Abstract Background Composite lipid indices have been reported to have associations with several cardiovascular diseases and their negative adverse events. Among these, there are four novel indices that can be easily calculated, namely, triglyceride-glucose index (TyG, calculated from fasting plasma glucose [FPG] and triglyceride [TG]), lipid accumulation product (LAP, calculated from waist circumference [WC] and TG), visceral adiposity index (VAI, calculated from WC, TG, body mass index [BMI], and high-density lipoprotein [HDL]), and atherogenic index of plasma (AIP, calculated from TG and HDL). Herein, we aimed to investigate the impact of these indices on the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods All the patients with ACS who underwent PCI at our institution during the 2015-2022 period were included in the analyses. Patients were divided based on each of the TyG, VAI, LAP, and AIP indices quartiles (Q). The median follow-up was 378 days and the outcome assessed was MACCE composed of all-cause mortality, myocardial infarction, stroke, target vessel revascularization, target lesion revascularization, and coronary artery bypass grafting surgery. Results There was a total of 13,682 patients with ACS undergoing PCI with a mean age of 62.67 ± 11 years and 72.61% male predominance. Regarding the TyG index, patients in Q4 had a higher incidence of MACCE, compared to those in Q1 (adjusted HR [aHR] 1.271, 95% CI 1.067 – 1.513], p-value < 0.01). While in the crude model, patients in Q2, Q3, and Q4 of LAP had significantly higher rates of MACCE, compared to Q1, this association was not observed in the age- and sex-adjusted model and fully-adjusted model. Similarly, there was no difference among the quartiles of VAI and AIP regarding the incidence of MACCE. Kaplan-Meier curves also show that there were significant differences among TyG and LAP quartiles (p-value = 0.0049 and p-value = 0.035, respectively). Conclusion As our findings suggest, patients with higher TyG levels, as a surrogate marker of insulin resistance, had a higher incidence of MACCE. LAP could also play an important role in the incidence of adverse events after PCI. These novel lipid indices could help clinicians in determining the risks of patients with ACS undergoing PCI in order to provide better care to them.Risk of MACCE in different quartilesKaplan Meier Curves for risk of MACCE

Seizure aggravation following coronavirus disease 2019 (COVID‐19) vaccines is a major cause behind vaccine hesitancy among persons with epilepsy (PwE), resulting in lower immunization rates. We systematically reviewed seizure‐activity‐related events in PwE following COVID‐19 vaccination. We systematically searched PubMed, Web of Science, Scopus, and Cochrane Library, until January 31, 2023, and included articles reporting seizure activity‐related events in PwE receiving COVID‐19 vaccination. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses were followed. The protocol was registered with PROSPERO (CRD42022312475). Outcomes included pooled incidence proportions of (a) increased seizure frequency, (b) status epilepticus (SE), and (c) change in seizure type. Of the 2207 studies, 16 entered the meta‐analysis. The pooled incidence proportion of increased seizure frequency (16 studies‐3245 PwE) was 5% (95% CI: 3%−7%, I2 = 52%). Regarding increased seizure frequency, no significant difference was observed between mRNA and viral vector (OR: 1.11, 95% CI: 0.49−2.52, I2 = 0%), and between mRNA and inactivated virus (OR: 1.60, 95% CI: 0.27−9.37; I2 = 0%). The pooled incidence proportion of SE (15 studies‐2387 PwE) was 0.08% (95% CI: 0.02%−0.33%, I2 = 0%). Ultimately, the pooled incidence proportion of change in seizure type (7 studies‐1172 PwE) was 1% (95% CI: 1%−2%, I2 = 0%). The meta‐analysis revealed post‐COVID‐19‐vaccination increased seizure frequency in 5% of PwE, with no difference between mRNA and viral vector or inactivated virus vaccines. Furthermore, we found 0.08% and 1% incidence proportions for postvaccination SE and change in seizure type, respectively. While noteworthy, these values are far less than reports for COVID‐19 infection, emphasizing vaccination importance in preventing COVID‐19 consequences in PwE.

OBJECTIVES:Chronic venous disease (CVD) of the lower extremities is one of the common venous diseases in different populations, with a wide range of clinical manifestations and undetermined exact prevalence owing to different population characteristics and measurement methods. This study aimed to estimate the prevalence of CVD among the modern Iranian urban population and determine its associated risk factors. METHODS:The Heart Assessment and Monitoring in Rajaie Hospital study, a longitudinal population-based cohort, aims to investigate the baseline prevalence and the 10-year incidence of cardiovascular diseases and associated risk factors in the adult population aged 30 to 75 years with no overt cardiovascular diseases in Tehran. Two instructed interventional cardiologists performed CVD evaluation using the Clinical-Etiology-Anatomy-Pathophysiology classification. CVD was graded as C1 to C6, and chronic venous insufficiency (CVI) as C3 to C6. A multivariable regression model was used to analyze the association between CVD and prespecified covariates of age, sex, body mass index (≥30 kg/m2), smoking, hypertension, diabetes mellitus, physical activity, dyslipidemia, and delivery method. RESULTS:CVD prevalence among 1176 participants was 36.5% (95% confidence interval [CI], 33.8-39.3) and was higher in women than men (44.2% vs 23.5%). CVI prevalence was only 0.7% (95% CI, 0.3-1.3). Multivariable analysis showed that advanced age (odds ratio [OR], 1.06; 95% CI, 1.04-1.08), female sex (OR, 2.98; 95% CI, 2.14-4.14), and body mass index of ≥30 (OR, 1.36; 95% CI, 1.03-1.81) were independently associated with CVD. Physical activity (OR, 0.77; 95% CI, 0.58-1.02) was nearly protective, whereas other factors, including traditional cardiovascular risk factors, had no meaningful association with CVD. CONCLUSIONS:Our findings showed that CVD was prevalent in the modern Iranian urban population. However, considering the very low prevalence of the higher stages of the disease, the benefit of mass screening is debatable, and better risk discriminators should be investigated.

The neuro-gliovascular unit is a crucial structure for providing a balanced well-functioning environment for neurons and their synapses. Activation of the immune system during the developmental period is believed to affect the gliovascular unit, which may trigger neurodevelopmental and neurological/neuropsychiatric diseases. In this study, we hypothesized that vulnerability of the male brain to a neonatal insult was conditioned by sex-dependent differences in the impairment of the hippocampal gliovascular unit. Male and female C57BL/6J pups received lipopolysaccharide (LPS) (1 mg/kg) or saline on postnatal day (P) 5. Brains were collected at P12 and morphological quantifications of hippocampal fibrillary glial acid protein (GFAP+) astrocytes and ionized calcium-binding adaptor molecule 1 protein (Iba1+) microglia were performed by using 3-D image analysis together with measuring the length of CD31+ and aquaporin-4 (AQP4+) vessels. We found a significant increase in the length of CD31+ capillaries in the male LPS group compared to the saline group; however, coverage of capillaries by astrocytic end-feet (AQP4+) was significantly reduced. In contrast, there was a significant increase in AQP4+ capillary length in female pups 1 week after LPS injection. GFAP+ astrocytes via morphological changes in the hippocampus showed significant enhancement in the activity 1 week following LPS injection in male mice. We propose that neonatal inflammation could induce susceptibility to neurodevelopmental disorders through modification of hippocampal gliovascular interface in a sex-dependent manner.

Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here we investigated the role of postnatal immune activation on hippocampal synaptopathology by targeting Reelin+ cells in mice with ASD-like behavior. C57/Bl6 mouse pups of both sexes received lipopolysaccharide (LPS, 1mg/kg) on postnatal day (P) 5. At P45, animal behavior was examined by marble burying and sociability test, followed by ex-vivo brain MRI diffusion kurtosis imaging (DKI). Hippocampal synaptogenesis, number and morphology of Reelin+ cells, and mRNA expression of trans-synaptic genes, including neurexin-3, neuroligin-1, and cell-adhesion molecule nectin-1 were analyzed at P12 and P45. Social withdrawal and increased stereotypic activities in males were related to increased mean diffusivity on MRI-DKI and overgrowth in hippocampus together with retention of long-thin immature synapses on apical dendrites, decreased volume and number of Reelin+ cells as well as reduced expression of trans-synaptic and cell-adhesion molecules. The study provides new insights into sex-dependent mechanisms that may underlie ASD-like behavior in males following PIA. We identify GABAergic interneurons as core components of dysmaturation of excitatory synapses in the hippocampus following postnatal infection and provide cellular and molecular substrates for the MRI findings with translational value.

Background Circular RNAs (circRNAs) play pivotal roles in proliferation, apoptosis, migration, and invasion of renal cell carcinoma (RCC) cells. This study is aimed to systematically summarize the current evidence regarding the clinical implications of circRNAs in RCC patients. Methods A systematic search in PubMed, Embase, and Web of Science was performed until January 1, 2022. The correlation between the expression of circRNAs and clinicopathological, prognostic, and diagnostic features of RCC was evaluated using the meta-analysis. Results Ultimately, 41 studies with 3485 RCC patients were included in this study: 26 studies for clinicopathological features, 31 studies for prognosis, and eight studies for diagnosis. Altered expression of circRNAs was significantly associated with clinicopathological characteristics of RCC, including tumor size, tumor stage, lymph node metastasis, distant metastasis, and TNM stage. The tumor promoter circRNAs were associated with reduced overall survival (OS) (Hazard Ratio (HR) = 1.98, 95% confidence interval [CI] 1.68-2.34) and disease/progression/recurrence-free survival (DFS/PFS/RFS) (HR = 2.34, 95% CI 1.85-2.97). Contrarily, the tumor suppressor circRNAs were linked with better OS (HR = 0.49, 95% CI 0.40-0.60) and DFS/PFS/RFS (HR = 0.40, 95% CI 0.28-0.59). The pooled sensitivity and specificity of circRNAs for RCC diagnosis in tissue samples were both 0.84. These results in fluid samples (serum and urine) were 0.78 and 0.69, respectively. Conclusion CircRNAs can serve as promising diagnostic and prognostic biomarkers for RCC.

Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to experimental hypoxic-ischemic (HI) injury in the neonatal brain, but it is unclear if galectin-3 has similar effects on infectious and sterile inflammation. Thus, we investigated the effect of galectin-3 on microglia in vitro under normal as well as infectious and sterile inflammatory conditions, and the effect of galectin-3 on neonatal brain injury following an infectious challenge in vivo. Conditions mimicking infectious or sterile inflammation were evaluated in primary microglia cell cultures from newborn mice, using LPS (10 ng/mL) and TNF-α (100 ng/mL). The response to galectin-3 was tested alone or together with LPS or TNF-α. Supernatants were collected 24 h after treatment and analyzed for 23 inflammatory mediators including pro- and anti-inflammatory cytokines and chemokines using multiplex protein analysis, as well as ELISA for MCP-1 and insulin-like growth factor (IGF)-1. Phosphorylation of proteins (AKT, ERK1/2, IκB-α, JNK, and p38) was determined in microglia cells. Neonatal brain injury was induced by a combination of LPS and HI (LPS + HI) in postnatal day 9 transgenic mice lacking functional galectin-3 and wild-type controls. LPS and TNF-α induced pro-inflammatory (9/11 vs. 9/10) and anti-inflammatory (6/6 vs. 2/6) cytokines, as well as chemokines (6/6 vs. 4/6) in a similar manner, except generally lower amplitude of the TNF-α-induced response. Galectin-3 alone had no effect on any of the proteins analyzed. Galectin-3 reduced the LPS- and TNF-α-induced microglia response for cytokines, chemokines, and phosphorylation of IκB-α. LPS decreased baseline IGF-1 levels, and the levels were restored by galectin-3. Brain injury or microglia response after LPS + HI was not affected by galectin-3 deficiency. Galectin-3 has no independent effect on microglia but modulates inflammatory activation in vitro. The effect was similar under infectious and sterile inflammatory conditions, suggesting that galectin-3 regulates inflammation not just by binding to LPS or toll-like receptor-4. Galectin-3 restores IGF-1 levels reduced by LPS-induced inflammation, suggesting a potential protective effect on infectious injury. However, galectin-3 deficiency did not affect microglia activation and was not beneficial in an injury model encompassing an infectious challenge.

To investigate the neuroprotective effects of NAC (N-Acetyl-Cysteine) in patients with AIS (Acute Ischemic Stroke). The study was a single blind placebo controlled trial. 62 patients were enrolled in the study, 31 patients in each arm. NAC was infused for the intervention group with doses of 100 mg/kg stat on admission then 10 mg/kg/hour for 10 hours in addition to standard treatment. The control group only received standard treatment. The blood sample for measuring MMP-9 (Matrix Metalloproteinase 9) was collected from both groups before and 24 hours after receiving NAC. NIHSS (National Institutes of Health Stroke Scale) was calculated for both groups before therapy, 24 hours, 2 weeks, 1 month and 3 months after therapy. Mean NIHSS in the intervention and control groups were 6.87 ± 4.15 and 8.11 ± 4.12 (p-value = 0.231) on admission, 4.52 ± 3.82 and 5.87 ± 4.36 (p-value = 0.193)24 hours after admission, 3.06 ± 2.74and 4.93 ± 4.69 (p-value = 0.061)2 weeks later, 2.39 ± 2.41 and 3.66 ± 4.98 (p-value = 0.2 25) one month later, and, 1.07 ± 2.12 and 2.36 ± 2.28 (p-value = 0.511) 3 months later respectively, which were not statistically significant. Also, the relationship between MMP9 and NIHSS was evaluated using Pearson correlation coefficient. There was no significant correlation between MMP9 changes and neurological deficits in any of the time intervals. In both intervention and control groups, the amount of MMP9 24 hours after injection was decreased dramatically (p-value = 0.000) and showed that MMP9 reduction was not dependent on NAC injection. NAC injection did not show clinical and laboratory benefits in patients with AIS in addition to standard therapy.

SummaryBackgroundSpatial characterization of vertical organization of neurons in human cerebral cortex, cortical columnarity or minicolumns, and its possible association with various psychiatric and neurological diseases has been investigated for many years.New methodIn this study, we obtained 3D coordinates of disector sampled cells from layer III of Brodmann area 4 of the human cerebral cortex using light microscopy and 140‐μm‐thick glycolmethacrylate sections. A new analytical tool called cylindrical K‐function was applied for spatial point pattern analysis of 3D datasets to see whether there is a spatially organized columnar structure. In order to demonstrate the behaviour of the cylindrical K‐function, the result from brain tissues was compared with two models: A homogeneous Poisson process exhibiting complete spatial randomness, and a Poisson line cluster point process. The latter is a point process model in 3D space, which exhibits spatial structure of points similar to minicolumns.ResultsThe data show in three out of four samples nonrandom patterns in the 3D neuronal positions with the direction of minicolumns perpendicular to the pial surface of the brain – without a priori assuming the existence of minicolumns.Comparison with existing methodsStudies on columnarity are difficult and have mainly been based on two‐dimensional images analysis of thin sections of the cerebral cortex with the a priori assumption that minicolumns existed.ConclusionsA clear difference from complete spatial randomness in the data could be detected with the new tool, the cylindrical K‐function, although classical functional summary statistics are less useful in this connection.

Introduction: The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog’s isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz). Materials and Methods: Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF) radiation emitted from a common Jammer at a distance of 1m from the jammer’s antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T), the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz) as stimuli. Results: The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. Conclusion: These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

BACKGROUND:The rapid development of wireless telecommunication technologies over the past decades, has led to significant changes in the exposure of the general public to electromagnetic fields. Nowadays, people are continuously exposed to different sources of electromagnetic fields such as mobile phones, mobile base stations, cordless phones, Wi-Fi routers, and power lines. Therefore, the last decade witnessed a rapidly growing concern about the possible health effects of exposure to electromagnetic fields emitted by these sources.MATERIALS AND METHODS:In this study that was aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted by a GSM mobile phone on the pattern of contraction in frog's isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz), pulse height of contractions, the time interval between two subsequent contractions and the latency period were measured.RESULTS:Our findings showed that the pulse height of contractions muscle could be affected by the exposure to electromagnetic fields. Especially, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields.CONCLUSION:These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

In this paper, we present a new surface area estimator in local stereology. This new estimator is called the 'Morse-type surface area estimator' and is obtained using a two-stage sampling procedure. First a plane section through a fixed reference point of a three-dimensional structure is taken. In this section plane, a modification of the area tangent count method is used. The Morse-type estimator generalizes Cruz-Orive's pivotal estimator for convex objects to nonconvex objects. The advantages of the Morse-type estimator over existing local surface area estimators are illustrated in a simulation study. The Morse-type estimator is well suited for computer-assisted confocal microscopy and we demonstrate its practicability in a biological application: the surface area estimation of the nuclei of giant-cell glioblastoma from microscopy images. We also present an interactive software that allows the user to efficiently obtain the estimator.

Background: Drug addiction is an impulsive, unconscious drug seeking behavior associated /INS;with neurobiological changes. This neurobiological disorder accompanies high recurrence even after long period of treatment. /INS;The present study, investigated the effects of Satureja kuzestanica essential oil (SKEO) a well-known Iranian traditional medicine, on acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in rats.

OBJECTIVE: The aim of this study was to determine the association between previously documented risk factors such as recurrent pyelonephritis with the incidence of renal scarring after acute pyelonephritis in children. MATERIAL AND METHODS: Children with acute pyelonephritis who were admitted to the Department of Pediatrics of a teaching hospital during 2007-2009 were enrolled in this study. DMSA scans were obtained 4-6 months after the last episode of pyelonephritis in all patients. RESULTS: A total of 80 children with acute pyelonephritis were enrolled in this study. Most of them were girls (77.5%), with a median age of 12 months. Nearly half of the children (n = 44; 55%) had one or more renal scars. The distribution of gender, CRP level and leukocytosis did not differ significantly regardingthe absence or presence of renal scars (p > 0.05). Most of the scars occurred in children who had presented with bilateral pyelonephritis (69.4% vs. 18.2%, p = 0.001). Most of the patients with renal scars had a positive history of vesicoureteral reflux (VUR) (75% vs.13.6%, p = 0.001). The significant roles of recurrent pyelonephritis and presence of VUR were further confirmed by multivariate analysis. CONCLUSIONS: According to our findings, presence of VUR and recurrent pyelonephritis are independently associated with a higher incidence of renal scarring.

Background Reports on agmatine are controversial showing that it may improve memory, it can deteriorate memory and some did not notice any interference with learning and memory. In the present study, the effect of directly intra-CA1 agmatine microinjection on water maze learning and memory has been assessed. Methods The cannuls were implanted in hippocampal CA1 regions of rats in a sterotaxic frame after general anesthesia. After one week recovery period, the animals were assessed in the reference memory version of water maze. Agmatine (1, 10, 100 or 200 μg/0.5 μl) or saline were infused 20 minutes before or immediately after training. Results Agmatine-treated rats did not show any significant difference neither in water maze acquisition nor in consolidation task in comparison with control and sham groups. Conclusion Agmatine does not affect water maze learning and memory.

The purpose of this study was to investigate any association between IgA deficiency (IgAD) and juvenile rheumatoid arthritis (JRA) among Iranian children.This case-control study was carried out on 83 children who were diagnosed as JRA according to American College of Rheumatology (ACR) criteria; Patients were admitted at the rheumatology clinic of Children's Medical Center, (Tehran). Serum immunoglobulins concentrations were determined by nephelometry method. Control group was 112 healthy children who were matched for age and gender. Informed consent obtained from all parents.Selective IgA deficiency (sIgAD) was found only in a boy (1.2%) among JRA children; however, partial IgA deficiency was found in 6(7.1%) of patients with JRA and in 12(10.7%) of control subjects, this difference was not statistically significant (p=0.46). Immunoglobulins levels in patients with JRA (IgM: 126.7±57.2, IgG: 1182.3±351 and IgA:169.3±98) were significantly higher than their controls (IgM: 104±52, IgG:802±220 and IgA: 94.6±47) (p<0.05). Patients with growth failure had higher IgM, IgG and IgA levels in comparison with patients without growth failure; however, this difference was significant about IgM and IgG levels (p<0.05).In contrast to other similar studies, the number of IgAD did not differ significantly between JRA patients and their control counterpart; this might be partly due to the high rate of consanguineous marriages in Iran that resulted in increased prevalence of clinically undiagnosed partial IgAD in general population. Hence, future epidemiological studies are warranted to make it clear.

Iran J Pediatr, Vol 21 (No 1); Mar 2011 among suspensions and the fourth among capsules in antibiotic production of the country. Amoxicillin possessed the first place, the production of which was more than ten times of erythromycin. The question was, can food industry have a role in this problem? According to the report of Iranian Veterinary Organization (www.ivo.org.ir), lincomycin and erythromycin are the only macrolides used in our meat and dairy industry and none of them is frequently used, erythromycin is the seventh antibiotic (and the only macrolide) used in poultry (Neomycin has the first place). Lincomycin is the 4th drug (and the only macrolide) in cows and sheep husbandary (Penicillin has the first place with a large distance). Age is an important factor in the rate of antibiotic resistance. Significant negative correlation has been found between the age of patients and the erythromycin-resistance[7]. Our study however did not show such a relationship between age and erythromycin resistance, we think the reason is that infants and young children (<5 years old) which have the highest resistance rate are not included in this study. We conclude that GABHS has a high rate of resistance to erythromycin in Mashhad, and although we couldn’t find a reasonable explanation for this high degree of resistance, erythromycin can no longer be used for empirical treatment of streptococcal pharyngitis in this city. This project was funded by the Research Vice Chancellor of Mashhad University of Medical Sciences.