Evaluation of the effect of topical chamomile (<Emphasis Type="Italic">Matricaria chamomilla</Emphasis> L.) oleogel as pain relief in migraine without aura: a randomized,double-blind,placebo-controlled,crossover study

Phytotherapy is a source of finding new remedies for migraine. Traditional chamomile oil (chamomile extraction in sesame oil) is a formulation in Persian medicine (PM) for pain relief in migraine. An oleogel preparation of reformulated traditional chamomile oil was prepared and then standardized based on chamazulene (as a marker in essential oil) and apigenin via gas chromatography (GC) and high-performance liquid chromatography (HPLC) methods, respectively. A crossover double-blind clinical trial was performed with 100 patients. Each patient took two tubes of drug and two tubes of placebo during the study. Visual analog scale (VAS) questionnaires were filled in by the patients and scores were given, ranging from 0 to 10 (based on the severity of pain) during 24 h. Other complications like nausea, vomiting, photophobia, and phonophobia were also monitored. There was 4.48?±?0.01 μl/ml of chamazulene and 0.233 mg/g of apigenin in the preparation (by correcting the amount with extraction ratio). Thirty-eight patients in the drug-placebo and 34 patients in the placebo-drug groups (a total number of 72 patients as per protocol) completed the process in the randomized controlled trial (RCT). Adapted results from the questionnaires showed that pain, nausea, vomiting, photophobia, and phonophobia significantly (p?<?0.001) decreased by using chamomile oleogel on the patients after 30 min. Results supported the efficacy of chamomile oleogel as a pain relief in migraine without aura.     

Machine Learning for Cardiovascular Biomechanics Modeling: Challenges and Beyond

Recent progress in machine learning (ML), together with advanced computational power, have provided new research opportunities in cardiovascular modeling. While classifying patient outcomes and medical image segmentation with ML have already shown significant promising results, ML for the prediction of biomechanics such as blood flow or tissue dynamics is in its infancy. This perspective article discusses some of the challenges in using ML for replacing well-established physics-based models in cardiovascular biomechanics. Specifically, we discuss the large landscape of input features in 3D patient-specific modeling as well as the high-dimensional output space of field variables that vary in space and time. We argue that the end purpose of such ML models needs to be clearly defined and the tradeoff between the loss in accuracy and the gained speedup carefully interpreted in the context of translational modeling. We also discuss several exciting venues where ML could be strategically used to augment traditional physics-based modeling in cardiovascular biomechanics. In these applications, ML is not replacing physics-based modeling, but providing opportunities to solve ill-defined problems, improve measurement data quality, enable a solution to computationally expensive problems, and interpret complex spatiotemporal data by extracting hidden patterns. In summary, we suggest a strategic integration of ML in cardiovascular biomechanics modeling where the ML model is not the end goal but rather a tool to facilitate enhanced modeling.

     

Improved COVID-19 ICU admission and mortality outcomes following treatment with statins: a systematic review and meta-analysis

IntroductionApproximately 1% of the world population has now been infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). With cases still rising and vaccines just beginning to rollout, we are still several months away from seeing reductions in daily case numbers, hospitalisations, and mortality. Therefore, there is a still an urgent need to control the disease spread by repurposing existing therapeutics. Owing to antiviral, anti-inflammatory, immunomodulatory, and cardioprotective actions, statin therapy has been considered as a plausible approach to improve COVID-19 outcomes.Material and methodsWe carried out a meta-analysis to investigate the effect of statins on 3 COVID-19 outcomes: intensive care unit (ICU) admission, tracheal intubation, and death. We systematically searched the PubMed, Web of Science, Scopus, and ProQuest databases using keywords related to our aims up to November 2, 2020. All published observational studies and randomised clinical trials on COVID-19 and statins were retrieved. Statistical analysis with random effects modelling was performed using STATA16 software.ResultsThe final selected studies (n = 24 studies; 32,715 patients) showed significant reductions in ICU admission (OR = 0.78, 95% CI: 0.58–1.06; n = 10; I² = 58.5%) and death (OR = 0.70, 95% CI: 0.55–0.88; n = 21; I² = 82.5%) outcomes, with no significant effect on tracheal intubation (OR = 0.79; 95% CI: 0.57–1.11; n = 7; I²= 89.0%). Furthermore, subgroup analysis suggested that death was reduced further by in-hospital application of stains (OR = 0.40, 95% CI: 0.22–0.73, n = 3; I² = 82.5%), compared with pre-hospital use (OR = 0.77, 95% CI: 0.60–0.98, n = 18; I² = 81.8%).ConclusionsThese findings call attention to the need for systematic clinical studies to assess both pre- and in-hospital use of statins as a potential means of reducing COVID-19 disease severity, particularly in terms of reduction of ICU admission and total mortality reduction.     

Induction of strong immune response against a multicomponent antigen of Mycobacterium tuberculosis in BALB/c mice using PLGA and DOTAP adjuvant

A promising strategy for preventing illness and death caused by Mycobacterium tuberculosis (Mtb) is vaccination. In this study, we aimed to evaluate the capacity of a multicomponent vaccine comprising HspX/EsxS‐fused protein, PLGA (poly (lactide‐co‐glycolide)) and DOTAP (1, 2‐dioleoyl‐3‐trimethylammonium propane) in eliciting immune responses against Mtb in BALB/c mice. A preparation of PLGA nanoparticles (NPs) containing fused protein and DOTAP adjuvant was made using double emulsion solvent evaporation (w/o/w) and lipid film hydration methods, respectively. After three subcutaneous immunization of BALB/c mice with various formulations, ELISA technique was used to measure interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) cytokines levels in splenocytes as well as serum anti‐HspX/EsxS IgG1 and IgG2a titers. The results of the current study showed that PLGA/HspX/EsxS/DOTAP formulation was able to induce higher levels of FN‐γ, IgG1, and IgG2a responses compared with BCG as the positive control, HspX/EsxS, HspX/EsxS/DOTAP and PLGA/HspX/EsxS formulations. Our results suggest that PLGA NPs, as delivery system, and DOTAP, as adjuvant, have a good potential to enhance immune responses against HspX/EsxS antigen after subcutaneous immunization of BALB/c mice.     

Sex differences in predictors and regional patterns of brain age gap estimates

The brain‐age‐gap estimate (brainAGE) quantifies the difference between chronological age and age predicted by applying machine‐learning models to neuroimaging data and is considered a biomarker of brain health. Understanding sex differences in brainAGE is a significant step toward precision medicine. Global and local brainAGE (G‐brainAGE and L‐brainAGE, respectively) were computed by applying machine learning algorithms to brain structural magnetic resonance imaging data from 1113 healthy young adults (54.45% females; age range: 22–37 years) participating in the Human Connectome Project. Sex differences were determined in G‐brainAGE and L‐brainAGE. Random forest regression was used to determine sex‐specific associations between G‐brainAGE and non‐imaging measures pertaining to sociodemographic characteristics and mental, physical, and cognitive functions. L‐brainAGE showed sex‐specific differences; in females, compared to males, L‐brainAGE was higher in the cerebellum and brainstem and lower in the prefrontal cortex and insula. Although sex differences in G‐brainAGE were minimal, associations between G‐brainAGE and non‐imaging measures differed between sexes with the exception of poor sleep quality, which was common to both. While univariate relationships were small, the most important predictor of higher G‐brainAGE was self‐identification as non‐white in males and systolic blood pressure in females. The results demonstrate the value of applying sex‐specific analyses and machine learning methods to advance our understanding of sex‐related differences in factors that influence the rate of brain aging and provide a foundation for targeted interventions.     

Effectiveness of ultrasound and median nerve gliding with and without shock-wave therapy in patients with moderate carpal tunnel syndrome

[Purpose] The aim of this research was to see how ultrasound and nerve gliding with and without shock wave therapy effects on clinical and sonographic data of patients with carpal tunnel syndrome (CTS). [Participants and Methods] Forty four patients with moderate carpal tunnel syndrome participated in this research. One group got shock-wave therapy in addition to median nerve glide exercises and ultrasound, whereas the other group received median nerve glide exercises and ultrasound alone. Hand grip strength (HGS), pinch grip strength (PGS), Visual Analogue Scale (VAS)-pain, Boston Questionnaire (BQ), and Cross-sectional area (CSA) of median nerve were examined before and after 10 sessions of treatment. [Results] HGS, PGS, VAS, BQ and CSA of median nerve improved considerably after therapy. [Conclusion] Patients with moderate CTS who received ultrasound and median nerve glide exercises with and without shock-wave therapy improved considerably without preference of adding shock-wave therapy to other treatment.     

Granulocyte Colony-Stimulating Factor for Amyotrophic Lateral Sclerosis: A Randomized,Double-Blind,Placebo-Controlled Study of Iranian Patients

MethodsForty subjects with ALS were randomly assigned to two groups, which received either subcutaneous G-CSF (5 µg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3 months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle testing, ALS Assessment Questionnaire-40, and nerve conduction studies. CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated at baseline.ResultsThe rate of disease progression did not differ significantly between the two groups. The reduction in ALSFRS-R scores was greater in female subjects in the G-CSF group than in their counterparts in the placebo group. There was a trend toward a positive correlation between baseline CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman''s ρ=0.370, p=0.070).ConclusionsWith the protocol implemented in this study, G-CSF is not a promising option for the treatment of ALS. Furthermore, it may accelerate disease progression in females.     

Potential prevention: Aloe vera mouthwash may reduce radiation-induced oral mucositis in head and neck cancer patients

In recent years,more head and neck cancer patients have been treated with radiotherapy. Radiation-induced mucositis is a common and dose limiting toxicity of radiotherapy among patients with head and neck cancers.Patients undergoing radiation therapy for head and neck cancer are also at increased risk of developing oral candidiasis.A number of new agents applied locally or systemically to prevent or treat radiation- induced mucositis have been investigated,but there is no widely accepted prophylactic or effective treatment for mucositis.Topical Aloe vera is widely used for mild sunburn,frostbites,and scalding burns.Studies have reported the beneficial effects of Aloe gel for wound healing,mucous membrane protection,and treatment of oral ulcers,in addition to antiinflammatory,immunomudulation,antifungal,scavenging free radicals,increasing collagen formation and inhibiting collagenase.Herein the author postulates that oral Aloe vera mouthwash may not only prevent radiation-induced mucositis by its wound healing and antiinflammatory mechanism,but also may reduce oral candidiasis of patients undergoing head and neck radiotherapy due to its antifungal and immunomodulatory properties.Hence,Aloe vera mouthwash may provide an alternative agent for treating radiation-induced oral mucositis and candidiasis in patients with head and neck cancers.     

A double‐blind,randomized, controlled trial on N‐acetylcysteine for the prevention of acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation

Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N‐acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double‐blind randomized placebo‐controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day ?6 to day +15. AKI was determined on the basis of the Risk–Injury–Failure–Loss–End‐stage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase‐associated lipocalin (uNGAL) on days ?6, ?3, +3, +9 and +15 as the secondary outcome. Moreover, transplant‐related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non‐parametric methods including Kaplan–Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analysed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant‐related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high‐dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients. Copyright © 2014 John Wiley & Sons, Ltd.