4th Week Research Articles

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.

Rationale and design of Dapagliflozin vErsus SacubiTrIl-valsartaN therapY in Heart Failure with reduced ejection fraction (DESTINY-HF): a pragmatic randomised controlled trial protocol

BackgroundHeart failure affects almost 64 million people, with more than half of it constituting heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT2) inhibitors...

Efficacy of Microneedle as an Assisted Therapy for Melasma: A Meta-analysis and Systematic Review of Randomized Controlled Trials.

Melasma is a common hyperpigmentary disorder, it has variety of treatment options, but it usually has a poor curative effect and high recurrence rate. Microneedles have shown certain prospects in the treatment of melasma as an assisted therapy, but there is no consensus on its efficacy and safety. To evaluate the efficacy and safety of microneedles as an adjuvant treatment for melasma. Statistical tools were used to adjust the improvement of MASI scores in all studies to obtain standardized mean differences (SMD), and then, meta-analysis were performed. Risk ratio (RR) was utilized to assess adverse reactions, clinical effectiveness, and patient satisfaction. The effects of microneedle-assisted treatment for melasma begin to manifest at the 4th week, with optimal results observed at the 24th week, and with a high patient satisfaction. Compared with oral medication alone, microneedle-assisted therapy began to be more effective at week 12 and continued by 24weeks. Compared with laser therapy alone, microneedle-assisted therapy also showed stronger efficacy, at the 8th week, microneedle-assisted treatment was significantly more effective, reaching its peak at the 12th week. Finally, in the comparison of microneedle and microinjection therapy, microneedle has always been more significant than micro-injection. Microneedle is a valuable adjunctive therapy for melasma treatment. It enhances long-term clinical outcomes compared to monotherapy and is associated with high patient satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prophylactic role of pentoxifylline against paclitaxel-induced neuropathy among patients with breast cancer: a randomized-controlled trial.

Paclitaxel-induced peripheral neuropathy (PN) is a significant clinical concern for which no approved treatment is currently available. The purpose of this trial was to investigate the neuro-prophylactic impact of pentoxifylline against paclitaxel-induced PN in patients diagnosed with breast cancer (BC). BC patients who were assigned to paclitaxel chemotherapy were randomly allocated to pentoxifylline or a control group for 12 weeks. The main outcomes included the assessment of PN incidence according to the defined Common Terminology Criteria for Adverse Events, quality of life (QoL) using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTx) scale, and neuropathic pain using the scale of self-reported Leeds Assessment for Neuropathic Symptoms and Signs (s-LANSS). The code of the clinical trial registration is NCT06562998. The current study included a total of 72 patients allocated into pentoxifylline arm (n = 35) and placebo arm (n = 37). By the 12th week, the prevalence of PN (grade 2 or 3) was significantly lower in the pentoxifylline arm 10/35 (28.6%) compared to 24/37 (64.9%) of the controls (P value = 0.016). The total FACT/GOG-NTx score indicated a considerably worse QoL in the control group [98.18 (10.2) vs. 81.43 (14.8) for pentoxifylline and the control group, respectively, P < 0.001] with a mean difference of -16.75 [95% confidence interval (CI): -23.97 to -9.53]. S-LANSS scale showed significantly higher scores after 6 weeks [13.72 (5.86) vs. 17.52 (3.16), P = 0.002] and 12 weeks [17.84 (4.25) vs. 23.80 (1.00), P < 0.001] for pentoxifylline and control group, respectively. In conclusion, the use of pentoxifylline showed a significant reduction in paclitaxel-induced PN, which improved their QoL.

Effects of Kabat rehabilitation versus mime therapy on facial disability and synkinesis in patients of Bell’s palsy

Objective: To compare the effects of Kabat rehabilitation and Mime therapy on facial disability and synkinesis in patients with Bell’s palsy. Method: The single-blind, randomised clinical trial was conducted at the Physiotherapy Department of the University of Lahore Teaching Hospital, Lahore, Pakistan, from May to October 2023, and comprised adults of either gender aged 25-50 years having sub-acute or chronic unilateral Bell's palsy of non-congenital origin. The patients were randomised into Kabat rehabilitation group A and mime therapy group B. Conventional physical therapy was given to both groups additionally. Facial disability was assessed using the Facial Disability Index scale, and synkinesis was observed using the House-Brackmann Facial Nerve Grading Scale. Data was analysed using SPSS 25. Results: Of the 72 patients, 41(56.9%) were females and 31(43.1%) were males. The overall mean age was 37.77±6.98 years, mean body mass index was 25.71±5.71kg/m2 and 41(56.9%) patients had left-sided palsy. Facial disability and synkinesis were significantly different in both groups post-intervention (p&lt;0.001), while intergroup differences were significant in the 3rd and 6th weeks (p&lt;0.001). Conclusion: Kabat rehabilitation led to more significant improvements in synkinesis and facial disability compared to mime therapy. Clinical Trial Number: Clinical trials.gov registration id: NCT06029855. Key Words: Bell’s palsy, Disability, Rehabilitation, Synkinesis.

Serum biochemical evaluation of healing of critical-sized long bone defects in rats treated with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds

Critical-sized long bone defects are those that would not heal spontaneously despite surgical stabilisation. The use of bioceramic scaffold has shown promising results in the repair of bone defects. The present study was undertaken to evaluate the serum biochemical parameters of Wistar rats treated for critical-sized segmental bone loss using biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds. The study was conducted in eighty male Wistar rats aged between 8-12 weeks, weighing 200-250 g body weight with critical-sized segmental defects in the femur. A 6 mm segmental mid-diaphyseal femoral defect was created under general anaesthesia. The bone defect was bridged with bioceramic scaffolds and retained in position with microplate and screws. Serum biochemical parameters serum calcium, phosphorous, acid phosphatase and alkaline phosphatase were evaluated four weeks before surgery, immediately after surgery and 4th, 8th, 12th, and 16th week after surgery. The evaluation of both serum calcium and phosphorous were found to be reliable indicators of new bone formation and mineralisation, whereas the evaluation of both serum acid phosphatase and alkaline phosphatase were found to be reliable indicators of bone healing during the treatment of critical-sized long bone defects in rats using biphasic hydroxyapatite and β-tricalcium phosphate bioceramic scaffolds Keywords: Beta-tricalcium phosphate, bioceramic scaffold, hydroxyapatite, serum acid phosphatase, serum alkaline phosphatase, serum calcium, serum phosphorous

Biomechanical evaluation of healing of critical-sized long bone defects in rats treated with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds

Critical-sized bone defects are those that would not heal spontaneously despite surgical stabilisation. These defects are treated using autografts, allografts, xenografts and synthetic bone grafts. The present study was undertaken to evaluate the efficacy of biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds in treating critical-sized segmental bone loss in rats. The study was conducted in sixty male Wistar rats aged between 8-12 weeks, weighing 200-250 g body weight with critical-sized defects in the right femur. A six-mm segmental mid-diaphyseal femoral defect was created under general anaesthesia. The bone defect was bridged with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds and retained in position with microplate and screws. Fifteen rats were sacrificed as per the guidelines of CCSEA during the 4th, 8th, 12th and 16th week post-surgery. The treated bone and contralateral femur were harvested and subjected to a three-point bending test, torsion test and compression test to compare the regained strength of the repaired right femur with that of the intact contralateral left femur. From the present study, it was observed that the use of biphasic hydroxyapatite and β-tricalcium phosphate bioceramic scaffolds in the treatment of critical-sized long bone defects in rats resulted in biomechanical properties of the healed right femur greatly superior to the femur with untreated critical-sized diaphyseal defect by sixteenth week post-surgery and was only slightly inferior to the normal intact left femur. The results were suggestive of using biphasic hydroxyapatite and β-tricalcium phosphate bioceramics scaffolds as a safe and promising alternative for the treatment of critical-sized bone defects Keywords: Beta-tricalcium phosphate, bioceramic scaffold, compression test, hydroxyapatite, three-point bending test and torsion test

Effects of Chitosan and N-Succinyl Chitosan on Metabolic Disorders Caused by Oral Administration of Olanzapine in Mice.

The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi's protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract.

The role of training and medication reminder wristwatch in adherence to treatment in geriatric patients diagnosed with hypertension: A randomized controlled trial.

The purpose of this study was to determine the effects of the training and medication reminder wristwatch on treatment adherence in geriatric patients diagnosed with hypertension. In this study, which was conducted as a randomized clinical trial with a pretest-posttest design, 90 patients were randomly divided into the training and medication reminder wristwatch (W) group (n = 30) group, the training (T) group (n = 30), and the control (C) group (n = 30). All patients answered the data collection forms before and after the interventions. By the end of the 12th week, the mean knowledge scores of the groups significantly differed from each other (t = -13.207, P < 0.001). The mean Hypertension Compliance Assessment Scale score of the W group was found to be significantly lower (t = 22.732, P < 0.001). The highest mean Medication Adherence Self-Efficacy Scale-Short Form score was found in the W group (t = -13.560, P < 0.001). In the posttest, the mean systolic blood pressure values of the patients were 142.7 ± 11.1 in the C group, 126.0 ± 13.0 mm Hg in the T group, and 120.0 ± 9.5 mm Hg in the W group (Kruskal-Wallis test = 38.065, P < 0.05). This study demonstrates that 12 weeks of a training program and the use of medication reminder wristwatches were effective in adherence to treatment. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2024; ••: ••-••.

Real-World Clinical Effectiveness of Liraglutide for Weight Management in Türkiye: Insights from the LIRA-TR Study

Introduction: Obesity is a complicated chronic disease associated with a series of other conditions. A weight loss of 5–10% has been shown to reduce obesity-related complications and improve quality of life. The efficacy and safety of liraglutide for reducing body weight have been demonstrated in clinical trials. This study evaluated the weight loss efficacy and adverse effects of liraglutide in those with obesity in the Turkish population. Methods: This is a retrospective cohort study; the patients that were included had a body mass index (BMI) of 27 or greater with additional comorbidities or a BMI of 30 or greater, and the patients were prescribed liraglutide for obesity treatment from the tertiary private clinic between January 2022 and January 2024. Their metabolic and anthropometric parameters were recorded at the initial appointment, and their body weight and adverse effects were followed up on during therapy. Results: For the 568 patients, of whom 487 (85.6%) were female, the mean values for age, weight, and BMI were 42.37 ± 10.50, 98.09 ± 17.48 kg, and 35.77 ± 5.45 kg/m2, respectively. Reductions in body weight at the 4th, 8th, 12th, and 24th weeks were 6.45 ± 2.32 kg, 10.66 ± 3.41 kg, 15.38 ± 8.30 kg, and 19 ± 9.06 kg, respectively; reductions in BMI at the 4th, 8th, 12th, and 24th weeks were 2.36 ± 1.00, 3.88 ± 1.25, 5.36 ± 1.76, and 7.09 ± 2.93, respectively; and the percentages of overall body weight loss at the 4th, 8th, 12th, and 24th weeks were 6.62 ± 2.1%, 10.75 ± 2.71%, 14.97 ± 6.8%, and 18.55 ± 4.63%, respectively (all p values &lt; 0.0001). The percentage of patients who lost more than 5% and more than 10% of their initial weight was 100% at the 24th week. The most common side effect was nausea; no pancreatitis was observed. Conclusions: The results of our study indicate that liraglutide is an efficacious and safe treatment option for obesity in the Turkish population, in accordance with the findings from previous research.

Accumulated subcutaneous fat in abdomen is associated with long COVID-19 symptoms among non-hospitalized patients: a prospective observational study.

Long COVID-19 symptoms may have a variety of potential overlapping causes. In this study, we aimed to investigate the potential correlation between abdominal adipose tissue and long COVID-19 symptoms in non-hospitalized patients in China. This is a prospective observational study. 424 subjects, recovered from COVID-19 for 2-4 weeks, were enrolled and 408 subjects were finished the follow-up investigation at baseline, 8th week and 12th week. Physical measurements were collected. Kaplan-Meier analysis and cox regression analysis were carried out to assess the correlation. A total of 72 subjects reported the long COVID-19 symptoms. The adjusted Kaplan-Meier analysis and Cox regression analysis revealed a significant correlation with accumulated subcutaneous fat (SFA ≥ 2.0 dm2) and the long COVID-19 symptoms (HR = 2.63, P < 0.001 for male, HR = 1.52, P = 0.048 for female). However, overweight and central obesity showed positive correlation only in women. This study suggested that accumulated subcutaneous fat in abdomen (SFA ≥ 2.0 dm2) was an important positive factor associated with long COVID-19 symptoms among Chinese non-hospitalized patients. Large investigation and prospective studies are needed to validate the correlation in the future.

Developing a Sitting Simple Baduanjin program for advanced cancer patients with the fatigue-sleep disturbance symptom cluster: A feasibility study.

We describe a development and feasibility study of a Sitting Simple Baduanjin program for advanced cancer patients suffering from the fatigue-sleep disturbance symptom cluster. This study was to evaluate the practicality and safety of the Sitting Simple Baduanjin intervention and determine its preliminary efficacy. This work employed a single-arm mixed-methods approach. The primary outcome measures were feasibility (i.e., recruitment, adherence, and satisfaction) and safety. Validated self-report questionnaires were used to evaluate the preliminary effects of the program, including fatigue, sleep quality, and quality of life at the 4th, 8th, and 12th weeks of the intervention. Qualitative interviews were also conducted after the program. A total of 30 participants were enrolled, of which 23 (77%) completed the 12-week Sitting Simple Baduanjin program. The mean adherence rate was 88% and no adverse events were reported. Statistically significant improvements were observed in terms of fatigue, sleep quality, and quality of life after program completion. Four themes emerged from the qualitative interview data: (a) acceptability of the Sitting Simple Baduanjin technique, (b) perceived benefits of exercise, (c) barriers, and (d) facilitators. The findings support the feasibility of the Sitting Simple Baduanjin program for advanced cancer patients and show promise in improving patients' levels of the fatigue-sleep disturbance symptom cluster and quality of life.

Chinese Herbal Medicines as Natural Alternative Products to Antibiotics in Weaned Piglets through Intestinal Microbiota Regulation.

During the growth process of weaned piglets, digestive problems such as gastrointestinal disorders and diarrhea are common. Farmers usually use antibiotics to help piglets grow smoothly. However, the overuse of antibiotics can lead to antibiotic resistance issues. Therefore, this study chose to use plant extracts as feed additives to explore their potential as alternatives to antibiotics. Additionally, Tilmicosin was used as the antibiotic because it is widely used in treating respiratory infections in piglets. Since traditional Chinese medicine often uses natural products, we selected Guizhi Li-Zhong (GLZ) extract as an alternative to antibiotics. The experiment involved 126 piglets, each 4 weeks old, which were randomly assigned to one of four groups: the sham group (basal diet without supplements, 10.3 ± 0.4 kg, n = 31), the low-dose GLZ group (basal diet with 0.05% GLZ, 10.9 ± 0.4 kg, n = 32), the regular-dose GLZ group (basal diet with 0.2% GLZ, 10.6 ± 0.4 kg, n = 32), and the regular-dose Tilmicosin antibiotic group (basal diet with 0.2% Tilmicosin, 10.2 ± 0.3 kg, n = 31). We recorded and compared the survival rate, growth rate, feed conversion ratio, and diarrhea incidence among four groups of weaned piglets from the 4th to the 10th weeks of age. Then, we examined the oxidative stress, inflammation, and apoptosis in small intestine tissue (jejunum and ileum) through immunohistochemistry and Western blot and compared the gut microbiota in large intestine tissue (colon and rectum) through a next-generation sequencing (NGS) analysis. Our results showed that weaned piglets supplemented with 0.05% and 0.2% GLZ had better survival rates, growth rates (p < 0.01), and feed conversion ratios (p < 0.01) compared to those receiving sham treatment. Even weaned piglets supplemented with 0.2% GLZ performed better than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). Furthermore, the incidence of diarrhea and small intestine injury (indicated by oxidative stress-, inflammation-, and apoptosis-related proteins) in piglets supplemented with 0.05% and 0.2% GLZ was lower than in piglets receiving sham treatment (p < 0.05). Even piglets supplemented with 0.2% GLZ had less injury than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). The NGS results further showed that GLZ treatment significantly improved beneficial bacteria in weaned piglets (p < 0.05), while antibiotic treatment reduced beneficial bacteria (p < 0.05). In summary, we recommend adding GLZ to the feed as an alternative to antibiotics. This not only effectively reduces intestinal damage but also improves the gut microbiota, thereby promoting the growth of weaning piglets.

The development of the external genitals in female human embryos and foetuses. Part 1: Perineal thick skin, clitoris and labia.

Concomitant with the rupture of the cloacal membrane in the 6th week of development, the intermediate layer of the perineal-skin epithelium thickens. We investigated its distribution and the development of the corresponding subcutaneous compartments in serial sections of female human embryos and foetuses and prepared 3D reconstructions to establish topographic relations. The thick-skin area becomes restricted to the outlets of the genital and intestinal tracts. The clitoris and labia majora become identifiable at ~7 weeks. The mesenchymal mass inside the clitoris soon divides into the glans and the cavernous bodies. The clitoral hood forms between 10 and 14 weeks as a fold of tissue that extends from proximal to distal over the glans. Due to the caudal bending of the clitoral shaft, the labia majora gradually cover the clitoris after ~14 weeks. The labia minora form at ~8 weeks from the ridges of thick-skin epithelium that flank the genital exit. They are continuous ventrolaterally with the clitoral hood and ventromedially with the apex of the cavernous body. Dorsally, their dense subcutaneous mesenchymal core extends to the anal canal. Between 8 and 14 weeks, the urethra lengthens axially, while the vaginal vestibule extends ventrally. In this period, the urethral plate of female embryos is mitotically active but does not increase in volume, which suggests that it contributes to vestibular growth. In conclusion, we observed a temporal correlation between the development of the thick-skin epithelium and that of the external genitals, with a distribution that is reminiscent of the dihydrotestosterone-sensitive skin.

Comparison of Outcomes of Bell’s Palsy Patients Treated with Steroid and Steroid with Antiviral Drug in a Tertiary Care Hospital

Background: Bell’s palsy is the most common acute mononeuropathy associated with idiopathic unilateral facial weakness, characterized by facial asymmetry. Though steroids have effectiveness in managing Bell’s palsy, the use of antiviral is still debatable. Objective: To compare the outcome of Bell’s palsy with treatment by steroid versus combination of steroid and antiviral drugs. Methodology: A prospective analytical study was performed on 84 patients with acute Bell’s palsy attending at Neurology outpatient department of Mymensingh Medical College Hospital from July 2014 to June 2016. The patients were divided into two groups purposively after initial assessment as per House-Brackmann grading system (HBS). Group-I patients were treated with oral prednisolone and oral valacyclovir and Group-II patients were treated with oral prednisolone only. Both groups received facial exercises as per demonstration and proper eye care throughout the study period. Follow-up was done after 2 weeks, 4 weeks and 3 months for collection of data about recovery according to reassessment. Results: The analysis revealed that recovery rates at all 3 follow-ups were higher in the combination group than that of the prednisolone-only group [29(67.44%) versus 18 (43.90%) at 2nd week follow-up, 35(81.39%) versus 25(60.97%) at 4th week follow up and 40 (93.02%) versus 30(73.17%) at 3rd month follow-up]. Moreover, the expected recovery rate was higher in severe Bell’s palsy patients in the combination group than in steroid-alone group (22, 88.0% complete recovery versus 13, 54.17% complete recovery at the end of 3 months of treatment) [p=0.034]. haemorrhagic shock, spinal cord damage, septic shock and crush syndrome. Conclusion: The study showed antiviral (valacyclovir) plus steroid (prednisolone) to be more effective than steroid (prednisolone) alone in the treatment of Bell’s palsy. Moreover, outcome was more favorable in combination groups presenting with severe disease. Lessen their severity. Journal of Monno Medical College December, 2023; 9 (2):58-62

The development of the external genitals in female human embryos and foetuses. Part 2: Vaginal vestibule, anal canal, perineal raphe and perineal cutaneous muscles.

Concomitant with the rupture of the cloacal membrane, the perineal skin epithelium thickens (see accompanying article). In this study, we establish in female embryos and foetuses that the thick skin area divides into ventral and dorsal areas at ~14 weeks and gradually becomes restricted to the vaginal vestibule and anal canal thereafter. The dense mesenchymal core of the labia minora, which forms at ~8 weeks, extends dorsally to the anal canal as a midline reinforcement. The skin epithelium overlying this reinforcement is much thinner than the flanking 'thick skin', and is supported by an interrupted basement membrane, which implies epithelial-mesenchymal transformation of the thin midline epithelium and the subsequent establishment of the perineal raphe by the merging of the adjacent thick epithelium. Meanwhile, the anogenital distance in the perineum increases rapidly in length. Perhaps as a consequence, the labia minora cover only the ventral third of the vaginal vestibule at 20 weeks. The endodermal ducts of Bartholin's glands are identifiable at 7 weeks, while acini form at ~12 weeks. The vestibular bulbs become identifiable at ~10 weeks and form vascular networks after ~14.5 weeks. After the rupture of the cloacal membrane, the diameter of the junction of the dorsal cloaca with the anal canal is just a pinhole but widens dorsoventrally after the 7th week. The cutaneous muscles of the perineal area form as a ventrally open U-shaped mesenchymal mass, from which the anal sphincter and bulbospongiosus muscle develop. In conclusion, our findings show that thick skin epithelium persists in the vaginal vestibule and anal canal.

Impact of core muscle strengthening on knee pain, patient outcomes, physical function, and cartilage thickness in knee osteoarthritis: Protocol for a randomized controlled trial

Knee Osteoarthritis (KOA) is a degenerative condition that significantly impacts individuals, causing disability. Routine rehabilitation methods primarily involve knee and hip strengthening exercises. While there is limited evidence supporting the potential benefits of core muscle strengthening in KOA rehabilitation, further research is needed to examine the effects of a structured core muscle strengthening protocol on pain, functional abilities, quality of life, and knee cartilage health. This double-blind, randomized controlled trial seeks to investigate the impact of integrating core muscle strengthening into routine rehabilitation. The study will randomly assign 80 participants to either routine rehabilitation or experimental groups, with both groups receiving routine rehabilitation combined with core strengthening exercises in the experimental group over a twelve-week period. The outcomes measured will include pain levels, patient-reported outcomes, physical functional abilities, core muscle and leg muscle strength, and cartilage height of the femur and tibia. Follow-up assessments will occur in the 4th, 8th, and 12th weeks. This novel study aims to provide valuable insights into the role of core strengthening in KOA rehabilitation, potentially influencing rehabilitation approaches and managing disease progression.•Incorporating core muscle strengthening into routine rehabilitation for KOA could open new possibilities for KOA management.•This study employs outcome measures recommended by OARSI for a thorough evaluation.•Additionally, it will investigate the impact on cartilage health, offering fresh insights into disease progression and the effects of exercise

Additively manufactured porous Ti6Al4V Alloy with excellent mechanical properties, corrosion resistance, in vitro and in vivo biocompatibility

In view of the insufficient bearing capacity of porous Ti6Al4V (TC4) alloy, four kinds of porous TC4 alloys with a wall thickness of 200 μm and a side length ranging from 400 to 700 μm were designed and subsequently prepared by Additive Manufacturing (Selective Laser Melting, SLM). The results indicated that the porous TC4 alloy was primarily comprised of α' phase and a small amount of β phase. As the side length increased, the size and volume of the acicular α' phase increased while the β phase decreased. Besides, the dislocation density also increased with the increase of side length. The porous TC4 alloy with a side length of 700 μm exhibited the maximum dislocation density of 6.07×1014 m2. The yield strength and elastic modulus initially decreased and then increased with the increase of side length. Moreover, the increase in side length induced the decrease of Icorr from 1.807 × 10−6 to 4.777 × 10−7 A/cm2, especially that sample 7–2 presented the best corrosion resistance with the smallest Icorr value (4.777 × 10−7 A/cm2). It was observed by in vitro assessment that the optical density (OD) of the porous TC4 alloys surpassed 75 % on days 1, 4, and 7. It was noteworthy that the OD value of the porous TC4 alloys with a side length of 700 μm surpassed 100 % on day 7. Furthermore, the number of adherent cells displayed an increasing trend with the increase in side length. After implanting into the alveolar bone of rabbits at 12th week, the porous TC4 alloy with a side length of 700 μm induced bone growth due to a higher percentage of bone volume compared to the dental implant. After 12 weeks of in vivo experiments, the results showed that the porous TC4 alloy could reduce the inflammatory response, promote the growth of bone tissue, and have excellent osteogenic properties.

Uji Potensi Antituberkulosis Ekstrak N-Heksan dan Ekstrak Etanol Daun Jeruk Nipis (Citrus Aurantiifolia) secara in Vitro

Tuberculosis is a disease caused by Mycobacterium tuberculosis which is widely suffered and causes death. Currently, antituberculosis treatment using synthetic chemicals has been widely resistant. The purpose of this study was to test the potential of lime extract to inhibit the growth of tuberculosis bacteria. This research method uses a quantitative approach and is experimental. The results of the study showed that the results of the phytochemical screening test showed the same group of chemical compounds in fresh leaves, simplex and ethanol extract of lime leaves, namely alkaloids, flavonoids, tannins, saponins, steroids and glycosides. While the n-hexane extract only contains steroids and glycosides. Then the effectiveness of antituberculosis can be seen from the ethanol extract being stronger than the n-hexane extract, namely in the 1st week there was inhibition while the n-hexane extract from the 1st week to the 4th week had bacterial growth.

EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT

B-ALL is the most common subtype of childhood Acute Lymphoblastic Leukemia (ALL), affecting approximately 85% of children worldwide. Minimal Residual Disease (MRD) monitoring during treatment of ALL is important for the prognosis of the disease. MRD monitoring, which enables early detection of relapse, determination of risk percentage and understanding the effectiveness of treatment, can be performed with multiple methods such as flow cytometry, qRT-PCR and NGS. Asparaginase is an enzyme that has been used in the treatment of ALL since the 1960s, converting asparagine to ammonia and aspartic acid, lowering serum asparagine levels and causing the death of malignant cells. In this study, we investigated the effect of asparaginase added to the ALL IC BFM 2009 treatment protocol in 62 B-ALL patients aged 0-18 years with MRD monitoring by flow cytometry. In our study, Escherichia Coli (E.Coli.) asparaginase was used primarily and PEG-asparaginase was used after allergy development. The effect of asparaginase on treatment was evaluated by evaluating asparagine concentration and asparaginase activity measured at TP1 (4th week after induction treatment) together with MRD levels. As a result of the study, it was observed that the added asparaginase positively affected the treatment and increased the negativity in MRD levels.