Unravelling the novel genetic diversity and marker-trait associations of corn leaf aphid resistance in wheat using microsatellite markers.

The study was conducted to identify novel simple sequence repeat (SSR) markers associated with resistance to corn aphid (CLA), Rhopalosiphum maidis L. in 48 selected bread wheat (Triticum aestivum L.) and wild wheat (Aegilops spp. & T. dicoccoides) genotypes during two consecutive cropping seasons (2018-19 and 2019-20). A total of 51 polymorphic markers containing 143 alleles were used for the analysis. The frequency of the major allele ranged from 0.552 (Xgwm113) to 0.938 (Xcfd45, Xgwm194 and Xgwm526), with a mean of 0.731. Gene diversity ranged from 0.116 (Xgwm526) to 0.489 (Xgwm113), with a mean of 0.354. The polymorphic information content (PIC) value for the SSR markers ranged from 0.107 (Xgwm526) to 0.370 (Xgwm113) with a mean of 0.282. The results of the STRUCTURE analysis revealed the presence of four main subgroups in the populations. Analysis of molecular variance (AMOVA) showed that the between-group difference was around 37 per cent of the total variation contributed to the diversity by the whole germplasm, while 63 per cent of the variation was attributed between individuals within the group. A general linear model (GLM) was used to identify marker-trait associations, which detected a total of 23 and 27 significant new marker-trait associations (MTAs) at the p < 0.01 significance level during the 2018-19 and 2019-20 crop seasons, respectively. The findings of this study have important implications for the identification of molecular markers associated with CLA resistance. These markers can increase the accuracy and efficiency of aphid-resistant germplasm selection, ultimately facilitating the transfer of resistance traits to desirable wheat genotypes.

Utilization rates of intravenous thrombolysis for acute ischemic stroke in Asian countries:: A systematic review and meta-analysis.

BACKGROUND: Despite intravenous thrombolysis (IVT) being used for the treatment of acute ischemic stroke (AIS) for over two decades, its accessibility remains limited in various regions of the world. The Asian region, which experiences the highest age-standardized incidence of AIS, currently lacks comprehensive data on the utilization of IVT. AIMS: This study aimed to provide precise estimates of IVT usage for AIS in Asian countries. METHODS: A literature search was conducted on PubMed and Google using appropriate search terms. English language, peer reviewed articles published after 2010 were included in the analysis. The pooled proportion was calculated utilizing the DerSimonian and Laird random-effects model. Additionally, a subgroup analysis was conducted, taking into account factors such as the study's country, the economic status of the country, specific Asian regions, publication year (before 2015 and from 2015 onwards), study location, study setting, hospital stroke protocol, and national stroke guidelines. RESULTS: 67 observational studies with 778,046 patients with AIS were included in the meta-analysis. The overall utilization rate of IVT was found to be 9.1%. High-income countries had a higher rate (11.3%) compared to lower-middle-income (8.1%) and upper-middle-income countries (9%). Central and North Asia had the highest rate (17.5%) and Southeast Asia had the lowest rate (6.8%). Studies conducted after 2015 had a higher thrombolysis rate (11.3%) compared to those before 2015 (1.5%). Presence of hospital stroke protocols (10.7%) and national stroke guidelines (10.1%) were associated with higher thrombolysis rates. CONCLUSION: The overall utilization rate of IVT for AIS in Asia stood at 9.1%, showcasing noteworthy disparities across countries, regions, and income brackets. To improve thrombolysis rates in the region, addressing prehospital delays, increasing public awareness, and implementing stroke protocols and national guidelines are key strategies.

Diagnostic pitfalls in young onset parkinsonism and its unique challenges: A case report from rural Nepal.

Parkinson's disease is a neurodegenerative disease resulting from the loss of dopamine-secreting neurons present in the substantia nigra of the brain. Parkinson's disease is classified as early-onset and late-onset disease based on the time of its presentation. Since young patients with Parkinson's disease have an atypical clinical presentation and have to deal with their careers, raising families, or both at the time of diagnosis and also have a higher risk of drug-related side effects, it poses unique challenges for the patient, clinical team, and community. We present the case of a 40-year-old female with young onset Parkinson's disease from rural Nepal and the challenges faced during and after the disease in a resource-limited setting.

Cervical vagal schwannoma, a rare differential of a neck swelling: A case report.

Cervical vagal schwannoma is a rare clinical entity that requires a different clinical approach than other neck swellings. Magnetic resonance imaging is the preferred initial diagnostic test. Complications may arise due to vagal stimulation in unsuspecting open biopsies. Surgical excision with perioperative vagal monitoring is recommended for the treatment of vagal schwannomas.

Safety and efficacy of endovascular thrombectomy in patients with severe cerebral venous thrombosis: A meta-analysis.

Background: Cerebral venous thrombosis (CVT) is a rare thrombotic condition which is traditionally treated with anti-coagulation therapy. Subsets of patients with severe CVT have been treated with endovascular thrombectomy (EVT). Despite the high estimated mortality associated with severe CVT, there has been only one randomized control trial done regarding safety and efficacy of EVT in severe CVT compared to standard medical management. Evidence in this area is lacking. Objective: The aim of this systematic review is to analyze all existing literature and generate robust information regarding the role of EVT in the management of patients with severe CVT. Methods: This systematic review and meta-analysis followed PRISMA guideline. PubMed, Embase, Google Scholar, and CNKI were searched for eligible studies from 2007 to 2021. Safety and efficacy of EVT were evaluated by meta-analyzing recanalization status, the good functional outcome at follow-up, recurrent CVT, new hematoma. A pooled proportion with a 95% confidence interval was derived from a meta-analysis of various outcomes (CI). Results: A total of 33 studies comprising 610 patients treated with EVT were included for analysis which comprised one randomized control trial, one prospective study and 31 retrospective studies. Based on pooled data, 85% of patients had good functional outcome, 62% had complete recanalization, 5% had all-cause mortality, and 3% had catheter related complications. The efficacy outcomes in this analysis had a significant heterogeneity and a subgroup analysis was also done to explain these findings. The minimum time of follow up was 3 months and varied EVT techniques were used across the studies. Conclusion: This meta-analysis suggests EVT may be safe and efficacious in treating patients with severe CVT. Registration: Our protocol was registered with PROSPERO: International prospective register of systematic reviews with the registration number CRD42021254760.

Safety and efficacy of low-cost alternative urokinase in acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low- and middle income countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS. METHODS: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021. RESULTS: A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; I2 = 0 %; P = 0.18). Symptomatic Intracerebral Hemorrhage (sICH) was found among 1.77 % of patients in the alteplase group compared to 2.83 % of patients in the UK group (OR: 0.84; 95 % CI: 0.56- 1.26; I2 = 0 %; P = 0.41). Similarly, mortality was found among 5.03 % of patients in the alteplase group compared to 5.42 % of patients in the UK group (OR: 0.87; 95 % CI: 0.66-1.14; I2 = 0 %; P = 0.30). CONCLUSION: Our meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.

Amyotrophic lateral sclerosis and retinal changes in optical coherence tomography: A systematic review and meta-analysis.

INTRODUCTION: Increasing evidence suggests Amyotrophic Lateral Sclerosis (ALS) as a widespread pathological process comprising nonmotor features like fatigue, mild sensory symptoms, cognitive decline, and visual impairment. Measurements of retinal nerve fiber layer (RNFL) thickness using Optical Coherence Tomography (OCT) may correlate with the neurodegeneration associated with ALS. In addition to RNFL thickness, other OCT parameters have been explored in the context of diagnosing ALS and predicting disease severity. In this study, we explore the possibility that OCT parameters of patients with ALS may differ significantly from those of healthy controls and thus serve as biomarkers for the disease and its progression. MATERIALS AND METHODS: Between 2010 and 2021, the PubMed and EMBASE databases were examined for English language literature. ALS severity was assessed using the revised ALS functional rating scale (ALSFRS-R). The pooled mean differences in RNFL thickness between ALS patients and controls were calculated using the Standard Mean Difference (Hedges's g) with a 95% confidence interval (CI) in STATA software version 16. RESULTS: Eleven studies were reviewed for data collection. RNFL thickness was not statistically significantly different between ALS patients (n = 412) and controls (n = 376) (Hedges's g = -0.22; 95% CI: -0.51 to 0.07, I2 = 73.04%, p = .14). However, the thickness of inner nuclear layer was significantly different between ALS patients and controls (Hedges's g = -0.38; 95% CI: -0.61 to 0.14, I2 = 14.85%, p = .00). CONCLUSION: Our meta-analysis found that RNFL thickness as a whole or by individual quadrants was not significantly different between ALS patients and controls while the inner nuclear layer (INL) was substantially thinner.

Low-dose alteplase for the management of acute ischemic stroke in South Asians: A systematic review on cost, efficacy and safety.

INTRODUCTION: South Asia is responsible for more than 40% of the stroke burden and stroke mortality in the developing world. South Asia, which is home to one-fourth of the world's population, is the most densely populated and one of the poorest regions. The majority of patients in this region are unable to afford intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). If low-dose alteplase proves effective and safe in South Asians, it may be a more cost-effective treatment option. METHODS: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Researchers searched PubMed, EMBASE, and Google Scholar for English literature from 2005 to 2021. END, ENI, good functional outcome, SICH, and all-cause mortality were used to assess efficacy and safety. RESULTS: In the low-dose alteplase treated patients, different studies reported 32 to 57% ENI 24 h after IVT, and 7% to 9.7% END. At 3 months follow-up, good functional outcome was achieved by 48%-76.92% of low-dose alteplase treated patients. SICH rates ranged from 0% to 16.6% across studies. Asymptomatic ICH occurred in 5-14% of patients. The mortality rate in all included studies varied from none to 25%. CONCLUSION: Our systematic review demonstrates that the use of low-dose alteplase for AIS in the South Asians offer comparable efficacy and reduced risk of SICH at a significantly lower cost than standard alteplase dose. Future well-randomized clinical trials are necessary to validate the findings of our study.

Therapeutic drug level of tacrolimus causing intracranial hemorrhage in a patient with renal transplant.

Tacrolimus is used in solid organ transplant patients to prevent rejection, and no case of intracerebral hemorrhage (ICH) has been reported till date. We report a case of 31-year-old man with diabetes and hypertension for ten years who had a renal transplant four years back; diagnosed with tacrolimus-induced ICH.

Salivary alpha-synuclein as a potential fluid biomarker in Parkinson's disease: A systematic review and meta-analysis.

Introduction: Lewy bodies are the pathological hallmarks of Parkinson's disease. There is a need for effective biomarker that is cost effective, less invasive, and easily reproducible with good sensitivity and specificity and can be used to diagnose the condition early and track its severity and progression. Alpha-synuclein (α-syn), an integral component of the Lewy body, is found in saliva and can be a potential answer to the above concerns. Methods: PubMed, EMBASE, Google Scholar, and CNKI databases, along with additional sites, were searched from January 2010 to August 2021. Standard mean difference (Hedges' g) with 95% CI was used to show an association. Statistical analysis was done using STATA software version 16 (StataCorp). Results: We found a significant reduction in the mean difference of total salivary α-syn among PD patients compared to healthy controls. However, the mean difference of oligomeric α-syn and oligo/total salivary α-syn ratio was significantly increased among PD patients compared to healthy controls. Conclusion: Our systematic review and meta-analysis found that salivary α-syn parameters (total, oligomeric, oligo/total) can be considered a simple, easy-to-use, cost-effective, and reliable diagnostic biomarker for PD and its progression.

Safety and efficacy of intravenous thrombolysis in acute ischemic stroke patients with a history of intracranial hemorrhage: A systematic review and meta-analysis.

Acute ischemic stroke (AIS) is a fatal and debilitating condition killing 2.7 million people each year worldwide. The most commonly used treatment modality for AIS is intravenous thrombolysis (IVT) with alteplase which is indicated for those presenting within 4.5 h of onset. Due to a lack of reliable evidence on harm or benefit, the 2019 American Heart Association/American Stroke Association (AHA/ASA) guidelines consider a history of previous intracranial hemorrhage (ICH) as potentially harmful and no longer an absolute contraindication for IVT in patients with AIS, and the U.S. Food and Drug Administration (FDA) removed chronic ICH as a specific contraindication for IVT from the label in 2015. Despite a shift in guidelines, physicians frequently face the dilemmatic choice whether to administer IVT in this subset of patients due to the risk of symptomatic intracranial hemorrhage (SICH). The benefit of IVT in such patients has not been thoroughly investigated, and there are only a few studies on the subject in the literature to date. We conducted the present meta-analysis in an aim to provide solid evidence on the efficacy and safety of IVT for treating AIS in patients with a history of remote ICH. Our meta-analysis found that IVT improves functional outcomes in AIS patients with prior remote ICH without increasing SICH or all-cause mortality. These findings may contribute to the decision-making process for IVT administration in AIS patients.

Bilateral thalamic infarction following cerebral venous thrombosis in a patient with ulcerative colitis.

Cerebral Venous Thrombosis is a rare extra-intestinal manifestation of ulcerative colitis. Ulcerative colitis is a hypercoagulable state and, if poorly managed, can predispose to thrombosis, including thrombosis of the cerebral veins.

Cerebral venous thrombosis in a patient with adenomyosis: A case report.

Cerebral venous thrombosis can be caused by different conditions such as infectious, structural, hypercoagulable states, hematological, hormonal, collagen, vascular diseases, and oral contraceptive pills among other causes. Adenomyosis has been rarely associated with Cerebral venous thrombosis (CVT). Increased CA-125 and iron deficiency anemia in adenomyosis may predispose to CVT.

An opportunity to improve Acute Ischemic Stroke care in the South Asian region through telestroke services.

The South Asian region accounts for more than 40% of the stroke burden of the developing world and is the highest contributor to global stroke mortality. Despite proven treatment guidelines, the limited number of neurologists, the number of dedicated stroke centers and the fact that most of these facilities are urban-centric renders poor access to thrombolysis in this region, especially in the rural areas. Studies have shown that thrombolysis using telestroke services are comparable to face-to-face thrombolysis. Telestroke, conducted through low-cost media such as smartphones or laptops, may form a cost-effective solution to improve access to appropriate stroke care in a resource-limited setting such as that of the South Asian region.

JAK2 and TET2 Mutation in Polycythemia Vera.

The Ten-Eleven Translocation-2 (TET2) gene, located on chromosome 4q24, has been implicated in hematological malignancies. The TET2 gene shows mutations in variable myeloid malignancies with the involvement of 15% of myeloproliferative neoplasms (MPNs). The inactivation of the TET2 gene in both mice and humans has shown a high degree of deregulation of the hematopoiesis process leading to hematological malignancies. Polycythemia vera (PV), an MPN characterized by increased red blood cell mass, has been associated with the TET2 gene. Furthermore, TET2 genes have been found to facilitate Janus kinase-2 and signal transducer activator of transcription 5, as well as modulate the epigenetic composition of genomic DNA. However, little is known about the role of TET2 mutations in patients with PV. Several studies have been conducted to further assess the significant role of TET2 gene function in various disease processes and prognoses to enhance the management and care of these patients.

Stem Cell Therapy and Its Significance in Pain Management.

Pain management has always been a challenging issue, which is why it has been a major focus of many rigorous studies. Chronic pain which typically lasts for more than three months is prevalent at an astounding rate of 11% to 19% of the adult population. Pain management techniques have gone through major advances in the last decade with no major improvement in the quality of life in affected populations. Recently there has been growing interest in the utilization of stem cells for pain management. Advancement of stem cell therapy has been noted for the past few years and is now being used in human clinical trials. Stem cell therapy has shown promising results in the management of neuropathic, discogenic back, osteoarthritis, and musculoskeletal pain. In this article, we will discuss the role of stem cells in the pain management of the aforementioned conditions, along with the mechanism, adverse effects, and risks of stem cell therapy.

A case report of multiple isolated intradural neurocysticercosis of the lumbo-sacral spine.

INTRODUCTION AND IMPORTANCE: Neurocysticercosis is the most common parasitic infection of the nervous system and it is mostly intracranial. Intradural intramedullary or extramedullary is the rarest involvement of intraspinal cysticercosis. Its isolated involvement is even rare, as it usually has intracranial association. We aim to report a rare case of isolated intraspinal neurocysticercosis and discuss the measures we can take for early management. Despite being an eradicable disease of public health importance, its prevalence is increasing widely in developed countries too. Therefore, we aim to discuss its pathogenesis, mode of spread, and preventive aspects as well. PRESENTATION OF CASE: A 40-year-old woman presented to our hospital with pain over the lower back region radiating to the right thigh. Magnetic Resonance Imaging (MRI) of her lumbosacral spine revealed a cystic lesion at the spinal level L5-S1. We confirmed the diagnosis via Histopathological examination (HPE) following surgery. DISCUSSION: Isolated intradural neurocysticercosis of the spine is extraordinarily rare involvement. It is caused by the larval stage of taenia solium. An MRI is the preferred imaging modality. Due to rarity and nonspecific clinic-radiological findings, diagnosis may often be missed. In our case, MRI revealed a cystic lesion at the L5-S1 level of the spine and multiple cystic lesions at the level were found intra-operatively. Its diagnosis is confirmed by HPE. Treatment can be medical or surgical according to the severity of the disease. CONCLUSION: Although rare, neurocysticercosis can cause irreversible neurological damage. Therefore, surgeons should consider it in the differential diagnosis of intraspinal lesions.

Safety and efficacy of Magnesium Sulfate in the management of Tetanus: A systematic review.

Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality rates in its severe form. Benzodiazepines used to treat muscle spasms pose a high risk of respiratory failure requiring mechanical ventilation, which is unaffordable and inaccessible for many. Magnesium sulfate, a cheap and widely available medication in all urban and rural health centres of LMICs for the treatment of eclampsia, can be used to control muscle spasms and dysautonomia. We thus conducted a systematic review of evidence to assess the safety and efficacy of magnesium sulfate in the treatment of tetanus. Any study published before April 15, 2021, discussing the efficacy and/or safety of MgSO4 infusion in the treatment of tetanus was systemically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our systematic review included data from 13 studies, three were randomised, double-blind and controlled trials. The remaining ten studies were observational; six prospective and four retrospective studies. Our review showed no mortality benefit associated with the use of magnesium sulfate. However, magnesium sulfate was found to be effective in reducing spasms along with diazepam, leading to better control of dysautonomia, reduced need for mechanical ventilation and shorter hospital stay by 3-7 days. The incidence of magnesium toxicity was very low in the studies included.

Role of female community health volunteers in ischemic stroke prevention, identification, referral and rehabilitation in Nepal.

For the past three decades, female community health volunteers (FCHVs) have been at the forefront of Nepal's health map and have contributed significantly to its improving health indicators such as maternal mortality rate and infant mortality rate. Given the changing epidemiology of Nepal and the shift of burden from communicable to non-communicable diseases (NCDs), it is important to revitalize their role with the changing times. The prevalence of ischemic stroke in Nepal is on the rise. However, very few people make it to the hospital within the time frame for thrombolysis and the patient's knowledge about ischemic stroke seems to play a major part. FCHVs can play a significant role in improving ischemic stroke care by raising awareness about the condition, its risk factors, and informing the public about the need for timely treatment. They can help screen for common risk factors such as obesity, hypertension and diabetes as well as monitor for treatment in previously diagnosed individuals. Randomized controlled trials have shown to yield favorable results in NCDs with engagement of FCHVs. With proper training and support, they can play an important role in improving ischemic stroke care in low- and middle-income countries like Nepal.

Low-cost alternatives for the management of acute ischemic stroke in low and middle-income countries.

Acute ischemic stroke (AIS) patients arriving within a suitable time frame are treated with recanalization therapy i.e. intravenous thrombolysis (IVT) with alteplase and/or mechanical thrombectomy (MT). IVT with alteplase is indicated in AIS patients presenting within 4.5 hours of onset regardless of vascular territory involved. MT is indicated in AIS patients presenting within 24 hours of onset with large vessel occlusion in the anterior circulation. However, MT is ludicrously expensive and requires exorbitant setup, devices, and expertise which is not currently feasible in LMICs. Therefore, in LMICs the only feasible recanalization option left for AIS patients is IVT. The cost of IVT varies across the LMICs, however, most of them cost around 2000-5000 USD. Apart from IVT, patients with AIS often have other significant medical costs including those for neuroimaging, intensive care, and prolonged rehabilitative treatment. In LMICs, these costs can only be afforded by a handful of patients. The majority of the LMICs have health insurance in their infancy and family members of AIS patients opt-out IVT due to the economic burden. In general, the current treatment guidelines for AIS are not very useful in LMICs because of cost-related issues among several other factors. In this editorial, we discuss evidence for alternative treatment strategies that can help tackle the rising epidemic of AIS in poor countries by improvising on existing clinical guidelines and seeking alternative treatment regimens.