Improvement In Function Research Articles

Ameliorative Effects of Zingiber officinale Rosc on Antibiotic-Associated Diarrhea and Improvement in Intestinal Function.

The global increase in antibiotic consumption is related to increased adverse effects, such as antibiotic-associated diarrhea (AAD). This study investigated the chemical properties of Zingiber officinale Rosc (ZO) extract and its ameliorative effects using a lincomycin-induced AAD mouse model. Intestinal tissues were evaluated for the expression of lysozyme, claudin-1, and α-defensin-1, which are associated with intestinal homeostasis. The cecum was analyzed to assess the concentration of short-chain fatty acids (SCFAs). The chemical properties analysis of ZO extracts revealed the levels of total neutral sugars, acidic sugars, proteins, and polyphenols to be 86.4%, 8.8%, 4.0%, and 0.8%, respectively. Furthermore, the monosaccharide composition of ZO was determined to include glucose (97.3%) and galactose (2.7%). ZO extract administration ameliorated the impact of AAD and associated weight loss, and water intake also returned to normal. Moreover, treatment with ZO extract restored the expression levels of lysozyme, α-defensin-1, and claudin-1 to normal levels. The decreased SCFA levels due to induced AAD showed a return to normal levels. The results indicate that ZO extract improved AAD, strengthened the intestinal barrier, and normalized SCFA levels, showing that ZO extract possesses intestinal-function strengthening effects.

(340) The Association Between Varicocele and Premature Ejaculation: Systematic Review

Abstract Introduction Premature ejaculation (PE) is one of the most common sexual disorders that negatively impacts couple’s satisfaction. Varicocele on the other hand is a highly prevalent condition affecting men population. A higher incidence of PE is observed among patients with varicocele, which incited several authors to evaluate the possible correlation between varicocele and PE. Others went beyond that to investigate whether varicocele repair can lead to an improvement in PE. Objective To systematically review the literature for all the studies exploring the relationship between PE and varicocele. Methods A systemic review was performed utilizing (PRISMA) statement. The PubMed, Google scholar and Scopus databases were used to look for articles published up to June 2023 using the appropriate keywords. Articles reporting an association between the presence of varicocele and PE and exploring changes in ejaculation latency time after varicocele correction were included. Data including study design, sample size, varicocele details, PE diagnostic method, outcome measured and tools used to measure it were collected. The Newcastle-Ottawa scale was used for assessing the quality of the included studies. Results A total of eight studies were identified, two of them were retrospective and six were prospective. Intravaginal ejaculation latency time (IELT) was used as a diagnostic tool for PE in 5 studies, Premature Ejaculation Diagnostic Tool (PEDT) in 1 study, Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores in 1 study, and subjective assessment in 2 studies. Two studies looked for the prevalence of PE among patients with and without varicocele. Both studies showed a significantly higher frequency of PE among varicocele patients. Whereas six studies evaluated the improvement in ejaculatory function after varicocelectomy; five of them revealed a statistically significant improvement. Quality check: only one study was of strong quality while the remaining 7 studies were of fair quality. Conclusions Limited evidence suggests the presence of positive relation between varicocele and PE. The small number of studies and patients, lack of enough prospective clinical trials, short term follow up, heterogenous study design and absence or diversity in the diagnostic tools used prevent our ability to build strong evidence. For the purpose of supporting the relation and validate it, further prospective studies on a larger number of patients with long-term follow up are needed to reach a solid verdict. Disclosure No.

The effectiveness of glucocorticoid treatment in post-COVID-19 pulmonary involvement

RationalePersistent respiratory symptoms following Coronavirus Disease 2019 (COVID-19) are associated with residual radiological changes in lung parenchyma, with a risk of development into lung fibrosis, and with impaired pulmonary function. Previous studies hinted at the possible efficacy of corticosteroids (CS) in facilitating the resolution of post-COVID residual changes in the lungs, but the available data is limited.AimTo evaluate the effects of CS treatment in post-COVID respiratory syndrome patients.Patients and methodsPost-COVID patients were recruited into a prospective single-center observational study and scheduled for an initial (V1) and follow-up visit (V2) at the Department of Respiratory Medicine and Tuberculosis, University Hospital Olomouc, comprising of pulmonary function testing, chest x-ray, and complex clinical examination. The decision to administer CS or maintain watchful waiting (WW) was in line with Czech national guidelines.ResultsThe study involved 2729 COVID-19 survivors (45.7% male; mean age: 54.6). From 2026 patients with complete V1 data, 131 patients were indicated for CS therapy. These patients showed significantly worse radiological and functional impairment at V1. Mean initial dose was 27.6 mg (SD ± 10,64), and the mean duration of CS therapy was 13.3 weeks (SD ± 10,06). Following therapy, significantly better improvement of static lung volumes and transfer factor for carbon monoxide (DLCO), and significantly better rates of good or complete radiological and subjective improvement were observed in the CS group compared to controls with available follow-up data (n = 894).ConclusionBetter improvement of pulmonary function, radiological findings and subjective symptoms were observed in patients CS compared to watchful waiting. Our findings suggest that glucocorticoid therapy could benefit selected patients with persistent dyspnea, significant radiological changes, and decreased DLCO.

(366) Potential Effectiveness of Focused Vibration Treatment for Psychogenic Erectile Dysfunction: A Case Series

Abstract Introduction The current non-pharmacological treatment of psychogenic erectile dysfunction (pED) is based on cognitive-behavioral interventions that often involve the participation of the partner, such as desensitization procedures, sensory focusing, and couples counseling. However, it is important to note that in many cases, patients may not have a stable partner or their partner cannot participate in the treatment. The application of local mechanical vibration has shown promising results in increasing skin blood flow and nitric oxide production in healthy young adults. The relaxation of smooth muscle in the penis initiates and maintains an erection. The local release of nitric oxide from autonomic dilator nerves and vascular endothelium is crucial in initiating and sustaining this process. Technological advances have allowed the design of vibrating devices that men can use during sexual encounters. Objective To determine if the on-demand use of a focused vibration device can increase blood flow and promote relaxation of erectile tissue to improve erectile function in patients with pED. Methods Seven sexually active men diagnosed with pED based on criteria for Erectile Disorder from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and without a stable partner, were instructed to use a vibrating device called TENUTO II during their sexual encounters for duration of 8 weeks. This device generates focal vibrations on the penis and the perineal area in intervals of 10 seconds of vibration followed by 10 seconds of pause, with a frequency of 50Hz and an amplitude of 2mm. The five-item Spanish version of the International Index of Erectile Function (IIEF-5) questionnaire was used to assess symptoms before and after the procedure and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire was used for evaluating satisfaction with treatment. Results After the using the device, all patients enrolled with a mean age of 36.1 years (range 28-45) experienced an improvement in erectile function, mean IIEF-5 score pretreatment was 11(range 5–13) mean posttreatment IIEF score was 20 (range 18-27). No adverse effects were reported during the treatment. Conclusions This case series suggests that use of an on-demand focused vibration device could be a potentially effective and safe therapeutic option for men with pED. However, further studies with a larger number of participants and a more rigorous research design are needed to confirm these preliminary findings. Disclosure Yes, this is sponsored by industry/sponsor: MysteryVibe. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Mysteryvibe.

The siRNA-mediated knockdown of AP-1 restores the function of the pulmonary artery and the right ventricle by reducing perivascular and interstitial fibrosis and key molecular players in cardiopulmonary disease.

Pulmonary hypertension (PH) is a complex multifactorial vascular pathology characterized by an increased pulmonary arterial pressure, vasoconstriction, remodelling of the pulmonary vasculature, thrombosis in situ and inflammation associated with right-side heart failure. Herein, we explored the potential beneficial effects of treatment with siRNA AP-1 on pulmonary arterial hypertension (PAH), right ventricular dysfunction along with perivascular and interstitial fibrosis in pulmonary artery-PA, right ventricle-RV and lung in an experimental animal model of monocrotaline (MCT)-induced PAH. Golden Syrian hamsters were divided into: (1) C group-healthy animals taken as control; (2) MCT group obtained by a single subcutaneous injection of 60mg/kg MCT at the beginning of the experiment; (3) MCT-siRNA AP-1 group received a one-time subcutaneous dose of MCT and subcutaneous injections containing 100nM siRNA AP-1, every two weeks. All animal groups received water and standard chow ad libitum for 12weeks. In comparison with the MCT group, siRNA AP-1 treatment had significant beneficial effects on investigated tissues contributing to: (1) a reduction in TGF-β1/ET-1/IL-1β/TNF-α plasma concentrations; (2) a reduced level of cytosolic ROS production in PA, RV and lung and notable improvements regarding the ultrastructure of these tissues; a decrease of inflammatory and fibrotic marker expressions in PA (COL1A/Fibronectin/Vimentin/α-SMA/CTGF/Calponin/MMP-9), RV and lung (COL1A/CTGF/Fibronectin/α-SMA/F-actin/OB-cadherin) and an increase of endothelial marker expressions (CD31/VE-cadherin) in PA; (4) structural and functional recoveries of the PA [reduced Vel, restored vascular reactivity (NA contraction, ACh relaxation)] and RV (enlarged internal cavity diameter in diastole, increased TAPSE and PRVOFs) associated with a decrease in systolic and diastolic blood pressure, and heart rate; (5) a reduced protein expression profile of AP-1S3/ pFAK/FAK/pERK/ERK and a significant decrease in the expression levels of miRNA-145, miRNA-210, miRNA-21, and miRNA-214 along with an increase of miRNA-124 and miRNA-204. The siRNA AP-1-based therapy led to an improvement of pulmonary arterial and right ventricular function accompanied by a regression of perivascular and interstitial fibrosis in PA, RV and lung and a down-regulation of key inflammatory and fibrotic markers in MCT-treated hamsters.

(126) Application of HIFEM Therapy Improves Orgasmic, Urinary and Erectile Function by Stimulation of Pelvic Floor Muscles

Abstract Introduction The weak pelvic floor in men contributes to various urological disorders. Treatment can be accomplished by strengthening the pelvic floor muscles (PFM) through pelvic floor muscle training. Nevertheless, such development of PFM is time-consuming and heavily dependent on the subject's ability to perform selective muscle contractions. An advantageous approach is the targeted stimulation of PFM which can be accomplished via electromagnetic stimulation. Particularly, the pelvic floor muscles can be non-invasively and selectively stimulated via the HIFEM field. This results in the natural development and rehabilitation of PFM, which, among other functions, plays a vital role in facilitating orgasmic, urinary and erectile function. Objective The aim of this study is to assess the safety and efficacy of the HIFEM pelvic procedure for the treatment of erectile dysfunction. Methods In this study, 28 males with a median age of 56 (30-72 years) were enrolled. The treatment was composed of ten weekly 28-minute sessions. Outcome measurements were collected via questionnaires and ultrasound imaging prior to and after the last treatment. To assess changes in erectile and sexual function, and prostate-related symptoms, the International Index of Erectile Function (IIEF) and International Prostate Symptom Score (IPSS) were used. Transverse B-Mode ultrasound video scans were recorded along the long axis of the penile shaft from the tip to the base with the penis in a flaccid state. A linear transducer was used, the depth was set at 2 cm, and the frame rate was approximately 30 frames per second. Separate video recordings of the left and right cavernosum were taken. The ultrasound scans were processed by the Morphometrix cloud-based algorithm. Adverse events were monitored during the study. Results All evaluation methods proved the efficiency of treatment on a statistically significant level. A significant improvement was detected in the majority (4 of 5) of the domains of IIEF, with the overall score improvement from a baseline value of 45.14±2.42 to 48.75±2.86 (+3.61 points). The most exceptional improvement was found in Sexual desire (+18.78%; p=1.06x10-3), Erectile dysfunction (+13.03%; p=5.7x10-4), and Orgasmic function (+10.69%; p=7.04x10-5) domains. The mean difference in the total score of the IPSS questionnaire reached -3.04 points (p=5.1x10-6), exceeding the corresponding minimal clinical difference (MIC=3 points). Overall, subjects, on average, shifted from moderately symptomatic (9.57±1.37 points) to mildly symptomatic (6.54±0.91 points). An increase in vascularity of both cavernosal was measured within 57% of patients who underwent ultrasound examination; specifically, a significant improvement was recorded in tissue segment count (TSC; +104%; p=1.17x10-4) and density (TSD; +81% p=2.20x10-3), pointing to better blood flow and delivery in examined tissues. No adverse event was observed. Conclusions The therapy administering HIFEM technology of the pelvic floor for selective PFM stimulation demonstrated significant improvement of erectile and orgasmic function and urinary symptoms. The questionnaire results corresponded with ultrasound measurements using a novel algorithm, identifying positive changes in the penile vascular system. Overall, the treatment may be considered a safe and a possible first-line solution for male patients suffering from dysfunctions linked to weakened pelvic floor muscles. Further investigation is needed. Disclosure Yes, this is sponsored by industry/sponsor: BTL. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: AFFIRM Science.

Association between occlusal features and masticatory function in Hong Kong preschool children: a survey with one-year longitudinal follow-up

BackgroundMastication is important for breaking down food, aiding swallowing and nutrients absorption, and is therefore fundamental to a child’s development. Studies have shown poor masticatory function to be associated with younger age and presence of caries. However, studies of the association between masticatory function and malocclusion yielded contradictory results. The aim of this study is therefore to investigate the association between three-dimensional occlusal features with masticatory function, among preschool children in Hong Kong.MethodsSelf-administered questionnaires on masticatory function in three domains, namely general chewing difficulty, requiring help when eating different food types and increased preference for soft food were completed by parents. Information on non-nutritive sucking habits and basic demographics were also collected in the questionnaire. Clinical examinations were conducted to record three-dimensional occlusal features and presence of caries. Baseline investigations and one-year follow-ups were undertaken for 1,566 and 996 preschool children. Association of poor masticatory function with occlusal features, sucking habits and caries was investigated using chi-squared tests. Binomial logistic regressions were then carried out incorporating any significant factors identified. Longitudinal analysis of the one-year follow-up data was carried out to investigate whether improved occlusal features, sucking habits and caries resulted in better masticatory function.ResultsIn the cross-sectional study, the first domain of general chewing difficulty was associated with caries and thumb/digit sucking. The second domain of requiring help when eating different food types was associated with the male sex, younger age, caries and pacifier use. The last domain of increased preference for soft foods was associated with caries and thumb/digit sucking. Occlusal features, including abnormal overjet and unilateral permanent molars not in contact, were significantly associated with poor masticatory function in the bivariate analyses, but were not significant in the logistic regressions. In the longitudinal analysis, general chewing difficulty was found to improve in those of older age and those with resolved anterior crossbite. Less help was required to eat meat in those with fewer caries. Similarly, less help was required to eat food containing bones in those with reduced pacifier use. Preferences for eating soft foods was reduced in those who developed a normal overjet.ConclusionsThe study identified significant relationships between masticatory difficulties and factors associated with age, gender, active caries, and non-nutritive oral habits such as thumb/digit sucking and pacifier use. Younger children and males required more assistance with certain food types. Active caries and thumb/digit sucking habits contributed to general masticatory difficulties and preference for soft foods. The one-year follow-up indicated that improvement in masticatory function varies across age cohorts and were associated with improved occlusal features, such as resolution of anterior crossbite and normalized overjet, reduced pacifier use, and a decrease in the number of decayed teeth.

(231) Low-Intensity Extracorporeal Shockwave Therapy Twice Per Week for Six Weeks May Result in Transient Subjective Improvements in Erectile Function

Abstract Introduction Low-intensity extracorporeal shockwave therapy (LiESWT) has been reported to result in subjective improvements in erectile function, but the ideal patient population and treatment protocol have not yet been established. Objective We aimed to assess improvements in International Index of Erectile Function – Erectile Function domain (IIEF-EF) scores following treatment with LiESWT of 1500 shocks of 0.2mJ/mm2 per treatment, twice a week for six weeks. We hypothesized that LiESWT results in subjective improvements of erectile function. Methods Patients were prospectively enrolled in a clinical trial examining changes in erectile function following LiESWT. The study was powered to detect a change in IIEF-EF scores of 5 points. Patients received 12 bi-weekly LiESWT treatments of 0.2mJ/mm2 at 5Hz, 1500 shocks delivered per treatment using the Storz Duolith T-Top Ultra shockwave device. Patients completed IIEF-EF, Sexual Encounter Profile (SEP) questions two and three, Global Assessment Questions (GAQ), and Erection Hardness Score (EHS) questionnaires prior to initiation of treatments and following completion of treatments at 1-2 weeks, 4-6 weeks, 3 months and 6 months post-treatment. Changes in questionnaire responses were compared to baseline responses. Data were analyzed using single variant one-tailed T-tests and one-tailed Fisher’s exact test. Values are reported as means ± standard error. Results Twenty-five patients completed all five study visits. Mean pre-treatment IIEF-EF score was 14.24 ± 1.21. Mean IIEF-EF scores increased to 15.80 ± 1.46 1-2 weeks following treatment (Study Time #2), 16.12 ± 1.46 4-6 weeks following treatment (Study Time #3), 18.12 ± 1.57 3 months following treatment (Study Time #4), and 16.36 ± 1.86 6 months following treatment (Study Time #5), though results only reached significance at Study Time #4 (p=0.016) and results were not sustained. Changes in IIEF-EF scores following treatment were evaluated by baseline ED severity (normal IIEF-EF 26-30, N=1; mild IIEF-EF 22-25, N=2; mild-moderate IIEF-EF 17-21, N=7; moderate IIEF-EF 11-16, N=10; severe IIEF-EF 6-10, N=5. Patients with IIEF-EF scores 11-21 reported significant improvements in IIEF-EF scores at all time points (Figure 1). Mean pre-treatment EHS score was 2.1±0.14. There was no significant improvement in EHS score following treatment at any time point, and no differences when analyzed based on pre-treatment ED severity. Similarly, no changes in SEP or GAQ positive response rates were noted following treatment. Conclusions Our results suggest that LiESWT using 1500 shocks per treatment with energy of 0.2mJ/mm2 twice per week for 6 weeks may transiently improve subjective erectile function as measured using IIEF-EF questionnaires, particularly for patients with mild-moderate to moderately severe ED, consistent with other studies. However, improvements may not be sustained 6 months following treatment. Disclosure No.

(162) Evaluating the Effectiveness of Testosterone Therapy Combined with PDE5 Inhibitors in Enhancing Erectile Function in Eugonadal Men

Abstract Introduction Historically, testosterone therapy (TTh) is not indicated in eugonadal men with erectile dysfunction (ED). Moreover, the 2018 AUA Guidelines state that TTh is not indicated as monotherapy for men suffering from ED but should be considered as combination therapy with PDE5i, as TTh may increase the efficacy of PDE5i therapy. Objective We investigated the benefits of providing TTh in combination with PDE5i therapy in marginally eugonadal men to determine its efficacy in improving erectile function. Methods A retrospective chart review was performed on men presenting with ED to an academic institution’s Men’s Health Clinic from 2010 to 2022. Objective data was gathered on key variables that affected patient-reported outcomes of ED, including age at presentation and comorbidities, as well as use of TTh and use of oral PDE5i. 177 eugonadal men were selected with the criteria of testosterone levels >300 ng/dL on initial presentation. Results were then statistically analyzed using a two-tailed student’s T test in R and p-values to determine the significance between variables and outcomes in ED. Results Out of our cohort of 179 eugonadal men presenting with ED, 42 patients were continued or started on concurrent TTh with oral PDE5i therapy added, and 83 were started on PDE5i monotherapy. Men in the dual-therapy group excluding those already on TTh began with a pre-therapy testosterone mean of 412.3 ng/dL compared to 443.0 ng/dL which was insignificant (p=0.22). There were no significant differences in presenting age (p=0.61) or comorbidities including hypertension (p=0.89) and diabetes (p=0.63) between the two groups. Additionally, there were no significant differences in lab values of HgA1c (p=0.34), cholesterol (p=0.80), triglycerides (p=0.27), or LDL (p=0.89). However, there was a lower initial HDL in the combination group of 45.1 mg/dL compared to 55.8 mg/dL (p = 0.036). Men in the dual-therapy group were more likely to report subjective improvement in ED symptoms compared to men taking PDE5is alone. This was supported by 33/42 (78.6%) of men in the dual therapy group reporting improved erectile function compared to 49/83 (59.0%) of men in the PDE5i only group (p = 0.029). Conclusions In conclusion, these results demonstrate that treatment of eugonadal men with concurrent TTh and PDE5i therapy demonstrated a significant improvement in erectile function as compared to PDE5i therapy alone. These findings suggest consideration of testosterone therapy in addition to PDE5i in clinical practice when treating marginally eugonadal men presenting with ED. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.

The Possibility of Improvement in Balance and Function Following Conjunct Effects of Transcranial Direct Current Stimulation and Whole-Body Vibration Therapy in Spastic Cerebral Palsy Patients: A Hypothesis Study

Cerebral palsy (CP) results from developmental brain injury, affecting posture and muscular coordination. Traditional treatments offer varying effectiveness, among them the most recent therapies are whole-body vibration therapy (WBVT) and transcranial direct current stimulation (tDCS). WBV enhances proprioceptive function, muscle mass, bone density, and joint stability by stimulating muscle spindle fibers and activating dormant motor units. It also modulates spastic reflexes through mechanoreceptors, proving more effective than traditional physiotherapy. tDCS, a non-invasive neuromodulation, reshapes cortical excitability and modulates synaptic plasticity by altering neuronal activity. It affects long-term potentiation and depression, crucial in learning and adaptive functions. tDCS's interaction with neurotransmitters, especially dopamine and GABA, and its effect on NMDA and dopaminergic receptors make it promising for CP rehabilitation. Both therapies offer novel insights into CP rehabilitation through their influence on central and peripheral neural system. This hypothesis study tends to explore the conjunct effects of transcranial direct current stimulation (tDCS) and whole-body vibration therapy (WBVT) on improving balance and function in children with spastic cerebral palsy. The hypothesis suggests that WBVT's vibratory input, alongside tDCS's central stimulation, enhances function by modulating neuronal excitability and sensory information. The tonic vibration reflex (TVR) from WBV is believed to amplify muscle strength and modulate spinal excitability. When integrated with tDCS, it might accelerate excitability in the motor cortex, essential for brain-injured patient rehabilitation. Despite evidence of individual benefits from both therapies, conjunct effects remain under-researched. Preliminary results show improvements in balance, gait velocity, and motor functions. Validating this combined approach could revolutionize treatment for children with spastic cerebral palsy.

Effectiveness of Low-Intensity Extracorporeal Shock Wave Therapy in Erectile Dysfunction: An Analysis of Sexual Function and Penile Hardness at Erection: An Umbrella Review.

The present umbrella review of five systematic reviews and meta-analyses was conducted to investigate the effectiveness of Low-Intensity Extracorporeal Shock Wave Therapy (Li-ESWT) in the treatment of vascular origin Erectile Dysfunction (ED). A search was carried out in the databases of Pubmed, Scopus, Medline, Scielo and Embase. Participants were divided into two groups: an experimental group receiving Li-ESWT and a control group receiving simulated shock waves. The main variable of this study is ED, measured using the International Index of Erectile Function-Erectile Function (IIEF-EF) and the Erection Hardness Score (EHS) scale. The results showed a statistically significant increase in the mean IIEF-EF score in the experimental group. Overall, four out of five articles reported an increase in the EHS score in the Li-ESWT group compared to the placebo. Concerning the treatment parameters, better outcomes were observed with an energy density of 0.09 mJ/mm2 and the application of 1500-2000 pulses. Additionally, a follow-up of 6-12 months resulted in greater improvement in ED compared to 3 months, although more studies investigating follow-ups beyond 12 months are needed. Obtaining conclusive and clear results is challenging; however, everything indicates that Li-ESWT is an innovative therapeutic alternative for vascular-origin ED due to its low risk and improvement in erectile function.

Supplementary Respiratory Therapy Improves Pulmonary Function in Pediatric Patients with Cerebral Palsy: A Systematic Review and Meta-Analysis

Background: Despite medical advances, individuals with cerebral palsy (CP) face significant respiratory challenges, leading to heightened hospitalization rates and early mortality among this population. We hypothesize that integrating supplementary respiratory therapy into standard rehabilitation will result in significant improvements in pulmonary function, enhanced respiratory muscle strength, and an overall increase in the quality of life among pediatric patients with CP. Methods: A systematic search of literature across five databases was conducted, and random-effects meta-analyses were performed to assess the impact of supplementary respiratory therapy on (a) pulmonary function: forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio, peak expiratory flow (PEF), and (b) respiratory muscle strength: maximal inspiratory and expiratory pressure (MIP, MEP), and (c) quality of life. Certainty of evidence was determined by the GRADE assessment. Results: Analysis of data from 11 eligible randomized controlled trials revealed clinically meaningful changes in pulmonary function. We found a relevant mean difference (MD) in absolute PEF of 0.50 L/s (95% confidence interval (CI): 0.19; 0.82 p = 0.0107). The certainty of the evidence ranged from moderate to high. Conclusions: This study presents current evidence on the impact of various supplementary respiratory therapies for CP patients classified under gross motor function classification level I–IV, demonstrating clinically meaningful improvements in pulmonary function and respiratory muscle strength. These improvements suggest the potential for an enhanced quality of life. Our findings hold the promise of serving as a foundational reference for potential revisions to conventional rehabilitation care, incorporating supplementary respiratory therapy.

Da-Chuan-Xiong Decoction Ameliorates Sodium Sensitivity and Plasma Norepinephrine via Attenuation of Brain Oxidative Stress in the DOCA-Salt Hypertensive Rats.

Da-Chuan-Xiong Decoction (DCXD) is an aqueous extract from a classic Chinese herbal formula composed of dried rhizomes of Ligusticum chuanxiong Hort and Gastrodia elata Bl. in the mass ratio of 4 : 1. It has been long used to treat chronic cardiovascular disease caused by blood stasis and wind pathogen in the clinic. This experimental study aimed to investigate the blood pressure (BP)-lowering effect of DCXD treatment on hypertension and underlying mechanisms. Male Sprague-Dawley rats were used in the experiment, and the hypertensive models were created by administering deoxycorticosterone acetate (DOCA) in conjunction with a high salt intake in uninephrectomized rats. DCXD was administered to hypertensive rats by oral gavage daily at a dose of 5 g/kg or 2.5 g/kg bodyweight for 28 days. The brain sodium sensitivity, ENaC function, superoxide anion level, NADPH oxidase activity, and expression of ENaC, p67phox, p47phox, and Rac1 in the paraventricular nucleus were assessed by using the appropriate methods. The 28 days of DCXD (5 g/kg) treatment significantly reduced the increased BP effectively, inhibited the enhanced heart index, kidney index, and 24 h urinary protein, and improved the progressive pathological changes of heart and kidney, which was comparable to that of the positive control amlodipine. DCXD treatment also caused a marked reduction in plasma norepinephrine and induced a significant improvement in brain sodium sensitivity and ENaC function in DOCA-salt hypertensive rats. Rats in DCXD-treated groups also exhibited decreased superoxide anion levels and NADPH oxidase activity in the paraventricular nucleus. The level of ENaC, p67phox, and Rac1 protein expression in the paraventricular nucleus was significantly downregulated by DCXD treatment in DOCA-salt hypertensive rats. These findings indicate that the depressor action and sympathetic inhibition of DCXD on salt-sensitive hypertension may be by ameliorating brain sodium sensitivity, modulating ENaC function, and inhibiting the expression of ENaC and NADPH oxidase in the hypothalamic paraventricular nucleus.

A review on Parkinson’s disease symptoms before and after deep brain stimulation treatment

Introduction: Parkinson’s disease (PD), followed by Alzheimer’s disease, is the most common progressive neurodegenerative disease. Tremors, rigidity, akinesia, and disorders are common PD symptoms. Over the last few decades, deep brain stimulation (DBS) of the subthalamic nucleus has become a standard treatment for advanced PD. The aim of this systematic review paper is to see the difference between the symptoms of PD before and after DBS. Methods: We conducted a literature search using PubMed and Google Scholar. We chose research from the past 10 years. We retrieved 64 papers, and seven duplicated papers were removed. We reviewed the abstract for the remaining 57 papers which led to the selection of 29 papers. After applying inclusion and exclusion criteria for the remaining 29 papers, 23 papers in the English language were chosen for our review. Results: Five Randomized Clinical Trials (RCTs) studied the outcomes of DBS and eight RCTs about effects on posture and motor function. Four RCTs investigated the effects on gait and balance, two on tremors, and the remaining two on posture. The effects of DBS on speech and language were compared in two RCTs. Three studies looked at cognitive performance. One RCT studied sleeping versus awake DBS on PD. These studies showed that with DBS treatment, there was significant improvement in posture, motor function, gait, balance, speech, and language. However, more studies are required for the further analysis on dysphagia and urinary dysfunction. Conclusion: Our study contributed to a better understanding of the advantages of DBS for a range of symptoms, but it concluded that additional RCT on dysphagia and urinary dysfunction was required to reach a reliable conclusion. More research is required to determine the effects of DBS on different motor and non-motor PD symptoms to standardize treatment.

Anterior vs Posterior Surgery for Patients With Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

The advantages and disadvantages of anterior vs posterior surgical approaches for patients with progressive degenerative cervical myelopathy (DCM) remain uncertain. Our primary objective was to evaluate patient-reported disability at 1 year after surgery. Our secondary objectives were to evaluate differences in patient profiles selected for each approach in routine clinical practice and to compare neurological function, neck and arm pain, health-related quality of life, adverse events, and rates of reoperations. We analyzed data from patients with DCM who were enrolled in an ongoing multicenter prospective observational cohort study. We controlled for differences in baseline characteristics and numbers of spinal levels treated using multivariable logistic regression. Adverse events were collected according to the Spinal Adverse Events Severity protocol. Among 559 patients, 261 (47%) underwent anterior surgery while 298 (53%) underwent posterior surgery. Patients treated posteriorly had significantly worse DCM severity and a greater number of vertebral levels involved. After adjusting for confounders, there was no significant difference between approaches for odds of achieving the minimum clinically important difference for the Neck Disability Index (odds ratio 1.23, 95% CI 0.82 to 1.86, P = .31). There was also no significant difference for change in modified Japanese Orthopedic Association scores, and differences in neck and arm pain and health-related quality of life did not exceed minimum clinically important differences. Patients treated anteriorly experienced greater rates of dysphagia, whereas patients treated posteriorly experienced greater rates of wound complications, neurological complications, and reoperations. Patients selected for posterior surgery had worse DCM and a greater number of vertebral levels involved. Despite this, anterior and posterior surgeries were associated with similar improvements in disability, neurological function, pain, and quality of life. Anterior surgery had a more favorable profile of adverse events, which suggests it might be a preferred option when feasible.

Effect of recombinant human thrombopoietin on platelets in rats with D-galactosamine salt-induced acute liver failure

To evaluate the effects of recombinant human thrombopoietin (rhTPO) on platelet count (PLT) and liver function in acute liver failure (ALF) rats by observing the dynamic changes of PLT, thrombopoietin (TPO) and liver function during ALF. Twenty-four male Sprague-Dawley (SD) rats were divided into model group, TPO group and interleukin-11 (IL-11) group using a random number table method, with eight rats in each group. All rats were intraperitoneally injected with D-galactosamine (D-GalN, 1 500 mg/kg, dosed within 72 hours) to induce the ALF model. After modeling, rats in TPO group was received subcutaneous injection of 15 μg/kg of rhTPO for 5 days, and rats in IL-11 group was received subcutaneous injection of 0.45 mg/kg of IL-11 for 5 days. Venous blood samples were collected before and at 1, 3, 5, 7 and 12 days after molding for whole blood cell detection. The level of TPO in serum was detected by enzyme-linked immunosorbent assay (ELISA). Liver function indexes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (ALB) were measured before and at 1, 3 and 5 days after modeling. The rats were sacrificed 12 days after the modeling, and the pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. Two rats in each group died within 24-48 hours after modeling. HE staining showed that all three groups of ALF rats showed large flake necrosis of hepatocytes, disorder of hepatic lobular structure, mesh scaffold collapse, hepatic sinus congestion and hemorrhage, and flake infiltration of inflammatory cells on day 12 after modeling. The levels of serum ALT, AST and TBil of rats in each group were significantly increased 1 day after modeling and then decreased. The level of ALB decreased significantly on the first day after modeling and then increased, but there was no significant difference in the trend of liver function indexes among the three groups. PLT in the three groups decreased rapidly on day 1 after modeling, and then recovered gradually with the improvement of liver function. The PLT of the TPO group rose to the peak value 7 days after molding and was significantly higher than that of the model group [PLT (×109/L): 1 673.3±347.5 vs. 855.3±447.0, P < 0.05], while there was no significant difference between the IL-11 group and the model group [PLT (×109/L): 1 350.3±386.6 vs. 855.3±447.0, P > 0.05]. The level of serum TPO of the three groups increased significantly on day 1 after modeling, then decreased, and dropped to the lowest value on day 5, but there was no significant difference in the trend of serum TPO level among the three groups. PLT in ALF rats decreased rapidly in the early stage and recovered gradually with the improvement of liver function, and the serum TPO level increased first and then decreased. Injection of rhTPO can significantly increase PLT in ALF rats, but has no significant effect on liver function and survival rate.

Total Knee Arthroplasty Versus Education and Exercise for Knee Osteoarthritis: A Propensity-Matched Analysis.

We estimate the treatment effect of total knee arthroplasty (TKA) versus an education and exercise (Edu+Ex) program on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for knee osteoarthritis (OA). Patients with knee OA who had undergone TKA were matched on a 1:1 ratio with participants in an Edu+Ex program based on a propensity score fitted to a range of pretreatment covariates. After matching, between-group differences in improvement (the treatment effect) in Knee Injury and Osteoarthritis Outcome Score 12-item version (0, worst to 100, best) pain, function, and quality of life from baseline to 3 and 12 months were estimated using linear mixed models, adjusting for unbalanced covariates, if any, after matching. The matched sample consisted of 522 patients (Edu+Ex, n=261; TKA, n=261) who were balanced on all pretreatment characteristics. At 12-month follow-up, TKA resulted in significantly greater improvements in pain (mean difference [MD] 22.8; 95% confidence interval [95% CI] 19.7-25.8), function (MD 21.2; 95% CI 17.7-24.4), and quality of life (MD 18.3; 15.0-21.6). Even so, at least one-third of patients receiving Edu+Ex had a clinically meaningful improvement in outcomes at 12 months compared with 75% of patients with TKA. TKA is associated with greater improvements in pain, function, and quality of life, but these findings also suggest that Edu+Ex may be a viable alternative to TKA in a meaningful proportion of patients, which may reduce overall TKA need. Confirmatory trials are needed.

Abstract WMP111: Intra-Arterial Administration of Cerebral Endothelial Cell Derived Small Extracellular Vesicles Reduces Neurovascular Damage and Improves Neurological Outcome After Acute Ischemia in the Aged Rat

Stroke is a leading cause of death and disability worldwide, mainly affecting the elderly. Endovascular thrombectomy (EVT) is a standard of care therapy for stroke patients with large-vessel occlusion, however, the majority of these patients do not achieve full functional improvement. The present study tested the hypothesis that intra-arterial (IA) administration of cerebral endothelial cell derived small extracellular vesicles (CEC-sEVs) following transient middle cerebral artery occlusion (tMCAO) improves stroke outcome in the aged rat. CEC-sEVs (1x10 11 particles/injection) isolated from healthy adult rats were employed. Male aged rats (18 months, n=10/group) subjected to 3h tMCAO were randomly divided into the experimental groups. To examine whether IA injection of CEC-sEVs improves stroke outcome, CEC-sEVs were administered via the internal carotid artery (ICA) immediately following reperfusion by withdrawal of the occlusion filament. To examine whether intravenous administration (IV) of CEC-sEVs during tMCAO and then followed by IA CEC-sEVs upon reperfusion further enhances stroke outcome, CEC-sEVs were given at 30 min of tMCAO via a tail vein and upon reperfusion via the ICA. The ischemic rats treated with IA saline were used as a control. Neurological outcome and infarct volume were assessed in a blinded manner. IA CEC-sEVs upon reperfusion significantly reduced infarct volume (24±5% vs 31±6% in saline, p&lt;0.05) which was associated with robust improvement of neurological function from weeks 2 to 4 after tMCAO compared to saline treated rats. Moreover, rats treated with CEC-sEVs IV at 30min followed by IA treatment upon reperfusion further reduced infarct volume (16±6%) compared to rats treated with IA saline or CEC-sEVs. These rats also exhibited robust and early improvement of neurological function starting at 1d after tMCAO. In conclusion, IA administration of CEC-sEVs upon reperfusion significantly reduces ischemic damage, while an additional early (30min post stroke) dose of IV CEC-sEVs further enhances and accelerates the therapeutic effect of IA CEC-sEVs in the aged rats after tMCAO. Our data suggest that CEC-sEVs could potentially may be a therapy to amplify the efficacy of EVT even for elderly patients with acute ischemic stroke.

Abstract 118: Vagus Nerve Stimulation Paired With Rehabilitation for Post-Stroke Arm Impairment: One Year Follow-Up of the VNS-REHAB Pivotal Trial

Background: Persistent post-stroke impairment of the arm and hand is debilitating after stroke. Pairing vagus nerve stimulation (VNS) with upper extremity (UE) rehabilitation improves such deficits after 5 months and was approved by the FDA in 2021. Here, we present 1-year outcomes from the VNS-REHAB pivotal trial. Methods: Stroke participants with moderate-to-severe UE impairment were randomized to task-specific rehabilitation plus either active VNS (n=53, VNS) or sham VNS (n=55, Control). After baseline assessment (Pre-therapy), both groups did 6 wk. of in-clinic therapy followed by a 3-mo. home exercise program combined with active or sham VNS (post90). Controls then crossed over to receive 6 wk. of active VNS followed by a 3-mo. home exercise program (Cross-over post90). Both groups continued active VNS with a home exercise program through 1 year, after which change from Pre-therapy baseline in Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT) scores were obtained. To determine whether participants made additional gains, 1 year outcome scores (n=70) were also compared to post90 (n=38, VNS) and Cross-over post90 (n=32, Control) scores. Data was available from 74 participants at one year, with others not available mainly due to COVID-19. Results: At 1-year, both FMA-UE and WMFT scores improved from Pre-therapy baseline by 5.3±6.9 (CI=3.7-6.9, p&lt;0.001) and 0.51±0.52 (CI=0.39-0.63, p&lt;0.001) points, respectively. FMA-UE change at 1-year was not significantly different from the post90 (VNS) and Cross-over post90 (control) timepoints (n=70, mean difference: -0.3±4.1, CI=-1.3-0.67, p=0.52), but WMFT was, by an additional 0.09 points (n=70, mean difference: 0.09±0.35, CI=0.01-0.18, p=0.03), indicating that participants either improved or maintained motor gains through 1 year. Conclusion: Improvements in arm and hand function with VNS were maintained at 1-year follow-up, supporting use of VNS paired with rehabilitation as a long-term treatment option for individuals with post-stroke UE impairment. Limitations include sample size and lack of details of therapeutic regimens over the long term. Future studies and an ongoing clinical registry will explore the long-term impact of active VNS in real-world settings.

Effect of Blend of Metanil Yellow and Tartrazine on Different Organs of Albino Rat

Background: Tartrazine and metanil yellow are organic azo dyes widely used in food products, drugs, and cosmetics. The present study was conducted to evaluate the toxic effect of these food colors on the liver, and kidneys of albino rats. The study also evaluates the protective effect of quercetin as an antioxidant against the toxic effect of these food colors. Methods: Eighty adult albino rats were divided into 8 groups. Control group, 3 groups were treated with a blend of tartrazine and metanil yellow in 3 doses of 25, 50, and 75 mg/kg for 30 days by gavage, one positive control group was treated with quercetin 50 mg/kg for 30 days, and three groups were treated with the blend of tartrazine and metanil yellow plus 50 mg/kg of quercetin. At the end of the experiment, serum samples were collected to evaluate liver and kidney functions. Liver, kidney samples were fixed in 10% formalin and routinely prepared for paraffin sectioning and staining for histopathological examination. Results: The study showed a significant elevation of liver and kidney function after treatment with the food color blend. Also, a significant improvement in liver and kidney function was observed after treatment with quercetin. Histopathological examination showed mild to moderate changes in the liver and kidney which improved after quercetin treatment. Conclusion: The current sub-chronic study concluded that a blend of tartrazine and metanil yellow caused significant biochemical and histological changes in different organs of albino rats. Therefore, prolonged consumption of these substances leads to adverse effects on human health. Also, quercetin is vital in protecting the body against the toxic effects of food color blends.