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Background and Purpose: Alzheimer's disease (AD) is the most-prevalent form of dementia and imposes substantial burdens at the personal and societal levels. The apolipoprotein E (APOE) ε4 allele is a genetic factor known to increase AD risk and exacerbate brain atrophy and its symptoms. We aimed to provide a comprehensive review of the impacts of APOE ε4 on brain atrophy in AD as well as in mild cognitive impairment (MCI) as a transitional stage of AD., Methods: We performed a coordinate-based meta-analysis of voxel-based morphometry studies to compare gray-matter atrophy patterns between carriers and noncarriers of APOE ε4. We obtained coordinate-based structural magnetic resonance imaging data from 1,135 individuals who met our inclusion criteria among 12 studies reported in PubMed and Google Scholar., Results: We found that atrophy of the hippocampus and parahippocampus was significantly greater in APOE ε4 carriers than in noncarriers, especially among those with AD and MCI, while there was no significant atrophy in these regions in healthy controls who were also carriers., Conclusions: The present meta-analysis has highlighted the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, which emphasizes the critical influence of the allele on neurodegeneration, especially in the hippocampus. These findings improve the understanding of AD pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals at risk of AD who carry the APOE ε4 allele., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Neurological Association.)

Objective: In TIA and stroke patients with carotid stenosis, estimations of future ipsilateral ischemic stroke risk and treatment decisions are currently primarily based on the degree of stenosis. Intraplaque hemorrhage (IPH), which can be readily visualized on carotid MRI, is increasingly established as an easy to assess and a very strong and independent predictor for ipsilateral stroke risk, stronger than any clinical risk factor. We developed a clinical prediction model (IMPROVE) incorporating IPH, degree of stenosis, and clinical risk factors to select patients with symptomatic carotid stenosis at high risk for stroke. Methods: IMPROVE was developed on pooled clinical and MRI data from five cohort studies of 760 recent TIA or minor stroke patients with carotid plaque who received optimal medical treatment. We used Cox proportional hazards models to determine the coefficients of IMPROVE. IMPROVE was internally validated using bootstrapping and converted to one- and three-year ipsilateral ischemic stroke risk. Results: The development dataset contained 65 ipsilateral incident ischemic strokes that occurred during a median follow-up of 1.2 years (IQR: 0.5-4.1). The IMPROVE model includes five predictors, which are in order of importance: degree of stenosis, presence of IPH on MRI, classification of last event (cerebral vs ocular), sex, and age. Internal validation revealed a good accuracy (C-statistic: 0.82; 95% CI: 0.77-0.87) and no evidence for miscalibration (calibration slope: 0.93). Interpretation: Using presence of IPH on MRI and only four conventional parameters, the IMPROVE model provides accurate individual stroke risk estimates, which may facilitate stratification for revascularization.

Introduction: In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI)., Methods: We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidβ-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study., Results: A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory., Discussion: This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy., Clinicaltrials: GOV: ID NCT04992975 (Clinicaltrial.gov 2023)., Competing Interests: Declaration of competing interest None of the authors have conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objective: Type 1 diabetes mellitus one of the biggest health concerns around the world, is difficult to manage during adolescence. Among the non-medical methods of controlling this disease is empowerment through self-efficacy. Poor self-efficacy leads to social anxiety and ultimately deficiencies in diabetes. There is also a correlation among health literacy, self-efficacy, and social anxiety. Thus, the present study aimed to evaluate the impact of a literacy promotion training program based on social learning theory on the self-efficacy and social anxiety of adolescents with T1DM., Methods: The current research is a semi-experimental type that was carried out with the cooperation of 66 adolescents aged 15-18 years with type 1 diabetes in Iran (Tehran, 2022). It has control and intervention groups. The endocrinology and diabetes clinics of the intervention and control groups were randomly selected in a multi-stage manner (endocrine and diabetes clinic of children's medical center hospital for the control group and endocrine and diabetes clinic of Mofid hospital for the intervention group) and the participants were selected by Simple Random Sampling method (draw). The training program designed based on Bandura's social learning theory was used to teach adolescents during seven consecutive sessions of 30-45 min during one week. Questionnaires were completed before and one month after the intervention. Data were analysed in SPSS-25 software., Findings: The intervention for adolescents with T1DM in intervention group compared to the control group had a significant effect on improve health literacy (P<0.001), self-efficacy (P<0.001), and social anxiety (P<0.05)., Conclusions: The results can also be used to improve the capabilities of adolescents with T1DM, reduce and prevent disease complications, and develop operational-educational programs in the centers from which these adolescents receive various services., Trial Registration: IRCT20210422051045N1., (© 2024. The Author(s).)

Introduction: Breast cancer is a severe life-threatening condition in which many women are involved yearly. One factor that has recently been noticed and investigated as a diagnostic predictor of this type of cancer is the number of tumor buds and the relation of this factor with a patient's survival rate., Materials and Methods: This study includes 150 female patients over 18 years old with a mean age of 53.99 ± 12.56 years old with breast cancer, which was diagnosed at various medical centers, including Rouhani Hospital itself, and referred to Rouhani Hospital Medical Center, Babol, Iran. The number of intratumoral and peritumoral buds in patients' microscopic slides were archived and evaluated along with tumor microenvironment on hematoxylin and eosin (H&E) slides and compared to other clinicopathological findings. This article precisely investigated the relationship between the number of intratumoral and peritumoral buds with patients' 5-year survival rate. Also, the relationship between age, tumor stage, grade, size, the number of lymph nodes involved, and the presence of metastasis with the number of intratumoral and peritumoral buds was studied., Results and Discussion: The result showed a significant statistical association between the number of intratumoral and peritumoral buds with tumor size, tumor stage, presence of metastasis, the number of lymph nodes involved, and 5-year survival rate. On the other hand, there is not a significant statistical association between the number of intratumoral and peritumoral buds with age and tumor grade., Conclusion: Our investigation revealed a significant statistical relationship between the number of tumor buds and patients' survival rate. So, this factor should be considered significant to help those patients increase their survival ratio., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Alzheimer's Disease (AD) is a neurodegenerative disease that commonly occurs in older people. It is characterized by both cognitive and functional impairment. However, as AD has an unclear pathological cause, it can be hard to diagnose with confidence. This is even more so in the early stage of Mild Cognitive Impairment (MCI). This paper proposes a U-Net based Generative Adversarial Network (GAN) to synthesize fluorodeoxyglucose - positron emission tomography (FDG-PET) from magnetic resonance imaging - T1 weighted imaging (MRI-T1WI) for further usage in AD diagnosis including its early-stage MCI. The experiments have displayed promising results with Structural Similarity Index Measure (SSIM) reaching 0.9714. Furthermore, three types of classifiers are developed, i.e., one Multi-Layer Perceptron (MLP) based classifier, two Graph Neural Network (GNN) based classifiers where one is for graph classification and the other is for node classification. 10-fold cross-validation has been conducted on all trials of experiments for classifier comparison. The performance of these three types of classifiers has been compared with the different input modalities setting and data fusion strategies. The results have shown that GNN based node classifier surpasses the other two types of classifiers, and has achieved the state-of-the-art (SOTA) performance with the best accuracy at 90.18% for 3-class classification, namely AD, MCI and normal control (NC) with the synthesized fluorodeoxyglucose - positron emission tomography (FDG-PET) features fused at the input level. Moreover, involving synthesized FDG-PET as part of the input with proper data fusion strategies has also proved to enhance all three types of classifiers' performance. This work provides support for the notion that machine learning-derived image analysis may be a useful approach to improving the diagnosis of AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of metal-organic frameworks (MOFs) as catalysts is reported in various industrial applications. In contrast to monometallic MOFs, heterometallic MOFs with mixed organic ligands showed enhanced catalytic properties. The catalytic properties of heterometallic MOFs can be enhanced by generating defects and the synergistic effect between the two heterometals at secondary building units. By using a solvothermal technique, a Cd-Zn heterometallic MOF with a new morphology, [Cd 2 Zn(DPTTZ) 0.5 (OBA) 3 (H 2 O)(HCOOH)] ( IUST-4 ) [DPTTZ = 2,5-di(4-pyridyl)thiazolo[5,4- d ]thiazole, OBA = 4,4'-oxybis(benzoic acid)], was synthesized via a mixed-ligand strategy and characterized by single-crystal and powder X-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. X-ray crystallographic analysis showed that IUST-4 is a neutral 3D metal-organic framework crystallized in the monoclinic system with space group C 2/ c . In this study, the catalytic properties of IUST-4 for the epoxidation of cyclooctene were investigated. IUST-4 was selected as the optimal catalyst for epoxy product production due to its high selectivity and yield. Moreover, the catalytic performance of IUST-4 was maintained despite five recycling cycles without significant degradation. The epoxidation of cyclooctene with IUST-4 has several advantages, including good selectivity, easy recovery, and short-time reaction.

Pomegranate ( Punica granatum L.) is very important in terms of horticulture and food around the world. The present research aimed to identify the random amplified polymorphic DNA (RAPD) markers associated with morphological traits in pomegranate genotypes. Significant differences were observed among the studied genotypes based on the recorded traits. The 18 RAPD primers produced a total of 154 polymorphic fragments among genotypes. Using multiple regression analysis between each of the morphological traits and 154 RAPD polymorphic bands, RAPD markers associated with each of the morphological traits were identified. In total, 11 markers showed significant correlations with fruit weight, 9 markers with 100-aril weight, 11 markers with anthocyanin, and 8 markers with total soluble solids. Some markers were associated with more than one morphological trait, showing that the association of a marker with more than one trait can be caused by the pleiotropic effects of quantitative trait loci related to each other in different traits. For instance, the BA6-1 marker showed positive correlations with fruit weight, fruit crown width, and leaf length. Also, OPG13-3 and BA6-10 markers showed positive correlations with total soluble solids and anthocyanin content. The informative markers identified related to morphological characteristics in pomegranate can be a suitable guide to identify the genotypes with valuable fruit traits. Also, these markers can be used in selecting suitable parents for population generation for mapping purposes., Competing Interests: None., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Selective epoxidation of olefins is of high interest in the chemical industry due to the many applications of epoxides. This study reports on the synthesis of Cd-MOF, [Cd(DPTTZ)(5-AIP)] (IUST-1) (where DPTTZ = 2, 5-di (pyridine-4-yl) thiazolo [5, 4-d] thiazole, 5-AIP = 5-Aminoisophthalic acid), by a reflux method, which can be considered as a fast and simple process. The morphology and structure of the synthesized IUST-1 were determined by using FE-SEM (Field Emission Scanning Electron Microscopy), EDX (Energy Dispersive Analysis of X-ray), Mapping (Elemental Mapping), CHNS (Elemental analysis), XRD (X-Ray Diffraction), FT-IR (Fourier Transform Infrared), and TGA (Thermo Gravimetric Analysis). The epoxidation of cyclooctene was investigated using the activity of catalytic IUST-1. The results showed that in the presence of tert-butyl hydroperoxide and CCl 4 in a 1:2 alkene/oxidant ratio, a high epoxide yield (99.8%) was obtained. In addition, IUST-1 can be easily separated by simple filtration and recycled five times successfully with a slight decrease in activity. This compound has some advantages such as high yield, short reaction time, and ease of reuse, which make it a suitable heterogeneous catalyst for the epoxidation of cyclooctene., (© 2023. Springer Nature Limited.)

Almond ( Prunus dulcis [Mill.] D.A. Webb syn. P. amygdalus Batsch) is one of the most important nut crops, and its kernel is the edible part that has a high nutritional value and is used in the confectionery and cosmetics industries. The present research aimed to identify random amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) molecular markers associated with important fruit traits in late-blooming almond genotypes through multiple regression analysis (MRA). The studied genotypes showed significant differences from each other in terms of the measured fruit-related traits. The ISSR primers used produced a total of 125 bands in the studied germplasm, of which 112 showed polymorphic bands. The RAPD primers produced a total of 190 DNA fragments, of which 172 fragments showed polymorphism among genotypes. Some polymorphic fragments of ISSR and RAPD showed significant correlations with the fruit traits measured. Some of these informative markers were associated with more than one trait, which could be caused by the pleiotropic effects of quantitative trait loci related to each other in different traits. For instance, some of the markers showed significant correlations with both nut weight and kernel weight, which indicates a positive correlation between these two traits. Informative markers identified in this study can be used to select suitable parents for population generation for mapping. It is also useful for selecting superior genotypes, especially when information about their genetic basis, such as a linkage map, is not available., Competing Interests: None., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Pollution of water by heavy metal ions such as Pb 2+ and Hg 2+ is considered as an important issue, because of the potential toxic effects these ions impose on environmental ecosystems and human health. A new Zn-based metal-organic framework, [Zn 2 (DPTTZ) (OBA) 2 ] (IUST-2), was synthesized through a solvothermal method by the reaction of 2, 5-di (4- pyridyl) thiazolo [5, 4-d] thiazole ligand (DPTTZ), the "V-shape" 4,4'-oxybis (benzoic acid) ligand (OBA) and zinc nitrate (Zn(NO 3 ) 2 ·6H 2 O). This novel MOF has been characterized by several analysis techniques such as fourier transform infrared spectroscopy (FT-IR), elemental analysis (EA), powder x-ray diffraction (PXRD), thermogravimetry analysis (TGA), differential thermal analysis (DTA), field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET) surface area analysis and single-crystal X-ray diffraction (SXRD). This 3D MOF was tested for removing Pb 2+ and Hg 2+ ions from water. The factors that were investigated on the elimination of Pb 2+ and Hg 2+ ions were of pH, adsorption time, and the effect of initial ions concentration. According to the results, this particular Zn-MOF had significant performance in eliminating Pb 2+ and Hg 2+ ions from water with a removal efficiency of more than 97% and 87% within 3 min, respectively., (© 2023. The Author(s).)

Background: The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously overlooked. Now, an appreciation for the post-COVID-19 condition, including its neurological manifestations, is growing, although there remain many unknowns regarding the etiology and risk factors of the condition, as well as how to effectively diagnose and treat it. Methods: Here, drawing upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, we have reviewed the current literature to provide a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Results: In this review, we provide a summary of the neurological symptoms associated with the post-COVID-19 condition, before discussing the possible mechanisms which may underly and manifest these symptoms. Following this, we explore the risk factors for developing neurological symptoms as a result of COVID-19 and the post-COVID-19 condition, as well as how COVID-19 infection may itself be a risk factor for the development of neurological disease in the future. Lastly, we evaluate how the post-COVID condition could be accurately diagnosed and effectively treated, including examples of the current guidelines, clinical outcomes, and tools that have been developed to aid in this process, as well as addressing the protection provided by COVID-19 vaccines against the post-COVID-19 condition. Conclusions: Overall, this review provides a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Impact statement With our understanding of the neurological complications of the post-COVID-19 condition currently lacking sufficient depth, this review aimed at highlighting the current knowns and unknowns of the post-COVID-19 condition. In this review, we draw upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, as well as explore the current published literature, to evaluate a range of topics associated with the neurological complications of the post-COVID-19 condition. As a result, we have provided a comprehensive review of the topic. The European Working Group on SARS-CoV-2 Many essential questions surrounding COVID-19 remain unanswered, including its neurological complications and associated sequalae. In this review, we aim at identifying the current gaps in our understanding of post-COVID-19 neurological sequalae and suggest how future studies should be undertaken to fill these gaps. This review will draw upon the current biological and mechanistic understanding of COVID-19 and post-COVID-19 complications to discuss the clinically relevant aspects associated with the neurological manifestations of post-COVID-19 syndrome. From our discussions, the following questions were considered highly relevant for contemplation.

A novel highly fluorescent cadmium metal-organic framework, [Cd (DPTTZ) (OBA)] (IUST-3), synthesized by using two linkers 2, 5-di (pyridine-4-yl) thiazolo [5, 4-d] thiazole (DPTTZ) and 4, 4'-oxybis (benzoic acid) (OBA) simultaneously, which exhibits a two-dimensional framework. The characteristics of this Cd-MOF were investigated by single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis, powder X-ray diffraction, and thermogravimetry analysis. The IUST-3 exhibits excellent luminescence property and good stability in water. Luminescent experiments indicate that the IUST-3 has remarkable sensitivity and selectivity for the detection of 4-nitroaniline (4-NA), and CrO 4 2- anion with K SV  = 1.03 × 10 5  M -1 (4-NA) and K SV  = 2.93 × 10 4  M -1 (CrO 4 2- ) and low limit of detection 0.52 µM (4-NA) and 1.37 µM (CrO 4 2- ). In addition, the possible fluorescence quenching mechanism was explored in this paper., (© 2023. The Author(s).)

Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term., Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions., Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe., Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection., Key Points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations., Competing Interests: All authors state that they have no relationships/activities/interests to disclose related to the content of this submission. Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Aims: COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell ® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell ® syrup, on moderate COVID-19 patients along with the current standard of care treatment., Methods: A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell ® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial., Results: Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL - 6 and TNF - α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant., Conclusion: Overall, the treatment with Inflawell ® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines., Trial Registration: The trial has been registered in  https://www.irct.ir  with unique identifier: IRCT20170315033086N10 ( https://en.irct.ir/trial/51631 ). IRCT is a primary registry in the WHO registry network ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries )., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Immune system disorders and increased inflammation in the male reproductive system can lead to fetal risk in the early stages of development and implantation. Antioxidants such as vitamin C can play a protective role against sperm inflammatory reactions. This study aimed to evaluate the effect of vitamin C on the expression of inflammatory and anti-inflammatory cytokine genes in the male partners of couples with recurrent pregnancy loss. In this randomized clinical trial, twenty male partners of couples with RPL were examined for sperm parameters and expression profile of some inflammatory and anti-inflammatory cytokine genes before and after treatment with vitamin C. There was a statistically significant higher rate of normal morphology and sperm concentration in each patient before and after treatment with vitamin C ( p ≤ 0.05). The mRNA levels of interleukin 6 and tumor necrosis factor-alpha were significantly decreased in the sperm of patients after treatment with vitamin C compared to before treatment. In contrast, the gene expression levels of interleukin 4 and transforming growth factor-beta showed a significant increase in the sperm of patients after treatment with vitamin C. Oral daily administration of vitamin C may be effective in the fertility potential of male partners of couples with RPL not only through the improvement of the sperm parameters but also by modulating the expression profile of inflammatory and anti-inflammatory genes. Further studies on protein levels are needed to clarify the role of TNF- ⍺ and IFN- γ as a prognostic value in evaluating the recurrent abortion risk in infertile male partners. This trial is registered with IRCT20180312039059N1., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Farzaneh Fesahat et al.)

Background: Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in many compounds. Recent evidence has displayed some cytotoxic effects of TiO 2 NPs on male reproduction., Objective: The effects of TiO 2 NP administration on sperm parameters and chromatin and seminiferous histopathology of male mice were investigated., Materials and Methods: In this experimental study, 32 NMRI male mice (35 ± 3 gr, 8-12-week-old) were divided into four groups (n = 8/each): treated groups were fed orally with 2.5 (group I), 5 (group II) and 10 (group III) mg/kg/day TiO 2 NPs for 40 days and the control group received phosphate buffered saline. Sperm parameters, DNA integrity and chromatin quality were assessed using chromomycin A3, aniline blue, toluidine blue staining and TUNEL. Hematoxylin eosin staining was performed to measure spermatogenic cells and the total diameter of seminiferous tubules. Also, sex hormone and malondyaldehyde levels were measured., Results: Abnormal sperm tails rose in group III (28.87 ± 4.91) in comparison with the control group (12.75 ± 3.95). However, chromomycin A3 staining and TUNEL showed higher levels in group III in comparison with the control group, whereas aniline blue and toluidine blue staining showed no differences. A significantly lower spermatogenesis index and lumen parameters were observed in group III. Leydig cell numbers, cellular diameters and the area of the seminiferous tubules were lower in the treated groups. The testosterone level was also lower in these groups and the percentage of malondyaldehyde in the seminal fluid was higher., Conclusion: Exact mechanisms of TiO 2 NPs are not clear; however, cytotoxic and genotoxic effects of TiO 2 NPs may relate to oxidative stress. Given their widespread use, TiO 2 NPs should be a public health focus of attention., Competing Interests: The authors have no financial or nonfinancial conflict of interest., (Copyright © 2021 Danafar et al.)

Background: The differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with early onset Alzheimer's or related dementias (EOARD). We report our experience on diagnostic lumbar puncture to diagnose EOARD at a tertiary neurocognitive referral center in Nottingham, England from March 2018 to October 2020., Objective: To assess amyloid-β42 (Aβ42), total tau, and Thr181-phosphorylated tau (p-tau) measurements in the cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and in relation to their follow-up cognitive performance., Methods: Thirty participants aged 32-68 years old (mean 59 years; 57% female) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, neuroradiological features (MRI, FDG-PET CT) and CSF Aβ42, total tau, and p-tau measurements., Results: Patients with MCI who progressed to AD (prodromal AD) had significantly higher CSF total (797.63 pg/ml) and p-tau (82.31 pg/ml), and lower Aβ42 levels (398.94 pg/ml) in comparison to their counterparts with stable MCI (total tau 303.67 pg/ml, p-tau 43.56 pg/ml, Aβ42 873.44 pg/ml) (p < 0.01 for CSF total and p-tau measures and p < 0.0001 for CSF Aβ42 measures). None of the CSF biomarkers correlated with any of the cognitive performance measures. Principal component analysis confirmed that the clinical diagnosis of MCI secondary to AD, namely prodromal AD (as per NIA-AA criteria) in younger adults, was associated with decreased CSF Aβ42., Conclusion: In early onset AD, low levels of CSF Aβ42 appear to be more sensitive than total and p-tau measures in differentiating AD MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness of making an earlier diagnosis.

Background Hope nurtures confidence and enhances positivity. It is known to be a critical factor in illness, recovery and healing. This study aimed to identify the views of hospitalized children with cancer about the circumstances and factors that create hope for them in the oncology ward. Methods: This qualitative study explored children's experiences using Photovoice, which is an arts-based approach. Twenty children aged 6-12 years diagnosed with various cancers at a Pediatric Hospital in Tehran, Iran, participated in this study. Participants were requested to take photographs of objects, circumstances, or anything that gave them hope or represented a sign of hope in the oncology ward. The photographs were then used to facilitate face-to-face interviews with these children. Data were analyzed using thematic analysis. Results: Data analysis revealed six main themes: emotional connectedness with nursing staff; the playroom as a means to soften the hospital space; the presence of a parent; symbols of recovery; a touch of nature in the hospital setting; and escaping the hospital cage. Discussion: Hopefulness among children can emanate from diverse events and circumstances within the hospital environment. Nurses and physicians need an understanding of children's perspectives to design interventions to improve hopefulness among hospitalized children with cancer.

Introduction: The increasing evidence of SARS-CoV-2 impact on the central nervous system (CNS) raises key questions on its impact for risk of later life cognitive decline, Alzheimer's disease (AD), and other dementia., Methods: The Alzheimer's Association and representatives from more than 30 countries-with technical guidance from the World Health Organization-have formed an international consortium to study the short-and long-term consequences of SARS-CoV-2 on the CNS-including the underlying biology that may contribute to AD and other dementias. This consortium will link teams from around the world covering more than 22 million COVID-19 cases to enroll two groups of individuals including people with disease, to be evaluated for follow-up evaluations at 6, 9, and 18 months, and people who are already enrolled in existing international research studies to add additional measures and markers of their underlying biology., Conclusions: The increasing evidence and understanding of SARS-CoV-2's impact on the CNS raises key questions on the impact for risk of later life cognitive decline, AD, and other dementia. This program of studies aims to better understand the long-term consequences that may impact the brain, cognition, and functioning-including the underlying biology that may contribute to AD and other dementias., (© 2021 the Alzheimer's Association.)

While some biomolecules have been explored to identify potential biomarkers for the prognosis of COVID-19 patients, there is no reliable prognostic indicator of the disease progression and severity. We aimed to evaluate the ability of the C-reactive protein (CRP) to predict COVID-19 infection outcome. This retrospective study was conducted on 429 patients diagnosed with COVID-19 between March 30, 2020, and April 30, 2020. The study population was divided into severe ( n  = 175) and nonsevere cases ( n  = 254). Data on demographic characteristics, clinical features, and laboratory findings on admission were collected. The proportion of patients with increased CRP levels was significantly higher in severe cases than in nonsevere patients. Analysis of the receiver operating characteristic (ROC) curve found that CRP could be used as an independent factor in predicting the severity of COVID-19. Also, patients with CRP >64.75 mg/L were more likely to have severe complications. In conclusion, CRP serum levels can predict the severity and progression of illness in patients with COVID-19., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Mahmoud Sadeghi-Haddad-Zavareh et al.)

Background: Early reports have detailed a range of neurological symptoms in patients with the SARS-CoV-2 infection. However, there is a lack of detailed description and incidence of the neurological disorders amongst hospitalized COVID-19 patients. We describe a range of neurological disorders (other than non-specific neurological symptoms), including their clinical, radiological, and laboratory findings, encountered in our cohort of COVID-19 patients admitted to a large tertiary institution. Methods: We reviewed our prospectively collated database of all adult Neurology referrals, Neurology and Stroke admissions and Neurological multi-disciplinary team meetings for all hospitalized patients with suspected or proven COVID-19 from 17 March 2020 to 31 August 2020. Results: Twenty-nine of 1,243 COVID-19 inpatients (2.3%) presented with COVID-19-related neurological disorders. The mean age was 68.9 ± 13.5(SD) years, age range of 34-97 years, and there were 16 males. Twenty two patients had confirmed, five were probable and two had suspected COVID-19 infection according to the WHO case classification. Eight patients (27%) required critical care admission. Neurological symptoms at presentation included acute confusion and delirium, seizures, and new focal neurological deficits. Based on the pre-defined neurological phenotype, COVID-19 patients were grouped into four main categories. Sixteen patients had cerebrovascular events (13 with acute ischemic stroke and three had hemorrhagic features), seven patients were found to have inflammatory, non-inflammatory and autoimmune encephalopathy (including two with known Multiple Sclerosis), whilst disorders of movement and peripheral nervous system were diagnosed in three patients each. Conclusion: Although the exact prevalence and etiology remain unclear, new onset of neurological disorders, in addition to anosmia, is non-sporadic during the acute COVID-19-infection. Longitudinal follow-up of these patients is required to determine the clinical and functional outcome, treatment response and long-term effects of the SARS-CoV-2 infection., 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 Dhillon, Dineen, Morris, Tanasescu, Nikfekr, Evans, Constantinescu and Hosseini.)

Background: Ischemic stroke with cognitive impairment is a considerable risk factor for developing dementia. Identifying imaging markers of cognitive impairment following ischemic stroke will help to develop prevention strategies against post-stroke dementia., Methods: We investigated the hippocampal functional connectivity (FC) pattern following ischemic stroke, using resting-state fMRI (rs-fMRI). Thirty-three cognitively impaired patients after ischemic stroke and sixteen age-matched controls with no known history of neurological disorder were recruited for the study. No patient had a direct ischaemic insult to hippocampus on the examination of brain imaging. Seven subfields of hippocampus were used as seeds region for FC analyses., Results: Across all hippocampal subfields, FC with the inferior parietal lobule was reduced in stroke patients as compared with healthy controls. This decreased FC included both supramarginal gyrus and angular gyrus. The FC of hippocampal subfields with cerebellum was increased. Importantly, the degree of the altered FC between hippocampal subfields and inferior parietal lobule was associated with their impaired memory function., Conclusion: Our results demonstrated that decreased hippocampal-inferior parietal lobule connectivity was associated with cognitive impairment in patients with ischemic stroke. These findings provide novel insights into the role of hippocampus in cognitive impairment following ischemic stroke., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: The goal of this study was to compare the risk of stroke between patients with carotid artery disease with and without the presence of intraplaque hemorrhage (IPH) on magnetic resonance imaging., Background: IPH in carotid stenosis increases the risk of cerebrovascular events. Uncertainty remains whether risk of stroke alone is increased and whether stroke is predicted independently of known risk factors., Methods: Data were pooled from 7 cohort studies including 560 patients with symptomatic carotid stenosis and 136 patients with asymptomatic carotid stenosis. Hazards of ipsilateral ischemic stroke (primary outcome) were compared between patients with and without IPH, adjusted for clinical risk factors., Results: IPH was present in 51.6% of patients with symptomatic carotid stenosis and 29.4% of patients with asymptomatic carotid stenosis. During 1,121 observed person-years, 66 ipsilateral strokes occurred. Presence of IPH at baseline increased the risk of ipsilateral stroke both in symptomatic (hazard ratio [HR]: 10.2; 95% confidence interval [CI]: 4.6 to 22.5) and asymptomatic (HR: 7.9; 95% CI: 1.3 to 47.6) patients. Among patients with symptomatic carotid stenosis, annualized event rates of ipsilateral stroke in those with IPH versus those without IPH were 9.0% versus 0.7% (<50% stenosis), 18.1% versus 2.1% (50% to 69% stenosis), and 29.3% versus 1.5% (70% to 99% stenosis). Annualized event rates among patients with asymptomatic carotid stenosis were 5.4% in those with IPH versus 0.8% in those without IPH. Multivariate analysis identified IPH (HR: 11.0; 95% CI: 4.8 to 25.1) and severe degree of stenosis (HR: 3.3; 95% CI: 1.4 to 7.8) as independent predictors of ipsilateral stroke., Conclusions: IPH is common in patients with symptomatic and asymptomatic carotid stenosis and is a stronger predictor of stroke than any known clinical risk factors. Magnetic resonance imaging might help identify patients with carotid disease who would benefit from revascularization., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Platelet-rich plasma (PRP) and hyaluronic acid have been shown to be useful in the treatment of knee osteoarthritis. However, investigations comparing the efficacy of these two drugs together are insufficient., Aim: To compare the outcomes of PRP vs hyaluronic acid injections in three groups of patients with bilateral knee osteoarthritis., Methods: This randomized controlled trial study involved 95 patients. Thirty-one subjects received a single injection of PRP (group PRP-1), 33 subjects received two injections of PRP at an interval of 3 wk (group PRP-2) and 31 subjects received three injections of hyaluronic acid at 1-wk intervals (group hyaluronic acid). The patients were investigated prospectively at the enrollment and at 4-, 8- and 12-wk follow-up with the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analogue Scale questionnaires., Results: Percentages of patients experiencing at least a 30% decrease in the total score for the WOMAC pain subscale from baseline to wk 12 of the intervention were 86%, 100% and 0% in the groups PRP-1, PRP-2 and hyaluronic acid, respectively ( P < 0.001). The mean total WOMAC scores for groups PRP-1, PRP-2 and hyaluronic acid at baseline were 63.71, 61.57 and 63.11, respectively. The WOMAC scores were significantly improved at final follow-up to 42.5, 35.32 and 57.26, respectively. The highest efficacy of PRP was observed in both groups at wk 4 with about 50% decrease in the symptoms compared with about 25% decrease for hyaluronic acid. Group PRP-2 had higher efficacy than group PRP-1. No major adverse effects were found during the study., Conclusion: PRP is a safe and efficient therapeutic option for treatment of knee osteoarthritis. It was demonstrated to be significantly better than hyaluronic acid. We also found that the efficacy of PRP increases after multiple injections., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest to declare., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Among the inflammatory factors, high-sensitivity C-reactive protein (hs-CRP) is one of the strongest predictors of cardiovascular disease. This study aimed to evaluate the relationship of serum hs-CRP level with shift work among reproductive age women., Methods: This cross-sectional study was conducted from September 2017 to May 2018 in three cities in Mazandaran Province, North of Iran. Through purposive sampling, 350 women (172 shift workers and 178 day workers) were recruited. The guideline recommended by the American Heart Association and the Centers for Disease Control and Prevention was used to interpret the result of hs-CRP measurement as the following: less than 1 µg/ml: low CVD risk; 1-3 µg/ml: moderate CVD risk; and more than 3 µg/ml: high CVD risk. The data were analyzed using the independent-sample t and the chi-square tests as well as the logistic regression analysis., Results: 11.1% of participants had a serum hs-CRP level of more than 3 µg/ml. This rate among shift workers was significantly greater than day workers (15.6% vs. 7.0%; p=0.012). After adjusting the effects of potential confounders shift work significantly increased the odds of serum hs-CRP level of more than 3 µg/ml by 2.45 times (OR=2.45, 95% CI: 1.01-5.93, p=0.047)., Conclusion: Shift work is a significant predictor of high serum hs-CRP level probably due to its association with sleep problems and occupational stress. Improving the knowledge of female shift workers about the importance of quality sleep can reduce their CVD risk and improve their health., Competing Interests: None declared.

Background: Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care., Methods: We will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group. Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2-4 consecutive days no later than 7 days from baseline. It will continue 4-5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2-3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12 months from the first day of treatment or, where sustained remission begins after the first 6 months, for an additional minimum of 6 months to assess later response., Discussion: The SINAPPS2 trial aims to test whether immunotherapy is efficacious and safe in psychosis associated with anti-neuronal membrane antibodies., Trial Registration: ISRCTN, 11177045. Registered on 2 May 2017. EudraCT, 2016-000118-31. Registered on 22 November 2016. ClinicalTrials.gov, NCT03194815. Registered on 21 June 2017.

Cryopreservation and subsequent survival of semen samples with low numbers of human spermatozoa in assisted reproductive technology (ART) facilities can be challenging. The aim of this study was to compare the quality of warmed human spermatozoa following vitrification using direct submerging (DS) in liquid nitrogen (LN 2 ) or with LN 2 vapour (V). Normozoospermic ejaculates were prepared by the swim-up technique and the motile sperm fraction was divided into three groups: (i) fresh (control); (ii) DS methods in LN 2 (DS Group); or (iii) cryopreserved in V (Group V). Cryopreservation was performed in a small volume using a Cryotech device. After warming, sperm parameters (motility, viability, acrosome, DNA fragmentation and chromatin integrity) were assessed using cytochemical assays. Progressive motility, viability, chromatin integrity and DNA fragmentation differed significantly after warming when compared with the control. Sperm progressive motility and total motility rates were significantly higher in the DS Group compared to Group V. However, normal morphology, acrosome integrity and DNA damage were not significantly different between two groups. Also, sperm chromatin condensation using chromomycin-A3 (CMA3) and Aniline Blue (AB) staining showed fewer alterations in the DS Group compared to Group V. The rates of spermatozoa with an intact acrosome decreased significantly after thawing from 81.30 ± 6.76% to 68.84 ± 14.70% in the DS Group and to 60.92 ± 8.06% in Group V. Cryopreservation of a small number of spermatozoa with the DS method showed superior outcomes with regard to motility, viability and chromatin configuration.

Shift work during reproductive age can be a risk factor for metabolic syndrome. The present study evaluated the association between shift work and metabolic syndrome during reproductive age. This multi-center cross-sectional correlational study was performed between September 2017 and May 2018. A total of 419 female shift and day workers were purposively recruited to the study from three central cities in Mazandaran, Iran. To diagnose metabolic syndrome based on the National Cholesterol Education Program Adult Treatment Panel III guidelines, the anthropometric measures, blood pressure, and levels of serum triglyceride, high-density lipoprotein and fasting blood sugar were taken. Data were analyzed using the independent-sample t, Chi-square and the Fisher's exact tests as well as the logistic regression analysis. Among the 419 participants, 28 were excluded during the study. The total prevalence of metabolic syndrome was 16.3%, and its prevalence among shift workers and day workers was 17.3 and 14.9%, respectively. The most prevalent components of metabolic syndrome were low serum level of high-density lipoprotein and abdominal obesity. Following adjustments for the effects of potential cofounders, the logistic regression analysis revealed that the odds of metabolic syndrome among shift workers was ~2 times greater than day workers (odds ratio, 1.83; 95% confidence interval, 0.088-3.79), although this association was statistically insignificant (P=0.10). The results of the current study suggest that shift work is associated with a greater risk of metabolic syndrome for women. The most important components of metabolic syndrome are low serum level of high-density lipoprotein and abdominal obesity, which are attributable to limited physical activity and high occupational stress. The risk of metabolic syndrome among female shift workers of reproductive age may be reduced through strategies, including awareness raising, dietary educations and provision of physical activity facilities in the workplace.

Background: Inflammatory bowel disease (IBD) is a chronic disease with a relapsing course of inflammation in the digestive system. Endoscopy and histopathology are the golden standard methods for detection and assessment of IBD. A distinct increase of fecal calprotectin level can be a useful marker for the diagnosis of IBD. The aim of this study was to evaluate the fecal calprotectin level in patients with IBD and without inflammatory diseases of the colon., Methods: Calprotectin levels of patients referred to the Ayatollah Rouhani Hospital of Babol, northern Iran with clinical symptoms of colon disease were evaluated. After a week, colonoscopy and biopsy were performed on all patients and they were divided into two groups. The first group included patients with confirmed IBD and the second group included patients with diseases other than IBD, patients with IBS and healthy persons. Then the measured fecal calprotectin level was compared between the two groups before colonoscopy., Results: We observed correlation between calprotection in these two groups (p<0.0001). 38 (86.8%) patients in the case group and 5 (13.2%) patients in the control group had positive fecal calprotectin test and 12 (23.1%) patients in the case group and 40 (76.9%) patients in the control group had negative results. Basad on ROC curve, the cutoff point of calprotectin was 127.65 with 73% sensitivity and 89% specificity. The area under the curve was 0.83 with 95% confidence interval, 0.74-0.91 (p<0.0001)., Conclusions: The results pointed to this fact that fecal calprotectin can be a noninvasive marker in differentiating IBD from IBS., Competing Interests: There was no conflict of interest.

Background: Cyclophosphamide (CP) is one of the most invasive chemotherapeutic agents, which used commonly despite of its wide spectrum toxicity. Clinical evidence showed toxic side effects of CP in multiple organ systems., Objective: The objective of the present study was to evaluate the effects of American ginseng on CP-induced testicular toxicity in rats., Materials and Methods: Adult male Wistar rats (220±30 gr) were randomly divided into four groups (n=7 in each). Group 1 as control received normal saline by gavage, group 2 received CP (6.1 mg/kg/day, i.p.) for a period of 50 days. Group 3 received American ginseng (500 mg/kg/day) by gavage. Group 4 received American ginseng (500 mg/kg/day) 1h prior to the administration of CP in the equal dose of group 2. The animals scarified one day after the last treatment and the effects of American ginseng on the sperm vital parameters, testicular functions, biochemical factors, and structural malformations evaluated., Results: Serum testosterone concentration was significantly decreased whereas the level of malondialdehyde and DNA damage were significantly increased in animals of CP group (p<0.01). Co-administration of American ginseng reversed these parameters and improved recovery in CP+ginseng group. In addition, seminiferous tubules of testis severely damaged in the CP group but ginseng improved histologic changes in CP+ginseng group., Conclusion: The findings confirmed the protective effects of American ginseng on toxicity induced by CP in the reproductive system of male rats., Competing Interests: The authors declare that there is no conflict of interest in this paper.

Aim: To present a concept analysis of pain in children's drawings and dialogs., Introduction: The complexity and subjectivity of the concept of pain in children remain ambiguous. As a result, children are exposed to inappropriate diagnosis and inadequate treatment. Children can describe or draw their painful experiences. Analysing the concept of pain based on children's experiences can help identify, assess and properly manage and treat pain in children., Design: Concept analysis., Methods: Walker and Avant's framework for concept analysis was used in this current study., Results: Major aspects of pain revealed in this concept analysis are affected by children's different concerns about pain. The description of pain in children with chronic diseases or chronic pain is completely different from that in healthy children. Children perceive pain to be internal, external and emotional. Pain in children is associated with poor psychological and emotional conditions, which add new features and aspects to the concept of pain. Children's descriptions and drawings of pain indicate different concepts of pain in their minds. From the perspective of children, pain has an identity that is formed based on reality., Conclusion: When developing pain evaluation tools, it is necessary to address the characteristics of pain. In the case of chronic pain, emotional effects of pain on children's psyche need extra attention. Child-based pain management guidelines can then be formulated with the results of relevant concept analyses. Pain assessment is a major part of pain management in children. By considering the characteristics of the concept of pain, the efficiency and usefulness of developed tools can be enhanced to create advancement in paediatric pain management.

Objective: Aim of this study was to evaluate the effects of vitamin C on sperm parameters, sperm chromatin quality and apoptosis resulted of vitrification in neat semen and prepared spermatozoa of normozoospermic samples., Material and Methods: Forty semen samples from normozoospermic men were included in this prospective study. Each sample was divided into five groups. Group I: control or fresh semen, group II: semen prepared by swim-up method and then vitrified, group III: neat semen was vitrified, group IV: vitamin C (600 μM) was added to prepared spermatozoa and then vitrified and group V: vitamin C (600 μM) was added to neat semen and then vitrified. After warming, sperm analysis was done accordingly. For evaluating the sperm chromatin/DNA integrity status and acrosome reaction, we used toluidine blue (TB), acridine orange (AO), terminal transferase mediated deoxyuridine triphosphate biotin end labeling (TUNEL) and double staining tests., Results: All of the sperm parameters (count, motility, morphology and viability) had significant differences (P < 0.05) between different groups, especially in group IV. Data showed sperm chromatin damages and acrosome reaction abnormality increased resulted of vitrification, but, in the groups that added vitamin C (IV, V) rate of damages was decreased and this was notable in the group IV., Conclusion: Vitamin C can attenuate the detrimental effects of vitrification on sperm parameters, chromatin quality and rate of apoptosis in both neat semen and prepared spermatozoa of normozoospermic samples., (Copyright © 2018. Published by Elsevier B.V.)

Subarachnoid hemorrhage as a presentation of cerebral venous sinus thrombosis (CVST) is a rare but recognized phenomenon. A high index of suspicion among clinicians and an awareness of subtle CT features can avoid delayed diagnosis of underlying CVST [Eur J Neurol., 17, 2010, 1249]. Prompt but careful anticoagulation can prevent significant associated morbidity and mortality.

Objective: Presence of vitrification method in sperm freezing and the introduction of solid surface vitrification beside rapid freezing in vapour, opens an easy and safe way to help infertility centres. While the effects of cryopreservation on motility, morphology and viability of sperm are documented, the question of the probable alteration of sperm DNA, chromatin and acrosome integrity after freezing and thawing procedures in different methods is still controversial., Materials and Methods: Normal sample were collected according to WHO strict criteria. Sperm suspensions were mixed 1:1 with 0.5 M sucrose and divided into four equal aliquots for freezing: fresh, nitrogen direct immersion vitrification (Vit), solid surface vitrification (SSV) and in vapour (Vapour). Sperm suspensions were transferred into a 0.25 ml sterile plastic. Then straw was inserted inside the 0.5 ml straw. For thawing, the straws were immersed in a 42 °C water bath. Beside the sperm parameters, we assessed the acrosome reaction by double staining, chromatin integrity by toluidine blue (Tb) and chromomycin A3 (CMA3) and DNA integrity by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) respectively., Results: In progressive motility, the highest rate occurred in Vit (39.9 ± 13.3). Moreover, the lowest rate of immotile sperm was in Vit (32.7 ± 16.3). In normal morphology, the group Vit was similar to the fresh, while SSV and Vapour were significantly different from the fresh. The percentage of acrosome-reacted sperms was more in Vit (81.3 ± 10.2) than the fresh group. TUNEL+ results showed that DNA fragmentation was significantly increased in Vit (p-value = 0.025). While in SSV and Vapour results were comparable to fresh. There was a significant correlation between TUNEL+ and normal morphology, TB, CMA3 and presence of intact acrosome., Conclusion: Sperm in Vapour was healthier in terms of DNA, chromatin and acrosome integrity. In contrast of higher motility and normal morphology; DNA, chromatin and acrosome integrity were decreased in Vit. However, these findings were more acceptable in SSV or Vapour., (Copyright © 2017. Published by Elsevier B.V.)

Background: Sperm motility is the reliable parameter that roles in success of intracytoplasmic sperm injection (ICSI), especially in azoospermia. Selection of appropriate culture duration, temperature and media for enhancing the sperm motility is an important issue in assisted reproduction program. The aim was to evaluate the sperm motion characteristics after culturing of testicular sperm extraction (TESE) samples at different temperatures and time intervals., Methods: In this prospective study, 27 TESE samples were collected from young azoospermic patients. The samples were cultured in Ham's F10+20% HAS, at different temperatures (incubation at 37 vs. 25 °C) and sperm total motility was assessed at different time intervals of 0, 24, 48 and 72 h post testicular biopsy., Results: In vitro culture at 25 °C changed sperm motility from 13% immediately after biopsy to 76% at 24 h, 43% at 48 h and 15% at 72 h. At 37 °C, the sperm motion feature was changed to 67% at 24 h, 38.40% at 48 h and 12.03% at 72 h. Sperm motility change at 24 h was incremental in both conditions of culturing, but significant at 25 °C (P≤0.05)., Conclusions: The ideal in vitro culture for testicular spermatozoa was at 25 °C after 1 day of culture, which optimized the sperm motility in azoospermic TESE samples., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background and Purpose: Magnetic resonance imaging (MRI)-defined carotid plaque hemorrhage (MRIPH) can predict recurrent cerebrovascular ischemic events in severe symptomatic carotid stenosis. It is less clear whether MRIPH can improve risk stratification despite optimized medical secondary prevention in those with moderate risk., Methods: One-hundred fifty-one symptomatic patients with 30% to 99% carotid artery stenosis (median age: 77, 60.5% men) clinically deemed to not benefit from endarterectomy were prospectively recruited to undergo MRI and clinical follow-up (mean, 22 months). The clinical carotid artery risk score could be evaluated in 88 patients. MRIPH+ve was defined as plaque intensity >150% that of adjacent muscle. Survival analyses were performed with recurrent infarction (stroke or diffusion-positive cerebral ischemia) as the main end point., Results: Fifty-five participants showed MRIPH+ve; 47 had low, 36 intermediate, and 5 high carotid artery risk scores. Cox regression showed MRIPH as a strong predictor of future infarction (hazard ratio, 5.2; 95% confidence interval, 1.64-16.34; P =0.005, corrected for degree of stenosis), also in the subgroup with 50% to 69% stenosis (hazard ratio, 4.1; 95% confidence interval, 1-16.8; P =0.049). The absolute risk of future infarction was 31.7% at 3 years in MRIPH+ve versus 1.8% in patients without ( P <0.002). MRIPH increased cumulative risk difference of future infarction by 47.1% at 3 years in those with intermediate carotid artery risk score ( P =0.004)., Conclusions: The study confirms MRIPH to be a powerful risk marker in symptomatic carotid stenosis with added value over current risk scores. For patients undergoing current secondary prevention medication with clinically uncertain benefit from recanalization, that is, those with moderate degree stenosis and intermediate carotid artery risk scores, MRIPH offers additional risk stratification., (© 2017 American Heart Association, Inc.)

Purpose To investigate associations between neuroimaging markers of cerebrovascular disease, including lesion topography and extent and severity of strategic and global cerebral tissue injury, and cognition in carotid artery disease (CAD). Materials and Methods All participants gave written informed consent to undergo brain magnetic resonance imaging and the Addenbrooke's Cognitive Examination-Revised. One hundred eight patients with symptomatic CAD but no dementia were included, and a score less than 82 represented cognitive impairment. Group comparison and interrelations between global cognitive and fluency performance, lesion topography, and ultrastructural damage were assessed with voxel-based statistics. Associations between cognition, medial temporal lobe atrophy (MTA), lesion volumes, and global white matter ultrastructural damage indexed as increased mean diffusivity were tested with regression analysis by controlling for age. Diagnostic accuracy of imaging markers selected from a multivariate prediction model was tested with receiver operating characteristic analysis. Results Cognitively impaired patients (n = 53 [49.1%], classified as having probable vascular cognitive disorder) were older than nonimpaired patients (P = .027) and had more frequent MTA (P < .001), more cortical infarctions (P = .016), and larger volumes of acute (P = .028) and chronic (P = .009) subcortical ischemic lesions. Lesion volumes did not correlate with global cognitive performance (lacunar infarctions, P = .060; acute lesions, P = .088; chronic subcortical ischemic lesions, P = .085). In contrast, cognitive performance correlated with presence of chronic ischemic lesions within the interhemispheric tracts and thalamic radiation (P < .05, false discovery rate corrected). Skeleton mean diffusivity showed the closest correlation with cognition (R 2 = 0.311, P < .001) and promising diagnostic accuracy for vascular cognitive disorder (area under the curve, 0.82 [95% confidence interval: 0.75, 0.90]). Findings were confirmed in subjects with a low risk of preclinical Alzheimer disease indexed by the absence of MTA (n = 85). Conclusion Subcortical white matter ischemic lesion locations and severity of ultrastructural tract damage contribute to cognitive impairment in symptomatic CAD, which suggests that subcortical disconnection within large-scale cognitive neural networks is a key mechanism of vascular cognitive disorder. Online supplemental material is available for this article.

Objective: Pruritus is a common and disturbing side effect of neuraxial opioids after cesarean section. The purpose of this study was to compare the efficacy of intravenous ondansetron and sub-hypnotic dose of propofol in control and treatment of intrathecal sufentanil induced pruritus in cesarean surgery., Methods: Totally, 90 parturient with American Society of Anesthesiology physical status grade I-II, undergoing spinal anesthesia with 2.5 μg sufentanil and 10 mg bupivacaine 0.5% were enrolled to this randomized, prospective, double-blind study. The women were randomly assigned to two groups who received 8 mg ondansetron or 10 mg propofol to treat pruritus grade ≥3. The patient was evaluated after 5 min and in the lack of successful treatment, the doses of two drugs repeated and if the pruritus is on-going, the exact treatment with naloxone was done., Findings: The incidence of pruritus was 69.3%. Both groups were well-matched. The peak time pruritus was 30-75 min after injection. The percentage of individuals consumed naloxone were 6.8% and 15.9% in ondansetron and propofol groups, respectively (P = 0.18). The mean score of satisfaction (according to visual analog scale criteria) was 9.09 ± 1.1 in ondansetron group and 9.3 ± 1.07 in the propofol group (P = 0.39)., Conclusion: Ondansetrone and sub-hypnotic dose of propofol are both safe and well-tolerated. Due to their same efficacy in the treatment of intrathecal sufentanil-induced pruritus, they can be widely used in clinical practice.

Background: The European Carotid Surgery Trial (ECST) risk model is a validated tool for predicting cerebrovascular risk in patients with symptomatic carotid disease. Carotid plaque hemorrhage as detected by MRI (MRIPH) and microembolic signals (MES) detected by transcranial Doppler (TCD) are 2 emerging modalities in assessing instability of the carotid plaque. The aim of this study was to assess the strength of association of MES and MRIPH with cerebrovascular recurrence in patients with symptomatic carotid artery disease in comparison with the ECST risk prediction model., Methods and Results: One hundred and thirty-four prospectively recruited patients (mean [SD]: age 72 [9.8] years, 33% female) with symptomatic severe (50% to 99%) carotid stenosis underwent preoperative TCD, MRI of the carotid arteries to assess MES, PH, and the ECST risk model. Patients were followed up until carotid endarterectomy, recurrent cerebral event, death, or study end. Event-free survival analysis was done using backward conditional Cox regression analysis.Of the 123 patients who had both TCD and MRI, 82 (66.7%) demonstrated PH and 46 (37.4%) had MES. 37 (30.1%) cerebrovascular events (21 transient ischemic attacks, 6 amaurosis fugax, and 10 strokes) were observed. Both carotid PH (HR=8.68; 95% CI 2.66 to 28.40, P<0.001) as well as MES (HR=3.28; 95% CI 1.68 to 6.42, P=0.001) were associated with cerebrovascular event recurrence. Combining MES and MRIPH improved the strength of association (HR=0.74, 95% CI 0.65 to 0.83; P<0.001). The ECST risk model was not associated with recurrence (HR=0.86; 95% CI 0.45 to 1.65; P=0.65)., Conclusions: The presence of carotid plaque hemorrhage is better associated with recurrent cerebrovascular events in patients with symptomatic severe carotid stenosis than the presence of microembolic signals; combining MES and MRIPH, further improves the association while the ECST risk score was insignificant., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Tramadol is a potent analgesic drug which interacts with mu-opioid and has low effect on other opioid receptors. Unlike other opioids, it has no clinically significant effect on respiratory or cardiovascular parameters. Alakaline phosphatase is a hydrolase enzyme that prefers alkaline condition and removes phosphate group from different substrates. In this study, the interaction between tramadol and calf liver alkaline phosphatase was investigated. The results showed that tramadol can bind to alakaline phosphatase and inhibit the enzyme in an un-competitive manner. Ki and IC50 values of tramadol were determined as about 91 and 92 μM, respectively. After enzyme purification, structural changes on alakaline phosphatase-drug interaction were studied by circular dichroism and fluorescence measurement. These data revealed the alteration in the content of secondary structures and also conformational changes in enzyme occurred when the drug bound to enzyme-substrate complex.

Objective: There is a recognized need to improve selection of patients with carotid artery stenosis for carotid endarterectomy (CEA). We assessed the value of magnetic resonance imaging (MRI)-defined carotid plaque hemorrhage (MRIPH) to predict recurrent ipsilateral cerebral ischemic events, and stroke in symptomatic carotid stenosis., Methods: One hundred seventy-nine symptomatic patients with ≥ 50% stenosis were prospectively recruited, underwent carotid MRI, and were clinically followed up until CEA, death, or ischemic event. MRIPH was diagnosed if the plaque signal intensity was >150% that of the adjacent muscle. Event-free survival analysis was done using Kaplan-Meier plots and Cox regression models controlling for known vascular risk factors. We also undertook a meta-analysis of reported data on MRIPH and recurrent events., Results: One hundred fourteen patients (63.7%) showed MRIPH, suffering 92% (57 of 62) of all recurrent ipsilateral events and all but 1 (25 of 26) future strokes. Patients without MRIPH had an estimated annual absolute stroke risk of only 0.6%. Cox multivariate regression analysis proved MRIPH as a strong predictor of recurrent ischemic events (hazard ratio [HR] = 12.0, 95% confidence interval [CI] = 4.8-30.1, p < 0.001) and stroke alone (HR = 35.0, 95% CI = 4.7-261.6, p = 0.001). Meta-analysis of published data confirmed this association between MRIPH and recurrent cerebral ischemic events in symptomatic carotid artery stenosis (odds ratio = 12.2, 95% CI = 5.5-27.1, p < 0.00001)., Interpretation: MRIPH independently and strongly predicts recurrent ipsilateral ischemic events, and stroke alone, in symptomatic ≥ 50% carotid artery stenosis. The very low stroke risk in patients without MRIPH puts into question current risk-benefit assessment for CEA in this subgroup., (© 2013 American Neurological Association.)

Background and Purpose: Women are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA) than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH) as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence., Methods: Prevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50-69%]) who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis., Results: Women with symptomatic carotid stenosis (50%≥) were less likely to have plaque hemorrhage (PH) than men (46% vs. 70%) with an adjusted OR of 0.23 [95% CI 0.10-0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067-0.50) not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15-0.98, P = 0.045). Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect. Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45-0.67, p<0.00001)., Conclusions: MRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA.

Background: Cerebrovascular disease is the second commonest cause of death, and over a third of stroke deaths occur in developing countries. To fulfil the current gap on data, this systematic review is focused on the frequency of stroke, risk factors, stroke types and mortality in Iran., Methods: Thirteen relevant articles were identified by keyword searching of PubMed, Iranmedex, Iranian University index Libraries and the official national data on burden of diseases., Results: The publication dates ranged from 1990 to 2008. The annual stroke incidence of various ages ranged from 23 to 103 per 100,000 population. This is comparable to the figures from Arab Countries, higher than sub-Saharan Africa, but lower than developed countries, India, the Caribbean, Latin America, and China. Similarly to other countries, ischaemic stroke was the commonest subtype. Likewise, the most common related risk factor is hypertension in adults, but cardiac causes in young stroke. The 28-day case fatality rate is reported at 19-31%., Conclusions: Data on the epidemiology of stroke, its pattern and risk factors from Iran is scarce, but the available data highlights relatively low incidence of stroke. This may reflect a similarity towards the neighbouring nations, and a contrast with the West.