Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. METHODS: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. RESULTS: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. CONCLUSION: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Impact of Probiotics on Gastrointestinal Function and Metabolic Status After Roux-en-Y Gastric Bypass: A Double-Blind, Randomized Trial.

PURPOSE: Postoperative changes in gut microbiota may occur in patients undergoing Roux-en-Y gastric bypass surgery. In this study, we evaluate the impact of administering probiotic tablets on the gastrointestinal function and metabolic status of these patients. MATERIALS AND METHODS: This double-blinded randomized clinical trial was conducted from 2021 to 2022 on 135 Roux-en-Y surgery candidates. The intervention group underwent the surgical procedure and started receiving probiotic supplements (Familact Co.) 1 week after surgery; the control group received a placebo. The laboratory and anthropometric data were measured and analyzed before and 3 and 6 months after the intervention. GIQLI questionnaire was also used at the beginning and 6 months after the intervention to evaluate GI symptoms. RESULTS: We observed significantly reduced BMI in both groups after surgeries (P < 0.001). The levels of FBS and HbA1C were significantly lower in the probiotic group compared to the placebo in 3 months (P = 0.02 and P = 0.001, respectively) and 6 months (P < 0.001 for both) after the intervention. The levels of vitamin B12 increased significantly in the probiotic group (P < 0.001), and the values were substantially higher than the placebo group in 3 and 6 months (P < 0.001), respectively. Analysis of the GIQLI questionnaire before and 6 months after interventions also revealed significant improvement in the GIQLI score in both groups (P < 0.001 for probiotics and P = 0.03 for placebo). CONCLUSION: Probiotic supplement administration following RYGB improves patients' vitamin and metabolic profile, as well as GI function, although it cannot significantly affect weight loss.

Neuroprotective effect of human cord blood-derived extracellular vesicles by improved neuromuscular function and reduced gliosis in a rat model of Huntington's disease.

Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.

Effects of Vitamin D and E Supplementation on Prevention of Bronchopulmonary Dysplasia (BPD) in Premature Neonates: A Systematic Review and Meta-Analysis.

BACKGROUND: Bronchopulmonary Dysplasia (BPD) has a multifactorial etiology. Vitamin E and vitamin D play an important role in lung development and can potentially be beneficial in the prevention of BPD. OBJECTIVE: The study aimed to compare the risk of BPD occurrence in preterm neonates supplemented with vitamin D or E versus those who did not get supplementation. METHODS: The literature search was conducted for this systematic review by searching the PubMed, Scopus, and Web of Science databases up to December 2022. Randomized controlled trials involved administering vitamin D or E to preterm neonates and examining the occurrence of BPD. We excluded non-English articles, and articles with non-relevant and insufficient data. We used the Critical Appraisal Skills Programme (CASP) checklist to assess the quality of the included studies. We used Egger's test to evaluate the risk of bias among the included studies. Heterogeneity was also assessed through Q-test and I2. We applied the random effect model for analysis. A P-value less than 0.05 was considered as significant. All the statistical analysis in the current study was performed using STATA 14. The Relative Risk (RR) was calculated as the effect size with 95% Confidence Interval (CI). RESULTS: Three eligible studies seeking the role of vitamin D in the prevention of BPD were analysed. Meta-analysis revealed that receiving vitamin D supplementation can significantly reduce the risk of BPD in preterm infants (RR = 0.357, 95% CI: 0.189-0.675, I2 = 0.0%; p = 0.002). Similarly, for assessing the role of Vitamin E in the prevention of BPD, three eligible studies were analysed. Vitamin E supplementation was not found to play a significant role in the reduction of BPD (RR = 0.659, 95%CI = 0.243-1.786, I2 = 38.7%; p = 0.412). CONCLUSION: Vitamin D supplementation could be beneficial in preventing BPD in preterm infants. However, evidence is not enough regarding vitamin E's role in reducing the incidence of BPD in preterm infants.

Memory loss induced by lisdexamfetamine in the rat: A behavioral, electrophysiological, and histopathological Study.

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.

Introducing fitting models for estimating age-specific dose and effective dose in paediatric patients undergoing head, chest and abdomen-pelvis imaging protocols: a patient study.

INTRODUCTION: Concerns regarding the adverse consequences of radiation have increased due to the expanded application of computed tomography (CT) in medical practice. Certain studies have indicated that the radiation dosage depends on the anatomical region, the imaging technique employed and patient-specific variables. The aim of this study is to present fitting models for the estimation of age-specific dose estimates (ASDE), in the same direction of size-specific dose estimates, and effective doses based on patient age, gender and the type of CT examination used in paediatric head, chest and abdomen-pelvis imaging. METHODS: A total of 583 paediatric patients were included in the study. Radiometric data were gathered from DICOM files. The patients were categorised into five distinct groups (under 15 years of age), and the effective dose, organ dose and ASDE were computed for the CT examinations involving the head, chest and abdomen-pelvis. Finally, the best fitting models were presented for estimation of ASDE and effective doses based on patient age, gender and the type of examination. RESULTS: The ASDE in head, chest, and abdomen-pelvis CT examinations increases with increasing age. As age increases, the effective dose in head and abdomen-pelvis CT scans decreased. However, for chest scans, the effective dose initially showed a decreasing trend until the first year of life; after that, it increases in correlation with age. CONCLUSIONS: Based on the presented fitting model for the ASDE, these CT scan quantities depend on factors such as patient age and the type of CT examination. For the effective dose, the gender was also included in the fitting model. By utilising the information about the scan type, region and age, it becomes feasible to estimate the ASDE and effective dose using the models provided in this study.

Chronic Administration of Lisdexamfetamine Induces Apoptosis and Inflammation and Reduces Sperm Quality in Adult Male Rats.

Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.

A challenging transseptal mitral valve in valve case report: Success and safety.

Key Clinical Message: Transcatheter mitral valve implantation (TMVI) is considered a less-invasive approach than open-heart surgery, favored in high-risk patients elected for valve replacement. Although seemingly suitable, this procedure is highly operator-dependent. Abstract: Transcatheter mitral valve implantation (TMVI) is an alternative in high-risk patients. We reported a 72-year-old patient with mitral bioprosthesis degeneration successfully receiving TMVI. The procedure has lower morbidity and mortality rate than the surgical approach but can be accompanied by several complications, especially when conducted by an inexperienced operator.

The elderberry diet protection against intrahippocampal Aß-induced memory dysfunction; the abrogated apoptosis and neuroinflammation.

This study evaluates whether elderberry (EB) effectively decreases the inflammation and oxidative stress in the brain cells to reduce Aß toxicity. In the Aß + EB group, EB powder was added to rats' routine diet for eight consecutive weeks. Then, spatial memory, working memory, and long-term memory, were measured using the Morris water maze, T-maze, and passive avoidance test. Also, in this investigation immunohistopathology, distribution of hippocampal cells, and gene expression was carried out. Voronoi tessellation method was used to estimate the spatial distribution of the cells in the hippocampus. In addition to improving the memory functions of rats with Aß toxicity, a reduction in astrogliosis and astrocytes process length and the number of branches and intersections distal to the soma was observed in their hippocampus compared to the control group. Further analysis indicated that the EB diet decreased the caspase-3 expression in the hippocampus of rats with Aß toxicity. Also, EB protected hippocampal pyramidal neurons against Aß toxicity and improved the spatial distribution of the hippocampal neurons. Moreover, EB decreased the expression of inflammatory and apoptotic genes. Overall, our study suggest that EB can be considered a potent modifier of astrocytes' reactivation and inflammatory responses.

Exposure to Δ9-tetrahydrocannabinol leads to a rise in caspase-3, morphological changes in microglial, and astrocyte reactivity in the cerebellum of rats.

The present study aimed to elucidate the effect of 10 mg/kg Δ9-tetrahydrocannabinol (THC) on cerebellar neuronal and glial morphology, apoptosis and inflammatory gene expression using a series of histological assays including stereology, Sholl analysis, immunofluorescence and real-time qPCR in male Wistar rats. A decrease in the number of Purkinje neurons and the thickness of the granular layer in the cerebellum was reported in THC-treated rats. Increased expression of Iba-1 and arborization of microglial processes were evidence of microgliosis and morphological changes in microglia. In addition, astrogliosis and changes in astrocyte morphology were other findings associated with THC administration. THC also led to an increase in caspase-3 positive cells and a decrease in autophagy and inflammatory gene expression such as mTOR, BECN1 and LAMP2. However, there were no significant changes in the volume of molecular layers and white matter, the spatial arrangement of granular layers and white matter, or the spatial arrangement of granular layers and white matter in the cerebellum. Taken together, our data showed both neuroprotective and neurodegenerative properties of THC in the cerebellum, which require further study in the future.

A rare case of mycotic aortic aneurysm with Clostridium perfringens culture.

Key Clinical Message: As only early diagnosis, prompt surgical intervention, and appropriate antibiotic therapy can decrease clostridial MAA mortality rate; keeping in mind a broad differential diagnosis in a patient with sepsis and unusual vascular symptoms is important. Abstract: Mycotic aortic aneurysm (MAA) is an infrequent but very consequential condition characterized by the pathological disruption of the aorta due to infection. Clostridium perfringens is a bacterium that falls under the taxonomic classification of the genus Clostridium. Although mycotic aneurysm is often not commonly linked with this infection, there are instances when it may function as a causative agent for MAA. Timely diagnosis and thorough therapeutic techniques, including surgical intervention and quick administration of appropriate antibiotics, can potentially reduce the mortality rate associated with clostridial MAA. In this study, we presented a clinical report detailing the diagnosis of a mycotic aneurysm caused by C. perfringens in the thoracic aorta in a 66-year-old male patient with a history of diabetes mellitus and a recent prostate biopsy. Furthermore, we discussed the surgical approach and overall management strategy to address this case.

Grafted Sertoli cells prevent neuronal cell death and memory loss induced by seizures.

Epilepsy significantly reduces the patient's quality of life, and we still need to develop new therapeutic approaches to control it. Transplantation of cells such as Sertoli cells (SCs), having a potent ability to release a variety of growth and immunoprotective substances, have made them a potential candidate to deal with neurological diseases like epilepsy. Hence, this study aims to evaluate whether SCs transplant effectively protects the hippocampus astrocytes and neurons to oppose seizure damage. For this purpose, the effects of bilateral intrahippocampal transplantation of SCs were investigated on the rats with the pentylenetetrazol (PTZ) induced seizure. After one-month, post-graft analysis was performed regarding behavior, immunohistopathology, and the distribution of the hippocampal cells. Our findings showed SCs transplantation reduced astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma of the hippocampus in the seizure group. In rats with grafted SCs, there was a drop in the hippocampal caspase-3 expression. Moreover, the SCs showed another protective impact, as shown by an improvement in pyramidal neurons' number and spatial distribution. The findings suggested that SCs transplantation can potently modify astrocytes' reactivation and inflammatory responses.

Elderberry diet improves gut-brain axis dysfunction, neuroinflammation, and cognitive impairment in the rat model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is related to a problem in the gut-brain axis. This experimental research aimed to shed light on the potential therapeutic application of elderberry (EB), which can work on the axis and get better the IBS symptoms. There were three groups (36 Sprague-Dawley rats) in this experiment, including control, IBS, and IBS with EB diet (IBS + EB). Making use of intracolonic instillation of 1 ml of 4% acetic acid for 30 s, IBS was induced. 7 days later, the EB extract (2%) was added to the diets of all animals for 8 weeks. Some histological, behavioral, and stereological techniques were used to detect the effects of EB on the gut and brain tissues. The findings showed that the EB diet improved locomotion and decreased anxiety-like behavior in the rat models of IBS. Moreover, the diet dropped the expression of TNF-α and increased mucosal layer thickness and the number of goblet and mast cells in colon tissue samples. In the hippocampal samples, administration of EB prevented astrogliosis and astrocyte reactivity. Although hippocampal and cortical neurons decreased markedly in the IBS group, EB prevented the drop in the number of neurons. Although lots of research is needed to elucidate the effectiveness of EB in IBS and its exact molecular mechanism, the result of this study showed that EB as an antioxidant and immune-modulatory agent could be a promising research target to prevent the impairment in the gut-brain axis, and could ameliorative classic IBS symptoms.

The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: A review.

MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of several target genes. miRNAs play a significant role in cancer biology, as they can downregulate their corresponding target genes by impeding the translation of mRNA (at the mRNA level) as well as degrading mRNAs by binding to the 3'-untranslated (UTR) regions (at the protein level). miRNAs may be employed as cancer biomarkers. Therefore, miRNAs are widely investigated for early detection of cancers which can lead to improved survival rates and quality of life. This is particularly important in the case of gastrointestinal cancers, where early detection of the disease could substantially impact patients' survival. MicroRNA-21 (miR-21 or miRNA-21) is one of the most frequently researched miRNAs, where it is involved in the pathophysiology of cancer and the downregulation of several tumor suppressor genes. In gastrointestinal cancers, miR-21 regulates phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), mothers against decapentaplegic homolog 7 (SMAD7), phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), matrix metalloproteinases (MMPs), ß-catenin, tropomyosin 1, maspin, and ras homolog gene family member B (RHOB). In this review, we investigate the functions of miR-21 in pathogenesis and its applications as a diagnostic and prognostic cancer biomarker in four different gastrointestinal cancers, including colorectal cancer (CRC), pancreatic cancer (PC), gastric cancer (GC), and esophageal cancer (EC).

Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review.

Background: Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects. Method: Electronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios. Result: Ten studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports. Conclusion: The results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects.

Dynamic changes in metabolites of the kynurenine pathway in Alzheimer's disease, Parkinson's disease, and Huntington's disease: A systematic Review and meta-analysis.

Background: Tryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide adenosine dinucleotide (NAD+), and metabolites of this pathway may have protective or degenerative effects on the nervous system. Thus, the KP may be involved in neurodegenerative diseases. Objectives: The purpose of this systematic review and meta-analysis is to assess the changes in KP metabolites such as TRP, kynurenine (KYN), kynurenic acid (KYNA), Anthranilic acid (AA), 3-hydroxykynurenine (3-HK), 5-Hydroxyindoleacetic acid (5-HIAA), and 3-Hydroxyanthranilic acid (3-HANA) in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) patients compared to the control group. Methods: We conducted a literature search using PubMed/Medline, Scopus, Google Scholar, Web of Science, and EMBASE electronic databases to find articles published up to 2022. Studies measuring TRP, KYN, KYNA, AA, 3-HK, 5-HIAA, 3-HANA in AD, PD, or HD patients and controls were identified. Standardized mean differences (SMDs) were used to determine the differences in the levels of the KP metabolites between the two groups. Results: A total of 30 studies compromising 689 patients and 774 controls were included in our meta-analysis. Our results showed that the blood levels of TRP was significantly lower in the AD (SMD=-0.68, 95% CI=-0.97 to -0.40, p=0.000, I2 = 41.8%, k=8, n=382), PD (SMD=-0.77, 95% CI=-1.24 to -0.30, p=0.001, I2 = 74.9%, k=4, n=352), and HD (SMD=-0.90, 95% CI=-1.71 to -0.10, p=0.028, I2 = 91.0%, k=5, n=369) patients compared to the controls. Moreover, the CSF levels of 3-HK in AD patients (p=0.020) and the blood levels of KYN in HD patients (p=0.020) were lower compared with controls. Conclusion: Overall, the findings of this meta-analysis support the hypothesis that the alterations in the KP may be involved in the pathogenesis of AD, PD, and HD. However, additional research is needed to show whether other KP metabolites also vary in AD, PD, and HD patients. So, the metabolites of KP can be used for better diagnosing these diseases.

Tramadol-induced apoptosis in auditory hair cells of adult male rats.

Reports have emerged on the sudden opioid-induced auditory hearing loss, and the underlying pathology is not fully understood. The present study aimed to determine the mechanism of action of these drugs in the inner ear. For this purpose, 20 rats were treated with 50 mg/kg tramadol daily for three weeks. Next, the stereological and immunohistochemical alteration of the inner hair cells under chronic exposure to tramadol was evaluated. The results revealed that tramadol induced hair cell degeneration and decreased bipolar neurons of the spiral ganglion and the thickness of stria vascularis. Moreover, immunohistochemistry showed that tramadol caused apoptosis in inner hair cells and bipolar neurons. These findings indicate that tramadol induces apoptosis in auditory hair cells, suggesting that tramadol may cause hearing loss and ototoxicity.

Cardiovascular Complications of COVID-19 among Pregnant Women and Their Fetuses: A Systematic Review.

BACKGROUND: COVID-19 is a viral infectious disease leading to a spectrum of clinical complications, especially cardiovascular. Evidence shows that this infection can potentially accompany a worse outcome in pregnant women. Cardiovascular complications in mothers and their fetuses are reported by previous studies. OBJECTIVE: In this systematic review, we aim to investigate the cardiovascular complications of COVID-19 during pregnancy in the mothers and fetus, according to the published literature. METHOD: We systematically searched the online databases of PubMed, Scopus, Web of Science, and Google Scholar, using relevant keywords up to April 2022. We included all observational studies reporting cardiovascular complications among COVID-19-affected pregnant women and their fetuses. RESULTS: We included 74 studies containing 47582 pregnant COVID-19 cases. Pre-eclampsia, hypertensive disorders, cardiomyopathy, heart failure, myocardial infarction, thrombosis formation, alterations in maternal-fetal Doppler patterns, and maternal and fetal arrhythmia were reported as cardiovascular complications. The highest incidences of pre-eclampsia/eclampsia among COVID-19 pregnant cases, reported by studies, were 69% and 62%, and the lowest were 0.5% and 3%. The highest and lowest incidences of fetal bradycardia were 20% and 3%, and regarding fetal tachycardia, 5.4% and 1%, respectively. CONCLUSION: SARS-CoV-2 infection during pregnancy can potentially be associated with cardiovascular complications in the mother, particularly pre-eclampsia and heart failure. Moreover, SARS-CoV-2 infection during pregnancy can potentially cause cardiovascular complications in the fetus, particularly arrhythmia.

The Diagnostic Value of Neutrophil to Lymphocyte Ratio as an Effective Biomarker for Eye Disorders: A Meta-Analysis.

The neutrophil to lymphocyte ratio (NLR) reflects a dynamic relationship between the innate (neutrophils) and adaptive (lymphocytes) cellular immune response. This systematic review and meta-analysis was conducted to critically evaluate the literature regarding the use of the NLR as a reliable means to detect several ocular disorders. Our study was registered with the PROSPERO (ID: CRD42022314850). Three databases, including PubMed, Embase, Scopus, and the Web of Science, were searched on September 9, 2022, with no restrictions on the article's language. Finally, 32 articles were recognized as eligible for our meta-analysis. We found that patients with eye diseases had significantly elevated levels of NLR in comparison to healthy controls (SMD =0.53, 95% CI =0.35-0.71, P < 0.001). In subgroup analysis, patients with keratoconus (SMD =0.69; 95% CI =0.33-1.05, P < 0.001), glaucoma (SMD =0.56, 95% CI =0.25-0.87, P < 0.001), pterygium (SMD =0.14; 95% CI =0.01-0.26, P < 0.001), and idiopathic epiretinal membrane (SMD =0.14; 95% CI =0.01-0.26, P < 0.001) had higher levels of NLR compared to healthy controls. However, NLR levels of patients with dry eye disease were similar to healthy controls (SMD =0.32, 95% CI = -0.49-1.13, P = 0.435). It can be said that NLR is a valuable marker of systemic inflammation, which is significantly increased in many eye disorders, suggesting that inflammation plays a key role in the pathophysiology of these diseases.

An elderberry-supplemented diet improves spermatogenesis in mice with busulfan-induced azoospermia.

CONTEXT: Approximately 40-50% of all infertility cases are due to male infertility, and one of the most important causes of infertility is azoospermia. AIMS: This study aimed to evaluate the potential effect of elderberry on the spermatogenesis process in the azoospermia mice model. METHOD: Thirty adult male mice were randomised into three groups: control; busulfan (45mg/kg); and busulfan+elderberry (2%), 6mL orally per animal. Sperm samples were collected from the tail of the epididymis, and testis specimens were also collected and then subjected to sperm parameters analysis, histopathological evaluation, reactive oxygen species (ROS), and glutathione (GSH) measurement to determine the mRNA expression and hormonal assay. CONCLUSIONS: It can be concluded that the elderberry diet may be considered a complementary treatment to improve the spermatogenesis process in busulfan-induced azoospermic mice. IMPLICATIONS: Considering some limitations, the elderberry diet can be an alternate option for improving testicular damage following chemotherapy.