Significant Treatment Effect Research Articles

Effect of Foliar Application of Selected Plant Growth Regulators on Growth and Yield of Soybean [Glycine max (L.) Merrill

Background: Soybean (Glycine max), a prized oilseed crop known for its nutritional richness, is the focus of a study aiming to boost production with minimal environmental impact. The research explores the application of plant growth regulators (PGRs), specifically Gibberellic Acid (GA3), Kinetin and Salicylic Acid, in field experiments during the kharif seasons of 2022 and 2023 in Beed, India. Methods: The study applied Gibberellic Acid (GA3), Kinetin and Salicylic Acid at different concentrations in field experiments. A comprehensive analysis of growth and yield attributes, including plant height, primary branches, Leaf Area Index (LAI), root nodules and Crop Growth Rate (CGR), was conducted to assess the influence of PGR treatments on soybean growth. Yield attributes such as pod count, pod weight, seed count per pod and 100-seed weight were scrutinized to understand their effects on soybean productivity. Result: The study highlighted significant effects of PGR treatments on soybean growth and yield. Notably, Kinetin at 500 ppm promoted the tallest plants, while GA3 at 200 ppm resulted in the shortest. Kinetin at 100 ppm increased primary branches and Salicylic Acid at 50 ppm exhibited the highest LAI and abundant root nodules. Kinetin at 500 ppm and Salicylic Acid at 50 ppm showed higher CGR, indicating efficient crop growth. For yield, Kinetin at 500 ppm excelled in pod count and weight. GA3 at 100 ppm was identified as the most effective PGR for enhancing various growth parameters and soybean seed yield, suggesting the potential of PGRs in sustainable cultivation, reducing reliance on chemical inputs.

Efficacy of Internet-based Cognitive Behavioral Therapy for Hong Kong University Students: A Randomized Controlled Trial

Purpose: This study examined the efficacy of a 10-week internet-based cognitive behavioral therapy (iCBT) program “REST Online” for Hong Kong university students with mild to moderate levels of psychological distress. Method: A total of 206 Hong Kong university students were randomized into: (1) web-based and (2) app-based iCBT, and (3) waitlist control (WLC) groups. Results: Compared with the WLC group, the participants in the two iCBT groups showed a significant reduction in psychological distress, depression and anxiety symptoms, and negative thoughts and emotions, and significant increase in positive thoughts and emotions, with medium to large effect sizes. The positive effects were sustained at the 3-month follow-up test. No significant intervention effects were found between the two iCBT groups except for anxiety symptoms. Discussion: The findings were discussed in terms of program design and service delivery, and suggestions for delivering digital mental health service in Hong Kong universities were proposed.

Evaluation of antimicrobial and non-steroidal anti-inflammatory treatments for BRD on health and welfare in fattening bulls: a cross-sectional study

Our study aimed to evaluate the effect of different treatments for BRD on health and welfare in fattening bulls. A total of 264 bulls were enrolled. Welfare was assessed on day 2 (T0) and day 15 (T1) after arrival. A decrease in the welfare level was observed from T0 to T1. All bulls were inspected clinically at T0 and T1 revealing an increase of skin lesions and lameness in T1. In both periods, a high incidence of respiratory disease was observed. A prevalence of 79.55% and 95.45% of Mycoplasma bovis using RT-PCR and culture at T0 and T1 respectively was observed. Blood samples were collected for haematology at T0 and T1. At T0, 36 animals were individually treated for BRD with an antimicrobial (IT), 54 received a metaphylactic treatment with tulathromycin (M), 150 received a metaphylactic treatment with tulathromycin plus a second antimicrobial (M + IT) whereas 24 were considered healthy and therefore not treated (NT). Additionally, 128 were treated with a non-steroid anti-inflammatory (NSAID). Neutrophils of M + IT were significantly higher than groups NT and M and the lymphocytes of M + IT were significantly lower than that of IT. White blood cells, neutrophils and N/L ratio of animals treated with an NSAID was significantly higher than that not treated. Lung inspection of 172 bulls at the abattoir indicated that 92.43% presented at least one lung lesion. A statistically significant effect of the NSAID treatment on the lung lesions was observed. Our findings indicate that BRD was a major welfare and health concern and evidence the difficulties of antimicrobial treatment of M. bovis.

PSIII-18 Effects of HiPhorius and Ronozyme HiPhos on performance of nursery pigs

Abstract The objective of this study was to evaluate the efficacy of the new phytase HiPhorius (encoded by a 6-phytase gene from Citrobacter braakii and expressed from Aspergillus oryzae; dsm-firmenich) compared with Ronozyme HiPhos (a 6-phytase product produced with a genetically modified strain of the filamentous fungus Aspergillus oryzae; dsm-firmenich) on performance of nursery pigs. A total of 528 weaned pigs [PIC Camborough female × PIC 337 boar; 19 d of age, initial body weight (BW) = 6.5 kg] were blocked by initial BW and gender and allotted to 48 pens which were randomly assigned to 1 of 4 dietary treatments (10 to 12 pigs/pen; 12 pens/treatment), including T1) Ronozyme HiPhos 3,000 FYT/kg, T2) HiPhorius 1,000 FYT/kg, T3) HiPhorius 1,500 FYT/kg, and T4) HiPhorius 2,000 FYT/kg. Pigs were fed a 3-phase feed-budget program, consisting of 1.4 kg/pig in Phase 1, 5.5 kg/pig in Phase 2, and Phase 3 diets fed to d 42 postweaning. Diets were formulated to be isocaloric and contained 1.41, 1.34, and 1.27% SID Lys for phase 1, 2, and 3, respectively. Phytase levels were tested at the same dose in phase 1 and 2 diets, while in phase 3, phytase levels were tested at 2,000 and 1,000 FYT/kg, respectively, for the Ronozyme HiPhos and HiPhorius treatments. During d 0-15 and d 0-22, pigs fed HiPhorius 1000 had reduced (P < 0.05) feed conversion than Ronozyme HiPhos and HiPhorius 2000. No significant treatment effects were observed on average daily gain (ADG) or average daily feed intake (ADFI) during these periods. During d 22-42, pigs fed HiPhorius 2,000 had greater ADG (P = 0.08), final BW (P = 0.09), and ADFI (P = 0.03) than HiPhorius 1,000 and Ronozyme HiPhos; however, there were no treatment effects on feed conversion. Overall (d 0 - 42), feeding HiPhorius 2,000 improved ADG compared with feeding Ronozyme HiPhos, HiPhorius 1,000, and HiPhorius 1,500 (476 vs. 458, 449, and 458 g, respectively; P = 0.07); however, similar ADFI and feed conversion were observed among treatments. Data from this study suggest that feeding HiPhorius at 2,000 FYT/kg provided greater ADG compared with feeding HiPhorius at reduced amounts or Ronozyme HiPhos. While the two sources of phytase had similar responses on nursery ADFI and feed conversion overall, feeding HiPhorius at 1,000 FYT/kg resulted in decreased feed conversion during the first 3 wk post-weaning.

260 Effect of different doses of phytase (HiPhorius) and two primary calcium sources on nutrient digestibility, retention and blood parameters in weaned piglets

Abstract An 18-d study evaluated the effect of increasing phytase levels in diets with limestone or Ca-formate on Ca and P digestibility, P retention, and blood inositol, Ca, and P in weaned piglets. At weaning, male piglets [n = 60; 29.8 ± 1.10 d of age; initial body weight (BW) = 8.8 ± 0.31 kg) were randomly allocated to ten diets formulated as a 2 × 5 factorial design with 2 primary Ca sources (limestone or Ca-formate) and 5 Ca/P levels. There was a positive control diet (PC; 0.76% Ca, 0.34 dP) and 4 negative control diets (NC; 0.56% Ca, 0.34% dP) supplemented with phytase at 0, 750, 1,500, and 3,000 FYT/kg. At d 10, piglets were individually housed in metabolism crates and fed 3.2 x metabolic weight. On d 14 to 18, fecal and total urine samples were collected. Apparent total tract digestibility (ATTD) was calculated for dry matter (DM), organic matter (OM), crude protein (CP), ash, Ca, and P using TiO2 as marker. Urinary P was measured to calculate P retention. These data were analyzed as a 2-way interaction. On d 0 (baseline), 8 and 18, blood samples were collected to analyze serum Ca and P, and plasma inositol. Blood data were analyzed as a 3-way interaction. Results indicated that piglets fed Ca-formate had greater ATTD of Ca (75.0% vs. 71.4%, P < 0.01) but decreased ATTD of P (66.4% vs. 68.8%, P < 0.01), than piglets fed limestone. Phytase supplementation improved ATTD of DM, ash, OM, CP, P, and Ca compared with the NC and PC. An interaction between Ca/P levels and Ca-sources was observed for urinary P (P = 0.03), as there were no differences between Ca sources in piglets fed the NC or the 750 FYT diets, but piglets fed the PC diet and the NC+1,500 or 3,000 FYT with limestone had greater urinary P compared with Ca-formate. A 2-way interaction between Ca/P levels and d was observed for plasma inositol (P = 0.012). On d 8 and 18, there was no difference between the NC and PC;, however, phytase supplementation at 750, 1,500, and 3,000 FYT increased plasma inositol on d 8 (58.2, 80.7, and 89.5 μmol) and d 18 (70.2, 85.4, and 106.4 μmol). There was only a main effect of Ca/P levels in serum P. Compared with the NC (73.7 mg/L), the PC and the NC+750, 1,500, and 3,000 FTU/kg increased serum P (90.3, 89.1, 87.6, and 93.2 mg/L, respectively, P < 0.01). There was no effect of Ca source on blood inositol and P. No significant dietary treatment effects were observed in serum Ca. In conclusion, using Ca-formate instead of limestone increases Ca digestibility but reduces P digestibility, likely due to a greater Ca solubility of Ca-formate. This suggests that diets should be formulated based on digestible Ca instead of total Ca.

102 Circadian patterns of behavior, respiration, rectal temperature, saliva melatonin, cytokine concentrations, and milk immune cells are altered by cooling heat-stressed lactating sows

Abstract Lactating sows are particularly vulnerable to heat stress (HS) due to the increased metabolism from milk production. A greater understanding of HS response could assist in mitigating its detrimental effects on animal production. Two core circadian clock genes were pinpointed in a recent genome study as potential mediators of HS response, indicating the possible alteration of circadian clocks by HS exposure. This study aimed to assess how cooling of lactating sows under natural heat stress conditions in the summer influenced circadian patterns of respiration rate (RR), rectal temperature (RT), behaviors, salivary concentration of cortisol and melatonin, milk cell populations and relative abundance of multiple cytokines in saliva. Lactating sows of mixed parities were divided into two treatment groups: treated with electronic cooling pad (C; n=9) and heat-stressed control (H; n=9). Experiments were conducted during two 48 h periods of increased environmental temperatures from summer heatwaves. During the initial 48 h period, rectal temperature (RT) was monitored every 60 min, rectal temperature (RT) every 30 min, and behaviors of eating, standing, sitting, laying, sleeping, drinking, and nursing every 5 min. Morning milk samples were collected following the completion of the first phase and utilized to categorize and count somatic cells. The second trial was approximately 1 wk later, and during this period saliva samples were collected every 4 h over the 48-h period. Results were analyzed for significant effect of treatments and interaction using periodic regression while circadian patterns were further detected by incorporating a Fourier series model utilizing sine-cosine variables that denote a fit and/or shift in circadian pattern. The analysis revealed that cooling decreased RT and RR while also modifying circadian patterns (P < 0.05). Cooling had no impact on the percentage of time spent in any activity over the 48-h period (P > 0.05). Nevertheless, the daily patterns of eating, standing, and sitting were different between the treatments (P < 0.05). A shift in eating time to later in the day in H sows relative to C sows related to a second rise in RT during the dark phase of the light-dark cycle (P < 0.05). Saliva melatonin concentrations were increased in C sows and circadian pattern altered relative to H (P < 0.05), but there was no effect on salivary cortisol concentrations (P > 0.05). Cooling reduced milk lymphocytes (P < 0.05) and influenced diurnal pattern of saliva cytokines including interleukins (IL) IL-1 alpha, IL-1 beta, IL-10, and IL-15 and transforming growth factor-beta 1. In conclusion, the cooling of heat-stressed sows altered the circadian patterns of physiology, behavior and melatonin, suggesting the need for additional research to investigate whether circadian disruption contributes to reduced production efficiency observed in HS animals.

Learning optimal biomarker-guided treatment policy for chronic disorders.

Electroencephalogram (EEG) provides noninvasive measures of brain activity and is found to be valuable for the diagnosis of some chronic disorders. Specifically, pre-treatment EEG signals in the alpha and theta frequency bands have demonstrated some association with antidepressant response, which is well-known to have a low response rate. We aim to design an integrated pipeline that improves the response rate of patients with major depressive disorder by developing a treatment policy guided by the resting state pre-treatment EEG recordings and other treatment effects modifiers. First, we design an innovative automatic site-specific EEG preprocessing pipeline to extract features with stronger signals than raw data. We then estimate the conditional average treatment effect (CATE) using causal forests and use a doubly robust technique to improve efficiency in the estimation of the average treatment effect. We present evidence of heterogeneity in the treatment effect and the modifying power of the EEG features, as well as a significant average treatment effect, a result that cannot be obtained with conventional methods. Finally, we employ an efficient policy learning algorithm to learn an optimal depth-2 treatment assignment decision tree and compare its performance with Q-Learning and outcome-weighted learning via simulation studies and an application to a large multi-site, double-blind, randomized controlled clinical trial, EMBARC.

Recurrent Ethanol Treatment does not Produce a Cumulative Effect on Plasma Leptin Levels in Rats

Background: Hypoleptinemia is a potent orexigenic signal. Chronic ethanol (EtOH) consumption is associated with weight gain in humans, and acute ethanol treatment leads to reductions in leptin concentrations in both fasted humans and rats. The objective of this study was to determine whether short-term recurrent ethanol treatment has a cumulative effect on plasma leptin levels in rats, and whether treatment in the fed or fasted state influences the leptin lowering effect of EtOH. We hypothesized that recurrent EtOH treatment would have a cumulative effect on leptin levels, and that these effects would be more pronounced in the fed state, when leptin levels are highest. Methods: Two separate groups of male Sprague Dawley rats were exposed to either oral or intravenous (IV) treatment with EtOH (2g/kg via oral gavage or 0.067 g/kg/min IV for 30 min; n=7/group) on three consecutive days. Each rat served as its own control and received saline treatment either 7 d prior to or 7 d following exposure to EtOH. The oral group was fasted 12-14 h (overnight) prior to treatment, while the IV group was not fasted. Plasma leptin and EtOH levels were measured each day at baseline and 3 h following EtOH treatment. Data are expressed as mean ± SEM. A two-way repeated measures ANOVA was used to test for differences in plasma leptin and EtOH levels due to treatment (saline vs. EtOH) or day (cumulative effect of treatment). Results: Post-treatment ethanol levels in the oral and IV groups (55 ± 6.9 and 45 ± 6.3 mM, respectively) were higher than saline-treated rats (p>0.001). Baseline leptin levels in the oral treatment (fasted) group were 3.4 ± 0.3 and 3.9 ± 0.2 ng/mL under saline and leptin treated conditions, respectively. There was a significant main effect of treatment but not of day in the oral group (p=0.04 and p=0.38, respectively). In the oral group, average daily change in leptin levels 3 h post treatment in saline and leptin treated rats were -0.18 ± 0.05 and -0.72 ± 0.1 ng/mL, respectively. Baseline leptin levels in the IV group (fed) were 7.8 ± 0.3 and 6.7 ± 0.1 ng/mL, in saline and leptin treated rats respectively. There was no significant main effect of treatment or day in the IV group (p=0.17 and p=0.41, respectively). In the IV group, average daily changes in leptin levels 3 h following treatment in saline and leptin treated rats were -1.7 ± 0.2 and -1.3 ± 0.3 ng/mL, respectively. Conclusion: Although we were able to replicate previous work indicating reduced leptin levels following acute EtOH treatment in fasted rats, our results do not support a cumulative leptin-lowering effect of recurrent EtOH treatment. Furthermore, IV EtOH treatment in the fed state did not have any impact on leptin levels. This suggests that the leptin-lowering effects of EtOH may either require the fasted state or may require ingestion and exposure of the GI system to EtOH. NIH R01 DK131165-01A1. 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.

Novel misos shape distinct microbial ecologies: opportunities for flavourful sustainable food innovation

Fermentation is resurgent around the world as people seek healthier, more sustainable, and tasty food options. This study explores the microbial ecology of miso, a traditional Japanese fermented paste, made with novel regional substrates to develop new plant-based foods. Eight novel miso varieties were developed using different protein-rich substrates: yellow peas, Gotland lentils, and fava beans (each with two treatments: standard and nixtamalisation), as well as rye bread and soybeans. The misos were produced at Noma, a restaurant in Copenhagen, Denmark. Samples were analysed with biological and technical triplicates at the beginning and end of fermentation. We also incorporated in this study six samples of novel misos produced following the same recipe at Inua, a former affiliate restaurant of Noma in Tokyo, Japan. To analyse microbial community structure and diversity, metabarcoding (16S and ITS) and shotgun metagenomic analyses were performed. The misos contain a greater range of microbes than is currently described for miso in the literature. The composition of the novel yellow pea misos was notably similar to the traditional soybean ones, suggesting they are a good alternative, which supports our culinary collaborators’ sensory conclusions. For bacteria, we found that overall substrate had the strongest effect, followed by time, treatment (nixtamalisation), and geography. For fungi, there was a slightly stronger effect of geography and a mild effect of substrate, and no significant effects for treatment or time. Based on an analysis of metagenome-assembled genomes (MAGs), strains of Staphylococccus epidermidis differentiated according to substrate. Carotenoid biosynthesis genes in these MAGs appeared in strains from Japan but not from Denmark, suggesting a possible gene-level geographical effect. The benign and possibly functional presence of S. epidermidis in these misos, a species typically associated with the human skin microbiome, suggests possible adaptation to the miso niche, and the flow of microbes between bodies and foods in certain fermentation as more common than is currently recognised. This study improves our understanding of miso ecology, highlights the potential for developing novel misos using diverse local ingredients, and suggests how fermentation innovation can contribute to studies of microbial ecology and evolution.

Development of an Exercise-based EV Therapy to Improve Skeletal Muscle Recovery After Immobilization

Introduction: Immobilization is necessary for recovery from illness or bone fractures; however, prolonged immobilization can result in significant loss of muscle mass and function. It is critical to recover muscle mass quickly following immobilization as severe muscle atrophy is correlated with increased likelihood of metabolic disorders, disability, and mortality. Physical rehabilitation can improve outcomes but is not always feasible. The purpose is to determine the extent to which EVs circulating in blood after endurance exercise training (EnVs) act as a safe and effective therapy to recover skeletal muscle mass following disuse. Methods: Donor C57BL/6 mice (n = 8-10, 4-month-old) were provided access to horizontal running wheels in a locked (sedentary) or unlocked (exercise) condition. After 4 weeks of voluntary running, EVs (SedVs or EnVs) were isolated from plasma using size exclusion chromatography according to manufactures guidelines, and concentration confirmed via nanoparticle tracking analysis (NanoSight NS3000). Recipient C57BL6/J mice (n = 5-8, 4-month-old) were subjected to single limb immobilization for 14 days. Upon remobilization, mice received a single intramuscular injection of PBS, SedVs, EnVs, or endurance plasma proteins, and remobilized for 3 and 14 days. Muscle samples were collected after remobilization and assessed for muscle cross-sectional-area (CSA) and capillarization. Results: Upon 3-day remobilization, EnVs did not significantly recover global fiber CSA and fiber-type specific CSA (Type IIa, Type IIx or Type IIb) or capillarization. Upon 14-day remobilization, EnVs did not significantly improve global fiber CSA and fiber-type specific CSA. However, a significant treatment effect was observed for capillary density (P = 0.0445), with increases observed for both SedV (P = 0.034) and EnV (P = 0.0117). Conclusion: EVs isolated from plasma after exercise can significantly improve skeletal muscle vascularization after immobilization, which may represent an important step toward full recovery of skeletal muscle mass. Partially support by NIH (NIAMS R01AR072735). 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.

Feasibility of Improving Glycemic Control via Heat Therapy in individuals at risk for Alzheimer’s Disease (FIGHT-AD): a pilot study

Impaired glycemic control increases the risk for type 2 diabetes and Alzheimer’s Disease (AD). Mechanisms such as impaired energy metabolism, cellular bioenergetic function, reduced intracellular protein homeostasis, and inflammation are all potential contributors to AD pathology. Heat therapy, via hot water immersion, has been shown to improve blood glucose regulation, insulin resistance, and inflammation. Given the potential contribution of these factors to brain health, heat therapy could offer immense clinical benefit to individuals at risk for AD. We performed a pilot study to test the feasibility of utilizing heat therapy in older individuals at risk for AD due to metabolic risk. The study intervention involved two pre-visits which included a cognitive function screen, sleep, diet, and physical activity questionnaires, as well as a glucose tolerance test and MRI scan. The intervention consisted of four weeks of heat therapy (3 visits/wk) for a total of 12 visits, followed by two post-intervention study visits identical to the pre-study visits. A total of 18 individuals (9 male, 9 female), average age 71.1 ± 3.9 y completed the intervention. Participants demonstrated metabolic risk based on average HbA1c values of 6.6 ± 0.67, Body Mass Index (BMI) of 29.1 ± 5.4, and 15 of the 18 participants were on hypertensive medications. Our cohort was highly diverse, with 33% underrepresented minority group representation. We had 96% participant adherence for the study (8 missed visits out of 216 total visits), and 1 study related Adverse Event (mild dizziness/nausea) that was mild. Overall, the research participants responded to a post-intervention survey saying they enjoyed participating in the study and it was not a burden on their schedules. In addition, we obtained preliminary data demonstrating a significant effect of the heat therapy intervention on body mass index, mean arterial pressure, and cerebral perfusion (p<0.05), and a trend for improved self-reported sleep quality (Pittsburgh Sleep Quality Index; p=0.06). Future studies of longer duration are needed to provide a comprehensive understanding of the impact of heat therapy on glucose homeostasis and brain health. NIH P30 AG035982 (KU ADRC), pilot funds to PCG. 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.

Investigation of Hydrogen Sulfide Therapy as a Strategy to Preserve Erectile Health During Androgen Deprivation

Severe erectile dysfunction is prevalent in men with prostate cancer that undergo androgen deprivation therapy (ADT). Androgen deprivation drives drastic changes in the erectile tissues of the corpus cavernosum and pre-penile arteries, which include endothelial dysfunction, vascular remodeling, and diminished vascular smooth muscle quality. Restorative therapies are desperately needed to preserve tissue function and quality during the ADT period. Hydrogen sulfide (H2S) is a gaseous cell signaling molecule with vasodilatory, antioxidant, and anti-inflammatory properties that promote endothelial and vascular health. Recent advancements suggest that H2S may influence cellular health through stimulation of autophagy and regulation of mitochondrial dynamics. Therefore, the objective of this study was to investigate the ability of SG1002, an H2S pro-drug, to preserve erectile function following prolonged ADT. We hypothesized that SG1002 would have a positive effect on erectile function associated with a stimulation of protective pathways related to cellular antioxidant defense, mitochondrial fusion, and autophagy in the corpus cavernosum. Male C57Bl/6 mice were divided into four cohorts, one cohort that underwent sham castration surgery and three cohorts that underwent castration. Castrations were performed at 14 weeks of age. The sham group and one castrated cohort were placed on a control diet. The other two cohorts were placed on identical diets at the time of castration that were supplemented with SG1002 at approximately 20 mg/kg/day or 100 mg/kg/day. Mice were studied 5 weeks following surgery. Erectile function was assessed in vivo by measurements of intracavernous pressure (ICP) and mean arterial pressure (MAP) in response to stimulation of the cavernous nerve. Relative content of 19 proteins in the corpus cavernosum tissue was determined by western blot. Group differences were determined by one-way or two-way ANOVA followed by Tukey’s post hoc test, with an α-level of 0.05. Erectile function was severely diminished among all castrated cohorts compared to sham mice (p<0.01). SG1002 administration elicited a modest but statistically significant augmentation of erectile function (p<0.05) that was equivalent between the two doses. Castration was associated with a significant decrease in the antioxidant proteins GCLC, SOD3, and TRX1, as well as the mediators of mitochondrial fusion MFN1 and MFN2, and the autophagy stimulatory protein ATG7 (p<0.05). There were no significant effects of SG1002 treatment on any of the proteins investigated. In conclusion, H2S therapy elicited a modest protective effect on erectile function that may have been mediated by its direct vasodilatory potential or neurological mechanisms. Further study will be needed to determine if any adverse structural changes associated with castration were affected by H2S therapy. Funding From the National Institutes of Health Grant numbers: R03DK131242 and R03DK131242-01S1. 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.

Lingguizhugan Decoction Improved Obesity by Modulating the Gut Microbiota and its Metabolites in Mice.

The global obese population is rapidly increasing, urgently requiring the development of effective and safe weight-loss medications. The classic Chinese medicine formulation Lingguizhugan Decoction has exerted a significant anti-obesity effect. However, the underlying mechanism is still unclear. This study aimed to explore the mechanism of LGZGD in the treatment of obesity based on the gut microbiota and its metabolites. Three different dosages of LGZGD were gavaged to ob/ob mice for 8 weeks. Body mass and visceral fat mass were evaluated. Additionally, the changes in gut microbiota, fecal and plasma metabolites in mice after LGZGD treatment were analyzed by metagenomics and non-targeted metabolomics. The results demonstrated a significant anti-obesity effect of LGZGD treatment in ob/ob mice. Furthermore, the metagenomic analysis revealed that LGZGD reduced the ratio of Firmicutes / Bacteroidetes (F to B) in the gut, restored gut microbiota diversity, and identified 3 enriched KEGG pathways, including energy metabolism, lipid metabolism, and energy production and conversion pathways. Based on non-targeted metabolomics analysis, 20 key metabolites in the feces and 30 key metabolites in the plasma responding to LGZGD treatment were identified, and the levels of Eicosapentaenoic acid (EPA) and Myristoleic acid (MA) might be the metabolites related to gut microbiota after LGZGD treatment. Their biological functions were mainly related to the metabolism pathway. These findings suggested that LGZGD had therapeutic potential for obesity. The mechanism of LGZGD alleviating obesity was associated with improving dysbiosis of the gut microbiota. LDZGD affected gut microbiota-derived metabolites of EPA and MA and may act on energy metabolism pathways.

C57BL/6J-Trex1em3Lutzy/J KO mouse as a type 1 IFN dependent model for SLE preclinical drug discovery

Abstract Systemic Lupus Erythematosus is a chronic autoimmune disease characterized by a broad spectrum of clinical manifestations. An important role of the type I interferon (IFN) pathway has been identified in SLE patients. No one mouse model completely recapitulates the complexity of the human disease. Nonetheless, mouse models of SLE have been instrumental in our understanding of the genetic and cellular requirements for SLE induction and represent a valuable resource for testing SLE therapies and drug candidates in vivo. Here we present preclinical reference data in a Trex1KO mouse model generated at the Jackson Laboratory using CRISPR technology. Trex1KO mice have a median survival of approximately 165 – 185 days. Body weight is significantly reduced in both male and female KO versus WT. Unlike NZBWF1/J and MRL/MpJ mouse models that develop lupus nephritis, the Trex1 KO develops dilated cardiomyopathy due to leukocyte infiltration and cardiomyocyte degeneration. Here we treated KO mice with anti-IFNα antibodies through 32 weeks of age. We observed a significant treatment effect on survival, reduction in leukocyte infiltration and degeneration of the heart, and percentage of T peripheral helper T cells in spleen. A mouse model recapitulating a role for type I IFN in disease pathogenesis has been lacking in the common models of SLE, and these data indicate that the Trex1KO model is relevant for the screening of targeted therapies of type I IFN and related pathways.

Effectiveness of behavioural change interventions to influence maternal and child healthcare-seeking behaviour in low and lower-middle-income countries: A systematic review of literature.

While behavioural change interventions are utilized in low- and lower-middle-income countries and may be essential in reducing maternal and child mortality, evidence on the effectiveness of such interventions is lacking. This review provides evidence on the effectiveness of behavioural change interventions designed to improve maternal and child healthcare-seeking behaviour in low- and lower-middle-income countries. We searched three electronic databases (PUBMED, EMBASE, and PsycINFO) for articles published in English and French between January 2013 and December 2022. Studies that evaluated interventions to increase maternal and child healthcare utilization, including antenatal care, skilled birth care, postnatal care, immunization uptake, and medication or referral compliance, were included. We identified and included 17 articles in the review. Overall, 11 studies found significant effects of the behavioural change interventions on the desired healthcare outcomes, 3 found partially significant effects, and 3 did not observe any significant impact. A major gap identified in the literature was the lack of studies reporting the effect of behavioural change interventions on women's non-cognitive and personality characteristics, as recent evidence suggests the importance of these factors in maternal and child healthcare-seeking behaviour in low-resource settings. This review highlights some intervention areas that show encouraging trends in maternal and child healthcare-seeking behaviours, including social influence, health education, and nudging through text message reminders.

Innovative decision making tools using discrete mathematics for stress urinary incontinence treatment.

In this study, we applied graph theory to clinical decision-making for Stress Urinary Incontinence (SUI) treatment. Utilizing discrete mathematics, we developed a system to visually understand the shortest path to the desired treatment outcomes by considering various patient variables. Focusing on women aged 35-50, we examined the effectiveness of Tension-free Vaginal Tape (TVT) surgery and Vaginal Erbium Laser (VEL) treatment for over 15years. The TVT group consisted of 102 patients who underwent surgery using either the Advantage Fit mid-urethral sling system (Boston Scientific Co., MA, USA) or the GYNECARE TVT retropubic system (Ethicon Inc., NJ, USA). The VEL group included 113 patients treated with a non-ablative Erbium: YAG laser (FotonaSmooth™ XS; Fotona d.o.o., Ljubljana, Slovenia), and there were 112 patients in the control group. We constructed a network diagram analyzing the correlations between health, demographic factors, treatment methods, and patient outcomes. By calculating the shortest path using heuristic functions, we identified significant correlations and treatment effects. This approach supports patient decision making by choosing between TVT and VEL treatments based on individual objectives. Our findings provide new insights into SUI treatment, highlighting the value of a data-driven personalized approach for clinical decision-making. This interdisciplinary study bridges the gap between mathematics and medicine, demonstrating the importance of a data-centric approach in clinical decisions.

The Effect of a Mental Health Intervention on Health Behaviors among Cancer Survivors

The Effect of a Mental Health Intervention on Health Behaviors among Cancer Survivors

Efficacy of Cognitive Behavioral Intervention in Improving Executive Function of Children with High Functioning Autism Spectrum Disorder: A Meta-analysis

This meta-analysis examines the efficacy of the cognitive behavioral approach to interventions toward the improvement of executive function for children/adolescents with high-functioning autism spectrum disorder (HF-ASD). This meta-analysis paper has identified ten studies involving 437 participants with high-functioning autism spectrum disorder aged between 5 and 18. All the participants reported IQs were at or above 70. A random effect meta-analysis yielded a moderately significant effect (Hedge g = 0.72) with significant heterogeneity [Q(10) = 228.36, p < .001]. There were considerable variations in the executive function domain, i.e., working memory (hedge g = 1.23) and inhibition (g = 0.47), showing significant treatment effects. On the other hand, cognitive flexibility (g = -0.51) and planning (g = -0.07) show non-significant effects toward cognitive behavioral interventions. The finding suggests that the cognitive behavioral approach to intervention demonstrates efficacy in improving executive function in children or adolescents with high-functioning autism spectrum disorder. All the cognitive behavioral intervention studies were conducted in developed countries, so differences between the approaches between developed and developing countries were inconclusive. Future studies are needed to investigate the effectiveness of cognitive behavioral techniques in intervention for low-functioning autism spectrum disorder children.

The addition of bortezomib to rituximab, high-dose cytarabine and dexamethasone in relapsed or refractory mantle cell lymphoma—a randomized, open-label phase III trial of the European mantle cell lymphoma network

The therapy of relapsed or refractory (r/r) mantle cell lymphoma (MCL) patients remains a major clinical challenge to date. We conducted a randomized, open-label, parallel-group phase-III trial hypothesizing superior efficacy of rituximab, high-dose cytarabine and dexamethasone with bortezomib (R-HAD + B) versus without (R-HAD) in r/r MCL ineligible for or relapsed after autologous stem cell transplant (ASCT). Primary endpoint was time to treatment failure (TTF), secondary endpoints included response rates, progression free survival, overall survival, and safety. In total, 128 of 175 planned patients were randomized to R-HAD + B (n = 64) or R-HAD (n = 64). Median TTF was 12 vs. 2.6 months (p = 0.045, MIPI-adjusted HR 0.69; 95%CI 0.47–1.02). Overall and complete response rates were 63 vs. 45% (p = 0.049) and 42 vs. 19% (p = 0.0062). A significant treatment effect was seen in the subgroup of patients >65 years (aHR 0.48, 0.29–0.79) and without previous ASCT (aHR 0.52, 0.28–0.96). Toxicity was mostly hematological and attributable to the chemotherapeutic backbone. Grade ≥3 leukocytopenia and lymphocytopenia were more common in R-HAD + B without differences in severe infections between both arms. Bortezomib in combination with chemotherapy can be effective in r/r MCL and should be evaluated further as a therapeutic option, especially if therapy with BTK inhibitors is not an option. Trial registration: NCT01449344.

Summer cover crop and temporary legume-cereal intercrop effects on soil microbial indicators, soil water and cash crop yields in a semi-arid environment

ContextFew studies have investigated summer cover crops as a replacement for bare fallow in semi-arid temperate regions, and summer cover crop impacts on soil biological function, water balances and subsequent winter crop yields in these regions remain largely unknown. ObjectiveThe 4-year field study aimed to determine the consequences of replacing a summer fallow with a summer growing cover crop on soil function, water balances and subsequent winter cash crop yields in a semi-arid region (486 mm mean annual rainfall) of the Australian southern cropping zone. MethodsA canola (Brassica napus)-wheat (Triticum aestivum L.) rotation with summer fallow was compared to the same rotation with either i) a single species (buckwheat, Fagopyrum esculentum L.) summer cover crop; ii) a four-species mixed brassica + cereal summer cover crop or iii) a cropping sequence with a temporary legume intercrop in the wheat phase of the rotation. Cover crop biomass production, soil water to a depth of 90 cm at cash crop sowing, crop yields and soil functional indices were quantified. ResultsCover crops produced 500–700 kg biomass ha−1 in the 2020 and 2021 seasons and 1000–2400 kg biomass ha−1 in 2022. The four-species mixed cover crop significantly lowered soil water (around 30 mm; P < 0.05) at the time of sowing the cash crop compared to the control and resulted in 15% reduction (P = 0.12) in canola seed yield in 2020, but no significant effect of cover crops of soil water and mineral N at sowing, or cash crop yields, were observed in subsequent seasons. In 2021 the temporary vetch intercrop produced > 1000 kg ha−1 biomass over 9 weeks, and led to a (non-significant) 10% wheat yield reduction. There was no significant effect of cover crop or temporary intercrop treatments on soil functions in the 2020 or 2021 seasons, but activities of several soil enzymes (leucine aminopeptidase, arylsulfatase and B-glucosidase; P < 0.05) and water-soluble carbon (P = 0.059) were significantly higher in the summer cover crop plots compared to control and intercrop plots in March 2022 following termination of the cover crops. These changes coincided with a significant increase in saturated hydraulic conductivity in the four-species cover crop plots in March 2022 compared to control plots. ImplicationsThe study did not provide any compelling evidence for benefits of summer cover crops over fallow in the short term (3–4 years). The relatively low cover crop biomass production over the 4-year study suggests summer cover crops are unlikely to substantially improve soil carbon levels in temperate, semi-arid cropping systems.