6-Methoxyflavone antagonizes chronic constriction injury and diabetes associated neuropathic nociception expression.

Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects.

From desolation to preservation: Investigating longitudinal trends in forest coverage and implications for future environmental strategies.

Pakistan's forest cover is experiencing significant degradation in the ongoing efforts to combat climate change. The current state of the climate catastrophe is acknowledged. Nevertheless, there is a significant lack of readiness to tackle it effectively, especially regarding safeguarding the welfare of forthcoming generations. Pakistan bears significant relevance for future generations in this global crisis. The primary objective of this study is to examine the environmental difficulties faced by Pakistan and emphasize the critical need to safeguard its natural resources, considering the well-being of present and future generations. By using rigorous correlation and robust least squares regression methods, we investigate the complex interplay of financial aid, environmental legislation, precipitation, population growth, foreign direct investment, and afforestation within the time frame spanning from 1990 to 2022. The findings demonstrate that providing financial aid for afforestation initiatives significantly expands forested areas in Pakistan. Furthermore, the expansion of the population, the implementation of rigorous environmental restrictions, and the yearly amount of precipitation all play a role in the augmentation of forest coverage in Pakistan. Nevertheless, an alarming pattern of diminishing forest coverage over the years presents noteworthy obstacles. The importance of governance in promoting afforestation initiatives and sustainable development is highlighted by the emergence of adequate regulatory quality as a key factor. The average amount of precipitation has a discernible beneficial influence, underscoring the significance of climatic factors. The results above emphasize the need to implement cautious water resource management strategies and regulations responsive to climatic conditions. Based on these observations, the study proposes promoting sustainable agricultural and forest management, adopting a well-balanced strategy towards population expansion, implementing regulatory changes, and prudent use of water resources.

Melatonin decreases GSDME mediated mesothelial cell pyroptosis and prevents peritoneal fibrosis and ultrafiltration failure.

Peritoneal fibrosis together with increased capillaries is the primary cause of peritoneal dialysis failure. Mesothelial cell loss is an initiating event for peritoneal fibrosis. We find that the elevated glucose concentrations in peritoneal dialysate drive mesothelial cell pyroptosis in a manner dependent on caspase-3 and Gasdermin E, driving downstream inflammatory responses, including the activation of macrophages. Moreover, pyroptosis is associated with elevated vascular endothelial growth factor A and C, two key factors in vascular angiogenesis and lymphatic vessel formation. GSDME deficiency mice are protected from high glucose induced peritoneal fibrosis and ultrafiltration failure. Application of melatonin abrogates mesothelial cell pyroptosis through a MT1R-mediated action, and successfully reduces peritoneal fibrosis and angiogenesis in an animal model while preserving dialysis efficacy. Mechanistically, melatonin treatment maintains mitochondrial integrity in mesothelial cells, meanwhile activating mTOR signaling through an increase in the glycolysis product dihydroxyacetone phosphate. These effects together with quenching free radicals by melatonin help mesothelial cells maintain a relatively stable internal environment in the face of high-glucose stress. Thus, Melatonin treatment holds some promise in preserving mesothelium integrity and in decreasing angiogenesis to protect peritoneum function in patients undergoing peritoneal dialysis.

The Efficacy of the Transversus Abdominis Plane Block in Abdominoplasty: A Systematic Review and Meta-Analysis.

The transversus abdominis plane (TAP) block is a regional abdominal anaesthetic technique frequently used within non-cosmetic abdominal surgery. Its use in cosmetic abdominoplasty procedures is less frequently documented. The literature is devoid of a meta-analysis to quantitatively amalgamate the results of individual reports analysing the efficacy of TAP block compared to alternative analgesic methods in abdominoplasty surgery. The authors aimed to conduct the first meta-analysis within the literature to evaluate this technique's effectiveness in abdominoplasties. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were referred to conduct this systematic review and meta-analysis. All observational and randomised controlled trials (RCTs) comparing the postoperative outcomes of patients who underwent abdominoplasties with TAP blocks versus no TAP blocks were included in this study. The time taken to first analgesia and the amount of analgesia used were the primary outcome measures. The secondary outcome measures include severity of pain, time to mobilisation, and length of stay. Random effect modelling was used for the analysis. The time taken to the first analgesic was significantly lower in the TAP cohort (p <0.05). In addition, there was a lower incidence of postoperative nausea/vomiting(OR 0.18, 95%CI 0.04 - 0.90, p=0.04). Mean total opioid use and operative time were comparable between the TAP and no TAP groups. A qualitative review of the visual analogue scale for pain amongst the included studies showed that it was lower in the TAP group. The authors report the first meta-analysis within the literature showing the efficacy of the TAP block in abdominoplasties. Further high-quality trials are recommended to further the current evidence base.

Autologous Fat Grafting for Post-mastectomy Pain Syndrome: A Systematic Review and Meta-Analysis.

Fat grafting has been described as a potential treatment for post-mastectomy pain syndrome (PMPS) following oncological breast surgery. The study's aim was to compare and contrast the current literature using a systematic review and meta-analysis to quantify the evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Databases, including MEDLINE, Google Scholar, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials (CENTRAL), were searched. Data synthesis was conducted using Review Manager 5.4 (Cochrane Collaboration, London, UK), with 95% confidence intervals. All randomised controlled trials (RCT) and observational studies comparing lipofilling for PMPS were included. A total of six studies met the inclusion criteria with five articles being used in data analysis for the mean percentage reduction in visual analogue scale (VAS) score. The primary outcome measure was the mean percentage reduction in the VAS pain score. Secondary outcomes included the Neuropathic Pain Symptom Inventory (NPSI) and the quality of life assessments post treatment. Overall, a total of 266 patients received fat transfer for PMPS, and 164 were in the control group. The mean percentage reduction in VAS score was 19.8 (10.82, 28.82; p < 0.0001). Secondary outcomes, including health-related quality of life, showed good outcomes post fat transfer. This involved breast softness, cosmesis, and psychosocial well-being. The results from this meta-analysis suggest that autologous fat grafting is an efficacious treatment for reducing pain caused by PMPS. The authors suggest more high-quality trials are needed to enhance the current evidence base.

Pitavastatin and Lovastatin Exhibit Calcium Channel Blocking Activity Which Potentiate Vasorelaxant Effects of Amlodipine: A New Futuristic Dimension in Statin's Pleiotropy.

Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits' intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods: Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 µM norepinephrine (N.E)-induced contractions were studied in isolated rabbit's aortic strips preparations. Relaxing effects on 80 mM KCL-induced vascular contractions were further verified by constructing Calcium Concentration Response Curves (CCRCs), in the absence and presence of three different concentrations of Pitavastatin and Lovastatin using CCRCs as negative control. Verapamil was used as a standard drug that has L-Type calcium channel binding activity. In other series of experiments, we studied drug interaction(s) among Pitavastatin, Lovastatin, and amlodipine. Results: The results of this study imply that Lovastatin is more potent than Pitavastatin for having comparatively lower EC50 (7.44 × 10-5 ± 0.16 M) in intact and (4.55 × 10-5 ± 0.10 M) in denuded aortae for KCL-induced contractions. Lovastatin amplitudes in intact and denuded aortae for KCL-induced contractions were, respectively, 24% and 35.5%; whereas amplitudes for Pitavastatin in intact and denuded aortae for KCL-induced contractions were 34% and 40%, respectively. A left shift in the EC50 values for the statins was seen when we added amlodipine in EC50 (Log Ca++ M). Right shift for CCRCs state that Pitavastatin and Lovastatin have calcium channel antagonistic effects. Lovastatin in test concentration (6.74 × 10-7 M) produced a right shift in relatively lower EC50 (-2.5 ± 0.10) Log Ca++ M as compared to Pitavastatin, which further confirms that lovastatin is relatively more potent. The right shift in EC50 resembles the right shift of Verapamil. Additive effect of Pitavastatin and Lovastatin was noted in presence of amlodipine (p < 0.05). Conclusions: KCL (80 mM)-induced vascular contractions were relaxed by Pitavastatin and Lovastatin via inhibitory effects on L-Type voltage-gated calcium channels. Lovastatin and Pitavastatin also relaxed Norepinephrine (1 µM)-induced contractions giving an insight for involvement of dual mode of action of Pitavastatin and Lovastatin.

The Efficacy of Antiseptic Treatment of Surgical Drains on Bacterial Colonisation and Surgical Site Infection Post Breast Surgery: A Systematic Review and Meta-Analysis.

Surgical site infection (SSI) is a common complication in women with post-operative drains following breast surgery, with the risk being as high as 19%. The authors aimed to conduct the first meta-analysis to determine the efficacy of antiseptic treatment of drains to reduce the incidence of infections by comparing it to drains with no antiseptic coating. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed with an extensive search of the electronic databases retrieving 114 articles. Four articles met the inclusion criteria. The primary outcome measure was the incidence of SSIs and secondary outcome measures included the incidence of bacterial colonisation in the bulb fluid and drain tube. The incidence of SSIs was significantly lower in the antiseptic group compared to the control (CI 95% 0.09 - 0.82, p = 0.02). In addition, there was a lower incidence of colonisation from both the bulb fluid and drain tube with P values of < 0.00001 and P < 0.0001 respectively. The authors report the first meta-analysis within the literature showing the efficacy of antiseptic treatment of surgical drains on colonisation and SSIs following breast surgery. More high-quality trials are recommended to further the current evidence base.

The Duration of Postoperative Antibiotics in Autologous Breast Reconstruction: A Systematic Review and Meta-Analysis.

Although prophylactic antibiotic use following autologous breast reconstruction post-mastectomy is a common practice, there is no consensus in the literature regarding its duration. Antibiotic stewardship is important to minimise multi-resistant organisms as well as mitigate the associated side effects. Currently, there are no published guidelines regarding the duration of prophylactic antibiotics in autologous breast reconstruction surgery following mastectomy. The authors searched the online literature regarding the administration of antibiotics for autologous breast reconstruction surgery post-mastectomy. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. The primary outcome measure was the incidence of surgical site infections (SSIs). Three studies met the inclusion criteria and included a total of 1,400 patients. Overall, 101 (7.2%) SSIs were observed. There was no significant difference in the rate of SSIs when comparing the use of antibiotics for less than or longer than 24 hours postoperatively (odds ratio = 1.434, p = 0.124). There is no significant difference between SSIs with the use of antibiotics for longer than 24 hours when compared to less than 24 hours. Further studies in the form of randomised controlled trials are required to assess the effects of prophylactic antibiotic duration in autologous breast reconstruction following mastectomy.

Titanium Versus Autologous Bone-Based Cranioplasty: A Systematic Review and Meta-Analysis.

At present, there is no gold standard when looking at reconstructive evidence for cranioplasty with the use of autologous bone as well as other synthetic materials. Titanium has been considered recently as a good option due to its unique properties such as strength and biocompatibility. Numerous studies have previously compared titanium with autologous bone for cranioplasty yet no meta-analysis has been performed within the literature to provide guidelines for craniofacial surgeons. A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of electronic information was conducted to identify all comparative studies of autologous bone vs. titanium implants in cranioplasty following a craniectomy. The primary outcomes were measured as re-operation rates and cosmesis, the secondary outcome measures included the incidence of complications, for example, bone resorption and infection. Five studies were selected, enrolling 323 cases. A high reoperation rate (p > 0.007) was seen in autologous cranioplasty using bone due to the significantly high resorption rate reported in this group. Cosmetic outcomes demonstrated no significant difference between the two groups examined. Finally, costs and infection rates (p > 0.18) were found to be comparable. Overall, titanium implants used in cranioplasty offer lower re-operation rates in comparison to autologous bone grafts whilst there was no major increase in adverse outcomes such as postoperative cost or rates.

Stem Cell Enriched Fat Grafts versus Autologous Fat Grafts in Reconstructive Surgery: Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the outcomes of stem cell-enrichment fat grafting (SCEFG) versus autologous fat grafting (AFG) for reconstructive purposes. METHODS: A systematic review and meta-analysis was performed as per the preferred reporting items for systematic reviews and meta-analyses. Guidelines and a search of electronic information was conducted to identify all Randomised Controlled Trials (RCTs), case-control studies and cohort studies comparing the outcomes of SCEFG versus AFG. Volume retention, fat necrosis, cancer recurrence, redness and swelling, infection, and cysts were primary outcome measures. Secondary outcome measures included patient satisfaction post-surgery, scar assessment, operation time and number of fat grafting sessions. Fixed and random effects modelling were used for the analysis. RESULTS: 16 studies enrolling 686 subjects were selected. Significant differences between the SCEFG and AFG groups were seen in mean volume retention (standardised mean difference = 3.00, P < 0.0001) and the incidence of redness and swelling (Odds Ratio [OR] = 441, P = 0.003). No significant difference between the two groups in terms of fat necrosis (OR = 2.23, P = 0.26), cancer recurrence (OR = 1.39, P = 0.58), infection (OR = 0.30, P = 0.48) and cysts (OR = 0.88, P = 0.91). For secondary outcomes, both cohorts had similar results in patient satisfaction, scar assessment and number of fat grafting sessions. Operation time was longer for the intervention group. CONCLUSIONS: SCEFG offers better outcomes when compared to AFG for reconstructive surgery as it improves the mean volume retention and does not worsen patient satisfaction and surgical complications except for self-limiting redness and swelling. Further clinical trials are recommended to support this argument and validate the use of SCEFG in clinical practice. LEVEL OF EVIDENCE III: 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 .

Evaluating the in-vivo effects of olive oil, soya bean oil, and vitamins against oxidized ghee toxicity.

The aim of this study was to examine the protective role of various lipids (olive and soya oil) and vitamin (E and C) against the toxicity of thermally oxidized ghee in rabbits. Vanaspati ghee was thermally oxidized on a hot plate at 100°C for ten consecutive hours, and the oxidized ghee was stored in a refrigerator at -20°C until administration. Thirty male rabbits were purchased as experimental animals at a local market and were divided into ten corresponding groups of three based on their body weight. The blood samples of 5 ml were collected on day 0, 7, and 14 of the experiment for the analysis of hematological and biochemical serum parameters. We observed that oxidized ghee significantly elevated ALT level by affecting liver hepatocytes. Furthermore, vitamin E rapidly decreased the ALT levels compared to vitamin C and other oils. The oxidized ghee caused a significant increase in cholesterol compared to the other groups. Vitamin E and C showed the best antioxidant activity and decreased cholesterol levels to normal. Histopathological examinations of the normal rabbits' liver sections revealed no significant histological abnormality. The liver of the rabbits fed with oxidized ghee had an intact lobular architecture but the portal tracts showed inflammation and mild fibrosis, the bile ducts showed proliferation, and the hepatocytes showed feathery degeneration. In the liver sections from the groups fed with oxidized ghee and different doses of olive oil inflammation in portal tracts and large vacuoles in the hepatocytes were observed. The group fed with oxidized ghee and vitamin E had intact lobular architecture with no significant histological abnormality in portal tracts but fatty changes were present in the hepatocytes. These findings support the antioxidant activity of vitamins C and E as they reduced liver infection caused by oxidized ghee. It was concluded that oxidized ghee was highly toxic and not safe for consumption. The present study indicated that soya bean oil and vitamin E were more effective in protecting against the toxicity of thermally oxidized ghee than olive oil and vitamin C.

Stem Cell-Enriched Fat Grafts Versus Autologous Fat Grafts for Facial Reconstruction: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study is to compare the outcomes of stem cell-enrichment fat grafting versus routine fat grafting for facial reconstruction purposes. METHODS: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses Guidelines and a search of electronic information was conducted to identify all randomized controlled trials, case control studies, and cohort studies comparing the outcomes of stem cell enrichment fat grafting versus routine fat grafting for facial reconstruction purposes. Volume retention and infection rate were primary outcome measures. Secondary outcome measures included patient satisfaction postsurgery, redness and swelling, fat necrosis, cysts, as well as operation time. Fixed and random effects modeling was used for the analysis. RESULTS: Eight studies enrolling 275 subjects were selected. There was a significant difference between the stem cell enrichment fat grafting and routine grafting groups in terms of mean volume retention (standardized mean difference, 2.49; P < 0.00001). However, there was no significant difference between the 2 groups in the rate of infection (odds ratio, 0.36; P = 0.30). For all secondary outcomes, the intervention group had similar results compared with the control group except for the operation time, which was shorter in the latter. CONCLUSIONS: Stem cell-enriched fat grafting is a superior option when compared with the routine fat grafting for facial reconstruction surgery because it improves the mean volume retention and does not worsen patient satisfaction and surgical complications.

Assessing the pharmacological and biochemical effects of Salvia hispanica (Chia seed) against oxidized Helianthus annuus (sunflower) oil in selected animals.

Oil oxidation is important in terms of taste, nutritive component quality and toxic effect of the oil. In this study, the oxidized sunflower oil was used along with chia seed in rabbits for the determination of its effects on various hematological and serum biochemical parameters as well as on liver histopathology. Three rabbits were fed with oxidized oil (obtained by heating) at the dose rate of 2 ml/kg body weight by mixing it with green fodder. The other rabbit groups were fed with Chia seed at dose rate of 1, 2 and 3 g/kg along with oxidized sunflower oil. Chia seed was fed alone to three rabbits at the dose rate of 2 g/kg body weight. All rabbits were fed regularly for twenty-one days. For the determination of hematological and biochemical parameters, whole blood and serum samples were collected on different days during feeding period. For histopathology, liver samples were used. Significant changes (p<0.05) were noted in the hematology and biochemical indices in the rabbits that were fed with oxidized sunflower oil alone, and along with different doses of Chia seed. In a dose-dependent manner, all these parameters were significantly improved (p<0.05), when the amount of Chia seed was increased. The biochemical and hematological indices were in normal range in the group fed only with Chia seed. In oxidized oil fed group, liver histopathological analysis showed that cholestasis was present at both sides (bile pigment secretion) and zone 3 necrosis with mild inflammatory cells. Mild vacuolization of hepatocytes was also observed. In Chia seed fed group, hepatocyte vacuolization and mild necrosis was noted. It was concluded that oxidized sunflower oil alters the biochemical and hematological parameters and causes liver abnormalities. Chia seeds act as an antioxidant and retrieve those alterations.

Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models.

Alzheimer's disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum of biological properties. In this regard, the antioxidant potentials of mono-carbonyl curcumin analogues (h1−h5) were investigated using in vitro antioxidant assays and hippocampal-based in vivo mouse models such as light−dark box, hole board, and Y-maze tests. In the in vitro assay, mono-carbonyl curcumin analogues h2 and h3 with methoxy and chloro-substituents, respectively, showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethylbenzothiazo-line-6-sulfonate (ABTS) free radical scavenging activities. In the in vivo studies, scopolamine administration significantly (p < 0.001) induced oxidative stress and memory impairment in mice, in comparison to the normal control group. The pretreatment with mono-carbonyl curcumin analogues, specifically h2 and h3, significantly decreased (123.71 ± 15.23 s (p < 0.001), n = 8; 156.53 ± 14.13 s (p < 0.001), n = 8) the duration of time spent in the light chamber and significantly enhanced (253.95 ± 19.05 s (p < 0.001), n = 8, and 239.57 ± 9.98 s (p < 0.001), n = 8) the time spent in the dark compartment in the light−dark box arena. The numbers of hole pokings were significantly (p < 0.001, n = 8) enhanced in the hole board test and substantially increased the percent spontaneous alternation performance (SAP %) in the Y-maze mouse models in comparison to the stress control group. In the biomarker analysis, the significant reduction in the lipid peroxidation (MDA) level and enhanced catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) activities in the brain hippocampus reveal their antioxidant and memory enhancing potentials. However, further research is needed to find out the appropriate mechanism of reducing oxidative stress in pathological models.

Phytochemical Investigation, Antioxidant Properties and In Vivo Evaluation of the Toxic Effects of Parthenium hysterophorus.

Parthenium hysterophorus L. is a poisonous Asteraceae weed. The phytochemical profile, antioxidant activity, total phenolic contents (TPC), total flavonoid contents (TFC), and cytotoxicity of Parthenium hysterophorus L. flower extract were evaluated in this study, and the toxic effects were assessed in rabbits. The HPLC-DAD system was used for phytochemical analysis. The hemolytic and DPPH assays were performed. The effects of orally administering the flower crude extract to rabbits (n = 5) at four different doses (10, 20, 40, and 80 mg/kg) for ten days on hematological and biochemical parameters were investigated. The crude extract of the flower contained phenolic compounds such as Gallic acid, Chlorogenic acid, Ellagic acid, and P Coumaric acid, which were detected at different retention times, according to the HPLC results. With a sample peak of 4667.475 %, chlorogenic acid was abundant. At concentrations of 80 µg, the methanolic extract of flowers had total phenolic contents (89.364 ± 4.715 g GAE/g) and total flavonoid contents (65.022 ± 2.694 g QE/g). In the DPPH free radical scavenging assay, 80 µg of extract had the highest cell inhibition of 76.90% with an IC50 value of 54.278 µg/µL, while in the hemolytic assay 200 µg of extract had the highest cell inhibition of 76.90% with an IC50 > 500. The biochemical and hematological parameters were altered in the flower extract-fed groups as compared to the control (p < 0.05). The toxic effects on the blood, liver, and kidneys were confirmed. The findings also confirmed the presence of phenolic and flavonoid content in the flower extract, both of which contribute to the plant's antioxidant potential.

Insulinotropic Potential of Moxifloxacin and Gemifloxacin: An In Vivo Rabbits Model Study Followed by Randomized Phase I Clinical Trial.

Fluoroquinolones (FQs) have been reported to cause dysglycemia in both diabetic and non-diabetic patients. However, diabetic patients are usually on polypharmacy, so we cannot attribute the dysglycemia specifically to FQs. To answer the question as to whether Moxifloxacin and Gemifloxacin influence blood glucose levels and serum insulin levels or otherwise, rabbits were used as experimental animals in an in vivo model followed by a phase I randomized clinical trial in euglycemic healthy volunteers. The effects on the serum insulin and blood glucose levels in the Moxifloxacin and Gemifloxacin treated groups were, respectively, determined on the fifth day in both the in-vivo rabbits model and in the test subjects of the phase I clinical trial. The effects of these drugs were also checked on the histomorphology of the pancreas in the rabbits. The findings of our study suggest that Moxifloxacin and Gemifloxacin significantly (p < 0.05) reduced the blood glucose levels via a subsequent significant shift in the serum insulin levels both in the in vivo animal model and in the test subjects of the phase I clinical trial. No prominent effects on the beta cells histomorphology were noted in this study. Moxifloxacin showed a more significant effect than Gemifloxacin. The insulinotropic effect was comparable to the effect of Glibenclamide. It is concluded that Moxifloxacin and Gemifloxacin have a significant blood glucose lowering effect mediated through insulinotropic action. (Clinical Trials.gov identifier: NCT04692623).

Comparison of Hand Therapy with or without Splinting Postfasciectomy for Dupuytren's Contracture: Systematic Review and Meta-Analysis.

This study aimed to compare the outcomes of hand therapy alone versus additional splinting post fasciectomy for Dupuytren's contracture patients. A systematic review and meta-analysis were conducted, and a search was performed identifying all relevant studies comparing the two groups. Primary outcome measures included Total active flexion and extension (TAF and TAE) and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Secondary outcome measures included pain intensity, grip strength, and global perceived effect and patients' satisfaction. A random effects model was used for the analysis. Four RCTs were identified enrolling 295 patients. There were no significant differences between hand therapy and splintage groups in terms of all outcomes (both primary and secondary). Splintage offers no added functional benefit to hand therapy alone for post fasciectomy patients with Dupuytren's contracture, however, orthotic regimes may still be applied on an intention to treat basis in those patients who develop an extension deficit postoperatively.