Neurosarcoidosis: An under-diagnosed cause of myelopathy.

Sarcoidosis is a granulomatous disorder with multi-organ involvement, and etiology still remains unknown. Neurosarcoidosis is the involvement of the nervous system in sarcoidosis. Spinal cord involvement is usually intra-dural, but extra-dural involvement can also occur. Here, we report a case of 30 years old lady presenting with subacute onset paraparesis with bladder and bowel involvement, which was finally diagnosed as sarcoidosis-associated myelopathy with the longitudinally extensive transverse myelitis (LETM) phenotype.

Data library of irradiated fuel salt and off-gas tank composition for a molten salt reactor concept produced with Serpent2 and SOURCES 4C codes.

This paper describes the methodology used to create a fuel data library comprising safeguards-relevant quantities that may be useful for verification of spent nuclear fuel (SNF) produced by simulating a concept Molten Salt Reactor (MSR). The Monte-Carlo particle transport code, Serpent2 and the calculation code SOURCES 4C were used to compile this fuel data library. The data library is based on the Compact Molten Salt Reactor (CMSR) concept being developed by Seaborg Technologies (based in Copenhagen, Denmark). The library includes data such as nuclide mass densities for a total of 1398 nuclides (in g/cm3), as well as total decay heat production (denoted by suffix the 'TOT_DH') in Watts, total gamma photon emission rates (denoted by the suffix 'TOT_GS') in photos per second, and the total activity (denoted by suffix 'TOT_A') in Becquerel. Lastly, the data also includes total neutron emission rates from 1) spontaneous fission (denoted by 'SF' and reported in neutrons per second per cm3), and 2) (ɑ, n) reactions (denoted by 'AN' and reported in neutrons per second per cm3) for the fuel salt. These quantities are reported for a range of burnup-initial enrichment-cooling time (or collectively known as, BIC) parameters. The resulting fuel data library is an extension of a previously published data library for the same reactor concept but with one significant change. The current library is based on a more realistic model of the CMSR involving movement of gaseous and volatile fission products (GFP and VFP) from the core via an Off-Gas System (OGS). The dataset is made available for public use in a compressed binary format as an HDF5 (or Hierarchical Data Format) file that can be parsed using data analysis tools such as Pandas.

Irradiated fuel salt data library for a molten salt reactor produced with Serpent2 and SOURCES 4C codes.

This paper describes the creation and description of a nuclear fuel isotopics dataset for irradiated fuel salt from a Molten Salt Reactor (MSR). The dataset has been created using simulations carried out using the Monte-Carlo particle transport code, Serpent 2.1.32 (released February 24, 2021) and the calculation code SOURCES 4C (released October 09, 2002) for computing properties of irradiated molten fuel salt. The dataset comprises isotopic mass densities of 1362 isotopes (including fission products and major and minor actinides) and their corresponding contributions to decay heat, gamma activity, and spontaneous fission rates computed by Serpent 2.1.32 as well as overall neutron emission rates from spontaneous fission and (ɑ, n) reactions computed by SOURCES 4C. These quantities are computed for a model MSR core utilizing a full-core 3D model of the Seaborg Compact Molten Salt Reactor (CMSR). The dataset spans a wide range of values of burnup (BU), initial enrichment (IE) and cooling time (CT) over which the above-mentioned quantities are reported. The structure of the dataset includes isotopic mass densities (in g/cm3), followed by isotope-wise contributions to decay heat (denoted by suffix '_DH' and reported in Watts), gamma photon emission rates (denoted by suffix '_GS' and reported photons per second), and spontaneous fission rates (denoted by suffix '_SF' and reported in fissions per second). In addition to these columns, the data also includes total neutron emission rates from 1) spontaneous fission (denoted by 'SF' and reported in neutrons per second per cm3), and 2) (ɑ, n) reactions (denoted by 'AN' and reported in neutrons per second per cm3). In total, the dataset has 310,575 rows of different combinations of fuel burnup, initial enrichment, and cooling time (BIC) values spanning the realistic possible range of these parameters. The dataset is made available for public use in a comma-separated value file that can be easily read using one of the numerous popular data analysis tools such as NumPy or Pandas.

Aortic valve surgery in the pediatric population: pathophysiology, clinical features and management.

There are several conditions where the function of the aortic valve can be compromised in the pediatric population. The aortic valve is composed of three leaflets which are thin and mobile and are attached to the aortic sinuses. Each leaflet is made up of connective tissue, forming a highly ordered network of extracellular matrix components. Together, this enables the aortic valve to open and close more than 100,000 times throughout the day. However, there are conditions where the structure of the aortic valve can be compromised resulting in its function being affected. Conditions such as congenital valvular aortic stenosis and abnormal valve morphology including bicuspid valves often necessitate intervention to improve symptoms and quality of life in children. Other conditions which result in requiring surgical intervention include infective endocarditis and trauma. In this article, we present the common forms of aortic valve disease in the pediatric population and the clinical presentation and pathophysiology of these. We also discuss the range of management options including medical management and percutaneous intervention. Surgical interventions such as Aortic annular enlargement techniques, the Ross procedure and the Ozaki procedure will also be discussed. The effectiveness, complications and long-term outcomes associated with these methods will be explored.

Outcomes Post-Nick's Aortic Root Enlargement Technique: Single-Center Experience.

BACKGROUND: Different techniques for aortic root enlargement (ARE) have been reported in the literature. Each technique comes with its own advantages and disadvantages. We report our outcomes of Nick's technique for ARE. METHODS: A single-center retrospective data analysis of 31 patients was performed. Patients were operated between May 2015 and November 2017 at Assuit University Heart Hospital, Assuit, Egypt. RESULTS: The median cardiopulmonary bypass time was 125 minutes (range: 90.0-160.0 minutes), with 90 minutes of cross-clamp (range: 60.0-110.0 minutes). Altogether 59% of the patients had mixed aortic valve diseases. Median intensive care unit and total hospital stay were 2 and 5 days, respectively. Patient-prosthesis mismatch was reported in one patient only (3.25%). Two patients died within 30 days. Median pressure gradient across the aortic valve was 20 mm Hg at 3 years of follow-up. CONCLUSION: The benefits of Nick's technique for ARE can be demonstrated in populations with younger patients and complicated pathology. Further research is required in larger patient populations.

Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India.

Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate-severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration.

Sleep, sleep homeostasis and arousal disturbances in alcoholism.

The effects of alcohol on human sleep were first described almost 70 years ago. Since then, accumulating evidences suggest that alcohol intake at bed time immediately induces sleep [reduces the time to fall asleep (sleep onset latency), and consolidates and enhances the quality (delta power) and the quantity of sleep]. Such potent sleep promoting activity makes alcohol as one of the most commonly used "over the counter" sleep aid. However, the somnogenic effects, after alcohol intake, slowly wane off and often followed by sleep disruptions during the rest of the night. Repeated use of alcohol leads to the development of rapid tolerance resulting into an alcohol abuse. Moreover, chronic and excessive alcohol intake leads to the development of alcohol use disorder (AUD). Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceed $18 billion. Thus, although alcohol associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, a conceptual framework and clinical research focused on understanding the relationship between alcohol and sleep is first described. In the next section, our new and exciting preclinical studies, to understand the cellular and molecular mechanism of how acute and chronic alcohol affects sleep, are described. In the end, based on observations from our recent findings and related literature, opportunities for the development of innovative strategies to prevent and treat AUD are proposed.

Activation of dopamine D2 receptors in the medial shell region of the nucleus accumbens increases Per1 expression to enhance alcohol consumption.

Circadian genes, including Per1, in the medial shell region of nucleus accumbens (mNAcSh), regulate binge alcohol consumption. However, the upstream mechanism regulating circadian genes-induced alcohol consumption is not known. Since activation of dopamine D2 receptors (D2R) increases Per1 gene expression, we hypothesised that local infusion of quinpirole, a D2R agonist, by increasing Per1 gene expression in the mNAcSh, will increase binge alcohol consumption in mice. We performed two experiments on male C57BL/6J mice, instrumented with bilateral guide cannulas above the mNAcSh, and exposed to a 4-day drinking-in-dark (DID) paradigm. The first experiment determined the effects of bilateral infusion of quinpirole (100 ng/300 nl/site) or DMSO (Vehicle group) in the mNAcSh on Per1 gene expression and alcohol consumption. The second experiment determined the effect of antisense-induced downregulation of Per1 in the mNAcSh on the quinpirole-induced increase in alcohol consumption. Control experiments were performed by exposing the animals to sucrose (10% w/v). After the experiment, animals were euthanised, brains removed and processed for localisation of injection sites and analysis of Per1 gene expression in the mNAcSh. As compared with the DMSO, local bilateral infusion of quinpirole significantly increased the expression of Per1 in the mNAcSh along with an increase in the amount of alcohol consumed in mice exposed to DID paradigm. In addition, local antisense-induced downregulation of Per1 significantly attenuated the effects of intro-accumbal infusion of quinpirole on alcohol consumption. Our results suggest that Per1 in the mNAcSh mediates D2R activation-induced increase in alcohol consumption.

Antisense-induced downregulation of major circadian genes modulates the expression of histone deacetylase-2 (HDAC-2) and CREB-binding protein (CBP) in the medial shell region of nucleus accumbens of mice exposed to chronic excessive alcohol consumption.

Circadian genes in the medial accumbal shell (mNAcSh) region regulate binge alcohol consumption. Here, we investigated if antisense-induced knockdown of major circadian genes (Per1, Per2, and NPAS2) in the mNAcSh of mice exposed to intermittent access two-bottle choice (IA2BC) paradigm modulates the expression of histone deacetylase-2 (HDAC-2) and CREB-binding protein (CBP), key epigenetic modifiers associated with withdrawal-associated behaviors such as anxiety. Adult male C57BL/6J mice (N = 28), surgically implanted with bilateral guide cannulas above the mNAcSh, were chronically (4 weeks) exposed to alcohol (20% v/v) or saccharin (0.03%) via IA2BC paradigm. In the fourth week, a mixture of antisense (AS-ODNs; N = 14/group) or nonsense (NS-ODNs; N = 14/group) oligodeoxynucleotides against circadian genes were bilaterally infused into the mNAcSh. Subsequently, alcohol/saccharin consumption and preference were measured followed by euthanization of animals and verification of microinjection sites by visual inspection and the expression of HDAC-2 and CBP by using RT-PCR along with the verification of antisense-induced downregulation of circadian genes in the mNAcSh. As compared with NS-ODNs, AS-ODNs infusion significantly attenuated the alcohol-induced increase in HDAC-2 and reduction in CBP expression in the mNAcSh along with a significant reduction in alcohol consumption and preference. No significant effect was observed on either saccharin consumption or preference. Our results suggest that circadian genes in the mNAcSh may have a causal to play in mediating epigenetic changes observed after chronic alcohol consumption.

Mitral valve paravalvular leaks: Comprehensive review of literature.

BACKGROUND: Mitral paravalvular leaks (mPVL) are a recognized complication for patients with mitral valve prostheses. Although clinically insignificant for many patients, it may pose life-threatening haemolysis and regurgitation-induced heart failure, and so clinicians should have a high index of suspicion in the presence of new symptoms. AIMS: This review discusses the pathogenesis, clinical features, diagnosis, imaging and treatment of mPVLs. METHODS: A comprehensive literature search was performed using PubMed, EMBASE, Cochrane database, Google Scholar and Ovid. Search terms used included "mitral valve paravalvular leak," "transthoracic echocardiography," "2D transoesophageal echocardiography," "3D transoesophageal echocardiography," "cardiac computed tomography," (CT) "cardiac magnetic resonance imaging," "intracardiac echocardiography," "cinefluoroscopy," "fluoroscopy," and "percutaneous closure." RESULTS: All patients with mPVLs should undergo regular full evaluation, including patient history, physical examination, laboratory work-up, imaging, and referral, if necessary. Echocardiography is fundamental to the diagnosis, and is augmented with cardiac magnetic resonance imaging, cardiac computerized tomography and fluoroscopy for further characterization and procedural planning amongst the structural heart team. CONCLUSION: The prevalence of mPVL is expected to increase proportionally to the growing number of surgical and transcatheter valve replacements conducted in the ageing population. Multimodal imaging is instrumental in guiding diagnostic and therapeutic strategies when managing mPVLs. Advances in imaging and capabilities of transcather devices will prompt growing uptake of percutaneous treatment over conventional, higher-risk surgery for mPVL management.

Antisense-induced knockdown of cAMP response element-binding protein downregulates Per1 gene expression in the shell region of nucleus accumbens resulting in reduced alcohol consumption in mice.

INTRODUCTION: We recently showed that circadian genes expressed in the shell region of nucleus accumbens (NAcSh) play a key role in alcohol consumption, though, the molecular mechanism of those effects is unclear. Because CREB-binding protein (CBP) promotes Per1 gene expression, we hypothesized that alcohol consumption would increase CBP expression in the NAcSh and antisense-induced knockdown of CBP would reduce Per1 expression and result in a reduction in alcohol consumption. METHODS: To test our hypothesis, we performed two experiments. The Drinking-in-the-dark (DID) paradigm was used to evaluate alcohol consumption in male C57BL/6J mice. In Experiment 1 we examined the effects of alcohol consumption on CBP gene expression in the NAcSh. Control animals were exposed to, sucrose [10% (w/v) taste and calorie] and water (consummatory behavior). In Experiment 2 examined the effects of CBP gene silencing on the expression of the Per1 gene in the NAcSh and alcohol consumption in mice exposed to alcohol using the DID paradigm. CBP gene silencing was achieved by local infusion of two doses of either CBP antisense oligodeoxynucleotides (AS-ODNs; Antisense group) or nonsense ODNs (NS-ODNs; Nonsense group) bilaterally microinjected into the NAcSh within 24 h before alcohol consumption on Day 4 of the DID paradigm. The microinfusion sites were verified by cresyl violet staining. RESULTS: Compared to sucrose, alcohol consumption, under the DID paradigm, significantly increased the expression of CBP in the NAcSh. Compared to Controls, bilateral infusion of CBP AS-ODNs significantly reduced the expression of Per1 in the NAcSh and alcohol consumption without affecting the amount of sucrose consumed. CONCLUSIONS: Our results suggest that CBP is an upstream regulator of Per1 expression in the NAcSh and may act via Per1 to modulate alcohol consumption.

Health Inequalities During COVID-19 and Their Effects on Morbidity and Mortality.

Inequalities in health have existed for many decades and have led to unjust consequences in morbidity and mortality. These have become even more apparent during the COVID-19 pandemic with individuals from black and minority ethnic groups, poorer socioeconomic backgrounds, urban and rurally deprived locations, and vulnerable groups of society suffering the full force of its effects. This review is highlighting the current disparities that exist within different societies, that subsequently demonstrate COVID-19, does in fact, discriminate against disadvantaged individuals. Also explored in detail are the measures that can and should be taken to improve equality and provide equitable distribution of healthcare resources amongst underprivileged communities.

Are open-source approaches the most efficient way forward for COVID-19 drug discovery?

Introduction: The COVID-19 pandemic has catalyzed the production of potential antivirals and vaccines from research organizations across the globe. The initial step for all drug discovery models is the identification of suitable targets. One approach organizations may take to tackle this involves issuing raw data publicly for collaboration with other organizations in order to spark discussion, collectively experiment and stay up to date with advances in scientific knowledge. Areas covered: Numerous organizations have released genomic data, amongst other tools, for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and this has led to the development of growing datasets of knowledge for continued collaboration amongst different scientific communities. A different technique employs a more closed, market-driven method in order to stay ahead financially in the race for developing a suitable antiviral or vaccine. The latter allows sustained motivation for company ambitions and progress has been made toward clinical trials for potential drugs. Expert opinion: A case can be made for both open and closed drug discovery models; however, due to the rapidly evolving nature of this deadly virus, organizations should collate their research and support one another to ensure satisfactory treatment can be approved in a timely manner.

Sudden cardiac death in children with congenital heart disease: a critical review of the literature.

Sudden cardiac death is an uncommon but yet catastrophic event, which can occur in neonates and young children. Although extensive research has been carried out assessing the underlying causes, there still remains a degree of uncertainty around this area. Congenital heart disease (CHD) is one known cause of sudden cardiac death in children, the aetiology of which embraces virally induced mechanisms, genetic susceptibility, drug-induced, and maternal factors. Screening tools and investigations including electrocardiograms and echocardiograms alongside a concise history taking and physical examination can be used to identify the potential cardiovascular risk factors of sudden death. This review has comprehensively studied the causes and risk factors for sudden cardiac death in children with CHD and provides a collation and summary of the evidence available so far underpinning the complex link between the two. Moreover, current screening and prevention methods are discussed in detail in order to increase awareness and understanding of how we can improve patient outcomes.

Pharmacological evaluation of the efficacy of Dysoxylum binectariferum stem bark and its active constituent rohitukine in regulation of dyslipidemia in rats.

The antidyslipidemic effect of the ethanolic extract of Dysoxylum binectariferum stem bark and its major active constituent rohitukine was evaluated in a high fat diet (HFD)-fed dyslipidemic rat model. Chronic feeding of ethanolic extract (200 mg/kg) in HFD-fed rats showed significant lipid lowering activity. The bioassay guided fractionation of ethanolic extract resulted in the identification of known alkaloid rohitukine as major active constituent. Rohitukine (50 mg/kg) significantly decreased the plasma levels of total cholesterol (24 %), phospholipids (25 %), triglycerides (27 %), very low density lipoprotein (27 %) and low density lipoprotein (32 %) accompanied with an increase in high density lipoprotein (21 %). The present study demonstrated that ethanolic extract of Dysoxylum binectariferum stem bark and its major constituent rohitukine both have antidyslipidemic as well as antioxidant potentials. The antidyslipidemic activity of rohitukine can be correlated to its effect on enzymes involved in lipid metabolism.

Influence of season and sex on hemato-biochemical traits in adult turkeys under arid tropical environment.

AIM: The objective of this study was to evaluate the effect of season and sex on hemato-biochemical parameters of turkey (Meleagris gallopavo) in the arid tropical environment. MATERIALS AND METHODS: The experiment was conducted on 20-week old turkeys consisting of 20 males and 20 females. Blood was collected from all turkeys during January and May. Hemoglobin (Hb), red blood cell (RBC), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were estimated in whole blood and glucose, protein, albumin, globulin, A/G ratio, calcium, phosphorus, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in serum. RESULT: Season has significant (p<0.05) effect on Hb concentration, RBC, and PCV in both male and female. Male has significantly higher (p<0.05) Hb concentration, RBC, and PCV. There is no significant effect of sex, and season was observed on MCV, MCH, and MCHC. Glucose, protein, albumin, globulin, and A/G ratio were significantly (p<0.05) affected by season and sex. AST and ALT were significantly (p<0.05) affected by season in both sexes. There is no significant difference was recorded on calcium, phosphorus due to season and sex. CONCLUSION: Under arid tropical environment, turkey hemato-biochemical parameters are influenced by both sex and season.

Viral Hepatitis in Pregnancy--A study of its Effect on Maternal and Foetal Outcome.

BACKGROUND AND AIMS: The outcome of Hepatitis during pregnancy has been observed to be widely different by various authors, ranging from the benign to fatal. A poor outcome has increasingly been observed in pregnant women suffering from Hepatitis in Central India. Hence, this study was undertaken to study the incidence, causative organisms and chief prognostic factors affecting the outcome of viral hepatitis in pregnant women. METHODS: Sixty-eight pregnant women reporting to the hospital with jaundice were enrolled as cases and their Haematological, Biochemical and Viral profiles were studied. Sixteen non- pregnant women were enrolled as controls and a similar workup was done. A comparison was done between the two groups We also divided the cases into two groups--survivors and non- survivors and tried to find out the factors predicting mortality. The unpaired student t test and chi square test were used to find out whether the differences were statistically significant. RESULTS: Viral Hepatitis in pregnancy caused a very high maternal mortality (19.1%) and foetal wastage (42.6%). Hepatitis E virus was the commonest causative organism (77.9%) responsible for viral hepatitis during pregnancy. It also caused the highest maternal mortality due to fulminant hepatic failure. Maternal mortality was significantly higher in those women presenting with features of encephalopathy, SIRS, high bilirubin levels and prolonged prothrombin time. Vertical transmission was noted in Hepatitis B and E. CONCLUSIONS: Hepatitis E is the chief causative organism causing fulminant hepatic failure in pregnant women in Central India. It lead to very high rates of maternal mortality and foetal wastage.

Cytoprotective and Anti-secretory Effects of Azadiradione Isolated from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat Models.

Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in-vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+-ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration.