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.

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.

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.

Patient perspectives on health care provider practices leading to an axial spondyloarthritis diagnosis: an exploratory qualitative research study.

BACKGROUND: The average time to a diagnosis for people with axial spondyloarthritis (axSpA) is 7-10 years. Delayed diagnosis may result in increased structural damage, worse physical function, and worse quality of life relative to patients with a timely axSpA diagnosis. Understanding patient experiences may provide insights for how to reduce diagnostic delays. OBJECTIVE: To provide foundational knowledge about patient experiences with healthcare providers leading to an axSpA diagnosis. METHODS: We conducted an exploratory qualitative research study with six focus groups interviews with participants recruited from three rheumatology clinics within the United States (MA (n = 3); CO (n = 2); PA (n = 1)) that included a total of 26 adults (10 females, 16 males) with rheumatologist confirmed diagnosis of axSpA in 2019. Focus groups were ~ 2 h, audio recorded, transcribed, and subject to dual coding. The codes reviewed were in relation to the patients' diagnostic experiences. RESULTS: Patients described frustrating and lengthy diagnostic journeys. They recognized that the causes of diagnostic delays in axSpA are multifactorial (e.g., no definitive diagnostic test, disease characteristics, lack of primary care provider's awareness about axSpA, trust). Patients described how doctors minimized or dismissed complaints about symptoms or told them that their issues were psychosomatic. Patients believed the healthcare system contributed to diagnostic delays (e.g., lack of time in clinical visits, difficulty accessing rheumatologists, health insurance challenges). Advice to physicians to reduce the diagnostic delay included allowing time for patients to give a complete picture of their illness experience, listening to, and believing patients, earlier referral to rheumatology, provision of HLA-B27 gene testing, and that physicians need to partner with their patients. CONCLUSIONS: Patients desire a definitive test that could be administered earlier in the course of axSpA. Until such a test is available, patients want clinicians who listen to, believe, and partner with them, and who will follow them until a diagnosis is reached. Educating primary care clinicians about guidelines and referral for diagnosis of axSpA could reduce diagnostic delay.

Correlation of C-reactive protein levels, gene polymorphism and platelets count in Dengue infection.

OBJECTIVE: To determine the correlation of polymorphism in C-reactive protein gene with variation in serum levels in dengue patients. METHODS: The cross-sectional study was conducted at Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan, from October 2017 to October 2018, and comprised blood samples from dengue patients which were used to measure the serum levels of C-reactive protein. Deoxyribonucleic acid extraction followed by tetra amplification-refractory mutation system polymerase chain reaction was used to analyse the genotype variation T>G for single nucleotide polymorphism rs199953854 using allele-specific primers. Correlation of serum C-reactive protein levels with the C-reactive protein polymorphism in dengue patients was explored. Data was analysed using SPSS 21. RESULTS: Of the 200 patients, 108(54%) had very high C-reactive protein levels, 48(24%) had levels slightly higher than the upper limit, 14(7%) had low and 30(15%) had normal levels. Also, 162(81%) patients had low platelets count. Amplification of only T alleles was noted. CONCLUSIONS: C-reactive protein levels were found to be increased with suppressed platelets count in dengue patients. Single nucleotide polymorphism rs199953854 appeared to have no polymorphism.

An Assessment of the Knowledge, Attitudes, and Practices of Patients and Families with Diagnoses of Hereditary Neuromuscular Disorders.

BACKGROUND: Hereditary neuromuscular disorders (NMDs) result in progressive disability with no definitive disease modifying treatments. There is a delay in diagnosis, and lack of awareness among affected individuals about these disorders, which can affect quality of life of patients. OBJECTIVE: The aim of this study is to identify gaps in patient knowledge, factors affecting attitudes toward the diagnoses, and specific practices to create better awareness among patients and healthcare providers to improve care and overall outcomes. METHODS: This is a cross-sectional study of 130 patients diagnosed with an NMD, recruited from the outpatient neurology clinics at the Aga Khan University Hospital. After telephonic consent, a 28 item survey questionnaire was administered. Knowledge, attitude, and practice scores were measured. RESULTS: One hundred and thirty of 198 study participants responded. The average age was 26.3 years; 75% were male. More than 38% (n = 50) had a middle grade or less education. The average knowledge, attitude, and practice scores were 7.9, 2.7, and 3.8 respectively. There was a low but statistically significant correlation between knowledge-attitude and attitude-practice scores. Almost 80% of respondents believed that dystrophy or spinal muscular atrophy is curable, while a majority considered that physical activity should be avoided. CONCLUSIONS: Our study presents new insights into the role of clarifying misconceptions about NMD and to correct attitudes among patients, their families and communities. It underscores the need for early interventions with demonstrably positive effects on disease progression such as physical therapy, as well as emphasizes the provision of accessible and affordable centers for such services.

Embryonal tumors with multi-layered rosettes: a disease of dysregulated miRNAs.

INTRODUCTION: ETMRs are highly lethal, pediatric embryonal brain tumors, previously classified as various histologic diagnoses including supratentorial primitive neuroectodermal tumors (sPNET) and CNS PNET. With recognition that these tumors harbor recurrent amplification of a novel oncogenic miRNA cluster on chr19, C19MC, ETMRs were designated as a distinct biological and molecular entity with a spectrum of histologic and clinical manifestations. METHODS: We reviewed published literature describing clinical presentation, the genetic and epigenetic drivers of oncogenesis, and recent therapeutic strategies adopted to combat these aggressive tumors. RESULTS: As a consequence of C19MC amplification, ETMRs upregulate several oncogenic and pluripotency proteins, including LIN28A, DNMT3B and MYCN, that confer a unique epigenetic signature reminiscent of nascent embryonic stem cells. In this review, we focus on the dysregulation of miRNAs in ETMR, the major pathogenic mechanism identified in this disease. CONCLUSION: Despite the use of multi-modal therapeutic regimens, ETMR patients have dismal survival. Understanding the unique biology of these tumors has provided new insights towards novel therapeutic targets.

Living donor financial assistance programs in liver transplantation: The global perspective.

Living donor liver transplantation (LDLT) has increased availability of liver transplantation, particularly in countries with limited access to deceased organ donors. It is unclear how individual countries address the financial impact of donation for potential living donors. Herein, living liver donor financial supports were examined, focusing on countries performing ≥10 LDLT per year in the World Health Organization Transplant Observatory. Categories included health insurance coverage, reimbursement of lost wages, employment protection, and other incentives designed to promote living liver donation. Overall, 26 countries have some form of asssistance in removing disincentives to ease the financial burden of living donation, ranging from childcare, accommodations, meals, and travel reimbursement, to coverage of medical complications post-donation. Most countries provide donation-related medical coverage. Fourteen provide reimbursement of lost wages and/or paid time off. Several unique programs were designed to incentivize living donation, including free entry to museums and observatories, parking and airline discounts, and exemptions on mortgages and medical deductibles. This study highlights the broad range of programs designed to support living liver donation in high-volume LDLT countries. The data collected in this study can provide a framework for other nations to propose and implement ethical reimbursement and incentivization for living liver donors.

Primary care physician perspectives on barriers to diagnosing axial Spondyloarthritis: a qualitative study.

BACKGROUND: The average delay in diagnosis for patients with axial spondyloarthritis (axSpA) is 7 to 10 years. Factors that contribute to this delay are multifactorial and include the lack of diagnostic criteria (although classification criteria exist) for axSpA and the difficulty in distinguishing inflammatory back pain, a key symptom of axSpA, from other highly prevalent forms of low back pain. We sought to describe reasons for diagnostic delay for axSpA provided by primary care physicians. METHODS: We conducted a qualitative research study which included 18 US primary care physicians, balanced by gender. Physicians provided informed consent to participate in an in-depth interview (< 60 min), conducted in person (n = 3) or over the phone (n = 15), in 2019. The analysis focuses on thoughts about factors contributing to diagnostic delay in axSpA. RESULTS: Physicians noted that the disease characteristics contributing to diagnostic delay include: back pain is common and axSpA is less prevalent, slow progression of axSpA, intermittent nature of axSpA pain, and in the absence of abnormal radiographs of the spine or sacroiliac joints, there is no definitive test for axSpA. Patient characteristics believed to contribute to diagnostic delay included having multiple conditions in need of attention, infrequent interactions with the health care system, and "doctor shopping." Doctors noted that patients wait until the last moments of the clinical encounter to discuss back pain. Problematic physician characteristics included lack of rapport with patients, lack of setting appropriate expectations, and attribution of back pain to other factors. Structural/system issues included short appointments, lack of continuity of care, insufficient insurance coverage for tests, lack of back pain clinics, and a shortage of rheumatologists. CONCLUSION: Primary care physicians agreed that lengthy axSpA diagnosis delays are challenging to address owing to the multifactorial causes (e.g., disease characteristics, patient characteristics, lack of definitive tests, system factors).