Controlled Design Research Articles

The Effect of a Biofeedback-Based Integrated Intervention for Older Adults with Orthostatic Hypotension: A Secondary Analysis on Psychological Health Outcomes in a Non-Randomized Pilot Trial

Background/Objectives: Aging-related physical changes and dysfunctions in the autonomic nervous system (ANS) often lead to orthostatic hypotension (OH) in older adults. OH negatively impacts both the physical and psychological well-being of those affected. Previous studies have demonstrated that the biofeedback-based integrated program (BBIP), a multicomponent intervention focused on heart rate variability biofeedback, effectively improves OH, as well as symptoms related to ANS function. This substudy aims to examine the effects of the BBIP on psychological health outcomes among community-dwelling older adults with OH. Methods: This study employed a non-randomized controlled trial design with a convenience sampling strategy. A total of 51 older adults with OH were recruited from two senior welfare centers and randomly assigned to either the intervention group (n = 27) or the control group (n = 24). The intervention group participated in a 12-week BBIP, which included weekly biofeedback sessions and group education on lifestyle modification to alleviate OH. Telephone counseling was also provided to promote compliance. Results: The intervention group showed significant improvements in health-related quality of life, depression, anxiety, and fall efficacy after the 12-week BBIP, whereas the control group exhibited no significant changes. There was a significant reduction in the percentage of participants in the intervention group reporting problems in all five dimensions of the EQ-5D (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Conclusions: The BBIP was effective in improving the psychological health outcomes of older adults with OH. Future studies should explore the long-term effects of the BBIP using a larger sample size and a randomized controlled trial design.

A quantitative study on the impact of a new outdoor advertising restrictions policy in Bristol (UK)

Abstract Background Bristol was the first city outside London to introduce a policy to restrict adverts for high fat, salt and sugar (HFSS) products and other unhealthy commodities (alcohol, gambling, payday loans) on council sites in 2021. This research evaluates the impact of this policy. Methods We conducted a controlled repeated cross-sectional study of Bristol (intervention) and neighbouring South Gloucestershire (control) residents before (n = 2,543) and after (n = 2,043) the policy came into effect. Self-reported exposure to adverts of HFSS products, alcohol and gambling and consumption/use of these products was collected. The intervention effect was analysed using a weighted controlled before-after design. In addition, we analysed 2020-23 timeseries of foods and drinks purchased by 1,012 households from Bristol (n = 217) and control areas (n = 795) from Kantar’s Worldpanel Take Home data. A controlled interrupted time series design was used to estimate the impact of the policy on weekly household purchases of energy and nutrients from HFSS products. Results Preliminary results did not indicate significant changes in exposure to unhealthy commodity adverts or consumption/use of unhealthy commodities post-intervention. However, the majority of results suggested a potential reduction; with for example a -22.1 (95% CI -47.3, 16.2) percentage point decrease in reported consumption of fast-food compared to controls. We also did not observe significant differences in weekly energy purchased from HFSS products compared to counterfactual; 897.6Kcal, 95%CI -57.7, 1,853.0, nor in purchases of fat (39.0g, 95%CI -20.1, 98.1), sugar (48.0g, 95%CI -19.8, 115.7) or salt (-0.4g, 95%CI -4.1, 3.2) from HFSS products. Conclusions Preliminary results indicate the new policy had no clear impact on exposure to unhealthy commodity adverts or purchasing and consumption of HFSS products. This may be attributable to the relatively small amount of total advertisement space owned by Bristol City Council (∼30%). Key messages • Policies restricting adverts of HFSS products and other unhealthy commodities are potentially effective tools to improve diet and to reduce diet-related diseases and public health inequalities. • We did not observe a measurable impact of this policy in Bristol, which may be attributable to the relatively small Council-owned advertisement estate within the total available advertisement space.

Effect of Propofol and Isoflurane on Hemodynamic changes during Spinal Surgery Under General Anesthesia

Background: Hemodynamic stability are vital requirements of up-to-date anesthesia. Both propofol and isoflurane meet these criteria though the clinical effects like postoperative nausea vomiting after administering propofol and isoflurane have been studied in various surgeries but have not been much evaluated or studied in patients undergoing major surgical procedures like spine surgeries, There’ is definite advantage of one technique over the other. Isoflurane has a low blood gas partition coefficient, which contributes to rapid induction and emergence from anaesthesia than with other volatile anesthetics in current clinical use. Propofol has been established as the intravenous agent that provides faster and smoother recovery & peri operative hemodynamic stability. Objective: To compare the effects of isoflurane and propofol regarding hemodynamic status in spinal surgery under general anaesthesia. Methods: After getting ethical approval, a randomized controlled trial study design was performed where patients were selected in the pre-anesthetic checkup room based on inclusion and exclusion criteria for those who were scheduled for spine surgeries under general anesthesia is admitted in the Department of Neurosurgery in East West Medical College from January 2023 – December 2024. A total number of 40 patients were selected. 20 patients were enrolled each in group A and group B by lottery method in a sealed envelope. They were divided into two groups by randomization; Group A and Group B. A written informed consent was taken from all selected patients. Patients were advised to fast for at least 8 hours before intervention. In Group A, anesthesia is maintained with propofol infusion, nitrous oxide (66%), and oxygen (33%) while in Group B, anesthesia is maintained with Isoflurane, nitrous oxide (66%), and oxygen (33%). All patients were given N2O in oxygen and 1.25% inspired concentration of Isoflurane (MAC -1.15). In Group A propofol infusion at rate of 80 μg/kg/min (fixed from the beginning). All data was collected at –Just after starting, 15 minutes, 30-minute, 1 hour, and >1 hour interval per operatively. Data was compiled, edited and plotted in tabular and figure form. P value was determined as significant when it was <0.05. Results: 40 patients yielded the following results. The mean age of Group A and B were 32.56±12.55 years and 34.6±12.5 years. Mean difference of heart rate was lower in Group A than that of Group B. Other parameters in both groups were confined to good and acceptable categories. But interestingly, there was a statistically significant difference found between Group A and Group B in Systolic Blood Pressure (SBP) & Diastolic Blood Pressure (DBP). The scoring was far better in Group A than Group B. Mean SBP was higher in Group B than Group A (p= >0.05). Similarly, mean DBP was also higher in Group B than Group A (p = >0.05). Conclusion: Propofol is better for maintaining hemodynamic status than Isoflurane for Spine surgery under General anaesthesia. EWMCJ Vol. 12, No. 1&2, January-July 2024: 21-26

Efficacies of different treatment strategies for infants hospitalized with acute bronchiolitis.

: Acute bronchiolitis is a common cause of hospitalization during infancy that carries significant morbidity and mortality rates. : This study compared the efficacy of different treatment modalities for infants with bronchiolitis in terms of hospital stay and clinical severity scores. : The PubMed database was searched for re- levant studies. Eligibility criteria included double-blind randomized controlled trial design, assessment of the effect of treatment on bronchiolitis in infants under 2 years of age, and publication in English from inception through July 31, 2020. The primary efficacy outcome was the length of hospital stay, while the secondary outcome was the clinical severity score. The standardized treatment effect and standard error of the effect size were calculated. : We identified 45 randomized controlled trials of 24 pairwise comparisons. These 45 trials included 5,061 participants and investigated 13 types of interventions (12 active, 1 placebo). Inhalation therapy with epinephrine (standard mean difference [SMD], -0.41; 95% confidence interval [CI], -0.8 to -0.03) and hypertonic saline (SMD, -0.29; 95% CI, -0.55 to -0.03) reduced the length of hospital stay compared with normal saline. Hypertonic saline was the most effective at improving the clinical severity score (SMD, -0.52; 95% CI, -0.95 to -0.10). : Inhalation therapy with epinephrine and hypertonic saline reduced the length of hospital stay and the clinical severity of bronchiolitis among infants under 2 years of age.

Feasibiliy, safety and patient perceptions of an exercise-based cardiac telerehabilitation programme

Abstract Background Despite proven benefits of exercise-based cardiac rehabilitation (EBCR), few patients with myocardial infarction (MI) complete these programs and there is a need to develop more flexible and evidence-based options. Purpose The aim of this study was to evaluate feasibility, safety, and patient perceptions of remotely delivered EBCR. Methods This study was conducted at 23 cardiac rehabilitation centres during the Covid-19 pandemic (March 2020-September 2022), when access to centre-based EBCR was restricted. A total of 231 patients with MI <80 years were included 2-4 weeks after discharge to participate in a remote EBCR programme 2 times/week for 3-4 months. Exercise was delivered through a real-time group-based video meeting, connecting the physiotherapist to patients exercising at home. Safety monitoring in terms of adverse events (AE) and serious adverse events (SAE) were recorded. Outcomes were assessed before and after remote EBCR completion and comprised tests of physical fitness and questionnaires: self-reported physical activity and exercise (Haskell questionnaire), physical capacity (VAS), kinesiophobia (TSK-Heart), health-related quality of life (EQ5D-VAS), self-efficacy for exercise, and patient acceptance of the program. Results Patients performed in median 19 (Q1 9 - Q3 23) remote EBCR sessions. A total of 16 AEs were registered during exercise (e.g chest pain, syncope, dizziness, musculoskeletal symptoms) which were all resolved. Two SAEs that required hospitalization were reported (chest pain, in-stent restenosis), both unrelated to exercise. At end of remote EBCR, significant improvements in physical fitness, self-reported exercise and physical capacity, kinesiophobia, and health-related quality of life were observed (Table 1). Delta values were similar to previous centre-based EBCR studies. Patients agreed that remote EBCR improved health care access (83%), was easy to use (94%), and 95% found exercise performance and interaction acceptable. Conclusions This study supports that remote EBCR is feasible and safe with a high patient acceptance post-MI. The clinical effectiveness needs to be confirmed in a randomized controlled design.

Combining Transcranial Direct Current Stimulation with Exercise to Improve Mobility, Stability, and Tremor Management in 25 Individuals with Parkinson’s Disease

Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by tremors, balance impairments, and mobility limitations. Innovative approaches like combining transcranial direct current stimulation (tDCS) with exercise show promise in addressing these symptoms. This study investigates the effects of exercise combined with tDCS on mobility and tremor management in PD patients. Methods: Twenty-five individuals aged 60−75 (66.6 ± 7.33), diagnosed with PD (Hoehn and Yahr stage 2−3), were assigned to three groups in a randomized controlled design: exercise with active tDCS (n = 8), exercise with sham tDCS (n = 8), and a control group (n = 9). Dual-task training sessions focusing on walking speed, balance, and force control were conducted over ten sessions. Results: No significant differences were detected across the groups for grip strength or force control measures (p > 0.05). Significant improvements were observed in the intervention group: the Timed Up and Go (TUG) test showed a significant reduction in time (mean difference = 2.498 s, p < 0.001, ηp2 = 0.331); anterior–posterior displacement significantly increased (mean difference = 21.375 mm, p = 0.0269, ηp2 = 0.303); and force-tremor decoupling improved, with coherence in the 1−4 Hz band significantly decreasing (p = 0.0067). Finally, changes in TUG from post- to pre-treatment values were significantly positively correlated with the changes in coherence (R = 0.468, p = 0.018). Conclusions: Combining tDCS with exercise enhances mobility and tremor management in PD patients. These findings support the potential for such interventions to improve functional outcomes and quality of life for individuals with PD.

Oral Care Performed with Breast Milk in Preterm Newborns Fed by Tube: A Randomized Controlled Study.

Objective: This study examined the effect of breast milk on oral care practices in neonatal intensive care units. Methods: This study involved 64 preterm infants (intervention/breast milk: 32, control/distilled water: 32) and was carried out with a prospective, parallel, randomized controlled design. The "Newborn Oral Health Assessment Tool (NOHAT)" was used to assess oral care. The Mann-Whitney U test, continuity correction test, Fisher's exact test, independent-samples T test, and Wilcoxon signed ranks test were used to analyze the data. Results: Examining the oral care performed using breast milk and distilled water with NOHAT scores, it was determined that there was a significant difference in the intervention group (p < 0.05). Conclusions: It is recommended to use breast milk for oral care.

Neuroprotective Effects of Heinsia crinita and Coconut Water in a Scopolamine-Induced Alzheimer's Model in Albino Rats: Biochemical Changes, Cellular Health, and Neuronal Activity

Aim: This study aimed to investigate the potential therapeutic effects of Heinsia Crinita and Tender Coconut water (TCW) on Alzheimer's disease, focusing on their phytochemical composition, antioxidant activity, and anti-inflammatory effects. The study aimed to identify potential therapeutic agents for Alzheimer's disease and contribute to the development of more effective and natural treatments for this devastating disorder. Study Design: The study used a randomized controlled trial design, with six groups: negative control (Group A), positive control (Group B), Donepezil-treated group (Group C), TCW-treated group (Group D), Heinsia Crinita-treated group (Group E) and TCW + Heinsia Crinita-treated group (Group F). Place and Duration of Study: The study was carried out in the University of Calabar, between February 2022 and January 2024. Methods: About 30 rats were used for the work. Alzheimer's disease-like neurotoxicity and neurodegeneration was inducee in 25 rats using scopolamine; 1.0 mg/kg, intraperitoneally (i.p.) and then treated with the respective interventions; TCW (2ml/kgBW) and Heinsia Crinita (500mg/kgBW). Histological analysis of the hippocampal tissue was performed using Hematoxylin and Eosin stain and Glial Fibrillary Acid Protein (GFAP) stain. Biochemical assays were conducted to determine Malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activity. Results: The results of the study showed that Heinsia Crinita may provide greater health benefits than Tender Coconut water due to its higher concentrations of bioactive compounds like alkaloids, flavonoids, and saponins, enhancing its medicinal properties, particularly its antioxidant and anti-inflammatory effects. Scopolamine induced histomorphological, immunochemical, and biochemical alterations. When combined with Tender Coconut water, Heinsia crinita (Group F) shows improved efficacy in reducing inflammation, cellular damage, and oxidative stress compared to Tender Coconut water alone. This combination is also as effective as Donepezil (Group C) in alleviating immunochemical alterations in a scopolamine-induced Alzheimer's model in Wistar rats, marked by reduced astrocyte activation, lower malondialdehyde (MDA) levels, and increased glutathione peroxidase (GPx) activity p &lt; 0.05. Conclusion: This study suggest that the combination of Heinsia Crinita and Tender Coconut water may serve as a promising therapeutic approach for addressing neurodegenerative conditions like Alzheimer's disease. The enhanced medicinal properties of Heinsia Crinita, particularly its ability to reduce oxidative stress and inflammation, coupled with the nutritional benefits of tender coconut water, could provide a synergistic effect that supports neuronal health and mitigates disease progression. This finding highlights the potential for natural products to be integrated into traditional medicine and modern therapeutic strategies.

Misconceptions about randomisation harm validity of randomised controlled trials.

The coherence theory of truth, the epistemology of evidence-based medicine, mathematical statistics, and axiomatic mathematics. To explore mathematical misconceptions inhering in randomised controlled trial designs, suggest improvements, encourage meta-methodological discussions and call for further interdisciplinary studies. Mathematical-statistical analyses and science-philosophical considerations. Randomisation does not (necessarily) generate equal samples, ergo, outcomes of usual RCTs are not as reliable as they claim. Moreover, ignoring initial sample discrepancies may cause inaccuracies similar to type I and type II errors. Insufficient awareness of these flaws harms final RCT statements about significance and evidence levels, hence their loss of trustworthiness. Statistical parameters such as the standard error of the mean may help to estimate the expected distinction between random samples. Researchers in EBM should be aware of systemic misconceptions in RCT standards. Pre-measurement can reduce shortcomings, e.g. through calculation how sample differences impact on usual RCT processing, or randomisation is given up in favour of mathematical minimisation of sample differences, i.e. optimising statistical sample equality. Moreover, the promising future of dynamic simulation models is highlighted.

High-intensity interval swimming improves cardiovascular endurance, while aquatic resistance training enhances muscular strength in older adults

The aim of this study was to examine the effects of free swimming (FS), aquatic resistance training (ART), and their combination (FS&ART) on the body composition, blood pressure, and physical fitness of older adults. The study employed a randomized controlled design, comparing three experimental groups with a control group. Eighty volunteers aged between sixty and seventy years (age: 66.2 ± 2.3 years; body mass index: 25.8 ± 4.3 kg/m²) participated in the 16-week intervention, consisting of two weekly sessions. Assessments were conducted at baseline and post-intervention, including anthropometric measurements, blood pressure readings, and the Senior Fitness Test. Significant differences were found between groups in post-intervention considering the chair stand test (p = 0.017; ES = 0.125), arm curl test (p = 0.029; ES = 0.111), 8-foot up and go test (p = 0.042; ES = 0.102), and walk test − 6 min (p = 0.005; ES = 0.156). Specifically, both ART (+ 20.1%; p < 0.05) and FS&ART (+ 19.5%; p < 0.05) showed significantly greater improvements in the chair stand test compared to the control group. Similarly, ART (+ 23.1%; p < 0.05) and FS&ART (+ 18.7%; p < 0.05) performed better than the control group. FS&ART also exhibited a significant improvement over the control group in the 8-foot up-and-go test (+ 14.6%; p < 0.05). In the 6-minute walk test, FS (+ 19.4%; p < 0.05) and FS&ART (+ 15.9%; p < 0.05) both significantly outperformed the control group. This study found that FS improves cardiovascular endurance, while ART enhances muscular strength and endurance in older adults, with combined benefits for agility, suggesting integration of combined modalities into community wellness initiatives for enhanced physical fitness and health outcomes.

Digital vs. conventional instructor-led midwifery training in Benue State, Nigeria: a randomized non-inferiority trial

BackgroundMany health education institutions in African countries such as Nigeria face increasing enrolment of students but lack an adequate number of instructors to train them. If digital learning can be demonstrated effective in augmenting knowledge and skills, this approach could help fill this gap and improve education efficiency. A needs assessment in two Nigerian midwifery schools confirmed that digital learning would be feasible and welcomed. In this study, the Midwifery Active Digitization Empowerment Initiative (MADE-I) program was tested to determine if digital delivery of the Fundamental Interventions, Referral and Safe Transfer (FIRST) course is at least equally effective for training midwifery students compared to conventional small-group delivery.MethodsA non-inferiority randomized controlled trial design was used, enrolling 130 s-year students from 2 midwifery schools in Benue State, Nigeria. Students were randomly assigned into six cohorts. Each cohort received half of the course on a Learning Management Platform on their mobile phones, the other half through standard small-group teaching. Students’ knowledge, thinking, and technical skills were assessed using a pre-test, post-test, Objective Structured Clinical Exam (OSCE), and daily modular quizzes. The data was analyzed using the difference-in-difference method.ResultsThe study revealed that post-intervention student knowledge and thinking skills did not significantly differ between digital learning (75.26%) and small-group learning arms of the trial (75.02%, p = 0.404). Student knowledge improved significantly compared to the pre-test in both groups (by 25.03 points in the digital arm, 26.39, in small-group). Some differences were observed between digital and small-group learning in disaggregated analysis by specific module and midwifery school. Although there was a trend toward small-group learning of technical skills being more effective than digital learning, no significant differences between groups were observed in the post-intervention OSCE. Students in both groups learned equally well regardless of age, gender, and midwifery school entrance exam score.ConclusionDigital learning is as effective as small-group learning, for midwifery trainees, in augmenting knowledge, thinking, and technical skills addressed in the FIRST course, and have lighter human resource requirements, an important consideration especially in LMIC. However, similar assessments would be needed to assess effectiveness for other digitally delivered clinical education programs.

Effectiveness of an HIV peer support precision matching platform: a randomized controlled trial protocol

BackgroundPeer support is a promising and significant way for people living with HIV (PLWH) to improve their health outcomes. Matching PLWH with HIV peer volunteers can effectively stimulate and mobilize the function of peer support in health management. We develop the online platform Aspark, which features a precision matching function for PLWH and volunteers. This protocol provides a comprehensive overview of the randomized controlled trial design based on Aspark.MethodA parallel randomized controlled trial using block randomization will be conducted at the Beijing YouAn Home of Loving Care. The intervention group (n = 70) will have access to all 12 features of Aspark, including precise volunteer matching, health management tools, drug interaction queries, and medication reminders. The control group (n = 70) will have access to two features of informational support on Aspark. The outcomes of both groups will be evaluated at baseline and at 3, 6, 9, and 12 months after platform registration. The primary outcome is perceived social support. The secondary outcomes include mental symptoms, quality of life, self-efficacy, medication adherence, and health behaviors. Linear mixed models or generalized linear mixed models will be applied to test the intervention effects.DiscussionThe Aspark trial is a randomized controlled trial designed to examine the influence of a mobile health (mHealth) application that integrates peer support and precision matching to strengthen social support for PLWH in China. This trial has the potential to significantly enhance social support for PLWH while also optimizing the delivery of peer support services and fully mobilizing the role of peer support in the overall health management of PLWH.Trial registrationClinical registration number: ChiCTR2300077454.

Hip Manipulation Increases Electromyography Amplitude and Hip Joint Performance: A Double-Blind Randomized Controlled Study

(1) Background: Activation of the gluteus medius (GM) muscle while minimizing the involvement of the tensor fascia latae (TFL) is crucial in treating many lower limb and lumbar spine injuries. Previous studies have demonstrated the effectiveness of joint manipulations in regulating muscle activity. The main objective of this study was to evaluate the effects of hip joint manipulation (HJM) on the muscle strength and activity (GM and TFL) of hip abductors in asymptomatic young participants. (2) Methods: The study followed a double-blind randomized controlled design. Thirty healthy, physically active women and men, free from spinal and lower limb injuries, voluntarily participated. The participants were allocated to two groups: those allocated to the HJM intervention and those in the control group receiving a sham intervention. They were assessed before and after the intervention using surface electromyography to measure muscle activation (EMGRMS) of the GM and TFL during maximal voluntary isometric hip abduction. (3) Results: HJM resulted in a significant increase in EMGRMS amplitude solely within the GM muscle (p &lt; 0.01); (4) Conclusions: This study suggests that HJM may increase EMGRMS amplitude in the GM muscle; however, the effects are neither statistically nor clinically significant when compared to the control group for most of the muscles analyzed.

Effects of Family Audio Recordings on Depression, Cognitive Function, and Sleep Quality of Individuals With Alzheimer's Disease: A Randomized Controlled Trial.

To explore the effects of family audio recordings on depression, cognitive function, and sleep quality among individuals with Alzheimer's disease in nursing homes. A randomized controlled study design was used, and 107 participants with Alzheimer's disease were stratified and randomly assigned to groups based on Clinical Dementia Rating Scale scores. The control group received usual care and health education, and the experimental group received usual care, health education, and a family audio recording intervention. The experimental group showed significantly lower depression scores compared to the control group post-intervention. A within-group comparison of sleep quality scores in the experimental group was significantly different. At post-intervention, cognitive function scores in the control group significantly decreased compared to before the intervention. Family audio recording interventions helped alleviate depression symptoms in individuals with Alzheimer's disease, improved their sleep quality, and delayed the progression of cognitive decline to some extent. [Journal of Gerontological Nursing, xx(x), xx-xx.].

Engineering texture and twins of Cu foils preparing by pulse electrodeposition and their properties

The controllable microstructure and the overall performance improvement of electrodeposited nano twinned Cu (nt-Cu) foil are crucial for the sustainable development of high energy density batteries and microelectronics technology. Although pulse electrodeposition (PED) and additives have been widely used in controlling nt-Cu foil, there is still a lack of research on the controllable microstructure of nt-Cu foil and its microstructure depended properties. In this study, nt-Cu foils with different orientations were prepared by adjusting the Toff time and additives during the PED process. The effects of these parameters on the microstructure and comprehensive properties of the nt-Cu foil were studied. The Toff time and polyethylene glycol (PEG)-3-mercapto-1-propanesulfonate sodium salt (MPS)-(chloride ions)Cl− (PEG-MPS-Cl−) additive changed the kinetic parameters of the electrochemical reaction and ultimately affected the reduction rate of Cu2+ and the overpotential of the deposition process. This modulation effectively regulated the nucleation and growth behavior of Cu atoms, thereby reducing the surface roughness of the nt-Cu foil, refining the grains, and forming nano-twins with different orientations. Due to the combined strengthening effect of grain refinement, dislocation, and texture orientation, (111) oriented nt-Cu foil demonstrated remarkable mechanical and frictional wear properties, whereas (220) oriented nt-Cu foil exhibited superior conductivity and corrosion resistance. These findings may offer promising prospects for the controllable design of engineering textures and nano-twin structures of high-performance nt-Cu foil by electrodeposition.

A novel interpretable deep learning-based computational framework designed synthetic enhancers with broad cross-species activity.

Enhancers play a critical role in dynamically regulating spatial-temporal gene expression and establishing cell identity, underscoring the significance of designing them with specific properties for applications in biosynthetic engineering and gene therapy. Despite numerous high-throughput methods facilitating genome-wide enhancer identification, deciphering the sequence determinants of their activity remains challenging. Here, we present the DREAM (DNA cis-Regulatory Elements with controllable Activity design platforM) framework, a novel deep learning-based approach for synthetic enhancer design. Proficient in uncovering subtle and intricate patterns within extensive enhancer screening data, DREAM achieves cutting-edge sequence-based enhancer activity prediction and highlights critical sequence features implicating strong enhancer activity. Leveraging DREAM, we have engineered enhancers that surpass the potency of the strongest enhancer within the Drosophila genome by approximately 3.6-fold. Remarkably, these synthetic enhancers exhibited conserved functionality across species that have diverged more than billion years, indicating that DREAM was able to learn highly conserved enhancer regulatory grammar. Additionally, we designed silencers and cell line-specific enhancers using DREAM, demonstrating its versatility. Overall, our study not only introduces an interpretable approach for enhancer design but also lays out a general framework applicable to the design of other types of cis-regulatory elements.

Effectiveness of gluteal control training in chronic low back pain patients with functional leg length inequality

Chronic low back pain (LBP) is a common musculoskeletal disorder and is often accompanied by functional leg length inequality (FLLI). However, little was known about the effects of gluteal muscle control training in patients with LBP and FLLI. This study was designed to investigate the effects of gluteal control training in patients with LBP and FLLI. This is a double-blinded, randomized controlled study design. Forty-eight LBP patients with FLLI were randomized to the gluteal control training (GT) (47.58 ± 9.42 years) or the regular training (RT) (47.38 ± 11.31 years) group and received allocated training for six weeks. The outcome measures were pelvic inclination (PI), ilium anterior tilt difference (IATD), FLLI, visual analogue scale (VAS), patient specific-functional scale (PSFS), Oswestry disability index (ODI), hip control ability, global rating of change scale (GRoC), and lower extremity strength and flexibility. The intervention effects were compared using two-way repeated measures analysis of variance and chi-square tests with α = 0.05. The results indicated that the GT group showed greater improvement (P < 0.01) in PI (1.03 ± 0.38∘ vs. 1.57 ± 0.51∘), IATD (0.68 ± 0.66∘ vs. 2.31 ± 0.66∘), FLLI (0.3 ± 0.22 vs. 0.59 ± 0.13 cm), VAS (1.41 ± 1.32 vs. 3.38 ± 1.51), hip control ability (2.20 ± 0.45 vs. 0.89 ± 0.74), GRoC at 3rd and 6th week as compared to the RT group. Hip strength and flexibility also improved more in the GT group (P < 0.05). In conclusion, gluteal control training was more effective in improving low back pain and dysfunctions, and should be integrated in the management plan in patients with LBP and FLLI.

Effect of serious games over conventional therapy in the rehabilitation of people with multiple sclerosis – a systematic review and meta-analysis

Purpose This meta-analysis aimed to quantify the effect of serious games over conventional therapy on upper-limb activity, balance, gait, fatigue, and cognitive functions in people with multiple sclerosis. Materials and methods Search strategies were developed for PubMed, Embase, Cochrane Library, and Scopus. Studies were selected if participants were adults with multiple sclerosis; the intervention consisted of a virtual reality serious game-based program; the control group received conventional therapy; outcomes included upper limb activity, balance, gait, fatigue, or cognitive functions; and used a randomized controlled trial design. Data were synthesized using a standardized mean difference with a random-effects model. Results From 2532 studies, seventeen trials were selected (n = 740). Overall, serious games programs effect on upper limb activity, gait, verbal memory, verbal fluency and attention seemed neutral. Balance functions appeared to be improved by semi-immersive virtual reality serious games (SMD = 0.48;95%CI = 0.12–0.84;p = 0.01;I2=0%), fatigue by treadmill serious games (SMD = 0.80;95%CI = 0.40–1.20;p < 0.001) and visuo-spatial memory by semi-immersive virtual reality general cognitive serious games (SMD = 0.35;95%CI = 0.04–0.65;p = 0.03;I2=0%). Conclusion This review suggests, with a very-low-to-low certainty of evidence, that while some specific serious games may improve balance, fatigue and visuo-spatial memory, their overall effect on upper limb activity, gait, and other cognitive functions appears neutral.

Optimal and simultaneous synthesis of fractional order QFT controllers and prefilters for non-minimum phase hydro power systems

Abstract Ideally, the operating frequency of the power units, working in parallel, must not deviate from its nominal value. However, due to the dynamic nature of the load, operating frequency varies throughout the day; thus, the control of governors in the prime movers is essential to balance out the demand, and prevent any frequency deviation. To address this, present study investigates the design of optimal and robust quantitative feedback theory based (QFT) controllers and pre-filters for single area load frequency control of hydro power systems. Hydropower system model considered in the present study features a right-hand side zero, thus exhibiting non-minimum phase; these characteristics make the control more challenging. Also, the work investigates the optimal design of the QFT controllers and prefilters simultaneously by automating the loop shaping procedure, which else follows a sequential manual process on Nichols charts. The proposed automation also empowers the control designer to predefine the controller structure. In the present work the design of fractional order QFT controllers and pre-filters is considered. The study also compares the proposed work with the methods proposed in the existing literature as well as the optimal controllers obtained using the time domain indices. The obtained results establishes that the developed fractional QFT controller offers good tracking, stability, and robustness to disturbances when compared to existing approaches. The proposed fractional order QFT controllers offer the elimination of the overshoot and the undershoot from the closed loop response of the system; outperforms the existing controllers in terms of disturbance rejection; offers 0% steady-state deviation, while providing improved phase margin (60.1°) for enhanced stability compared to existing controllers. Also, the proposed QFT-GA attains the ideal values for both the peak complementary sensitivity functions; thus, establishing excellent robustness. Also, the proposed controllers ensure adequate tolerance to frequency deviation in case of load change.

Analysis of the Effect of Preoperative Eye Position Fixation Training in Patients With Pterygium: A Randomized Controlled Trial.

This study evaluated the effect of preoperative ocular fixation training on patients undergoing pterygium surgery. Before pterygium excision, patients were trained to perform eye position fixation training, which is beneficial for surgeons performing microsurgery. The study analysed the effectiveness of preoperative eye position fixation training in patients with pterygium by randomised controlled experimental design. The number of occurrences of self-turning, operation time, self-rating depression scale scores and self-rating anxiety scale scores of the experimental group (EG) were lower than those of the control group (CG). The recurrence rate and the incidence of conjunctival tear and conjunctival suture loosening in the EG were significantly lower than those in the CG. The use of eye fixation training prior to pterygium surgery can facilitate the activities of the surgeon, reduce the operation time, reduce the occurrence of complications and reduce the recurrence rate after the operation. Eye fixation training is worthy of application in patients with pterygium.