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Background: Biallelic variants in HPCA were linked to isolated dystonia (formerly DYT2) in 2015. Since then, the clinical spectrum of HPCA -related disorder has expanded up to including a complex syndrome encompassing neurodevelopmental delay, generalized dystonia with bulbar involvement, and infantile seizures., Cases: We report four individuals with a new phenotype of childhood-onset choreo-dystonia belonging to two unrelated Iranian pedigrees and harboring a novel homozygous nonsense pathogenic variant NM_002143.3:c.49C>T p.(Arg17*) in HPCA . Although the families are both Iranian, haplotype analysis of the exome data did not reveal a founder effect of the variant., Literature Review: A systematic review of articles on HPCA and dystonia published since the disease gene discovery (PubMed; search on July 09, 2022; search strategy "HPCA AND dystonia", "HPCA AND movement disorder", "hippocalcin AND dystonia", and "hippocalcin AND movement disorder"; no language restriction) resulted in 18 references reporting 10 cases from six families. HPCA -related dystonia was isolated or in various combinations with neurodevelopmental delay, intellectual disability, seizures, cognitive decline, and psychiatric comorbidity. Onset of dystonia ranged from infancy to early adulthood. Dystonia started in the limbs or neck and became generalized in most cases. Brain MRI was unremarkable in nearly all cases where performed. There was poor or no response to common antidystonic medications in most cases., Conclusions: Our case series expands the pheno-genotypic spectrum of HPCA -related disorder by describing childhood-onset choreo-dystonia as a new phenotype, reporting on a recurrent novel pathogenic nonsense variant in HPCA , and suggesting that exon 2 of HPCA might be a mutational hotspot., Competing Interests: Biological samples of pedigree A were collected as part of the SYNaPS Study Group collaboration funded by The Wellcome Trust and strategic award (Synaptopathies) funding (WT093205MA and WT104033AIA) and research was conducted as part of the Queen Square Genomics group at University College London, supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The authors declare that there are no conflicts of interest relevant to this work., (© 2022 International Parkinson and Movement Disorder Society.)

As defined by the World Health Organization, the Eastern Mediterranean Region (EMR), given its special geopolitical situation and internal/external conflicts, faces an increase in illegal activities such as drug production and trafficking, highlighting the need for a comprehensive understanding of the substance use situation. On the basis of a review of published papers between 2015 and 2021 we briefly review substance use in the EMR with special focus on the emerging drugs pertinent to this region, namely tramadol, captagon and khat., Competing Interests: None., (© The Author(s) 2021.)

The objective of the current study was to evaluate the phytochemical and pharmacological potential of the Cornus macrophylla . C. macrophylla belongs to the family Cornaceae. It is locally known as khadang and is used for the treatment of different diseases such as analgesic, tonic, diuretic, malaria, inflammation, allergy, infections, cancer, diabetes, and lipid peroxidative. The crude extract and different fractions of C. macrophyll were evaluated by gas chromatography and mass spectroscopy (GC-MS), which identified the most potent bioactive phytochemicals. The antioxidant ability of C. macrophylla was studied by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and 1,1 diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude and subsequent fractions of the C. macrophylla were also tested against anti-inflammatory enzymes using COX-2 (Cyclooxygenase-2) and 5-LOX (5-lipoxygenase) assays. The molecular docking was carried out using molecular operating environment (MOE) software. The GC-MS study of C. macrophylla confirmed forty-eight compounds in ethyl acetate (Et.AC) fraction and revealed that the Et.AC fraction was the most active fraction. The antioxidant ability of the Et.AC fraction showed an IC 50 values of 09.54 μg/mL and 7.8 μg/mL against ABTS and DPPH assay respectively. Among all the fractions of C. macrophylla , Et.AC showed excellent activity against COX-2 and 5-LOX enzyme. The observed IC 50 values were 93.35 μg/mL against COX-2 and 75.64 μg/mL for 5-LOX respectively. Molecular docking studies supported these in vitro results and confirmed the anti-inflammatory potential of C. macrophylla. C. macrophylla has promising potential as a source for the development of new drugs against inflammation in the future.

This research was planned to synthesize cyano-acetate derivatives of succinimide and evaluate its comparative biological efficacy as anti-inflammatory, anti-cholinesterase and anti-diabetic, which was further validated by molecular docking studies. The three cyano-acetate derivatives of succinimide including compound 23 Methyl 2-cyano-2-(2,5-dioxopyrrolidin-3-yl)acetate, compound 31 Methyl 2-cyano-2-(1-methyl-2,5-dioxopyrrolidin-3-yl)acetate and compound 44 Methyl 2-cyano-2-(1-ethyl-2,5-dioxopyrrolidin-3-yl) acetate were synthesized. The mentioned compounds were checked for in vitro anti-inflammatory, anti-cholinesterase and anti-diabetic (α-amylase inhibition) activity. To validate the in vitro results, computational studies were carried out using molecular operating environment to analyse the BE, i.e. binding energies of all synthesized compounds against the respective enzymes. The Compounds 23, 31, 44 exhibited anti-inflammatory via inhibiting COX-2 (IC 50 value of 204.08, 68.60 and 50.93 µM, respectively), COX-1 (IC 50 value of 287, 185, and 143 µM, respectively) and 5-LOX (IC 50 value of 138, 50.76 and 20, 87 µM respectively) . They exhibited choline-mimetic potential, such as compound 23, 31 and 44 inhibited AChE enzyme (IC 50 value of 240, 174, and 134 µM, respectively) and BChE enzyme (IC 50 value of 203, 134 and 97 µM, respectively). The Compounds 23, 31, 44 exhibited anti-diabetic effect via inhibiting α-amylase enzyme (IC 50 values of 250, 106 and 60 µM, respectively). Molecular docking studies revealed that the synthesized compounds have good binding affinity in the binding pockets of AChE, BChE, COX-2, 5-LOX and α-amylase enzyme and showed high binding energies. The synthesized succinimide derivatives, i.e. compound 23, 31, 44 showed marked inhibitory activities against cyclooxygenase, lipoxygenase, α-amylase and cholinesterase enzymes. Among these three, compound 44 and 31 showed strong anti-inflammatory and anti-diabetic activity while they displayed moderate anti-cholinesterase activity supported by molecular docking results.Communicated by Ramaswamy H. Sarma.

Background: Measuring family caregivers' quality of life plays a significant role in improving the quality, efficiency, development, and provision of efficient services for patients with COVID-19. As a result, evaluating the quality of life requires the use of valid and reliable measures that are culturally appropriate. This study was conducted to determine the psychometric properties of the Persian version of the Quality of Life in Life-Threatening Illness-Family Carer Version (QOLLTI - F) in patients with COVID-19., Methods: This methodological study was carried out in 2021 at Baqiyatallah Hospital in Tehran. After gaining approval from the tool creator, the translation was carried out utilizing the forward-backward approach. Cognitive interviews with 10 family caregivers of COVID-19 patients were used to demonstrate face validity. Moreover, construct validity was identified by performing exploratory factor analysis (EFA) ( n = 251), confirmatory factor analysis (CFA) ( n = 200), and convergent validation using Zarit Burden Interview (ZBI) questionnaire. For scale reliability, internal consistency and stability were performed using Cronbach's Alpha Coefficient and test-retest, respectively., Results: 451 family caregivers of patients with COVID-19 were enrolled in this study. Three factors with a cumulative variance of 51.85% were extracted during EFA: (1) Caregiver's physical-emotional status, (2) Satisfaction with the situation, and (3) Caregiver's concerns. CFA showed that the model enjoyed a moderate to a good fit of information (RMSEA: 0.087; NFI: 0.98; CFI: 0.91; IFI: 0.91; GFI 0.89; standardized RMR: 0.070). A significant correlation was found between the Persian version of the ZBI and participants' total scores of QOLLTI - F v3 ( r = -0.196, P = 0.000). Cronbach's Alpha Coefficient = 0.719 and ICC stability reliability = 0.71 of the questionnaire were confirmed., Conclusion: The Persian version of the QOLLTI - F v3 is a valid and reliable scale that can measure family caregivers' quality of life during a Life-Threatening illness in patients with COVID-19. This instrument may be utilized in clinical trials and research to enhance the quality of life for family carers in Iranian society., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fereidouni, Ebadi, Rassouli, Hosseini, Mollahadi, Khorshidvand, Javid, Ansari, Rezaei and Barasteh.)

Background: Syphilis rates have increased substantially over the past decade. Women are an important population because of negative sequalae and adverse maternal outcomes including congenital syphilis. We assessed whether racial and ethnic disparities in primary and secondary (P&S) syphilis among heterosexually active women differ by region and age group., Methods: We synthesized 4 national surveys to estimate numbers of heterosexually active women in the United States from 2014 to 2018 by region, race and ethnicity, and age group (18-24, 25-29, 30-44, and ≥45 years). We calculated annual P&S syphilis diagnosis rates, assessing disparities with rate differences and rate ratios comparing White, Hispanic, and Black heterosexually active women., Results: Nationally, annual rates were 6.42 and 2.20 times as high among Black and Hispanic than among White heterosexually active women (10.99, 3.77, and 1.71 per 100,000, respectively). Younger women experienced a disproportionate burden of P&S syphilis and the highest disparities. Regionally, the Northeast had the highest Black-White and Hispanic-White disparities using a relative disparity measure (relative rate), and the West had the highest disparities using an absolute disparity measure (rate difference)., Conclusions: To meet the racial and ethnic disparity goals of the Sexually Transmitted Infections National Strategic Plan, tailored local interventions that address the social and structural factors associated with disparities are needed for different age groups., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflicts of interest to disclose. This work was supported by Centers for Disease Control and Prevention/National Center for HIV, Viral Hepatitis, STD, and TB Prevention Epidemiological and Economic Modeling Agreement (No. 5U38PS004650). The findings and conclusions are solely the responsibility of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the Department of Health and Human Services., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

To improve the survivability of Lactobacillus rhamnosus probiotics, nanoliposomes (NLs) coated with chitosan (CH)-gelatin (GE) polyelectrolytes have been synthesized and characterized. The produced CH-GE-coated NLs containing L. rhamnosus had mean sizes in the range of 134.8-495.8 nm. HRTEM showed the smooth spherical shape of the vesicles. ATR-FTIR findings indicated the successful coating of the produced NLs by the used CH-GE polyelectrolytes. According to DSC results, CH-GE polyelectrolytes desorption on the surface of NLs altered the physical characteristics of the phospholipid bilayers. Here, an increase in the melting temperature (T m ) from 119.9 to 127.5 °C in L. rhamnosus-loaded CH-GE-coated NLs made this system more stable than uncoated liposomes. Furthermore, the CH-GE coated nanoparticles loaded with L. rhamnosus exhibited a significant enhancement in the viability of cells under simulated gastrointestinal fluids (SGF/SIF). These results may guide the potential application of polyelectrolytes-coated NLs as a carrier of probiotic cells in functional food development., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Colorectal cancer is the third most malignant cancer worldwide. Despite novel treatment options, the incidence and mortality rates of colon cancer continue to increase in most countries, especially in US, European and Asian countries. Colorectal carcinogenesis is multifactorial, including dietary and genetic factors, as well as lacking physical activity. Vegetables and fruits contain high amounts of secondary metabolites, which might reduce the risk for colorectal carcinogenesis. Flavonoids are important bioactive polyphenolic compounds. There are more than 4,000 different flavonoids, including flavanones, flavonoids, isoflavonoids, flavones, and catechins in a large variety of plant., Hypothesis: Among various other flavonoids, naringin in Citrus fruits has been a subject of intense scrutiny for its activity against many types of cancer, including colorectal cancer. We hypothesize that naringin is capable to inhibit the growth of transformed colonocytes and to induce programmed cell death in colon cancer cells., Results: We comprehensively review the inhibitory effects of naringin on colorectal cancers and address the underlying mechanistic pathways such as NF-κB/IL-6/STAT3, PI3K/AKT/mTOR, apoptosis, NF-κB-COX-2-iNOS, and β-catenin pathways., Conclusion: Naringin suppresses colorectal inflammation and carcinogenesis by various signaling pathways. Randomized clinical trials are needed to determine their effectiveness in combating colorectal cancer., (Copyright © 2021. Published by Elsevier GmbH.)

Aim: The gold standard technique of Sentinel Lymph Node Biopsy (SLNB) is the dual technique of radioactive tracer with blue dye. The aim of this study was to assess the node identification rate and feasibility in terms of ease of use of this technique for SLNB in breast cancer patients. Methods: Retrospectively collected data of 143 breast cancer patients with clinically and radiologically negative axilla were analysed. SLNB procedures were performed using the superparamagnetic iron oxide (SPIO) nanoparticles. Sentinel lymph nodes were identified using the Sentimag magnetometer and visual aid. Results: A total of 146 SLNB procedures were undertaken on 143 patients. Lymph node identification rate (IR) was 97.9%. Thirty seven patients (25.3%) were detected with cancer in their lymph nodes, 19% had at least one macrometastasis, 6% at least one micrometastasis and 1% had ITCs. The mean average lymph node retrieval was 2.2 nodes per procedure. Mild brownish discolouration was noted around the injection site. No allergic reaction or side effect of Sienna+î tracer / Magtraceî was reported., Conclusion: The new magnetic detection method of sentinel lymph nodes (Sentimag) is effective, feasible and comparable to the gold standard technique of sentinel lymph node biopsy in patients with breast cancer., (Celsius.)

Myasthenia gravis (MG) is an immune-mediated potentially treatable disease in which rapid diagnosis and proper treatment can control symptoms. Treatment should be individualized in each patient according to distribution (ocular or generalized) and severity of the weakness, antibody status, thymus pathology, patient comorbidities, and preferences. A group of Iranian neuromuscular specialists have written these recommendations to treat MG based on national conditions. Four of the authors performed an extensive literature review, including PubMed, EMBASE, and Google Scholar, from 1932 to 2020 before the central meeting to define headings and subheadings. The experts held a 2-day session where the primary drafts were discussed point by point. Primary algorithms for the management of MG patients were prepared in the panel discussion. After the panel, the discussions continued in virtual group discussions, and the prepared guideline was finalized after agreement and concordance between the panel members. Finally, a total of 71 expert recommendations were included. We attempted to develop a guideline based on Iran's local requirements. We hope that these guidelines help healthcare professionals in proper treatment and follow-up of patients with MG., (2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Caralluma edulis is a well-known species of the genus Caralluma from Apocynaceae, commonly known as chunga. Caralluma species are mostly succulent perennial herbs, several of which are edible species. The plant has an outstanding therapeutic background in the traditional system of treatment. It has been recommended for the treatment of a number medical disorders such as hypertension, Alzheimer's disease, rheumatism, gastric problems and leprosy. Traditionally the stem was boiled in water and this extract was then used to cure diabetes. The pharmacological effects of C. edulis have also been explored in various in vitro and in vivo experiments. In this regard, the extract of the plant exhibited strong antioxidant, and analgesic activity against inflammation as well as xylene-mediated ear edema as topical effects. The significant anti-hyperlipidemic effect of the plant extract is also reported. However, the extract was found insignificant in the reversal of alloxan-induced diabetes in the rabbit model at test doses. These pharmacological effects are strongly supported by the presence of different bioactive phytochemicals in the plant. These groups of compounds include sterols, terpenoids, flavonoids, and pregnane glycosides. C. edulis is a very potential member of the genus Caralluma with strong traditional history, phytochemistry and phytopharmacology, and needs further exploration for clinically used lead compounds. In this review, we have focused on combining different reported data on the traditional uses of the plant, its phytochemical profile and pharmacological effects in different experimental assay along with subsequent future prospects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiological syndrome characterized by such symptoms as headaches, altered consciousness, blurred vision, seizure, and focal neurological deficits. We herein present well-documented PRES cases and discuss the risk factors and characteristic imaging patterns of this syndrome., Materials and Methods: We prospectively examined 31 patients with PRES in Alzahra Hospital, Isfahan, Iran, and compared the underlying diseases of PRES in terms of their clinical features and cranial magnetic resonance imaging (MRI) findings., Results: The most common underlying disease was hypertension (90.3%), followed by systemic lupus erythematosus (32.3%), preeclampsia (25.8%), chronic renal failure (22.6%), and rheumatoid arthritis (22.6%). Interestingly, we also reported heroin abuse as a possible risk factor for PRES (9.7%). The most frequent clinical signs were headaches (54.8%), seizure (54.8%), and blurred vision (35.5%). The most frequent lesions on cranial MRI were in the parieto-occipital area (87.1%), followed by the cerebellum (19.4%) and the frontal lobe (12.9%). Other abnormalities on MRI were less common. In addition, 16.1% of the study population had vasospasm on magnetic resonance arteriography (MRA). Clinical recovery was followed by radiological resolution in all the patients., Conclusions: The clinical presentation is nonspecific, most patients present with a combination of symptoms, particularly headaches and seizure. MRI is crucial for the diagnosis of PRES, and MRA is useful in that it can identify associated vasospasm. Timely diagnosis and treatment are required to avoid a devastating outcome., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Advanced Biomedical Research.)

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Mental and neurological diseases including depression, Parkinson's disease, dementia, epilepsy, anxiety disorders and bipolar disorders account for a considerable amount of the world's disease burden. Unfortunately, drugs used in the treatment of neurological diseases are expensive, symptomatic and they produce undesirable side effects. People from different cultures prefer to use medicinal plants for the treatment of various ailments ranging from plain to perplex disorders because they are most affordable, cost effective and easily accessible source of treatment in the primary healthcare system throughout the world. Withania coagulans, an erect grayish under-shrub belongs to family Solanaceae. It is common in Pakistan, East India, Iran and Afghanistan. The objective of this study was to analyze the anti-seizure activity of crude methanolic extract of Withania coagulans fruits (MeWc). For screening of this activity, maximal electroshock seizures model (MES) and chemically-induced seizures models were used. In maximal electroshock seizures test MeWc showed significant dose dependent percent protection against hind-limb tonic extension; significant and dose-dependent increase in latency to myoclonic jerks and tonic clonic convulsions and decrease in seizures duration were observed in PTZ-induced seizures. In strychnine-induced convulsions MeWc significantly increased latency to hind-limb tonic extension and percent protection from death in a dose-dependent manner. Thus, it was inferred from the experiments that extract of Withania coagulans showed anticonvulsant activity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pompe disease, also denoted as acid maltase or acid α-glucosidase deficiency or glycogen storage disease type II, is a rare, autosomal recessive lysosomal storage disorder. Several reports have previously described Pompe disease in Iran and considering increased awareness of related subspecialties and physicians, the disease's diagnosis is growing. Objective: This guideline's main objective was to develop a national guideline for Pompe disease based on national and international evidence adapting with national necessities. Methods: A group of expert clinicians with particular interests and experience in diagnosing and managing Pompe disease participated in developing this guideline. This group included adult neurologists, pediatric neurologists, pulmonologists, endocrinologists, cardiologists, pathologists, and physiatrists. After developing search terms, four authors performed an extensive literature review, including Embase, PubMed, and Google Scholar, from 1932 to current publications before the main meeting. Before the main consensus session, each panel member prepared an initial draft according to pertinent data in diagnosis and management and was presented in the panel discussion. Primary algorithms for the diagnosis and management of patients were prepared in the panel discussion. The prepared consensus was finalized after agreement and concordance between the panel members. Conclusion: Herein, we attempted to develop a consensus based on Iran's local requirements. The authors hope that disseminating these consensuses will help healthcare professionals in Iran achieve the diagnosis, suitable treatment, and better follow-up of patients with infantile-onset Pompe disease and late-onset Pompe disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fatehi, Ashrafi, Babaee, Ansari, Beiraghi Toosi, Boostani, Eshraghi, Fakharian, Hadipour, Haghi Ashtiani, Moravej, Nilipour, Sarraf, Sayadpour Zanjani and Nafissi.)

Background: Despite declining HIV infection rates, persistent racial and ethnic disparities remain. Appropriate calculations of diagnosis rates by HIV transmission category, race and ethnicity, and geography are needed to monitor progress towards reducing systematic disparities in health outcomes. We estimated the number of heterosexually active adults (HAAs) by sex and state to calculate appropriate HIV diagnosis rates and disparity measures within subnational regions., Methods: The analysis included all HIV diagnoses attributed to heterosexual transmission in 2018 in the United States, in 50 states and the District of Columbia. Logistic regression models estimated the probability of past-year heterosexual activity among adults in three national health surveys, by sex, age group, race and ethnicity, education category, and marital status. Model-based probabilities were applied to estimated counts of HAAs by state, which were synthesized through meta-analysis. HIV diagnoses were overlaid to calculate racial- and ethnic-specific rates, rate differences (RDs), and rate ratios (RRs) among HAAs by sex and state., Results: Nationally, HAA women have a two-fold higher HIV diagnosis rate than HAA men (rate per 100,000 HAAs, women: 6.57; men: 3.09). Compared to White non-Hispanic HAAs, Black HAAs have a 20-fold higher HIV diagnosis rate (RR, men: 21.28, women: 19.55; RD, men: 15.40, women: 31.78) and Hispanic HAAs have a 4-fold higher HIV diagnosis rate (RR, men: 4.68, RD, women: 4.15; RD, men: 2.79, RD, women: 5.39). Disparities were ubiquitous across regions, with >75% of states in each region having Black-to-White RR ≥10., Conclusion: The racial and ethnic disparities across regions suggests a system-wide failure particularly with respect to preventing HIV among Black and Hispanic women. Pervasive disparities emphasize the role for coordinated federal responses such as the current Ending the HIV Epidemic (EHE) initiative., Competing Interests: The authors have declared that no competing interests exist.

Objective: The basic objective of this systematic review was to identify potential biomarkers for chronic stress., Methods: A systematic review of studies linking biomarkers in people with chronic stress was conducted using PRISMA guidelines. The last 40 years' studies were included in the systematic review with no age restrictions; animal studies were excluded from the study. Electronic databases including PubMed, Embase, and Google Scholar were searched for the study purpose. The studies were searched using the combinations of search terms that comprised chronic stress together with the keywords hypothalamic-pituitary-adrenal axis (HPA axis), autonomic nervous system (ANS), immune system, metabolic biomarkers, cortisol, hair cortisol, salivary cortisol, urinary cortisol, epinephrine, norepinephrine, adrenocorticotropic hormone (ACTH), brain-derived neurotropic factor (BDNF), metabolic biomarkers, antioxidants, glucose, hemoglobin, C-reactive protein (CRP), cytokines, pro-inflammatory cytokines, anti-inflammatory cytokines, and tumor necrosis factor (TNF)., Results: A total of 37 studies out of 671 studies met the eligibility criteria and were included in this review. Potential diagnostic biomarkers of chronic stress included cortisol, ACTH, BDNF, catecholamines, glucose, HbA1c, triglycerides, cholesterol, prolactin, oxytocin, dehydroepiandrosterone sulfate (DHEA-S), CRP, and interleukin - 6 and 8. While the others including antioxidants and natural killer (NK) cells require further validation. Taken together, addition, these stress biomarkers have critical prognostic capacities for stress-associated diseases and therapeutic guidance., Conclusion: This systematic review provides an update to the literature by highlighting the role of physiological biomarkers in chronic stress and describing their prognostic and therapeutic values., (Copyright: © International Journal of Health Sciences.)

Introduction: Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine., Methods: In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis., Results: The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements., Conclusion: The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental; therefore, more studies are needed to investigate a causal relationship., Competing Interests: Conflict of interest The authors declare no conflicts of interests., (Copyright© 2021 Iranian Neuroscience Society.)

Physids belong to Class Gastropoda; belong to Phylum Mollusca and being bioindicators, intermediate hosts of parasites and pests hold a key position in the ecosystem. There are three species of Genus Physa i.e. P. fontinalis, Physa acuta and P. gyrina water bodies of Central Punjab and were characterized on the basis of molecular markers High level of genetic diversity was revealed by polymorphic RAPD, however SSR markers were not amplified. The multivariate analysis revealed polymorphism ranging from 9.09 percent to 50 percent among the three Physid species. Total number of 79 loci were observed for the three species under study and 24 loci were observed to be polymorphic. These RAPD fragment(s) can be developed into co dominant markers (SCAR) by cloning and can be further sequenced for the development of the Physa species specific markers to identify the introduced and native species in Pakistan.

Physids belong to Class Gastropoda; Phylum Mollusca have important position in food web and act as bio indicators, pests and intermediate host. Being resistant these are called cockroaches of malacology. Physid snails were collected from different water bodies of Faisalabad (Punjab) and were identified up to species using morphological markers. The morphometry of the specimens was carried out with the help of a digital Vernier caliper in millimeters (mm) using linear measurement of shell characters. Linear regression analysis of the AL/SW ratio vs AL and SL/SW ratio vs AL indicated that allometric growth exists only in Physa acuta when compared with P.gyrina and P. fontinalis. This study will lead to assess the status of the Physid species in Central Punjab. The Principal component analysis shows that the Component 1 (Shell Length) and component 2 (Shell Width) are the most prolific components and nearly 80 percent of the identification. The distance between P. acuta and P. fontinalis is 5.4699, P. acuta and P. gyrina is 7.6411, P. fontinalis and P. gyrina is 16.6080 showing that P. acuta resembles with P. fontinalis, and both these specimens donot resemble with P. gyrina. P.acuta is an invasive species and shows bioactivity making it a potent candidate for bioactive substances.

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic autoimmune demyelinating peripheral neuropathy that leads to symmetrical muscular weakness, sensory deficit, hyporeflexia, chronic fatigue, and impaired quality of life (QoL). The current study aims to investigate the effects of gabapentin versus pregabalin on pain, sleep disturbances, and QoL in CIDP patients., Methods: This clinical trial was conducted on 40 patients diagnosed with CIDP randomly allocated to treatment with 100-500 mg gabapentin (n=20) or 50-300 mg pregabalin (n=20) both co-medicated with 37.5 mg venlafaxine. The dose of gabapentin/pregabalin was adjusted based on the patient's tolerability/response to the treatment. Visual analogue scale (VAS), Pittsburg Sleep Quality Questionnaire and Short Form Health Survey (SF-36) were filled at baseline, within three, six, nine and 12 months after the interventions to assess pain severity, sleep quality and QoL, respectively. The Iranian Registry of Clinical Trials (IRCT) code: IRCT20200217046523N16, https://fa.irct.ir/search/result?query=IRCT20200217046523N16., Results: Gabapentin revealed a dose-dependent efficacy in pain severity ( P -value =0.004, r=0.287), sleep quality ( P -value <0.001, r=0.387) and QoL ( P -value =0.001, r=-0.378), but pregabalin ( P -value >0.05). Co-medication of gabapentin plus venlafaxine could significantly improve sleep quality ( P -value =0.009) and QoL ( P -value =0.004), but pain severity ( P -value =0.796). Pregabalin plus venlafaxine showed statistically significant improvement in pain ( P -value =0.046), sleep quality ( P -value <0.001) and QoL ( P -value <0.001). The comparison of the two medications revealed the superiority of pregabalin in pain relief ( P -value >0.001) and QoL ( P -value =0.03) to pregabalin., Conclusion: Based on this study, the co-medication of pregabalin and venlafaxine led to remarkable superior outcomes compared to venlafaxine plus gabapentin in the management of pain, sleep quality, and QoL due to CIDP., Competing Interests: None., (AJND Copyright © 2021.)

The pharmaceutical industry spends billions of dollars every year for marketing its products to US health care providers. This study investigates the association between industry marketing payments and physicians' prescription in New York and Massachusetts, and examines the effect of the Massachusetts payment restriction policy on this association in comparison with the New York State that has no payment restriction policy. Three panel data models (fixed effects regression (FE), first difference regression (FD), and first difference with lagged independent variable (LFD)) were used to establish the association accounting for unobserved confounders and reverse causality. The main indicator is the total amount of industry payments for meals, drug samples, consulting fees, etc. (excluding research funding, and ownership). Dependent variables are a) yearly days' supply of Medicare Part D prescriptions, b) yearly costs of prescribed prescriptions. Secular time trends, as well as differences between the two states were controlled in all models. All three panel models showed significant positive association between industry payments and physician prescriptions. Particularly, these models show that in the base year (2014), a 1% increase in the annual industry payments was associated with (0.01%-0.04%) increase in days' supply of medication, and (0.01%-0.05%) increase in prescription costs for NYS providers. Moreover, FE and FD models show that compared to NYS physicians, the association of industry payments with days' supply and costs of Medicare Part D prescriptions was (0.01%-0.02%) smaller for MA physicians. Because of the smaller sample size and lower power, the LFD model did not detect a significant difference between the NYS and MA providers. The findings of this study provide additional evidence that industry payments are associated with increases in the volume and cost of Medicare prescriptions. Moreover, these findings provide preliminary evidence that payment restriction policies negatively moderate this association, which calls for further research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

COVID-19 poses grave challenges for mass gatherings. One of the world's largest annual gatherings, Arbaeen, occurs in Iraq. We studied respiratory symptoms and risk and protective factors using representative sampling of Arbaeen pilgrims in 2019 to inform prevention of COVID-19 transmission. Structured sampling was used to recruit walking pilgrims. A questionnaire asked about respiratory symptoms, risk, and preventive factors, including hygiene-related resources of toilet facilities. The commonest symptom reported by the 1842 participants (63.3% male, 36.7% female) was cough (25.6%). Eating in mawkibs (rest areas) with indoor kitchens and drinking only packaged water were associated with lower risk of cough (AOR = 0.72, CI = 0.56-0.94; AOR = 0.60; CI = 0.45-0.78, p < 0.05). Facemask use was associated with increased risk of cough (AOR = 2.71, CI = 2.08-3.53, p < 0.05). Handwashing was not protective against cough, or against (one or more of) cough, fever, or breathlessness in multivariate analysis. Toilet facilities often lacked running water (32.1%) and soap (26.1%), and had shared hand towels (17%). To reduce risk of respiratory infections including COVID-19 during Arbaeen or other mass gatherings, needs include running water, soap, and hygienic hand drying options or hand sanitiser. Education on proper handwashing and facemask approaches and monitoring around food preparation and eating spaces are needed.

The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose >7000 years ago. A wide age-range of patients (6-83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 ± 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: Currently available 3-dimensional (3D) modeling and printing techniques allow for the creation of patient-specific models based on 3D medical imaging data. The authors hypothesized that a low-cost, patient-specific, cardiac computed tomography-based phantom, created using desktop 3D printing and casting, would have comparable image quality, accuracy, and usability to an existing commercially available echocardiographic phantom., Design: Blinded comparative study., Setting: Simulation laboratory at a single academic institution., Participants: Voluntary cardiac anesthesiologists at a single academic institution., Interventions: Stage 1 of the study consisted of an online questionnaire in which a set of basic transesophageal echocardiography (TEE) views obtained from the 3D printed phantom and commercial phantom were presented to participants, who had to identify the views and evaluate their fidelity to clinical images on a Likert scale. In stage 2, participants performed an unblinded basic TEE examination on both phantoms., Measurements and Main Results: The time needed to acquire each basic view was recorded. Overall usability of the phantoms was assessed through a questionnaire. The participants could recognize most of the views. Fidelity ratings for both phantoms were similar (p < 0.05), with the exception of a midesophageal 2-chamber view that was observed better on the 3D printed phantom. The time required to obtain the views was shorter for the 3D printed phantom, although not statistically significant for most views. The overall user experience was better for the 3D phantom for all categories examined (p < 0.05)., Conclusions: The study suggested that a 3D-printed TEE phantom is comparable with the commercially available one with good usability., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Few studies have reported the association of Guillain-Barre syndrome (GBS) and coronavirus disease-2019 (COVID-19) infection. In this study, we reported GBS in six patients infected with COVID-19 and reviewed all existing literature about GBS in association with COVID-19. Methods: This study was performed in three referral centers of COVID-19 in Iran, and six patients with the diagnosis of GBS were enrolled. Patients enrolled in the study with acute progressive weakness according to the demyelinating or axonal variant of GBS, according to Uncini's criteria. Results: Four of our patients had axonal polyneuropathy, two patients had demyelinating polyneuropathy, and one patient required mechanical ventilation. All our patients had a favorable response to treatment. In one patient, the GBS symptoms recurred four months after the first episode. Conclusion: Limited case reports suggest a possible association between GBS and COVID-19. Such associations may be an incidental concurrence or a real cause-and-effect linkage; however, more patients with epidemiological studies are necessary to support a causal relationship., (Copyright © 2020 Iranian Neurological Association, and Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Objectives: In the United States, rising rates of overdose deaths and recent outbreaks of hepatitis C virus and HIV infection are associated with injection drug use. We updated a 2014 review of systems-level opioid policy interventions by focusing on evidence published during 2014-2018 and new and expanded opioid policies., Methods: We searched the MEDLINE database, consistent with the 2014 review. We included articles that provided original empirical evidence on the effects of systems-level interventions on opioid use, overdose, or death; were from the United States or Canada; had a clear comparison group; and were published from January 1, 2014, through July 19, 2018. Two raters screened articles and extracted full-text data for qualitative synthesis of consistent or contradictory findings across studies. Given the rapidly evolving field, the review was supplemented with a search of additional articles through November 17, 2019, to assess consistency of more recent findings., Results: The keyword search yielded 535 studies, 66 of which met inclusion criteria. The most studied interventions were prescription drug monitoring programs (PDMPs) (59.1%), and the least studied interventions were clinical guideline changes (7.6%). The most common outcome was opioid use (77.3%). Few articles evaluated combination interventions (18.2%). Study findings included the following: PDMP effectiveness depends on policy design, with robust PDMPs needed for impact; health insurer and pharmacy benefit management strategies, pill-mill laws, pain clinic regulations, and patient/health care provider educational interventions reduced inappropriate prescribing; and marijuana laws led to a decrease in adverse opioid-related outcomes. Naloxone distribution programs were understudied, and evidence of their effectiveness was mixed. In the evidence published after our search's 4-year window, findings on opioid guidelines and education were consistent and findings for other policies differed., Conclusions: Although robust PDMPs and marijuana laws are promising, they do not target all outcomes, and multipronged interventions are needed. Future research should address marijuana laws, harm-reduction interventions, health insurer policies, patient/health care provider education, and the effects of simultaneous interventions on opioid-related outcomes.

Background: Alcohol is a leading risk factor for death and disability globally. Due to the Islamic prohibition of alcohol consumption, alcohol policy is an under-studied and sensitive topic in Muslim majority countries (MMCs). In addition, drinkers in these countries may face barriers to treatment access due to stigma or the legal status of alcohol. Using Iran as a case study this paper explores how alcohol treatment is planned and delivered in the complex environment of an MMC., Method: We searched academic and grey literature, clinical manuals, guidelines and policy documents for information on the development and implementation of alcohol treatment policy in Iran. The search was conducted in English, Persian and Arabic. We conducted 6 consultations to verify information obtained. We analysed information based on the Walt & Gilson health policy analysis triangle, which identifies context, process, actors and content as key factors for understanding policy., Results: Iran initiated an alcohol-specific national strategy in 2011-2012 that aims to prevent, reduce and treat alcohol use disorders. This strategy has been designed to be implemented on a multi-sectoral level. Screening and prevention are mainly initiated in primary health care and cases are referred accordingly. Alcohol treatment is provided in specialised outpatient and inpatient settings. Due to contextual factors such as stigma, feasibility and affordability, alcohol outpatient units are planned to be integrated into existing public/ private drug addiction treatment facilities. However, the Ministry of Health has faced many challenges in implementing this pilot project. To date only small numbers of outpatient and inpatient units have formally commenced offering alcohol treatment., Conclusion: Implementing alcohol treatment has been challenging for Iran. Approval of new treatment programs may not be seen as a priority because of the low prevalence of alcohol use disorders in the country. Also, policy makers are implementing treatment services with caution due to the existing alcohol prohibition for the country's Muslim majority population. Barriers to treatment seeking need to be addressed at the micro and macro levels. Support from international agencies such as the WHO could assist MMCs to develop appropriate services that are feasible for their unique alcohol policy environment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Since its introduction in 1984, Percutaneous Transvenous Mitral Commissurotomy (PTMC) has become established as a safe and effective treatment for rheumatic Mitral Stenosis (MS).( Ben Farhat et al., 1998) 1 Chronic pressure and volume overload imposed by MS causes left atrial (LA) and Left Atrial Appendage (LAA) dysfunction. Risk of cerebrovascular accident (CVA) is increased approximately 17-fold in patients of MS in Atrial Fibrillation (AF) and is present even in patients of MS in sinus rhythm (SR). This study was undertaken to evaluate the effect of PTMC on LAA function by Trans-esophageal echocardiography (TEE) Doppler and Doppler Tissue Imaging (DTI)., Methods: Total 70 cases were enrolled in this study. Patients with symptomatic severe MS (Mitral Valve Area <1.5cm2), in SR, who underwent a successful PTMC during the period from May 2016 to May 2019 were selected. All the patients underwent Clinical examination, ECG, detailed TTE and TEE before, immediately after (within 24 h) & after 6 months of PTMC., Results: There was non significant improvement in Left Atrial appendage fractional area change {LAAAC (%)} immediately Post PTMC but there was significant improvement at 6 months Post PTMC. There was significant increase in LAA PW Doppler velocities (LAAEDE, LAALDE and LAAF velocity) immediately Post PTMC which got further improved significantly at 6 months of follow up. There was significant increase in LAA DTI velocities (E LAA , A LAA and S LAA velocity) immediately Post PTMC which got further improved significantly at 6 months of follow up., Conclusion: PTMC improves left atrial appendage function in patients with mitral stenosis., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Arbaeen is an annual religious procession in Iraq with an estimated 17-20 million participants. Public health risks associated with such a mass gathering can be serious at both local and global levels. This is the first quantitative examination of risk factors for, and symptoms of, infectious disease among Arbaeen participants., Methods: A cross-sectional survey was conducted of a convenience sample of 191 Arbaeen participants in 2017. Interviewers administered a structured questionnaire. Questions included food sources, preventive measures used and symptoms of infectious diseases during the procession., Results: Data were collected for 191 participants (143 males, 58 females). The most prevalent symptoms were respiratory (runny nose: 22.6%, cough: 22.5%). Diarrhoea was reported by 12.6% of participants, with a strong association with high-income country origin and eating (commercial) street food (odds ratios 6.1 and 4.1, respectively, p < 0.05). All symptoms investigated, except breathlessness, were more prevalent in high-income country participants (p < 0.05)., Conclusion: Street food and high-income country origin were independent risk factors for respiratory or gastrointestinal infection symptoms in this sample of Arbaeen participants. However, these results cannot be generalised due to possible selection bias. Further studies are required to inform policy development and health system preparedness to reduce Arbaeen-associated health risks., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Multiple sclerosis (MS) is a common autoimmune inflammatory disease in the central nervous system (CNS) without exact pathology. Environmental factors such as infections have a causal or protective role in MS. Helicobacter pylori (HP) is one of the infections in digestive diseases and previous studies reported controversial findings of this infection role in MS. So, we conducted this study to assess the frequency of HP infection in patients with MS in comparison to the healthy population. Methods: This cross-sectional study was undertaken between 2015 and 2019. 191 participants including 58 patients with clinically isolated syndrome (CIS), 57 patients with relapsing-remitting MS (RRMS), 39 patients with secondary progressive MS (SPMS), and 39 age- and sex-matched healthy controls (HCs) were tested for the presence of HP immunoglobulin G (IgG) and IgM antibodies (Abs) in their serum sample. Results: The frequency of HP IgG seropositivity in patients with SPMS was significantly higher than patients with CIS [Odds ratio (OR): 6.333, 95% confidence interval (CI): 2.522-15.906, P < 0.001], patients with RRMS (OR: 4.583, 95% CI: 1.842-11.407, P = 0.001), and HCs (OR: 8.485, 95% CI: 3.058-23.540, P < 0.001). We did not find a significant difference among other study groups regarding IgG seropositivity. No significant difference among groups regarding HP IgM seropositivity was evident. On univariate model, Expanded Disability Status Scale (EDSS) score (OR: 1.038, 95% CI: 1.038-1.460, P = 0.017) and SPMS (OR: 4.583, 95% CI: 1.842-11.407, P = 0.001) were predictor for HP IgG seropositivity. On multivariate model, only SPMS had higher risk for HP IgG seropositivity compared to RRMS (OR: 5.554, 95% CI: 1.327-23.253, P = 0.019). We did not find a significant association between clinical and demographic variables with HP IgM seropositivity. Conclusion: Based on our findings, progressive MS and HP infection may have association. Further longitudinal studies with large sample size are needed to determine the role of HP infection in MS., (Copyright © 2020 Iranian Neurological Association, and Tehran University of Medical Sciences.)

Background: Fat infiltration in individual muscles of sporadic inclusion body myositis (sIBM) patients has rarely been assessed., Methods: Sixteen sIBM patients were assessed using MRI of the thighs and lower legs (LL). The severity of fat infiltration, proximal-to-distal and side asymmetries, and the correlations with clinical and functional parameters were investigated., Results: All the patients had fat-infiltrated muscles, and thighs were more severely affected than LL. A proximal-to-distal gradient of fat infiltration was mainly observed for adductors, quadriceps, sartorius, and medial gastrocnemius muscles. A strong negative correlation was observed between the whole muscle fat fraction in the thighs and LL and the Inclusion Body Myositis Functional Rating Scale and Medical Research Council scores for the lower limbs., Conclusions: Fat infiltration in individual muscles of sIBM patients is heterogeneous in terms of proximal-to-distal gradient and severity was correlated with clinical scores. These results should be considered for both natural history investigation and clinical trials., (© 2020 Wiley Periodicals, Inc.)

Background: Muslim majority countries (MMCs) typically have limited alcohol policy development due to Islamic prohibition of alcohol consumption. In response to recent increases in alcohol consumption and related harms, MMCs have introduced civil alcohol policies, ranging from total prohibition to European-style regulations. Using Iran as a case study, we describe how alcohol prohibition is translated into policy in the face of influences from globalisation., Methods: We collected information from publicly available literature and policy documents, because of the sensitivity of the topic of alcohol in Iran. The search was conducted in English and Persian. We verified information through consultations with policy actors. We also reviewed newspapers over periods just before the 1979 Islamic revolution, and before and after the 2011 alcohol policy (2008-2010; 2014-2016) was introduced. We analysed policy content based on WHO policy recommendations and used the Walt & Gilson health framework to identify policy content, context, actors and process., Results: Despite its broad approach of civil prohibition with concessions for the non-Muslim population, Iran has developed approaches to reduce the harmful impacts of alcohol and adopted nine of ten policy interventions recommended by WHO. Pricing policy was the only intervention not used. We identified contextual challenges, such as resources, stigma and cultural offence that influence policy development., Conclusion: MMCs face challenges in creating civil alcohol policies. Iran has taken steps, including a national alcohol strategy, to reduce alcohol-related harms. The socio-cultural, governance and historical context have shaped Iran's adaptation of policy interventions recommended by WHO., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in SMN1 is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non-SMN1-related spinal muscular atrophies are caused by variants in a number of genes, including VRK1, encoding the vaccinia-related kinase 1 (VRK1). VRK1 variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly., Results: Here, we report an association of a novel homozygous splice variant in VRK1 (c.1159 + 1G>A) with childhood-onset SMA or juvenile lower motor disease with brisk tendon reflexes without pontocerebellar hypoplasia and normal intellectual ability in a family with five affected individuals. We show that the VRK1 splice variant in patients causes decreased splicing efficiency and a mRNA frameshift that escapes the nonsense-mediated decay machinery and results in a premature termination codon., Conclusions: Our findings unveil the impact of the variant on the VRK1 transcript and further support the implication of VRK1 in the pathogenesis of lower motor neuron diseases., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Variants in MCM3AP , encoding the germinal-centre associated nuclear protein, have been associated with progressive polyneuropathy with or without intellectual disability and ptosis in some cases, and with a complex phenotype with immunodeficiency, skin changes and myelodysplasia. MCM3AP encoded protein functions as an acetyltransferase that acetylates the replication protein, MCM3, and plays a key role in the regulation of DNA replication. In this study, we report a novel variant in MCM3AP (p.Ile954Thr), in a family including three affected individuals with characteristic features of Charcot-Marie-Tooth neuropathy and multiple sclerosis, an inflammatory condition of the central nervous system without known genetic cause. The affected individuals were homozygous for a missense MCM3AP variant, located at the Sac3 domain, which was predicted to affect conserved amino acid likely important for the function of the germinal-centre associated nuclear protein. Our data support further expansion of the clinical spectrum linked to MCM3AP variant and highlight that MCM3AP should be considered in patients with accompaniment of recessive motor axonal Charcot-Marie-Tooth neuropathy and multiple sclerosis., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objectives: This study researched right atrial (RA) deformation indexes and their association with all-cause mortality among subjects with or without heart failure (HF)., Background: Although left atrial dysfunction is well described in HF, patterns of RA dysfunction and their prognostic implications are unclear. Cardiac magnetic resonance (CMR) imaging can provide excellent visualization of the RA. We used CMR to characterize RA phasic function in HF and to assess its prognostic implications., Methods: This study prospectively examined 608 adults without HF (n = 407), as well as adults with HF with a reduced ejection fraction (HFrEF) (n = 105) or with HF with a preserved ejection fraction (HFpEF) (n = 96). Phasic RA function was measured via volume measurements and feature-tracking methods to derive longitudinal strain. All-cause death was ascertained over a median follow-up of 38.9 months. Standardized hazard ratios (HRs) were computed via Cox regression., Results: Measures of RA phasic function were more prominently impaired in subjects with HFrEF than those in subjects with HFpEF. In analyses that adjusted for demographic factors, HF status, left ventricular ejection fraction, right ventricular end-diastolic volume index, and right ventricular ejection fraction, RA reservoir strain (HR: 0.66; 95% confidence interval [CI]: 0.47 to 0.92; p = 0.0154), RA expansion index (HR: 0.53; 95% CI: 0.31 to 0.91; p = 0.0116), RA conduit strain (HR: 0.58; 95% CI: 0.40 to 0.84; p = 0.0039), and RA conduit strain rate (HR: 1.51; 95% CI: 1.02 to 2.220; p = 0.0373) independently predicted all-cause mortality. In contrast, RA booster pump function and RA volume index did not independently predict the risk of death., Conclusions: Phasic RA function is predictive of the risk of all-cause death in a diverse group of subjects with and without HF. RA conduit and reservoir function are independent predictors of mortality., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Background: Exit-site infection (ESI) and tunnel infection (TI) of the peritoneal dialysis (PD) catheter are significant causes of catheter or even method loss as well as patient morbidity. Among the methods that have been in use thus far, the removal and replacement of the catheter often needs to be followed by switching temporarily to hemodialysis, whereas catheter splicing or unroofing of the tunnel tract and shaving/removal of the superficial catheter cuff have not gained universal acceptance thus far. Methods: We treat chronic ESI with exit-site relocation under local anesthetic with removal of the external cuff. For the purposes of this study, we conducted a retrospective cohort analysis of all exit-site relocations performed using that technique over a 5-year period. Results: Twenty-seven patients (16 male, mean age 58 years, range 23 - 81 years) with chronic ESI underwent exit-site relocation under local anesthetic as a day-case procedure. Follow-up was 47.5 ± 22.4 months (range 10.8 - 79.4 months). No dialysate leaks occurred following the procedure. Peritoneal dialysis was resumed immediately. The procedure resulted in long-term resolution of the infection in 20 of the 27 patients (74%). In 7 patients (26%), the catheter had to be removed eventually, either because of ESI recurrence (5 patients) or TI (2 patients), which in 2 cases was subsequently complicated by PD peritonitis, and the patients were switched to hemodialysis. Conclusion: The technique described herein is a safe, straightforward, and effective method for the treatment of chronic ESI while the patient remains on PD and avoids switching to hemodialysis., (Copyright © 2019 International Society for Peritoneal Dialysis.)

There is controversy regarding the utility of left ventricular (LV) mechanics assessed by feature-tracking steady-state free-precession (FT-SSFP), a readily implementable technique in clinical practice. In particular, whether LV mechanics assessed by FT-SSFP predicts outcomes in subjects with heart failure (HF) with reduced ejection fraction (HFrEF), with preserved ejection fraction (HFpEF), or without HF is unknown. We aimed to assess whether LV mechanics measured with FT-SSFP cine magnetic resonance imaging (MRI) predicts adverse outcomes. We prospectively enrolled 612 adults without HF (n = 402), with HF with reduced ejection fraction (HFrEF; n = 113), or HFpEF (n = 97) and assessed LV strain using FT-SSFP cine MRI. Over a median follow-up of 39.5 months, 75 participants had an HF admission, and 85 died. In Cox proportional hazards models, lower global longitudinal (Standardized hazard ratio 1.56, 95% confidence interval [CI] 1.22 to 2.00, p = 0.0004), circumferential (Standardized HR 1.46, 95% CI 1.08 to 1.95, p = 0.0123), and radial strain (Standardized HR 0.59, 95% CI 0.43 to 0.83, p = 0.0019) were independently associated with the composite endpoint, after adjustment for HF status, LV ejection fraction (LVEF), age, sex, ethnicity, body mass index, systolic and diastolic blood pressure, hypertension, diabetes, coronary artery disease, and glomerular filtration rate. Furthermore, global longitudinal strain stratified the risk of adverse outcomes across tertiles better than LVEF. In analyses that included only participants with a preserved LVEF, systolic radial, circumferential and longitudinal strain were independently predictive of adverse outcomes. We conclude that LV longitudinal, circumferential and radial strain measured using FT-SSFP cine MRI (a readily implementable technique in clinical practice) predict the risk of adverse events, independently of LVEF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Large artery stiffening contributes to the pathophysiology of heart failure (HF) and associated comorbidities. MGP (matrix Gla-protein) is a potent inhibitor of vascular calcification. MGP activation is vitamin K-dependent. We aimed (1) to compare dp-ucMGP (dephospho-uncarboxylated MGP) levels between subjects with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) and subjects without HF; (2) to assess the relationship between dp-ucMGP levels and arterial stiffness; and (3) to assess the relationship between warfarin use, dp-ucMGP levels, and arterial stiffness in HF. We enrolled 348 subjects with HFpEF (n=96), HFrEF (n=53), or no HF (n=199). Carotid-femoral pulse wave velocity, a measure of large artery stiffness, was measured with arterial tonometry. Dp-ucMGP was measured with ELISA. Dp-ucMGP levels were greater in both HFrEF (582 pmol/L; 95% CI, 444-721 pmol/L) and HFpEF (549 pmol/L; 95% CI, 455-643 pmol/L) compared with controls (426 pmol/L; 95% CI, 377-475 pmol/L; ANCOVA P=0.0067). Levels of dp-ucMGP were positively associated with carotid-femoral pulse wave velocity (standardized β, 0.31; 95% CI, 0.19-0.42; P<0.0001), which was also true in analyses restricted to patients with HF (standardized β, 0.34; 95% CI, 0.16-0.52; P=0.0002). Warfarin use was significantly associated with carotid-femoral pulse wave velocity (standardized β, 0.13; 95% CI, 0.004-0.26; P=0.043), but this relationship was eliminated after adjustment for dp-ucMGP. In conclusion, levels of dp-ucMGP are increased in HFpEF and HFrEF and are independently associated with arterial stiffness. Future studies should investigate whether vitamin K supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffness in HFpEF and HFrEF.

Background The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement ( AVR ). Methods and Results We enrolled 38 participants with symptomatic severe aortic stenosis scheduled to undergo surgical AVR . Aortic root characteristic impedance, wave reflections parameters (reflection magnitude, reflected wave transit time), and myocardial extracellular mass were measured with cardiac magnetic resonance imaging and arterial tonometry Cardiac magnetic resonance imaging was repeated at 6 months in 30 participants. A reduction in cellular mass (133.6 versus 113.9 g; P=0.002) but not extracellular mass (42.3 versus 40.6 g; P=0.67) was seen after AVR . Participants with higher extracellular mass exhibited greater reflection magnitude (0.68 versus 0.54; P=0.006) and lower aortic root characteristic impedance (56.3 versus 96.9 dynes/s per cm 5 ; P=0.006). Reflection magnitude was a significant predictor of smaller improvement in the quality of life (Kansas City Cardiomyopathy Questionnaire score) after AVR ( R=-0.51; P=0.0026). The 6-minute walk distance at 6 months after AVR was positively correlated with the reflected wave transit time ( R=0.52; P=0.01). Conclusions Consistent with animal studies, arterial wave reflections are associated with interstitial volume expansion in severe aortic stenosis and predict a smaller improvement in quality of life following AVR . Future trials should assess whether wave reflections represent a potential therapeutic target to mitigate myocardial interstitial remodeling and to improve the clinical status of this patient population.

Background: This study was designed to investigate the difference in the prevalence of neuronal autoantibodies in patients diagnosed with established temporal lobe epilepsy (TLE) of unknown cause with mesial temporal sclerosis (MTS) and patients with TLE without MTS. Methods: In an observational cohort study design, we included thirty-three consecutive adult patients and divided them into two groups with and without MTS. We evaluated anti-neuronal and nuclear antibodies with immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: From the thirty-three consecutive patients with epilepsy 17 (51.1%) had MTS of which 12 had unilateral and 5 had bilateral MTS. No significant difference was detected between seropositive and seronegative patients in MTS versus non-MTS groups. The studied autoantibodies were present in 16 patients, including gamma-aminobutyric acid receptor (GABA-R) antibodies being the most common in 11 (33.3%), followed by N-methyl-D-aspartate receptor (NMDA-R) in 2 (6.1%), glutamic acid decarboxylase receptor (GAD-R) in 1 (3.0%), anti-phospholipid (APL) antibody in 1 (3.0%), CV2 in 1 (3.0%), Tr in 1 (3.0%), recoverin in 1 (3.0%), and double-stranded deoxyribonucleic acid (dsDNA) antibody in 1 (3.0%) of our patients with focal epilepsy. In both MTS and non-MTS groups, eight patients were positive for antibodies; four patients were positive for GABA in the MTS group and seven for GABA in the non-MTS group. Conclusion: Neuronal antibodies were presented in half of patients with focal epilepsy, GABA antibody being the leading one. No specific magnetic resonance imaging (MRI) findings were found in the seropositive group. Our results suggest that screening for relevant antibodies may enable us to offer a possible treatment to this group of patients.

Objectives: With the increase in the life expectancy of older adults, the scoring diagnosis of osteoporosis has been highly reported hence rising the incidence of fragility fractures due to decrease in bone mineral density (BMD), thereby significantly impacting the quality of life and health status of elderly population. The aim of this study is to identify the impact of different exercise regimes in improving the BMD among osteoporotic females., Methodology: A trial was conducted on 93 diagnosed postmenopausal osteoporotic females aged 50-75 years screened on the basis of physical activity readiness-questionnaire and YOU form randomly divided equally into three groups', that is, aerobic, anaerobic, and osteoanabolic exercises using an envelope method. The intervention was given on the basis of American College of Sports Medicine (ACSM), frequency, intensity, time, and type protocol for the period of 12 weeks. The pre- and post-BMD was determined to find out the improvements on the t -value of the participants. The outcome measure was calculated using a peripheral dual X-ray absorptiometry scan (bone densitometer)., Results: At 95% of confidence interval, the pre- and post-median difference observed within the osteoanabolic group was 0.4 followed by 0.3 and 0.1 in the aerobic and anaerobic groups, respectively. The level of significance was determined by applying the Friedman test revealing a statistically significant difference P < 0.001 between the groups. Further, post hoc analysis shows that osteoanabolic exercises were more significant in comparison with aerobic and anaerobic exercises., Conclusion: Structured physical exercises based on ACSM protocol show improvement among the osteoporotic females; however, the impact of osteoanabolic exercises significantly increased the BMD, thus reducing the t -value. However, larger scale studies in different clinical settings are recommended for more accurate results.

Objective: The purpose of this study was to investigate the electromyographic activity of lumbar multifidus (MF) and erector spinae (ES) muscle during forward walking (FW) and backward walking (BW) in participants with and without chronic low back pain (CLBP)., Methods: Twenty-one patients with CLBP were recruited from outpatient department of Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia. Twenty-one age-matched healthy controls without CLBP were recruited from community. Maximum voluntary isometric contraction (MVIC) was quantified for MF and ES using standard guidelines. Electromyographic activity of MF and ES was recorded using surface electrodes during FW and BW on a motorized treadmill, which was later normalized by respective MVIC's of each muscle., Results: Muscle activity (in percentage MVIC) was determined to be higher for both the muscles during BW. Activity of MF muscle was significantly higher in CLBP patients compared with healthy controls ( P < .04). Electromyographic activity of MF and ES was significantly increased during BW (MF: P < .001; ES: P < .001) compared with FW in both healthy and CLBP groups., Conclusion: BW leads to greater activation of the paraspinal muscles. Along with global extensor (ES), activity of core extensor (MF) is also higher during BW than FW in both healthy participants and CLBP patients. BW is a more favorable aerobic activity to enhance lumbar paraspinal recruitment. These findings may have important clinical implications in the rehabilitation of CLBP.

Background: The prognostic importance of left atrial (LA) dysfunction is increasingly recognized. Magnetic resonance imaging can provide excellent visualization of the LA wall. We aimed to study the association of LA dysfunction measured using feature-tracking magnetic resonance imaging with incident adverse cardiovascular events among subjects with or without heart failure (HF) at baseline., Methods and Results: We prospectively studied 640 adults without HF (n=419), HF with preserved ejection fraction (n=101), or HF with reduced ejection fraction (n=120). We measured phasic LA function by volumetric and feature-tracking methods to derive longitudinal strain. The composite outcome of incident HF hospitalization or death was adjudicated during a median follow-up of 37.1 months. Measures of LA phasic function were more prominently impaired in subjects with HF with reduced ejection fraction than among subjects with HF with preserved ejection fraction. In unadjusted Cox proportional hazards models, all measures of phasic LA function and volumes (maximum, minimum, and diastatic) were associated with the composite outcome. However, in analyses that adjusted for clinical risk factors, HF status, maximum LA volume, left ventricular mass, and left ventricular ejection fraction, measures of conduit and reservoir LA function, but not booster-pump function, were associated with the composite outcome. The strongest associations were observed for conduit longitudinal strain (standardized hazard ratio, 0.66; 95% CI, 0.49-0.88; P=0.004), conduit strain rate (standardized hazard ratio, 1.59; 95% CI, 1.16-2.16; P=0.0035), and reservoir strain (standardized hazard ratio, 0.68; 95% CI, 0.52-0.89; P=0.0055)., Conclusions: Phasic LA function measured using magnetic resonance imaging feature tracking is independently predictive of the risk of incident HF admission or death, even after adjusting for LA volume and left ventricular remodeling.