Development Institute Research Articles

OPTIMIZATION OF ASSESSMENT OF RISKS AND NEEDS OF PRISONERS IN THE IMPLEMENTATION OF THE INDEPENDENCE DEVELOPMENT PROGRAM IN CLASS IIA COMMUNITY INSTITUTIONS PEMATANG SIANTAR BENGKULU

In social life, children's development tends to be in the spotlight because children are predicted to be the next generation who are the hopes of parents, families, religion, and even the state. Concerns about a child's future arise when a child comes into conflict with the law due to a criminal act he or she has committed and is serving a prison term. However, these concerns were dispelled by the presence of legislation which ensured that this country paid more attention to its human resources. This research aims to produce a service based on a humanistic approach carried out by correctional officers for assisted children, where later this service can become a forum for developing children during their criminal period as well as preparing children for a better life after the criminal process is completed. This study used qualitative research methods. By taking a humanistic concept which refers to basic needs, security needs, social and affection needs as well as self-actualization needs which will later be applied to the Class IIA Bengkulu Special Development Institute for Children.

Protocol for a nationwide case-control study of firearm violence prevention tactics and policies in K-12 schools.

Most U.S. K-12 schools have adopted safety tactics and policies like arming teachers and installing metal detectors, to address intentional school gun violence. However, there is minimal research on their effectiveness. Furthermore, sociodemographic factors may influence their implementation. Controlled studies are necessary to investigate their impact on gun violence and related disciplinary outcomes. The paper outlines the protocol for a case-control study examining gun violence prevention policies in U.S. K-12 schools. The study aims to investigate if there is an association between the total number and type of specific safety tactics and policies and the occurrence of intentional shootings in K-12 public schools, student disciplinary outcomes, and if urbanicity, economic, and racial factors modify these associations. We will create a nationally representative dataset for this study and ascertain a full census of case schools (schools that experienced intentional gunfire on the campus during school hours since 2015) through national school shooting databases. Matched control schools will be randomly selected from U.S. Department of Education's national database of all public schools. We will analyze 27 school safety strategies organized into seven key exposure groupings. Supported by the National Institutes for Child Health and Development (R01HD108027-01) and having received Institutional Review Board approval, our study is currently in the data collection phase. Our analytical plan will determine the association between the number and type of school safety tactics and policies with the occurrence of intentional shootings and suspensions and expulsions in a national sample of approximately 650 K-12 public schools. Additional analyses will investigate the effect modification of specific covariates. As the first national, controlled study, its results will provide novel and needed data on the effectiveness of school safety tactics and policies in preventing intentional shootings at K-12 public schools.

Development of new hormonal male contraception for the couple.

Current options for male contraception are limited to condoms, the withdrawal method, or a vasectomy. Studies indicate that men have expressed growing interest in bearing responsibility for family planning. To review prior studies investigating the role of an androgen-only or androgen with progestin regimen for hormonal male contraception and to provide an update of a promising new hormonal agent, a transdermal gel. Thus far, there have been six studies conducted in couples evaluating the contraceptive efficacy of an androgen-only or androgen co-administered with a progestin regimen for hormonal male contraception. The only ongoing study is by the National Institute of Child Health and Human Development, in collaboration with the Population Council. They have developed a novel transdermal gel containing testosterone and segesterone acetate (Nestorone), a progestin. An ongoing phase II study enrolling more than 460 couples has shown great potential with respect to the product's efficacy, safety, reversibility, and acceptability. As this agent advances in development, a rapid at-home test for sperm concentration will provide couples with immediate feedback regarding their potential for pregnancy. There is promise for the first-of-its-kind hormonal male contraceptive, a transdermal gel, to achieve market approval for distribution in the United States and elsewhere. Its safety, efficacy, reversibility, and user-control are all appealing qualities that make it readily adoptable for clinical practice.

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation

Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains

Bacterial diversity could contribute to the diversity of tuberculosis infection and treatment outcomes observed clinically, but the biological basis of this association is poorly understood. The aim of this study was to identify associations between phenogenomic variation in Mycobacterium tuberculosis and tuberculosis clinical features. We developed a high-throughput platform to define phenotype-genotype relationships in M tuberculosis clinical isolates, which we tested on a set of 158 drug-sensitive M tuberculosis strains sampled from a large tuberculosis clinical study in Ho Chi Minh City, Viet Nam. We tagged the strains with unique genetic barcodes in multiplicate, allowing us to pool the strains for in-vitro competitive fitness assays across 16 host-relevant antibiotic and metabolic conditions. Relative fitness was quantified by deep sequencing, enumerating output barcode read counts relative to input normalised values. We performed a genome-wide association study to identify phylogenetically linked and monogenic mutations associated with the in-vitro fitness phenotypes. These genetic determinants were further associated with relevant clinical outcomes (cavitary disease and treatment failure) by calculating odds ratios (ORs) with binomial logistic regressions. We also assessed the population-level transmission of strains associated with cavitary disease and treatment failure using terminal branch length analysis of the phylogenetic data. M tuberculosis clinical strains had diverse growth characteristics in host-like metabolic and drug conditions. These fitness phenotypes were highly heritable, and we identified monogenic and phylogenetically linked variants associated with the fitness phenotypes. These data enabled us to define two genetic features that were associated with clinical outcomes. First, mutations in Rv1339, a phosphodiesterase, which were associated with slow growth in glycerol, were further associated with treatment failure (OR 5·34, 95% CI 1·21-23·58, p=0·027). Second, we identified a phenotypically distinct slow-growing subclade of lineage 1 strains (L1.1.1.1) that was associated with cavitary disease (OR 2·49, 1·11-5·59, p=0·027) and treatment failure (OR 4·76, 1·53-14·78, p=0·0069), and which had shorter terminal branch lengths on the phylogenetic tree, suggesting increased transmission. Slow growth under various antibiotic and metabolic conditions served as in-vitro intermediate phenotypes underlying the association between M tuberculosis monogenic and phylogenetically linked mutations and outcomes such as cavitary disease, treatment failure, and transmission potential. These data suggest that Mtuberculosis growth regulation is an adaptive advantage for bacterial success in human populations, at least in some circumstances. These data further suggest markers for the underlying bacterial processes that contribute to these clinical outcomes. National Health and Medical Research Council/A∗STAR, National Institutes of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the Wellcome Trust Fellowship in Public Health and Tropical Medicine.

Personalized lung care: Bronchopulmonary dysplasia risk prediction tool tailored for neonates born in resource-limited settings.

Predicting bronchopulmonary dysplasia (BPD) to assess the risk-benefit of therapy is necessary considering the side effects of medications. We developed and validated an instrument for predicting BPD and compared it with an instrument currently used for neonates born in a Brazilian hospital. This was a retrospective cohort study of patients born between 2016 and 2020 with a gestational age (GA) between 23 and 30 weeks. Predictive equations were elaborated using methods of component variable selection collected on the 14th day of life; 70% of the sample was randomly selected for the construction of risk prediction equations and the remaining 30% for their validation, application, and comparison with the National Institute of Child Health and Human Development (NICHD) instrument. The sensitivity, specificity, and predictive values of the equations were calculated. The equation that used variables with p < 5% in Fisher's exact test presented the best results: specificity of 98% and positive predictive value of 93% and could be used for BPD prediction of all small-for-gestational-age (SGA) infants. The NICHD calculator applied to our population had a specificity of 93% and a positive predictive value of 75% and could not be applied to extremely SGA infants. Our tool can predict the risk of BPD on the 14th day of life, has higher specificity and positive predictive value to our population than the NICHD instrument, and can be suitable for SGA infants. The results must be confirmed by applying it to other populations to validate our tool.

PECARN prediction rules for CT imaging of children presenting to the emergency department with blunt abdominal or minor head trauma: a multicentre prospective validation study

The intra-abdominal injury and traumatic brain injury prediction rules derived by the Pediatric Emergency Care Applied Research Network (PECARN) were designed to reduce inappropriate use of CT in children with abdominal and head trauma, respectively. We aimed to validate these prediction rules for children presenting to emergency departments with blunt abdominal or minor head trauma. For this prospective validation study, we enrolled children and adolescents younger than 18 years presenting to six emergency departments in Sacramento (CA), Dallas (TX), Houston (TX), San Diego (CA), Los Angeles (CA), and Oakland (CA), USA between Dec 27, 2016, and Sept 1, 2021. We excluded patients who were pregnant or had pre-existing neurological disorders preventing examination, penetrating trauma, injuries more than 24 h before arrival, CT or MRI before transfer, or high suspicion of non-accidental trauma. Children presenting with blunt abdominal trauma were enrolled into an abdominal trauma cohort, and children with minor head trauma were enrolled into one of two age-segregated minor head trauma cohorts (younger than 2 years vs aged 2 years and older). Enrolled children were clinically examined in the emergency department, and CT scans were obtained at the attending clinician's discretion. All enrolled children were evaluated against the variables of the pertinent PECARN prediction rule before CT results were seen. The primary outcome of interest in the abdominal trauma cohort was intra-abdominal injury undergoing acute intervention (therapeutic laparotomy, angiographic embolisation, blood transfusion, intravenous fluid for ≥2 days for pancreatic or gastrointestinal injuries, or death from intra-abdominal injury). In the age-segregated minor head trauma cohorts, the primary outcome of interest was clinically important traumatic brain injury (neurosurgery, intubation for >24 h for traumatic brain injury, or hospital admission ≥2 nights for ongoing symptoms and CT-confirmed traumatic brain injury; or death from traumatic brain injury). 7542 children with blunt abdominal trauma and 19 999 children with minor head trauma were enrolled. The intra-abdominal injury rule had a sensitivity of 100·0% (95% CI 98·0-100·0; correct test for 145 of 145 patients with intra-abdominal injury undergoing acute intervention) and a negative predictive value (NPV) of 100·0% (95% CI 99·9-100·0; correct test for 3488 of 3488 patients without intra-abdominal injuries undergoing acute intervention). The traumatic brain injury rule for children younger than 2 years had a sensitivity of 100·0% (93·1-100·0; 42 of 42) for clinically important traumatic brain injuries and an NPV of 100·0%; 99·9-100·0; 2940 of 2940), whereas the traumatic brain injury rule for children aged 2 years and older had a sensitivity of 98·8% (95·8-99·9; 168 of 170) and an NPV of 100·0% (99·9-100·0; 6015 of 6017). The two children who were misclassified by the traumatic brain injury rule were admitted to hospital for observation but did not need neurosurgery. The PECARN intra-abdominal injury and traumatic brain injury rules were validated with a high degree of accuracy. Their implementation in paediatric emergency departments can therefore be considered a safe strategy to minimise inappropriate CT use in children needing high-quality care for abdominal or head trauma. The Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Autophagy Is Required for Cell Growth and Protein Anabolism in Lung Cancer

Background: Rampant and unregulated cell growth is a key hallmark of cancer pathology; however, much remains to be discovered about the process that allow for pathological growth in cancerous cells. Recently, we demonstrated that the autophagy-related cysteine protease ATG4B is required for protein anabolism in skeletal muscle, indicating a previously undescribed mechanism by which autophagy directly acts as a recycling/remodeling system for cellular anabolism. Purpose: To investigate if ATG4B is responsible for growth in cancer, and if inhibition of ATG4B is a successful strategy to target cancer growth. Hypothesis: We hypothesized that ATG4B would be higher in cancerous tissues versus healthy ones, and that inhibition of ATG4B by NSC185058 would inhibit cell growth and reduce protein anabolism. Methods: We used the UALCAN web tool to analyze the TCGA data set for differences in ATG4B gene expression in lung adenocarcinoma, comparing healthy to cancerous tissues as well as across cancer stages. Separately, we used the A549 lung cancer cell line as a model to study the effects of ATG4B inhibition, treating cells with 100 μM NSC185058 or equimolar DMSO as a vehicle control, and analyzing treated cells for proliferation and protein synthesis rates. Welch’s t-test was used to calculate differences in TCGA data, while a two-tailed student’s t-test was used to determine differences in proliferation at indicated time points, with an α-level of 0.05. Results: ATG4B expression is 22% higher in cancerous tissues vs healthy controls (p&lt;0.05), and also higher in stages 1-4 of lung adenocarcinoma (Healthy vs Stage 1: +25%, Healthy vs Stage 2: +23%, Healthy vs Stage 3: +13%, Healthy vs Stage 4: +30%, p&lt;0.05). Treatment with NSC185058 suppresses cell growth across 72 hours (24 hour VC vs NSC: -59%, 48 hour VC vs NSC: -83%, 72 Hour VC vs NSC: -90%), and reduces 24-hour rates of protein synthesis by 56% (p&lt;0.05) in cancer cells. Conclusions: ATG4B expression is increased in lung adenocarcinoma, including in early-stage cancer, and inhibition by NSC185058 drastically reduces anabolism in cancerous cells. We posit that autophagy, mediated by ATG4B is required for protein anabolism in lung cancer, and that targeting this process represents a novel strategy to combat cancer pathology. This work was generously funded by the Huffnes Institute and School of Education and Human Development at Texas A&amp;M University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Long-latency and Volitional Responses Modulate Upper Extremity Movements During a Novel Visuomotor Tracking Task

Precise upper limb movements are essential for daily tasks and motor function. These movements are governed by feedforward and feedback mechanisms. Feedforward responses enable anticipatory movement planning, while feedback responses utilize sensory information for real-time corrections. Long-latency reflexes (LLRs) represent crucial feedback responses during unexpected perturbations. LLRs are integral in maintaining motor control and can adapt based on various factors. However, the mechanisms governing LLRs, especially in the upper extremity, remain unclear. Methods: Forty healthy participants performed a visuomotor elbow flexion task with one arm while the opposite limb remained static. Muscle activity of the biceps and triceps muscles of both upper extremities was recorded during perturbations. Participants completed a task with varying speeds and resistance levels. Electromyography data was analyzed across pre-perturbation, short-latency reflex (SLR), long-latency reflex (LLR), and voluntary response (VR) phases. Results: In response to unexpected upper extremity perturbations, participants predominantly relied on two core strategies. Inhibitory long-latency reflexes within the biceps played a central role, with participants emphasizing inhibition to maintain movement stability in a window of 50-120 ms after the disturbance. Furthermore, volitional control, primarily executed through the triceps muscles, emerged as another dominant approach, allowing participants to actively regain precision and control after the perturbation in a volitional manner starting from 120 ms. Participants’ response to perturbations reflected the task context and perceived urgency. Over repeated trials, participants refined their response strategies, becoming more precise and effcient. Variations in movement speed and resistance influenced muscle activity. Preliminary evidence suggested the involvement of cross-transcortical communication in response to perturbations, with delayed responses observed in the non-participating upper extremity. Conclusion: This study reveals that participants use both long-latency and volitional responses to counteract perturbations during an upper extremity visuomotor task, adapting their response strategies over time. Biceps inhibitory LLRs and triceps voluntary activation characterize feedback control in this context. These findings shed light on the dynamic nature of upper extremity feedback responses during unpredictable perturbations and suggest the involvement of cross-transcortical communication. Understanding these mechanisms can inform rehabilitation strategies for individuals with neurological conditions affecting motor control. Research Support: This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: R01HD084645, R01HD082109. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Genomic and epigenomic changes by low force electrically induced exercise of human paralyzed muscle

Musculoskeletal deterioration following complete paralysis, such as after a spinal cord injury, results in osteoporotic bone and atrophic, glycolytic, and insulin-resistant skeletal muscle. Decreased bone integrity can be overloaded with very little force; therefore, high force contractions should be avoided in people with long-term spinal cord injury. Together, these changes compromise systemic metabolism for people with SCI and contribute to the development of secondary non-communicable diseases. Electrically induced exercise training offers a unique strategy to ensure full muscle recruitment without high force levels by using high current intensity and a low stimulation frequency (&lt;5Hz) to prevent force summation of stimulus pulses. While acute epigenomic and genomic changes have been found with this low force exercise method; how long-term training affects skeletal muscle and systemic biomarkers of health remains unknown. Purpose: We seek to determine the long-term genomic and epigenomic response of low-force electrically induced exercise in paralyzed skeletal muscle. Methods: 10 males with a complete SCI completed at least 6-months of unilateral electrically induced exercise training using low-force (3Hz) stimulation. Participants completed at least 5 exercise training sessions per week for at least 6-months. A muscle fatigue assessment and fasting venous blood draw were performed before and after training. Percutaneous muscle biopsies were obtained from a trained and untrained vastus lateralis. Gene expression was measured using the Affymetrix HTA 2.0 array and epigenomic expression was measured using Illumina’s MethylEPIC array. Parametric tests were used to compare pre and post training. All participants provided written consent approved by the University of Iowa Institutional Review Board in compliance with the Declaration of Helsinki. Results: Participants maintained a high compliance by completing 119±19% of the training sessions for 7.2±1.2 months. There was a 115±34% change improvement of the fatigue index after training (p=0.002). Serum concentrations of insulin, hsCRP, and myostatin were decreased by 43±8% (p=0.155), 26±8%(p=0.047), 35±9%(p=0.098) after exercise training, respectively. Serum BDNF increased by 68±14%(p=0.093) after exercise training. There was a strong correlation between the primary principal component and the trained limb (R2=0.20, p=0.046). There were 693 and 671 genes to be significantly up or down regulated after exercise training (FDR &lt; 0.05). Of the genes most responsive to exercise training, MYH6, MYH7, and MYL3 were increased in expression and decreased in median methylation. MSTN and ACTN3 were decreased in genomic expression with an increase in median methylation after exercise training. Conclusions: Low-force electrically induced exercise training improved fatigability, a muscle oxidative phenotype transition, and improved serum biomarkers associated with metabolism and inflammation. Together, these data highlight the impact low-force electrically induced exercise can have on paralyzed muscle and is suggestive that this rehabilitation strategy may provide benefits for people living with paralysis. Research Support: This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: R01HD084645, R01HD082109. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Body Water Compartment and Sympathovagal Balance: Association with Visuomotor Retention in Young Adults

Cognitive functions are important for visuomotor learning and are associated with physiological factors such as body fluid compartment and cardiovascular reactivity. Previous studies found that body fluid compartment is associated with brain blood flow, which is regulated via sympathovagal balance. However, more evidence is needed to determine whether body fluid compartment and cardiovascular reactivity are associated with visuomotor learning. The purpose of this study was to explore the relationship of body fluid compartment and cardiovascular reactivity to visuomotor learning. We hypothesized that these physiological factors are associated with overall learning retention using upper extremity (including feedforward, volitional, and feedback conditions). Methods: Thirty young adults (12 males, 24.6 ± 3.9 years, right hand dominant) participated in this study. Participants tracked a sinusoidal wave with left arm at pre-test, learning, and post-test sessions on the first visit and at retention test session on the second visit seven days later. Participants performed one set of nine trials during each test and five sets of three trials during learning. Resistance and wave velocity were different in each trial. Learning error was calculated by the averaged absolute distance between the tracking line and the target line. Heart rate (HR), systolic blood pressure (SBP), and low to high frequency power ratio of heart rate variability (LF/HF) were continuously recorded during baseline before pre-test and during tests and learning. We analyzed participants’ extracellular to intracellular body water ratio (ECW/ICW) using an InBody body composition analyzer and tested their cognitive function with Picture Sequence Memory (PSMT), Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and List Sorting Working Memory Tests from NIH Cognitive Toolbox. Data were statistically analyzed using linear regression analysis and quartile analysis. Results: ECW/ICW was associated with young adults’ ability to retain visuomotor learning after one week (R2 = 0.138, p = 0.043), whereas HR, SBP, and LF/HF at each session were not significantly associated with visuomotor retention. No differences were found in pre-test error among quartiles of five cognitive tests. Significant differences in retention error among quartiles were only found in PSMT, with participants scoring in the highest quartile of PSMT having lower SBP during the first visit and lower retention error compared to the lowest quartile. This finding suggests that young adults with better episodic memory were less stressed during learning and had better visuomotor retention. Conclusion: These findings support that ECW/ICW is associated with not only cognitive function but also visuomotor retention. In addition, cardiovascular reactivity during visuomotor learning may provide information for retention behavior. Relationship of body water compartment and sympathovagal balance to feedforward and feedback conditions in learning will be further discussed. Research Support: This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: R01HD084645, R01HD082109. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Physico-chemical, functional, pasting and structural characteristics of two malted maize flours produce under optimal conditions

Maize is a popular gluten-free grain, used in many dishes in Africa and elsewhere. It provides numerous nutrients (especially starch) and contains antinutritional factors (phytates). To reduce these factors and improve the nutritional and physical potential of maize, a number of treatments are required, including malting. This study therefore investigated the physicochemical, functional, structural, and pasting properties of two malted maize varieties (Atp-Y and Coca-sr) produce under optimal conditions. After receiving the two maize varieties from the Agricultural Research Institute for development, the Atp-Y variety was soaked for 30 h at 18.66 °C with 0.37% plant salt, followed by germination at 30 °C for 218.58 h and a ripening period of 40 h, while the Coca-sr variety was soaked for 3.90 h at 20.57 °C with 0.0219% plant salt, followed by germination at 30 °C for 251.55 h and a ripening period of 58.73 h. The flours obtained were subjected to physicochemical, structural, pasting and functional analysis. These analyses showed that the protein, fibre, ash, carbohydrate, starch and energy density content were significantly influenced by the variety. The Atp-Y variety had the highest contents of Ca (855.00 mg/100 g), Na (125.36 mg/100 g) and Cu (0.53 mg/100 g). The availability of Ca, Na and divalent cations was significantly higher in the Atp-Y variety. The Coca-sr variety contributed the most to achieving the protein (40.02 to 73.88%) and lipid (27.30 to 38.08%) requirements of children aged 0 to 59 months. The contents of phytates, cyanides and condensed tannins were similar in both varieties, while oxalates (7.88 mg/100 g), trypsin inhibitors (2.07 mg/100 g) and hydrolyzed tannins (15.02 mg EC/g) were more abundant in the Coca-sr variety. Phenols, flavonoids and saponins ranged between 45.96 and 68.39 mg GAE/g, 32.13 and 39.27 mg CE/g and 0.45 mg/100 g, respectively. No significant differences were found in the physical and functional properties, although the Atp-Y variety had a higher water retention and swelling capacity. Malting variety and conditions had no significant effect on Pasting Time, Setback, Setback ratio and Stability ratio in contrast to Pasting Temperature, Peak viscosity, Holding viscosity, Breakdown and Final viscosity. The Atp-Y grade exhibited the highest pasting parameters when pasting temperature was excluded. Scanning electron microscopy showed that the microscopic structure varied from one variety to another, although the grains had similar sizes. The Microscopic dispersions of grains testifies to the enzymatic activity in the Coca-sr variety, the compact surface layer with protruding grains testifies to the fiber richness of the Atp-Y variety. The grain distribution of the particles showed that more than 50% of the grains in both types were 400 µm in size. X-ray diffraction (XRD) showed that the degradation of the crystalline structure of the starch depended on the variety and the physiological phenomena taking place there. These results clearly show that these flours are well suited for the formulation of foods with high energy and nutritional value. However, they could also be used as sweeteners in panification or as raw materials in the brewing industry.

Endurance training and essential amino acid intervention synergize to ameliorate fructose-induced metabolic dysfunction in mice

Purpose: Excessive fructose (FRU) consumption can rapidly produce multiple features of metabolic syndrome, including dysregulation of systemic metabolism, insulin resistance, and diabetes. Essential amino acids (EAAs) and endurance exercise training (ET) improve abnormal metabolism in various disease conditions, yet their combined effect and metabolic mechanism remain unclear. Thus, the current study aimed to investigate metabolic kinetic mechanism and the combined effect of EAA and ET on fructose-induced metabolic dysfunction. Materials and methods: Mice were randomly divided into 5 groups with an 8-week intervention: normal chow (CON), FRU, FRU+ET, FRU+EAA or FRU+ET+ EAA, followed by stable isotope tracer infusions ([U-13C16]palmitate, [D2]glucose, and [D5]glycerol) or D2O administration to determine substrate metabolic flux rates and their contribution to TCA cycle flux and protein synthesis rates of various organs, respectively. Summary of results: FRU-induced adverse changes in body weight and physical function were reversed by ET, EAA, or ET+EAA. In stable isotope tracing analysis, ET and ET+EAA alleviated hyperglycemia by suppressing hepatic glucose production rate, while EAA and ET+EAA normalized palmitate turnover and contribution to TCA cycle in various organs. Additionally, the altered protein synthesis measured using a D2O labeling method was normalized by ET and ET+EAA. Conclusion:These findings suggest that the combined treatment of dietary EAAs and ET more effectively mitigates fructose-induced metabolic dysfunction by normalizing hepatic glucose production rate, protein synthesis rates, and fatty acid metabolism. This research was supported by a grant of the Korea Health Technology R&amp;D Project through the Korea Health industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea (HI22C2208), and the National Research Foundation of Korea (NRF), funded by the Korea government (MSIT) (No. 2021R1A2C3005801), and partially funded by MYOCARE INC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

HepScope: CNN-based single-cell discrimination of malignant hepatocytes

Background: Hepatocellular carcinoma (HCC) poses a significant global health challenge. This study aims to identify robust single-cell biomarkers specifically designed to distinguish between malignant and non-malignant hepatocytes, thereby advancing precision medicine strategies for HCC. Methods: At the single-cell level, we investigated the reliability of established marker genes for malignant hepatocytes in distinguishing them from their non-malignant counterparts. Leveraging one of the largest integrated single-cell transcriptomics (scRNA-seq) datasets of healthy and diseased liver tissues, alongside independent scRNA-seq, spatial transcriptomics (stRNA-seq), bulk RNA-seq, and bulk proteome datasets, we defined a signature gene set, denoted as HepScope. Five other publicly available gene sets related to HCC were used for comparison with HepScope. The development of machine learning (ML) and 1-dimensional convolutional neural network (1D-CNN) models involved utilizing normalized expression of signature genes from scRNA-seq datasets. The HepScope-1D-CNN model was developed to assess differentiation performance by considering the expression values of each signature gene across different tissues and within the same tissue. Finally, we calculated a risk score based on the signature genes to evaluate its prognostic capability. Result: We demonstrated the lack of specificity and consistency among current HCC marker genes in distinguishing malignant hepatocytes from non-malignant hepatocytes. The differential expression (DEG) analysis identified 113 genes upregulated in malignant hepatocytes, forming the HepScope. In contrast to HepScope, the expression values of the five other publicly available gene sets did not exhibit the ability to discriminate between malignant and non-malignant hepatocytes. Utilizing the genes from HepScope, the Gaussian Naive Bayes ML model proficiently distinguished between malignant and non-malignant hepatocytes. The HepScope-CNN model showed the highest performance and effciency compared to other 1D-CNN models trained with different gene sets. Conclusion: In conclusion, our study reveals a novel gene set designed to precisely identify malignant hepatocytes at the single-cell level. This research holds promise for advancing precision medicine in HCC, providing valuable insights into the development of targeted therapies and personalized treatment strategies. We acknowledge support provided by the National Research Foundation (NRF) of Korea (2020R1A6A1A03043539, 2020M3A9D8037604, and 2022R1C1C1004756) and the Korea Health Technology R&amp;D Project of the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea (HR22C1734). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

의료진과의 커뮤니케이션이 장애인 삶의 만족에 미치는 영향: 가족건강성의 매개효과

The purpose of this study is to examine the relationship between communication with healthcare professionals and life satisfaction among individuals with disabilities, and to verify the mediating effect of family strength in this relationship. For this purpose, data from the 3rd wave (2020) Disability and Life Dynamics Panel conducted by the Korea Disabled People’s Development Institute in 2020 were utilized, with a sample of 3,937 individuals with disabilities aged 19 and above. The analysis employed Process Macro to verify the mediating effects. The main findings of the study are as follows. Firstly, higher communication with healthcare professionals had a significant positive effect on life satisfaction. Secondly, increased communication with healthcare professionals also had a significant positive effect on family strength. Thirdly, family strength demonstrated a complete mediating effect in the relationship between communication with healthcare professionals and life satisfaction. Based on the research results and discussions, there is a suggested need for services that guarantee and support the participation of disabled individuals and their families in the medical decision-making process.

Effectiveness of food safety for halal industry in Indonesia

The present work aimed to identify and analyse stakeholders’ role in improving food safety and halalness in Semarang City. The effectiveness of food safety control can be ensured by one actor, and requires various related actors’ role. The present work used a combination of qualitative and quantitative approaches (mixed method). The data were collected using a Focus Group Discussion (FGD) held with relevant stakeholders, including Semarang City Health Office, Semarang City Trade Office, Semarang Food and Drug Administration Center, business association, academics, entrepreneurs, Consumer Development and Protection Institute, and consumers. In regard to priority aspect, it was found that emphasis must be given to three main aspects by stakeholders, namely economic, socio-cultural, and institutional, which could be used to ensure food safety and halalness for the people. Moreover, based on the stakeholder analysis results, the actors with significant influence and high dependency were entrepreneurs, Semarang City Health Office, Semarang Food and Drug Administration Center, Agency for Drug and Food Control, and academics. Meanwhile, the actors with firm convergence were Semarang City Health Office, Semarang Food and Drug Administration Center, and business associations since they share a commitment to building food safety. Furthermore, based on the FGD results, some improvements are required regarding food control that the food safety network has carried out, along with establishing food safety and halal regulation.

수업 체계성과 일관성이 대학생의 학업 성취도에 미치는 영향 분석

This study explores the association between instructional practices and college students’ achievement. Using National Assessment of Student Engagement in Learning(NASEL) data from Korean Educational Development Institute, we conducted random effect and fixed effect models to verify whether the increase in instructional organization and coherence moderates the achievement of students, especially for those with low level of cognitive competence. Results revealed that both instructional organization and coherence were positively related to student achievement. Furthermore, these instructional practices appeared to improve achievement especially for students with lower level of cognitive learning competence. These findings suggest that instructional organization and coherence may be an effective instructional practice in enhancing underprepared students’ achievement in higher education.

Gut microbiome correlates of recurrent urinary tract infection: a longitudinal, multi-center study

Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC). 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences. Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E.coli abundance 7-14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages. The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E.coli among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics. This work was supported in part by awards from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.'s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Similar rates of denial in NICHD and control interviews with alleged child abuse victims in the Netherlands

AbstractPurposeIn the current study, we investigated whether denial and avoidance rates differed statistically significantly based on the interview protocol used.MethodWe examined 38 National Institute of Child Health and Human Development (NICHD) interview transcripts, and 30 control transcripts from interviews from an earlier study (Applied Cognitive Psychology, 2022, 36, 7) conducted with alleged child victims of abuse at Dutch child protection services.ResultsWe detected 57 denial and 282 avoidance statements across the 68 interviews. No statistically significant differences emerged between (1) the proportion of denials using NICHD (42%, n = 16/38) and control interviews (30%, n = 9/30), and (2) the average number of denial statements between NICHD (M = 0.84) and control interviews (M = 0.83). Furthermore, denials (and avoidances) were not more or less likely to occur in response to certain types of questions, even though the majority of denials in our sample occurred in response to option‐posing questions (60%, n = 34/57). Denials did occur statistically significantly less often within the first half of the individual interviews in NICHD than in control interviews.ConclusionsOur findings call attention to the difficulties child protection services face in investigative interviews with alleged child victims.

Senna alata with Selenium Mitigates Liver and Kidney Injury from Isoniazid and Rifampicin in Mice

Aim: This study aimed to evaluate the ameliorative potentials of S. alata in combination with Selenium on liver and kidney injury induced by Isoniazid-Rifampicin (INH-RIF). Study Design: Original Research work. Place and Duration of Study: Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development (NIPRD), Idu, Abuja, between August and October 2023. Methods: Hydroethanolic extract of S. alata (EESA) was obtained by maceration, 25 Swiss mice (25-35g) were divided into 5 groups, GP1 received distill water, GP 2-5 INH-RIF 150mg/kg for the first two days; while groups 3-5 received S.alata 100mg/kg, 200mg/kg and 400mg/kg in combinAtion with Selenium 1mg/kg respectively from day 3 till day 14 orally. Sera samples were obtained and organs (liver and kidney) for weighing and histopathology on day 15. Results: This study showed that S.alata (EESA) (100mg/kg) and Selenium (1mg/kg) showed no reduction (P&gt;.05) in the biochemical parameters (AST, ALP, ALT, BUN, Uric acid, and creatinine); histo-anatomy of both organs showed injury. The 200mg/kg EESA/Se (1mg/kg) reduced significantly (P&lt;.05) elevated parameters for liver only (ALT, ALP); liver histo-picture showed no lesion; 400mg/kg combination decreased all parameters significantly (P&lt;.05); histo-pathology showed no lesion in both organs. Weights of the liver showed significant reduction (P=.0025, .0052, and .0027) at 100, 200, and 400mg/kg respectively; but no significant difference in weights of the kidney compared to the toxic group. Conclusion: It was concluded that EESA 200mg/kg with Selenium 1mg/kg can mitigate the toxic effects of Isoniazid-Rifampicin on the liver, while EESA/Se 400mg/kg combination has ameliorative potentials on liver and kidney toxicity from INH-RIF. These effects may be dose-dependent. It was recommended that 400mg/kg of EESA and 1mg/kg of Selenium combination be considered in drug development.