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Introduction: Sleep deprivation can cause hyperalgesia and interfere with analgesic treatments. The aim of the present study was to establish an obligatory sleep-abstinence model and also evaluate the effects of intracerebroventricular (ICV) injection of crocin on pain perception in Wistar rats. Methods: In this experimental study, 35 adult male Wistar rats were randomly divided into 5 groups (n=7). The intra-ventricular cannulation was done for all rats before sleep deprivation. Sleep deprivation was performed by placing animals on a chamber equipped with an automatic animated conveyor (5 s with an interval of 3 min) for 72 h. Subsequently, the sleep-deprived animals received ICV injection of saline (MOD), Morphine 10 µg (MOR), Crocin 10 ug (Cr10), and Crocin40 µg (Cr40) using a microsyringe. Besides, a non-sleep-deprived group was allocated as a Control Group (NC) and only received an ICV injection of saline. Fifteen minutes after the ICV injections, pain perception was evaluated by the hot plate test (54±0.4◦C). Results: Compared with the NC group, latency significantly decreased in the MOD group (6.28±0.48 vs. 4.28± 0.48, p

OBJECTIVES: The pace of population aging is growing rapidly around the world. Aging is associated with the emergence of different health status including geriatric syndrome such as frailty, diabetes, cardiovascular diseases, and dementia. These conditions are the most prominent challenges for health care systems and also elderly people. Therefore, understanding these changes can help scientists to prevent and treat significant health issues and also improve the functional ability of older adults. METHODS: This is a protocol of the first wave of Birjand Longitudinal Aging Study that is an ongoing community-based prospective cohort study with a following up at least 10 years. This study carries out on aged population ≥ 60 years which were residents in Birjand County (urban and rural older subjects). The selection of the participants of this study in urban areas is based on an age group weighted multistage stratified random sample while in the rural region the sample was selected from all ten rural regions of Birjand County by simple random sampling. The rural region sampling was based on the list of the aged population which were under the coverage of the rural health center. Sociodemographic, past medical history, lifestyle, sleep, activities of daily living, cognitive function, quality of life, and social capital were evaluated by interviewing with the participants and one of the informants. Anthropometric measures, electrocardiography, and interpretation of ophthalmologic examination were carried out by experts. Fasting Blood samples were collected and bio-banked in − 80 °C. then finally biochemical and hematologic markers were measured. RESULTS: This is the protocol of stage one baseline of Birjand Longitudinal Aging Study (BLAS). The BLAS is an enjoining study, the first phase of its baseline was carried out on a community- dwelling aged population sample ≥ 60 years who were residents in urban and rural regions of Birjand County. This is a community based prospective cohort study with at least 10 years follow up of participants. The data for 65% of older subjects (response rate = 65%) that lived in clusters were collected. CONCLUSIONS: This study can help scientists to recognize some risk factors related to the aging process and also aware policymakers about the necessity to create heath care services at regional and even national levels.

Introduction: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic and is accompanied by extraordinary morbidity and mortality. Critically ill COVID-19 patients have frequent thrombotic problems and laboratory evidence of hypercoagulability. The spectrum of presentations and complications of COVID-19 is still evolving. We describe a patient with unusual visual symptoms as the presenting signs of COVID-19. Case Presentation: In this case report, we describe a patient who presented with acute severe bilateral visual loss and headache. On neurological examination, cranial nerves were normal. There was no motor and sensorial abnormality. While the patient was in the emergency room, he was tested positive for COVID-19 via nasopharyngeal swab polymerase chain reaction (PCR) as part of COVID-19 surveillance. An unenhanced brain CT scan showed infarction in the occipital cortex bilaterally due to ischemic stroke involving the Posterior Cerebral Artery (PCA). A few hours later, oxygen saturation was 42%, and a sudden decline of consciousness was observed, progressing to coma. The neurosurgery intervention failed to change the patient's status, and he was pronounced dead in the next few hours. Conclusions: This case illuminates a wide range of COVID-19-related symptomatology and highlights the need for clinicians to be aware of different clinical appearances associated with this infection.

In this article, we will discuss scientific aspects of an old Persian story, Simorgh, in the book of The Conference of the Birds. The story is fulfilled with artistic and philosophical metaphors that make sense in two hot topics of the contemporary modern sciences i.e. cognitive science and complexity science. The poet addresses some humanity’s bygone concerns and fundamental questions about self, the quality that shapes a person’s uniqueness, and essential existence. The sophisticated language used in the poem contains allusions, symbols, and implications that are interpreted in five main topics. We think that the story deserves to be the touchstone for questions on the nature of the mind, including the profound question of humanity’s search for self and meaning of life.

There is increasing evidence that maternal diabetes mellitus during the pregnancy is associated with a higher risk of neurodevelopmental and neurofunctional anomalies including motor dysfunctions, learning deficits, and behavioral problems in offspring. The cerebellum is a part of the brain that has long been recognized as a center of movement balance and motor coordination. Moreover, recent studies in humans and animals have also implicated the cerebellum in cognitive processing, sensory discrimination, attention, and learning and memory. Synaptogenesis is one of the most crucial events during the development of the central nervous system. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles and is considered to be a marker for synaptic density and synaptogenesis. Here, we review the manuscripts focusing on the negative impacts of maternal diabetes in pregnancy on the expression or localization of SYP in the developing cerebellar cortex. We believe that the alteration in synaptogenesis or synapse density may be part of the cascade of events through which diabetes in pregnant women affects the newborn's cerebellum.

Diabetes during the pregnancy period impairs hippocampal development, and is associated with neurocognitive and neurobehavioral problems in the offspring. Synaptogenesis is one of the most important events in the development of the nervous system, and is known as a mechanism by which the memory process takes place. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles in the hippocampus involved also in learning and memory. The present study aimed to examine the effects of maternal diabetes on the expression and distribution pattern of SYP, as a marker of synaptogenesis, in the developing rat hippocampus using Immunofluorescence staining and real-time PCR. Wistar female rats were maintained as diabetic from a week before pregnancy through parturition and male offspring was euthanized at postnatal day (P) 0, 7, and 14. Our results showed a significant down-regulation in mRNA expression of SYP in the offspring born to diabetic animals at P7, and P14 (P ⩽ 0.05 each). Regarding to the density of SYP expressing hippocampal neurons, we found a marked decrease in the distribution pattern of SYP in all hippocampal subfields of Streptozotocin (STZ)-D group rat neonates, especially in one and two weeks of age (P ⩽ 0.05 each). Moreover, the results revealed no significant changes in either gene expression or distribution pattern of SYP--positive neurons in insulin-treated group compared with the controls. The present study demonstrated that diabetes in pregnancy has negative impacts on synaptogenesis in the offspring's hippocampus. Furthermore, the rigid maternal glycaemia control by insulin treatment in most cases normalized these effects.

Trauma is one of the most important issues of most healthcare systems accompanying with head trauma in the most cases. We sought to determine the scoring system and initial Computed Tomography (CT) findings predicting the death at hospital discharge (early death) in patients with traumatic brain injury based on Marshall and Rotterdam CT scores. This is a cross sectional study on traumatic neurosurgical patients with mild-to-severe traumatic brain injury admitted to the emergency department of Emam Reza Hospital, Birjand University of Medical Sciences. Patients≥18 years old with TBI during last 24 hours with GCS≤13 were included and exclusion criteria were multiple trauma, penetrating injuries, previous history of anticoagulant therapy, pregnancy, not willingness for participation. Their initial CT and status at hospital discharge, one and three months (dead or alive) were reviewed, and both CT scores were calculated. We examined whether each score is related to death using SPSS11 by The Mann–Whitney U at the level of p≤0.05. Overall, 98 patients were included. Mean age was 43.52±21.29. Most patients were male (63.3%). Mean Marshall and Rotterdam CT scores were 3.2±1.3 and 2.5±1. The mortality at two weeks, one moth and three months were 19.4%, 20.4%, and 20.4%. Rotterdam CT score was significantly different based on type of hematoma. Median GCS score in alive and dead patients on 2 weeks were 10 and 4 (p=0.0001), at one month were 10 and 4 (p=0.0001), and at three months were 10 and 4 (p=0.0001). The median Marshall CT score on 2 weeks were 2 and 4 (p=0.0001), at one month were 2 and 4 (p=0.0001), and at three months were 2 and 4 (p=0.0001). The median Rotterdam CT score on 2 weeks were 2 and 4 (p=0.0001), at one month were 2 and 3 (p=0.001), and at three months were 2 and 3 (p=0.001). The Rotterdam CT score was significantly correlated with mortality at two weeks, one month and three months (p=0.004, p=0.001, and p=0.001, respectively). The Marshall CT score was not significantly correlated with mortality at any time. The Rotterdam CT score was more accurate for prediction of mortality on 2 weeks (ROC80.9), at one month (ROC80.7), and at three months were (ROC80.7) than The Rotterdam CT score (ROC 76, 74.1, and 74.1, respectively). This study concluded that The Marshall CT score was more accurate for prediction of mortality on 2 weeks, at one month, and at three months were than The Marshall CT score with higher ROC. The correlation of the Rotterdam CT score with mortality was significant.

Background & Aim: The most common primary brain tumors of the central nervous system are gliomas. Among a number of different biomolecular events, a strong relation between oxidative stress pathways and the development of this cancer has been proved. Oxidative stress (OS) is the consequence of an imbalance between pro-oxidants and antioxidants towards pro-oxidants. The pro-oxidants cause lipid peroxidation of cell membranes, protein, DNA oxidation and changes in brain cell growth. In this study, the pro-oxidant–antioxidant balance (PAB) was determined in patients with gliomas. Methods & Materials/Patients: Sera of 49 patients with high grade glioma (grade IV WHO) which is called glioblastoma multiform (GBM) and 49 healthy subjects were collected and PAB test was measured. Results: A significant increase of PAB value was observed in patients with GBM (158.10±85.71 HK unit) in comparison to control group (74.54±33.54 HK). Conclusion: The PAB assay showed the oxidative stress in glioblastoma. In further research, this easy elucidation of oxidative stress in these patients can be applied to evaluate the effectiveness of antioxidant therapies in patients with GBM.Keywords: Prooxidant-antioxidant; Balance; High

INTRODUCTION: Poisoning is one of the most important health issues in the world. There is no exact statistic regarding the epidemiology of poisoning in Iran. The aim of this systematic review was to study the epidemiology of poisoning of adults in Iran. METHODS: All the published papers regarding the epidemiology and patterns of adult poisonings in different parts of Iran were reviewed in bibliographical databases, including SID, Iran Medex, Medlib, Magiran and Embase, Scopus, PubMed, and Google Scholar, without time limitation up to March 21, 2016. We searched for the terms poisoning, Iran, and epidemiology. After the final analysis, 38 articles that fulfilled all the required conditions were selected. RESULT: In this article, we show that in most Iranian cities, except Ahvaz, pharmaceutical drugs, especially psychiatric pharmaceutical drugs, are the most common cause of poisoning in adults. In the Southwest region of Iran, poisoning due to envenomation is a very common. Although pesticide and opioid poisonings are less common, they are an important cause of death due to poisoning in Iran. CONCLUSION: Pharmaceutical drugs are the most common cause of poisoning in most Iranian cities and it is recommended not to store pharmaceutical drugs at home and to set special rules regarding proper description of pharmaceutical drugs. More public health instruction is essential in the Southwest cities of Iran in order to reduce animal poisonings. Language: en

Cavernous angiomas of the upper brainstem causing hemiparkinsonism are very rare. Due to their difficult-to-reach localization, brainstem cavernomas, in particular those in anterior locations, continue to present a therapeutic challenge. The authors report on a 16-year-old boy with a pontomesencephalic cavernoma who developed hemiparkinsonism and hemiparesis after hemorrhage. After complete surgical removal of the pontomesencephalic cavernoma via a pterional transsylvian approach, his symptoms resolved. Although pontomesencephalic cavernomas occupying the ventral portion of the brainstem are regarded as problematic for resection, the pterional transsylvian approach provides an excellent route for removal of cavernomas that are in contact with the ventral surface of the midbrain in the interpeduncular cistern. Surgical removal of this type of lesion is recommended because resolution of clinical symptoms, including hemiparkinsonism, can be achieved.

There is sufficient evidence that diabetes during pregnancy is associated with a higher risk of neurodevelopmental anomalies including learning deficits, behavioral problems and motor dysfunctions in the offspring. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles and is considered as a marker for synaptogenesis and synaptic density. This study aimed to examine the effects of maternal diabetes in pregnancy on the expression and localization of SYP in the developing rat cerebellum. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was euthanized at postnatal day (P) 0, 7, and 14. The results revealed a significant down-regulation in the mRNA expression of SYP in the offspring born to diabetic animals at both P7 and P14 (P

The obstructive sleep apnea (OSA) is one of the most important sleep disorders characterized by obstruction of the respiratory tract and cessation in respiratory flow level. Currently, apnea diagnosis is mainly based on the Polysomnography (PSG) testing during sleeping hours, however, recording the entire signals during nights is a very costly, time-consuming and difficult task. The goal of this study is to provide and validate an automatic algorithm to analyze four PSG-recordings and detect the occurrence of sleep apnea by noninvasive features. Four PSG signals were extracted from oxygen saturation (SaO2), Transitional air flow (Air Flow), abdominal movements during breathing (Abdomen mov.) and movements of the chest (Thoracic mov.). We describe a fuzzy algorithm to compensate the imprecise information about the range of signal loss, regarding the expert opinions. Signal classification is implemented minute-by-minute and for 30 labeled samples of MIT/BIH data sets (acquired from PhysioNet). The obtained data from 18 apnea subjects (11 males and 7 females, mean age 43 years) were categorized in three output signals of apnea, hypopnea and normal breathing. The proposed algorithm shows proficiency in diagnosing OSA with acceptable sensitivity and specificity, respectively 86% and 87%.

Diabetes during pregnancy is associated with the deficits in balance and motor coordination and altered social behaviors in offspring. In the present study, we have investigated the effect of maternal diabetes and insulin treatment on the cerebellar volume and morphogenesis of the cerebellar cortex of rat neonates during the first two postnatal weeks. Sprague Dawley female rats were maintained diabetic from a week before pregnancy through parturition. At the end of pregnancy, the male offspring euthanized on postnatal days (P) 0, 7, and 14. Cavalieri's principle and fractionator methods were used to estimate the cerebellar volume, the thickness and the number of cells in the different layers of the cerebellar cortex. In spite of P0, there was a significant reduction in the cerebellar volume and the thickness of the external granule, molecular, and internal granule layers between the diabetic and the control animals. In diabetic group, the granular and purkinje cell densities were increased at P0. Moreover, the number of granular and purkinje cells in the cerebellum of diabetic neonates was reduced in comparison with the control group at P7 and P14. There were no significant differences in either the volume and thickness or the number of cells in the different layers of the cerebellar cortex between the insulin-treated diabetic group and controls. Our data indicate that diabetes in pregnancy disrupts the morphogenesis of cerebellar cortex. This dysmorphogenesis may be part of the cascade of events through which diabetes during pregnancy affects motor coordination and social behaviors in offspring.

Zolpidem is a non-benzodiazepine hypnotic drug used in short-term insomnia management. It is considered to be a safer drug than benzodiazepines. Zolpidem was initially considered to have lower incidences of dependence and tolerance than benzodiazepines. However, studies, have shown that zolpidem can lead to dependency. Although various cases of zolpidem dependence have been reported till date, but there is few published reports regards the medication to be used in the detoxification. We present a 21-year-old woman with history of zolpidem dependency. She had previously been using zolpidem for 3 years. She admitted and treated with replacement therapy with benzodiazepine. The equivalent diazepam was calculated (100 mg) and the replacement therapy consisted of 70 mg diazepam divided in doses of 20 mg in the morning, 20 mg midday, and 30 mg at night. A psychiatrist and a psychologist visited her in the morning and evening, respectively. Diazepam was tapered by 5 mg per day after 48 h; she was discharged when the dose was tapered to 60 mg per day with subsequent daily outpatient visits for continued dose tapering. Dose tapering was more gradual in comparison to the inpatient setting, namely by 5 mg every 5 days; overall, final tapering to a 20 mg daily dose took 60 days. She stopped diazepam usage after 65 days. She was followed-up for a 6-month period and urinary immunoassays ruled out benzodiazepine usage; all urinary tests were negative. This case of zolpidem dependency successfully treated by substitution with an equipotent, longer half-life benzodiazepine followed by tapering of benzodiazepine to discontinuation; this method can help in the prevention of seizures. Furthermore, it is advisable to manage replacement therapy in an inpatient setting. This method can help in the prevention of seizures. Meanwhile, it is advisable to manage replacement therapy in an inpatient setting.

Objectives To present long-term outcome and to identify predictors of seizure freedom after vagus nerve stimulation (VNS). Methods All patients who had undergone VNS implantation in the Epilepsy Centre Bethel were retrospectively reviewed. There were 144 patients who had undergone complete presurgical evaluation, including detailed clinical history, magnetic resonance imaging, and long-term video-EEG with ictal and interictal recordings. After implantation, all patients were examined at regular intervals of 4 weeks for 6–9 months. During this period the antiepileptic medication remained constant. All patients included in this study were followed up for a minimum of 2 years. Result Ten patients remained seizure-free for more than 1 year after VNS implantation (6.9%). Seizures improved in 89 patients (61.8%) but no changes were observed in 45 patients (31.3%). The following factors were significant in the univariate analysis: age at implantation, multifocal interictal epileptiform discharges, unilateral interictal epileptiform discharge, cortical dysgenesis, and psychomotor seizure. Stepwise multivariate analysis showed that unilateral interictal epileptiform discharges (IEDs), P =0.014, HR=0.112 (95% CIs, 0.019–0.642), cortical dysgenesis P =0.007, HR=0.065 (95% CIs, 0.009–0.481) and younger age at implantation P =0.026, HR=7.533 (95% CIs 1.28–44.50) were independent predictors of seizure freedom in the long-term follow-up. Conclusion VNS implantation may render patients with some forms of cortical dysgenesis (parietooccipital polymicrogyria, macrogyria) seizure-free. Patients with unilateral IEDs and earlier implantation achieved the most benefit from VNS.

Background: Occipital nerve stimulation is being used for various pain syndromes. Here, we expand its use for the treatment of refractory occipital pain after occipitocervical fusion. Case Description: We describe a case of occipital neuralgia in a 60-year-old man following posterior occipitocervical fusion. The maximum pain intensity was rated 9/10 on the visual analogue scale (VAS). Since pain proved to be refractory to analgetic medication, two quadripolar electrodes (Resume II, Medtronic) were implanted in the occipital region to stimulate the occipital nerve bilaterally. The patient experienced a dramatic response during test stimulation for 10 days with externalized electrodes, and a pacemaker (Synergy, Medtronic) was connected to the electrodes. While on chronic stimulation (bipolar 6 V, 210 μs, 130 Hz) improvement of pain was maintained, reflected by a decrease in the VAS score to 1/10 at 12 months of follow-up. Conclusion: Occipital nerve stimulation for medical refractory occipital neuralgia after occipitocervical fusion is an effective method expanding the indications for its use.

Meningiomas are usually slow-growing benign tumors, for which complete removal can be difficult and recurrence is an issue. In this study the relationship between pathodiagnostic parameters, histological grade, and MIB-1 monoclonal antibody expression in meningioma diagnosed over 10 years in Shohada Hospital, Tehran, was assessed. All cases were re-evaluated according to the latest World Health Organization (WHO) Classification. Between January 1997 and December 2006, a total of 4885 intracranial tumors were diagnosed at Shohada Hospital, 378 (7.74%) of which were meningiomas. All slides stained with hematoxylin and eosin were reviewed by two independent pathologists and all the diagnoses reconfirmed; histological anaplasia was classified according to the grading of the WHO Working Group 2000 as benign (Grade I), atypical with incipient signs of anaplasia (Grade II), or overtly anaplastic (Grade III). The mean age of patients with meningiomas was 49.11+/-12.99 years (range 6-78 years, median=50); females outnumbered males by a ratio of 1.7 to 1. Presenting symptoms were headache/vertigo (66.7%) and epilepsy (28.5%). Convexity meningiomas were most common, followed by meningiomas of the sphenoid ridge and cerebellopontine angle. There was no relationship between the location of the tumor and the histopathological features. The association between mitotic rate, increased cellularity, nucleo-cytoplasmic ratio, and sheet-like spreading was especially strong. Histopathological study of completely resected meningiomas showed that loss of architecture, frequent mitotic figures, a high cellularity, increased nucleo-cytoplasmic ratio, a prominent nucleolus, brain invasion, and necrosis were correlated with the grade of the meningiomas. Overall, the mitotic count was the most important marker for tumor grade.

Background Methadone is commonly administered for chronic pain relief and treatment of opioid dependence. Concurrent with its increased consumption, toxicities and fatalities have increased. One of the adverse effects of opioid analgesics, including methadone, is that of nephrotoxicity. Opioids can have an effect on renal function through several different mechanisms. Methods We searched common bibliographical databases for the terms methadone, toxicity, poisoning, kidney, renal, and nephrotoxicity and summarize our findings in this review. Results Methadone can have both direct and indirect effects on the kidney. These effects include rhabdomyolysis (leading to acute kidney injury), volumetric changes, renal lipidosis and amyloidosis, kidney growth during pregnancy, and kidney transplant rejection. Conclusion Improved understanding of the effects of methadone on kidney function can promote safer and more confident use of the drug.

Background No previous studies have examined marital status of patients with epilepsy and epilepsy-related factors on perceived and enacted stigmas in Iran. In the present study, marital status of patients with epilepsy (PWE’s) in Birjand city in the east of Iran was investigated. Methods A multicenter cross-sectional study was conducted to identify factors contributing to the marital status of PWE’s in a cross-sectional study with 471 participants. Diagnosis of epilepsy in participants (374 cases) was confirmed by at least two neurologists. Results Marriage rate of PWE’s was 27.3% (n = 102 patients) and divorce rate was 54.8% (n = 205 patients). Divorce rate in women was significantly higher than in men (62.6% vs. 46.4%; P 0.05). Conclusions The stigma of epilepsy has impacts on marital status of PWE’s. The PWE’s suffering from the enacted stigma of epilepsy are significantly more likely to get divorced in comparison with other patients.