Intrathecal baclofen efficacy for managing motor function and spasticity severity in patients with cerebral palsy: a systematic review and meta-analysis.

BACKGROUND: Spasticity can significantly affect a patient's quality of life, caregiver satisfaction, and the financial burden on the healthcare system. Baclofen is one of only a few options for treating spasticity. The purpose of this study is to investigate the impact of intrathecal baclofen (ITB) therapy on severe40.23 spasticity and motor function in patients with cerebral palsy. METHODS: We conducted a systematic review in PubMed, Scopus, Ovid, and the Cochrane Library in accordance with the PRISMA guidelines. We included studies based on eligibility criteria that included desired participants (cerebral palsy patients with spasticity), interventions (intrathecal baclofen), and outcomes (the Ashworth scales and the Gross Motor Function Measure [GMFM]). The within-group Cohen's d standardized mean differences (SMD) were analyzed using the random effect model. RESULTS: We screened 768 papers and included 19 in the severity of spasticity section and 6 in the motor function section. The pre-intervention average spasticity score (SD) was 3.2 (0.78), and the post-intervention average score (SD) was 1.9 (0.72), showing a 40.25% reduction. The SMD for spasticity reduction was - 1.7000 (95% CI [-2.1546; -1.2454], p-value < 0.0001), involving 343 patients with a weighted average age of 15.78 years and a weighted average baclofen dose of 289 µg/day. The SMD for the MAS and Ashworth Scale subgroups were - 1.7845 (95% CI [-2.8704; -0.6986]) and - 1.4837 (95% CI [-1.8585; -1.1088]), respectively. We found no relationship between the participants' mean age, baclofen dose, measurement time, and the results. The pre-intervention average GMFM (SD) was 40.03 (26.01), and the post-intervention average score (SD) was 43.88 (26.18), showing a 9.62% increase. The SMD for motor function using GMFM was 0.1503 (95% CI [0.0784; 0.2223], p-value = 0.0030), involving 117 patients with a weighted average age of 13.63 and a weighted average baclofen dose of 203 µg/day. In 501 ITB implantations, 203 medical complications were reported, including six new-onset seizures (2.96% of medical complications), seven increased seizure frequency (3.45%), 33 infections (16.26%), eight meningitis (3.94%), and 16 cerebrospinal fluid leaks (7.88%). Delivery system complications, including 75 catheter and pump complications, were also reported. CONCLUSION: Despite the risk of complications, ITB has a significant impact on the reduction of spasticity. A small but statistically significant improvement in motor function was also noted in a group of patients.

Cell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides.

Bioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery and design of bioactive peptides. Yet, suitable experimental approaches are required to validate candidates in high throughput and at low cost. Here, we established a cell-free protein synthesis (CFPS) pipeline for the rapid and inexpensive production of antimicrobial peptides (AMPs) directly from DNA templates. To validate our platform, we used deep learning to design thousands of AMPs de novo. Using computational methods, we prioritized 500 candidates that we produced and screened with our CFPS pipeline. We identified 30 functional AMPs, which we characterized further through molecular dynamics simulations, antimicrobial activity and toxicity. Notably, six de novo-AMPs feature broad-spectrum activity against multidrug-resistant pathogens and do not develop bacterial resistance. Our work demonstrates the potential of CFPS for high throughput and low-cost production and testing of bioactive peptides within less than 24 h.

Early Childhood COVID-19: A Comparative Report of 20,506 Cases.

This report includes a retrospective analysis of 20506 children aged under 6 years old admitted with Coronavirus Disease of 2019 in Iranian hospitals. The total mortality rate was 2.9%, and 5.7% required mechanical ventilation. We demonstrate a higher mortality rate in comparison with existing studies as well as identifying clinical predictors of survival.

Endoscopic Evaluation of De Novo Esophagitis and Barrett's Esophagus, 5 Years After Sleeve Gastrectomy.

PURPOSE: Sleeve gastrectomy (SG) is the most common bariatric procedure worldwide. It has been reported that there is a strong association between SG and the development of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE). This study was conducted to evaluate esophagogastroduodenoscopy (EGD) findings in patients with a history of SG with more than 5-year follow-up. METHODS: This is a retrospective cohort study of prospectively maintained database. Inclusion criteria included patients who underwent SG between April 2015 and March 2016, aged 18 and above, BMI ≥ 40 kg/m2. Patients with 5 years of follow-up were invited to take part in the study and underwent EGD and biopsy. RESULTS: One hundred twenty-six patients were recruited with a mean age of 44.6 ± 11.1 years. After a 5-year follow-up, there were 31 (29.5%) patients with reflux esophagitis. The grades of GERD were A, B, and C in 16 (15.2), 12 (11.4), and 3 (2.9%) patients, respectively. Incidence of BE was 5.7% after 5 years from SG. There was a 16.6% lost to follow-up at 5 years after SG. CONCLUSION: The diagnosis and severity of GERD and the search for BE justify endoscopic surveillance in all long-term post-sleeve patients, regardless of reflux symptoms.

Clinical theranostics applications of photo-acoustic imaging as a future prospect for cancer.

Photoacoustic imaging (PAI) of biological tissue has been a fast developing biomedical multi-wave imaging modality, after its introduction in the mid90s. PAI couples laser excitation to acoustic detection. Especially, in recent years its significant advantages in onco-surgery has attracted much attention due to its ability to detect malignant tissues. Monitoring cancer angiogenesis, assessment of blood oxygen saturation, functional brain imaging, evaluation of cortical blood volume, detection of skin/conjunctival melanoma depth, assessment of met-hemoglobin, investigating tumor hypoxia andcancer lymph node metastases are some of its promising applications. Moreover, as a real-time monitoring strategy, PAI allows intraoperative imaging of micro-metastases and residual islands in onco-surgery. Herein, we provide a brief introduction to biophysics and fundamentals of PAI, potential novel endogenous and exogenous contrast agents, and novel techniques to develop engineered and targeted contrast agents with theranostic applications. We also summarize the clinical trial pipelines for PAI. Furthermore, we discuss the potential obstacles and limitation of PAI theranostic agents for further clinical applications and strategies to overcome these hurdles.

Next-Generation Anti-Angiogenic Therapies as a Future Prospect for Glioma Immunotherapy; From Bench to Bedside.

Glioblastoma (grade IV glioma) is the most aggressive histopathological subtype of glial tumors with inordinate microvascular proliferation as one of its key pathological features. Extensive angiogenesis in the tumor microenvironment supplies oxygen and nutrients to tumoral cells; retains their survival under hypoxic conditions; and induces an immunosuppressive microenvironment. Anti-angiogenesis therapy for high-grade gliomas has long been studied as an adjuvant immunotherapy strategy to overcome tumor growth. In the current review, we discussed the underlying molecular mechanisms contributing to glioblastoma aberrant angiogenesis. Further, we discussed clinical applications of monoclonal antibodies, tyrosine kinase inhibitors, and aptamers as three major subgroups of anti-angiogenic immunotherapeutics and their limitations. Moreover, we reviewed clinical and preclinical applications of small interfering RNAs (siRNAs) as the next-generation anti-angiogenic therapeutics and summarized their potential advantages and limitations. siRNAs may serve as next-generation anti-angiogenic therapeutics for glioma. Additionally, application of nanoparticles as a delivery vehicle could increase their selectivity and lower their off-target effects.

Hurt, tired and queasy: Specific variants in the ATPase domain of the TRAP1 mitochondrial chaperone are associated with common, chronic "functional" symptomatology including pain, fatigue and gastrointestinal dysmotility.

Functional disorders are common conditions with a substantial impact on a patients' wellbeing, and can be diagnostically elusive. There are bidirectional associations between functional disorders and mitochondrial dysfunction. In this study, provided clinical information and the exon sequence of the TRAP1 mitochondrial chaperone were retrospectively reviewed with a focus on the functional categories of chronic pain, fatigue and gastrointestinal dysmotility. Very-highly conserved TRAP1 variants were identified in 73 of 930 unrelated patients. Functional symptomatology is strongly associated with specific variants in the ATPase binding pocket. In particular, the combined presence of all three functional categories is strongly associated with p.Ile253Val (OR 7.5, P = 0.0001) and with two other interacting variants (OR 18, P = 0.0005). Considering a 1-2% combined variant prevalence and high odds ratios, these variants may be an important factor in the etiology of functional symptomatology.

Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome.

Mutations in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases are associated with a range of clinical phenotypes. Here, we report a novel disorder in three adult patients with a phenotype including cataracts, short-stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, and skeletal dysplasia. Using SNP genotyping and whole-exome sequencing, we identified a single likely causal variant, a missense mutation in a conserved residue of the nuclear gene IARS2, encoding mitochondrial isoleucyl-tRNA synthetase. The mutation is homozygous in the affected patients, heterozygous in carriers, and absent in control chromosomes. IARS2 protein level was reduced in skin cells cultured from one of the patients, consistent with a pathogenic effect of the mutation. Compound heterozygous mutations in IARS2 were independently identified in a previously unreported patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome. This is the first report of clinical findings associated with IARS2 mutations.

The effect of oxybutynin on cardiac autonomic modulation in healthy subjects.

PURPOSE: The aim of this study was to assess the various doses of oral oxybutynin on cardiac autonomic modulation by measuring short-term heart rate variability (HRV) indexes during supine rest position. METHODS: Eight male healthy subjects (20-23 years) participated in the double-blind crossover randomized study. The single dose of oxybutynin (2.5, 5 and 10 mg) or placebo was given to the volunteers in four sessions within 5-day intervals. Before and minutes of 30, 60, 90 and 120 after administration, lead II electrocardiogram (ECG) was recorded for 5 min. ECG extracted RR intervals data became the base of the calculation of time domain and frequency domain HRV parameters, which indicate cardiac autonomic activity. Statistical analysis was done by using the nonparametric Wilcoxon and Kruskal-Wallis tests. RESULTS: The data analysis has revealed that MNN (P < 0.001), SDNN (P < 0.05), PNN50% (P < 0.01), RMSSD (P < 0.001), HFnu (P < 0.05) and LF/HF ratio (P < 0.05) values were significantly increased relative to baseline at various time points in all the groups except in placebo group. LFnu (P < 0.05) values were significantly increased relative to baseline at various time points in all the groups except in placebo group. CONCLUSIONS: Our findings have revealed that acute consumption of 2.5, 5 and 10 mg oxybutynin (an anticholinergic compound) in the juvenile healthy male subjects produces a cholinergic effect according to time and frequency domain of HRV indexes.

Expanded genetic codes in next generation sequencing enable decontamination and mitochondrial enrichment.

We have developed a PCR method, coined Déjà vu PCR, that utilizes six nucleotides in PCR with two methyl specific restriction enzymes that respectively digest these additional nucleotides. Use of this enzyme-and-nucleotide combination enables what we term a "DNA diode", where DNA can advance in a laboratory in only one direction and cannot feedback into upstream assays. Here we describe aspects of this method that enable consecutive amplification with the introduction of a 5th and 6th base while simultaneously providing methylation dependent mitochondrial DNA enrichment. These additional nucleotides enable a novel DNA decontamination technique that generates ephemeral and easy to decontaminate DNA.

Study of Iranian breast cancer registration via established online system during 2011.

The present paper reports the results of a project aimed at providing Iran with a an online registry for breast cancer patients. A new ad hoc system/software has been developed in order to collect patients' data from the first visit to follow-up visits, including tests and Herceptin based therapy. The system has been designed to address both healthcare personnel needs, but also decision makers' information needs. After having identified in the country the laboratories performing the specific tests and the pharmacies that distribute Hercepting, the developed software have been installed in order to build the operational network representing the input points for the register. In 8 months of usage the results are: • Total number of Patients: 2240 inhabitant • Total number of doctors have participated in the program: 229 persons • Number of provinces contributing to the project: 17 provinces out of 30. Online registry of breast cancer is country's requirement because this system not only delivers services for laboratories, pharmacies and all physicians for their patients' follow up and monitoring, but also provides ability to access and analyze collected data for managers and experts.

Effect of submaximal aerobic exercise in hypoxic conditions on proteinuria and hematuria in physically trained young men.

INTRODUCTION: Exercise-induced proteinuria is predominantly caused by alterations in renal hemodynamics. The present study was conducted to determine the effect of aerobic exercise in hypoxia on proteinuria and hematuria. MATERIALS AND METHODS: The study population consisted of 17 physically trained healthy young men. They were asked to attend in 4 sets of 30-minute running sessions, separated by 72-hour resting intervals, to attain 70% of maximal heart rate in normoxia (fraction of inspired oxygen of 0.21) and 3 different levels of hypoxia (lower fraction of inspired oxygen equivalent to the heights of 2750 m, 3250 m, and 3750 m above the sea level). Urine samples were collected before exercise and immediately and 1 hour after each session to measure total protein, albumin, beta2-microglobulin, and erythrocyte count. RESULTS: Postexercise urinary total protein, albumin, and beta2-microglobulin showed significant increases compared to basline values, while no significant difference was found in urinary total protein between hypoxia and normoxia conditions. However, there was a significant positive correlation between the amount of albuminuria and the height (P = .01), and a significant difference in beta2-microglobulinuria between normoxia and the simulated 2750-m altitude (P = .007), which disappeared at higher elevations. None of the participants developed hematuria. CONCLUSIONS: Aerobic exercise with moderate intensity in trained men might induce mixed proteinuria with glomerular predominance correlated with height, while tubular component loses this relation at altitudes above 2750 m. Further research on the influence of exercise on urinary abnormalities, particularly in different environmental conditions, is recommended.