Evaluation of protective effects of non-selective cannabinoid receptor agonist WIN 55,212-2 against the nitroglycerine-induced acute and chronic animal models of migraine: A mechanistic study

Aim: Migraine is a neurological debilitating disorder. Previous studies have shown that cannabinoid receptor agonists have analgesic effects in various models of pain. In this study, therefore, we investigated anti-nociceptive effects of WIN 55,212-2, and the role of either CB1 or CB2 receptors in nitroglycerine (NTG)-induced animal model of migraine. Methods: The present study was conducted on both male and female rats receiving NTG (10 mg/kg, i.p.) to induce acute (single dose of NTG) and chronic (repetitive doses of NTG) models of migraine. Additionally, three groups received WIN 55,212-2 (0.33, 1, 3 mg/kg, i.p.) 45 min before behavioral tests. Additionally, AM251 and AM630 (CB1 and CB2 receptor antagonist, respectively, 1 mg/kg, i.p.) were used to evaluate the possible involvement of CB1 and CB2 receptors during the protective effects of WIN 55,212-2. Key findings: We found that NTG (10 mg/kg, i.p.) in both acute and chronic models increased sensitivity to pain. In acute model, we found that WIN 55,212-2 (almost high doses) decreases the level of pain mainly through CB1 receptor due to CB1 antagonist abrogates its protective effects, however, in formalin test CB2 receptors also had crucial roles in both phases at 3 mg/kg of WIN 55,212-2. In chronic model, WIN 55,212-2 (0.33, 1 and 3 mg/kg) significantly attenuated NTG-induced hyperalgesia through both CB1 and CB2 receptors. Significance: Our data supported the argument that activation of CB1 and CB2 receptors by WIN 55,212-2 may be considered a new medication for migraine, however in lack of each receptor leads to different responses from deletion to the reduction of analgesic effects. © 2019 Elsevier Inc

The effects of hydro-ethanolic extract of Capparis spinosa (C. spinosa) on lipopolysaccharide (LPS)-induced inflammation and cognitive impairment: Evidence from in vivo and in vitro studies

Ethnopharmacological relevance: Capparis spinose (C. spinosa) belonging to Capparaeae, originates from dry areas in the west or central Asia and Mediterranean basin. For thousands of years, C. spinosa has been reported to be used as a therapeutic traditional medicine to relieve various ailments including rheumatism, pain and inflammatory diseases. Aim of the study: There are several studies mentioning that systemic inflammation results in learning and memory impairments through the activation of microglia. The objective of this study was to investigate the effect of C. spinosa on both in vivo and in vitro models of neuroinflammation and cognitive impairment using lipopolysaccharide (LPS). Materials and methods: In vivo: 40 male rats were used in the present study. Cognitive impairment was induced using LPS (1 mg/kg/d; i.p.) for 4 weeks. Treatment with C. spinosa (100 and 300 mg/kg/d; p.o.) was performed 1 h before LPS administration. At the end of the experiment, rats were undergone for behavioral and biochemical analysis. In vitro: Primary microglia isolated from mouse was used in the present study. The cells were pretreated with C. spinosa extract (10�300 μg/ml) and then stimulated with LPS (1 μg/ml). The expression levels of inflammatory and anti-inflammatory cytokines were elucidated using Real-Time PCR and ELISA methods. Results: The escape latency in the Morris water maze test in the LPS group was significantly greater than the control group (p < 0.001), while, in extract-treated groups, it was less than the LPS group (p < 0.001). Additionally, we found that the levels of IL-1β, TNF-α, and iNOS/Arg-1 ratio was also significantly lower in extract-treated groups than the LPS group (p < 0.001). The results revealed that C. spinosa extract significantly reduced the levels of TNF-α, iNOS, COX-2, IL-1β, IL-6, NO and PGE2, and the ratios of iNOS/Arg-1 and NO/urea, following the LPS-induced inflammation in microglia (p < 0.001). Conclusions: Our finding provides evidence that C. spinosa has a neuroprotective effect, and might be considered as an effective therapeutic agent for the treatment of neurodegenerative diseases that are accompanied by microglial activation, such as AD. © 202

The efficacy of N-Acetylcysteine in severe COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial

Objectives: Severe acute respiratory infection (SARI) caused by the SARS-CoV-2 virus may cause lung failure and the need for mechanical ventilation. Infection with SARS-COV-2 can lead to activation of inflammatory factors, increased reactive oxygen species, and cell damage. In addition to mucolytic effects, N-Acetylcysteine has antioxidant effects that we believe can help patients recover. In this study, we evaluate the efficacy of N-Acetylcysteine in patients with severe COVID-19. Trial design: This is a prospective, randomized, single-blinded, phase 3 controlled clinical trial with two arms (ratio 1:1) parallel-group design of 40 patients, using the placebo in the control group. Participants: All severe COVID-19 patients with at least one of the following five conditions: (respiration rate > 30 per minute), hypoxemia (O2 � saturation, arterial oxygen partial pressure ratio 50 of lung area during 24 48 h), Lactate dehydrogenase (LDH) > 245 U / l, Progressive lymphopenia, and admitted to the intensive care unit of Shahid Mohammadi Hospital in Bandar Abbas and have positive PCR test results for SARS-Cov-2 and sign the written consent of the study will be included. Patients will be excluded from the study if they have a history of hypersensitivity to N-Acetylcysteine, pregnancy, or refuse to participate in the study. Intervention and comparator: After randomization, participants in the intervention group receive standard of care (SOC) according to the National Committee of COVID-19 plus N-acetylcysteine (EXI-NACE 200mg/mL, in 10mL ampules of saline for parenteral injection (EXIR pharmaceutical company)) at a dose of 300 mg/kg equivalent to 20 gr as a slow single intravenous injection on the first day of hospitalization. In the control group patients receive SOC and placebo (Sterile water for injection as the same dose). The placebo is identical in appearance to the N-acetylcysteine injection (EXIR pharmaceutical company as well). Main outcomes: The primary endpoint for this study is a composite endpoint for the length of hospitalization in the intensive care unit and the patient's clinical condition. These outcomes were measured at the baseline (before the intervention) and on the 14th day after the intervention or on the discharge day. Randomisation: Eligible participants (40) will be randomized in two arms in the ratio of 1: 1 (20 per arm) using online web-based tools and by permuted block randomization method. To ensure randomization concealment, random sequence codes are assigned to patients by the treatment team at the time of admission without knowing that each code is in the intervention or comparator group. Blinding (masking): All participants will be informed about participating in the study and the possible side effects of medication and placebo. Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. Numbers to be randomised (sample size): A total of 40 patients participate in this study, which are randomly divided; 20 patients in the intervention group will receive SOC and N-acetylcysteine, 20 patients in the control group will receive SOC and placebo. Trial status: First version of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on February 14, 2021, with the local code 990573, and the recruitment started on March 2, 2021 and the expected recruitment end date is April 1, 2021. Trial registration: The protocol was registered before starting participant recruitment entitled: Evaluation of the efficacy of N-Acetylcysteine in severe COVID-19 patients: a randomized controlled phase III clinical trial, IRCT20200509047364N3, at Iranian Registry of clinical trials on 20 February 2021. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). © 2021, The Author(s)

A case of fatal strongyloidiasis in a patient with chronic lymphocytic leukemia and molecular characterization of the isolate

Strongyloides stercoralis is a human intestinal parasite which may lead to complicated strongyloidiasis in immunocompromised. Here, a case of complicated strongyloidiasis in a patient with chronic lymphocytic leukemia is reported. Presence of numerous S. stercoralis larvae in feces and sputum confirmed the diagnosis of hyperinfection syndrome in this patient. Following recovery of filariform larvae from agar plate culture of the stool, the isolate was characterized for the ITS1 region of ribosomal DNA gene by nested-PCR and sequencing. Albendazole therapy did not have cure effects; and just at the beginning of taking ivermectin, the patient died. The most important clue to prevent such fatal consequences is early diagnosis and proper treatment

Electrochemical Oxidation and Determination of Antiviral Drug Acyclovir by Modified Carbon Paste Electrode With Magnetic CdO Nanoparticles

With the development of nanomaterials in electrochemical sensors, the use of nanostructures to modify the electrode surface has been shown to improve the kinetics of the electron transfer process. In this study, a sensor was developed for the electrochemical determination of Acyclovir (ACV) based on the modified carbon paste electrode (CPE) by CdO/Fe3O4. The magnetic CdO nanoparticles characterization was studied by energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). To study of the modified CPE surface morphology, scanning electron microscopy (SEM) was used. At the optimal conditions, a noteworthy enhancement in the electrochemical behavior of ACV was observed at the surface of the modified CPE compared to the unmodified CPE. A detection limit of 300 nM and a linear range of 1�100 μM were obtained for the quantitative monitoring of ACV at the modified CPE surface using differential pulse voltammetry (DPV) in phosphate buffer. The RSD (relative standard deviation) of the electrode response was &lt;4.3 indicating the development of a high precision method. Also, satisfactory results were obtained in the determination of ACV with the modified electrode in tablet, blood serum, and urine samples with a satisfactory relative recovery (RR) in the range of 94.0�104.4. © Copyright © 2020 Naghian, Marzi Khosrowshahi, Sohouli, Pazoki-Toroudi, Sobhani-Nasab, Rahimi-Nasrabadi and Ahmadi

National guidelines for cognitive assessment and rehabilitation of Iranian traumatic brain injury patients

Background: Individuals with moderate to severe traumatic brain injury (TBI) often have prolonged cognitive impairments, resulting in long-term problems with their real-life activities. Given the urgent need for evidence-based recommendations for neuropsychological management of Iranian TBI patients, the current work aimed to adapt eligible international guidelines for cognitive assessment and rehabilitation of the TBI patients in Iran. Methods: The project was led by an executive committee, under the supervision of the Iranian Ministry of Health and Medical Education (MOHME). Following a systematic literature search and selection process, four guidelines were included for adaptation. Clinical recommendations of the source guidelines were tabulated as possible clinical scenarios for 90 PICO clinical questions covering all relevant phases of care. After summing up the scenarios, our initial list of recommendations was drafted according to the Iranian patients� conditions. The final decision-making, with the contribution of a national interdisciplinary panel of 37 experts from across the country, was conducted in two rounds using online and offline survey forms (Round 1), and face-to-face and telephone meetings (Round 2). Results: A total of 63 recommendations in six sections were included in the final list of recommendations, among which 24 were considered as key recommendations. In addition, some of the recommendations were identified as fundamental, meaning that proper implementation of the other recommendations is largely dependent on their implementation. Conclusion: Iranian health policy makers and rehabilitation program managers are recommended to address some fundamental issues to provide the necessary infrastructure to set up an efficient cognitive rehabilitation service system. © 2020 Academy of Medical Sciences of I.R. Iran. All rights reserved

A search for the decay B+→K+ννˉB^+ \to K^+ \nu \bar{\nu}

We search for the rare flavor-changing neutral-current decay $B^+ \to K^+ \nu \bar{\nu}$ in a data sample of 82 fb$^{-1}$ collected with the {\sl BABAR} detector at the PEP-II B-factory. Signal events are selected by examining the properties of the system recoiling against either a reconstructed hadronic or semileptonic charged-B decay. Using these two independent samples we obtain a combined limit of ${\mathcal B}(B^+ \to K^+ \nu \bar{\nu})<5.2 \times 10^{-5}$ at the 90% confidence level. In addition, by selecting for pions rather than kaons, we obtain a limit of ${\mathcal B}(B^+ \to \pi^+ \nu \bar{\nu})<1.0 \times 10^{-4}$ using only the hadronic B reconstruction method.Comment: 7 pages, 8 postscript figures, submitted to Phys. Rev. Let

High-reflectivity broadband distributed Bragg reflector lattice matched to ZnTe

We report on the realization of a high quality distributed Bragg reflector with both high and low refractive index layers lattice matched to ZnTe. Our structure is grown by molecular beam epitaxy and is based on binary compounds only. The high refractive index layer is made of ZnTe, while the low index material is made of a short period triple superlattice containing MgSe, MgTe, and ZnTe. The high refractive index step of Delta_n=0.5 in the structure results in a broad stopband and the reflectivity coefficient exceeding 99% for only 15 Bragg pairs.Comment: 4 pages, 3 figure

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation

EuFe2_2As2_2 under high pressure: an antiferromagnetic bulk superconductor

We report the ac magnetic susceptibility $\chi_{ac}$ and resistivity $\rho$ measurements of EuFe$_2$As$_2$ under high pressure $P$. By observing nearly 100% superconducting shielding and zero resistivity at $P$ = 28 kbar, we establish that $P$-induced superconductivity occurs at $T_c \sim$~30 K in EuFe$_2$As$_2$. $\rho$ shows an anomalous nearly linear temperature dependence from room temperature down to $T_c$ at the same $P$. $\chi_{ac}$ indicates that an antiferromagnetic order of Eu$^{2+}$ moments with $T_N \sim$~20 K persists in the superconducting phase. The temperature dependence of the upper critical field is also determined.Comment: To appear in J. Phys. Soc. Jpn., Vol. 78 No.