Oral and topical analgesia in pediatric electrodiagnostic studies.

INTRODUCTION/AIMS: Electrodiagnostic examinations, such as nerve conduction studies (NCS) and needle electromyography (EMG), are perceived as painful by children and their parents/guardians. Methods to reduce peri-procedural pain improve compliance and have neurocognitive and neuropsychiatric benefits. This study aimed to assess the efficacy of combined oral and topical analgesics (COTA), oral analgesics (OA), and placebo in reducing pain during NCS/EMG in children. METHODS: We performed a double-blind, randomized, placebo-controlled trial on children presenting to our neurophysiology lab. Patients were stratified into two age groups (6M-6Y and 7Y-18Y) and randomized into three arms: COTA, OA, and placebo. Pain scores post-NCS/EMG were assessed using the Modified Behavioral Pain Scale (MBPS) and Faces Pain Scale-Revised (FPS-R). RESULTS: One hundred thirteen participants were enrolled. A comparison of participants from both age groups combined revealed no significant differences in guardian FPS-R scores across all arms for NCS and EMG. A significant difference in the distribution of post-NCS FPS-R score severities in children aged 7Y-18Y was noted between OA and placebo (p = .007). EMG was more painful than NCS across all arms (p < .05). In children aged 6M-6Y undergoing at least 10 muscle samplings during EMG, those receiving COTA had significantly lower pain scores (p = .014). DISCUSSION: This study reveals the complexity of pediatric pain perception during NCS/EMG and highlights that other methods to reduce experienced pain are required. Our findings suggest that procedural characteristics, such as number of muscles sampled, may influence the effectiveness of analgesia and serve as a foundation for future research aimed at optimizing pain management strategies.

One-Step Construction of Hierarchical Porous and Defect-Rich Zn2+-Doped NH2-MIL-125(Ti) to Enhance Photocatalytic Degradation of Tetracycline Hydrochloride.

The development of efficient metal-organic framework (MOF) photocatalysts for the degradation of tetracycline hydrochloride (TC) is crucial for environmental and public health. Herein, NH2-MIL-125(Ti) flakes (namely, ZnxTi1-x-NML), featuring defect-rich and Zn2+-doping, were synthesized using a one-step solvothermal method. For the first time, the crystal structure of Zn-doped NML was determined by combining extended X-ray absorption with fine structure spectroscopy. The formation mechanisms of the flake morphology with hierarchical porous structures were thoroughly investigated. Compared to NH2-MIL-125(Ti), Zn0.15Ti0.85-NML achieved a 3.4-fold increase in removal of TC under simulated sunlight. The adjusted electronic structure enhances superoxide radical production, coupled with a flake-like and porous architecture that promotes reaction sites, improved mass transfer, and reduced charge distances. Combined with theoretical calculations of the density of states and electrostatic potential, the ligand-metal-metal charge transfer process was elucidated. The possible pathway for the photocatalytic degradation of TC by Zn0.15Ti0.85-NML was further speculated. Moreover, the safety of the photocatalytic pathway was assessed by predicting the toxicity of the degradation intermediates. Our findings link the structure of MOFs to their catalytic efficiency, guiding the creation of sustainable photocatalysts.

Normative values and factors affecting saphenous nerve responses in a south Asian population: a cross-sectional neurophysiological study at a tertiary care hospital in Pakistan.

BACKGROUND: The saphenous nerve, a sensory branch of the femoral nerve, is not commonly included in routine lower extremity nerve conduction studies due to a high frequency of non-recordable responses in healthy subjects. However, saphenous nerve conduction studies are sometimes utilized for the diagnostic assessment of isolated lumbosacral plexus, femoral, or saphenous mononeuropathies. Our study aims to determine normative saphenous nerve response values in a healthy Pakistani population and to investigate their associations with patient body mass index, age, and gender. METHODS: This cross-sectional descriptive study was undertaken over a 3­month period (May to July 2021) at a neurophysiology department of a tertiary care center in Pakistan. Healthy subjects underwent neurological examination, anthropometric measurements, and bilateral SN nerve conduction studies, with recording of peak-latency, peak-to-peak amplitude and conduction velocity. Statistical analyses and linear regression were conducted to evaluate associations between nerve conduction study variables and patient characteristics. Statistical analyses were also run to assess patient characteristics affecting recordability of saphenous nerve responses. A p-value < 0.05 was considered statistically significant. RESULTS: Among 117 subjects, 79.5% (n = 93) had recordable saphenous nerve responses. Median peak-latency, amplitude, and conduction velocity were 3.2 (3.0-3.3) m/s, 7.7 (5.8-9.9) uV, and 44.0 (42.0-47.0) m/s, respectively. Bilaterally absent responses were observed in 20.5% (n = 24) of subjects. Obese participants had a significantly higher number of absent saphenous responses (p = 0.033). Females had shorter peak-latency (p = 0.006) and higher conduction velocity (p = 0.012). CONCLUSIONS: Saphenous nerve responses can be used to assess unilateral femoral and saphenous nerve pathologies, provided they are recordable on the asymptomatic side for comparison. Absent bilateral saphenous nerve responses should be interpreted with caution given their prevalence in healthy individuals. Patient characteristics should be taken into consideration when interpreting recordable and nonrecordable saphenous nerve responses.

Public policy interventions to mitigate household food insecurity in Canada: a systematic review.

OBJECTIVE: The objective of this systematic review is to synthesise the evidence on public policy interventions and their ability to reduce household food insecurity (HFI) in Canada. DESIGN: Four databases were searched up to October 2023. Only studies that reported on public policy interventions that might reduce HFI were included, regardless of whether that was the primary purpose of the study. Title and abstract screening, full-text screening, data extraction, risk of bias and certainty of the evidence assessments were conducted by two reviewers. RESULTS: Seventeen relevant studies covering three intervention categories were included: income supplementation, housing assistance programmes and food retailer subsidies. Income supplementation had a positive effect on reducing HFI with a moderate to high level of certainty. Housing assistance programmes and food retailer studies may have little to no effect on HFI; however, there is low certainty in the evidence that could change as evidence emerges. CONCLUSION: The evidence suggests that income supplementation likely reduces HFI for low-income Canadians. Many questions remain in terms of how to optimise this intervention and additional high-quality studies are still needed.

Anogeissus Latifolia: A Comprehensive Review from Ethanobotanical Insights to Future Pharmacological Frontiers.

Anogeissus latifolia, commonly known as Axlewood, Indian Gum Tree, or Gum Ghatti, belongs to the Combretaceae family and is native to India, Nepal, Myanmar, and Sri Lanka. It thrives in most tropical and subtropical regions of India. Different parts of the plant contain various proteins, carbohydrates, sugars (arabinose, galactose, mannose, xylose, rhamnose, and glucuronic acid), minerals (magnesium and calcium salts of ghattic acid), and a wide range of phytochemicals such as alkaloids, flavonoids, phenols, terpenoids, sterols, saponins, tannins, coumarins, quinine, and ellagic acid. Studies have indicated the potential of Anogeissus latifolia in managing various health conditions, including antimicrobial, anti-inflammatory, anti-diabetic, anti-parasitic, antioxidant, hepatoprotective, wound healing, and hypolipidemic effects. However, like many medicinal plants, Anogeissus latifolia demonstrates a dose-dependent toxicity profile, particularly when administered intraperitoneally. Research efforts have been directed towards elucidating its safety profile, and findings suggest that it can be considered safe when administered within prescribed dosages. This paper aims to provide a comprehensive review encompassing the ethnobotanical significance, morphological characteristics, phytochemistry, pharmacological actions, and toxicological aspects of Anogeissus latifolia. Additionally, it explores future research perspectives in the field of Anogeissus latifolia pharmacology and therapeutics.

Impact of acidic beverages on composition and surface characteristics of human teeth: scanning electron microscopic, stereomicroscopic and energy dispersive x-ray analyses.

OBJECTIVES: The objective of this study was to evaluate the effect of acidic beverages on the surface topography and elemental composition of human teeth. METHODS: A total of five highly acidic beverages (Red Bull, Pepsi, Apple Cidra, Tang Mosambi, and Tang Orange) were investigated. The tooth specimens of experimental groups were submerged in each beverage and incubated at 37 °C for 7 days, whereas, the tooth specimens of control groups were placed in distilled water. Afterwards, tooth specimens were analyzed using scanning electron microscopic (SEM), stereomicroscopic, and energy dispersive x-ray (EDX) techniques. RESULTS: All experimental groups revealed a decline in the tooth elements compared to controls, however, such decline was not statistically significant. Nevertheless, comparing the experimental groups, the Red Bull beverage caused a marked reduction in the percentage of both calcium and phosphorus elements compared to the Pepsi, Apple Cidra, Tang Mosambi, and Tang Orange beverages but it was insignificant as well in contrast to its control counterpart. All five acidic beverages demonstrated erosive potential under SEM analysis; however, each group of specimens showed a diverse amount of demineralization. In addition, all experimental groups exhibited significant discoloration of tooth specimens compared to their respective control counterparts. CONCLUSIONS: Within the limitations of study, all five acidic beverages demonstrated erosive potential in the simulated in vitro conditions under SEM analysis; however, each group of specimens exhibited a different extent of demineralization. In addition, the overall effect of all beverages was insignificant under EDX analysis as no substantial difference was revealed between the elemental composition of experimental and control group specimens.

Multidisciplinary treatment of a patient with TMJ ankylosis and a severe dentofacial discrepancy: A case report.

INTRODUCTION: Temporomandibular joint (TMJ) ankylosis is a debilitating condition characterised by the fusion of bony or fibrous tissues in the TMJ, resulting in restricted mouth opening, functional challenges and facial deformities. This report highlights the complexity and multifaceted nature of TMJ ankylosis and emphasises the significance of early intervention and a multidisciplinary approach. Distraction osteogenesis has emerged as a successful method for managing TMJ ankylosis and associated facial asymmetry. Post-distraction orthodontic management is essential to address occlusal changes, including posterior open bite and crossbite. DIAGNOSIS AND TREATMENT PLAN: A 17-year-old boy with unilateral right-sided TMJ ankylosis presented with restricted mouth opening, facial asymmetry and functional difficulties. Multidisciplinary treatment planning involved distraction osteogenesis, condylectomy, coronoidectomy and orthodontic correction to achieve proper occlusion and facial aesthetics. RESULTS: The treatment significantly improved facial aesthetics, mouth opening, occlusion and the patient's confidence and self-esteem. CONCLUSION: This case report underscores the complexity of TMJ ankylosis and the need for a comprehensive approach, including surgical and orthodontic interventions. Collaboration among healthcare professionals and ongoing research is vital to refine treatment approaches and improve the quality of life for patients with TMJ ankylosis.

Effects of oral steroid sparing immunosuppressive drugs in long term maintenance treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

Background and objectives: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired treatable autoimmune disorder. Due to limited availability and affordability of IV immunoglobulins and therapeutic plasma exchange in Pakistan, oral immunosuppressive drugs (ISDs) are used despite limited role in literature. The study aimed to determine the response to ISDs in CIDP patients by assessing the frequency of remission, reduction of disability using a neuropathy related disability score called Inflammatory Neuropathy Cause and Treatment score (or INCAT score), as well as reduction in steroid maintenance dose. Methods: The retrospective observational study of six months duration (May to October, 2020) was carried out in Aga Khan University Hospital, Karachi, Pakistan. Medical record of all the patients with idiopathic CIDP taking oral ISDs in last five years was selected which included bio-data, clinical signs and symptoms, medication details, and INCAT scores. Descriptive statistics were described i.e. frequency, percentages, mean/standard deviation using Microsoft Excel v.2021. Results: Out of thirteen patients, Azathioprine was used in nine, Mycophenolate mofetil in two and Cyclosporine in two, with remission (INCAT score improvement ≥ 1) achieved in eight, one and zero patients respectively. Duration of ISDs ranged from three to twenty-four months (average 15.8 months). Patients with monoclonal paraproteinemia and prior exposure to ISDs had a poor response to the introduction of subsequent ISDs. Conclusion: The study describes preliminary experience of the potential role of relatively cheaper and more convenient oral ISDs (especially Azathioprine) as an alternative or sparing agent to first line agents for CIDP and sets the stage for larger scale studies and randomized controlled trials.

The spectrum of hereditary neuromuscular disorders in the Pakistani population.

Hereditary neuromuscular disorders (NMDs) are a broad group of clinically heterogeneous disorders with varying inheritance patterns, that are associated with over 500 implicated genes. In the context of a highly consanguineous Pakistani population, we expect that autosomal recessive NMDs may have a higher prevalence compared with patients of European descent. This is the first study to offer a detailed description of the spectrum of genes causing hereditary NMDs in the Pakistani population using NGS testing. To study the clinical and genetic profiles of patients presenting for evaluation of a hereditary neuromuscular disorder. This is a retrospective chart review of patients seen in the Neuromuscular Disorders Clinic and referred to the Genetics Clinic with a suspected hereditary neuromuscular disorder, between 2016 and 2020 at the Aga Khan University Hospital, Karachi and Mukhtiar A. Sheikh Hospital, Multan, Pakistan. The genetic testing for these patients included NGS-based single gene sequencing, NGS-based multi-gene panel and whole exome sequencing. In a total of 112 patients studied, 35 (31.3%) were female. The mean age of onset in all patients was 14.6 years (SD ±12.1 years), with the average age at presentation to the clinic of 22.4 years (SD ±14.10 years). Forty-seven (41.9%) patients had a positive genetic test result, 53 (47.3%) had one or more variants of uncertain significance (VUS), and 12 (10.7%) had a negative result. Upon further genotype-phenotype correlation and family segregation analysis, the diagnostic yield improved, with 59 (52.7%) patients reaching a diagnosis of a hereditary NMD. We also report probable founder variants in COL6A2, FKTN, GNE, and SGCB, previously reported in populations that have possible shared ancestry with the Pakistani population. Our findings reemphasizes that the rate of VUSs can be reduced by clinical correlation and family segregation studies.

Support for an area-heterogeneity tradeoff for biodiversity in croplands.

Rapid expansion of the human population poses a challenge for wildlife conservation in agricultural landscapes. One proposal for addressing this challenge is to increase biodiversity in such landscapes by increasing crop diversity. However, studies report both positive and negative effects of crop diversity on biodiversity. One possible explanation, derived from the "area-heterogeneity tradeoff hypothesis," is that the effect of crop diversity on biodiversity depends on a tradeoff between increasing the number of crop types in a landscape and decreasing the amount of each single crop type. This should cause positive effects of increasing crop diversity at low to intermediate crop diversity and negative effects at intermediate to high crop diversity. We also propose two factors that could change the point at which the effect of increasing crop diversity shifts from positive to negative. First, we predicted that this shift would occur at a lower crop diversity when the surrounding landscape contains less semi-natural habitat and at a higher crop diversity when the landscape contains more semi-natural habitat. This should increase the likelihood of detecting negative effects of crop diversity when semi-natural cover is low and positive effects when it is high. Second, we predicted that the shift from a positive to negative effect would occur at a lower crop diversity when it is measured locally than when it is measured at greater distances from the site, making detection of negative crop diversity effects more likely when measurements are at local extents. We tested these predictions using data on the biodiversity of herbaceous plants, butterflies, syrphid flies, woody plants, bees, carabid beetles, spiders, and birds at 221 crop field edges in Eastern Ontario, Canada. We found support for an area-crop diversity tradeoff. Semi-natural cover and measurement extent influenced the biodiversity-crop diversity relationship, with positive effects when semi-natural cover was high and negative effects when semi-natural cover was low and when crop diversity was measured at local extents. The results suggest that policies/guidelines designed to increase crop diversity will not benefit biodiversity in the landscapes where conservation action is most urgently needed, that is, in landscapes with high agricultural use and low semi-natural cover.

Bioactivity-Guided Synthesis: In Silico and In Vitro Studies of ß-Glucosidase Inhibitors to Cope with Hepatic Cytotoxicity.

The major cause of hyperglycemia can generally be attributed to ß-glucosidase as per its involvement in non-alcoholic fatty liver disease. This clinical condition leads to liver carcinoma (HepG2 cancer). The phthalimides and phthalamic acid classes possess inhibitory potential against glucosidase, forming the basis for designing new phthalimide and phthalamic acid analogs to test their ability as potent inhibitors of ß-glucosidase. The study also covers in silico (molecular docking and MD simulations) and in vitro (ß-glucosidase and HepG2 cancer cell line assays) analyses. The phthalimide and phthalamic acid derivatives were synthesized, followed by spectroscopic characterization. The mechanistic complexities associated with ß-glucosidase inhibition were identified via the docking of the synthesized compounds inside the active site of the protein, and the results were analyzed in terms of the best binding energy and appropriate docking pose. The top-ranked compounds were subjected to extensive MD simulation studies to understand the mode of interaction of the synthesized compounds and binding energies, as well as the contribution of individual residues towards binding affinities. Lower RMSD/RMSF values were observed for 2c and 3c, respectively, in the active site, confirming more stabilized, ligand-bound complexes when compared to the free state. An anisotropic network model was used to unravel the role of loop fluctuation in the context of ligand binding and the dynamics that are distinct to the bound and free states, supported by a 3D surface plot. An in vitro study revealed that 1c (IC50 = 1.26 µM) is far better than standard acarbose (2.15 µM), confirming the potential of this compound against the target protein. Given the appreciable potential of the candidate compounds against ß-glucosidase, the synthesized compounds were further tested for their cytotoxic activity against hepatic carcinoma on HepG2 cancer cell lines. The cytotoxicity profile of the synthesized compounds was performed against HepG2 cancer cell lines. The resultant IC50 value (0.048 µM) for 3c is better than the standard (thalidomide: IC50 0.053 µM). The results promise the hypothesis that the synthesized compounds might become potential drug candidates, given the fact that the ß-glucosidase inhibition of 1c is 40% better than the standard, whereas compound 3c holds more anti-tumor activity (greater than 9%) against the HepG2 cell line than the known drug.

Phycoremediation of industrial wastewater using Vaucheria debaryana and Cladophora glomerata.

Rapid urbanization and industrialization are regarded as the leading causes of environmental pollution, mainly aquatic pollution. This study was carried out to investigate the use of algal species Cladophora glomerata (CG) and Vaucheria debaryana (VD) as a cost-effective and environmentally friendly phycoremediators for composite industrial effluent. After the pot experimentation using algal species, a considerable decrease in electrical conductivity (EC: 49.10-81.46%), dissolved oxygen (DO: 3.76-8.60%), biological oxygen demand (BOD: 7.81-39.28%), chemical oxygen demand (COD: 7.81-39.28%), total suspended solids (TSS: 38.09-62.21%), and total dissolved solids (TDS: 38.09-62.21%) was observed. Before and after experimentation, the heavy metals were also quantified using atomic absorption spectrophotometry (AAS), and considerable reduction was observed in Cd (41.02-48.75%) and Pb (48.72-57.03%) concentrations. The Cd concentration determined in CTCG (control treatment for Cladophora glomerata containing tap water), CG (treatment pot for Cladophora glomerata containing industrial effluents), CTVD (control pot for Vaucheria debaryana containing tap water), and VD (treatment pot for Vaucheria debaryana containing industrial effluents) biomass was 0.06, 0.499, 0.035, and 0.476 mg/kg, respectively. The Pb uptake determined in CTCG, CG, CTVD, and VD was 0.32, 1.12, 0.31, and 0.49 mg/kg, respectively, using wet digestion method and ASS. The data revealed that C. glomerata has the highest bioconcentration factor for Cd (98.42%), followed by Pb (92.57%) in treatment pots containing industrial effluents (CG and VD). Furthermore, C. glomerata showed the highest bioconcentration factor for Pb (86.49%) as compared to Cd (75%) in tap water (CTCG and CTVD). The t test analysis revealed that heavy metal concentrations significantly (p ≤ 0.05) reduced through the phycoremediation process. The analysis found that C. glomerata removed 48.75% of Cd and 57.027% of Pb from industrial effluents. Phytotoxicity assay was also performed by cultivating Triticum sp. in order to analyze the toxicity of the untreated (control) and treated water samples. Phytotoxicity result shows that the effluent treated with both Cladophora glomerata and Vaucheria debaryana gives better wheat (Triticum sp.) plant % germination, plant height (cm), and root height (cm). The highest plant % germination was showed by treated CTCG (90%), followed by CTVD (80%) and CG (70%) and VD (70%). The study concluded that phycoremediation using C. glomerata and V. debaryana is one of the environment-friendly approaches. The proposed algal-based strategy is economically viable and environmentally sustainable that can be utilized for the remediation of industrial effluents.

Machine learning for rhabdomyosarcoma histopathology.

Correctly diagnosing a rare childhood cancer such as sarcoma can be critical to assigning the correct treatment regimen. With a finite number of pathologists worldwide specializing in pediatric/young adult sarcoma histopathology, access to expert differential diagnosis early in case assessment is limited for many global regions. The lack of highly-trained sarcoma pathologists is especially pronounced in low to middle-income countries, where pathology expertise may be limited despite a similar rate of sarcoma incidence. To address this issue in part, we developed a deep learning convolutional neural network (CNN)-based differential diagnosis system to act as a pre-pathologist screening tool that quantifies diagnosis likelihood amongst trained soft-tissue sarcoma subtypes based on whole histopathology tissue slides. The CNN model is trained on a cohort of 424 centrally-reviewed histopathology tissue slides of alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma and clear-cell sarcoma tumors, all initially diagnosed at the originating institution and subsequently validated by central review. This CNN model was able to accurately classify the withheld testing cohort with resulting receiver operating characteristic (ROC) area under curve (AUC) values above 0.889 for all tested sarcoma subtypes. We subsequently used the CNN model to classify an externally-sourced cohort of human alveolar and embryonal rhabdomyosarcoma samples and a cohort of 318 histopathology tissue sections from genetically engineered mouse models of rhabdomyosarcoma. Finally, we investigated the overall robustness of the trained CNN model with respect to histopathological variations such as anaplasia, and classification outcomes on histopathology slides from untrained disease models. Overall positive results from our validation studies coupled with the limited worldwide availability of sarcoma pathology expertise suggests the potential of machine learning to assist local pathologists in quickly narrowing the differential diagnosis of sarcoma subtype in children, adolescents, and young adults.

Building the ecosystem for pediatric neuro-oncology care in Pakistan: Results of a 7-year long twinning program between Canada and Pakistan.

BACKGROUND: Low- and middle-income countries sustain the majority of pediatric cancer burden, with significantly poorer survival rates compared to high-income countries. Collaboration between institutions in low- and middle-income countries and high-income countries is one of the ways to improve cancer outcomes. METHODS: Patient characteristics and effects of a pediatric neuro-oncology twinning program between the Hospital for Sick Children in Toronto, Canada and several hospitals in Karachi, Pakistan over 7 years are described in this article. RESULTS: A total of 460 patients were included in the study. The most common primary central nervous system tumors were low-grade gliomas (26.7%), followed by medulloblastomas (18%), high-grade gliomas (15%), ependymomas (11%), and craniopharyngiomas (11.7%). Changes to the proposed management plans were made in consultation with expert physicians from the Hospital for Sick Children in Toronto, Canada. On average, 24% of the discussed cases required a change in the original management plan over the course of the twinning program. However, a decreasing trend in change in management plans was observed, from 36% during the first 3.5 years to 16% in the last 3 years. This program also led to the launch of a national pediatric neuro-oncology telemedicine program in Pakistan. CONCLUSIONS: Multidisciplinary and collaborative efforts by experts from across the world have aided in the correct diagnosis and treatment of children with brain tumors and helped establish local treatment protocols. This experience may be a model for other low- and middle-income countries that are planning on creating similar programs.

Centers for Medicare & Medicaid Services' Hospital Harm Measures for Severe Hypoglycemia and Hyperglycemia: Is Your Hospital Ready?

Poor inpatient glycemic management is associated with increased lengths of stay and in-hospital morbidity and mortality. Improving inpatient glycemic outcomes can be difficult because there are no standardized benchmarks, and many hospitals lack the capacity to electronically extract and analyze glucose data. The Centers for Medicare & Medicaid Services recently proposed new electronic clinical quality measures to be incorporated into its mandatory Hospital Inpatient Quality Reporting Program. Among these measures is an assessment of hospital harm from severe hypoglycemia and severe hyperglycemia. Hospitals must be ready to collect the necessary data for these new measures by January 2023. The new measures could bring welcome attention to the need to implement guideline-based inpatient glycemic management. However, some hospitals that serve high-risk populations may be at risk for losing funding if they are unable to comply.

First Report of Cerebral Venous Thrombosis Following Inactivated-Virus Covid Vaccination (Sinopharm and Sinovac).

Cerebral venous thrombosis (CVT) is an uncommon cerebrovascular disease, which has been reported with covid infection as well as covid vaccines, particularly AstraZeneca and Janssen vaccines. We present four consecutive cases of CVT after receiving either Sinopharm or Sinovac vaccine, both of which are composed of an inactivated-virus. All the patients recovered well with anticoagulation and discharged with a good functional outcome. This is the first case series reporting CVT following the administration of these vaccines.

Three New Acrylic Acid Derivatives from Achillea mellifolium as Potential Inhibitors of Urease from Jack Bean and α-Glucosidase from Saccharomyces cerevisiae.

(1) Background: Achillea mellifolium belongs to a highly reputed family of medicinal plants, with plant extract being used as medicine in indigenous system. However, limited data is available regarding the exploitation of the medicinal potential of isolated pure compounds from this family; (2) Methods: A whole plant extract was partitioned into fractions and on the basis of biological activity, an ethyl acetate fraction was selected for isolation of pure compounds. Isolated compounds were characterized using different spectroscopic techniques. The compounds isolated from this study were tested for their medicinal potential using in-vitro enzyme assay, coupled with in-silico studies; (3) Results: Three new acrylic acid derivatives (1-3) have been isolated from the ethyl acetate fraction of Achillea mellifolium. The characterization of these compounds (1-3) was carried out using UV/Vis, FT-IR, 1D and 2D-NMR spectroscopy (1H-NMR, 13C-NMR, HMBC, NOESY) and mass spectrometry. These acrylic acid derivatives were further evaluated for their enzyme inhibition potential against urease from jack bean and α glucosidase from Saccharomyces cerevisiae, using both in-silico and in-vitro approaches. In-vitro studies showed that compound 3 has the highest inhibition against urease enzyme (IC50 =10.46 ± 0.03 µΜ), followed by compound 1 and compound 2 with percent inhibition and IC50 value of 16.87 ± 0.02 c and 13.71 ± 0.07 µΜ, respectively, compared to the standard (thiourea-IC50 = 21.5 ± 0.01 µΜ). The investigated IC50 value of compound 3 against the urease enzyme is two times lower compared to thiourea, suggesting that this compound is twice as active compared to the standard drug. On the other hand, all three compounds (1-3) revealed mild inhibition potential against α-glucosidase. In-silico molecular docking studies, in combination with MD simulations and free energy, calculations were also performed to rationalize their time evolved mode of interaction inside the active pocket. Binding energies were computed using a MMPBSA approach, and the role of individual residues to overall binding of the inhibitors inside the active pockets were also computed; (4) Conclusions: Together, these studies confirm the inhibitory potential of isolated acrylic acid derivatives against both urease and α-glucosidase enzymes; however, their inhibition potential is better for urease enzyme even when compared to the standard.

Sporadic Creutzfeldt-Jakob Disease: Diagnosing Typical and Atypical Presentations under Limited Circumstances.

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible disorder of the central nervous system caused by the transformation of normal prion protein into an abnormal misfolded form. The process begins spontaneously and runs a vicious cycle to cause spongiform encephalopathy, rapidly resulting in death. Amply described in the western literature, CJD is scarcely reported in Asia due to certain limitations including missed diagnosis, under-reporting, and rarity of the disease. Brain MRI, electroencephalogram, cerebrospinal fluid testing, and biopsy of the infected brain tissue support the diagnosis in cases of clinical suspicion. However, the diagnosis can still be made with limited available resources in developing countries. METHOD: A review of CJD cases evaluated in the neurology department of a tertiary care hospital in Pakistan was done from 2002 to 2018. RESULTS: Eleven cases labeled as sCJD are identified based on the European MRI-CJD consortium criteria. This is the first study on CJD from Pakistan, which includes both the typical and atypical presentations. CONCLUSION: Even with limited testing available, the diagnosis of CJD can be made with confidence in the developing countries, provided the suspicion is kept high in cases of rapid onset dementia and acute behavioral changes.

Selecting the Next Generation of Surgeons: General Surgery Program Directors and Coordinators Perspective on USMLE Changes and Holistic Approach.

INTRODUCTION: The United States Medical Licensing Examination (USMLE) was designed as a universal assessment tool for states to determine physician's medical licensure's candidacy. Recent changes in the USMLE exam have changed the way future surgical residency candidate applications will be reviewed. The survey aimed to assess the effect of changes in USMLE exams-USMLE Step 1 pass/fail, complete dissolution of USMLE clinical skills exam, and the role of holistic review in future surgical residency candidacy selection. METHODS: An anonymous online survey was created and distributed to general surgery program directors and coordinators across the USA. The survey aimed to assess attitudes toward changes to USMLE exams and the potential changes with a holistic review of candidate applications. RESULTS: The response rate was 63.7%. Most program directors and coordinators disagree with changing USMLE Step 1 to a pass/fail scoring system. The majority felt that contacts, the medical school's name, and performance in clinical electives and sub-internships would hold more significance. They also believe that a holistic review of application will decrease socioeconomic discrepancies and promote a more diverse and inclusive resident cohort. CONCLUSION: Step 2 clinical knowledge (CK) will gain more importance in future residency matches because of the change in the scoring system of Step 1. The medical school's name, personal contacts, and clinical performance in rotations will hold more significance.