12-week Trial Research Articles

Quantifying Parental Perceptions of Their Experiences With Their Young Children's Use of Power Mobility Devices.

To quantify and explore parental perceptions of their experiences with their child's use of the Explorer Mini (EM) and a modified ride-on car (mROC) in young children with cerebral palsy. Data were gathered throughout a multisite, randomized, counterbalanced AB crossover 16-week clinical trial, wherein all participants used device A (EM) and device B (mROC) for 8-weeks each. Semistructured parent interviews were conducted at baseline (T0), post-intervention period 1 (T1), and post-intervention period 2 (T2). The Linguistic Inquiry and Word Count program was used to objectively analyze the transcribed interviews. Twenty-four child-parent dyads participated in the study. Parental perceptions were related to children's gross motor abilities, cognitive development scores, and device use order (EM-mROC or mROC-EM). Parents were positive about a potential means of helping their children. While most preferred the EM, opinions were contingent on the PM device, device use order, and child-centered factors.

Exploring the Benefits of Herbal Medicine Composite 5 (HRMC5) for Skin Health Enhancement

The skin, as the body’s largest organ, is vital for protecting against environmental stressors, regulating temperature, and preventing water loss. Here, we examined the potential of a mixture of five traditional Korean herbal extracts—Cimicifuga racemosa, Paeonia lactiflora, Phellodendron amurense, Rheum rhaponticum, and Scutellaria baicalensis—referred to as herbal medicine composite 5 (HRMC5) for enhancing skin health and managing menopausal symptoms. High-performance liquid chromatography identified 14 bioactive compounds, including flavonoids, phenolic acids, anthraquinones, and alkaloids. In vitro studies revealed an optimal concentration of 0.625 g/L for cell survival and UV protection, with the mixture demonstrating significant wound-healing properties comparable to epidermal growth factor. HRMC5 exhibited anti-inflammatory effects by downregulating COX2 expression and upregulating the key skin barrier proteins. A 4-week clinical trial involving 20 postmenopausal women showed significant improvements in skin redness, hemoglobin concentration, and skin moisture content. Visual analog scale assessments indicated substantial reductions in facial flushing severity and the associated sweating. The topical application of HRMC5 cream offered potential advantages over ingested phytoestrogens by reducing the systemic side effects. These findings suggest that HRMC5 is a promising non-invasive treatment for vasomotor symptoms in menopausal women and overall skin health, warranting further research on its long-term efficacy and safety in larger populations.

Smartphone application for improving self-awareness of adherence to edoxaban treatment: a randomised controlled trial (ADHERE-APP)

Abstract Background Adherence to oral anticoagulants is essential for stroke prevention in patients with atrial fibrillation (AF). This study aims to test the feasibility and effectiveness of the smartphone app-based intervention to improve drug adherence in patients with AF. Methods This prospective, randomised, open-label, multicentre trial (ADHERE-APP) enrolled a total of 502 patients at 9 university hospitals in South Korea from November 2021 to January 2023. Patients with AF aged ≥19 years requiring oral anticoagulation,and were treated with edoxaban were enrolled. Patients were randomized in a 1:1 ratio to the conventional treatment group and the app conditional feedback group. Patients in the app conditional feedback group used a smartphone application that pushed alarms for taking medication and measuring blood pressure (BP) and heart rate (HR) at specific times of the day. In addition to medication alarms, the habit of measuring one’s BP and HR could improve drug adherence by increasing self-awareness of the disease. The automatic BP machine was connected to the smartphone via Bluetooth and the measured BP and HR were automatically updated on the smartphone app. The primary endpoint was adherence to edoxaban as measured by pill count at 12 and 24 weeks. In addition, we evaluated the differential effect of the smartphone application by age on the primary endpoint. Results Among the 502 patients, the mean age was 66.0±10.0 years and 67.7% were male. Of the 372 patients who completed 12-weeks trial, edoxaban adherence at 12 weeks was high in both arms, with no difference in the primary outcome (96.5% [92.5%-100.0%] vs. 98.0% [93.2%-99.5%], P = 0.488). or in secondary outcomes, including the proportion of patients achieving adherence ≥ 80% or 95%. In patients aged >65 years, adherence to edoxaban was higher in the app conditional feedback group than in the conventional treatment group (95.8% [93.0%-99.5%] vs. 98.0% [95.8%-99.5%], P = 0.049). Conclusions Overall adherence to edoxaban was much higher than expected in patients with AF. There was no difference in edoxaban adherence between the app conditional feedback group and the conventional treatment group, however, in older patients, app feedback increased medication adherence.

Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial.

Transcranial direct current stimulation (tDCS) has been proposed as a new treatment in major depressive disorder (MDD). This is a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured using the Hamilton Depression Rating Scale (mean = 19.07 ± 2.73). A total of 174 participants (120 women, 54 men) were randomized to active (n = 87, mean age = 37.09 ± 11.14 years) or sham (n = 87, mean age = 38.32 ± 10.92 years) treatment. tDCS consisted of five sessions per week for 3 weeks then three sessions per week for 7 weeks in a 10-week trial, followed by a 10-week open-label phase. Each session lasted 30 min; the anode was placed over the left dorsolateral prefrontal cortex and the cathode over the right dorsolateral prefrontal cortex (active tDCS 2 mA and sham tDCS 0 mA, with brief ramp up and down to mimic active stimulation). As the primary outcome, depressive symptoms showed significant improvement when measured using the Hamilton Depression Rating Scale: active 9.41 ± 6.25 point improvement (10-week mean = 9.58 ± 6.02) and sham 7.14 ± 6.10 point improvement (10-week mean = 11.66 ± 5.96) (95% confidence interval = 0.51-4.01, P = 0.012). There were no differences in discontinuation rates. In summary, a 10-week home-based tDCS treatment with remote supervision in MDD showed high efficacy, acceptability and safety. ClinicalTrials.gov registration: NCT05202119.

Mating behaviour and cholesterol nutritional strategies promoted ovarian development of female swimming crab (Portunus trituberculatus).

Female crabs enter a stage of rapid ovarian development after mating, and cholesterol is a substrate for steroid hormone synthesis. Therefore, in this experiment, an 8-week feeding trial was conducted to investigate the effects of mating treatments (mated crab and unmated crab) and three dietary cholesterol levels (0·09 %, 0·79 % and 1·40 %) on ovarian development, cholesterol metabolism and steroid hormones metabolism of adult female swimming crab (Portunus trituberculatus). The results indicated that crabs fed the diet with 0·79 % cholesterol significantly increased gonadosomatic index (GSI) and vitellogenin (VTG) content than other treatments in the same mating status. Moreover, mated crabs had markedly increased GSI and VTG content in the ovary and hepatopancreas than unmated crabs. The histological observation found that exogenous vitellogenic oocytes appeared in the mated crabs, while previtellogenic oocytes and endogenous vitellogenic oocytes were the primary oocytes in unmated crabs. The transmission electron microscopy analysis showed that when fed diet with 0·79 % cholesterol, the unmated crabs contained more rough endoplasmic reticulum and mated crabs had higher yolk content than other treatments. Furthermore, mating treatment and dietary 0·79 % cholesterol level both promoted cholesterol deposition by up-regulation of the mRNA and protein expression levels of class B scavenger receptors 1 (Srb1), while stimulating the secretion of steroid hormones by up-regulation of the mRNA and protein expression of steroidogenic acute regulatory protein (Star). Overall, the present results indicated that mating behaviour plays a leading role in promoting ovarian development, and dietary 0·79 % cholesterol level can further promote ovarian development after mating.

Impact of defatted black soldier fly (Hermetia illucens) larvae meal on health, muscle texture, and intestinal microbiota in Pacific white shrimp (Penaeus vannamei)

Defatted black soldier fly larvae meal is a highly promising substitute for fishmeal, with its impact on gut health and muscle quality in Pacific white shrimp (Penaeus vannamei) being crucial for its further development and utilization. This study conducted an 8-week feeding trial to evaluate the effects of replacing fishmeal with defatted black soldier fly (Hermetia illucens) larvae meal (DBSFLM) on the growth, muscle texture, and gut health of P. vannamei. Six isonitrogenous and isolipidic diets were formulated, with DBSFLM added at levels of 0 %, 4.12 %, 8.24 %, 12.36 %, 16.48 %, and 20.61 % to replace different proportions of fishmeal. The results showed that adding up to 20.61 % DBSFLM to replace 75 % of fishmeal did not significantly affect shrimp growth performance. The optimal inclusion level of DBSFLM is 4.12 % to 8.24 %, which not only reduces intestinal inflammation and enhances gut microbiota interactions but also improves muscle texture and flavor, while boosting immunity and antioxidant capacity. However, adding more than 16.48 % DBSFLM leads to intestinal inflammation and hepatocellular damage, and negatively affects muscle texture and amino acid composition. Overall, while adding up to 20.61 % DBSFLM (to replace 75 % of fishmeal) does not affect shrimp growth, an inclusion level of no more than 12.36 % (to replace 45 % of fishmeal) is recommended for optimal flavor and health.

Dietary superdosing of phytase positively affects growth, mineral utilization and amino acid availability of channel catfish (Ictalurus punctatus)

The present study investigated the effects of supplementing high levels (superdosing) of dietary phytase on growth performance, mineral utilization and digestibility of amino acids in different regions of the gastrointestinal (GI) tract of fingerling channel catfish. The negative control (NC) diet was formulated with primarily soybean meal as a protein feedstuff which contributed 0.61 % total phosphorus (P) but was deficient in available P at 0.11 % of diet. Five other diets were formulated either with supplemental monocalcium phosphate at 1 % of diet in the positive control (PC), or supplemented with Quantum Blue phytase (AB Vista, Plantation, Florida) at 1000, 2000, 4000, or 8000 phytase units (FTU)/kg of diet. Groups of 20 catfish were each stocked into 24 aquaria operated as a closed, recirculating system with biological and mechanical filtration. All dietary treatments were assigned randomly to quadruplicate aquaria and initially fed at 6 % of total body weight per day. Feed quantities were adjusted weekly after weighing all fish in each aquarium as a group, and feeding levels were maintained close to apparent satiation throughout the 8-week feeding trial. Phytase supplementation significantly (P < 0.05) increased various responses of channel catfish including weight gain, feed efficiency, and protein retention compared to catfish fed the NC diet, resulting in values that were similar to catfish fed the PC diet. Moreover, catfish fed the phytase-supplemented diets had higher bone ash, calcium (Ca), magnesium (Mg), P, manganese (Mn), and zinc (Zn), as well as retention of Ca, Mg, P, iron (Fe), Mn, and Zn in whole-body tissues. Additionally, apparent availability of P from the posterior intestinal region increased with dietary phytase supplementation, with reduced excretion of nitrogen, Ca, Mg, P, copper (Cu), Mn, and Zn observed in comparison to fish fed the NC diet. Apparent digestibility coefficients for many of the indispensable and dispensable amino acids were increased by phytase supplementation, except for histidine, methionine, threonine, and taurine. This improvement in amino acid availability occurred only in the posterior region of the gastrointestinal tract. Channel catfish fed the diet containing 4000 FTU/kg diet had the highest postprandial plasma phosphorus level most of the time, except at 24 h after feeding. Based on these various responses, the optimal dietary phytase dosage was determined to average 5492 FTU/kg diet.

Enhancing social interaction in nursing homes through public tabletop displays: A field study of R2S

The prevalence of social isolation among nursing home residents highlights the need for innovative solutions to enhance their social interactions and wellbeing. Despite extensive efforts over recent decades to develop in-room systems or public applications under caregivers’ supervision, there remains a gap in designing public social technologies that can be integrated into residents’ daily lives. Furthermore, the challenges associated with low adoption and the complexities of evaluating such technologies in public care settings have limited our understanding of their impact on residents' social activities and experiences. To address this, our study introduces R2S, a tabletop display system designed to encourage older adults to view, share, and discuss news articles collaboratively in public care environments. A 6-week field trial was conducted in a Dutch care home to investigate the influence on residents’ daily social activities, R2S's utilization, and residents’ perceived user experiences and social emotions. The results reveal that R2S can generally promote daily social interactions among residents, even altering their long-established social habits. Five usage patterns of social technologies within public care environments were identified to provide insights into designing systems in comparable contexts. The participants reported a highly positive user experience with the system. Although their affective social benefits were not significant, they substantially outweighed the affective costs. These findings not only deepen the understanding of how technology can enhance social interaction in public care settings but also provide insights to inform the design and implementation of related technologies in the future.

Development and feasibility testing of a time-restricted eating intervention for women living with overweight/obesity and HIV in a resource-limited setting of South Africa

BackgroundHuman Immunodeficiency Virus (HIV) and type 2 diabetes (T2D) are amongst the leading causes of death in South Africa. The preferred first-line anti-retroviral treatment contains dolutegravir (DTG), shown to increase body weight, may compound the already high rates of obesity and associated risk for T2D. South Africa has widespread food insecurity, making traditional dietary strategies difficult to implement. Time-restricted eating (TRE) may be an appropriate intervention in resource-limited communities.MethodsThis article outlines the development and feasibility testing of a TRE intervention to inform the design of a TRE randomised controlled trial in women (20–45 years old) living with overweight/obesity and HIV, receiving DTG-based treatment from a resource-limited community in Cape Town, South Africa. Factors influencing TRE adoption were identified using the Capability, Opportunity, Motivation – Behaviour model and the Theoretical Domains Framework, combining in-depth interviews (IDIs) and focus group discussions. Participants from the IDIs went on to participate in a single arm 4-week TRE pilot trial where feasibility was explored in terms of reach, acceptability, applicability, and implementation integrity. An iterative, thematic analysis approach was employed to analyse the qualitative data.ResultsParticipants included 33 isiXhosa-speaking women (mean age 37.1 years, mean BMI 35.9 kg/m2). Thematic analysis identified psychological capability (knowledge of fasting), social influences (cultural preferences, family support), and reflective motivation (awareness of weight, health impact, motivation for TRE) as key factors influencing adoption of TRE for weight management. In a 4-week TRE pilot trial (n = 12), retention was 100%. Positive outcomes perceived included improved energy, appetite control and weight loss. TRE was perceived as acceptable, easy, and enjoyable. Family support facilitated adherence, while habitual and social eating and drinking practices were barriers. Compliance was high, aided by self-selected eating times, reminders, and weekly calls. Recommendations included the incorporation of dietary education sessions and text messages to provide additional support and reminders.ConclusionsThis study indicates that TRE is a feasible weight management strategy in women living with overweight/obesity and HIV, receiving DTG-based treatment in a resource-limited community. These findings will ensure that the forthcoming TRE randomised controlled trial is adapted and optimised to the local South African context.

Crassocephalum crepidioides as a sustainable protein supplement in Chocolatemahseer (Neolissochilus hexagonolepis) diets: Implications for growth,health, and economic viability in sustainable aquaculture

This study investigated the potential of Crassocephalum crepidioides, an abundant weed as a protein supplement in chocolate mahseer (Neolissochilus hexagonolepis) diets. The plant replaced a combination of fish meal and mustard oil cake at 0%, 25%, 50%, 75%, and 100% in experimental diets. A 12-week feeding trial was conducted to assess growth performance, survival, biomass yield, digestive enzyme activity, blood parameters, and economic viability. Results indicated that C. crepidioides can effectively replace up to 61.3% of the combined fish meal and mustard oil cake protein without negatively impacting fish health or growth, while reducing feed costs. Fish fed diets with 25% replacement showed improved weight gain (15.5±0.7 g) and biomass yield (6.05±0.25 kg/m³) compared to the control (14.6±0.8 g and 5.75±0.28 kg/m³, respectively). Survival rates were high across all treatments (94.0- 97.3%). Digestive enzyme activities and blood parameters remained within normal ranges for inclusion levels up to 75%. Economic analysis revealed potential cost savings of up to 15.5% when incorporating C. crepidioides into mahseer diets. This finding presents an opportunity to develop low-cost fish feed for resource-poor farmers in Meghalaya, effectively converting a local weed into a valuable aquaculture input, with broader implications for sustainable aquaculture practices globally.

Effect of weekly high-dose vitamin D3 supplementation on the association between circulatory FGF-23 and A1c levels in people with vitamin D deficiency: A randomized controlled 10-week follow-up trial

Effect of weekly high-dose vitamin D3 supplementation on the association between circulatory FGF-23 and A1c levels in people with vitamin D deficiency: A randomized controlled 10-week follow-up trial

Comparative effectiveness trial: Modular behavior approach for young autistic children compared to comprehensive behavioral intervention.

This 24-week single-blind trial tested a modular approach for young autistic children (MAYAC) that was delivered for fewer hours per week and modified based on child progress and parental input compared to comprehensive behavioral intervention treatment as usual (CBI, TAU). Participants were autistic children, ages 18-60 months of age. MAYAC was initially 5 h of intervention per week, one of which was parent training and the other four direct therapy focusing on social communication and engagement, but additional modules could be added for up to 10 h per week. Comprehensive behavior intervention was delivered for ≥15 h per week. Outcome measures included the Vineland Adaptive Behavior Scales; VABS, the Ohio Autism Clinical Improvement Scale - Autism Severity; OACIS - AS and the Pervasive Developmental Disorder Behavior Inventory - Parent; PDDBI-P. Implementation and parent satisfaction measures were also collected. Fifty-six children, mean age of 34 months, were randomized. Within-group analysis revealed significant improvements from baseline to week 24 for both MAYAC (p < 0.0001) and CBI, TAU (p < 0.0001) on the VABS. The noninferiority test was performed to test between group differences and MAYAC was not inferior to CBI, TAU on the VABS (p = 0.0144). On the OACIS - AS, 48.0% of MAYAC and 45.5% of CBI were treatment responders there were no significant changes on the PDDBI-P, for either group. Treatment fidelity was high for both groups (>95%) as was parent satisfaction. Findings from this small trial are promising and suggest MAYAC may be an alternative for some young autistic children and their families to CBI, TAU.

The influence of a vegan diet on body composition, performance and the menstrual cycle in young, recreationally trained women– a 12-week controlled trial

The influence of a vegan diet on body composition, performance and the menstrual cycle in young, recreationally trained women– a 12-week controlled trial

Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment Reduces Variability in Brain Function in Schizophrenia: Data From a Double-Blind, Randomized, Sham-Controlled Trial.

There is increasing awareness of interindividual variability in brain function, with potentially major implications for repetitive transcranial magnetic stimulation (rTMS) efficacy. We perform a secondary analysis using data from a double-blind randomized controlled 4-week trial of 20 Hz active versus sham rTMS to dorsolateral prefrontal cortex (DLPFC) during a working memory task in participants with schizophrenia. We hypothesized that rTMS would change local functional activity and variability in the active group compared with sham. 83 participants were randomized in the original trial, and offered neuroimaging pre- and post-treatment. Of those who successfully completed both scans (n = 57), rigorous quality control left n = 42 (active/sham: n = 19/23), who were included in this analysis. Working memory-evoked activity during an N-Back (3-Back vs 1-Back) task was contrasted. Changes in local brain activity were examined from an 8mm ROI around the rTMS coordinates. Individual variability was examined as the mean correlational distance (MCD) in brain activity pattern from each participant to others within the same group. We observed an increase in task-evoked left DLPFC activity in the active group compared with sham (F1,36 = 5.83, False Discovery Rate (FDR))-corrected P = .04). Although whole-brain activation patterns were similar in both groups, active rTMS reduced the MCD in activation pattern compared with sham (F1,36 = 32.57, P < .0001). Reduction in MCD was associated with improvements in attention performance (F1,16 = 14.82, P = .0014, uncorrected). Active rTMS to DLPFC reduces individual variability of brain function in people with schizophrenia. Given that individual variability is typically higher in schizophrenia patients compared with controls, such reduction may "normalize" brain function during higher-order cognitive processing.

DNA methylation of serotonin genes as predictive biomarkers of antidepressant treatment response

Selective serotonin reuptake inhibitors (SSRI) are frequently ineffective in treating depressive episodes and biomarkers are needed to optimize antidepressant treatment outcomes. DNA methylation levels of serotonin transporter (SLC6A4) and tryptophan hydroxylase 2 genes (TPH2) have been suggested to predict antidepressant clinical outcomes but their applicability remains uncertain. In this study, we: 1) evaluated SLC6A4/TPH2 methylation biomarker potential for predicting clinical outcomes after escitalopram treatment; 2) evaluated whether changes in SLC6A4/TPH2 methylation are informative of treatment mechanisms. We used a cohort of 90 unmedicated patients with major depressive disorder that were part of a 12-week open-label longitudinal trial and compared our observations with previous findings. Depressive symptoms were measured at baseline and after 8 and 12 weeks of treatment using the Hamilton Depression Rating Scale (HAMD6/17). We found an association between baseline TPH2 methylation and both clinical response (β:3.43; p = 0.01; 95 % CI:[0.80; 6.06]) and change in depressive symptoms after 8 weeks (β:−45.44; p = 0.01; 95 %CI:[− −78.58; −12.30]). However, we found no evidence for predictive value of any gene (TPH2 AUC: 0.74 95 % CI:[0.42;0.79]; SLC6A4: AUC: 0.61; 95 % CI: [0.48–0.78]). Methylation levels changed at the trend level for CpG sites of SLC6A4 and TPH2 over the course of 12 weeks of treatment. In addition, similar to previous observations, we found a trend for an association between methylation of SLC6A4 CpG2 (chr17:30,236,083) and HAMD17 change after 12 weeks. Our findings suggest that although TPH2 and SLC6A4 methylation may be informative of antidepressant treatment outcome, they are unlikely to prove useful as clinical predictor tools.

Effect of low vs high dietary-advanced glycation end products on insulin-sensitivity and inflammatory- markers among overweight/obese Asian-Indian adults-A randomised controlled trial

The present study investigated the effect of low vs high-dietary-Advanced Glycation End products-based diets on oral disposition index-(DIo)-a marker of islet β-cell function and cardiometabolic risks factors in 38-overweight and obese Asian Indian-adults (aged 25–45 years with body-mass-index (BMI) ≥23kg/m2) through 12-week isocaloric crossover feeding trial. Biochemical-measures included-glucose tolerance test (GTT), Insulin assay (0,30 and 120 min), lipid-profile, serum-adiponectin, serum-AGE and serum-Thiobarbituric acid reactive substances-(TBARS) assessed both at baseline and end of each intervention. Generalised linear models showed that low-dAGE diet significantly improved in oral disposition index [Least Square Mean (SE), +0.3 (0.1); p = 0.03] compared to high-dAGE diet. The low-dAGE diet also showed a significant reduction in 30-minutes plasmapost-glucose-challenge-value:(-8.1[3.8] (mg/dl) vs 3.8 [3.8] (mg/dl); p = 0.01), serum-AGEs-(-3.2 [0.2] (μg/ml) vs -0.8 [0.2] (μg/ml); p = <0.0001) compared to high-dAGE diet. In summary, low-dAGE diets exhibited improvement in the insulin-sensitivity and reduction in the inflammatory levels compared to high-dAGE diets. Hence, study first time in India revealed that low dAGE diets could be a potential strategy to reduce diabetes risk.

Stocking density affects growth, feed utilisation, metabolism, welfare and associated mRNA transcripts in liver and muscle of rainbow trout more pronouncedly than dietary fish meal inclusion level

In aquaculture, stocking density and diet composition are critical factors that influence the performance and welfare of the farmed animal. However, there is limited information on their interactive effects. In this context, applying a 2 × 2 factorial design, we conducted a 12-week feeding trial to evaluate the effect of stocking density (low, LSD: 3.3–15 kg m−3 and high, HSD: 5.8–25 kg m−3; initial-final values) and dietary fish meal content (high, HFM: 30 % and low, LFM: 15 %) on growth, feed utilisation, metabolic oxygen consumption, tissue indices, carcass composition, plasma metabolites, and transcriptional regulation of growth, metabolism and welfare-related biomarker mRNAs in liver and muscle of the juvenile rainbow trout. At the whole-animal level, the HSD group showed significantly higher routine metabolic rate and feed intake indicating higher energy demand; but growth and feed efficiency was lower in HSD than the LSD group. Morpho-anatomically, HSD fish had lower relative gut length and higher intra-peritoneal fat index than LSD fish. Lower plasma free amino acids and glucose levels reiterated high energy expenditure in HSD, and elevated albumin levels indicated potential oxidative stress in the HSD group. Correspondingly, at the transcriptional level, hepatic mRNA levels of antioxidative enzymes (sod, cat, gst, g6pd) and stress-related molecular chaperone hsp90 were up-regulated in HSD; while the transcript abundance of growth-axis markers (ghr, igf1 igf2) and nutrient-sensor mtor were decreased. In muscle, proteolytic pathway components fbx32 and murf1 were upregulated in HSD, and concurrently mtor was also upregulated suggesting higher protein turnover in this group. With respect to the effect of dietary fish meal inclusion levels, LFM showed decrease in growth, hepatic igf2 expression, and lower plasma triglycerides and free amino acid levels than HFM group. However, the sensory appearance of flesh was found to be slightly better in LFM. Significant diet-husbandry interactions were not observed phenotypically, but the mRNA abundance of hepatic markers (ampk1, hsp70, mhc1 and tnfa) linked to energy-sensing, stress and immune response were differentially regulated. Overall, the study shows that high stocking density has a greater degree of impact on fish growth and welfare than reduction in dietary fishmeal inclusion, with limited interactional effects.

Development and Validation of SCACOMS, a Composite Scale for Assessing Disease Progression and Treatment Effects in Spinocerebellar Ataxia.

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.

Influence of cocaine use reduction on markers of immune function

This study determined the effects of reduced cocaine use on immune function. Treatment seeking participants with Cocaine Use Disorder enrolled in a 12-week contingency management trial to reduce cocaine use. Participants were randomly assigned 1:1:1 to High Value Reinforcers (i.e., $55/negative urine sample) for cocaine abstinence (n = 41), Low Value Reinforcers (i.e., $13/negative urine sample) for cocaine abstinence (n = 33) or Non-Contingent Control (n = 33). Immune measures were collected at 6-week intervals. The High Value group had greatest use reductions, increased erythema and IL-6 and decreased IL-10 and CCL5, suggesting an activated immune response. Cocaine use reduction may promote changes in immune health.

Effects of metformin and curcumin in women with polycystic ovary syndrome: A factorial clinical trial

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder in women, associated with dyslipidemia, insulin resistance, and hormonal imbalances. Metformin and curcumin have shown promise in improving these metabolic and hormonal parameters individually, but their combined effects in PCOS remain unclear. MethodsWe conducted a randomized, double-blind, placebo-controlled, 12-week factorial trial involving 200 women with PCOS. Participants were randomly assigned in a 1:1:1:1 ratio to receive metformin (500-mg/8 h) + placebo, nanocurcumin soft gel capsule (80-mg/8 h) + placebo, metformin (500-mg/8 h) + nanocurcumin (80-mg/8 h), or double placebo. Lipid profiles, glucose metabolism markers, hormonal parameters, body weight, and body mass index (BMI) were assessed at baseline and week 12. ResultsThe combination of metformin and curcumin demonstrated significant improvements in lipid profiles, glucose metabolism, hormonal parameters, body weight, and BMI compared to individual agents or placebo. Greater reductions in low-density lipoproteins (LDL) cholesterol, total cholesterol (TC), and triglyceride (TG) levels were observed with the combination therapy, along with increased high-density lipoproteins (HDL) cholesterol. Additionally, the combination therapy significantly improved markers of glucose metabolism and showed synergistic effects in reducing body weight and BMI. Reductions in testosterone and improvements in Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) levels were also observed with combination therapy. ConclusionThe combination of metformin and curcumin demonstrates superior efficacy in improving lipid profiles, glucose metabolism, hormonal parameters, body weight, and BMI in women with PCOS compared to individual agents or placebo. This highlights the potential synergistic effects of combining these agents for the management of PCOS.