The impact of leptomeningeal collaterals in acute ischemic stroke: a systematic review and meta-analysis.

OBJECTIVES: Leptomeningeal collaterals provide an alternate pathway to maintain cerebral blood flow in stroke to prevent ischemia, but their role in predicting the outcome is still unclear. So, our study aims at assessing the significance of collateral blood flow (CBF) in acute stroke. METHODS: Electronic databases were searched under different MeSH terms from January 2000 to February 2019. Studies were included if there was available data on good and poor CBF in acute ischemic stroke (AIS). The clinical outcomes included were modified Rankin scale (mRS), recanalization, mortality, and symptomatic intracranial hemorrhage (sICH) at 90 days. Data was analyzed using a random-effect model. RESULTS: A total of 47 studies with 8194 patients were included. Pooled meta-analysis revealed that there exist twofold higher likelihood of favorable clinical outcome (mRS ≤ 2) at 90 days with good CBF compared with poor CBF (RR: 2.27; 95% CI: 1.94-2.65; p < 0.00001) irrespective of the thrombolytic therapy [RR with IVT: 2.90; 95% CI: 2.14-3.94; p < 0.00001, and RR with IAT/EVT: 1.99; 95% CI: 1.55-2.55; p < 0.00001]. Moreover, there exists onefold higher probability of successful recanalization with good CBF (RR: 1.31; 95% CI: 1.15-1.49; p < 0.00001). However, there was 54% and 64% lower risk of sICH and mortality respectively in patients with good CBF in AIS (p < 0.00001). CONCLUSIONS: The relative risk of favorable clinical outcome is more in patients with good pretreatment CBF. This could be explained due to better chances of recanalization combined with a lesser risk of intracerebral hemorrhage with good CBF status.

Predictors of 30-day mortality using machine learning approach following carotid endarterectomy.

BACKGROUND: Preoperative prognostication of 30-day mortality in patients with carotid endarterectomy (CEA) can optimize surgical risk stratification and guide the decision-making process to improve survival. This study aims to develop and validate a set of predictive variables of 30-day mortality following CEA. METHODS: The patient cohort was identified from the American College of Surgeons National Surgical Quality Improvement Program (2005-2016). We performed logistic regression (enter, stepwise, and forward) and least absolute shrinkage and selection operator (LASSO) method for the selection of variables, which resulted in 28-candidate models. The final model was selected based upon clinical knowledge and numerical results. RESULTS: Statistical analysis included 65,807 patients with 30-day mortality in 0.7% (n = 466) patients. The median age of our cohort was 71.0 years (range, 16-89 years). The model with 9 predictive factors which included age, body mass index, functional health status, American Society of Anesthesiologist grade, chronic obstructive pulmonary disorder, preoperative serum albumin, preoperative hematocrit, preoperative serum creatinine, and preoperative platelet count-performed best on discrimination, calibration, Brier score, and decision analysis to develop a machine learning algorithm. Logistic regression showed higher AUCs than LASSO across these different models. The predictive probability derived from the best model was converted into an open-accessible scoring system. CONCLUSION: Machine learning algorithms show promising results for predicting 30-day mortality following CEA. These algorithms can be useful aids for counseling patients, assessing preoperative medical risks, and predicting survival after surgery.

Risk factors for clinical and radiological worsening following Chiari malformation type I surgery in the pediatric population.

OBJECTIVE: Foramen magnum (FM) decompression with or without duraplasty is considered a common treatment strategy for Chiari malformation type I (CM-I). The authors' objective was to determine a predictive model of risk factors for clinical and radiological worsening after CM-I surgery. METHODS: A retrospective review of electronic health records was conducted at an academic tertiary care hospital from 2001 to 2019. A multivariable Cox proportional hazards regression model was used to determine the risk factors. The Kaplan-Meier estimate was plotted to delineate outcomes based on FM size. FM was measured as the preoperative distance between the basion and opisthion and dichotomized into < 34 mm and ≥ 34 mm. Syrinx was measured preoperatively and postoperatively in the craniocaudal and anteroposterior directions using a T2-weighted MRI sequence. RESULTS: A total of 454 patients (231 females [50.9%]) with a median (range) age of 8.0 (0-18) years were included in the study. The median duration of follow-up was 21.0 months (range 3.0-144.0 years). The model suggested that patients with symptoms consisting of occipital/tussive headache (HR 4.05, 95% CI 1.34-12.17, p = 0.01), cranial nerve symptoms (HR 3.46, 95% CI 1.16-10.2, p = 0.02), and brainstem/spinal cord symptoms (HR 3.25, 95% CI 1.01-11.49, p = 0.05) had higher risk, whereas those who underwent arachnoid dissection/adhesion lysis had 75% lower likelihood (HR 0.25, 95% CI 0.10-0.64, p = 0.004) of clinical worsening postoperatively. Similarly, patients with evidence of brainstem/spinal cord symptoms (HR 7.9, 95% CI 2.84-9.50, p = 0.03), scoliosis (HR 1.04, 95% CI 1.01-2.80, p = 0.04), and preoperative syrinx (HR 16.1, 95% CI 1.95-132.7, p = 0.03) had significantly higher likelihood of postoperative worsening of syrinx. Patients with symptoms consisting of occipital/tussive headache (HR 5.44, 95% CI 1.86-15.9, p = 0.002), cranial nerve symptoms (HR 2.80, 95% CI 1.02-7.68, p = 0.04), and nonspecific symptoms (HR 6.70, 95% CI 1.99-22.6, p = 0.002) had significantly higher likelihood, whereas patients with FM ≥ 34 mm and those who underwent arachnoid dissection/adhesion lysis had 73% (HR 0.27, 95% CI 0.08-0.89, p = 0.03) and 70% (HR 0.30, 95% CI 0.12-0.73, p = 0.008) lower likelihood of reoperation, respectively. The Kaplan-Meier curve showed that patients with FM size ≥ 34 mm had significantly better clinical (p = 0.02) and syrinx (p = 0.03) improvement postoperatively when the tonsils were resected. CONCLUSIONS: These results showed that preoperative and intraoperative factors may help to provide better clinical decision-making for CM-I surgery. Patients with FM size ≥ 34 mm may have better outcomes when the tonsils are resected.

Evaluating the effectiveness of Moringa oleifera leaf capsules in controlling glycemic and hypertension levels in type 2 diabetes patients.

Moringa oleifera (MO) phytochemicals and therapeutic properties improve hyperglycemia and treat type 2 diabetes. Thus, this study examined the effects of MO leaf capsules on blood glucose management in type 2 diabetic mellitus (T2DM) and hypertension and their safety. A prospective placebo-controlled experiment randomly assigned 24 patients to receive 3g and 6g of MO leaf capsules twice a day or a placebo for three months. Pre- and post-study lab and clinical outcomes were assessed. The placebo control group and 3g MO leaf showed a minor change, whereas 6g and control placebo showed a considerable drop in examined features. MO usage was safe. In T2DM patients, MO leaves lowered blood pressure, requiring further study. MO leaves may help T2DM patients manage blood pressure and blood sugar, according to the study. MO's therapeutic components need more research.

Predictors of hearing functional outcome following surgery for cerebellopontine angle meningioma.

OBJECTIVE: Cerebellopontine angle (CPA) meningiomas can affect hearing function and require expeditious treatment to prevent permanent hearing loss. The authors sought to determine the factors associated with functional hearing outcome in CPA meningioma patients treated with surgery and/or radiation therapy in the form of either stereotactic radiosurgery or stereotactic radiation therapy. METHODS: Consecutive patients with CPA meningiomas who had presented at our hospital from 2008 to 2018 were identified through retrospective chart review. Hearing function (as defined by pure tone average (PTA) and speech discrimination score (SDS) on Audiogram) was assessed before and after surgery for CPA meningioma. Audiograms with PTA > 50 dB and SDS < 69% were defined as poor hearing functional outcome. Multivariable Cox Proportional Hazards Regression Model was used to assess the associations between pre-operative hearing functional assessment and post-operative hearing functional outcomes. RESULTS: The study cohort included 31 patients (80.6% females, with a mean age of 61.3 ± 15.2 years) with a median clinical follow-up of 5 months (range: 1 week-98 months). The mean pre-operative PTA and SDS were 23.8 ± 11.2 dB and 64.4 ± 22.2% respectively. At the last visit, there was significant hearing recovery, with an improvement of 29.7 ± 18.0 dB (p < 0.001) and 87.6 ± 17.8% (p < 0.001) in PTA and SDS respectively. After adjusting for age, gender, tumor volume, location, and tumor classification, Multivariable Cox Proportional Hazards Regression Model was conducted which revealed that patients undergoing surgery through retro sigmoid approach [Hazards Ratio (HR): 32.1, 95% Confidence Interval (CI): 2.11-491.0, p = 0.01] and gross total resection (GTR) (HR: 2.99, 95% CI: 1.09-9.32, p = 0.05) had significantly higher risk of poor hearing functional outcome compared to petrosal approach and near/subtotal resection. Moreover, patients with poor preoperative hearing had 85% higher chance of poor hearing functional outcome postoperatively (HR: 0.15, 95%CI: 0.03-0.59, p = 0.007). CONCLUSION: Postoperative improvement in hearing is a reasonable expectation following surgery for CPA meningioma. Preoperative hearing, surgical approach and extent of surgical resection are predictive factors of postoperative hearing function outcome and can therefore aid in identification of patients at higher risk of hearing loss.

Segmental spinal neurofibromatosis 1: a novel phenotype.

INTRODUCTION: Segmental neurofibromatosis (SNF) is a rare subtype of neurofibromatosis (NF). The disease is characterized by features circumscribed to one or more body cutaneous and/or subcutaneous segments. This is a classic example of somatic mosaicism which occurs by postzygotic mut ation of the NF1 gene late in the course of embryonic development affecting localized neural crest lines in the fetus. Spinal neurofibromatosis, on the other hand, is characterized by histologically proven bilateral neurofibromas of the spinal roots. METHODS: Hereby we describe a novel manifestation of spinal SNF. RESULTS: Our case report demonstrated one patient who had segmental spinal expression of the disease classified as true mosaic/segmental NF1 along with its management plan treated at one of the largest NF1 centers to exist. CONCLUSION: This will aid in understanding the rare clinical presentation and treatment options for this novel phenotype.

Neurotrauma in the Syrian War: analysis of 41,143 cases from July 2013-July 2015.

INTRODUCTION: Despite nearly a decade of conflict, little is known about trauma and injuries resulting from the Syrian war. METHODS: Secondary analysis was conducted of an administrative dataset of patient presentations to a network of 95 war-affected hospitals in Syria from July 2013-July 2015. Logistic regression was performed to identify factors associated with mortality of neurotrauma patients. RESULTS: Of 193,618 overall trauma presentations, 41,143 were for neurotrauma (37,410 head trauma, 1407 spinal trauma, and 3133 peripheral nervous system). There were 31,359 males (76.2%) and 9784 females (23.8%). Males aged 19-30 years (10,113; 24.6%) were the largest single demographic group. Presumed non-combatants including females, elders, and children under 13 years (16,214; 39.4%) were the largest group of patients overall. There were 16,881 (41.0%) presentations with blunt injuries (blunt/crush injuries) and 21,307 (51.8%) patients with penetrating injuries (shrapnel, cut, gunshot). A total of 36,589 patients (89.6%) were treated and discharged from the hospital, 2100 (5.1%) were transferred to another facility, 2050 patients (5.0%) died in-hospital, 26 remained in the hospital (0.1%), and 108 (0.3%) had unknown disposition. The median length of hospital stay was 1 day. There were 4034 (9.7%) neurosurgical procedures documented. Patients with combined neurotrauma and general trauma suffered 30 times higher mortality than neurotrauma alone (aOR: 30.4; 95% CI: 20.8-44.2, p < 0.0001). CONCLUSION: The Syrian War resulted in large volumes of neurotrauma patients. Presumed non-combatants comprised 39.4% of patients who survived to treatment at a facility. Further study is needed on long-term needs of neurotrauma victims of the Syrian war.

Myelomeningocele among Pakistani population.

OBJECTIVE: To investigate the mutation in Vangl1 gene in patients of myelomeningocele. METHODS: The cross-sectional study was conducted from July 2017 to December 2017 in the Dow Diagnostic and Research Laboratory, Karachi, after approval from the ethics review committee of Dow University of Health Sciences, Karachi, and comprised clinically diagnosed infants and 10 healthy individuals from the outpatient department of Jinnah Postgraduate Medical Centre, Karachi. Several anatomical parameters were considered, such as size and site of the cyst. Blood samples were drawn and polymerase chain reaction was conducted for the identification of mutation in Vangl1 gene. Mutation analysis was carried out by aligning the sequence with the reference sequence. RESULTS: Of the 60 subjects, 50(83.3%) were cases with age range 0-10 years, and 10(16.6%) were age matched controls. Majority of the patients 44 (88%) were aged <1 year. Novel mutation in Vangl1 gene was identified at position 239, showing the substitution of valine with glycineV239G. Lumbar region was the most common site for the presentation of myelomeningocele in most of the patients 46(92%). CONCLUSIONS: The rare mutation of myelomeningocele was found present in the sample, and the disease was found mostly in the lumbar region.

Microsurgical resection of foramen magnum meningioma: multi-institutional retrospective case series and proposed surgical risk scoring system.

PURPOSE: Foramen magnum meningiomas (FMMs) are a major surgical challenge, due to relevant surgical morbidity and mortality. The paper aims to review the clinical (symptomatic improvement, complication rate, length of hospital stay) and radiological outcome (completeness of resection) of microsurgical resection of FMMs, and to identify predictors of complications. METHODS: A multi-institutional retrospective review of prospectively maintained database of FMMs included 51 patients (74.5% females) with a median tumor volume of 8.18 cm3 (range, 1.77-57.9 cm3) and median follow-up of 36 months (range, 0.30-180.0 months). Tumors were resected though suboccipital approach (58.8%) or posterior-lateral approaches (39.3%), including far-lateral, extreme lateral and transcondylar approaches. RESULTS: Gross-total resection (GTR) was achieved in 80.4% and 98% of cases did not present tumor regrowth or recurrence. Clinical symptoms improved in 34 patients (66.7%) and worsened in 5 (9.8%). The median length of hospital stay was 5 days. Mortality was null. Postoperative complications developed in 15 patients (29.4%), with cerebrospinal fluid leak (7.8%) and lower cranial nerves deficits (7.8%) as the most frequent. Craniospinal location (p = 0.03), location anterior to the dentate ligament (DL) (p = 0.02), involvement of vertebral artery (VA) (p = 0.03) were significantly associated with complication rate. These three elements allow calculating the Foramen Magnum Meningioma Risk Score (FRMMRS), to estimate the risk of post-operative complications. CONCLUSION: Microsurgical resection allows for high GTR rate and low rate of tumor regrowth or recurrence, despite complications in one third of the patients. The FMMRS allows classifying FMMs and estimating the risk of post-operative complications.

Assessment of the efficacy of teriparatide treatment for osteoporosis on lumbar fusion surgery outcomes: a systematic review and meta-analysis.

Treatment of osteoporosis with medications like teriparatide, a parathyroid hormone, is known to improve bone density and reduce the risk of osteoporotic vertebral fractures. Anecdotal and limited surgical series have described the utility of this treatment for osteoporotic patients prior to spinal fusion surgery, but there is variability in adoption of this strategy as well as consensus regarding optimal treatment duration before and after surgery. In this study, the clinical results of the use of teriparatide for this application are reviewed and critically examined. We conducted a systematic review of electronic databases using different MeSH terms from 1980 to 2020. Pooled and subgroup analyses were performed using fixed and random effect models based upon the heterogeneity (I2). The results were reported as either mean difference (MD) or odds ratio (OR) with 95% confidence interval (CI). A total of 771 patients from 12 studies were identified. Three hundred seventy-seven patients (90.8% females) were treated with teriparatide. Lumbar spinal fusion rates were significantly higher among patients who received teriparatide compared to the non-teriparatide group (OR 2.15, 95%CI 1.56-2.97, p < 0.00001). Subgroup analysis revealed that patients receiving teriparatide demonstrated 2.12-fold and 2.23-fold higher likelihood of fusion compared to those in the bisphosphonate (OR 2.12, 95%CI 1.45-3.11, p = 0.0001) and placebo (OR 2.23, 95%CI 1.22-4.08, p = 0.009) cohorts, respectively. The treatment effect of teriparatide was associated with significantly reduced subsequent vertebral fractures (OR 0.16, 95%CI 0.06-0.41, p = 0.0002), sagittal malalignment (MD - 3.85, 95%CI: -6.49 to - 1.21, p = 0.004), limb visual analogue score (VAS) (MD - 0.36, 95%CI - 0.64 to - 0.09, p = 0.008), and spinal VAS (MD - 0.24, 95%CI - 0.44 to - 0.04, p = 0.02) compared to the non-teriparatide group. Patients using teriparatide had 30% less likelihood of screw loosening at last follow-up compared to the non-teriparatide group; however, this was not statistically significant (OR 0.70, 95%CI 0.43-1.14, p = 0.15). There did not exist any statistically significant difference between the two comparative groups in terms of pseudoarthrosis (OR 0.54, 95%CI 0.24-1.21, p = 0.13), cage subsidence (OR 1.30, 95%CI 0.38-4.52, p = 0.68), and bone mineral density (MD 0.04, 95%CI - 0.19-0.29, p = 0.74) at last follow-up examination. This meta-analysis corroborates the effectiveness of teriparatide resulting in higher fusion rates. Further study is required to determine the optimal duration of treatment and timing of surgery.

Stereotactic radiosurgery for head and neck paragangliomas: a systematic review and meta-analysis.

Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56 years (44-69 years). With a median clinical and radiological follow-up of 44 months (9-161 months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p = 0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r = - 0.4, p = 0.001), right-sided tumor (r = - 0.3, p = 0.03), primary SRS (r = - 0.5, p ≤ 0.001), and initial clinical presentation of hearing loss (r = - 0.4, p = 0.001). To achieve a LC ≥ 90%, a median marginal dose (Gy) of 15 (range, 12-30 Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.

Advances in surgical hemostasis: a comprehensive review and meta-analysis on topical tranexamic acid in spinal deformity surgery.

Tranexamic acid (TXA) is an effective and commonly used hemostatic agent for perioperative blood loss in various surgical specialties. It is being increasingly used in spinal deformity surgery. We aimed to evaluate the safety and efficacy of topical TXA (tTXA) compared to both placebo and/or intravenous (IV) TXA in patients undergoing spinal deformity surgery. We conducted a systematic review of the electronic databases using different MeSH terms from January 1970 to August 2019. Pooled and subgroup analysis was performed using fixed and random-effect model based upon the heterogeneity (I2). A total of 609 patients (tTXA: n = 258, 42.4%) from 8 studies were included. We found that there was a statistically significant difference in terms of (i) postoperative blood loss [mean difference (MD) - 147.1, 95% CI - 189.5 to - 104.8, p < 0.00001], (ii) postoperative hemoglobin level (MD 1.09, 95% CI 0.45 to 1.72, p = 0.0008), (iii) operative time (MD 7.47, 95% CI 2.94 to 12.00, p < 0.00001), (iv) postoperative transfusion rate [odds ratio (OR) 0.39, 95% CI 0.20 to 0.78, p = 0.007], postoperative drain output (MD, - 184.0, 95% CI - 222.03 to - 146.04, p < 0.00001), and (v) duration of hospital stay (MD - 1.14, 95% CI - 1.44 to - 0.85, p < 0.00001) in patients treated with tTXA compared to the control group. However, there was no significant difference in terms of intraoperative blood loss (p = 0.13) and complications (p = 0.23) between the two comparative groups. Furthermore, low-dose (250-500 mg) tTXA (p < 0.00001) reduced postoperative blood loss more effectively compared to high-dose tTXA (1-3 g) (p = 0.001). Our meta-analysis corroborates the effectiveness and safety of tTXA in spinal deformity surgery.

Impact of COVID-19 on neurological manifestations: an overview of stroke presentation in pandemic.

Corona virus disease 2019 (COVID-19) pandemic has become a globally challenging issue after its emergence in December 2019 from Wuhan, China. Despite its common presentation as respiratory distress, patients with COVID-19 have also shown neurological manifestation especially stroke. Therefore, the authors sought to determine the etiology, underlying risk factors, and outcomes among patients with COVID-19 presenting with stroke. We conducted a systematic review of the electronic database (PubMed, Google Scholar, Scopus, Medline, EMBASE, and Cochrane library) using different MeSH terms from November 2019 to June 2020. A total of 39 patients with stroke from 6 studies were included. The mean age of our included patients was 61.4 ± 14.2 years. Majority of the patients (n = 36, 92.3%) with COVID-19 had ischemic stroke, 5.1% (n = 2) had hemorrhagic stroke, and 2.6% (n = 1) had cerebral venous thrombosis at the time of initial clinical presentation. Almost all of the patients presented had underlying risk factors predisposing to stroke which included diabetes mellitus, hyperlipidemia, hypertension, and previous history of cerebrovascular disease. 51.2% (n = 20) of the included patients infected with COVID-19 with stroke died, while remaining patients were either discharged home or transferred to a rehabilitation unit. Exploring the neurological manifestation in terms of stroke among patients with COVID-19 is a step towards better understanding of the virus, preventing further spread, and treating the patients affected by this pandemic.

Association of hepatitis E seropositivity and altered progesterone levels in pregnant women of low socioeconomic status from capital region of Pakistan.

OBJECTIVE: To investigate the seroprevalence of hepatitis E virus infection, risk factors and its association with progesterone levels in pregnant women from low socioeconomic background. METHODS: The cross-sectional study was conducted in Rawalpindi and Islamabad, Pakistan, from January to July 2012, and comprised pregnant asymptomatic healthy females from different clinics and hospitals of the twin cities. Data was collected using a predesigned demographic questionnaire to determine socioeconomic status. Prevalence of anti-hepatitis E virus antibodies and progesterone levels were determined using enzyme-linked immunosorbent assay kits. RESULTS: Of the 90 women, 35(39%) were in the 21-25 year age group, and 55(61%) belonged to low socioeconomic background. The overall prevalence of seropositive hepatitis E virus immunoglobulin-G was 54(60%) and immunoglobulin-M was 12(13.3%). In the first trimester, the levels of progesterone were higher in patients positive for immunoglobulin-M compared to immunoglobulin-G (p<0.001). CONCLUSION: Low socioeconomic status appeared to be a potential risk factor associated with high hepatitis E virus seroprevalence and alterations in the normal progesterone levels during pregnancy.

Elucidation of marine fungi derived anthraquinones as mycobacterial mycolic acid synthesis inhibitors: an in silico approach.

Tuberculosis (TB) is a leading cause of mortality amongst infectious diseases. While the anti-TB drugs can cure TB, the non-compliance and rapidly increasing resistance is of serious concern. The study aimed to search novel potent inhibitor(s) against MabA and PKS18 targets of Mycobacterium tuberculosis (M.tb.) by virtual screening of anthraquinones from marine fungi. The target proteins MabA and PKS18 involved in M.tb. mycolic acid biosynthesis were retrieved from RCSB Protein Data Bank. Chemical structures of 100 marine fungal anthraquinones were retrieved from the PubChem database. These were filtered through Lipinski's rule of five (for druglikeness) and in silico ADME/Tox analysis (for pharmacokinetic properties) and subjected to molecular docking analysis using AutoDock 4.2. The molecular interaction revealed averufin to possess dual inhibitory potential against M.tb. MabA and PKS18 with binding energy of - 8.84 kcal/mol and - 8.23 kcal/mol, and Ki values of 1.79 and 3.12 µM respectively. Averufin exhibits improved drug-like properties, ADMET profile and binding affinity to both targets as compared to control drugs. Our study suggests that averufin a natural anthraquinone, satisfies all the in silico parameters tested and is expected to efficiently inhibit M.tb. mycolic acid pathway. It might therefore emerge as a promising dual-targeted, novel natural anti-TB lead in future.

Stereotactic radiosurgery versus stereotactic radiotherapy in the management of intracranial meningiomas: a systematic review and meta-analysis.

OBJECTIVEStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.METHODSA systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.RESULTSA total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61-1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26-0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21-3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06-4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67-12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4-10 years compared to SRS, but this was not statistically significant (p = 0.29).CONCLUSIONSSRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.

Contrasting effects of biochar, compost and farm manure on alleviation of nickel toxicity in maize (Zea mays L.) in relation to plant growth, photosynthesis and metal uptake.

Nickel (Ni) toxicity in agricultural crops is a widespread problem while little is known about the role of biochar (BC) and other organic amendments like farm manure (FM) from cattle farm and compost (Cmp) on its alleviation. A greenhouse experiment was conducted to evaluate the effects of BC, Cmp and FM on physiological and biochemical characteristics of maize (Zea mays L.) under Ni stress. Maize was grown in Ni spiked soil without and with two rates of the amendments (equivalent to 1% and 2% organic carbon, OC) applied separately to the soil. After harvest, plant height, root length, dry weight, chlorophyll contents, gas exchange characteristics and trace elements in plants were determined. In addition, post-harvest soil characteristics like pHs, ECe and bioavailable Ni were also determined. Compared to the control, all of the amendments increased plant height, root length, shoot and root dry weight with the maximum increase in all parameters by FM (2% OC) treatment. Similarly, total chlorophyll contents and gas exchange characteristics significantly increased with the application of amendments being maximum with FM (2% OC) application. Amendments significantly increased copper, zinc, manganese and iron concentrations and decreased Ni concentrations in the plants. The highest reduction in shoot Ni concentration was recorded with FM (2% OC) followed by BC (2% OC) being 73.2% and 61.1% lower compared to the control, respectively. The maximum increase in soil pH and decrease in AB-DTPA extractable Ni was recorded with BC (2% OC) followed by FM (2% OC). It is concluded that FM (2% OC) was the most effective in reducing Ni toxicity to plants by reducing Ni uptake while BC (2% OC) was the most effective in decreasing bioavailable Ni in the soil through increasing soil pH. However, long-term field studies are needed to evaluate the effects of these amendments in reducing Ni toxicity in plants.

Is telestroke more effective than conventional treatment for acute ischemic stroke? A systematic review and meta-analysis of patient outcomes and thrombolysis rates.

BACKGROUND: Telestroke systems operate through remote communication, providing distant stroke evaluation through expert healthcare providers. The aim of this study was to assess whether the implementation of a telestroke system influenced stroke treatment outcomes in acute ischemic stroke (AIS) patients compared with conventional in-person treatment. AIMS: The study group evaluated multiple studies from electronic databases, comparing telemedicine (TM) and non-telemedicine (NTM) AIS patients between 1999 and 2022. We aimed to evaluate baseline characteristics, critical treatment times, and clinical outcomes. SUMMARY OF REVIEW: A total of 12,540 AIS patients were included in our study with 7936 (63.9%) thrombolyzed patients. Of the thrombolyzed patients, 4150 (51.7%) were treated with TM, while 3873 (48.3%) were not. The mean age of TM and NTM cohorts was 70.45 ± 4.68 and 70.42 ± 4.63, respectively (p > 0.05). Mean National Institute of Health Stroke Scale scores were comparable, with the TM group reporting a non-significantly higher mean (11.89 ± 3.29.6 vs. 11.13 ± 3.65, p > 0.05). No significant difference in outcomes was found for symptoms onset-to-intravenous tissue plasminogen activator (ivtPA) times (144.09 ± 18.87 vs. 147.18 ± 25.97, p = 0.632) and door-to-needle times (73.03 ± 20.04 vs. 65.91 ± 25.96, p = 0.321). Modified Rankin scale scores (0-2) were evaluated, and no significant difference was detected between cohorts (odds ratio (OR): 1.06, 95% confidence interval (CI): 0.89-1.29, p = 0.500). Outcomes did not indicate any significance between both cohorts for 90-day mortality (OR: 1.16, 95% CI: 0.94-1.43, p = 0.17) or symptomatic intracranial hemorrhage (OR: 0.99, 95% CI: 0.73-1.34, p = 0.93). Results between groups were also non-significant when analyzing the rate of thrombolysis with ivtPA (30.86%± 30.7 vs. 20.5%± 18.6, p = 0.372) and endovascular mechanical thrombectomy (11.8%± 11.7 vs. 18.7%± 18.9, p = 0.508). CONCLUSION: The use of telestroke in the treatment of AIS patients is safe with minimal non-significant differences in long-term outcomes and rates of thrombolysis compared with face-to-face treatment. Further studies comparing the different methods of TM are needed to assess the efficacy of TM in stroke treatment.

Tumour suppressor protein sMEK1 links to IRE1 signalling pathway to modulate its activity during ER stress.

The Endoplasmic Reticulum is a pervasive, dynamic cellular organelle that performs a wide range of functions in the eukaryotic cell, including protein folding and maturation. Upon stress, ER activates an adaptive cellular pathway, namely Unfolded Protein Response, that transduces information from ER to nucleus, restoring homeostasis in the ER milieu. UPR consists of three membrane-tethered sensors; IRE1, PERK and ATF6. Among all the UPR sensors, the IRE1 branch acts as a central pathway that orchestrates several pathways to determine cell fate. However, the detailed knowledge underlying the whole process is not understood yet. Previously, we determined the sMEK1 as one of the interacting partners of IRE1. sMEK1 is a protein phosphatase, which has been indicated in a number of critical cellular functions like apoptosis, cell proliferation, and tumour suppression. In this study, we evaluated the role of sMEK1 on the IRE1 signalling pathway. Our data indicate that sMEK1 can inhibit IRE1 phosphorylation under ER stress. This inhibitory effect of sMEK1 could be reflected in its downstream effectors, Xbp1 and RIDD, which are downregulated in the presence of sMEK1. We also found that the repressing effect of sMEK1 was specific to the IRE1 signalling pathway and could be preserved even under prolonged ER stress. Our findings also indicate that sMEK1 can inhibit IRE1 and its downstream molecules under ER stress irrespective of other UPR sensors. These results help to draw the mechanistic details giving insights into different molecular connections of UPR with other pathways.