2-week Period Research Articles

Temporal Changes in Depressive Symptoms Among Goodville Farm Game Players: A 6-Week Observational Study.

Aim of the Study: The primary objective was to evaluate the potential impact of the Goodville farm game on depressive symptoms. Methods: The Goodville game, characterized by its unique farming features, incorporates elements of emotional well-being and various mental health assessment tools, enabling players to monitor and improve their emotional state. Using self-reported Patient Health Questionnaire-8 (PHQ-8) data from 1717 US and UK players, changes were monitored weekly over a 6-week period. The study focused on the game's ability to integrate emotional well-being elements and various mental health assessments to facilitate self-monitoring and improvement of players' emotional states. Results: There was a significant overall time effect (F = 154.498, df = 1711, P < 0.001), indicating a moderate-to-large effect size, with progressive decreases in PHQ-8 scores throughout the period. About 60% of players reported reduced depressive symptom severity, with around 35% experiencing complete symptom relief. More significant improvements were observed in players with higher initial severity. No correlations were found between symptom changes and demographic data or the number of active playing days. Conclusion: Goodville demonstrates potential as a digital mental health intervention in reducing depressive symptoms through its specific characteristics designed to improve emotional well-being. The study emphasizes the need to consider baseline severity and highlights the therapeutic promise of authentic farming game features. Despite the absence of a control group, the findings contribute meaningful insights into digital interventions for mental health care and set a direction for future studies to validate and expand upon these results.

Effects of 6-Week Weighted-Jump-Squat Training With and Without Eccentric Load Reduction on Explosive Performance.

To compare the effects of 6-week barbell weighted-jump-squat (WJS) training with and without eccentric load reduction on explosive performance. Twenty well-trained male athletes were randomly assigned to either an experimental group (n = 10) or a control group (n = 10). Participants completed 12 WJS training sessions (6 sets of 5 repetitions of barbell back squat at 30% of 1-repetition maximum[1RM]) twice a week over a 6-week period. While thecontrol group used 0% eccentric loading (ie,traditional WJS), theexperimental group utilized a 50% eccentric loading reduction with a mechanical braking unit (ie,eccentric load set at 15% of 1RM). Performance assessments, including countermovement jump, 20-m sprint, standing long jump, and 1RM barbell back squat, were conducted both before (pretests) and after (posttests) the intervention. Both theexperimental group and thecontrol group demonstrated a significant increase in countermovement-jump height (+6.4% [4.0%] vs +4.9% [5.7%]; P < .001) and peak power output (+2.3% [2.7%] vs +1.9% [5.1%]; P = .017), faster 20-m sprint times (+9.4% [4.8%] vs +9.2% [5.5%]; P < .001), longer standing long jump (+3.1% [2.5%] vs +3.0% [3.3%]; P < .001), and higher 1RM back squat (+6.4% [4.0%] vs +4.9% [5.7%]; P < .001) from pretests to posttests. However, there was no significant condition × time interaction for any variable (all P ≥ .294). Both WJS training methods, with and without load reduction in the eccentric phase, effectively enhance explosive performance. Nevertheless, athletes in later stages of injury rehabilitation or intense training may find reducing eccentric load a more tolerable strategy for achieving similar performance gains compared with traditional isoinertial loading.

The Effects Of Chronotype And Social Jetlag On Blood Biomarkers During Wlff 2-week Critical Training Period

The Effects Of Chronotype And Social Jetlag On Blood Biomarkers During Wlff 2-week Critical Training Period

Positive autobiographical memories to counteract low mood in remitted depression: A longitudinal daily-life investigation.

Positive autobiographical memories (AMs) have the potential to repair low mood, but previously depressed individuals have difficulty leveraging their positive AMs for emotion regulation purposes. We examined whether previously depressed individuals benefit from guided, deliberate recollection of preselected AMs to counteract low mood in daily life, utilizing individuals' smartphones to facilitate recollection. Sixty participants enrolled in 2020 were randomly allocated to retrieval of positive or everyday activity AMs and completed ecological momentary assessment of emotional experience for 3 weeks. Participants first created a pool of six memories for the digital AM diary. This was followed by a training week with two recollection tasks daily and a 2-week follow-up period where the diary could be used spontaneously. The positive condition experienced a greater increase in feelings of happiness and a greater decrease in feelings of sadness from pre- to post-AM recollection. While participants in the positive condition used the AM technique more frequently overall during the 2-week follow-up, the effect of condition was moderated by changes in feelings of sadness. The more participants experienced an emotional benefit during the training week, the more they used it spontaneously. Emotional vividness of untrained positive AMs at the 2-week follow-up differed depending on whether they were assessed before or after the first pandemic lockdown. Residual depressive symptoms decreased in both conditions over the study course, while mental well-being remained unchanged. Strengthening positive, self-affirming AMs in daily life may provide a tool to support regulation of transient low mood in those remitted from depression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effect of add-on naldemedine treatment in patients with cancer and opioid-induced constipation insufficiently responding to magnesium oxide: a pooled, subgroup analysis of two randomized controlled trials.

To evaluate the additive effect of naldemedine tosylate (naldemedine) on opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment. We combined two randomized, double-blind, placebo-controlled, phase IIb and III trials of naldemedine and conducted a post hoc subgroup analysis. We evaluated the effect and safety of naldemedine in 116 patients who received naldemedine in addition to magnesium oxide (naldemedine group) and 117 patients who received placebo in addition to magnesium oxide (placebo group). Both groups included patients insufficiently responding to magnesium oxide for opioid-induced constipation. Effect was assessed using spontaneous bowel movement responder rate, complete spontaneous bowel movement responder rate, changes in spontaneous bowel movements and complete spontaneous bowel movements. Safety was also assessed. During the 2-week treatment period, the responder rates for spontaneous bowel movement and complete spontaneous bowel movement were 73.3 and 43.1% in naldemedine group, respectively, which were significantly higher (P<0.0001) than 41.9 and 14.5% in placebo group, respectively. Median time to first spontaneous bowel movement and first complete spontaneous bowel movement was significantly shorter (P<0.0001) in the naldemedine group (4.0 and 21.3h, respectively) than in the placebo group (27.7 and 211.7h, respectively). The incidence of adverse events and diarrhoea was significantly higher (P<0.05) in the naldemedine group than in the placebo group, while the incidence of serious adverse events and severe diarrhoea was not significantly different between the naldemedine and placebo groups. The study suggested the addition of naldemedine as an effective treatment option for opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment.

Efficacy and safety of ketogenic diet in infants with epilepsy: KIWE RCT

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with &gt; 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Cucurbita Pepo L. Seed Oil Modulates Dyslipidemia and Neuronal Dysfunction in Tramadol-Induced Toxicity in Wistar Albino Rats.

Objective: The modulating effects of Cucurbita pepo seed oil (CPSO) on dyslipidemia and neuronal dysfunction in tramadol toxicity were studied. Methods: Fifty-six albino rats were divided into seven groups of eight rats each after a 2-week acclimatization period. All animals had unrestricted access to water and feed, and treatments were administered orally once daily for 42 days. Glutamate dehydrogenase and glutaminase activities were assessed using brain homogenate, while lipid profiles were analyzed in serum samples. Results: Tramadol toxicity was evidenced by significant (P < 0.05) increases in brain glutamate dehydrogenase along with significant (P < 0.05) decreases in the activities of glutaminase in the group administered only tramadol. Also, serum levels of total cholesterol, LDL-C and triglycerides also increased significantly (P < 0.05) following administration of tramadol with decreased level of HDL-C (P < 0.05). However, treatment with CPSO significantly restored the activities and levels of the altered biochemical parameters in a dose-dependent manner. The results of the biochemical investigation using the lipid profile and the enzymes of glutamate metabolism were corroborated by the results obtained from the histopathological examination of the brain. Conclusion: The results of this study therefore suggest that tramadol-induced dyslipidemia and neuronal dysfunction be managed and prevented by the administration of Cucurbita pepo seed oil.

Lomitapide for the treatment of paediatric patients with homozygous familial hypercholesterolaemia (APH-19): results from the efficacy phase of an open-label, multicentre, phase 3 study

Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder characterised by extremely high concentrations of LDL cholesterol, leading to early-onset atherosclerosis. Lomitapide is an orally administered microsomal triglyceride transfer protein (MTP) inhibitor that effectively lowers LDL cholesterol and is approved for adults with HoFH. We aimed to investigate the efficacy and safety of lomitapide in paediatric patients with HoFH receiving standard-of-care lipid-lowering therapy. APH-19 is an open-label, single-arm, phase 3 trial performed at 12 study centres in Germany, Israel, Italy, Saudi Arabia, Spain, and Tunisia. A 6-week run-in period was followed by a 24-week efficacy phase and an 80-week safety phase. Patients aged 5-17 years, on stable lipid-lowering therapy, with HoFH diagnosed using the criteria from the 2014 European Atherosclerosis Society Consensus Panel on HoFH were titrated to maximum tolerated doses of oral lomitapide, starting at 2 mg (patients aged 5-15 years) or 5 mg (patients aged 16-17 years). The primary endpoint was the percentage change from baseline to week 24 in LDL cholesterol, which was assessed in patients who had received at least one dose of lomitapide, and who had a baseline and at least one post-baseline measurement. The secondary outcomes were the percentage change from baseline at week 24 in total cholesterol, non-HDL cholesterol, VLDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04681170. Between Dec 20, 2020, and Oct 16, 2022, 43 patients were included and treated (24 [56%] were female and 19 [44%] were male, and median age was 10·7 years [7·0-14·0]). Mean change from baseline in LDL cholesterol at week 24 was -53·5% (95% CI -61·6 to -45·4, p<0·0001). Mean percentage reductions were observed at week 24 for non-HDL cholesterol (-53·9%, 95% CI -61·7 to -46·1, p<0·0001), total cholesterol (-50·0%, 95% CI -57·6 to -42·4, p<0·0001), VLDL cholesterol (-50·2%, -59·1 to -41·2, p<0·0001), apolipoprotein B (-52·4%, -60·3 to -44·5, p<0·0001), triglycerides was -49·9% (-58·8 to -41·0, p<0·0001), and lipoprotein(a) (-11·3%, -32·9 to 10·3 [in 21 patients with measurements in mg/dL]; -23·6%, -38·2 to -9·0 [in 22 patients with measurements in nmol/L]; p=0·0070 combined). Adverse events were mostly mild, and gastrointestinal and hepatic in nature. Adverse events of special interest were reported for five (12%) patients (gastrointestinal in two patients and hepatic in three). One serious treatment-emergent adverse event was reported (also classed as an adverse event of special interest): an increase in hepatic enzymes, resulting in two dose interruptions, two dose reductions, and a repeated dose escalation. Lomitapide provided a significant, clinically meaningful LDL cholesterol reduction and has the potential to be an efficient, LDL receptor-independent option for paediatric patients with HoFH. Amryt Pharmaceuticals.

Effect of feeding mechanically processed alfalfa silage on production performance of mid-lactation dairy cows

Improving the digestibility and utilization of feedstuffs through processing methods may result in improved production and efficiency of dairy cattle. Our objective was to determine the effect of an intensive mechanical processing technique applied to wilted alfalfa before ensiling on dairy cow performance when fed as part of a TMR. Thirty-six mid-lactation Holstein dairy cows (primiparous and multiparous) were fed diets of similar composition (28.5% alfalfa haylage, 31.2% corn silage and 40.3% concentrates) that differed by pre-ensiling processing technique of alfalfa silage over a 6-week experimental period in a randomized complete block design. Treatments were alfalfa either conventionally chopped (CON) or mechanically processed (MPR). Neither BW, change in BW, BCS nor change in BCS differed between diets. Apparent DM, NDF, ADF, and CP digestibility were greater in MPR compared with CON. The DMI was lesser in MPR compared with CON during wk 5. Furthermore, forage NDF intake was lesser in MPR compared with CON during wk 5. Milk yield did not differ between MPR and CON, but milk fat yield and content were higher in MPR compared with CON. Consequently, 4% FCM and ECM were 1.5 kg/d greater in MPR compared with CON. Gross feed efficiency (ECM/DMI) was greater in MPR compared with CON during wk 5 and 6. Our results suggest that feeding a mechanically processed alfalfa silage enhanced fiber digestibility and subsequently improved dairy cattle gross feed efficiency in mid-lactation dairy cattle by the end of the experimental period. Further research is needed to elucidate physiological responses and practicality of implementing this processing method in a typical production setting.

Magnetic Resonance-Guided StereotacticRadioablation for SeptalVentricular Tachycardias.

Stereotactic arrhythmia radioablation (STAR) was introduced to treat ventricular tachycardia (VT) refractory to catheter ablation. No data are now available in the septal VT substrate setting, representing a challenge when using conventional techniques. This study sought to evaluate the arrhythmic burden in patients with septal VT treated with magnetic resonance-guided STAR (MRgSTAR). We enrolled consecutive patients with septal VT substrate. The therapy target was achieved by combining anatomic/functional and electrophysiologic information. Patients were treated with a single fraction of 25Gy adopting MRgSTAR. All patients were clinically followed up, and all implantable cardiac devices were remotely monitored. The efficacy outcome included recurrences of any sustained VT beyond the 6-week blanking period after MRgSTAR. The safety outcome was the incidence of adverse events and atrioventricular block. We included 11 patients with septal substrate VT (median age: 68 years; Q1-Q3: 64.5-78 years; 100% male). Clinical presentation was an electrical storm in 81.8% of patients. No complications occurred after MRgSTAR, and 6(54.5%) patients were discharged on the same day of treatment. During a mean follow-up of 12 ± 6months, the efficacy outcome occurred in 3 (27.3%) cases. A significative reduction of implantable cardioverter-defibrillator (ICD) therapy (23.6 before MRgSTAR vs 1.7 after MRgSTAR; P< 0.001) was observed. Left ventricular ejection fraction increased significantly after treatment (38% [Q1-Q3: 33.5%-42.0%] before MRgSTAR vs 43.8% [Q1-Q3: 35%-47%] after MRgSTAR; P=0.04). No adverse effects were observed in the implantable cardioverter-defibrillator and lead system; in the 7 patients with preserved atrioventricular conduction, no atrioventricular block was reported. MRgSTAR represents a safe and effective strategy for treating septal VT.

LEDoxy-SL: A Placebo-Controlled, Double-Blind, Randomized, 24-Month Trial of Six Weeks of Daily Doxycycline Plus Hygiene-Based Essential Care for Reducing Progression of Filarial Lymphedema in Sri Lanka.

Morbidity management of filarial lymphedema remains a challenge even during the post-lymphatic filariasis elimination era in Sri Lanka despite provision of the predominantly hygiene-based WHO Essential Package of Care. Because prior studies have suggested that 6 weeks of doxycycline may reduce progression of limb lymphedema, we conducted a randomized, placebo-controlled, superiority study to evaluate this possibility in Sri Lanka. Patients aged 14 to 65 years with lymphedema in one or both legs received either 200 mg of doxycycline daily for 6 weeks or matching placebo. The primary efficacy endpoint was improvement or lack of progression in lymphedema stage at 24 months postenrollment. Secondary endpoints included change in lymphedema stage at 12 and 24 months, frequency of acute adenolymphangitis episodes, and perceived disability measured by the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). Training and supplies for limb hygiene were provided throughout the study. Two hundred participants (100 in each arm) with lymphedema of Dreyer stages 1 to 3 were enrolled. By the end of the 2-year study, 29% of the doxycycline patients and 34% of those on placebo showed improvement (i.e., a decrease in lymphedema stage), whereas 11% and 15% of the two groups showed worsening of the lymphedema. Adenolymphangitis rates were comparable in the two groups (43 doxycycline and 38 placebo recipients), although attacks lasted slightly longer in placebo patients (6.5 days versus 5.2 days). In both groups, perceived disability improved initially, with partial rebound in the second year. Only 34 adverse events affecting 24 patients (11%) occurred during the 6-week treatment period. Although doxycycline did not significantly impact lymphedema progression in this study, the results clearly indicate that clinical and personal benefits can be obtained from intensive hygiene management alone.

Effect of patient gender on the decision of ceiling of care: an European study of emergency physicians' treatment decisions in simulated cases.

Gender bias in healthcare can significantly influence clinical decision-making, potentially leading to disparities in treatment outcomes. This study addresses the impact of patient gender on the decision-making process for establishing a ceiling of care in emergency medicine, particularly the decision to limit tracheal intubation. To determine whether patient gender influences emergency physicians' decisions regarding the recommendation for tracheal intubation in critically ill patients. A European survey-based study was conducted using a standardized clinical scenario to assess physicians' decisions in a controlled setting. The survey targeted European emergency physicians over a 2-week period in April 2024. A total of 3423 physicians participated, with a median age of 40 years and a distribution of 46% women. Physicians were presented with a clinical vignette of a 75-year-old patient in acute respiratory distress. The vignettes were randomized to vary only by the patient's gender (woman/man) and level of functional status: (1) can grocery shop alone, (2) cannot grocery shop alone but can bathe independently, or (3) cannot perform either task independently. The primary outcome was the recommendation for intubation, with secondary analyses exploring the influence of patient functional status levels. Multivariable logistic regression was used to adjust for potential confounders, including physician gender, age, experience, and practice setting. A total of 3423 physicians responded, mostly from France, Spain, Italy, and the UK (1,532, 494, 247, and 245 respectively). Women patients were less likely to be intubated compared to male patients [67.9% vs. 71.7%; difference 3.81%; 95% confidence interval (CI), 0.7-6.9%]. The likelihood of recommending intubation decreased with lower levels of patient functional status. Women physician gender was also associated with a reduced likelihood of recommending intubation. This study suggests a significant gender-based disparity in emergency care decision-making, with women patients being less likely to receive recommendations for intubation. However, these results should be interpreted with caution due to potential limitations in the representativity of respondents and the uncertain applicability of survey responses to real-life clinical practice.

Low-intensity blood flow restriction (LI-BFR) and moderate-intensity improves quadriceps strength and thigh circumference in older women

Background and objectives. Weakness and atrophy in the quadriceps femoris lead to decreased functional capacity, heightened fall risk, and increased mortality among older women. While moderate-intensity strength training is generally recommended for the elderly, higher-intensity exercises carry a greater risk of injury. Low-intensity exercises with blood flow restriction offer an alternative, providing comparable benefits to high-intensity training. This study aims to evaluate the effects of moderate-intensity and low-intensity blood flow restriction exercises on quadriceps femoris strength and thigh circumference in healthy elderly women. Materials and methods. The sample size was of 88 subjects equally randomized into a moderate-intensity group and a blood-flow restriction group. The moderate-intensity group performed strengthening exercises with a load of ≥40–60% of 1RM, 3 sets, 36 repetitions. The blood-flow restriction group conducted exercises at 20–30% of 1RM, completing 75 repetitions across 4 sets, using a pressure cuff applied to the upper thigh at 50 mmHg or 40% of the Arterial Occlusion Pressure (AOP). Both groups exercised twice a week over a 6-week period. Muscle strength (assessed via dynamometer and 1RM) and thigh circumference were recorded before and after the intervention. Results. After six weeks of intervention, both groups showed a significant increase in muscle strength and thigh circumference (p &lt;0.001). However, no notable differences were observed between the moderate intensity group and the blood flow restriction group regarding quadriceps strength (dynamometer), quadriceps 1RM strength, or thigh circumference (p &gt;0.05). Muscle soreness was reported in 18% of participants in the moderate intensity group. Conclusion. Low-intensity resistance exercises with blood flow restriction in older women can promote strength gains and muscle hypertrophy comparable to moderate-intensity training, while offering a safer alternative.

Patient Experience Survey as a Tool to Support Quality Improvement of a Geriatric Service in the Emergency Department (ED)

Abstract Background The aim of this survey was to valuate patient’s satisfaction with a Frailty Intervention Therapy Team (FITT) and gain insight into their thoughts about the service. Patients’ feedback is a vital component in monitoring and improving the quality of care. The data collected will help develop the service ensuring it’s patient centred and tailored to their needs. Methods A qualitative approach was taken in the form of a patient satisfaction survey. To limit bias responses, non-patient facing clerical facilitated the completion of the questionnaire with the patient. Results 27 surveys were administered over a 5-week period with an 81% response rate (n=22). 91% of patients surveyed felt the purpose of the FITT service was clearly explained to them, the team member had clearly introduced themselves and the team used both written and verbal information well –indicating an effective and efficient style of communication. 100% of patients reported that FITT treated them with dignity and respect. 18% of patients reported they were not involved in decision making relating to the care they received. The ED environment was rated as poor by 14% of patients, long wait time to be seen was also a concern. While some areas of patient concerns cannot be directly targeted by the team alone, we have a duty of care to highlight these concerns to the wider ED staff and hospital group. Conclusion A ‘what matters to you’ question has been incorporated into the assessment paperwork, to ensure patients’ wishes are being formally captured and placed centrally within care management planning. Communication to the patient was supported by providing a FITT information leaflet. Additional seating was procured by FITT to promote improvements in comfort and facilitate safe transfers of older patients in the ED. Patient feedback was presented to the ED governance group, including major themes of patient concern.

A Multiomics Evaluation of the Countermeasure Influence of 4-Week Cranberry Beverage Supplementation on Exercise-Induced Changes in Innate Immunity.

This study examined the effect of a 4-week unsweetened cranberry beverage (CRAN) (317 mg polyphenols) versus placebo beverage (PLAC) ingestion (240 mL/day) on moderating exercise-induced changes in innate immunity. Participants included 25 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind crossover design was used with two 4-week supplementation periods and a 2-week washout period. Supplementation periods were followed by an intensive 2.25 h cycling bout. Six blood samples were collected before and after supplementation (in an overnight fasted state) and at 0 h, 1.5 h, 3 h, and 24 h post-exercise. Stool and urine samples were collected pre- and post-supplementation. Outcome measures included serum creatine kinase, myoglobin, and cortisol, complete blood counts, plasma untargeted proteomics, plasma-targeted oxylipins, untargeted urine metabolomics, and stool microbiome composition via whole genome shotgun (WGS) sequencing. Urine CRAN-linked metabolites increased significantly after supplementation, but no trial differences in alpha or beta microbiota diversity were found in the stool samples. The 2.25 h cycling bout caused significant increases in plasma arachidonic acid (ARA) and 53 oxylipins (FDR q-value < 0.05). The patterns of increase for ARA, four oxylipins generated from ARA-cytochrome P-450 (CYP) (5,6-, 8,9-, 11,12-, and 14,15-diHETrEs), two oxylipins from linoleic acid (LA) and CYP (9,10-DiHOME, 12,13-DiHOME), and two oxylipins generated from LA and lipoxygenase (LOX) (9-HODE, 13-HODE) were slightly but significantly higher for the CRAN versus PLAC trial (all interaction effects, p < 0.05). The untargeted proteomics analysis showed that two protein clusters differed significantly between the CRAN and PLAC trials, with CRAN-related elevations in proteins related to innate immune activation and reduced levels of proteins related to the regulation of the complement cascade, platelet activation, and binding and uptake of ligands by scavenger receptors. No trial differences were found for cortisol and muscle damage biomarkers. CRAN versus PLAC juice resulted in a significant increase in CRAN-related metabolites but no differences in the gut microbiome. CRAN supplementation was associated with a transient and modest but significant post-exercise elevation in selected oxylipins and proteins associated with the innate immune system.

Associations between the multitrajectory neuroplasticity of neuronavigated rTMS-mediated angular gyrus networks and brain gene expression in AD spectrum patients with sleep disorders.

The multifactorial influence of repetitive transcranial magnetic stimulation (rTMS) on neuroplasticity in neural networks is associated with improvements in cognitive dysfunction and sleep disorders. The mechanisms of rTMS and the transcriptional-neuronal correlation in Alzheimer's disease (AD) patients with sleep disorders have not been fully elucidated. Forty-six elderly participants with cognitive impairment (23 patients with low sleep quality and 23 patients with high sleep quality) underwent 4-week periods of neuronavigated rTMS of the angular gyrus and neuroimaging tests, and gene expression data for six post mortem brains were collected from another database. Transcription-neuroimaging association analysis was used to evaluate the effects on cognitive dysfunction and the underlying biological mechanisms involved. Distinct variable neuroplasticity in the anterior and posterior angular gyrus networks was detected in the low sleep quality group. These interactions were associated with multiple gene pathways, and the comprehensive effects were associated with improvements in episodic memory. Multitrajectory neuroplasticity is associated with complex biological mechanisms in AD-spectrum patients with sleep disorders. This was the first transcription-neuroimaging study to demonstrate that multitrajectory neuroplasticity in neural circuits was induced via neuronavigated rTMS, which was associated with complex gene expression in AD-spectrum patients with sleep disorders. The interactions between sleep quality and neuronavigated rTMS were coupled with multiple gene pathways and improvements in episodic memory. The present strategy for integrating neuroimaging, rTMS intervention, and genetic data provide a new approach to comprehending the biological mechanisms involved in AD.

Hydroxytyrosol has a cardioprotective effect through dardarin and asprosin

IntroductionIn this investigation, we explored the potential involvement of dardarin (LRRK2) and asprosin in the protective efficacy of hydroxytyrosol (HT) against heart damage induced by corn syrup in rats.Material and methodsThe research was conducted at the Adıyaman University Experimental Research Center during the period from December 8, 2021, to July 12, 2023. Rats were categorized into four groups (&lt;i&gt;n&lt;/i&gt; = 6) as follows: control, HT, corn syrup, and corn syrup + HT. Over a span of 6 weeks, rats were administered water infused with 30% corn syrup. Simultaneously, a 4 ml/kg/day solution containing HT was orally administered, both independently and in conjunction with corn syrup, throughout the 6-week period. The molecular parameters of LRRK2 and asprosin in the cardiac tissue were assessed through histopathological examination.ResultsIn this study, it was observed that the LRRK2 level increased and the asprosin level decreased in the control group as a result of administration of corn syrup. After HT treatment, the LRRK2 level decreased non-significantly, while the asprosin level increased significantly. No difference was seen in the HT-only group compared to the control.ConclusionsThe protective effect of HT against damage to the heart due to corn syrup consumption may be mediated by LRRK2 and asprosin.

Edible cannabis for chronic low back pain: associations with pain, mood, and intoxication.

Cannabis, commonly known for both therapeutic and intoxicating effects, is gaining accessibility on legal markets and traction as a potential alternative therapy for pain mediation, particularly in those suffering from chronic low back pain. However, the effectiveness in this population of legal market forms of cannabis, particularly commonly used edibles, is unknown. Therefore, this study utilized a naturalistic prospective design where participants with chronic low back pain with intentions to initiate cannabis use for treatment were recruited and self-selected edible cannabis products containing varying amounts of delta- 9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Products were categorized as CBD-dominant, THC-dominant, or combined THC and CBD (THC + CBD). 249 participants [140 female (56.62%), mean (SD) age of 46.30 (16.02), 90% White] were tracked over 2weeks of ad libitum use and assessed during a naturalistic acute cannabis administration session on changes in pain, mood, and subjective drug effects. During acute administration, a significant correlation between THC dose and short-term pain relief was found, suggesting that higher THC doses were associated with greater pain reduction (p < .05). In addition, THC was associated with higher levels of subjective cannabis drug effects (p < .001), regardless of whether CBD was also in the edible product. Acute CBD dose was primarily associated with short-term tension relief (p < .05); however, there were no associations between CBD dose and acute pain. Over the 2-week ad libitum administration period results suggested pain reductions across participants using all forms of cannabis. However, trends suggested that more frequent use of CBD-dominant edible cannabis may be associated with greater reductions in perceived pain over the 2-week observation period (p = .07). These findings support the short-term analgesic effects of THC and anxiolytic effects of CBD and further suggest that orally-administered THC and CBD should continue to be evaluated for the potential to provide both acute and extended relief from chronic low back pain. https://clinicaltrials.gov/study/NCT03522324?locStr=Boulder,%20CO&country=United%20States&state=Colorado&city=Boulder&cond=chronic%20low%20back%20pain&intr=Cannabis&rank=1, identifier NCT03522324.

Effects of relative humidity on physiology and behavior of laying hens exposed to high ambient temperatures.

This study investigated how different relative humidity (RH) would impact behavior and physiology of laying hens. One hundred-eighty laying hens (Hy-Line Brown), aged 68-week-old (1,908 ± 78g), were exposed to daily ambient temperatures of 30°C with RH set at 25% (RH25), 50% (RH50), or 75% (RH75) for 12h a day (9:00 am to 9:00 pm) from 70 to 74 weeks of age. All hens had been raised at 24°C and 50% RH during 2-week adaptation period. Each RH treatment consisted of 10 replicates with 6 hens each in a completely randomized design. Results indicated that rectal temperature, respiratory rate, and heart rate were increased (P ≤ 0.05) in the RH75 group compared with the RH25 and RH50 groups. Plasma malondialdehyde concentrations were elevated in the RH75 group compared RH50 at 3, 7, and 21 days (P ≤ 0.05) following the RH exposure. Plasma glutathione peroxidase activity was lowered (P ≤ 0.05) in the RH75 group compared with the RH25 and RH50 groups at 21 days. Increasing RH led to decreased feeding behavior but showed a tendency to increase drinking behavior. Wings elevated and panting behaviors were higher in the RH75 group compared with the RH25 and RH50 groups (P ≤ 0.05). In conclusion, these findings suggest that elevated RH at constant ambient temperature could negatively influence the behavior and physiology of laying hens.

The usability of a wireless vocal fold vibration switch for individuals with complex communication needs: a caregiver-inclusive iterative home-based evaluation

Purpose: A vocal fold vibration switch is a type of access technology that detects voluntary vibrations of the vocal cords. In two sequential usability studies, we evaluated successive prototypes of a novel wireless vocal fold vibration switch. Methods: Each usability study enroled 7 dyads consisting of individuals with complex communication needs and their caregivers. Each study entailed a 2-week period of independent home use flanked by initial and final usability tests. Each usability test comprised nine tasks including donning and configuration of the switch, connecting it to other devices, and actual activation of the switch. Perceived task difficulty was measured via nine 21-point scales, while caregiver impressions were captured through open-ended questions, both encapsulated within a usability questionnaire. Caregivers described their experience in an open-ended interview in the second usability study. Results: Perceived task difficulty was uniformly low with both prototypes. The vast majority of tasks could be completed either independently or with hints. A small number of contraindications for use were identified with the second prototype, which included episodes of dystonia and heavy breathing, and some aspects of the physical design and robustness were flagged as needing further improvement. Conclusions: The overall qualitative feedback was overwhelmingly positive with caregivers generally desiring to keep and eager to recommend the device to others. Additionally, caregivers expressed that the vocal fold vibration switch expanded the switch user’s capabilities, and they foresaw applications beyond the study setting. Overall, our findings suggest that the wireless vocal fold vibration switch is useable in the home setting.