Investigation of efficacy of asenapine on passive avoidance learning and memory and oxidative stress in animal model of seizure-induced with pentylenetetrazole

Asenapine (ASE) has been used for treatment of bipolar disorder. There is also evidence that it may be useful in the treatment of neurodegenerative disorders. In this regard, the efficacy of ASE in an experimental model of seizure and memory impairment caused by seizures in rats has been investigated in the present study. Seizures in male Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)), and the anticonvulsant effect of ASE (0.5 and 1 mg/kg, i.p.) was evaluated. The effect on memory was assessed using passive avoidance (PA) test in a shuttle box apparatus. After behavioral tests, the animals underwent deep anesthesia and were euthanized painlessly. Serum was isolated for oxidative stress assays (nitric oxide (NO), and glutathione (GSH)). Intraperitoneal injection of ASE decreased the mean number of myoclonic jerks and duration of generalized tonic clonic seizures (GTCS) and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, ASE caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that ASE was able to significantly increase GSH serum levels and significantly reduce NO serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of ASE in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway

The first reported case of a palpable and hypoechoic burned out testicular tumor

Primary extra gonadal germ cell tumors are rare.In case of the diagnosis of a midline retroperitoneal mass in a male, germ cell tumors should be taken into consideration. It is commonly accepted to consider  retroperitoneal germ cell tumors as the metastasis of a viable or burned out testicular tumor. In such casesorchiectomy should be performed since the burned out site in the testis could continue to harbor malignancy despite systemic chemotherapy.A 45-year-old man presented as an outpatient with complaints of back pain.He was diagnosed with a retroperitoneal mass and a palpable testis mass.Due to increased serum tumor markers and the testicular mass,he underwent radical orchiectomy. Pathological study revealed a burned out tumor.Following chemotherapy, retroperitoneal lymph node dissection(RPLND)was performed and despite the residual and enhanced retroperitoneal lymph nodes in his CT scan, none of the resected lymph nodes showed a viable tumor.However and despite the rising number of reports onthis disease, our case had adifferent presentation both at initial diagnosis and during follow up after chemotherapy.This is the first reported case of a palpable and hypoechoic burned out testicular tumor. Key words testis,burned out tumor,lymphadenectomy,tumo

The role of pineal gland on blood glucose in rabbit pups was born from hypoxic mothers

It has been showed that maternal hypoxia leads to postnatal dysfunctions such as abnormalities in endocrine function and also pineal gland has a variety of physiological functions. We aimed role of maternal hypoxia interaction with pineal gland effect on blood glucose of rabbit pups. We used fifteen healthy pregnant rabbits, medium breeds and divided them into three groups according thirds of pregnancy. In each group two rabbits were used as controls in which they inspired normal air. The remaining three rabbits as cases were subjected to hypoxia for 10 days during three thirds of pregnancy. Epiphysectomy operation was performed on 31st day of life at all of rabbit pups. Blood samples of rabbit pups were collected and plasma glucose was determined one day before and ten days after epiphysectomy. The mean values for plasma glucose concentrations were 106.71±8.00 and 114.21±13.04 mg/dl in case and control groups in all of thirds of pregnancy respectively before epiphysectomy. After epiphysectomy glucose concentration decreased at all of rabbit pups both case and control groups but this gradient was more in controls than cases. We suggested influence of epiphysis gland on plasma glucose concentration in rabbit pups

Lentinula edodes substrate formulation using multilayer perceptron-genetic algorithm: a critical production checkpoint

Shiitake (Lentinula edodes) is one of the most widely grown and consumed mushroom species worldwide. They are a potential source of food and medicine because they are rich in nutrients and contain various minerals, vitamins, essential macro- and micronutrients, and bioactive compounds. The reuse of agricultural and industrial residues is crucial from an ecological and economic perspective. In this study, the running length (RL) of L. edodes cultured on 64 substrate compositions obtained from different ratios of bagasse (B), wheat bran (WB), and beech sawdust (BS) was recorded at intervals of 5 days after cultivation until the 40th day. Multilayer perceptron-genetic algorithm (MLP-GA), multiple linear regression, stepwise regression, principal component regression, ordinary least squares regression, and partial least squares regression were used to predict and optimize the RL and running rate (RR) of L. edodes. The statistical values showed higher prediction accuracies of the MLP-GA models (92% and 97%, respectively) compared with those of the regression models (52% and 71%, respectively) for RL and RR. The high degree of fit between the forecasted and actual values of the RL and RR of L. edodes confirmed the superior performance of the developed MLP-GA models. An optimization analysis on the established MLP-GA models showed that a substrate containing 15.1% B, 45.1% WB, and 10.16% BS and a running time of 28 days and 10 h could result in the maximum L. edodes RL (10.69 cm). Moreover, the highest RR of L. edodes (0.44 cm d−1) could be obtained by a substrate containing 30.7% B, 90.4% WB, and 0.0% BS. MLP-GA was observed to be an effective method for predicting and consequently selecting the best substrate composition for the maximal RL and RR of L. edodes

Latitude, Vitamin D, Melatonin, and Gut Microbiota Act in Concert to Initiate Multiple Sclerosis: A New Mechanistic Pathway

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the etiology of MS is still largely unknown, scientists believe that the interaction of several endogenous and exogenous factors may be involved in this disease. Epidemiologists have seen an increased prevalence of MS in countries at high latitudes, where the sunlight is limited and where the populations have vitamin D deficiency and high melatonin levels. Although the functions and synthesis of vitamin D and melatonin are contrary to each other, both are involved in the immune system. While melatonin synthesis is affected by light, vitamin D deficiency may be involved in melatonin secretion. On the other hand, vitamin D deficiency reduces intestinal calcium absorption leading to gut stasis and subsequently increasing gut permeability. The latter allows gut microbiota to transfer more endotoxins such as lipopolysaccharides (LPS) into the blood. LPS stimulates the production of inflammatory cytokines within the CNS, especially the pineal gland. This review summarizes the current findings on the correlation between latitude, sunlight and vitamin D, and details their effects on intestinal calcium absorption, gut microbiota and neuroinflammatory mediators in MS. We also propose a new mechanistic pathway for the initiation of MS

Culture-based diversity of endophytic fungi of three species of Ferula grown in Iran

A total of 1,348 endophytic fungal strains were isolated from Ferula ovina, F. galbaniflua, and F. persica. They included Eurotiales (16 species), Pleosporales (11 species), Botryosphaeriales (1 species), Cladosporiales (2 species), Helotiales (6 species), Hypocreales (31 species), Sordariales (7 species), Glomerellales (2 species), and Polyporales (1 species). F. ovina had the richest species composition of endophytic fungi, and the endophytic fungi were most abundant in their roots compared to shoots. Chao, Margalef, Shannon, Simpson, Berger–Parker, Menhinick, and Camargo indices showed that F. ovina roots had the most endophytic fungal species. The frequency distribution of fungal species isolated from Ferula spp. fell into the log-series model, and F. ovina roots had the highest Fisher alpha. The dominance indices showed that there are no dominant species in the endophytic fungal community isolated from Ferula spp., indicating community stability. Evenness values were 0.69, 0.90, 0.94, and 0.57 for endophytic fungi isolated from F. ovina roots, F. ovina shoots, F. galbaniflua roots, and F. persica roots, respectively, indicating a species distribution that tends toward evenness. The fungal species community isolated from each of F. ovina roots, F. ovina shoots, F. galbaniflua roots, and F. persica roots was a diverse species group originating from a homogeneous habitat. Their distribution followed a log-normal distribution, suggesting that the interactions of numerous independent environmental factors multiplicatively control species abundances. Principal component analysis showed that the highest species diversity and dominance were observed in the endophytic fungal community isolated from F. ovina and F. persica roots, respectively

Melatonin Therapy Modulates Cerebral Metabolism and Enhances Remyelination by Increasing PDK4 in a Mouse Model of Multiple Sclerosis

Metabolic disturbances have been implicated in demyelinating diseases including multiple sclerosis (MS). Melatonin, a naturally occurring hormone, has emerged as a potent neuroprotective candidate to reduce myelin loss and improve MS outcomes. In this study, we evaluated the effect of melatonin, at both physiological and pharmacological doses, on oligodendrocytes metabolism in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Results showed that melatonin decreased neurological disability scores and enhanced remyelination, significantly increasing myelin protein levels including MBP, MOG, and MOBP. In addition, melatonin attenuated inflammation by reducing pro-inflammatory cytokines (IL-1β and TNF-α) and increasing anti-inflammatory cytokines (IL-4 and IL-10). Moreover, melatonin significantly increased brain concentrations of lactate, N-acetylaspartate (NAA), and 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR). Pyruvate dehydrogenase kinase-4 (PDK-4) mRNA and protein expression levels were also increased in melatonin-treated, compared to untreated EAE mice. However, melatonin significantly inhibited active and total pyruvate dehydrogenase complex (PDC), an enzyme under the control of PDK4. In summary, although PDC activity was reduced by melatonin, it caused a reduction in inflammatory mediators while stimulating oligodendrogenesis, suggesting that oligodendrocytes are forced to use an alternative pathway to synthesize fatty acids for remyelination. We propose that combining melatonin and PDK inhibitors may provide greater benefits for MS patients than the use of melatonin therapy alone

Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding: Bill & Melinda Gates Foundation

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

The Global Burden of Diseases, Injuries and Risk Factors 2017 includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data.; We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs s1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury