Baseline Week Research Articles

A 4-Week Morning Light Treatment Reduces Amygdala Reactivity and Clinical Symptoms in Adults with Traumatic Stress

Trauma leads to mental health problems including posttraumatic stress disorder (PTSD), depression, and anxiety. New treatments are needed for traumatic stress that can overcome barriers to care while targeting underlying biological mechanisms of the pathology. Morning light treatment has potential as a novel intervention for traumatic stress. We conducted a randomized clinical trial testing 3 doses of a 4-week morning light treatment in people with traumatic stress to evaluate brain mechanisms underlying the treatment. Forty-six participants completed a baseline week followed by a 4-week morning light treatment (15, 30 or 60 mins each morning). Functional magnetic resonance imaging was conducted at pre- and post-treatment using an emotional faces task to probe the amygdala, based on prior work showing direct effects of light on the amygdala and the role of amygdala in traumatic stress. Clinician-rated symptoms and self-reported symptoms were also assessed at pre- and post-treatment. No group differences were observed in left amygdala reactivity, but right amygdala reactivity reduced only in the 30 and 60 min groups with medium effect sizes. Clinical symptoms reduced in all groups with medium to large effect sizes. Self-reported depression and anxiety scores reduced more in the 60 min than in the 15 min group (p=0.02). The results suggest that 4 weeks of morning light treatment of at least 30 minutes per day can reduce amygdala reactivity and symptoms of traumatic stress. Morning light treatment should be further explored as a potential treatment for traumatic stress, given it is relatively safe, acceptable, accessible and scalable.

Abstract 4120229: Shift in body mass index category and associated cardiometabolic risk factors: a post hoc analysis from the SURMOUNT-4 trial

Background: In SURMOUNT-4, participants with obesity demonstrated a mean weight reduction of 21% during the 36-week lead-in with the maximum tolerated dose (MTD) of tirzepatide (TZP). During the 52-week double-blind period, participants who switched to placebo (PBO) experienced a 14% weight regain, while those who continued TZP achieved an additional 6% weight reduction. This post hoc analysis assessed whether participants who shifted to a lower BMI category had improved cardiometabolic factors. Methods: Shift in BMI category (<25 kg/m 2 , 25 to <30 kg/m 2 , 30 to <35 kg/m 2 , 35 to <40 kg/m 2 , and ≥40 kg/m 2 ) from baseline (week 0) during the lead-in period (week 36) and at the primary endpoint (week 88) and from week 36 to week 88 was assessed in participants from SURMOUNT-4 randomized to TZP MTD (N=332) or PBO (N=329). BMI shifts were grouped into “improved” (shift to ≥1 lower category) or “not improved” (stable/attenuated [no change/shift to a higher category]). Changes from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, vitals and lipid profile were assessed. Results: From weeks 0 to 36, 296 (89%) participants improved in BMI category with TZP, and none had attenuated (Table). From weeks 36 to 88, 130 (39%) participants improved in BMI category with TZP, while the majority (99%) randomized to PBO did not. Overall, from weeks 0 to 88, 304 (92%) vs 189 (57%) participants improved in BMI category with TZP vs PBO, respectively, where the improvements observed in the PBO group originated from the 36-week lead-in period. In general, participants who improved in BMI category at week 88 were noted to have greater improvements in cardiometabolic parameters with TZP vs PBO, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, triglycerides, and cholesterol (total, non-HDL-c, LDL-c, and VLDL-c). Conclusions: In this post hoc analysis of SURMOUNT-4, the majority of TZP-treated participants shifted to lower “improved” BMI categories. Shift to an improved BMI category was accompanied by improved cardiometabolic risk factors, suggesting that TZP treatment may lower further cardiovascular outcomes. Relevant outcomes trials are ongoing.

Virtual Coach-Guided Online Acceptance and Commitment Therapy for Chronic Pain: Pilot Feasibility Randomized Controlled Trial.

Veterans are disproportionately affected by chronic pain, with high rates of pain diagnoses (47%-56%) and a 40% higher rate of prevalence of severe pain than nonveterans. This is often accompanied by negative functional outcomes and higher mortality. Combined with research suggesting medical treatments for chronic pain are often insufficient, there is an urgent need for nonmedical pain self-management programs. An interactive online platform to deliver an efficacious treatment for chronic pain such as acceptance and commitment therapy (ACT) could be a valuable option to assist veterans with pain care at home. This study aims to evaluate the virtual coach-guided Veteran ACT for Chronic Pain (VACT-CP) online program compared to a waitlist and treatment as usual (WL+TAU) control group through a small pilot feasibility randomized controlled trial. The primary aim was to evaluate the feasibility and acceptability of VACT-CP and study procedures, such as ease of recruitment, treatment receptivity, attrition and retention, sustained participation, system usability, and assessment of trial procedures. Secondary aims explored differences in the VACT-CP and WL+TAU groups on pre- and posttest (week 7) outcome measures for pain, mental health, functioning, and ACT processes. Veterans with chronic pain were recruited and randomized to either the VACT-CP (n=20) or the WL+TAU (n=22) group in a parallel group trial design. Self-report surveys were administered to participants at baseline (week 0), at the intervention midpoint (week 3), immediately after the intervention (week 7), and at the 1-month follow-up (week 11). We used Wilcoxon signed rank tests with the intention-to-treat sample to describe changes in secondary outcomes from pre- to postintervention within each group. Study procedures showed good feasibility related to recruitment, enrollment, randomization, and study completion rates. Participants reported that VACT-CP was easy to use (System Usability Scale: mean 79.6, SD 12.8; median 82.5, IQR 70-87.5); they completed an average of 5 of the 7 total VACT-CP modules with high postintervention satisfaction rates. Qualitative feedback suggested a positive response to program usability, content tailoring, veteran centeredness, and perceived impact on pain management. Although the pilot feasibility trial was not powered to detect differences in clinical outcomes and significant findings should be interpreted with caution, the VACT-CP group experienced significant increases in chronic pain acceptance (P<.001) and decreases in depressive symptoms (P=.03). VACT-CP showed encouraging evidence of feasibility, usability, and acceptance, while also providing promising initial results in improving a key process in ACT for chronic pain-chronic pain acceptance-after online program use. A full-scale efficacy trial is needed to assess changes in clinical outcomes. ClinicalTrials.gov NCT03655132; http://clinicaltrials.gov/ct2/show/NCT03655132. RR2-10.2196/45887.

Effectiveness of telerehabilitation-based mckenzie method versus manual therapy in low-back pain management: a randomised controlled trial

Abstract Background Studies comparing the effectiveness of telerehabilitation and spinal manual therapy (SMT) for chronic non-specific low-back pain (NSLBP) are limited. This study aimed to compare the efficacy of the telerehabilitation-based McKenzie therapy (TBMT) and SMT among patients with NSLBP. Methods Forty-nine consenting patients randomised into either TBMT (n = 28) or SMT (n = 21) group completed the study. TBMT is a mobile phone-based telerehabilitation involving the ‘McKenzie extension protocol’. SMT is a grade II (10 oscillations) posterior-anterior central vertebral pressure on the offending spinous process. Both interventions were applied thrice weekly for eight weeks, and outcomes were assessed on Pain Intensity (PI), Activity Limitation (AL), Participation Restriction (PR), and Health-related Quality of Life (HRQoL) in the fourth and eighth weeks. Results Within-group comparison across baseline, 4th and 8th week indicate that SMT had a significant effect on PI (F = 132.804, p = 0.001), AL (F = 75.984, p = 0.001), PR (F = 99.428, p = 0.001) and for all the scales of SF-12 except for mental health domain (p &gt; 0.05). Similarly, TBMT had a significant effect on PI (F = 243.631; p = 0.001), AL (F = 85.930; p = 0.001), PR (F = 48.425; p = 0.001), and for all the scales except also for mental health domain (p &gt; 0.05). However, there were no significant differences (p &gt; 0.05) in the treatment effects between SMT and TBMT, except for the ‘health perception’ (p = 0.045) scale at week four and the ‘mental health’ scale (p = 0.023) at week eight. Conclusion Telerehabilitation-based McKenzie method and SMT are effective in chronic NSLBP, with TBMT leading to significantly higher long-term health perception improvement. Trial Registration Pan African Clinical Trial Registry (PACTR202010667228786), Registered 27 October 2020-Retrospectively registered.

The WE-RISE™ multi-domain intervention: a feasibility study for the potential reversal of cognitive frailty in Malaysian older persons of lower socioeconomic status

BackgroundCognitive frailty (CF) is an emerging concern among older persons, particularly within lower socioeconomic statuses (SES) populations. Currently, there is limited evidence on the potential reversibility of CF through multi-domain interventions within this demographic. This study aimed to investigate the effectiveness of the WE-RISE™ multi-domain intervention in addressing the potential reversibility of CF among community-dwelling older persons of lower SES, the intervention effects on multiple health dimensions, and to determine if WE-RISE™ is of low cost.MethodsThis 24-week randomised controlled trial included 55 community-dwelling older persons of lower SES with CF, who were randomised into either the WE-RISE™ intervention group (n = 27), or the control group receiving usual care (n = 28). The WE-RISE™ intervention comprised of 12 weeks of instructor led, community-based intervention, followed by 12 weeks of WE-RISE™@Home. CF status, cognitive and physical function, nutrition, disability, health-related quality of life, exercise self-efficacy and depression were assessed at baseline, 12th and 24th weeks. Changes in CF status was analysed descriptively, while intervention effects were analyzed with split plot ANOVA. The cost of the WE-RISE™ intervention was calculated using activity-based costing.ResultsAt baseline, all participants in both the intervention and control groups (100%) were classified as CF. Following 12 weeks of the WE-RISE™ intervention, 74.1% of participants in the experimental group no longer met the criteria for cognitive frailty, with 63% maintaining this improvement at 24 weeks. In contrast, the CF status of participants in the control group remained largely unchanged, with only 10.7% showing improvement at 12 weeks and falling to 3.6% at 24 weeks. Significant intervention effects were observed for cognition, physical function, body composition, disability, health-related quality of life and self-perceived exercise self-efficacy (p < 0.05) following participation in WE-RISE™. The cost per intervention session was RM4.06 (≈ RM3.88), and the cost per subject for 48 sessions was RM194.74 (≈ RM187.01).ConclusionThe WE-RISE™ multi-domain intervention has demonstrated potential in reversing CF among older persons of lower SES, leading to significant improvements across multiple health dimensions at a low cost. WE-RISE™ shows promise to enrich the well-being of ageing societies, contribute to societal health, and ensure equitable access to healthcare, supporting broader implementation by enhancing equitable access to health programs and addressing the needs of older persons, WE-RISE™.Trial registrationThis trial was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619001055190) on the 29th of July 2019 – retrospectively registered.

Efficacy of Fecal Microbial Transplantation for Improving Symptoms of Irritable Bowel Syndrome - A Pilot Study for Voluntary Participants in Korea

Irritable bowel syndrome (IBS) is a chronic, intractable functional disease. It is inferred that fecal microbiota transplantation (FMT) may have favorable efficacy on IBS by gut microbial modification. The aim of this study was to investigate the efficacy of FMT for improving severity in patients with IBS. Patients who voluntarily wanted FMT were consecutively enrolled. The study subjects were classified by subtype of IBS by the ROME IV criteria. The IBS-symptom severity score (IBS-SSS) was used to evaluate the efficacy of FMT. The subjects completed a questionnaire at baseline week 0 and weeks 4, 12, and 24 after FMT. FMT was performed by esophagogastroduodenoscopy using frozen stock stool solution. If the follow-up IBS-SSS achieved less than 75 points, it was defined as remission. Adverse events were also gathered. Twenty-one subjects were included from October 2023 until July 2024. There were 7 patients with IBS-C, 10 patients with IBS-D, 2 patients with IBS-M, and 2 patients with IBS-U type. The mean SSS of the IBS-D group was 244.0±64.2, which was higher than IBS-C group (192.9±85.4). Alleviations in IBS-SSS after FMT were observed in 19 subjects (19/21, 90.5%) at week 4. At week 12, 71.4% (5/7) in the IBS-C group and 20.0% (2/10) in the IBS-D group achieved remission. The remission states were maintained up to week 24 and no serious adverse events were reported. FMT might be an effective treatment option for improving symptoms of mild to moderate IBS, especially IBS-C.

The Consumption of Lacticaseibacillus rhamnosus HDB1258 Changes Human Gut Microbiota and Induces Immune Enhancement Through NK Cell Activation.

The gut microbiota can play an important role in enhancing the host's complex immune system. In this regard, many studies indicate that probiotics consumption has a beneficial impact on alterations in the composition of the gut microbiota. Our previous study demonstrated that the oral administration of Lacticaseibacillus rhamnosus HDB1258 (HDB1258) enhances immune cell activity and alters the composition of gut microbiota in C57BL/6 mice, thereby showing its potential as a novel immunostimulatory ingredient. Therefore, this clinical trial assessed the effects of HDB1258 on human natural killer (NK) cell activity and changes in gut microbiota. It also investigated the correlation between gut microbiota and NK cell activity following HDB1258 supplementation. Participants (n = 71) were randomized into placebo and HDB1258 groups, and NK cell activity and gut microbiota were investigated at baseline (week 0) and endline (week 8). The present study showed that HDB1258 significantly increased NK cell activity and resulted in positive regulatory effects on the gut microbial balance in subjects compared to the placebo group. HDB1258 affected the gut microbial balance by inducing the growth of beneficial bacteria such as Lactococcus and Sutterella. Especially, the changes in Escherichia-Shigella composition were negatively correlated with the changes in NK cell activity after HDB1258 consumption. There was also a positive correlation between the NK cell activity in the HDB1258 group and the composition of Prevotella 9 and Adlercreutzia. These findings suggest that HDB1258 may improve the host's intestinal environment by regulating gut bacteria related to immune response and promote NK cell activation. This study was registered at clinical research information service (CRIS: KCT0008204).

Soundscape augmentation as a nonpharmacological intervention to reduce the behavioural effect of dementia: a randomized controlled trial

Soundscape is an important environmental factor that influences people's behaviour and well-being. People with dementia can benefit from a personalized soundscape to improve the behavioural and psychological syndrome of dementia. This paper is based on a single-blind, repeated-measure pilot randomized clinical trial of soundscape augmentation on the treatment effect of people with severe dementia. Participants were randomized to a personalized soundscape intervention delivered in their room in the morning and evening or treatment-as-usual, with two baseline weeks and four weekly post-randomization assessments of the primary and secondary behavioural outcomes. A linear mixed effects model showed that the soundscape intervention was possible and acceptable. There were improvements in the Neuropsychiatric Inventory (resistance to care) and a significant reduction in aggression in the soundscape group. This study is the first pilot randomized controlled trial of a soundscape intervention for older adults with dementia to improve the behavioural and psychological syndrome of dementia. In this pilot study, soundscape augmentation was a feasible and effective non-pharmacological approach to reducing resistance and improving participants' behaviour. Further studies with larger samples are recommended to confirm our findings. Longitudinal studies are necessary to investigate the long-term effect of an augmented sonic environment on people with dementia.

The dose effectiveness of extracorporeal shockwave on plantar flexor spasticity of ankle in stroke patients: a randomized controlled trial

BackgroundExtracorporeal shockwave therapy (ESWT) has been proven beneficial for post-stroke spasticity (PSS) of ankle plantar flexor muscles. This study aims to investigate the dose-response effectiveness of focused-ESWT and the duration of its effect on the treatment of ankle PSS in stroke patients.MethodsIn this double-blinded randomized controlled trial, stroke patients diagnosed with PSS in the ankle plantar flexor muscles were randomly assigned to two groups. The experimental group received double-dose ESWT (4000 pulses per session) targeting spastic calf muscles, while the control group received half the dose (2000 pulses per session). Both groups underwent four sessions over two weeks. The outcomes, including modified Ashworth Scale (MAS), modified Tardieu Scale (MTS), passive range of motion (PROM) of the ankle, Timed Up and Go (TUG) Test, Barthel index and strain elastography were evaluated at baseline, 1st, 4th, 12th, and 24th week after ESWT.ResultsWithin-group analysis revealed significant improvements in MAS, PROM, TUG Test, and Barthel index for the double-dose ESWT group and improvements in Barthel index for the control group. Between-group analysis revealed greater improvements in TUG Test, Barthel Index and strain elastography for the double-dose ESWT group. Generalized estimating equations analysis indicated that the double-dose ESWT group achieved superior outcomes in the TUG Test, Barthel Index, and strain elastography across various time points and groups.ConclusionsDouble-dose ESWT showed better functional improvement and elastography compared to the control group. ESWT demonstrated dose-response effectiveness for PSS of ankle-equinus.Trial registrationNCT05878223.

Being Present-CML: A mindfulness-based intervention for patients with chronic myeloid leukemia taking tyrosine kinase inhibitors.

353 Background: Tyrosine kinase inhibitors (TKIs) prolong the lives of patients with chronic phase chronic myeloid leukemia (CP-CML) but can cause side effects that negatively impact quality of life. Mindfulness-based interventions (MBIs) have improved symptoms in patients with solid tumors but have not been studied in patients with CP-CML. We sought to determine if a MBI is feasible and acceptable to patients with CP-CML and explored its preliminary efficacy. Methods: Being Present-CML is a prospective, single-arm clinical trial of an 8-week, online MBI developed for patients with GI cancers (Atreya, et al. PLoS One, 2018) and adapted to include qigong. Participants were recruited from a single academic institution. Eligibility included adult patients with CP-CML taking TKIs. Participants played audio-guided meditations at least 5 times per week on a secure website and participated in weekly, instructor-led meditation and qigong sessions on Zoom. Feasibility was assessed through measurement of recruitment and attrition. Adherence was determined by web capture. Acceptability was determined from surveys and qualitative interviews. Preliminary efficacy was evaluated by patient-reported outcome measures (PROMs) at baseline (week 0) and post-intervention (week 8). Descriptive statistics and two-tailed paired t-tests (p&lt;0.05) were used to summarize the data. Interim results were presented previously; here we report the final results. Results: Between October 2020-September 2021, 121 eligible participants were approached to participate, and 46 patients (38%) consented. The median age was 49.5 years (range 23-75), 54.3% (n=25/46) were male, and 82.6% (n=38/46) were non-Hispanic White. At time of study start, 82.6% (n=38/36) were taking dasatinib, 84.7% (n=39/46) had a BCR-ABL1 PCR transcript ≤1%, and a median time since diagnosis of 70.5 months (range 1-234). Of 46 participants, 35 (76.1%) completed end of study procedures. The median number of audio meditations listened to per participant was 28.7 with an average of 4.1 per week. The median number of 8 weekly classes attended and/or recordings viewed per participant was 7 (range 0-8). At baseline, participants had an average NCCN Distress Thermometer score of 4.86 (range 0-8), which improved to 3.5 by week 8 (p=0.02). Nearly all participants would recommend the to others (median score of 9 on a 1-10 scale; 10=extremely likely). Conclusions: Patients with CP-CML taking TKIs found the MBI to be feasible and acceptable. PROM results suggest potential for distress reduction in this patient population. Clinical trial information: NCT04605211 .

Trajectory of symptoms reported in remote symptom monitoring over the course of oncology treatment for lung cancer.

250 Background: Electronic patient reported outcomes (ePROs) enable patients to report symptoms from treatment in real time using their mobile device. This analysis sought to better understand the trajectory of reported symptoms via remote symptom monitoring (RSM) during treatment for patients with lung cancer. Methods: We approached patients with lung cancer initiating treatment at the Mitchell Cancer Institute (MCI) between March 2022-October 2023 to participate in an RSM program. Patients were eligible if they were initiating treatment (chemotherapy, targeted therapy, or immunotherapy) for the first time at MCI. Patients seeking a second opinion were excluded. Enrolled patients received a symptom survey (PRO-CTCAE questions) once a week via text or email. Alerts were forwarded to the clinical care team for symptom management. Patients completed symptom assessments for 24 weeks or until withdrawal. At 24 weeks, patients were given the ability to continue symptom assessments if they were continuing treatment. Patient demographics including age at enrollment, race, sex, cancer type, cancer stage, and PRO data were collected from electronic health records and the PRO platform (Carevive). Descriptive statistics were calculated using frequencies and percentages for categorical variables and median and interquartile ranges (IQR) for continuous variables. Results: Of 80 patients approached, a total of 57 (71%) patients with lung cancer were enrolled in RSM; 20% were Black or African American and 80% were White; median age was 66 (IQR 61-73). Over 24 weeks, 732 symptom alerts were reported; 75% considered moderate and 25% considered severe. Overall, the most frequently reported symptom was pain (29%), followed by dyspnea/cough (25%) and constipation (13%). At baseline (week 0), 78 moderate symptoms and 39 severe symptoms alerts were reported. At week 24, 10 moderate symptoms and 4 severe symptoms alerts were reported. Overall, there was a decrease in symptom alerts over time for both moderate and severe alerts. Specific symptom trajectories followed similar patterns. Conclusions: In our sample, most symptoms were reported during the initial three months of treatment with a subsequent decrease in symptom alerts over time, indicating effective monitoring and management by clinical teams engaged in RSM. Future research is needed to understand if symptom improvement correlates with enhanced quality of life, reduced hospitalizations, and prolonged survival, as well as a lessened burden of call volume on the clinical team. Future analyses should also be done to compare similar results of different disease types.

Dairy calves' time spent in the cow herd in a calf-driven cow-calf contact system during two-step separation with a nose flap

Although originally developed for weaning of beef calves, nose flaps are also used on dairy farms nowadays to wean calves which are reared with contact to their dam or a foster cow. These calves are often weaned younger than beef calves and the time they wear nose flaps is highly variable, since it is unknown for how long younger calves need to wear the nose flap in order to induce an effective weaning. The aim of our study was therefore to track changes in dam-contact initiated by dairy calves after insertion of a nose flap in order to determine the minimum duration a nose flap needs to be worn to effectively reduce suckling motivation of calves. The study was conducted in two sequential experiments using 3-month-old dairy calves that were reared with full-time dam contact. Calves were weaned with a nose flap over either 14 (experiment I, 9 calves in herd A and 9 calves in herd B) or 7 days (experiment II, 11 calves in herd A and 12 calves in herd B) before they were fence-line separated from their dams. The total time a calf spent within the cow herd (TIC) per day was determined from continuous video recordings during 7 days before nose flap insertion (baseline), as well as during the 7 or 14 days in which calves had free access to the cow area while wearing the nose flap. Statistical analysis was conducted using linear mixed effects models. Results from both experiments showed that calves reduced their TIC at the fourth day of wearing the nose flap compared to their individual baseline (p=0.03 and p=0.001 respectively). In experiment I, calves showed a further numerical reduction in TIC from day 4 to day 5, while in experiment II, calves showed no further reduction in TIC after the 4 days of wearing the nose flap. After these 4 or 5 days respectively, TIC of calves in both experiments stayed at a constant low level of several hours per day. Taken together, these results indicate that in 3-month-old dairy calves it needs at least 4 days until the motivation to spend time with the cow decreases after insertion of a nose flap, while there seems to be no further decrease in motivation when using a nose flap longer than this time. However, results were subject to considerable inter-individual variability already during the baseline week and need replication in a pasture-based setting with less space-restrictions.

Effects of an 8-Week Active Play Intervention on Body Composition and Fundamental Motor Skills in Preschool Children.

Objective: Examine the effect of an 8-week teacher-guided active play intervention on preschoolers' body composition and fundamental motor skills. Methods: Participants were from two local preschool centers randomly assigned to either the intervention (n = 25, 3.91 ± 0.53 years) or the control group (n = 25, 3.69 ± 0.81 years). All measures were assessed at baseline (week 0), post-intervention (weeks 9-11), and follow-up (weeks 30-33). Bioelectrical Impedance assessed body composition (fat mass (FM) and fat-free mass (FFM)). The Peabody Developmental Motor Scales, Second Edition (PDMS-2) assessed fundamental motor skills (gross motor quartile (GMQ)). Results: A significant Group × Time interaction for GMQ at post-intervention (p = 0.03), with the intervention group scoring significantly higher on GMQ. A significant main effect of Time (p < 0.001) indicated that GMQ increased in both groups across the 33-week period. For FM, a significant main effect of Time at both post-intervention (p < 0.05) and follow-up testing (p < 0.001) indicated that participants increased FM over the 33-week period. Lastly, there was a significant main effect of Time for FFM at post-intervention (p = 0.003) and follow-up (p < 0.001). Interestingly, there was a significant Group × Time interaction (p < 0.05) at follow-up testing showing that FFM increased over time but significantly more for the control group. Conclusions: Results indicate that active play interventions might be a successful pathway to improve gross motor skills in young children. Further research is needed to understand the effect that active play interventions have on body composition in preschoolers.

Sleep dysfunction and gut dysbiosis related amino acids metabolism disorders in cynomolgus monkeys after middle cerebral artery occlusion

IntroductionThis study aimed to explore the characteristics of post-stroke sleep dysfunction and verify their association with gut dysbiosis and the related amino acid metabolism disorders. This was achieved by using fecal microbiota transplantation (FMT) in a non-human primate stroke model. MethodsTwenty adult male cynomolgus monkeys were divided into the sham (n = 4), middle cerebral artery occlusion (MCAO, n = 5), MCAO + FMT (n = 3), and donor (n = 8) groups. The MCAO+FMT group received FMT at post-MCAO week 4. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine (Gln) in the cerebrospinal fluid (CSF) were measured at baseline and postoperative weeks 4, 8, and 12. ResultsAt postoperative weeks 4, 8, and 12, the MCAO group showed decreased sleep efficiency, measured as the percentage of sleep during the whole night (82.3 ± 3.2 % vs 91.3 ± 2.5 %, 79.0 ± 3.75 % vs 90.8 ± 3.2 %, and 69.5 ± 4.8 % vs 90.5 ± 2.7 %; all P < 0.05), lower relative abundance of Lactobacillus (all P < 0.05), and reduced GABA concentrations in the CSF (317.3 ± 30.6 nmol/L vs 437.7 ± 25.6 nmol/L, 303.1 ± 48.9 nmol/L vs 4 40.9 ± 37.8 nmol/L, and 337.9 ± 49.4 nmol/L vs 457.4 ± 39.2 nmol/L; all P < 0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7 ± 1.1 % vs 79.0 ± 3.75 %, and 84.1 ± 2.0 % vs 69.5 ± 4.8 %; both P < 0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1 ± 25.4 nmol/L vs 303.1 ± 48.9 nmol/L, P < 0.05) was higher in the MCAO+FMT group than in the MCAO group. ConclusionsPost-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as Lactobacillus, GABA, and Gln in the CSF and can be ameliorated using FMT.

Internet-based cognitive behavioral therapy for individuals with gambling disorder in Indonesia: protocol for a pilot and feasibility study.

Gambling disorder (GD) has become a wide concern in Indonesia, as many negative consequences arise from this psychiatric condition. Prompt treatment with an appropriate method of delivery is required to achieve optimal outcomes in GD patients. This protocol paper outlines a study to determine the effectiveness, acceptability, and feasibility of internet-based cognitive behavioral therapy (iCBT) in treating GD in Indonesia. This non-randomized pilot and feasibility study will recruit 20 people with GD. All participants will receive the iCBT intervention through self-learning videos and guided weekly group sessions. The effectiveness of the intervention will be assessed at baseline (week 0), post- treatment completion (week 10), and 6 weeks post-treatment (week 16). The outcomes measured will be the change in gambling symptoms, gambling urges, cognitive distortions, readiness to change, emotional problems, and quality of life of the participants. The feasibility of iCBT for GD patients in Indonesia will be assessed by this study. The study's results will give an indication of the acceptability of the intervention and the feasibility of a subsequent conclusive trial. The delivery of iCBT may help to address the issue of treatment access in an extensive geographical region and provide immediate implications as a treatment resource for GD in practice.

HLA-DR+ regulatory T cells and IL-10 are associated with success or failure of desensitization outcomes.

Omalizumab (XOLAIR®)-assisted multi-food oral immunotherapy (mOIT) has been shown to safely, effectively, and rapidly desensitize patients with multiple food allergies. In our clinical trial (NCT02626611) on omalizumab-assisted mOIT, different desensitization outcomes (success or failure of desensitization) were observed following a period of either continued or discontinued mOIT. However, the association between the immunological changes induced by omalizumab-assisted mOIT and desensitization outcomes has not yet been fully elucidated. In this study, due to the key roles of regulatory T (Treg) cells and the type 2 helper T cell (Th2) pathway in immune tolerance to food allergens, we aimed to characterize their association with the desensitization outcomes of omalizumab-assisted mOIT. Mass cytometry and multiplex cytokine assays were performed on blood samples obtained from participants with allergies to peanut, cashew, or milk in our phase 2 clinical study (NCT02626611). Comprehensive statistical and bioinformatic analyses were conducted on high-dimensional cytometry-based single-cell data and high-throughput multiplex cytokine data. Our results demonstrated that the frequency of HLA-DR+ Treg cells, and the production of Th2 cytokines (IL-4, IL-5, IL-13, and IL-9) as well as the immunoregulatory cytokine IL-10 by peripheral blood mononuclear cells (PBMCs) was significantly increased in cultures with allergen compared to cultures with media alone at baseline (Week 0). We also observed increased frequency of allergen responsive HLA-DR+ Treg cells and enhanced production of IL-10 by PBMCs in participants who achieved successful desensitization compared to those with failure of desensitization. However, the production of Th2 cytokines by PBMCs did not show significant differences between participants with different desensitization outcomes (success vs. failure of desensitization), despite omalizumab-assisted mOIT inducing a significant reduction in the production of Th2 cytokines. We demonstrated that the frequency of HLA-DR+ Treg cells and IL-10 cytokine production by PBMCs are associated with desensitization outcomes of omalizumab-assisted mOIT. These findings suggest potential immunological parameters that could be targeted to enhance desensitization success rates.

Management of Knee Osteoarthritis with integrative approach using Regimenal therapy (Massage and Medicated Steam Fomentation) and Pharmacotherapy (Habb-e -Muqil): A Case Study

Osteoarthritis (OA) is the most common progressive musculoskeletal disorder, that is characterized by pathological changes in cartilage, bone, synovium, ligament, muscle, and periarticular fat, leading to joint dysfunction, pain, stiffness, functional limitation, and loss of day to day life activities. It affects an estimated more than 240 million people worldwide. It can involve almost any joint but typically affects the hands, knees, hips, and feet. In India, 28.7% of adults ≥ 40 years of age and 45.5% of adults ≥ 60 years of age have KOA. The annual incidence rate of KOA in India is 2.4%. The management of KOA involves a comprehensive approach, including non pharmacological management, pharmacological management, and surgical management. In Unani medicine, KOA comes within the domain of a broader term, “Waja-ul-Mafasil”, which refers to joint pain. It occurs due to quantitative and qualitative derangement of Akhlat (humors) and derangement of optimal temperament (Mizaj). We present the case of a 48 year old male patient, who was presented to the OPD of Regimenal therapies at National Institute of Unani Medicine, Bengaluru. Patient complains of bilateral knee pain, stiffness, limited mobility and difficulty in daily activities since 3 years. Pain exaggerates on walking for more than 50 minutes and standing continuously for more than 30 minutes. The patient was assessed and examined clinically prior to intervention and was diagnosed with bilateral KOA, which was further accentuated by radiological investigations. The patient received treatment for 6 weeks. The patient was assessed using multiple assessment parameters at baseline, 3rd and 6th week. The patient reported improvement in both subjective and objective parameters. The study found that massage therapy and steam fomentation along with pharmacotherapy can be an effective approach in treatment for KOA, however it merits further research. Keywords: Osteoarthritis, joint pain, bilateral knee pain, stiffness, limited mobility

The Effects of Imeglimin on Muscle Strength in Patients with Type 2 Diabetes: A Prospective Cohort Study.

A bidirectional relationship has been observed between type 2 diabetes mellitus and sarcopenia, especially among older adults. While previous studies have reported that imeglimin improves mitochondrial function, they have not assessed its effects on muscle strength in patients with type 2 diabetes. Therefore, we aimed to investigate the effects of imeglimin on muscle strength in patients with type 2 diabetes. In this prospective cohort study, we recruited consenting patients with type 2 diabetes (20-75years). Changes in lean body mass (LBM), fat mass, quadriceps muscle strength, and grip strength from baseline (week 0) to week 24 were evaluated and compared between patients treated with imeglimin therapy (group I) and those who did not take imeglimin (controls, group C). We recruited 27 patients treated with imeglimin (group I) and 29 controls (group C), and 50 of them completed the study (group I: n = 23; group C: n = 27). The change in LBM, total body fat mass, or skeletal muscle index from baseline to week 24 did not differ significantly between the two groups. However, group I exhibited a significantly higher percent change in quadriceps knee extension strength from baseline to week 24 than group C (13 ± 19% and 2.1 ± 14%, p = 0.022). Conversely, the difference in percent change in grip strength was not significant. Multivariable analysis showed that imeglimin use was significantly associated with a percent change in quadriceps knee extension strength, independent of age, sex, body mass index, and skeletal mass index (β = 0.325, p = 0.0014). Imeglimin positively affected muscle strength in patients with type 2 diabetes without altering LBM. Therefore, imeglimin exerts a unique effect on skeletal muscles in humans. Further randomized controlled trials are needed to validate these findings. This research was registered in the University Hospital Medical Information Network (UMIN, UMIN000054715).

Impact of MAOA Gene Polymorphism on the Efficacy of Antidepressant Treatment and Craving Severity for Betel Quid Use Disorder.

Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale-Brown Obsessive-Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 (p = 0.0194), 4 (p = 0.0078), 6 (p = 0.0277), and 8 (p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 (p = 0.0313), 4 (p = 0.0134), 6 (p = 0.0061), and 8 (p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score (p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD.

Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients

BackgroundRetinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients.MethodsThis prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients.ResultsRBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71–22.92) versus 9.59 (6.57–13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7.ConclusionPlasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.