Exploring the link between pyrethroids exposure and dopaminergic degeneration through morphometric, immunofluorescence, and in-silico approaches: the therapeutic role of chitosan-encapsulated curcumin nanoparticles.

Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson's disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE's toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.

Preparation of orodispersible tablets of bosentan using xylitol and menthol as dissolution enhancers.

Bosentan is a drug used to treat pulmonary hypertension via dual endothelial receptor antagonism. Bosentan has a restricted oral bioavailability, a problem that's mostly due to poor solubility and hepatic metabolism. It is extensively used for the elderly and children who require a friendly dosage form like orodispersible tablets. So, the goal of this research work was to hasten the dissolution rate of bosentan to produce an orodispersible tablet with immediate drug release. Bosentan was exposed to ethanol-assisted kneading with a rise of xylitol or menthol concentrations (1:1 and 1:2 molar ratio of bosentan with excipient). In addition to observing the dissolution behavior, the resulting dry products were investigated using Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). The FTIR reflected possible hydrogen bonding with xylitol and menthol. DSC studies reflected a reduction in the enthalpy and Tm. These results with XRD data reflected partial co-amorphization in the case of xylitol and eutaxia in the case of menthol. These modifications were related to an accelerated dissolving rate. The developed systems were fabricated as orodispersible tablets which exhibited immediate release of bosentan. Thus, the current study offered simple co-processing for the preparation of orodispersible bosentan tablets.

Use of potentially inappropriate medication for elderly patients in tertiary care hospital of Riyadh, Saudi Arabia.

Background and objectives: The elderly population is affected by chronic diseases and lifelong medication. The American Geriatrics Society (AGS) Beers Criteria is a comprehensive approach to medication usage in the older population to reduce potentially inappropriate medication (PIM) use. The purpose of this study was to assess the usage of PIMs in elderly patients upon discharge from tertiary care hospital settings in Riyadh, Saudi Arabia, using the AGS Beers Criteria 2019. Methods: The data was obtained from the medical records of 1237 patients (>65 years) who were discharged from medical or surgical wards at two hospitals affiliated with King Abdulaziz Medical City. The data was analyzed to determine the prevalence of PIM prescription, and the proportional odds of the independent factors influencing outcomes were estimated using ordinal regression analysis for criteria 1 and 2, while Binary regression analysis was conducted for criterion 3. Results: There were approximately equal numbers of male and female participants in our study (male: 50.8 % vs. female: 49.2 %). One-third of the patients were above the age of 80 years, with 41 % being between the ages of 70 and 80 years. Moreover, almost 70 % of the samples had chronic illnesses. The overall prevalence of PIMs was 29.2 %, with 11 % of PIMs to be avoided in elderly patients and 17 % to be used with caution in the elderly, while disease-specific PIMs were identified in 1.2 % of the patients. The most common PIM class was proton pump inhibitors (44.41 %), and patients discharged from the surgical unit were more likely to be prescribed PIMs. Proton pump inhibitors (44.41 %) were the most inappropriately prescribed drug class, and patients discharged from the surgical unit were more likely to be prescribed PIMs. Conclusion: The study noticed that male gender, the presence of multiple diseases, and obesity are associated with more than one PIM prescription. There is a need to streamline the surgical department's prescription procedure to eliminate prescription disparities. Prescription monitoring is recommended to avoid medication errors, particularly in patients who are taking multiple medications.

Efficacy and Safety of Variable Treatment Options in the Prevention of Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis.

There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine the most effective possible treatment among the single treatment options or the combined treatment options for decreasing the morbidity and mortality of HE. We evaluated the outcomes by various parameters such as the quality of life, reduction in ammonia, all causes of mortality, adverse events, reversal of minimal HE, and development of overt HE. We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023 for studies that assess various treatment options for HE. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The Cochrane Tool was used to assess the randomized controlled trials' quality (RCT), while the NIH tool was used to assess the quality of the included cohort studies. Utilizing the R software, the network meta-analysis was conducted. In addition to a significant variation in cases of (Lactulose and Rifaximin) compared with Rifaximin (RR= 0.39, 95% CI [0.17; 0.89]), the results demonstrated a significantly lower incidence of overt HE in (Lactulose and Rifaximin) compared with placebo (RR=0.19, 95% CI [0.09; 0.40]). Most arms demonstrated a statistically significant reduction in the incidence of overt HE compared to albumin and placebo. The results also demonstrated a significant reduction in ammonia between L-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07]). This network meta-analysis has significant data for managing subclinical HE in people without a history of overt HE. Our analysis showed that (Lactulose and Rifaximin), followed by (Rifaximin and L-carnitine), followed by (Lactulose and Rifaximin with zinc) were the best combinations regarding overt HE. LOLA reduced ammonia best, followed by Nitazoxanide and finally Lactulose. (Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly.

Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels.

Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.

Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). RESULTS: We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). CONCLUSION: PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.

Concordance between muscle mass assessed by bioelectrical impedance analysis and by muscle ultrasound: a cross-sectional study in a cohort of patients on chronic hemodialysis.

BACKGROUND: Sarcopenia is a common problem in hemodialysis (HD) patients, and it is diagnosed by low muscle mass, strength and/or low physical performance. Muscle ultrasound (US) is a non-invasive portable tool that might be used for assessment of muscle mass. The aim of the current study was to investigate the concordance between muscle US and bioelectrical impedance analysis (BIA) in diagnosis of sarcopenia in HD patients. METHODS: This cross-sectional study included 41 HD patients. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People (EWGSOP). The skeletal mass index was measured by BIA and the muscle strength was measured by handgrip strength. Muscle US was used to measure cross-sectional area (CSA) and thickness of quadriceps and biceps muscles. RESULTS: The current study included 41 patients on HD (25 males), with a mean (SD) age of 44.18 (13.11) years and a median HD duration of 48 months. Sarcopenia was diagnosed in 58.5% of the patients. Patients with sarcopenia had significantly lower quadriceps muscle CSA than those without sarcopenia. The optimal cut-offs of quadriceps muscle CSA for both males and females for the diagnosis of sarcopenia were 2.96 and 2.92 cm2, respectively. CONCLUSION: Sarcopenia is prevalent among Egyptian HD patients. US on quadriceps muscle CSA could be used for diagnosis of sarcopenia in these patients.

CXC chemokine ligand 13 and galectin-9 plasma levels collaboratively provide prediction of disease activity and progression-free survival in chronic lymphocytic leukemia.

The clinical outcome of lymphocytic leukemia (CLL) is quite heterogeneous. The purpose of this observational study was to investigate the clinical merit of measuring plasma galectin-9 and CXCL-13 concentrations as predictors of CLL activity, prognosis, and early indicators of therapeutic response. These biomarkers were compared with other prognostic indicators, progression-free survival (PFS), time to first treatment (TTT), and overall survival (OS) over a follow-up period (4 years). First, plasma galectin-9 and CXCL-13 concentrations were analyzed in CLL patients at the time of diagnosis as well as healthy controls. Compared to controls, CLL patients had significantly higher serum levels of CXCL-13 and galectin-9. Second, we observed that CLL patients with high soluble CXCL-13 and galectin-9 levels had advanced clinical stages, poor prognosis, 17p del, short PFS, short TTT, and therapy resistance. The levels of CXCL-13, ß2-microglobulin, LDH, CD38%, and high grade of Rai-stage were all strongly correlated with the galectin-9 levels. Soluble CXCL-13 and galectin-9 had very good specificity and sensitivity in detecting CLL disease progression and high-risk patients with the superiority of galectin-9 over CXCL-13. Although the two biomarkers were equal in prediction of TTT and treatment response, the soluble CXCL13 was superior in prediction of OS. High CXCL-13 and galectin-9 plasma levels upon CLL diagnosis are associated with disease activity, progression, advanced clinical stages, short periods of PFS, short TTT, and unfavorable treatment response.

Inhaled corticosteroids' effect on COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

Background: More than six million people died due to COVID-19, and 10-15% of infected individuals suffer from post-covid syndrome. Corticosteroids are widely used in the management of severe COVID-19 and post-acute COVID-19 symptoms. This study synthesizes current evidence of the effectiveness of inhaled corticosteroids (ICS) on mortality, hospital length-of-stay (LOS), and improvement of smell scores in patients with COVID-19. Methods: We searched Embase, Web of Science, PubMed, Cochrane Library, and Scopus until Aug 2022. The Cochrane risk of bias tool was used to assess the quality of studies. We evaluated the effectiveness of ICS in COVID-19 patients through measures of mortality, LOS, alleviation of post-acute COVID-19 symptoms, time to sustained self-reported cure, and sense of smell (visual analog scale (VAS)). Results: Ten studies were included in the meta-analysis. Our study showed a significant decrease in the LOS in ICS patients over placebo (MD = -1.52, 95% CI [-2.77 to -0.28], p-value = 0.02). Patients treated with intranasal corticosteroids (INC) showed a significant improvement in VAS smell scores from week three to week four (MD =1.52, 95% CI [0.27 to 2.78], p-value = 0.02), and alleviation of COVID-related symptoms after 14 days (RR = 1.17, 95% CI [1.09 to 1.26], p-value < 0.0001). No significant differences were detected in mortality (RR= 0.69, 95% CI [0.36 to 1.35], p-value = 0.28) and time to sustained self-reported cure (MD = -1.28, 95% CI [-6.77 to 4.20], p-value = 0.65). Conclusion: We concluded that the use of ICS decreased patient LOS and improved COVID-19-related symptoms. INC may have a role in improving the smell score. Therefore, using INC and ICS for two weeks or more may prove beneficial. Current data do not demonstrate an effect on mortality or time to sustained self-reported cure. However, the evidence is inconclusive, and more studies are needed for more precise data.

A Systematic Review and Network Meta-Analysis of the Outcomes of Patients With Total Knee Arthroplasty Using Cemented, Uncemented, or Hybrid Techniques.

In this study, we aim to explore the differences among the three types of fixation methods for the components of the knee joint in patients who underwent total knee arthroplasty (TKA). These methods are cemented, uncemented, and hybrid fixation. Cemented fixation means that a special type of grout is used to attach the components to the bone. Uncemented fixation means that the components are designed to fit tightly into the bone and allow new bone growth to secure them. Hybrid fixation means that a combination of cemented and uncemented fixation is used for different components. We searched four online databases to find studies relevant to our research question. We use the R program (R Foundation for Statistical Computing, Vienna, Austria) for network meta-analysis (NMA) to analyze the data from the studies. We calculate the mean difference (MD) and the 95% confidence interval (CI) for each outcome, which are statistical measures of the difference and the uncertainty between methods. We use these measures for continuous outcomes, meaning they can have any value. For dichotomous outcomes, meaning they can only have two values, we use the risk ratio (RR) and the 95% CI, which are statistical measures of the relative risk and the uncertainty between methods. We assess the quality of randomized controlled trials, which are studies that randomly assign participants to different methods, using the Cochrane Risk of Bias Assessment Tool 1, a tool that evaluates the potential biases in the studies. We include 21 studies, and our analysis shows that cemented TKA reveals a statistically significant decrease in pain with hybrid TKA (MD = -2.82). That said, we find no significant differences between uncemented and cemented or hybrid (MD = -0.80 and -2.02, respectively). The results show that there is no significant difference between uncemented TKA and cemented TKA or hybrid technique (RR = 0.87, 95% CI 0.35-2.14; RR = 0.73, 95% CI 0.22-2.39, respectively). Also, we find no significant difference between cemented TKA and hybrid TKA (RR = 0.84, 95% CI 0.24-2.93). Cemented TKA is associated with a lower risk of deep vein thrombosis (DVT) incidence rate. Moreover, it shows a significant decrease in pain compared to hybrid TKA. Future research is needed to compare among the three interventions.

A Systematic Review and Meta-Analysis of Conventional Versus Robotic-Assisted Total Knee Arthroplasty.

This study aims to compare the outcomes and advantages of total knee arthroplasty (TKA) performed using conventional surgical techniques with those conducted using robotic-assisted methods in terms of operation time, Oxford knee score, range of motion, tourniquet time, and Western Ontario and McMaster Universities Arthritis index. We performed a literature search through five databases, namely, PubMed, Cochrane Central, Scopus, Embase, and Web of Science, from inception until July 3, 2023. Randomized clinical trials (RCTs) and cohorts comparing conventional TKA with robotic-assisted TKA were included. The risk of bias of the included RCTs was determined using the Cochrane risk of bias tool and the National Institutes of Health tool for cohort studies. We conducted a meta-analysis using Review Manager 5.4. To analyze continuous data, we calculated the mean difference (MD) along with its corresponding 95% confidence interval (CI). By synthesizing data from a comprehensive analysis, the study unveiled noteworthy distinctions between robotic-assisted arthroplasty and conventional arthroplasty across critical parameters. First, a substantial alteration in the hip-knee-ankle (HKA) angle was observed, with the robotic-assisted approach demonstrating a significant difference (MD = 0.84, 95% CI = 0.25-1.43, p = 0.005). Second, in terms of operative time, a notable reduction in surgical duration was noted with conventional TKA (MD = 16.85, 95% CI = 8.08-25.63, p = 0.0002). The assessment of tourniquet time exhibited a significantly longer duration for robotic-assisted arthroplasty (MD = 35.70, 95% CI = 27.80-43.61, p < 0.001). Our findings indicate that conventional TKA outperforms robotic-assisted TKA, primarily due to its shorter operative and tourniquet times, along with a more favorable change in the HKA angle. However, it is worth noting that robotic-assisted TKA showed a slight advantage in pain outcomes, although this advantage was not statistically significant. To gain a more comprehensive understanding, we recommend conducting a large-scale randomized controlled trial that directly compares both TKA methods. This trial should evaluate costs and long-term outcomes while ensuring consistent follow-up durations among studies. Such an approach would greatly assist orthopedic decision-making and contribute to improved TKA outcomes.

Robotic Versus Conventional Unicompartmental Knee Surgery: A Comprehensive Systematic Review and Meta-Analysis.

Robotic-assisted surgery is a computer-controlled technique that may improve the accuracy and outcomes of unicompartmental total knee arthroplasty (TKA), a partial knee replacement surgery. The purpose of a meta-analysis about robotic-assisted versus conventional surgery for unicompartmental TKA is to compare the effectiveness of these two methods based on the current evidence. Our meta-analysis can help inform clinical decisions and guidelines for surgeons and patients who are considering unicompartmental TKA as a treatment option. We searched four online databases for studies that compared the two methods until March 2023. We used RevMan software to combine the data from the studies. We calculated the mean difference (MD) and the 95% confidence interval (CI) for each outcome, which are statistical measures of the difference and the uncertainty between the two methods. We included 16 studies in our analysis. We found that robotic-assisted surgery had a better hip-knee-ankle angle, which is a measure of how well the knee is aligned, than conventional surgery (MD = 0.86, 95% CI = 0.16-1.56). We also found that robotic-assisted surgery had a better Oxford Knee score, which is a measure of how well the knee functions, than conventional surgery (MD = 3.03, 95% CI = 0.96-5.110). This study compared the results of conventional and robotic-assisted unicompartmental knee arthroplasty in 12 studies. We concluded that robotic-assisted surgery may have some benefits over conventional surgery in terms of alignment and function of the knee. However, we did not find any significant difference between the two methods in terms of other outcomes, such as pain, range of motion, health status, and joint awareness. Therefore, we suggest that more research is needed to confirm these results and evaluate the long-term effects and cost-effectiveness of robotic-assisted surgery.

The efficacy and safety of direct factor Xa inhibitors versus vitamin K antagonists for atrial fibrillation in patients on hemodialysis: a meta-analysis of randomized controlled trials.

Background: Direct factor Xa inhibitors have been extensively prescribed for multiple indications; however, hemodialysis patients have been excluded from most of the randomized controlled trials (RCTs) of direct factor Xa inhibitors. Therefore, the efficacy and safety of direct factor Xa inhibitors versus vitamin K antagonists (VKAs) in hemodialysis patients is uncertain. Methods: A systematic review and meta-analysis of RCTs was conducted by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through November 25, 2022. We used the fixed-effect model to pool the risk ratio (RR) with a 95% confidence interval (CI). RevMan v5.4 software was used to pool dichotomous outcomes using RR and continuous outcomes using mean difference presented with the corresponding CI. Results: Three RCTs with a total of 341 patients were included in our analysis. There was no difference between direct factor Xa inhibitors and VKAs regarding all-cause mortality (RR, 0.99; 95% CI [0.76, 1.30]; P = 0.96), cardiovascular mortality (RR, 1.35; 95% CI [0.71, 2.60]; P = 0.36), noncardiovascular mortality (RR, 0.75; 95% CI [0.53, 1.05]; P = 0.09), sudden mortality (RR, 1.33; 95% CI [0.53, 3.33]; P = 0.54), any cerebrovascular event (RR, 0.52; 95% CI [0.21, 1.29]; P = 0.16), ischemic stroke (RR, 0.51; 95% CI [0.19, 1.37]; P = 0.18), and hemorrhagic stroke (RR, 0.61; 95% CI [0.10, 3.70]; P = 0.59). Conclusion: In patients with atrial fibrillation who are on hemodialysis, direct factor Xa inhibitors and VKAs were similar in terms of efficacy and safety outcomes. However, evidence is still sparse, warranting dedicated RCTs.

Lidocaine Infusion Versus Duloxetine for Prevention and Management of Taxane-Induced Peripheral Neuropathy among Breast Cancer Patients-A Randomized Controlled Study.

BACKGROUND: Taxane-induced peripheral neuropathy (TIPN) among breast cancer patients is considered one of the most devastating side effects affecting compliance to chemotherapy protocol and patients' quality of life (QOL). OBJECTIVES: This trial aimed to evaluate the effect of lidocaine infusion vs oral duloxetine on the incidence and severity of TIPN and QOL in patients with breast cancer scheduled for neoadjuvant taxane therapy (TT). STUDY DESIGN: Prospective, randomized, single-blinded, controlled trial. SETTING: This study was carried out on 60 patients with breast cancer scheduled for 12 weeks of TT at the Medical Research Institute Hospital, Alexandria University after obtaining local Ethics Committee approval (IORG008812) and getting a written informed consent from each patient. It was registered in the "clinical trials library for protocol registration and results system" with the number NCT04732455. METHODS: Sixty women scheduled for TT weekly for 12 weeks, were randomly allocated to receive intravenous saline infusion in the control group (GC), or lidocaine 2mg/kg with saline infusion in the lidocaine group (GL), or saline infusion and 30 mg duloxetine in the duloxetine group (GD). All infusions were administered over 40 minutes before each TT. Oral duloxetine was prescribed once daily starting from the night before commencing TT and continued for 12 weeks. Douleur Neuropathique en 4 Questions (DN4) questionnaire was filled weekly to detect the incidence of neuropathic pain (NP). The nerve conduction study (NCS) aimed to detect and measure the degree of neuropathy before starting the chemotherapy protocol and post-12 weeks of Taxol Therapy. NP Scale was measured weekly to assess the severity of NP symptoms. Patients' QOL was evaluated by the European Organization for Research and Treatment of Cancer QOL Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-Item Scale. RESULTS: Thirty-five percent of patients reported DN4 > 4 points in GC after 6 weeks of TT in comparison to 5% in GL and 0% in GD (P = .005). Moreover, the incidence rose to 75% in GC compared to 20% in GL and 25% GD at the end of TT (P < 0.001). The severity of symptoms, global pain intensity, and patients' unpleasantness were significantly more in GC than GL and GD in the last 4 weeks of TT (P < 0.05). NCS showed that 55% and 25% of patients developed mild and moderate axonal neuropathy, respectively, in GC. In contrast, mild neuropathy was developed in 20% and 25% of patients in GL and GD, respectively, and moderate neuropathy in 5% in both groups. The negative impact of TT on QOL was more significant in GC than GL and GD at weeks 8 and 12 of TT (P < 0.001). LIMITATIONS: Limited reference data for all treatment regimens to include in the Discussion section. CONCLUSIONS: Lidocaine and duloxetine have a comparable effect to decrease the incidence and severity of TIPN. Moreover, patients' QOL was significantly better in both groups. KEY WORDS: Lidocaine infusion, duloxetine, taxane-induced peripheral neuropathy, breast cancer, DN4.

Efficacy of prostaglandin E2 versus prostaglandin F2 alpha assisted with narrowband-UVB in stable vitiligo.

In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work to compare the significance of two different subtypes of prostaglandins [prostaglandin E2 (PGE2) versus prostaglandin F2 alpha (PGF2α)], assisted with NB-UVB phototherapy, in treatment of stable vitiligo. This study was conducted on 30 patients with stable non-segmental vitiligo. Three approximately similar vitiliginous areas were chosen in each patient and assigned into 3 groups. Each group treated with intradermal injection of either PGE2 (group I), PGF2α (group II), or saline as placebo (group III) at frequency once/week for 12 weeks. Concomitantly, all groups received NB-UVB phototherapy twice weekly for 3 months. The outcomes of this study discovered that the therapeutic efficacy of intradermal injection of either PGE2 or PGF2α assisted with NB-UVB phototherapy was comparable with non-significant difference between them in spite of being significantly higher than NB-UVB alone. However, there were a significantly earlier onset of repigmentation and higher degree of satisfaction regarding areas treated with PGE2 than those treated with PGF2α. In conclusion, both PGF2α and PGE2 intradermal injection could be considered as quite simple and affordable techniques in the treatment of stable vitiligo with no reported side effects and good patient satisfaction.

Topical Oxybutynin 3% Gel Versus Aluminum Chloride 15% Lotion in Treatment of Primary Focal Hyperhidrosis.

INTRODUCTION: Hyperhidrosis is excessive sweating beyond thermoregulatory needs. It is a potentially disabling condition with challenging management. Aluminum chloride is the established topical treatment; however, response remains unsatisfactory. Oxybutynin is an anticholinergic drug that stands as a therapeutic chance for hyperhidrosis. OBJECTIVES: comparing the efficacy of topical oxybutynin 3% gel versus aluminum chloride 15% lotion in treatment of primary focal hyperhidrosis. METHODS: Forty patients with hyperhidrosis were randomly distributed into 2 equal groups treated by either topical oxybutynin 3% gel or topical aluminum chloride 15% lotion once daily night application for 4 weeks (both groups). Evaluation was done at 2 and 4 weeks of treatment and after 1 month of the end of treatment for follow up by Minor iodine starch test, hyperhidrosis disease severity scale (HDSS) and dermatology life quality index (DLQI). RESULTS: Both treatment modalities were effective with insignificant differences between patients of both groups regarding improvement in Minor iodine starch test and HDSS after 2 weeks of treatment (P = 0.561, 0.33 respectively). Oxybutynin 3% gel yielded significantly better improvement of Minor's test, HDSS and patient's quality of life at the end of 4 weeks of treatment with lower recurrence rate than aluminum chloride 15% lotion at 1 month follow up. Minimal adverse effects were noted in both studied groups. CONCLUSIONS: Oxybutynin 3% gel could be considered as a promising treatment modality for hyperhidrosis with higher efficacy than aluminum chloride 15% lotion and lower recurrence rate.

Safety and efficacy of total ankle arthroplasty versus ankle arthrodesis for ankle osteoarthritis: A systematic review and meta-analysis.

Osteoarthritis is the most common joint disease-causing pain and disability, and its management keeps creating a debate. So, we aimed to compare the safety and efficacy of total ankle arthroplasty and ankle arthrodesis for ankle osteoarthritis. We searched PubMed, Cochrane, Scopus, and Web of Science till August 2021. The outcomes were pooled as Mean difference (MD) or Risk Ratio (RR), and 95% confidence interval. We included 36 studies. The results showed a significantly lower risk of infections in total ankle arthroplasty (TAA) than ankle arthrodesis (AA) (RR= 0.63, 95% CI [0.57, 0.70], p < 0.00001), amputations (RR= 0.40, 95% CI [0.22, 0.72], p = 0.002), postoperative non-union (RR= 0.11, 95% CI [0.03, 0.34], p = 0.0002), and a significant increase of overall range of motion in TAA than AA. Our results preferred total ankle arthroplasty over ankle arthrodesis in terms of lowering the rates of infections, amputations, and postoperative non-union, with better change in the overall range of motion.

Design Hybrid Porous Organic/Inorganic Polymers Containing Polyhedral Oligomeric Silsesquioxane/Pyrene/Anthracene Moieties as a High-Performance Electrode for Supercapacitor.

We synthesized two hybrid organic-inorganic porous polymers (HPP) through the Heck reaction of 9,10 dibromoanthracene (A-Br2) or 1,3,6,8-tetrabromopyrene (P-Br4)/A-Br2 as co-monomers with octavinylsilsesquioxane (OVS), in order to afford OVS-A HPP and OVS-P-A HPP, respectively. The chemical structures of these two hybrid porous polymers were validated through FTIR and solid-state 13C and 29Si NMR spectroscopy. The thermal stability and porosity of these materials were measured by TGA and N2 adsorption/desorption analyses, demonstrating that OVS-A HPP has higher thermal stability (Td10: 579 °C) and surface area (433 m2 g-1) than OVS-P-A HPP (Td10: 377 °C and 98 m2 g-1) due to its higher cross-linking density. Furthermore, the electrochemical analysis showed that OVS-P-A HPP has a higher specific capacitance (177 F g -1 at 0.5 A F g-1) when compared to OVS-A HPP (120 F g -1 at 0.5 A F g-1). The electron-rich phenyl rings and Faradaic reaction between the π-conjugated network and anthracene moiety may be attributed to their excellent electrochemical performance of OVS-P-A HPP.

Meta-analysis of the relation between irritable bowel syndrome and antibodies against endogenous gonadotropin-releasing hormone and its receptor.

This meta-analysis assessed the association between gonadotropin hormone-releasing hormone (GnRH) antibodies and irritable bowel syndrome (IBS). We defined a search strategy and implemented it with PubMed, Ovid, Scopus, and Web of Science databases for English language publications. The data were evaluated for acceptability, and randomized controlled studies as well as case-control, cross-sectional, and cohort studies reporting the prevalence of GnRH antibodies in IBS patients were included. The total number of patients in the included studies was 1095: 270 patients in the IBS group and 825 patients in the control group. By comparing the IBS group and the control group, we found a statistically significant association between IBS and the increased prevalence of GnRH IgM antibodies (risk ratio = 2.29, 95% confidence interval = 1.58 to 3.31, P < 0.0001). We also found a statistically significant association between IBS and increased prevalence of GnRH receptor IgM antibodies compared with controls (risk ratio = 3.80, 95% confidence interval = 1.72 to 8.38, P = 0.001). The meta-analysis revealed a statistically significant association between IBS and increased prevalence of GnRH IgM and GnRH receptor IgM antibodies.

Physical therapy interventions for the management of hand tremors in patients with Parkinson's disease: a systematic review.

BACKGROUND: Several physical therapy modalities have been used to improve hand tremors in patients with Parkinson's disease (PD). However, little is known about the efficacy of these techniques. Therefore, we conducted this study to synthesize evidence from published studies on the efficacy of physical therapy techniques for hand tremors in PD patients. METHODS: We followed the PRISMA statement and Cochrane handbook guidelines when conducting this study. We conducted an electronic literature search of PubMed, Cochrane Central Register of Clinical Trials, Web of Science, Ovid, and Embase, and then we selected clinical trials assessing the efficacy of any physical therapy intervention for hand tremors in patients with PD. Study outcomes were extracted, and evidence was synthesized narratively. RESULTS: A total of six modalities described in six studies were included in this systematic review. Out of the six interventions, the tremor's glove and electrical stimulation showed significant improvements in root mean square angular velocity (59% and 43.8%, respectively) and UPDRS tremor score (P < 0.05 for both). Also, eccentric exercises were associated with significant reductions in the mean resting tremor amplitude (P < 0.05). These data were dependent on single studies; therefore, a meta-analysis was not feasible. CONCLUSION: Several physical therapy interventions, such as electrical stimulation, exercises, transcranial low voltage pulsed electromagnetic fields, weights, and virtual reality showed promising results in reducing hand tremors. However, this evidence was based on a limited number of included studies, and more RCTs with larger sample sizes are required to confirm the efficacy of these interventions.