: The authors present a comprehensive description of perioperative management, outcomes, and complications from a large group of North American children undergoing complex cranial vault reconstruction. Transfusion remains the rule for the vast majority of patients. The occurrence of numerous significant complications together with large variability in perioperative management and outcomes suggest targets for improvement.

Intraoperative optimization to decrease postoperative PRBC transfusion in children undergoing craniofacial reconstruction.

BACKGROUND: Craniofacial reconstructive surgery for craniosynostosis is associated with large blood loss and intraoperative transfusion. This blood loss may continue through the initial postoperative period, potentially resulting in transfusion postoperatively. The purpose of this study is to determine if there is an association between any modifiable intraoperative factors and postoperative blood transfusion in this patient population. METHODS: A cohort of 55 pediatric patients who underwent primary craniofacial reconstruction at Vanderbilt Children's Hospital from January 1, 2013 to April 31, 2014 was analyzed. The authors analyzed 20 different demographic and perioperative variables for statistical associations with postoperative PRBC transfusion using multiple logistic regression with optimal models being selected by Bayesian model averaging. RESULTS: The optimal regression model only included initial PACU Hct as a predictor and showed a significant association between this variable and postoperative PRBC transfusion (odds ratio 0.69, 95% CI 0.55-0.87, P = 0.0016). Based on the average decrease in postoperative hematocrit (Hct) and the postoperative transfusion trigger, an initial PACU Hct threshold of 30 was calculated. In our patient sample, an initial PACU Hct above 30 was associated with a 50% decrease in the absolute risk of receiving a PRBC transfusion postoperatively. CONCLUSIONS: Based on this retrospective analysis, it may be justifiable to transfuse residual volume from previously exposed intraoperative PRBCs to a Hct above 30 to decrease the likelihood of subsequent blood transfusions from different donors in the postoperative period.

A study survey on molnupiravir treatment in COVID-19 patients at home in Ninh Thuan province, Vietnam.

OBJECTIVE: Molnupiravir (MOV) is an oral antiviral drug that received use authorization in Vietnam for the treatment of mild COVID-19 (F0). There was a need to develop alternative approaches that allowed patients to access medication, decongest hospitals, clinics, and facilities, and protect people from infection. During the COVID-19 crisis, the Ninh Thuan Health Authorities implemented the home delivery of medication by community health workers. This study conducted in collaboration with two important Italian entities [the Aldo Moro University of Bari City and the 118 Department of Territorial Emergency System (118 SET) of Taranto City] aimed to evaluate the implementation of home delivery F0 treatment package assessing the rate of infection recovering during the coronavirus pandemic in Ninh Thuan province, Vietnam. PATIENTS AND METHODS: A convergent mixed methods research, based on a longitudinal study with quantitative research and qualitative assessments, evaluated four implementation outcomes: the feasibility, fidelity, coverage, sustainability, and effectiveness of the initiative. Data sources included routinely collected data, a telephonic survey of patients, an analysis of set-up and recurrent costs, as well as descriptive exploratory qualitative and quantitative analysis. RESULTS: After taking the MOV for 5 days, only 35 out of the initial 400 F0 patients remained positive, while 365 patients (91.2%) were negative (CT≥30). Whilst, the successful rate after using the drug during the course accounted for 99.85% and 100% after the entire treatment course, without any death. After 5 days of taking the drug, a positive test result (CT<30) was associated with age group ≥60 (OR=2.7) and comorbidities (OR=3.0) (p<0.05) compared to negative and positive results (CT≥30). Negative factors impacting F0 at home include a shortage of healthcare workers, inadequate supply of thermometers and SpO2 meters, and insufficient financial support for healthcare workers. CONCLUSIONS: MOV caused a reduction in the risk of hospitalization or death in mild COVID-19 patients, and molnupiravir was also found to be well tolerated and safe without any major adverse events during the administration period.

Symptomatic cerebral vasospasm following resection of a medulloblastoma in a child.

BACKGROUND: Vasospasm may occur following intracranial tumor resection but is uncommon following resection of tumors in the posterior fossa. METHODS: Case report. RESULTS: Here, we report an unusual pediatric case of symptomatic cerebral vasospasm following resection of a posterior fossa medulloblastoma in a 10-year-old child. CT angiogram and serial Transcranial Doppler (TCD) studies confirmed the presence of vasospasm and response to hemodynamic augmentation therapy, resulting in favorable outcome. CONCLUSION: This case illustrates an unusual complication of posterior fossa tumor resection, and the potential utility of TCD studies in the detection and management of vasospasm in pediatric neurocritical care.

Prolonged cardiac arrest and resuscitation by extracorporeal life support: favourable outcome without preceding anticoagulation in an experimental setting.

State-of-the-art cardiopulmonary resuscitation (CPR) restores circulation with inconsistent blood-flow and pressure. Extracorporeal life support (ECLS) following CPR opens the opportunity for "controlled reperfusion". In animal experiments investigating CPR with ECLS, systemic anticoagulation before induced cardiac arrest is normal, but a major point of dispute, since preliminary heparinization in patients undergoing unwitnessed cardiac arrest is impossible. In this study, we investigated options for ECLS after an experimental 15 minutes normothermic cardiac arrest, without preceding anticoagulation, in pigs. Neurological recovery was assessed by a scoring system, electroencephalography and brain magnetic resonance imaging. Additionally, brain histology was performed on day seven after cardiac arrest. We demonstrated that preliminary heparin administration was not necessary for survival or neurological recovery in this setting. Heparin flushing of the cannulae seemed sufficient to avoid thrombus formation. These findings may ease the way to using ECLS in patients with sudden cardiac arrest.

Sarcopenic obesity: epidemiology, pathophysiology, cardiovascular disease, mortality, and management.

Sarcopenic obesity is defined as the coexistence of sarcopenia and obesity in the same individual, characterized by of the co-presence of body fat accumulation and muscle loss. This condition is currently a major concern as it is associated with frailty and disabilities such as cardiovascular disease, fractures, dementia, cancer, and increased all-cause mortality. Particularly, older individuals remain at risk of sarcopenic obesity. Progress at several levels is needed to improve the global prognostic outlook for this condition, including the elaboration and implementation of a more uniform definition that may favor the identification and specification of prevalence by age group. Furthermore, improvements in the understanding of the pathogenesis of sarcopenic obesity may lead to the development of more specific therapeutic interventions to improve prognosis. We reviewed the knowledge on sarcopenic obesity and its associations with cardiovascular diseases and mortality.

Oral administration of ginseng berry concentrate improves lactate metabolism and increases endurance performance in mice.

In the present study, to determine the efficacy of oral supplementation of ginseng berry extracts in augmenting exercise performance and exercise-associated metabolism, male mice were given orally 200 and 400 mg/kg of body weight (BW) of GBC for nine weeks. Although there are no differences in pre-exercise blood lactate levels among (1) the control group that received neither exercise nor GBC, (2) the group that performed only twice-weekly endurance exercise, and (3) and (4) the groups that combined twice-weekly endurance exercise with either 200 or 400 mg/kg GBC, statistically significant reductions in post-exercise blood lactate levels were observed in the groups that combined twice-weekly endurance exercise with oral administration of either 200 or 400 mg/kg GBC. Histological analysis showed no muscle hypertrophy, but transcriptome analysis revealed changes in gene sets related to lactate metabolism and mitochondrial function. GBC intake increased nicotinamide adenine dinucleotide levels in the gastrocnemius, possibly enhancing the mitochondrial electron transport system and lactate metabolism. Further molecular mechanisms are needed to confirm this hypothesis. [BMB Reports 2023; 56(6): 353-358].

Increasing sustainability in pork production by using high inclusion levels of co-products distillers dried grains with solubles, wheat middling and canola meal doesn't affect pig growth performance and meat quality but reduces boar taint.

OBJECTIVE: The present study is to examine the effect of high inclusion of co-products in pig diets (referred to as an alternative diet) during the finishing stage on pig growth performance, meat quality and boar taint compounds. METHODS: Growing pigs were fed an alternative diet made with distillers dried grains with solubles (25%), canola meal (20%), and wheat middling (15%) or a control diet based on barley and soybean meal to investigate the impact of co-products on pig performance and meat quality. Sixteen female and sixteen entire male Duroc×(Large White×Landrace) pigs (22.6±2.07 kg, body weight±standard error) were equally allocated to the diets. RESULTS: Pigs fed the alternative diet had a lower feed intake; however, growth rate and feed conversion efficiency were unaffected by diet. A diet by sex interaction was found for gain:feed whereby males fed the alternative diet had the best feed conversion (p<0.01). Pork from pigs fed the alternative diet had lower a* and Chroma and protein % (p<0.05), while other meat quality characteristics were unaffected. The alternative diet reduced backfat skatole levels (p<0.001). CONCLUSION: A diet containing high inclusion levels of co-products can be fed to pigs during the finishing stage without detrimental effects on pig performance or meat quality and with the potential to enhance pork flavour. This finding suggests a solution to increase the sustainable development of pig production.

A daily and complete PM2.5 dataset derived from space observations for Vietnam from 2012 to 2020.

PM2.5 pollution is a serious problem in Vietnam and around the world, having bad impacts on human health, animals and environment. Regular monitoring at a large scale is important to assess the status of air pollution, develop solutions and evaluate the effectiveness of policy implementation. However, air quality monitoring stations in Vietnam are limited. In this article, we propose an approach to estimate daily PM2.5 concentration from 2012 to 2020 over the Vietnamese territory, which is strongly affected by cloudy conditions, using a modern statistical model named Mixed Effect Model (MEM) on a dataset consisting of ground PM2.5 measurements, integrated satellite Aerosol Optical Depth (AOD), meteorological and land use maps. The result of this approach is the first long-term, full coverage and high quality PM2.5 dataset of Vietnam. The daily mean PM2.5 maps have high validation results in comparison with ground PM2.5 measurement (Pearson r of 0.87, R2 of 0.75, RMSE of 11.76 µg/m3, and MRE of 36.57 % on a total of 13,886 data samples). The aggregated monthly and annual average maps from 2012 to 2020 in Vietnam have outstanding quality when compared with another global PM2.5 product. The PM2.5 concentration maps has shown spatial distribution and seasonal variations of PM2.5 concentration in Vietnam in a long period from 2012 to 2020 and has been used in other studies and applications in the environment and public health at the national scale, which has not been possible before because of the lack of monitoring stations and an appropriate PM2.5 modeling approach.

Mitochondria-associated programmed cell death as a therapeutic target for age-related disease.

Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically, mediate cell fate. Evidence has shown mitochondria as points of convergence for diverse cell death-inducing pathways that trigger the various mechanisms underlying apoptotic and nonapoptotic programmed cell death. Thus, dysfunctional cellular pathways eventually lead or contribute to various age-related diseases, such as neurodegenerative, cardiovascular and metabolic diseases. Thus, mitochondrion-associated programmed cell death-based treatments show great therapeutic potential, providing novel insights in clinical trials. This review discusses mitochondrial quality control networks with activity triggered by stimuli and that maintain cellular homeostasis via mitohormesis, the mitochondrial unfolded protein response, and mitophagy. The review also presents details on various forms of mitochondria-associated programmed cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, parthanatos, and paraptosis, and highlights their involvement in age-related disease pathogenesis, collectively suggesting therapeutic directions for further research.

Applications of Artificial Intelligence and Machine Learning in Disasters and Public Health Emergencies.

Indexed literature (from 2015 to 2020) on artificial intelligence (AI) technologies and machine learning algorithms (ML) pertaining to disasters and public health emergencies were reviewed. Search strategies were developed and conducted for PubMed and Compendex. Articles that met inclusion criteria were filtered iteratively by title followed by abstract review and full text review. Articles were organized to identify novel approaches and breadth of potential AI applications. A total of 1217 articles were initially retrieved by the search. Upon relevant title review, 1003 articles remained. Following abstract screening, 667 articles remained. Full text review for relevance yielded 202 articles. Articles that met inclusion criteria totaled 56 articles. Those identifying specific roles of AI and ML (17 articles) were grouped by topics highlighting utility of AI and ML in disaster and public health emergency contexts. Development and use of AI and ML have increased dramatically over the past few years. This review discusses and highlights potential contextual applications and limitations of AI and ML in disaster and public health emergency scenarios.

Prevalence of Physical Activity, Screen Time, and Sleep, and Associations with Adiposity and Motor Development among Preschool-Age Children in Vietnam: The SUNRISE Vietnam Pilot Study.

OBJECTIVES: Global childhood obesity is of great concern. In 2019, the World Health Organization released global guidelines on movement behaviors for the children under 5 y of age to combat this epidemic. This study aimed to estimate the prevalence of Vietnamese preschoolers meeting the guidelines, and examined whether guideline compliance is associated with adiposity and motor development. METHODS: A cross-sectional study was conducted on 103 healthy preschoolers who were conveniently sampled from preschools in urban and rural areas around Ho Chi Minh city. Time spent in different intensities of physical activity and sedentary behavior was measured using Actigraph GT3X + accelerometers over three consecutive days. Sleep and screen time were obtained via parent questionnaires. Children were classified as meeting or not meeting the global guidelines. Height, weight, and motor skills were measured by the research staff. Regression models were applied to quantify the association between guideline compliance and adiposity and motor development, adjusting for age and sex. RESULTS: While 17.5% of children met all three guidelines, 5.8% met no guidelines. The prevalences of children who met guidelines for physical activity time, sleep duration, and screen time were 50.4%, 81.4%, and 44.7%, respectively. There was no association between guideline compliance and adiposity and motor development. CONCLUSION: This study found a low proportion of children who met the global guidelines, whereas a high proportion of those with overweight and obesity was reported. Health programs should promote more physical activities of various intensities in young children.

Retinopathy signs in people without diabetes: the multi-ethnic study of atherosclerosis.

OBJECTIVE: To describe the prevalence of retinopathy and associations with cardiovascular risk factors in persons without diabetes in 4 racial/ethnic groups (white, black, Hispanic, and Chinese). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 6176 subjects aged 45-84 years without diabetes, selected from 6 United States communities. METHODS: Fundus images were taken using 45° digital camera through dark-adapted pupils and were graded for retinopathy as defined by the Early Treatment Diabetic Retinopathy Study severity scale: microaneurysms, hemorrhages, cotton wool spots, intraretinal microvascular abnormalities, hard exudates, venous beading, and new vessels. MAIN OUTCOME MEASURES: Retinopathy and the association with cardiovascular risk factors. RESULTS: Prevalence rates of retinopathy in persons without diabetes were 12.5% overall, varying from 11.9% (white), 13.9% (black), 12.6% (Hispanic), to 17.2% (Chinese). Hypertension was strongly associated with retinopathy (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.23-1.75). After adjusting for age, gender, race, and other parameters, smoking (OR, 1.50; 95% CI, 1.09-2.06) and increased internal carotid intima media thickness (OR, 1.22; 95% CI, 1.05-1.41) were associated with retinopathy. A range of serum inflammatory factors were examined, but none were found to be significant. CONCLUSIONS: Retinopathy in persons without diabetes is common, varies with race/ethnicity, and associated with cardiovascular risk factors, including hypertension, smoking, and carotid artery intima media thickness.