Assessment of Neurology Residency Program Websites across North America during COVID-19.

With virtual interviews for residency applications, residency program websites have become increasingly important resources for applicants. We evaluated the comprehensiveness of US and Canadian neurology residency program website, comparing this to published rankings of the best neurology and neurosurgery hospitals (for US programs) and number of residency positions (for US and Canadian programs). US program websites were found to be largely more comprehensive than Canadian websites, more extensive websites were associated with better program rankings and fewer residency seats in the US, and US regional differences in comprehensiveness were present. We recommend standardized guidelines to increase website comprehensiveness across programs.

A Pragmatic Scoring Tool to Predict Hydroxyurea Response Among ß-Thalassemia Major Patients in Pakistan.

Despite high prevalence and incidence of ß-thalassemia in Pakistan, there is very limited work on the use of hydroxyurea (HU) in thalassemia patients in the country. This is the first insight regarding genetic profiling of BCL11A and HU responses in Pakistani ß-thalassemia. It correlates single-nucleotide polymorphisms on BCL11A (rs4671393, rs766432) and HBG2 (XmnI), age at first transfusion, and ß-globin mutations with HU response in ß-thalassemia major (BTM). Of 272 patients treated with HU, 98 were complete responders, 55 partial responders, and 119 nonresponders. Our analysis shows that HU response was significantly associated with patients having IVSI-1 or CD 30 mutation (P<0.001), age at first transfusion >1 year (P<0.001), and with the presence of XmnI polymorphism (P<0.001). The single-nucleotide polymorphisms of BCL11A were more prevalent among responders, but could not show significant association with HU response (P>0.05). Cumulative effect of all 5 predicting factors through simple binary scoring indicates that the likelihood of HU response increases with the number of primary and secondary genetic modifiers (P<0.001). Predictors scoring is a pragmatic tool to foresee HU response in patients with BTM. The authors recommend a score of ≥2 for starting HU therapy in Pakistani patients with BTM.

A Systematic Review of Randomized Controlled Trials Comparing Renal Sympathetic Denervation Versus Sham Procedure for the Management of Uncontrolled Hypertension.

ABSTRACT: The efficacy of renal sympathetic denervation (RSD) in the treatment of uncontrolled hypertension (HTN) remains uncertain. A systematic review of randomized controlled trials was performed to evaluate the efficacy and safety of RSD for resistant HTN. PubMed, EMBASE, MEDLINE, Cochrane, Directory of Open Access Journals, CINAHL, and Google Scholar were searched from January 01, 2001, through July 30, 2020. Randomized controlled trials comparing RSD with the sham procedure for uncontrolled HTN were selected. The primary efficacy outcome was the reduction in ambulatory systolic blood pressure. We used random-effects models. Nine prospective clinical trials met the inclusion criteria. The ReSet and Symplicity HTN-3 Trial showed no significant changes because of discrepancies in complete circumferential ablation during RSD. The Relief study, The Radiance HTN solo, and the SPYRAL HTN OFF medical trials showed a significant reduction in systolic blood pressure in the group that had undergone the intervention compared with the sham group attributed to rigorous trial design. In conclusion, our systematic review suggests that efficacy of RSD seems to be superior to sham-controlled interventions provided circumferential denervation is performed. However, difference in efficacy is marginal.

Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile.

Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a-4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1 H NMR and 13 C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+ /K+ -ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.

Metabolomics and marker-based stability studies of methanol extract of seeds of Syzygium cumini L.

Though, herbal medicines are prone to deterioration upon storage due to their complex nature, but less attention has been paid to investigating stability of such products to assign shelf-life. Therefore, the present study aimed to assess the accelerated stability of methanolic extract of seeds of Syzygium cumini. The extract was kept at three different storage conditions (30oC/60% RH, 40oC/75% RH and 60oC/85% RH) for a period of 6 months. The samples withdrawn at 0 (before starting the study), 1, 2, 3, 4 and 6 months were analyzed to get UV-Visible metabolomics fingerprints and determine caffeic acid contents using RP-HPLC. The comparison of metabolomics fingerprints indicated that the extract was stable for 1 month at all the three storage conditions. However, caffeic acid contents were found to be intact for a longer period of time. Following the zero order degradation, caffeic acid was predicted to be stable for more than 3 years, if kept at 25oC. The results of the present study indicate that metabolomes of methanol extract of seeds of Syzygium cumini change very fast, suggesting the development of stable formulations.

Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction.

AIMS: Whole body and myocardial insulin resistance are features of non-insulin-dependent diabetes mellitus (NIDDM) and left-ventricular dysfunction (LVD). We determined whether abnormalities of insulin receptor substrate-1 (IRS1), IRS1-associated PI3K (IRS1-PI3K), and glucose transporter 4 (GLUT4) contribute to tissue-specific insulin resistance. METHODS AND RESULTS: We collected skeletal muscle (n = 27) and myocardial biopsies (n = 24) from control patients (n = 7), patients with NIDDM (n = 9) and patients with LVD (n = 8), who were characterized by euglycaemic-hyperinsulinaemic clamp and positron emission tomography. Comparative studies were carried out in three mouse models. We demonstrate an unrecognized reduction of IRS1 in skeletal muscle of LVD patients and an unexpected increase in cardiac IRS1-PI3K activity in NIDDM and LVD patients. In NIDDM, there was a concomitant reduction in sarcolemmal GLUT4, whereas in patients with LVD sarcolemmal GLUT4 was increased. We confirm activation of IRS1-PI3K and reduction in sarcolemmal GLUT4 in the insulin resistant ob/ob mouse heart where we also demonstrate perturbation of GLUT4 docking and fusion. A direct relationship between PI3K and GLUT4 was demonstrated in mice expressing activated PI3K in the heart and increased GLUT4 at the sarcolemma was confirmed in a mouse model of LVD. CONCLUSION: Our data show that the mechanisms of myocardial insulin resistance are different between NIDDM and LVD.

Gender and Racial Trends Among Vascular Neurology Fellowship Programs: By Design or By Default.

Introduction Benefits of increasing diversity in teams include the addition of different perspectives leading to increased innovation and creativity, faster problem solving, improved workforce morale, and reduced burnout leading to improved patient outcomes. This article reviewed the trend of gender and racial disparity in vascular neurology fellowship programs. Methods We retrospectively analyzed the data extracted from the Accreditation Council for Graduate Medical Education (ACGME)'s annual Data Resource Books from 2007 to 2019. ACGME cataloged gender as men and women and race/ethnicity was categorized as White/Non-Hispanic, Asian or Pacific Island, Hispanic, Black/Non-Hispanic, Native American/Alaskan, others, and unknown. Counts, proportions, relative, and absolute percentage changes were calculated to highlight trends in resident appointments over time and across the specialty of vascular neurology. Results The representation of females increased steadily; with a relative increase of 11.78% from the year 2007 to 2019. Race/ethnicity was reported starting from the year 2011. When averaged across the nine-year study period, 35% of the study sample was White (Non-Hispanic), followed by Asian/Pacific Islanders at 25%. The representation of Hispanics was 4.8%, Black/African Americans were 3%, Native Americans/ Alaskans were 0.23% and Others were 13% of the total study population. For 17.7% of the fellows, racial data were not known and was categorized as Unknown racial distribution. Conclusion Our study concludes that gender and racial disparity persists within the fellowship programs of vascular neurology. Effective strategies at individual, administrative, and national levels are needed to engage women and under-represented minorities in vascular neurology as a career choice.

Sticky Floor, Broken Ladder, and Glass Ceiling: Gender and Racial Trends Among Neurosurgery Residents.

Introduction Diversity and equity in academic medicine are critically important in improving healthcare standards and patient-related outcomes. Gender and racial disparities are some major challenges faced by the health system. This article reviews the gender and racial trends among residents of neurosurgery in the United States (US). Methods We retrospectively analyzed the data extracted from the Accreditation Council for Graduate Medical Education (ACGME)'s annual Data Resource Books from 2007 to 2019. ACGME cataloged gender as men and women and race/ethnicity was categorized as White/non-Hispanic, Asian or Pacific Island, Hispanic, Black/non-Hispanic, Native American/Alaskan, others, and unknown. Counts, proportions, relative, and absolute percentage changes were calculated to highlight trends in resident appointments over time and across the specialty of neurosurgery. Results The number of female residents increased steadily from 10.6% in 2007 to 19.3% in 2019; with an absolute increase of 8.74%, a relative increase of 63.9%, and a simultaneous decrease in male residents. When averaged across the nine-year study period, 51% of the study sample was White (non-Hispanic), followed by Asian/Pacific Islanders at 15.2%. The representation of Hispanics was 4.3%, Black/African Americans were 4.5%, Native Americans/Alaskans were 0.2%, and others were 8% of the total study population. Conclusion Our study concludes that gender and racial disparity persist within the neurosurgery residency training programs in the US. Concrete efforts at all academic levels are needed to provide greater support for the females and for the careers of underrepresented minority (URM) trainees to ensure their increased representation in neurosurgery.

Visual rehabilitation of people with oculocutaneous albinism in a tertiary clinical setting in Pakistan.

PURPOSE: All people with oculocutaneous albinism (OCA) have reduced vision. This study aimed to assess the benefits of low vision aids for people with OCA. METHODS: Seventy-seven consecutive people with OCA age 4 years and above examined in a low vision clinic were included in the study. Uncorrected and best-corrected visual acuity (VA), VA with low vision devices, types of low vision aids, and refractive errors data were analyzed. RESULTS: Of the 77 people with OCA, 57% were in the age group between 4 and 15 years and 43% in the age group of 16 years and above. At the time of presentation, the percentages of visually impaired, severe visually impaired, and blind (using WHO low vision criteria) were 52%, 22%, and 25%. Among them, 39% has near VA of 1 M or better. Difference in the means of the spherical equivalent refractive error in the right eyes and left eyes was -0.494 diopters (-01.686, 0.699; 95% confidence interval). VA improved significantly after adequate refractive correction by more than one log MAR lines in 38.6% (P < 0.01). With low vision devices, in 85.7% (n = 66) participants, VA was enhanced to normal level (6/18 or better) in the better eye while 7.8% still remained in the blind category. Telescopes were prescribed to 61% people for the enhancement of distance VA and hand hold magnifiers were prescribed to 22% people to meet their needs. CONCLUSION: Low vision aids can be successfully used in visual rehabilitation of people with OCA to meet their needs.

Relationship between inward FDI and environmental degradation for Pakistan: an exploration of pollution haven hypothesis through ARDL approach.

In many developing countries, rising pollution and FDI inflows are positively correlated. This paper explores the existence of pollution haven hypothesis in Pakistan by employing the autoregressive distributed lag (ARDL) bounds test on yearly data from 1971 to 2014 for foreign direct investment inflow and four pollutants, i.e., CO2 emissions, CO2 emissions from solid fuels, SO2 emissions, and GHG emissions. In each case, eight different models are tested by incorporating different explanatory variables with foreign direct investment inflow. The outcome of this study shows that in some of the models a positive long-term relationship exists between FDI inflow and CO2 emissions, CO2 emissions from solid fuels, and GHG emissions and a negative long-term relationship between FDI inflow and SO2 emissions. Overall, we found no conclusive evidence of the existence of the pollution haven hypothesis for Pakistan. As Pakistan is taking active measures to attract more FDI, it is essential to introduce appropriate environmental policies and institutional reforms that do not hinder FDI inflows.

Seizure symptoms and ambulatory EEG findings: incidence of epileptiform discharges.

AIMS: Ambulatory video-EEG monitoring has been utilized as a cost-effective alternative to inpatient video-EEG monitoring for non-surgical diagnostic evaluation of symptoms suggestive of epileptic seizures. We aimed to assess incidence of epileptiform discharges in ambulatory video-EEG recordings according to seizure symptom history obtained during clinical evaluation. METHODS: This was a retrospective cohort study. We queried seizure symptoms from 9,221 consecutive ambulatory video-EEG studies in 35 states over one calendar year. We assessed incidence of epileptiform discharges for each symptom, including symptoms that conformed to a category heading, even if not included in the ILAE 2017 symptom list. We report incidences, odds ratios, and corresponding p values using Fisher's exact test and univariate logistic regression. We applied multivariable logistic regression to generate odds ratios for the six symptom categories that are controlled for the presence of other symptoms. RESULTS: History that included motor symptoms (OR=1.53) or automatisms (OR=1.42) was associated with increased occurrence of epileptiform discharges, whereas history of sensory symptoms (OR=0.76) predicted lack of epileptiform discharges. Patient-reported symptoms that were associated with increased occurrence of epileptiform discharges included lip-smacking, moaning, verbal automatism, aggression, eye-blinking, déjà vu, muscle pain, urinary incontinence, choking and jerking. On the other hand, auditory hallucination memory deficits, lightheadedness, syncope, giddiness, fibromyalgia and chronic pain predicted absence of epileptiform discharges. The majority of epileptiform discharges consisted only of interictal sharp waves or spikes. CONCLUSIONS: Our study shows that the use of ILAE 2017 symptom categories may help guide ambulatory video-EEG studies.

Stoichioproteomics reveal oxygen usage bias, key proteins and pathways in glioma.

BACKGROUND: The five-year survival rate and therapeutic effect of malignant glioma is low. Identification of key/associated proteins and pathways in glioma is necessary for developing effective diagnosis and targeted therapy of glioma. In addition, Glioma involves hypoxia-specific microenvironment, whether hypoxia restriction influences the stoichioproteomic characteristics of expressed proteins is unknown. METHODS: In this study, we analyzed the most comprehensive immunohistochemical data from 12 human glioma samples and 4 normal cell types of cerebral cortex, identified differentially expressed proteins (DEPs), and researched the oxygen contents of DEPs, highly and lowly expressed proteins. Further we located key genes on human genome to determine their locations and enriched them for key functional pathways. RESULTS: Our results showed that although no difference was detected on whole proteome, the average oxygen content of highly expressed proteins is 6.65% higher than that of lowly expressed proteins in glioma. A total of 1480 differentially expressed proteins were identified in glioma, including 226 up regulated proteins and 1254 down regulated proteins. The average oxygen content of up regulated proteins is 2.56% higher than that of down regulated proteins in glioma. The localization of differentially expressed genes on human genome showed that most genes were on chromosome 1 and least on Y. The up regulated proteins were significantly enriched in pathways including cell cycle, pathways in cancer, oocyte meiosis, DNA replication etc. Functional dissection of the up regulated proteins with high oxygen contents showed that 51.28% of the proteins were involved in cell cycle and cyclins. CONCLUSIONS: Element signature of oxygen limitation could not be detected in glioma, just as what happened in plants and microbes. Unsaved use of oxygen by the highly expressed proteins and DEPs were adapted to the fast division of glioma cells. This study can help to reveal the molecular mechanism of glioma, and provide a new approach for studies of cancer-related biomacromolecules. In addition, this study lays a foundation for application of stoichioproteomics in precision medicine.

A Spectrum of Hematological Disorders in Children with Pancytopenia Based on Bone Marrow Examination in a Tertiary Care Hospital.

Introduction Pancytopenia is a common presentation in the pediatric population. It is a manifestation of various diseases, and its etiology can be explained on the basis of bone marrow examination. The study aims to determine the etiological factors leading to pancytopenia via bone marrow examination in pediatric patients presenting in our hospital. Materials and methods This retrospective cross-sectional study was conducted in the Department of Pathology at a public sector tertiary care hospital. Data were recorded by convenience sampling from the patients' database from January 2015 to April 2018. Patients aged 2 months to 15 years who had pancytopenia on peripheral blood smear and were admitted for bone marrow examination were included in the study. Patients who were beyond these age limits, diagnosed cases of aplastic anemia and leukemia, and those with a recent history of blood transfusion were excluded from the study. The analysis was done via the Statistical Package for Social Sciences (SPSS) v.23.0 (IBM SPSS Statistics, Armonk, NY, USA), and descriptive statistics were applied. Results Of 115 cases, 58 (50.4%) were males and 57 (49.6%) were females. Megaloblastic anemia was present in 32 (27.8%) patients, and it was the most common cause of pancytopenia. Non-malignant disorders were seen in 95 cases (82.6%) and malignant disorders were seen in 20 (17.4%) cases. Conclusion Megaloblastic anemia is the most common cause, and acute lymphoblastic leukemia is the most common malignant cause of pancytopenia in children. There was no significant gender predilection among causes of pancytopenia.

Assessment of Knowledge, Attitude, and Practices Regarding Self-medication for Acne Among Medical Students.

Introduction Acne is one of the most common skin conditions worldwide. Self-medication for acne is a fairly common practice among medical students. The objective of our study was to identify the prevalence of self-medication and to assess its knowledge, attitude, and practices among medical students. Materials and methods This descriptive cross-sectional study was conducted at Rawalpindi Medical University, Rawalpindi, Pakistan, from January 2019 to June 2019. Data were collected by using the convenient sampling technique. Students were asked to fill a semi-structured questionnaire. Students of all the medical years studying in our university were included in the study. Data were entered and analyzed using the Statistical Package for Social Sciences (SPSS) version 23.0 (IBM Corp., Armonk, US). Results Out of 349 students, 244 (69.9%) suffered from acne and self-medication was practiced by 123 (50.4%) acne sufferers. The practice of self-medication was significantly higher in students having acne lesions on the face (52.2%). The most common source of information was reported to be acquaintances (55.8%). Most of the students had knowledge of the dosage of drugs (46.3%) and precautions for their use (41.5%). Sixty-three percent of the students were of the opinion that self-medication is part of self-care. Most of the students read the expiration date on the drug label (88.6%). Conclusion Acne is a highly prevalent condition among medical students and the practice of self-medication among acne sufferers is high. The practice of self-medication and visits to dermatologists were both significantly more common in the students with lesions on the face. The knowledge of students regarding self-medication of acne was not adequate.

Epidemiology, Bacteriological Profile, and Antibiotic Sensitivity Pattern of Burn Wounds in the Burn Unit of a Tertiary Care Hospital.

INTRODUCTION:  Burn wounds are commonly infected by organisms which delay wound healing. Therefore, it is necessary to evaluate the flora obtained from wounds of burn patients in order to determine the most effective treatment. The aim of this study was to determine the frequencies of various bacteria isolated from burn wounds and to determine their antimicrobial susceptibility.  Materials and methods: This descriptive cross-sectional study was conducted from January 2018 to November 2018 which included consecutive samples of burn wounds from patients admitted to the burn ward of a tertiary care hospital. Bacteria and their antimicrobial susceptibility were determined by swab cultures and sensitivity tests by standard aseptic techniques. Data were analysed via the Statistical Package for Social Sciences (SPSS), v23.0 (IBM SPSS Statistics, Armonk, NY). Chi-square tests were applied between qualitative variables, while the Kruskal-Wallis test was applied to compare the means of asymmetrical data. Bacterial isolates and their susceptibility pattern were represented as frequencies and pie charts. RESULTS:  A total of 178 samples were obtained from 109 patients from burn wounds. One hundred and twenty-two wounds (68.5%) showed growth and 56 (31.4%) showed no growth after 24 hours of incubation. Positive cultures were significantly more frequent in wounds of greater than one-week duration (p < 0.002). Out of 158 bacterial isolates, the most common isolate was Pseudomonas aeruginosa - 41 specimens (24.91%), followed by Staphylococcus aureus - 38 specimens (24.05%), Acinetobacter - 27 (17.09%), Klebsiella - 24 (15.19%), Escherichia coli - 13 (8.23%), Proteus - 7 (4.43%), other coliforms - 6 (3.8%), Enterococcus - 1 (0.63%), and Enterobacter - 1 (0.63%). Drug resistance to penicillin G, ampicillin, Augmentin, ceftazidime, cefotaxime, ceftriaxone, meropenem, and piperacillin+tazobactam was exceptionally high. CONCLUSION:  The most common bacterial isolates are Pseudomonas aeruginosa and Staphylococcus aureus. Piperacillin+tazobactam against Pseudomonas aeruginosa and vancomycin and linezolid against Staphylococcus aureus are highly effective and can be used as empirical therapies.

Outcome of ambulatory video-EEG monitoring in a ˜10,000 patient nationwide cohort.

PURPOSE: We evaluate outcome of in-home diagnostic ambulatory video-EEG monitoring (AVEM) performed on a nationwide cohort of patients over one calendar year, and we compare our findings with outcomes of inpatient adult and pediatric VEM performed during the same year at two academic epilepsy centers. METHODS: This is a retrospective cohort study. We obtained AVEM outcome data from an independent ambulatory-EEG testing facility. Inpatient VEM data from a 4-bed adult epilepsy center and an 8-bed pediatric epilepsy center were also included. Primary outcome measure was composite percentage of VEM records with epileptiform activity on EEG tracings or at least one video-recorded pushbutton event. We assessed patient-reported symptoms documented in AVEM event diaries. RESULTS: Of 9221 AVEM recordings performed across 28 states, 62.5% attained primary outcome. At least one patient-activated pushbutton event was captured on video in 54% of AVEM recordings (53.6% in adults, 56.1% in children). Epileptiform activity was reported in 1657 (18.0%) AVEM recordings (1473 [88.9%] only interictal, 9 [0.5%] only ictal, 175 [10.6%] both interictal and ictal). Most common patient-reported symptomatology during AVEM pushbutton events was behavioral/autonomic/emotional in adults and children. Compared to AVEM, inpatient VEM captured more confirmed representative events in adult and pediatric samples. CONCLUSIONS: AVEM is useful for non-urgent diagnostic evaluation of events.

Herpes Simplex Virus Encephalitis: Atypical Presentation as a Right Middle Cerebral Artery Stroke.

Herpes simplex virus encephalitis (HSVE) is a medical emergency associated with high mortality and morbidity. Definitive diagnosis is established by history, clinical examination, neuroimaging studies, supportive electroencephalogram (EEG) findings, and cerebrospinal fluid (CSF) analysis. We report a case of HSVE presenting as a stroke mimic in a 76-year-old female with a history of atrial fibrillation on warfarin. She was admitted to our medical intensive care unit with intermittent fever, lethargy, and new onset left-sided hemiparesis. A computed tomography (CT) of the head showed a right middle cerebral artery (MCA) acute ischemic stroke with midline shift and a dense right MCA sign. Brain magnetic resonance imaging (MRI) showed evidence of acute stroke with consideration of herpes encephalitis. CSF analysis was positive for herpes simplex virus (HSV) type one. She recovered with high-dose intravenous acyclovir therapy. Our patient was a diagnostic dilemma, initially being diagnosed with an acute ischemic stroke and yet found to have HSVE, which mimicked an acute ischemic stroke. Delay in treatment may result in devastating clinical outcomes that may include severe cognitive, focal neurological deficits, persistent seizures, and even death. This case highlights the importance of a multidisciplinary approach and the need for increased awareness of an atypical presentation of HSVE among emergency physicians, neurologist, intensivists, and radiologists.

Epilepsy and Cannabis: A Literature Review.

Epilepsy is considered to be one of the most common non-communicable neurological diseases especially in low to middle-income countries. Approximately one-third of patients with epilepsy have seizures that are resistant to antiepileptic medications. Clinical trials for the treatment of medically refractory epilepsy have mostly focused on new drug treatments, and result in a significant portion of subjects whose seizures remain refractory to medication. The off-label use of cannabis sativa plant in treating seizures is known since ancient times. The active ingredients of this plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the latter considered safer and more effective in treating seizures, and with less adverse psychotropic effects. Clinical trials prior to two years ago have shown little to no significant effects of cannabis in reducing seizures. These trials seem to be underpowered, with a sample size less than 15. In contrast, more recent studies that have included over 100 participants showed that CBD use resulted in a significant reduction in seizure frequency. Adverse effects of CBD overall appear to be benign, while more concerning adverse effects (e.g., elevated liver enzymes) improve with continued CBD use or dose reduction. In most of the trials, CBD is used in adjunct with epilepsy medication, therefore it remains to be determined whether CBD is itself antiepileptic or a potentiator of traditional antiepileptic medications. Future trials may evaluate the efficacy of CBD in treating seizures due to specific etiologies (e.g., post-traumatic, post-stroke, idiopathic).

The Landscape of Protein Tyrosine Phosphatase (Shp2) and Cancer.

Role of Shp2: The dysregulation of cell signaling cascades associated with the cell differentiation and growth, due to the deletion, insertion or point mutation in specific amino acids which alters the intrinsic conformation of the protein, can ultimately lead to a fatal cancer disease. The protein tyrosine phosphatase has been recognized as a key regulator of extracellular stimuli such as cytokine receptor and receptor tyrosine kinase signaling. In the last era, the PTPN11 gene (encode a Shp2 protein) and its association with acute myeloid, juvenile myelomonocytic, and B-cell acute lymphoblastic leukemia, Noonan syndrome, and myelodysplastic have been recognized as the cause of such deadly disease due to the occurrence of germline mutations in the interface of PTP and SH2 domain. Conclusion: The current study was designed to focus on the allosteric regulation (autoinhibition) of the of Shp2 protein. Subsequently, it will cover the last 10-year recap of Shp2 protein, their role in cancer, and regulation in numerous ways (allosteric regulation).

Potential New Cysteine Sparing Mutation in the NOTCH3 Gene in a Patient with Nonfamilial CADASIL-like Disease.

BACKGROUND: Several different mutations have been reported in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We present a unique case with transversion not involving cysteine on neurogenic locus notch homolog protein 3 gene. CASE DESCRIPTION: We present a case of 65-year-old woman with new ischemic stroke resulting in right hemiparesis. She has previously suffered minor strokes at age 56, 58, and 60 years and migraine headaches between age 10 and 50 years. Magnetic resonance imaging demonstrated multifocal chronic ischemic infarctions with encephalomalacia in the left posterior parietal, parieto-occipital regions and the pons. An analysis of the protein sequence of notch 3 gene did not demonstrate any alterations characteristics of CADASIL disease. There was a deoxyribonucleic acid variant with transversion of alanine with tyrosine and change of histidine with leucine on notch 3 gene. None of the family members had any clinical manifestations suggestive of CADASIL. CONCLUSION: We report the first report of deoxyribonucleic acid variation in notch 3 gene associated with clinical features of CADASIL without any familial component.