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Systematic HIV program evaluation requires looking at all steps of the HIV cascade of care, from diagnosis to treatment outcomes. Our study was carried out to assess the treatment cascade of people living with HIV (PLWH) in Iran in 2019. We used data from the HIV Case Registry System of Iran through December 2019. We estimated the number of PLWH in 2019 by using Spectrum, and then the proportion of them being diagnosed, linked to care, received antiretroviral treatment and suppressed viral load. We estimated that there are 59,314 (UI: 32,685-125,636) PLWH in Iran, of whom 22,054 people (37% of PLWH) were diagnosed. At the end of 2019, of whom, 14,685 (25% of PLWH) people received antiretroviral therapy. Also, of whom 6338 (11% of PLWH) people had viral load suppression by 2019. Our results showed that about one-third of total PLWH were diagnosed, while this defect is somewhat less in children than adults. To reach the 90.90.90 targets Iran needs to developed the current national HIV care guidelines, which recommend best strategies to scale up the case finding and linkage to care among undiagnosed people specifically those who infected by sexual contact in general and key populations as well.

Metastatic breast cancer remains a serious health concern and numerous investigations recommended medicinal plants as a complementary therapy. Crocin is one of the known anticancer bio-component. Recently, the inhibitory effect of metformin has been studied on the various aspects of cancer. However, no study reported their combination effects on metastatic breast cancer. In the present study, we have assessed their anti-metastatic effects on in vitro and in vivo breast cancer models. Using MTT assay, scratch, and adhesion tests, we have evaluated the cytotoxic, anti-invasive and anti-adhesion effects of crocin and metformin on 4T1 cell line, respectively. Their protective effects and MMP9 as well as VEGF protein expression levels (Western blotting) investigated in the 4T1 murine breast cancer model. Our results showed that both crocin and metformin reduced cell viability, delayed scratch healing and inhibited the cell adhesion, in vitro. While crocin alone restored the mice's weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation. These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.

Transcranial direct current stimulation (tDCS) is a therapeutic and complementary treatment in several cognitive diseases, psychiatric disorders, and disabilities that occur due to an accident or stroke. In the current research, we aimed to boost some parts of the stimulation structure and proposed a new electrode scheme in the mentioned approach. After segmenting magnetic resonance imaging (MRI) scans and using a tissue correction routine algorithm, we attempted to create an appropriate head model and electrode placement according to electric stimulation, whereby we completed tDCS processing. The considered electrodes are divided into two general categories. All the considered electrodes consist of rectangular, circular, triangular, and empty triangular patches with specific dimensions. We investigated common electrode schemes and introduced better electrode schemes for more effective cortical stimulation. We observed that the triangular electrodes in the conventional and anodal arrangement in the triangular 4 × 1 HD-tDCS create more electric field than others. Also, we calculated the current density and attempted to substantially improve it. Therefore, we recommended the empty triangular schemes. We investigated the designed model thoroughly and observed that it increased the current density not only in the conventional but also in the HD-tDCS. Graphical abstract.

Despite the poor regenerative capacity of the adult central nervous system (CNS) in mammals, two distinct regions, subventricular zone (SVZ) and the subgranular zone (SGZ), continue to generate new functional neurons throughout life which integrate into the pre-existing neuronal circuitry. This process is not fixed but highly modulated, revealing many intrinsic and extrinsic mechanisms by which this performance can be optimized for a given environment. The capacity for self-renewal, proliferation, migration, and multi-lineage potency of neural stem cells (NSCs) underlines the necessity of controlling stem cell fate. In this context, the native and local microenvironment plays a critical role, and the application of this highly organized architecture in the CNS has been considered as a fundamental concept in the generation of new effective therapeutic strategies in tissue engineering approaches. The brain extracellular matrix (ECM) is composed of biomacromolecules, including glycosaminoglycans, proteoglycans, and glycoproteins that provide various biological actions through biophysical and biochemical signaling pathways. Herein, we review predominantly the structure and function of the mentioned ECM composition and their regulatory impact on multiple and diversity of biological functions, including neural regeneration, survival, migration, differentiation, and final destiny of NSCs.

Colorectal cancer (CC) is an important human malignancy with high cancer related death worldwide. The chemotherapy using doxorubicin hydrochloride is one of the most common cancer therapeutic methods. However, drug resistance lowers the treatment efficacy in CC patients. The combination therapies seem to be more promising by taking the advantage of synergistic effects. The present study aimed to evaluate a new strategy to enhance the anticancer activity of doxorubicin in Caco-2 CC cell line by co-administration of melatonin. The effects of doxorubicin, melatonin, and their combinations (Dox-Mel) were investigated on the proliferation and viability, morphological alterations, and tumor spheroid formation. Flow cytometry was employed to compare the apoptotic situation of the cells in study groups. Changes in metastatic potential of the cells were assessed by wound healing assay and trans-well migration assays. Moreover, expression of BAX, SMAC, BCL-2, SURVIVIN, MMP-2, and MMP-9 genes were evaluated by quantitative real time PCR and western blotting. Our study showed that doxorubicin, melatonin, and Dox-Mel significantly decreased the proliferation and viability, tumor spheroid formation, invasion, and migration. Furthermore, the changes were in a concentration and time dependent manner. There was an increase in apoptosis rate in the treatment groups. Expression of genes involved in apoptosis and cell motility were altered significantly. It was observed that anticancer activity of Dox-Mel combination was significantly more than doxorubicin and melatonin treatments alone. We showed an enhanced apoptotic and anticancer activity of doxorubicin and melatonin combination chemotherapy on CC cell line than doxorubicin or melatonin treatments alone. This combination could promote the treatment efficiency and alleviate the un-intended side effects by lowering the dose of doxorubicin prescription.

Many chemotherapeutic regimens have been investigated for advanced unresectable and metastatic pancreatic cancer (PC), but with only minimal improvement in survival and prognosis. Here, we investigated anti-cancer function of free and nano-encapsulated hydroxytyrosol (Hyd) and curcumin (Cur), and its combinations (Hyd-Cur) on PANC-1 cell line. The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nano-encapsulated Hyd and Cur were synthesized, and MTT assay was performed to evaluate cytotoxic effects of free and nano-encapsulated Hyd, Cur, and Hyd-Cur. Effects of free and nano-encapsulated Hyd, Cur, and Hyd-Cur were evaluated on viability, migration, morphological alterations, colony formation, and apoptosis on PANC-1 cells. We observed that free and nano-encapsulated Hyd, Cur, and Hyd-Cur significantly increased apoptosis rates as well as significantly decreased viability, migration, and colony formation in PANC-1 cells. According to our results, Hyd-Cur combination and nano-encapsulation therapy exerts more profound apoptotic and anti-proliferative effects on PANC-1 cells than free Hyd or Hyd monotherapy.

Objective: A new national clinical guideline for the management of tuberculosis and HIV in Iranian prisons was released in 2011. The aim of this study was to compare HIV indicators in the case and control prisons after implementation of the new guideline. Methods: This report examines outcomes observed during the pilot phase of its implementation at a case prison from October 2013 to June 2014 compared to a control prison that had not yet implemented the guideline. The case prison included incarcerated individuals in the Great Tehran Prison. A prison in Alborz province was considered as a control group. Pearson’s Chi-squared, two-sample t-test, paired t-test and Kruskal-Wallis were used for the analysis. Results: The intervention significantly increased the total number of inmates tested for HIV and of diagnoses of HIV-positive inmates in the case prison compared to the control prison (P Conclusion: We recommend the implementation of this guideline in all Iranian prisons.

Background: Antiretroviral medications have improved the survival and life quality of people living with HIV and turned HIV into a chronic controllable disease. However, the success of HIV treatment depends on many factors; patient adherence is one the most important indicators. In this study, we explored the potential barriers to an effective adherence antiretroviral therapy (ART) among the HIV-positive prisoners of Ghezel-Hesar prison, Iran. Methods: To explore and identify the barriers toward ART adherence, a focus group discussion was held with six prisoners eligible for ART but rejected to be treated or did not retain on ART. The prisoners were recruited through purposive sampling method. All the words, behaviors and even body languages were precisely recorded and analyzed to reach the final results. Results: The most reported obstacles toward ART adherence were the lack of trust in the effectiveness of medications and drug complications. Other reasons were inadequate nutrition, lack of amenities, social stigma, lack of economic and psychological support, misbehavior of prison staff and inadequate methadone prescription for those with opium addiction. Conclusion: Due to the results and the fact that adequate Methadone prescription for opium addiction, improving life quality and receiving emotional and medical support from staff could improve adherence to HIV medication in prisoners,comprehensive education of prisoners about their health condition along with staff education may improve the life condition of HIV infected prisoners and may cause dramatic improvement in ART adherence and prisoners health.

Background: Cytokines as important mediators have a critical role in appropriate immune responses, the irregular production of which can lead to Multiple Sclerosis (MS). Proinflammatory cytokine interleukin-1 (IL-1) triggers inflammatory responses. Function and production of the cytokine are influenced by IL-1 coding gene polymorphism and those antagonists gene polymorphism. Objective: The aim of the present study was to evaluate the possible correlation between MS and IL-1 related alleles in Azeri population of Iran. Methods: Variable number tandem repeats (VNTR) genotypes of 150 MS patients and 220 healthy non-relative controls were determined. Result: n the healthy controls, genotype TT at IL-1A (-889) location was significantly higher than the MS patients (p=0.0001). However, a significant difference was not found between the two groups in genotypic/allelic frequency at IL- 1B+ 3953 location. Evaluation of the IL-1RA gene revealed that genotype 1/2, and genotype 1/3 were significantly higher in the healthy controls and MS patients, respectively. Our findings indicated that the consumption of fast-food in MS patients was significantly higher than controls (p= Conclusion: Polymorphisms of the IL-1B genes and common alleles of IL-1RA were not considered as risk factors for MS disease. However, genotype TT at IL-1A (-889) location and the rare allele of IL-1RA3 can be a potential risk factor for the disease. Furthermore, inappropriate dieting behaviors and consumption of fast-food can increase the risk of MS.

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of neoplastic proliferation of a plasma cell in the bone marrow that produces a monoclonal immunoglobulin. The immune checkpoint inhibitors against programmed death-1/programmed death-1 ligand and cytotoxic T-lymphocyte antigen 4 axis have demonstrated appropriate anticancer activity in several solid tumors and liquid cancers, and are rapidly transforming the practice of medical oncology. However, in a high percentage of patients, the efficacy of immune checkpoints blockade remains limited due to innate or primary resistance. Moreover, the malignancies progress in many patients due to acquired or secondary resistance, even after the clinical response to immune checkpoints' blockade. The evidence shows that multiple tumor-intrinsic and tumor-extrinsic factors and alterations in signaling pathways are involved in primary and secondary resistance to immune checkpoints blockade. Improved identification of intrinsic and extrinsic factors and mechanisms of resistance or response to immune checkpoints blockade may not only provide novel prognostic or predictive biomarkers but also guide the optimal combination/sequencing of immune checkpoint blockade therapy in the clinic. Here, we review the underlying biology and role of immune checkpoints blockade in patients with MM. Furthermore, we review the host and tumor-related factor effects on immune checkpoints blockade in MM immunotherapy.

Introduction: The most common causes of the abrupt onset of unilateral facial weakness are stroke and Bell’s palsy. The drug regimen together with electrical stimulation was more effective in treating Bell’s palsy than conventional drug treatment alone. We aimed to evaluate more effective and safe therapies for the treatment of Bell’s palsy. Methods: This clinical interventional study was conducted on 30 diabetic patients with Bell’s palsy who referred to a pain clinic for 1 year and were treated by low-level laser (LLL). The system of House-Brackmann was used for assessing the severity of nerve damage and patients were evaluated by electromyography and nerve conduction study (NCS) before and after treatment with low-level laser. These patients had not consumed any other medication for facial nerve palsy. Results: In the present study, 30 cases with poorly controlled diabetes mellitus (18 females and 12 males) were studied. After 12 sessions of low-level laser therapy (LLLT), we could observe complete recovery in 18 patients and partial recovery in 6 patients after 3 months. Conclusion: The recovery rate showed that LLLT is a safe, reliable and proper alternative approach for the treatment of facial nerve palsy, especially in the presence of underlying conditions such as diabetes mellitus.

Objectives: The objective of the present study was to determine the prevalence of HIV and risk behaviors among the inmates’ visitors at the Great Tehran Prison in 2018.This population is more likely to be infected with HIV due to their relationship with inmates. However, they have not been prioritized to the other populations in comparison to inmates who are usually prioritized over others. Methods: Using a convenient sampling method, we recruited inmates’ visitorsat the Great Tehran Prison in 2018. An anonymous questionnaire collected information on the participant’s demographic characteristics, relationship with inmate, imprisonment history, drug-related risk behaviors, and HIV-related risk behaviors.Rapid HIV blood test detected HIV positive people. To examine the association between risk behaviors and HIV infection, we used a multivariate logistic regression model to calculate the adjusted Odds Ratio (OR)(adjusted Odds ratio of 23.140, 95% CI OR: 1.994–268.5).1 Results: 1131 visitors were asked to participate in the study; out of which 1120 consented (99%).Out of the 1120 participants, 55.2% were female, and the majority (72.4%) aged older than 35 years. Of those who had a sexual partner, 50% did not usea condom in the last 6 months. Overall, HIV prevalence was 0.4% in the inmate visitors, but it was significantly higher among those with a history of drug injection(p=0.003). Conclusion: Our findings indicated that overall the HIV prevalence is low among inmates’ visitors; Subgroups with a history of injection have high HIV prevalence which needs to be prioritized for HIV screening and treatment.

PurposeThe aim of present study was to integrate vital noncommunicable diseases (coronary artery disease, hypertension, diabetes mellitus and mental health disorders) into Prison-Based Active Health Services Provision (PAHSP).Design/methodology/approachOn Jan 1, 2018, there were 230,000 prisoners in Iran. Timely and systematic detection and diagnosis of chronic health conditions among this population are imperative. The collaboration between healthcare providers in prison and members of the multidisciplinary team of the healthcare community outside prison initiated an active health service provision approach for HIV and tuberculosis (TB). Guidelines for the control of HIV and TB in prison were piloted, and the finalized version was named “Prison-based Active Health Services Provision” (PAHSP), which has been scaled up in 16 of 260 Iranian prisons.FindingThe PAHSP approach emphasizes the importance of early identification of key symptoms and risk factors. This approach provides an opportunity for improved prevention and treatment, enabling prisoners identified at risk or those who have been diagnosed with a target disease to be followed up and receive the appropriate health care.Originality/valueInitiatives such as screening for chronic health conditions coupled with treatment will reduce the burden of chronic illness among prisoners and the broader community, thereby saving on healthcare costs and lives.

PurposeThe aim of this study was to compare the defined indicators of tuberculosis (TB) control program in the intervention and control prisons, after implementation of the national clinical protocol for TB and HIV management in Iranian prisons, suggesting active health service provision in all steps of service provision.Design/methodology/approachThis was quasi-experimental study conducted among inmates of two prisons in Iran. Great Tehran prison was purposively chosen as the intervention prison and Karaj prison was purposively chosen as control prison as well. Intervention and control prisons were compared in terms of the TB indicators within three periods (before intervention, during implementation and follow-up period) from October 2013 to June 2014.FindingsNumber of inmates with TB symptoms who underwent TB workup was four times more in intervention prison compared to control prison (9.3 vs 2.5 cases out of 1,000 inmates per month in the case prison compared to the control prison). Such difference was also significant in the intervention prison, comparing before and during the intervention period. The patient finding in case prison increased significantly after the intervention (223.6 vs 81.8 cases out of 100,000 inmates per year). The number of TB cases who received HIV testing increased from 50 to 100%.Originality/valueActive health service provision has significantly improved indicators in the intervention prison. The authors recommend implementation of this guideline in all prisons of Iran. Integration of other diseases with high burden among prisoners is also recommended in the active health services provision.

Purpose: Stroke is one of the most common conditions causing death. There have been few studies examining the effects of alpha lipoic acid (ALA) on stroke patients. In this regard, the present randomized controlled clinical trial was conducted to examine the effects of ALA supplementation on serum albumin, and inflammatory and oxidative stress markers in stroke patients. Methods: The present paralleled randomized controlled clinical trial involved 42 stroke patients who were over 40 years and under enteral feeding. The participants were randomly assigned into two groups and finally 40 patients completed the study. Patients in alpha lipoic acid group (n=19) took 1200 mg ALA supplement daily along with their meal, and participants in control group (n=21) underwent the routine hospital diet for 3 weeks. Fasting blood samples were obtained and albumin, oxidative stress, and inflammatory indices were assessed at baseline, as well as at the end of the trial. Results: After 3 weeks, treatment of patients with ALA led to a significant decrease in tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) levels (P=0.01) compared to baseline. But serum levels of albumin, total antioxidant capacity (TAC), malondialdehyde (MDA), highsensitivity C-reactive protein (hs-CRP), IL-6 and TNF-α did not change significantly vs. control group (P>0.05). Conclusion: ALA did not significantly change the serum levels of albumin and inflammatory as well as antioxidant capacity indices in stroke patients compared with the control group. More clinical trials with large sample sizes and long duration are needed to clarify the effects of ALA on these patients.

PurposeAlthough the pathogenesis of stroke is not yet completely elucidated, factors such as oxidative stress and inflammation have been shown to play an important role in this regard. The purpose of this paper is to investigate the effects of whey protein plus lipoic acid on the inflammatory and oxidative stress markers and the prognosis in acute ischemic stroke (AIS) patients.Design/methodology/approachA double-blind, randomized controlled clinical trial was conducted among 42 patients with the first episode of AIS at the Imam Reza Hospital of the Tabriz University of Medical Sciences. The blind research staff randomly assigned patients to two groups of receiving usual hospital gavage (control group) and 1,200 mg of lipoic acid plus 20 g of whey protein in addition to usual hospital gavage (intervention group) for midday meal. Levels of albumin, Interleukin-6 (IL-6), tumor necrosis factor (TNF-α), high-sensitivity C-reactive protein (hs-CRP) and clinical outcomes including severity of neurologic damage according to National Institutes of Health Stroke Scale (NIHSS) and functional state based on modified Rankin Scale (mRS) were evaluated initially and three weeks later.FindingsThere were no significant differences in demographic and baseline characteristics between the two groups (p> 0.05). After three weeks, hs-CRP (pp= 0.02) and TNF-α(p= 0.01) levels significantly reduced in the intervention group, but no significant changes were observed in cases of albumin, malondialdehyde (MDA) and total antioxidant capacity (TAC) in this group (p> 0.05). Instead, only IL-6 decreased significantly in the control group (pp > 0.05). While there was significant betterment in clinical prognosis parameters within groups, no significant changes were found between groups.Originality/valueThe investigation implied that whey protein plus lipoic acid supplementation has no significant effects on inflammatory and oxidative stress markers compared to the control group of AIS patients. More studies in this field are needed to approve the result.

Fog computing is an emerging technology to address computing and networking bottlenecks in large scale deployment of IoT applications. It is a promising complementary computing paradigm to cloud computing where computational, networking, storage and acceleration elements are deployed at the edge and network layers in a multi-tier, distributed and possibly cooperative manner. These elements may be virtualized computing functions placed at edge devices or network elements on demand, realizing the “computing everywhere” concept. To put the current research in perspective, this paper provides an inclusive taxonomy for architectural, algorithmic and technologic aspects of fog computing. The computing paradigms and their architectural distinctions, including cloud, edge, mobile edge and fog computing are subsequently reviewed. Practical deployment of fog computing includes a number of different aspects such as system design, application design, software implementation, security, computing resource management and networking. A comprehensive survey of all these aspects from the architectural point of view is covered. Current reference architectures and major application-specific architectures describing their salient features and distinctions in the context of fog computing are explored. Base architectures for application, software, security, computing resource management and networking are presented and are evaluated using a proposed maturity model.

Purpose: Malnutrition is extensively prevalent amongst critically ill patients afflicted by ischemic stroke (IS). This study purpose was to evaluate the protein whey effect on inflammatory and antioxidant markers and functional prognosis in acute IS patients. Methods: out of 42 patients with acute IS who were referred to Imam Reza Educational Hospital, Tabriz, Iran, 40 patients participated in the study. Twenty-one patients as control group received the hospital routine formula, and 19 patients as intervention group received 20 g/daily of whey protein through oral gavage. Inflammation and oxidative stress indicators (e.g., albumin, malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and high sensitivity C reactive protein (hs-CRP)and clinical variables included in were evaluated using National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) during admission and also 3 weeks after intervention. Results: Whey protein supplementation significantly decreased the NIHSS and mRS scores, TNF-α, IL-6, and hs-CRP by passing 3 weeks from intervention (P

Purpose Multimorbidity (MM) (presence of more than one chronic condition within a same patient) imposes a heavy burden on patients and health care systems. In contrast to high-income countries, the epidemiology of this phenomenon is unclear in low- and middle-income countries, particularly among Iranian population. Methods This was a retrospective cohort study using Iranian Health Insurance Organization claims database. A framework was developed for identifying a set of 18 chronic conditions from the pharmacy claims data in Iran. All 2013 outpatient utilizers (aged 18 years or older) were included. Data were analyzed according to number of chronic conditions, gender, and age. The association between MM and utilizations of health services was examined for 2013 to 2016. Results In total, 481 733 people were included. Cardiovascular diseases (including hypertension) (19.1%), depression/anxiety/sleep disorders (13.7%), and acid-related disorders (10.3%) were the three most prevalent conditions. MM was present in 21.1%. Although prevalence of MM is higher in older age groups and was present in 40% of individuals aged 65 and older, the absolute number of multimorbid patients was higher in those younger than 65 years (66 271 vs 35 386). MM was more prevalent among women (22.1%) compared with men (19.5). After multivariate adjustment for age group and sex, each additional chronic condition was associated with an increase of 2.23 physician visits, 2.86 drugs dispensed, 2.32 laboratory tests, and 1.6 medical imaging. Conclusions Our findings challenge the current single-disease-based assumption implicit in Iranian health care system. To take account of MM, complementary strategies should be designed and implement in health care system.

Aims To assess the prevalence of and factors related to complementary and integrative medicine (CIM) use among multiple sclerosis (MS) patients, using a translated and adapted version of a standard international questionnaire. Methods International complementary and alternative medicine questionnaire (I-CAM-Q) was used. A cross-sectional study was done to assess the prevalence of and factors associated with CIM use among MS patients in Southern Iran. Patients who were randomly selected from MS registry center, were interviewed via phone calls. Results Three hundred patients were enrolled in the study; 69% of them were female. Their mean age was 36.6±8.53 years and the mean duration of the disease was 5.6 ± 4.22 years. In all, 99.3% (95% CI) of the patients had used at least one type of CIM. Herbal medicines and dietary supplements were the most commonly used CIM type (97.3%; 95% CI). Praying was the most common modality among all CIM subgroups (81.3%; 95% CI). Long term illness (MS) was selected as the main reason for the last use of all CIM types. Having non-tertiary education and having sequel due to MS were related to visiting a CIM provider (adjusted odds ratio (AOR) = 2.32, 95% confidence interval (CI) = 1.22–4.43), (AOR = 2.67, 95% CI = 1.47–4.83) respectively. Being female was related to the use of self-help practices (AOR = 3.41, 95% CI = 1.5–7.72). Conclusion There is a high prevalence of CIM use among MS patients. Therefore, patient- physician communication about CIM use should be emphasized.

The study assessed the HIV treatment cascade of people living with HIV (PLWH) in Iran and the reasons for gaps in HIV services in 2014. We did the cascade analysis using the WHO HIV test–treat–retain cascade analysis tool (2014). To measure the gaps, we checked the records for all PLWH reported to the national HIV surveillance till September 2014 to define how many were alive, linked to HIV care, assessed for CD4 cell count, started antiretroviral therapy (ART), and reported to be alive up to five years after ART. To assess the reasons for gaps in the cascade, we ran desk review, four focus group discussions and 51 in-depth interviews with key informants including PLWH. Spectrum model estimated 75,700 PLWH in Iran, of whom only 22,647 people (%30) were diagnosed. Of those who were diagnosed with HIV, 16,266 people (%72) had enrolled in HIV care. About 13% of all PLWH were retained in HIV care and only 9% (6745 people) had ever been tested for CD4 cell count. Only 8% (6018 people) of all PLWH had received ART by September 2014. We found the biggest gap in the HIV treatment cascade to be HIV diagnosis as only 30% of PLWH have been diagnosed. Innovative strategies to improve HIV testing, particularly those that work best for key populations, are critical to reach the 90–90-90 targets.

© 2021 American Academy of Neurology, Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Simple Summary Bladder cancer (BC) is the fourth most common cancer among men and the tenth most common cancer among women. Since the overall prognosis for BC has not changed in the last 30 years, there is a compelling medical need to develop new diagnostic and therapeutic approaches. Nanotechnology has been extensively developed for cancer management, including cancer diagnosis, detection, and treatment. Several nanoparticles (NP) can be used in in vitro cancer diagnostics, in vivo imaging enhancement, and drug loading techniques. In this review, we examine the current state of nanotechnology in the diagnosis and treatment of bladder cancer. We investigated the function of metal NPs, polymeric NPs, liposomes, and exosomes accompanied therapeutic agents for BC therapy, and then focused on the potential of nanotechnology to improve conventional approaches in sensing. Abstract Bladder cancer (BC) is the second most common cancer of the urinary tract in men and the fourth most common cancer in women, and its incidence rises with age. There are many conventional methods for diagnosis and treatment of BC. There are some current biomarkers and clinical tests for the diagnosis and treatment of BC. For example, radiotherapy combined with chemotherapy and surgical, but residual tumor cells mostly cause tumor recurrence. In addition, chemotherapy after transurethral resection causes high side effects, and lack of selectivity, and low sensitivity in sensing. Therefore, it is essential to improve new procedures for the diagnosis and treatment of BC. Nanotechnology has recently sparked an interest in a variety of areas, including medicine, chemistry, physics, and biology. Nanoparticles (NP) have been used in tumor therapies as appropriate tools for enhancing drug delivery efficacy and enabling therapeutic performance. It is noteworthy, nanomaterial could be reduced the limitation of conventional cancer diagnosis and treatments. Since, the major disadvantages of therapeutic drugs are their insolubility in an aqueous solvent, for instance, paclitaxel (PTX) is one of the important therapeutic agents utilized to treating BC, due to its ability to prevent cancer cell growth. However, its major problem is the poor solubility, which has confirmed to be a challenge when improving stable formulations for BC treatment. In order to reduce this challenge, anti-cancer drugs can be loaded into NPs that can improve water solubility. In our review, we state several nanosystem, which can effective and useful for the diagnosis, treatment of BC. We investigate the function of metal NPs, polymeric NPs, liposomes, and exosomes accompanied therapeutic agents for BC Therapy, and then focused on the potential of nanotechnology to improve conventional approaches in sensing.

Background and Purpose: Stroke is reported as a consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in several reports. However, data are sparse regarding the details of these patients in a multinational and large scale. Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke, intracranial hemorrhage, and cerebral venous or sinus thrombosis among SARS-CoV-2–infected patients. We further investigated the risk of large vessel occlusion, stroke severity as measured by the National Institutes of Health Stroke Scale, and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with acute ischemic stroke. In addition, we explored the neuroimaging findings, features of patients who were asymptomatic for SARS-CoV-2 infection at stroke onset, and the impact of geographic regions and countries’ health expenditure on outcomes. Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least 1 eligible stroke patient. Of 432 patients included, 323 (74.8%) had acute ischemic stroke, 91 (21.1%) intracranial hemorrhage, and 18 (4.2%) cerebral venous or sinus thrombosis. A total of 183 (42.4%) patients were women, 104 (24.1%) patients were P =0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; P Conclusions: We observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.

Stroke lesion segmentation plays a crucial role in neuroimage processing. So far, different methods have been used for brain lesion segmentation. Some of them include a manual tracing method, and others are automated approaches. The majority of these approaches normally require the Magnetic Resonance (MR) imaging sequences as their inputs, and in some cases, tunable parameters should be determined. We use the Ischemic Stroke Lesion Segmentation (ISLES2015) standard MR imaging, which includes training and test MR imaging samples. Here, we consider an ensemble of several approaches to stroke lesion segmentation that are named Lesion Segmentation Toolbox (LST), Automated Lesion Identification (ALI), lesion_Guassian Naive Bias (GNB), Lesion Identification with Neighborhood Data Analysis (LINDA), DeepMedic, and DeepMedic+Conditional Random Fields (CRF). LST in particular includes two different methods, Lesion Growth Algorithm (LGA) and Lesion Prediction Algorithm (LPA). To examine each approach, the structure of its algorithm is thoroughly discussed; then, the results of these approaches are shown, and the performance of them is evaluated using some statistic parameters. The ultimate results of the parameters are obtained by averaging the results of all samples. Dice similarity coefficient (DC) and Precision of DeepMedic+CRF are more than the other approaches. Regarding the other metrics (Recall, Average Symmetric Surface Distance (ASSD), and Hausdorff's Distance (HD)), the results are a bit different. Among the examined approaches, DeepMedic+CRF yields the best DC than others. Accordingly, the performance of DeepMedic+CRF is better than the rests. Calculations clearly show that the DC of DeepMedic+CRF is approximately 3% higher than single DeepMedic, and on average, 22% more than other approaches.

Segmentation of brain Magnetic Resonance Imaging (MRI) has a significant role in computational modeling of transcranial Direct Current Stimulation (tDCS); hence, it is important to choose the appropriate method that can be utilized with adequate precision. Some tissues such as Cerebrospinal fluid (CSF) and white matter (WM) usually get damaged after segmentation, because of their low thickness. This defect appears in the form of small cavities on their wall. So, it causes many problems in the modeling and processing of tDCS. The modified automated correction routine compensates the results error adequately. Accordingly, the improved masks make the complete head model without any discontinuities in the CSF and WM surfaces, and the electric field magnitudes after stimulation, illustrate this improvement effectively.

COVID-19 pandemic has led to a change in the way we manage acute medical illnesses. This pandemic had a negative impact on stroke care worldwide. The World Stroke Organization (WSO) has raised concerns due to the lack of available care and compromised acute stroke services globally. The numbers of thrombolysis and thrombectomy therapies are declining. As well as, the rates and door-to treatment times for thrombolysis and thrombectomy therapies are increasing. The stroke units are being reallocated to serve COVID-19 patients, and stroke teams are being redeployed to COVID-19 centers. Covid 19 confirmed cases and deaths are rising day by day. This pandemic clearly threatened and threatening all stroke care achievements regionally. Managing stroke patients during this pandemic is even more challenging at our region. The Middle East and North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO) is the main stroke organization regionally. MENA-SINO urges the need to developing new strategies and recommendations for stroke care during this pandemic. This will require multiple channels of interventions and create a protective code stroke with fast triaging path. Developing and expanding the tele-stroke programs are urgently required. There is an urgent need for enhancing collaboration and cooperation between stroke expertise regionally and internationally. Integrating such measures will inevitably lead to an improvement and upgrading of the services to a satisfactory level.

In order to optimize the capability of transcranial Direct Current Stimulation (tDCS), electrode arrangements and the inward current stimulation are taken into account as two crucial factors. In this contribution, in order to specify the electrode positions, a detailed protocol is investigated, in which regarding the intended targeted regions, the optimal montages with an arbitrary number of electrodes are developed. After designing the positions of all active and returned electrodes, the corresponding inward current density is determined for each electrode. The outcomes of the simulation and the electric field distributions in the hand cortex prove that the proposed protocol is capable of improving the tDCS efficiency substantially in all head layers. Furthermore, in order to compare our approach with the other works found in the literature, a performance evaluation is curried out by calculating the maximum electric field distribution in the targeted region. This study shows that it improves tDCS efficiency virtually 2.5 times in comparison to High Definition (HD) montages in the gray matter and nearly 1.5 times in comparison to the other inner layers. Such an outstanding achievement in the gray matter can be regarded as an interesting standpoint in tDCS-rehabilitation studies.

Objectives In the present study, we sought to investigate the association between red cell distribution width (RDW) and stroke severity and outcome in patients who underwent anti-thrombolytic therapy with tissue plasminogen activator (tPA). Results In this prospective study, 282 stroke patients who underwent tPA injection were included. The categorization of RDW to 13% values revealed insignificant difference in stroke severity score, accounting for the mean 36-h NIHSS of 8.19 ± 8.2 in normal RDW values and 9.94 ± 8.28in higher RDW group (p = 0.64). In seventh day, NIHSS was 6.46 ± 7.28 in normal RDW group and was 8.52 ± 8.35 in increased RDW group (p = 0.058). Neither the 36-h, nor the seventh day and 3-month mRS demonstrated significant difference between those with normal and higher RDW values.

Male sex is more prone to cerebrovascular disorders, yet the exact role of androgens in cerebralischemia remains unclear. Here we reviewed current understanding of testosterone (TES)neuroprotective activity against ischemic stroke and mechanisms underlying these effects inaging. TES may exert a neuroprotective effect in aging through pathways including inhibition ofoxidant molecules production, enhancing the enzymatic antioxidant capacity of the brain andmodulation of apoptotic cell death. Given this, a better understanding of the neuroprotectiveroles of TES may propose an effective therapeutic strategy to improve the quality of life anddecrease androgen-related cerebrovascular problems in the aging men.

Background and purpose Optic neuritis (ON) is a common clinical manifestation of Multiple Sclerosis (MS), which is associated with reduced visual acuity, blurred vision, blindness and retro-bulbar pain. In several studies, specific relations between optic nerve diameter and hemodynamics of the eye bulb arteries with ON have been reported. However, no consensus has been reached in this regard. We aim at determining the alterations in optic nerve diameter and eye bulb arteries hemodynamics in ON in MS patients. Methods This case-control study includes 40 patients, who at least had experienced one phase of ON, in one of their eyes. To measure hemodynamics of arteries in the affected eyes, a color Doppler imaging was performed and end diastolic velocity (EDV), peak systolic velocity (PSV), peripheral resistance indices i.e. resistance index (RI) and pulsatile index (PI) were measured in posterior ciliary artery (PCA) and ophthalmic artery (OA). Also, optic nerve diameter was measured using sonography. Non-affected eyes of these patients were considered as control group. Results There were no significant differences in EDV, PSV, RI and PI in PCA and OA. The mean optic nerve diameter in the affected eyes was 4.73 mm, whereas, it was 4.31 mm in unaffected eyes, which was significantly different (P = .02). Conclusion These results indicate that there is a significant relation between eye involvement and increased optic nerve diameter in MS patients with chronic ON. While, there were no significant relations in EDV, PSV, RI and PI in PCA and OA comparing two groups.

The prevalence of HIV is substantially higher among prisoners than the general population, while the incidence varies considerably in different regions around the world. If we consider Sub-Saharan Africa as one region with the highest prevalence of HIV, data on African prisoners would be limited. Despite the low prevalence of HIV in the Middle East and North Africa, its incidence is rising in these regions with a few exceptions; there are insufficient data on HIV prevalence in prisons. A similar situation is present in both Pacific and Central Asia as well as in Eastern Europe. A high rate of infection is mainly observed among prisoners in Western and Central parts of Europe, since the data from these are more available than other parts. Nowadays, the sexual transmission mode and tattooing are important ways in HIV risks among prisoners after injecting drug use as the most common route of HIV transmission in all regions. However, it is difficult to compare and analyze the prevalence of HIV among prisoners in different regions regarding the limited data and different methods which they used in collecting data. Eventually, it can certainly be said that prisons are one of the high-risk places for HIV transmission; on the other hand, can be a suitable place for implementing HIV case-finding, linkage to treatment and harm reduction programs.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by a spectrum of clinicopathologic signs and a complex etiology. PD results from the degeneration of dopaminergic (DAergic) neurons in the substantia nigra. Current therapies for PD are only able to alleviate symptoms without stopping disease progression. In addition, the available therapeutic strategies do not have long-lasting effects. Furthermore, these therapies cause different ranges of adverse side effects. There is great interest in neurotrophic factors (NTFs) due to their ability to promote the survival of different neural cells. These factors are divided into four families: neurotrophins, neurokines, the glial cell line-derived NTF family of ligands, and the newly recognized cerebral DA NTF/mesencephalic astrocyte-derived NTF family. The protective and therapeutic effects of these factors on DAergic neurons make them suitable for the prevention of progressive cell loss in PD. Based on the above premise, we focus on the protective effects of NTFs, especially CDNF and MANF, on nigrostriatal DAergic neurons in PD.

Reza Deljavan,1 Mehdi Farhoudi,1 Homayoun Sadeghi-Bazargani2 1Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Objective: The aim of this study was to determine the in-hospital survival of patients referred to the 2 stroke centers in North-West of Iran during a full seasonal year from April 2015. Methods: All the consecutive patients with stroke admitted to the 2 main stroke centers at Tabriz (Imam Reza University Hospital and Razi University Hospital) were recruited in this study. Stroke patients from both ischemic and hemorrhagic subtypes were selected based on the registry data and International Classification of Diseases, 10th edition. At admission, details of examination including vital signs, neurologic and systemic examination, Modified Rankin Scale, and Glasgow Coma Scale were recorded. Baseline hematological and biochemical parameter assessments as well as computerized tomographic scanning were conducted. Cox regression was used to investigate and detect potential predictors of in-hospital survival. Results: A total of 1,990 patients with stroke were studied. Males comprised 52.1% (1,036) of the subjects. The mean age of the patients was 65.8 years. Three hundred and fifty-seven (17.9%) patients had hemorrhagic stroke vs 1,633 (82.1%) with ischemic stroke. In-hospital case-fatality proportion was 12.5% (95% CI: 11.1–14). Based on modified Rankin Scale score at admission, 1,377 of 1,990 patients (69.2%) had a poor outcome (modified Rankin Scale score ≥3) at the admission time. The regression analysis showed that at least 7 variables could independently predict hospital survival of patients with stroke including age ≥65 years, higher admission modified Rankin Scale score, lower admission Glasgow Coma Scale score, hemorrhagic stroke nature, diabetes, having valvular heart disease, and having aspiration pneumonia. Conclusion: The case-fatality of stroke in the present study setting is high and needs to be appropriately addressed through prevention or management of some of these factors such as diabetes, pneumonia, and valvular heart diseases. Keywords: stroke, mortality, hemorrhagic stroke, ischemic stroke, prognostic models

Background Circle of Willis (COW) is a network of cerebral artery which continually supplies the brain with blood. Any disturbance in this supply will result in trauma or even death. One of these damages is known as brain Aneurysm. Clinical methods for diagnosing aneurysm can only measure blood velocity; while, in order to understand the causes of these occurrences it is necessary to have information about the amount of pressure and wall shear stress, which is possible through computational models. Objective In this study purpose is achieving exact information of hemodynamic blood flow in COW with an aneurysm and investigation of effective factors on growth and rupture of aneurysm. Methods Here, realistic three-dimensional models have been produced from angiography images. Considering fluid-structure interaction have been simulated by the ANSYS.CFX software. Results Hemodynamic Studying of the COW and intra-aneurysm showed that the WSS and wall tension in the neck of aneurysms for case A are 129.5 Pa, and 12.2 kPa and for case B they are 53.3 Pa and 56.2 kPa, and more than their fundus, thus neck of aneurysm is prone to rupture. Conclusion This study showed that the distribution of parameters was dependent on the geometry of the COW, and maximum values are seen in areas prone to aneurysm formation.

Aim: To evaluate the feasibility of the revised “Clinical Guideline for HIV and TB” in the Great Tehran Prison during October 2013 to June 2014. Methods: The guideline includes all aspects of HIV/TB diagnosis based on active case finding (ACF), treatment and care services. Before the implementation, a fo-cus group discussion was conducted, and attended by experts on jail diseases. The objective was to identify defects and limitations of the guideline after the discussion, the guideline was revised. The Great Tehran Prison contains three separate units; all prisoners are taken first to “reception and identification unit (quarantine)” and then send to two housing units according to their legal status. An HIV ACF strategy was employed in the quarantine, and two units through a vol-untary provider-initiated HIV testing. Three staffs of the triangular clinic trained the prisoners about common routes of HIV transmission and the symptoms of TB in the units. In the quarantine, all prisoners were examined for all HIV-risk factors, HIV testing and symptoms of TB. In unit one, healthcare staff continued the ACF process, while in unit two, the trained prisoners were assigned as the healthcare communica-tors to proceed with caution the strategy. At this caring process, when the test result was positive, then the process of care, treatment and follow ups was initiated. More-over, the use of directly observed therapy (DOTs) for antiretroviral therapy (ART) and TB was applied to the sick prisoners. There was also a follow-up caring for re-leased prisoner to refer them to care and treatment services outside the prison. Results: The guideline was implemented in the prison successfully. Conclusion: Regarding feasibility of the guideline, the investigators of this study suggest that the guideline should be implemented in other prisons across the country.

Aim: To reduce in-hospital intervals by developing a prehospital notification (PHN) protocol which directly notifies a neurologist to prepare for possible treatment. Methods: A 24/7 connection was established between emergency medical services dispatch and the on-call neurologist. A database of all patients with in-hospital stroke code activation was developed, door-to-computed tomography (CT) time and door-to-needle time was recorded from January 2013 to December 2016. The statistical results were considered significant at p < 0.05. Result: PHN resulted in a significant reduction in door-to-CT time (median 14 vs 20; p < 0.001). Among patients who were treated with intravenous thrombolysis, door-to-needle time was significantly shorter in patients with PHN compared with non-PHN group (median 42 vs 70; p < 0.001). Conclusion: PHN effectively reduced door-to-CT and door-to-needle times. © 2018 2018 Reshad Mirnour.

A finite element model was developed to investigate the effect of loading regimes caused by various daily activities on the mechanical behaviour of the head-neck taper junction in modular hip replacements. The activities included stair up, stair down, sit to stand, stand to sit, one leg standing and knee bending. To present the real mechanical environment of the junction, in addition to the force components, the frictional moments produced by the frictional sliding of the head and cup were applied to a CoCr/CoCr junction having a 12/14 taper with a proximal mismatch angle of 0.024°. This study revealed that stair up with the highest fretting work per unit of length (1.62 × 10

Monoclonal antibodies (mAbs) targeting the hepatitis C virus (HCV) envelope have been raised mainly against envelope protein 2 (E2), while the antigenic epitopes of envelope protein 1 (E1) are not fully identified. Here we describe the detailed characterization of a human mAb, designated A6, generated from an HCV genotype 1b infected patient. ELISA results showed reactivity of mAb A6 to full-length HCV E1E2 of genotypes 1a, 1b and 2a. Epitope mapping identified a region spanning amino acids 230–239 within the N-terminal region of E1 as critical for binding. Antibody binding to this epitope was not conformation dependent. Neutralization assays showed that mAb A6 lacks neutralizing capacity and does not interfere with the activity of known neutralizing antibodies. In summary, mAb A6 is an important tool to study the structure and function of E1 within the viral envelope, a crucial step in the development of an effective prophylactic HCV vaccine.

Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results.

Summary Aim: Atherosclerotic lesions in the carotid arteries lead to a broad range of cerebrovascular disorders such as vascular dementia and ischaemic stroke. Recent studies have verified the beneficial role of atorvastatin (AV) in atherosclerosis. Despite a large body of studies, the mechanisms underlying this effect have not been completely explained. In this study, several experiments were performed on atherosclerotic rat models to investigate the anti-inflammatory and anti-apoptotic effect of AV in the carotid artery. Methods: In this experimental study, 40 male Wistar rats (250 ± 25 g) were randomly divided into four groups: rats on a normal diet (ND; n = 10); a high-cholesterol diet (HD; n = 10); a high-cholesterol diet plus AV (HD + AV; n = 10); and the AV control group (AV; n = 10). Cleavage of caspase-3 protein, expression of B-cell lymphoma 2 (Bcl-2) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) were determined by immunoblotting assay in the carotid artery homogenate. Plasma atherogenic indices, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by colorimetric assay at the end of the experiment. Plasma levels of oxidised LDL (oxLDL) were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Results: After eight weeks of feeding with a high-cholesterol diet, an elevated level of oxLDL was observed in the plasma in the HD group compared with the ND group [214.42 ± 17.46 vs 69.13 ± 9.92 mg/dl (5.55 ± 0.45 vs 1.78 ± 0.26 mmol/l); p < 0.01]. AV administration significantly reduced oxLDL levels in the HD + AV compared to the HD group [126.52 ± 9.46 vs 214.42 ± 17.46 mg/dl (3.28 ± 0.25 vs 5.55 ± 0.45 mmol/l); p < 0.01]. Results also showed that compared with the HC group, the HC + AV group had lower levels of p38 phosphorylation (p < 0.05) and higher levels of Bcl-2 expression (p < 0.05). Lower levels of cleaved caspase-3 were observed in the HC + AV group in comparison with the HC group (p < 0.05). Conclusions: The resultant data suggest that the anti-apoptotic effect of AV could be partially mediated by the pro-inflammatory protein p38 MAPK and the anti-apoptotic protein Bcl-2 in the rat carotid artery. Atorvastatin can therefore be considered a target drug in the prevention or development of atherosclerotic events.

Studies have shown an increase in the incidence of MS in Iran. The aim of our study was to evaluate the relationship between environmental exposure and MS in Iran. This case-control study was conducted on 660 MS patients and 421 controls. Many environmental factors are compared between the two groups. Our findings demonstrated that prematurity ([OR = 4.99 (95% CI 1.34–18.68), P = 0.017]), history of measles and mumps ([OR = 1.60 (95% CI 1.05–2.45), P = 0.029; OR = 1.85 (95% CI 1.22–2.78), P = 0.003, respectively]), breast feeding [OR = 2.90 (95% CI 1.49–5.65), P = 0.002], head trauma in childhood ([OR = 8.21 (95% CI 1.56–43.06), P = 0.013]), vaccination in adulthood ([OR = 4.57 (95% CI 1.14–18.41), P = 0.032, respectively]), migraine ([OR = 3.50 (95% CI 1.61–7.59), P = 0.002]), family history of MS, IBD, migraine, and collagen vascular diseases ([OR = 2.73 (95% CI 1.56–4.78), P

We propose an improved version of brain emotional learning (BEL) model trained via learning automata (LA) for speech emotion recognition. Inspiring from the limbic system in mammalian brain, the original BEL model is composed of two neural network components, namely amygdala and orbitofrontal cortex. In this modified BEL model, named brain emotional learning based on learning automata (BELBLA), we have employed the theory of the stochastic LA in error back-propagation to train the BEL model in decreasing the high computational complexity of the traditional gradient method. Hence, the performance of the model can be enhanced. For a speech emotion recognition task, we extract the usual features, such as energy, pitch, formants, amplitude, zero crossing rate and MFCC, from average short-term signals of the emotional Berlin dataset. The experimental results show that the BELBLA outperforms some opponents, like hidden Markov model, Gaussian mixture model, k-nearest neighbor, support vector machines and artificial neural networks, for this application.

Increase in the average life span and interest in correlation between food and human health have led to researches to find and utilise the functional materials in rice. Octacosanol in rice grain is well known for its potential benefit. This study was conducted to evaluate the Korean rice (Oryza sativa L.) genotypes and landraces for octacosanol contents and antioxidant activity. Octacosanol contents in 223 cultivars of Korean rice ranged from 0.78 to 6.06 mg 100 g−1. Thirteen genotypes and landraces had high contents of octacosanol (4 mg 100 g−1). The antioxidant activity in Korean rice ranged from 12 to 96%. Among the tested genotypes and landraces, red-coloured rice accessions had more than 90% antioxidant activity. Genotypes with high level of octacosanol and antioxidant activity may be useful for rice breeders to develop functional varieties and food processing as nutraceutical materials.

Background: Multiple sclerosis (MS) is a neurologic disorder with a considerable global burden. During the last decades, some pharmaceutical treatments have been approved for patients with MS. Dimethyl fumarate (DMF) is one of these drugs which has been reported to have early promising results in recent studies, but the efficacy of this drug in patients with MS is still being studied in different parts of the world. In the present study, we evaluated the effectiveness of DMF therapy on reducing relapses, lesions, and disability in Iranian patients with MS.Methods: The present single-arm before-after study was approved by the Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran [Iranian Registry of Clinical Trial (IRCT) code: IRCT20190121042439N1]. Every patient who was diagnosed with relapsing MS was considered eligible to enroll in the present clinical trial. Before receiving DMF therapy, the baseline liver function tests and complete blood count were obtained from all individuals. Also, a baseline brain magnetic resonance imaging (MRI) was obtained and Expanded Disability Status Scale (EDSS) was documented from all patients. After receiving 240 mg DMF twice daily for 12 months, the laboratory and imaging measurements as well as EDSS were repeated. Furthermore, the total number of relapses within the study period was recorded. Satisfaction with DMF treatment was determined by answering a yes-no question.Results: A total number of 50 patients enrolled in the study and most of them were female (80%). There was a significant decrease in EDSS score and gadolinium (GD)-enhancing lesions after the study period (P < 0.001 for each). Moreover, the attacks significantly dropped after the study period (P < 0.001) and 86% of patients were satisfied with their treatment.Conclusion: The findings of this study showed that 240 mg DMF administered twice daily can effectively reduce disability and provide satisfaction within the first year of therapy in patients with MS.

Gastric cancer (GC) is one of the prevalent human malignancies and the third most common cause of cancer-related death worldwide. The doxorubicin hydrochloride is one of the important chemotherapeutic anticancer agents, with a limited therapeutic efficacy for treatment of GC. Therefore, taking advantage of synergistic effects by strategies like combination therapy seems appropriate and promising in treatment of GC. The aim of this study was to investigate a novel method to enhance the therapeutic efficacy of doxorubicin (as a chemotherapeutic agent) by co-administration of curcumin (as a bioactive herbal compound) in GC treatment. In the present study, the effects of curcumin, doxorubicin, and their combinations (Dox-Cur) were evaluated on the viability, morphological features, tumor spheroid formation, migration, invasion, and apoptosis of gastric adenocarcinoma cell line (AGS). Moreover, expression levels of BAX, BCL-2, and CASP9 genes were assessed among AGS cells treated with curcumin, doxorubicin, and Dox-Cur. The obtained results showed that all of curcumin, doxorubicin, and Dox-Cur treatments significantly decreased the viability, tumor spheroid formation, migration, and invasion in the GC model cells. Furthermore, apoptosis rates in AGS cells were increased in a concentration- and time-dependent manner in all of the treatment groups. Moreover, the anticancer activity of the Dox-Cur combination was significantly more than curcumin and doxorubicin treatments alone. According to the results, Dox-Cur combination therapy exerts more profound apoptotic and anticancer effects on the AGS cell line than curcumin or doxorubicin monotherapy.

Background: Today, the medical world faces an increase in the incidence of chronic diseases. Medication adherence is an essential component of the effective treatment of such diseases and failure to it, especially in the elderly, has a negative impact on health. Objectives: The current study aimed at determining the level of medication adherence in the elderly with chronic diseases referring to academic medical centers in Ardabil, Iran. Methods: In the current cross sectional study, 222 elderly patients with chronic diseases (i e, musculoskeletal, diabetes, cardiovascular and renal conditions) referring to the clinics of Imam Khomeini, Fatemi, and Alavi hospitals in Ardabil in 2018 were selected by convenience sampling method. Data were collected using a questionnaire including demographic characteristics and the Morisky medication adherence scale (MMAS). The data were analyzed using descriptive statistics and multivariate logistic regression analysis with SPSS version 16. Results: The mean age of the elderly was 68.25 ± 7.65 years; 187 (84%) subjects had unsatisfactory medication adherence (score 6). The probability of satisfactory adherence to medication was higher in the elderly with higher level of education, but other variables such as age, gender, occupational status, income level, network of life, place of residence, marital status, and type of chronic disease had no significant effect on medication adherence. Conclusions: The high level of medication non-adherence in the elderly with chronic diseases is a matter of concern and it seems necessary to perform studies on the barriers to medication adherence in the elderly and solve them.

The present study aimed to evaluate the preventive role of physical and cognitive training separately or in combination on memory dysfunction, inflammatory factors and apoptotic markers in the hippocampal-ischemia model of rat. The ischemia model was established by infusion of endothelin-1 (ET-1) into the animal's hippocampus using stereotaxic surgery. Physical, cognitive and combination training groups exposed to voluntary running wheel exercise or modified Barnes maze cognitive task or combination of this interventions for 4 weeks, respectively. Next, Morris water maze (MWM) and novel object recognition (NOR) tasks were used to assess recognition and spatial learning and memories. Western blotting was used to evaluate the protein levels of Nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-alpha receptor 1 (TNFR1), cytochrome c, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 in the hippocampal tissue. Hippocampal ischemia significantly impaired recognition and spatial learning and memory with an increase of inflammatory and apoptotic proteins in the hippocampus tissue. Interventions in combination or separately significantly improved performance of ischemia-received animals in memory tasks. Furthermore, both physical and cognitive paradigms also reduced inflammatory and apoptotic factors in the hippocampus of ischemia-received rats. These findings indicate that physical and cognitive training separately or in combination attenuates the deleterious effect of ischemia on cognition through its anti-inflammatory and anti-apoptotic properties.

Disturbances in mitochondrial biogenesis and bioenergetics, combined with neuroinflammation, play cardinal roles in the cognitive impairment during aging that is further exacerbated by transient cerebral ischemia. Both near-infrared (NIR) photobiomodulation (PBM) and Coenzyme Q 10 (CoQ 10 ) administration are known to stimulate mitochondrial electron transport that potentially may reverse the effects of cerebral ischemia in aged animals. We tested the hypothesis that the effects of PBM and CoQ 10 , separately or in combination, improve cognition in a mouse model of transient cerebral ischemia superimposed on a model of aging. We modeled aging by 6-week administration of D-galactose (500 mg/kg subcutaneous) to mice. We subsequently induced transient cerebral ischemia by bilateral occlusion of the common carotid artery (BCCAO). We treated the mice with PBM (810 nm transcranial laser) or CoQ 10 (500 mg/kg by gavage), or both, for 2 weeks after surgery. We assessed cognitive function by the Barnes and Lashley III mazes and the What-Where-Which (WWWhich) task. PBM or CoQ 10 , and both, improved spatial and episodic memory in the mice. Separately and together, the treatments lowered reactive oxygen species and raised ATP and general mitochondrial activity as well as biomarkers of mitochondrial biogenesis, including SIRT1, PGC-1α, NRF1, and TFAM. Neuroinflammatory responsiveness declined, as indicated by decreased iNOS, TNF-α, and IL-1β levels with the PBM and CoQ 10 treatments. Collectively, the findings of this preclinical study imply that the procognitive effects of NIR PBM and CoQ 10 treatments, separately or in combination, are beneficial in a model of transient global brain ischemia superimposed on a model of aging in mice.

Summary: Hepatitis B virus (HBV) infection is known as a life-threatening liver infection and leads to chronic liver disease if left untreated. Nevertheless, the prevalence of HBV infection has been reduced by an approved vaccination approach using recombinant Hepatitis B surface Antigen (HBsAg) and Alum, known as the HBV vaccine. Alum can be used as an adjuvant to increase HBsAg immunogenicity as a strong Th2 stimulator. There is a vital need to stimulate Th1 immunity by HBsAg vaccination; however, the present vaccine does not induce a prophylactic immune response in some groups. The main aim of the present study was to induce a Th1 cytokine pattern and stimulate an immune response after HBsAg vaccination. Experimental mice were fed selenium nanoparticles (SeNPs) and were later immunized with 5 μg of Hepatitis B Vaccine. After a period of 30 days, the experimental animals were given two booster doses of SeNPs during their vaccination course. Group one, i.e., the control vaccine group, was only administered the HBsAg vaccine. The two treated groups, Groups 2 and 3, were daily fed different doses of SeNPs (100 μg and 200 μg, respectively) via gavage. Group four was considered the control group and was only given phosphate buffered saline (PBS). Lymphocyte proliferation, IFN-γ and IL-4 levels, total antibody and the isotypes of IgG1, IgG2a, IgG2b, and IgM were measured by Enzyme Linked Immunosorbent Assay (ELISA). The administration of SeNPs and the HBs antigen vaccine affected the lymphocyte proliferation; moreover, the total antibody responses also increased the IFN-γ level and induced a Th1 response. Conclusions: The present study proposed that the administration of SeNPs with a conventional HBs antigen vaccine induces a better immune response with a Th1 bias. Keywords: Selenium nanoparticles, Hepatitis B vaccine, IFN-γ, Th1 immune response