What we Know so far about Myxovirus Resistance Protein A (MxA) as a Biomarker of Interferon-Beta Therapy in Patients with Multiple Sclerosis: a Systematic Review

Introduction: Multiple sclerosis (MS) is one of the most common neurological disabling diseases in human societies with no complete cure. IFN-β has been proven to be an important advance in the MS treatment, but early identification of treatment failure is its major concern. Some researches revealed that MxA is an appropriate biomarker for predicting response to IFN-β, so we performed this study to evaluate the relationship between MxA level and response to INF- β treatment.Methods: International and internal databases were searched using “MxA”, “Myxovirus resistance protein A”, “IFN-β”, “interferon Beta”, “multiple sclerosis” and “MS keywords until October 2019. Inclusion criteria were original studies considering the MxA assays in MS patients under IFN-β therapy. Some reported cut-offs from partially the same settings (7 studies) were pooled using the weighted average. Finally, the overall statements of the included studies were compared and discussed to obtain a comprehensive conclusion about the clinical value of MxA assays in patient monitoring and designing their treatment plan. Results: A total of 456 articles were identified. The Screening was led to exclusion of 427 articles. Finally, 28 original studies met the inclusion criteria for this systematic review. Almost all studies have concluded that the MxA is significantly correlated with response to IFN-β therapy and also MxA expression is under the direct effect of Neutralizing antibody (NAb) against IFN-β. Reported cut-offs for MxA ranged from 3.3 to 6.3 NR and the weighted average of them was estimated to be 4.1 NR. Conclusion: It could be suggested that in patients under IFN-β therapy with an active disease which doesn’t fulfill the criteria for the breakthrough disease, MxA level can help to determine whether to continue the drug and follow up a patient or change the treatment regimen

Epidemiology of familial multiple sclerosis in Iran: a national registry-based study

Background Admittedly, little is known about the epidemiological signatures of familial multiple sclerosis (FMS) in different geographical regions of Iran. Objective To determine the epidemiology and the risk of FMS incidence in several provinces of Iran with a different ethnic population including, Fars, Tehran, Isfahan (Persians), and Mazandaran (Mazanis), Kermanshah (Kurds), and Chaharmahal and Bakhtiari (Lors). Methods This cross-sectional registry-based study was performed on nationwide MS registry of Iran (NMSRI) data collected from 2018 to 2021. This system, registers baseline characteristics, clinical presentations and symptoms, diagnostic and treatments at regional and national levels. Results A total of 9200 patients including, 7003 (76.1%) female and 2197 (23.9%) male, were participated. About 19% of patients reported a family history of MS; the order from highest to lowest FMS prevalence was as follows: Fars (26.5%), Chaharmahal and Bakhtiari (21.1%), Tehran (20.5%), Isfahan (20.3%), Mazandaran (18.0%), and Kermanshah (12.5%). Of all FMS cases, 74.7% (1308 cases) were female and 25.3% (442 cases) were male. FMS occurrence was much more common in females than males (P-value = 0.001). Further, the mean age at onset was 30 years among FMS cases. A substantially higher probability of relapsing-remitting MS and secondary-progressive MS was found among FMS cases than sporadic MS (SMS) (P_value = 0.001). There was no significant difference in Expanded Disability Status Scale (EDSS) scores between FMS and SMS. The majority of FMS cases were observed among first-degree relatives, with the highest rate in siblings. There was a significant association between MS risk and positive familial history in both maternal and paternal aunt/uncle (P_value = 0.043 and P_value = 0.019, respectively). Multiple sclerosis occurrence among offspring of females was higher than males (P_value = 0.027). Conclusions In summary, our findings imply a noteworthy upward trend of FMS in Iran, even more than the global prevalence, which suggests a unique Atlas of FMS prevalence in this multi-ethnic population. Despite the highest rate of FMS within Persian and Lor ethnicities, no statistically significant difference was observed among the provinces

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Evaluating the diagnosis and treatment of neuro-Behçet’s disease with cascade sign appearance in brainstem: a case report

This study aimed to investigate a case of neuro-Behçet’s disease misdiagnosed as acute ischemic stroke or multiple sclerosis (MS). The studied case was a 29-year-old man with subacute onset of hemiparesis, dysarthria, and ataxia who was diagnosed as acute ischemic stroke at first. Due to no significant improvement, the patient was managed as an MS case, but he did not experience any improvements again. We noticed a history of oral and genital aphthous and cascade sign appearance in his brain MRI. Then, Behçet’s disease with secondary parenchymal involvement of brainstem was confirmed. The patient received infliximab, which resulted in clinico-radiological recovery. Practical Implications. Given the prevalence of Behçet’s disease in the Middle East, the possibility of its diagnosis should be considered in patients with atypical history or imaging for ischemic stroke or MS

P4QSP^4QS: A Peer-to-Peer Privacy Preserving Query Service for Location-Based Mobile Applications

The location-based services provide an interesting combination of cyber and physical worlds. However, they can also threaten the users' privacy. Existing privacy preserving protocols require trusted nodes, with serious security and computational bottlenecks. In this paper, we propose a novel distributed anonymizing protocol based on peer-to-peer architecture. Each mobile node is responsible for anonymizing a specific zone. The mobile nodes collaborate in anonymizing their queries, without the need not get access to any information about each other. In the proposed protocol, each request will be sent with a randomly chosen ticket. The encrypted response produced by the server is sent to a particular mobile node (called broker node) over the network, based on the hash value of this ticket. The user will query the broker to get the response. All parts of the messages are encrypted except the fields required for the anonymizer and the broker. This will secure the packet exchange over the P2P network. The proposed protocol was implemented and tested successfully, and the experimental results showed that it could be deployed efficiently to achieve user privacy in location-based services

P4QS : a peer-to-peer privacy preserving query service for location-based mobile applications

The location-based services provide an interesting combination of cyber and physical worlds. However, they can also threaten the users' privacy. Existing privacy preserving protocols require trusted nodes, with serious security and computational bottlenecks. In this paper, we propose a novel distributed anonymizing protocol based on peer-To-peer architecture. Each mobile node is responsible for anonymizing a specific zone. The mobile nodes collaborate in anonymizing their queries, without the need of getting access to any information about each other. In the proposed protocol, each request will be sent with a randomly chosen ticket. The encrypted response produced by the server is sent to a particular mobile node (called broker node) over the network, based on the hash value of this ticket. The user will query the broker to get the response. All parts of the messages are encrypted except the fields required for the anonymizer and the broker. This will secure the packet exchange over the P2P network. The proposed protocol was implemented and tested successfully, and the experimental results showed that it could be deployed efficiently to achieve user privacy in location-based services

Attitude and practice of pediatrics and gynecology physicians in the cities of Sari and Babol regarding non-initiation and discontinuation of resuscitation in cases of gravely Ill newborns

(Received 6 June, 2009; Accepted 23 July, 2009)AbstractBackground and purpose: There are some debates with decision making for withdrawal/ withholding of life sustaining treatment in infants with adverse prognoses and incurable conditions. This study is conducted to review attitudes and practice of pediatrics and gynecology physicians in this field.Materials and methods: This survey was conducted during 2009 in Sari and Babol. A total of 140 pediatricians, gynecologists and residents/fellows in these fields were recruited by census; 106 doctors completed an anonymous questionnaire (response rate 75.7%).Results: More than 70 percent of respondents disagreed and less than a quarter of them agreed with euthanasia. Thus far, none of the doctors prescribed drugs to expedite neonatal death. Withdrawal of life sustaining treatment in infants with adverse prognoses and incurable conditions was uncommon, and reported by one fifth of physicians in their diagnosis of infants with multiple congenital anomalies.Influential factors in their decision to withdraw life sustaining treatment in these infants were: the number of children, the insistence of hospital staff, the request from parents, the infant's sex, lack of hospital facilities, parental history of infertility and family income, respectively. Religious beliefs were effective for withdrawal/withholding of life sustaining treatment in the decision making process and was led to an agreement more with the approval of the law in the majority of cases.Conclusion: This study revealed that attitude and sanctity of life, overcomes the attitude regarding to quality of life from most of the physicians. Law approval in this field is necessaryJ Mazand Univ Med Sci 2009; 19(70): 33-40 (Persian