Improvement In Function Research Articles

Predictors and prognosis of pulmonary hypertension complicating interstitial lung disease in systemic sclerosis.

To identify those with concurrent pulmonary hypertension (PH) and interstitial lung disease (ILD) in systemic sclerosis (SSc) and determine their disease severity, therapeutic approach, and survival. Consecutive SSc patients enrolled in the Australian Scleroderma Cohort Study (ASCS) who were diagnosed on right heart catherisation with pulmonary hypertension were included. Logistic regression was used to determine the associations of ILD with PH hemodynamic parameters and therapeutic approach. Kaplan-Meier survival curves were used to estimate survival. Of 1,883 SSc patients, 164 (8.7%) developed incident PH over a median follow up of 4.3 (1.7-7.9) years. Of these, 43.9% had concurrent ILD at PH diagnosis (PH-ILD) and 56.1% had Group 1 PAH. Extensive ILD was present at PH diagnosis in 40.3%. Despite these distinct PH cohorts, a similar frequency of each PH cohort was treated with vasodilatory therapy at PH diagnosis, regardless of the presence or severity of ILD. The majority (87.5%) of those with extensive ILD and PH received upfront vasodilatory therapy at PH diagnosis with no difference in its tolerability or therapy cessation compared with Group 1 PAH. Although vasodilator therapy was not associated with a survival advantage in those with extensive ILD, its use was associated with an improvement in symptoms, physical function, and quality of life (QoL). Despite vasodilator therapy, survival in SSc-PH is poor, with the presence of concurrent ILD associated with worse survival. Although vasodilator therapy commenced at PH diagnosis does not portray an improved survival in PH with extensive ILD, it appears well tolerated and may improve symptoms, physical function, and QoL.

RNA processing modification mediated subtypes illustrate the distinctive features of tumor microenvironment in hepatocellular carcinoma.

Multiple transcript isoforms of genes can be formed by processing and modifying the 5' and 3' ends of RNA. Herein, the aim of this study is to uncover the characteristics of RNA processing modification (RPM) in hepatocellular carcinoma (HCC), and to identify novel biomarkers and potential targets for treatment. Firstly, integrated bioinformatics analysis was carried out to identify risk prognostic RPM regulators (RPMRs). Then, we used these RPMRs to identify subtypes of HCC and explore differences in immune microenvironment and cellular function improvement pathways between the sub-types. Finally, we used the principal component analysis algorithms to estimate RPMscore, which were applied to 5 cohorts. Lower RPMscore among patients correlated with a declined survival rate, increased immune infiltration, and raised expression of immune checkpoints, aligning with the "immunity tidal model theory". The RPMscore exhibited robust, which was validated in multiple datasets. Mechanistically, low RPMscore can create an immunosuppressive microenvironment in HCC by manipulating tumor-associated macrophages. Preclinically, patients with high RPMscore might benefit from immunotherapy. The RPMscore is helpful in clustering HCC patients with distinct prognosis and immunotherapy. Our RPMscore model can help clinicians to select personalized therapy for HCC patients, and RPMscore may act a part in the development of HCC.

Vagus nerve stimulation for enhanced stroke recovery after intracerebral hemorrhage: illustrative case.

Randomized controlled trial (RCT) evidence has revealed the efficacy of vagus nerve stimulation (VNS) paired with rehabilitation therapy, over therapy alone, for upper-limb functional recovery after ischemic stroke. However, this technique has not yet been described for the recovery of chronic motor deficits after hemorrhagic stroke. Three years after left putaminal intracerebral hemorrhagic stroke with chronic upper-limb functional deficits, a patient was treated with VNS for enhanced stroke recovery. VNS was paired with 6 weeks of in-clinic physical therapy, resulting in upper-limb functional improvement of 14 points on the Fugl-Meyer Assessment Upper Extremity (FMA-UE) index for stroke recovery (maximum score of 66 equating to normal function). This improvement was more than 1 standard deviation above the improvement documented in the first successful RCT of VNS paired with therapy for ischemic stroke (5.0 ± 4.4 improvement on FMA-UE). VNS is a promising therapy for enhanced recovery after hemorrhagic stroke and may offer greater improvement in function compared to that after ischemic stroke. Improvement in function can occur years after the time of intracerebral hemorrhage.

Rationale and design of Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol II (TASTE-2): a multicentre randomised controlled trial

BackgroundEdaravone dexborneol is believed to be a novel cytoprotective drug, demonstrating a synergistic combination of antioxidative and anti-inflammatory properties in animal models. The Treatment of Acute Ischaemic Stroke with Edaravone...

Efficacy of brain-computer interfaces on upper extremity motor function rehabilitation after stroke: A systematic review and meta-analysis.

The recovery of upper limb function is crucial to the daily life activities of stroke patients. Brain-computer interface technology may have potential benefits in treating upper limb dysfunction. To systematically evaluate the efficacy of brain-computer interfaces (BCI) in the rehabilitation of upper limb motor function in stroke patients. Six databases up to July 2023 were reviewed according to the PRSIMA guidelines. Randomized controlled trials of BCI-based upper limb functional rehabilitation for stroke patients were selected for meta-analysis by pooling standardized mean difference (SMD) to summarize the evidence. The Cochrane risk of bias tool was used to assess the methodological quality of the included studies. Twenty-five studies were included. The studies showed that BCI had a small effect on the improvement of upper limb function after the intervention. In terms of total duration of training, < 12 hours of training may result in better rehabilitation, but training duration greater than 12 hours suggests a non significant therapeutic effect of BCI training. This meta-analysis suggests that BCI has a slight efficacy in improving upper limb function and has favorable long-term outcomes. In terms of total duration of training, < 12 hours of training may lead to better rehabilitation.

Exploring the Influence of Gut-Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics.

Recent research exploring the relationship between the gut and the brain suggests that the condition of the gut microbiota can influence cognitive health. A well-balanced gut microbiota may help reduce inflammation, which is linked to neurodegenerative conditions. Prebiotics, probiotics, and symbiotics are nutritional supplements and functional food components associated with gastrointestinal well-being. The bidirectional communication of the gut-brain axis is essential for maintaining homeostasis, with pre-, pro-, and symbiotics potentially affecting various cognitive functions such as attention, perception, and memory. Numerous studies have consistently shown that incorporating pre-, pro-, and symbiotics into a healthy diet can lead to improvements in cognitive functions and mood. Maintaining a healthy gut microbiota can support optimal cognitive function, which is crucial for disease prevention in our fast-paced, Westernized society. Our results indicate cognitive benefits in healthy older individuals with probiotic supplementation but not in healthy older individuals who have good and adequate levels of physical activity. Additionally, it appears that there are cognitive benefits in patients with mild cognitive impairment and Alzheimer's disease, while mixed results seem to arise in younger and healthier individuals. However, it is important to acknowledge that individual responses may vary, and the use of these dietary supplements should be tailored to each individual's unique health circumstances and needs.

CORTICOSTEROID AND LIDOCAIN INJECTION FOR TREATMENT OF HIP OSTEOARTHRITIS : AN UPDATE SYSTEMATIC REVIEW

Background: Intraarticular corticosteroid injections (ICSI) can relieve pain in patients with symptomatic osteoarthritis (OA) for weeks. A recent randomized controlled trial showed superior pain improvement following ICSI compared to treatment without injection over a period of 6 months. Atchia et al. compared ICSI to saline-injection and treatment without injection and found ICSI to be the only treatment resulting in significant improvement in both pain and function. The aim: The aim of this study to show about corticosteroid and lidocaine injection for treatment of hip osteoarthritis. Methods: By the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. This search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed, SagePub, and Google Scholar were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search get 7 articles, whereas the results of our search on SagePub get 6 articles, on Google Scholar 1690 articles. Records remove before screening are 1438, so we get 265 articles fos screening. After we screened based on record exclude, we compiled a total of 10 papers. We included five research that met the criteria. Conclusion: Ultrasound guided intra-articular hip injection of corticosteroid and local anaesthetic, administered with advice and education, is a clinically effective treatment for rapid and sustained symptom response compared with advice and education alone for people with hip osteoarthritis. These findings provide evidence to inform international guidelines and support treatment decision making for policy makers, payers (commissioners), GPs, and clinicians in musculoskeletal services.

Recovery of memory decline during aging - role of epigenetics

Aging is a natural phenomenon associated with the accumulation of multiple alterations, including memory loss. Such deterioration of memory is based on the susceptibility of specific brain regions and the disorders that coincide with aging in those areas. Previous findings suggest that the optimal expression of synaptic plasticity-related genes is essential for memory formation and consolidation. Epigenetic modifications are one of the most crucial factors that cause memory deterioration by inducing the differential expression of synaptic plasticity-related genes. Understanding the fundamental cause of cognitive alterations that arise with aging is very essential for the development of therapeutic and/or preventive approaches. Several strategies have been employed to restore or reverse the memory decline caused by age-associated epigenetic alterations. The present article emphasizes the role of epigenetic alterations caused by histone modifications, DNA methylation, and non-coding ribonucleic acids (RNAs) on memory during aging. Also, we highlight the mechanistic switches of brain aging, including physical exercise, nutraceuticals, epigenetic modifiers, modulators of non-coding RNAs, and associated targets for therapeutic interventions. The emerging field of neuropharmacology and pharmacoepigenomics provides evidence that small drug molecules are currently employed to treat memory loss associated with aging, particularly by targeting epigenetic systems like DNA methylation, chromatin remodeling, histone modifications, and small non-coding RNAs. Therefore, targeting epigenetic modifications could be a potential therapeutic approach for the improvement of synaptic plasticity, neuronal activities, memory, and other brain functions during aging.

Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series.

Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) co-administration increases pegloticase response rate and mitigates IR risk but CKD limits MTX use. This pooled case series examined pegloticase + MTX co-therapy in uncontrolled gout patients with and without CKD. Cases of pegloticase + MTX co-therapy in existing datasets were retrospectively examined. Baseline eGFR classified patients as CKD (eGFR < 60 mL/min/1.73 m2) or non-CKD (eGFR ≥ 60 mL/min/1.73 m2). Patient characteristics, treatment parameters, laboratory values, urate-lowering response rate (≥12 pegloticase infusions received and SU < 6 mg/dL just before infusion 12), and AEs were examined. Fifteen CKD (eGFR: 43.2 ± 11.3 mL/min/1.73 m2; SU: 8.6 ± 2.2 mg/dL), 27 non-CKD (eGFR: 82.9 ± 19.0 mL/min/1.73 m2; SU: 9.5 ± 1.7 mg/dL) patients were included. Comorbidity profiles were similar, but CKD patients were older (72.0 ± 9.9 vs 52.3 ± 14.3 years) and more often female (33.3% vs 7.4%). Treatment parameters were similar with 4-week MTX Run-in followed by mean of 14.7 ± 8.1 [CKD] vs 14.1 ± 7.1 [non-CKD] pegloticase infusions. However, CKD patients had lower MTX dose (14.8 ± 5.8 vs 19.3 ± 4.9 mg/week). Urate-lowering response was similar (92% vs 86%). eGFR increased during treatment in 60% of CKD (+11.5 ± 20.9 mL/min/1.73 m2, 87% stable/improved CKD-stage) and 44% of non-CKD (+4.2 ± 15.0 mL/min/1.73 m2) patients. AEs were similar (≥1 AE CKD: 53%, non-CKD: 67%; gout flare most-reported). One case each of pancytopenia and IR (mild) occurred in non-CKD patients. These real-world data show similar pegloticase + MTX efficacy in CKD and non-CKD patients. No new safety signals were identified, with most CKD patients showing renal function stability or improvement during therapy.

Females show worse functional outcome and quality of life compared to males 2 years after meniscus surgery:Data analysis from the German Arthroscopy Registry.

The purpose of this study was to investigate the impact of sex on knee function, activity and quality of life following meniscus surgery using data from the German Arthroscopy Registry. This is a retrospective cohort study with data collected between 2017 and 2022. Patient-reported outcome measures (PROMs), namely Knee Injury and Osteoarthritis Outcome Score (KOOS), EuroQol Visual Analogue Scale (EQ Scale), and Marx Activity Rating Scale (MARS), were collected preoperatively and at 6, 12and 24 months postoperatively. Data were analysed to examine differences between male and female patients regarding PROMs, pre-existing conditions, meniscus lesion typesand surgical treatments. A total of 1106 female (36.6%) and 1945 male patients (63.7%) were included. Males were significantly younger than females and had a higher body mass index. Overall, there were four times more medial meniscus lesions (MMLs) (77.5%) than lateral meniscus lesions (LMLs) (27.9%). Degenerative LMLs were more frequent in females, while traumatic LMLs were more common in males. Frequencies of traumatic and degenerative MMLs were similar among males and females. Males had higher absolute KOOS irrespective of treatment or meniscus lesion type. Meniscus repair resulted in similar improvements in ΔKOOS for both sexes, while meniscus resection exhibited higher absolute KOOS for males at each time point. Males generally had higher EQ Scale and MARS than females. Greater improvements in knee function, activity and quality of life were observed in males. While MMLs appear to be comparable among sexes, the nature of LML differed significantly. These results may help surgeons to refine patient selection for specific treatments to improve overall clinical outcomes. Level III.

Women's Experiences of Sequelae After Mastectomy: A 3, 6, and 12 Months' Follow-up Study.

Postoperative experiences after breast cancer surgery, such as lymphedema, phantom breast sensations, persistent chronic pain, and changes in body image and sexuality, can negatively impact women's quality of life. To investigate women's experiences of sequelae at 3, 6, and 12 months after mastectomy. A survey including women ≥18 years, cognitively intact, and Danish speaking was conducted from May 2021 to October 2021. The researchers contacted the participants by telephone using 4 validated questionnaires investigating phantom sensation, body image, quality of life, and sexuality. Forty-four women were eligible for participation, and 23 (14 women aged ≤65 years and 9 women aged >66 years) were included in the analysis. The results showed an overall decrease in the severity of physical sequelae and an improvement in body image and sexual function. However, the women reported concerns about the future and decreased sexual enjoyment. Nearly half of the women received information about sexuality from healthcare professionals. The study demonstrated decreased sequelae during the follow-up period. Still, there seem to be unanswered questions concerning the quality of life and the content of information regarding sexuality. The findings require attention and further research to benefit the individual woman and her partner in accommodating the consequences after mastectomy. Persistent pain and concerns for the future are present for half of the women after 1 year. Information about possible changes in sexuality is not standard. A nurse-patient dialogue that discusses hospitalization and sexuality on an individual level can be a way to address concerns and challenges.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report

BACKGROUND Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

Role of Regenerative Therapeutics in Diabetic Peripheral Neuropathy: Current Advances and Future Prospects

Diabetes is a chronic metabolic condition that has far-reaching consequences for human health. If there is no appropriate therapeutic treatment, diabetic peripheral neuropathy might lead to foot ulceration and limb amputation. Conventional pharmacological therapy have weak anti-DPN activity. By stimulating nerve regeneration, addressing underlying causes of the disorder, and alleviating symptoms, stem cell therapy for diabetic peripheral neuropathy has the potential to alter the management of this debilitating illness. One of its most significant advantages is its ability to regenerate damaged nerves, as stem cells may differentiate into a variety of cell types, including neurons and supporting cells. Preclinical and early-phase clinical research has resulted in improvements in nerve conduction, pain alleviation, and sensory function in patients with diabetic peripheral neuropathy. Stem cell therapy can be tailored to each patient's specific ailment, ensuring personalized care that improves therapeutic outcomes. Future research may uncover further benefits and applications for stem cell treatment, such as refining stem cell source selection, experimenting with novel delivery systems, and capitalizing on tissue engineering advances. Combining stem cell therapy with gene editing or bioengineering procedures may improve regenerative potential in the treatment of diabetic peripheral neuropathy. To completely reap the benefits of stem cell therapy in diabetic peripheral neuropathy, obstacles must be overcome and treatment procedures must be improved. Stem cell therapy has the potential to revolutionize the treatment of diabetic peripheral neuropathy by encouraging nerve regeneration, and symptom relief. The present review discusses the noteworthy developments in various regenerative therapies for diabetic peripheral neuropathy.

Effects of combined dietary intervention and physical-cognitive exercise on cognitive function and cardiometabolic health of postmenopausal women with obesity: a randomized controlled trial

BackgroundPostmenopausal women with obesity are markedly at risk of cognitive impairment and several health issues. Emerging evidence demonstrated that both diet and exercise, particularly physical-cognitive exercise are involved in cognitive and health benefits. However, the comparative effect of diet, exercise, and combined interventions in postmenopausal women with obesity on cognition and cardiometabolic health is still lacking. Identifying the effective health promotion program and understanding changes in cardiometabolic health linking these interventions to cognition would have important medical implications. This RCT aimed to examine the effect of single and combined interventions of diet and exercise on cognitive function and cardiometabolic health in postmenopausal women with obesity.MethodsNinety-two postmenopausal women with obesity were randomly assigned to diet group (intermittent fasting 2 days/week, 3 months), exercise group (physical-cognitive exercise 3 days/week, 3 months), combined group, or control group (n = 23/group). All cognitive outcomes and cardiometabolic outcomes were measured at baseline and post-3 months. Primary outcomes were executive functions, memory, and plasma BDNF levels. Secondary outcomes were global cognition, attention, language domain, plasma adiponectin levels, IL-6 levels, metabolic parameters, and physical function.ResultsAt the end of the 3-month intervention, the exercise and combined group demonstrated significant memory improvement which was accompanied by significant improvements in plasma BDNF level, insulin levels, HOMA-IR, %body fat, and muscle strength when compared to controls (p < 0.05). Only the combined intervention group demonstrated a significant improvement in executive function and increased plasma adiponectin levels when compared to control (p < 0.05). Surprisingly, no cognitive improvement was observed in the diet group (p > 0.05). Significant reduction in cholesterol levels was shown in the diet and combined groups when compared to controls (p < 0.05). Among the three intervention groups, there were no significant differences in all cognitive outcomes and cardiometabolic outcomes (p > 0.05). However, all three intervention groups showed significant improvements in plasma BDNF levels, weight, BMI, WHR, fat mass, and predicted VO2 max, when compared to control (p < 0.05).ConclusionThese findings suggest that combined physical-cognitive exercise and dietary intervention are promising interventions to improve cognition and obesity-related complications of postmenopausal women with obesity.Trial registrationNCT04768725 (https://clinicaltrials.gov) 24th February 2021.

Effects of high frequency strengthening on pain sensitivity and function in female runners with chronic patellofemoral pain

ObjectiveTo investigate the effects of a high frequency strengthening program on function, pain, and pain sensitization in female runners with chronic patellofemoral pain (PFP). DesignCross-sectional study. SettingUniversity laboratory. ParticipantsThirty female runners (mean age 32 ± 8.1 years) with chronic PFP completed an 8-week home strengthening program. Main outcome measuresVariables assessed at baseline, 8-weeks, and 12 weeks included single leg step down test (SLSD), pain, Anterior Knee Pain Scale (AKPS), University of Wisconsin Running Injury and Recovery Index (UWRI), and quantitative sensory testing. ResultsThere was large and statistically significant improvement at 8 and 12 weeks for average knee pain (ηp2 = 0.334, p < 0.001), worst knee pain (ηp2 = 0.351, p < 0.001), SLSD (ηp2 = 0.161, p = 0.001), AKPS (ηp2 = 0.463, p < 0.001), and UWRI (ηp2 = 0.366, p < 0.001). A medium to large effect and statistically significant improvement in pressure pain threshold testing was found for all local and remote structures (ηp2 range, 0.110 to 0.293, range p < 0.001 to p = 0.009) at 8 and 12 weeks. ConclusionsThere was a significant decrease in local and remote hyperalgesia via mechanical and thermal pain sensitivity testing in female runners with chronic PFP. There was a large effect and significant improvement in self-reported pain and function.

Effects of a fall prevention exercise regimen on physical and psychosocial outcomes in elderly community dwellers: a randomized comparative study.

There is a need for comprehensive programs that address both the physical and psychosocial aspects of fall prevention for the elderly. This study assessed the efficacy of the exercise regimen on various health metrics for elderly community dwellers. Forty-four participants were divided into experimental and control groups. The experimental group adhered to a 9-step core exercise regimen for fall prevention, practicing three times a week for 30 minutes across 10 weeks, while the control group maintained their regular daily activities without any specific exercise program. Before and after the intervention, participants underwent the timed up-and-go t est to evaluate the physical function, the berg balance scale (BBS) and one-legged stance test (OLST) for balance assessment, the activity-specific balance confidence scale for fall-related self-efficacy, and measures for health-related quality of life. Participants in the experimental group showed significant improvements in physical function (p = .04, Cohen's effect size (d) = 0.2). and balance ability on BBS (p < .01, d = 0.2) and OLST (p < .01, d = 1.3) compared to the control group. Furthermore, there was a notable enhancement in the quality of life indicators for this group, especially in areas such as physical function (p = .04, d = 0.2), physical-role limitation (p = .04, d = 0.2), mental health (p = .01, d = 0.3), vitality (p = .02, d = 0.4), body pain (p = .04, d = 0.5), and general health (p = .04, d = 0.4). These findings highlight the potential of the fall prevention exercise program in improving physical health aspects, but its influence on specific psychosocial elements remains to be determined.

Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy.

Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such as limited in vivo persistence, reduced tumor infiltration, and low absolute NK cell numbers. This review outlines several strategies aiming to overcome these challenges. The developed strategies include optimizing NK cell expansion methods and improving NK cell antitumor responses by cytokine stimulation and genetic manipulations. Using K562 cells expressing membrane IL-15 or IL-21 with or without additional activating ligands like 4-1BBL allows "massive" NK cell expansion and makes multiple cell dosing and "off-the-shelf" efforts feasible. Further improvements in NK cell function can be reached by inducing memory-like NK cells, developing chimeric antigen receptor (CAR)-NK cells, or isolating NK-cell-based tumor-infiltrating lymphocytes (TILs). Memory-like NK cells demonstrate higher in vivo persistence and cytotoxicity, with early clinical trials demonstrating safety and promising efficacy. Recent trials using CAR-NK cells have also demonstrated a lack of any major toxicity, including cytokine release syndrome, and, yet, promising clinical activity. Recent data support that the presence of TIL-NK cells is associated with improved overall patient survival in different types of solid tumors such as head and neck, colorectal, breast, and gastric carcinomas, among the most significant. In conclusion, this review presents insights into the diverse strategies available for NK cell expansion, including the roles played by various cytokines, feeder cells, and culture material in influencing the activation phenotype, telomere length, and cytotoxic potential of expanded NK cells. Notably, genetically modified K562 cells have demonstrated significant efficacy in promoting NK cell expansion. Furthermore, culturing NK cells with IL-2 and IL-15 has been shown to improve expansion rates, while the presence of IL-12 and IL-21 has been linked to enhanced cytotoxic function. Overall, this review provides an overview of NK cell expansion methodologies, highlighting the current landscape of clinical trials and the key advancements to enhance NK-cell-based adoptive cell therapy.

Psychostimulant Medications for Physical Function and Spasticity in Children With Cerebral Palsy: Protocol for a Randomized Controlled Trial.

Cerebral palsy (CP) is a prevalent nonprogressive disorder that leads to impaired movement (ie, spasticity), posture, and balance, which affects functions such as walking and upper extremity tasks. Current medical treatments show efficacy in improving motor performance but have considerable side effects. Emerging off-label use of central nervous system (CNS) medications for improving motor performance has shown promising results in children with CP and other populations. The aim of this study is to describe a protocol for a pilot randomized controlled trial (RCT) to examine the safety, tolerability, and efficacy of methylphenidate (MPH) and modafinil on spasticity and motor performance in children with CP. This will be a protocol study for a pilot, triple-masked, placebo-controlled RCT (a class I trial following the American Academy of Neurology criteria) with blinded patients, outcome assessors, and intervention delivery team. Eligible children should be diagnosed with CP levels I or II based on the Gross Motor Function Classification System and be aged between 7 and 12 years. Thirty-six children with CP will be randomized into 3 groups to receive (1) MPH (2.5 mg of MPH + 100 mg placebo), (2) modafinil (100 mg modafinil + 2.5 mg placebo), or (3) a placebo (2.5 mg placebo + 100 mg placebo), in addition to physical therapy for 12 weeks. Primary outcomes include the Gross Motor Function Measure-66 and the Modified Ashworth Scale. Secondary outcomes include the Timed Up and Go test, 5 Time Sit to Stand test, Modified Clinical Test for Sensory Interaction of Balance, and 10-Meter Walk Test. The protocol has been accepted by Kuwait University (VDR/EC-225) and the Ministry of Health of Kuwait (2022/2157). The inclusion of participants will start in June 2024. The combination of CNS stimulant medications and controlling for rehabilitation has not been studied yet. The findings of this study may determine if using CNS stimulant medications is beneficial for the reduction of spasticity and improvement of physical function in children with spastic CP. ClinicalTrials.gov NCT05675098; https://clinicaltrials.gov/study/NCT05675098. PRR1-10.2196/53728.

(273) Influences of Oral Dehydroepiandrosterone (DHEA) Administration on Hormonal Profile, Menopausal Clinical Symptoms and Sexual Function in Early Postmenopausal Symptomatic Women

Abstract Introduction Dehydroepiandrosterone (DHEA) and its sulfate (DHEAs) are steroid hormones secreted by the adrenal glands. The aging process is associated with decreased levels of DHEA and DHEAs, which are the initial causes of many age-related changes. Objective We aimed to evaluate the effects of oral administration of DHEA (50mg/day) on hormonal profile, menopausal clinical symptoms and sexual function in early postmenopausal symptomatic Caucasian women at baseline and after 2, 4 and 6 months of treatment. Methods For our prospective clinical trial, 42 symptomatic early postmenopausal women (50–55±3.5 years) were selected. Participants were divided into two groups. The study group (n-22) received oral DHEA 50mg/day for 6 months and the control group (n-20) received placebo. Serum levels of DHEA, DHEAs, androstenedione (A4), allopregnanolone (3α,5α- THP), progesterone (P4), 17OH progesterone (17OHP), cortisol, testosterone (T), dihydrotestosterone (DHT), estrone (E1), estradiol (E2), SHBG, LH, FSH and β-Endorphin were determined at baseline and after 2, 4 and 6 months of treatment. The results of the Menopause Rating Scale (MRS) and the McCoy Female Sexuality Questionnaire (MFSQ) were evaluated before and after the treatment. Results During the treatment period in the study group, a progressive increase in serum levels of DHEA, DHEAs, A4, T, DHT, E2, E1, 3α,5α-THP and β-Endorphin were observed. P4 and 17OHP levels showed only a slight increase. By the 4th month of treatment and final data, a decrease in cortisol levels was observed. LH and FSH levels gradually decreased. SHBG levels remained constant. After 6 months of treatment, assessing the results of the MRS in the DHEA group showed a progressive improvement of menopausal symptoms. The results of the McCoy questionnaire were also improved in the study group. Conclusions DHEA administration had a significant effect on certain endocrine parameters in early postmenopausal symptomatic Caucasian women, was associated with improvements of menopausal physical symptoms, sexual function and psycho-emotional parameters. Our findings support the hypothesis that administration of DHEA in symptomatic postmenopausal women restores both androgenic and estrogenic milieu and reduces most of the clinical symptoms caused by the changes of these environments during postmenopausal period. On this basis we can assume, that DHEA may be considered as a potentially effective medication for MHT. However, conducting further, more specific clinical trials are needed. Disclosure No.

(094) Evaluation of Female Sexuality After Vaginal Hysterectomy in a Cohort of Tunisian Women

Abstract Introduction Researchers indicate that hysterectomy might adversely affect pelvic anatomy and therefore female sexuality. However, only a few studies focused on evaluating female sexuality after vaginal hysterectomy. Objective This study aimed to evaluate female sexual function after a vaginal hysterectomy. Methods This was a monocentric prospective study conducted in the gynecology-obstetrics department of Ben Arous regional hospital over a period of 5 years [January 2016-December 2020]. We included all patients who underwent vaginal hysterectomy. Selected women received a preoperative evaluation of their sexual function using the Female sexual function index (FSFI). They were invited for two follow-ups at 12 and 24 months after surgery. The main outcomes measured were frequency of sexual intercourse, dyspareunia, orgasm, vaginal dryness, sexual desire, and FSFI scores. Results A total number of 109 women underwent vaginal hysterectomy over the study period. The mean age was 41 years ranging from 31 to 69 years. Only 79 patients completed the required follow-ups in order to evaluate their satisfaction and the impact of surgery on their sexuality. The percentage of women engaging in sexual intercourse increased significantly from 70.8% before vaginal hysterectomy (VH) to 77.21% and 75.9% at 12 and 24 months after respectively. The rate of dyspareunia dropped significantly from 40.5% before surgery to 5% and 3.8 % at 12 and 14 months after VH. The rate of women experiencing orgasm increased significantly from 63.2% before VH to 72.1% and 70.8 % after 12 and 24 months. Low sexual desire also decreased significantly from 10.1% before VH to 6.3% and 5% respectively at 12 and 24 months. The percentage of women experiencing satisfactory vaginal lubrication increased from 36.7% to 46.8% and 45.5%. Average FSFI significantly increased from 24.58 prior to the surgery to 26.82 and 27.55 at the 12 months and 24 months follow-ups respectively. Conclusions Female sexual function is a major cause of women's concern for scheduled hysterectomy. Our results showed a significant improvement in female sexual function after a vaginal hysterectomy. Therefore, the vaginal route for hysterectomy should be encouraged among middle-aged women as a minimally invasive technique that does not affect female sexual function or feminine shape. Disclosure No.