bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nod2 Deficiency Augments Th17 Responses and Exacerbates Autoimmune Arthritis
Authors: Napier Ruth J. , Lee Ellen J. , Vance Emily E. , Snow Paige E. , Samson Kimberly A. , Dawson Clare E. , Moran Amy E. , Stenzel Peter , Davey Michael P. , Sakaguchi Shimon , Rosenzweig Holly L. 
Published: August 2018

Abstract
Arthritis in a genetically susceptible SKG strain of mice models a theoretical paradigm wherein autoimmune arthritis arises because of interplay between preexisting autoreactive T cells and environmental stimuli. SKG mice have a point mutation in ZAP-70 that results in attenuated TCR signaling, altered thymic selection, and spontaneous production of autoreactive T cells that cause arthritis following exposure to microbial β-glucans. In this study, we identify Nod2, an innate immune receptor, as a critical suppressor of arthritis in SKG mice. SKG mice deficient in Nod2 (Nod2−/−SKG) developed a dramatically exacerbated form of arthritis, which was independent of sex and microbiota, but required the skg mutation in T cells. Worsened arthritis in Nod2−/−SKG mice was accompanied by expansion of Th17 cells, which to some measure coproduced TNF, GM-CSF, and IL-22, along with elevated IL-17A levels within joint synovial fluid. Importantly, neutralization of IL-17A mitigated arthritis in Nod2−/−SKG mice, indicating that Nod2-mediated protection occurs through suppression of the Th17 response. Nod2 deficiency did not alter regulatory T cell development or function. Instead, Nod2 deficiency resulted in an enhanced fundamental ability of SKG CD4+ T cells (from naive mice) to produce increased levels of IL-17 and to passively transfer arthritis to lymphopenic recipients on a single-cell level. These data reveal a previously unconsidered role for T cell–intrinsic Nod2 as an endogenous negative regulator of Th17 responses and arthritogenic T cells. Based on our findings, future studies aimed at understanding a negative regulatory function of Nod2 within autoreactive T cells could provide novel therapeutic strategies for treatment of patients with arthritis.
Spectrum of clinicohematological profile and its correlation with average parasite density in visceral leishmaniasis
Authors: Kumar Vijay , Agarwal Poojan , Marwah Sadhna , Nigam A. S. , Tiwari Awantika 
Published: August 2018

Background:Leishmaniasis is the prevalent in tropical and subtropical regions of the world. Demonstration of Leishman-Donovan (LD) bodies in the bone marrow aspirates (BMA) is vital to diagnosis of visceral leishmaniasis (VL). In the present study, we studied the clinicohematological parameters encountered in VL and correlated them with parasite load on BMA.Methods:Retrospective analysis over 3 years was done; clinical details, biochemical profile, complete hemogram with peripheral smear findings, and BMA smears were reviewed and average parasite density (APD) calculated in each case. Multivariate analysis and tests of significance were applied.Results:The study included 28 patients. Splenomegaly showed a positive trend with APD. rK39 antigen detection test was 100% positive in select cases. A strong negative correlation was observed between albumin to globulin ratio and grade of APD. BMA revealed hemophagocytosis (HPS) in 78.57% cases and it had a significant strong correlation with APD (P= 0.014). A significant correlation was also observed between APD and bone marrow plasma cell percentage (P= 0.01). LD bodies were noted in unusual locations such as within myelocytes (14.2%), plasma cells (7.1%), and megakaryocytes (10.7%).Conclusion:HPS and bone marrow plasmacytosis were two statistically significant findings, which showed positive correlation with parasite load. The presence of these two findings should prompt hematopathologists for more focused search of hemoparasites in BMA to arrive at a definitive diagnosis. This will avoid unnecessary workups and improve the prognosis. To the best of our knowledge, a statistical correlation between APD and clinicohematological parameters has never been previously studied.
Development of immunodetection system for botulinum neurotoxin serotype E
Authors: Sarita R. , Ponmariappan Sarkaraisamy , Sharma Arti , Kamboj Dev Vrat , Jain A. K. 
Published: August 2018

Background & objectives:
Botulism, a potentially fatal paralytic illness, is caused by the botulinum neurotoxins (BoNTs) secreted by Clostridium botulinum. It is an obligate anaerobic, Gram-positive, spore-forming bacterium. BoNTs are classified into seven serotypes based on the serological properties. Among these seven serotypes, A, B, E and, rarely, F are responsible for human botulism. The present study was undertaken to develop an enzyme-linked immunosorbent assay (ELISA)-based detection system for the detection of BoNT/E.

Methods:
The synthetic gene coding the light chain of BoNT serotype E (BoNT/E LC) was constructed using the polymerase chain reaction primer overlapping method, cloned into pQE30UA vector and then transformed into Escherichia coli M15 host cells. Recombinant protein expression was optimized using different concentrations of isopropyl-β-D-1-thiogalactopyranoside (IPTG), different temperature and the rBoNT/E LC protein was purified in native conditions using affinity column chromatography. The purified recombinant protein was checked by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and further confirmed by western blot and matrix-assisted laser desorption ionization-tandem time-of-flight (MALDI-TOF). Polyclonal antibodies were generated against rBoNT/E LC using Freund's adjuvant in BALB/c mice and rabbit. Sandwich ELISA was optimized for the detection of rBoNT/E LC and native crude BoNT/E, and food matrix interference was tested. The developed antibodies were further evaluated for their specificity/cross-reactivity with BoNT serotypes and other bacterial toxins.

Results:
BoNT/E LC was successfully cloned, and the maximum expression was achieved in 16 h of post-induction using 0.5 mM IPTG concentration at 25°C. Polyclonal antibodies were generated in BALB/c mice and rabbit and the antibody titre was raised up to 128,000 after the 2nd booster dose. The developed polyclonal antibodies were highly specific and sensitive with a detection limit about 50 ng/ml for rBoNT/E LC and 2.5×103 MLD50 of native crude BoNT/E at a dilution of 1:3000 of mouse (capturing) and rabbit (revealing) antibodies. Further, different liquid, semisolid and solid food matrices were tested, and rBoNT/E LC was detected in almost all food samples, but different levels of interference were detected in different food matrices.

Interpretation & conclusions:
There is no immune detection system available commercially in India to detect botulism. The developed system might be useful for the detection of botulinum toxin in food and clinical samples. Further work is in progress.
Therapeutic implications of nano-encapsulated rifabutin, azithromycin & ethambutol against experimental Mycobacterium avium infection in mice
Authors: Grewal Tapinder Kaur , Majeed Shahnawaz , Sharma Sadhna 
Published: August 2018

Background & objectives:

Mycobacterium avium causes atypical infection in both immunocompetent and immunocompromised individuals. Conventional chemotherapy for M. avium infection is not efficient due to lengthy course of treatment and drug-associated toxic side effects. The present study was aimed at reducing dosing frequency of antimicrobial regimen consisting of azithromycin (AZM), rifabutin (RBT) and ethambutol (EMB) by encapsulation of drugs in nanoparticles (NPs) in experimental M. avium infection in mice.

Methods:
Poly (DL-lactide-co-glycolide) NPs containing anti-M. avium drugs were prepared, characterized and studied for their pharmacokinetics and pharmacodynamics parameters. Drug-loaded NPs were further analyzed for their therapeutic efficacy against experimental M. avium infection in mice.

Results:
Drug-loaded NPs were of size 227.3±16.4 for RBT, 334.35±11.7 for AZM and 509.85±20.5 for EMB with smooth surface morphology and negative zeta potential. AZM, EMB and RBT from NPs were detectable for 6, 4 and 5 days, respectively, in the mice plasma, whereas free drugs were cleared from mice circulation within 24 h. Chemotherapeutic effects of weekly administered drug-loaded NPs were equivalent to daily administered free drugs.

Interpretation & conclusions:
Our findings showed that NPs gave sustained release of drugs inside plasma and organs, thus decreasing dosage frequency, and their weekly dosage had therapeutic efficacy equivalent to daily dosage of free drugs.
S961, a biosynthetic insulin receptor antagonist, downregulates insulin receptor expression & suppresses the growth of breast cancer cells
Authors: Sharma Prateek , Kumar Sanjeev 
Published: August 2018

Background & objectives:
Insulin resistance associated with hyperinsulinaemia and overexpression of insulin receptors (IRs) have been intricately linked to the pathogenesis and treatment outcomes of the breast carcinoma. Studies have revealed that upregulated expression of IRs in breast cancer pathogenesis regulates several aspects of the malignant phenotype, including cell proliferation and metastasis. This study was aimed to investigate the pivotal role of an IR antagonist S961 on IR signalling and other biological parameters in MCF-7, MDA-MB-231 and T47D cell lines.

Methods:
The effect of human insulin and S961 on growth, proliferation rate and clonogenic potential of breast cancer cells was evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay and clonogenic assay. The mRNA expression of IR isoforms (IR-A and IR-B) was measured in the breast carcinoma cells using quantitative PCR.

Results:
The study revealed that breast cancer cells predominantly expressed IR-A isoform and showed extensive growth and proliferation owing to IR overexpression. It was found that S961 downregulated the IRs (IR-A and IR-B) with nanomolar dose and efficiently blocked expression of IRs even in the presence of insulin. IR mRNA expression levels were significantly downregulated in the continued presence of S961. S961 also inhibited cellular proliferation and colony formation in breast tumour cells.

Interpretation & conclusions:
IR antagonist, S961 showed distinct antagonism in vitro and appeared to be a powerful therapeutic modality that might provide insight into the pathogenesis of impaired IR signalling.
Feasibility and Utility of Tele-Neurorehabilitation Service in India: Experience from a Quaternary Center
Authors: Khanna Meeka , Gowda Guru S. , Bagevadi Virupaksha Irappa , Gupta Anupam , Kulkarni Karishma , Shyam R. P. S. , Basavaraju Vinay , Ramesh Manjunatha B. , N. Sashidhara H. , Manjunatha Narayana , Channaveerachari Naveen Kumar , Math Suresh Bada 
Published: August 2018

ABSTRACT
Background: Neurological rehabilitation service in developing countries like India is a great challenge in view of limited resources and manpower. Currently, neurological rehabilitation with a multidisciplinary team is limited to a few major cities in the country. Tele-neurorehabilitation (TNR) is considered as an alternative and innovative approach in health care. It connects the needy patients with the health-care providers with minimum inconvenience and yields cost-effective health care. Aim: The aim of this study was to study the socioclinical parameters, feasibility, and utility of TNR services in India. Methodology: A retrospective file review of TNR consultations provided through Telemedicine Center at a quaternary hospital-based research center in south India between August 2012 and January 2016. Results: A total of 37 consultations were provided to the patients belonging to four districts of Karnataka. The mean age of the patients was 34.7 (±19.5) years, 23 (62.1%) were aged between 19 and 60 years, and 31 (83.8%) were male. Thirty-one patients (83.8%) had central nervous system-related disorders such as stroke, cerebral palsy, and tubercular meningitis with sequelae or neuromuscular disorders such as Guillain–Barre Syndrome and Duchenne muscular dystrophy. Twelve patients (32.4%) were advised to consult higher centers in the vicinity, and the rest was referred to the district hospital. Conclusion: The findings suggest that TNR services are feasible, effective, and less resource intensive in delivering quality telemedicine care in India. More clinical studies are required to elucidate its full utility at different levels and in different parts of the country.
The Effect of Statins in Epilepsy: A Systematic Review
Authors: Quintana-Pájaro Loraine De Jesús , Ramos-Villegas Yancarlos , Cortecero-Sabalza Eileen , Joaquim Andrei F. , Agrawal Amit , Narvaez-Rojas Alexis Rafael , Moscote-Salazar Luis Rafael 
Published: August 2018

ABSTRACT
Background and Objectives: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, used for the management of hypercholesterolemia and related atherosclerotic diseases. Several studies have indicated the neuroprotective effects of statins on several neuropathological conditions. However, the role of these medications in epilepsy is still unclear. The purpose is to evaluate and summarize the level of evidence on the efficacy of statins in neuronal hyperexcitability and the neuroinflammatory processes of epilepsy. Methods: A systematic review was performed. Eligibility Criteria: This review involved studies conducted in humans and nonhuman experimental models, covering the use of an inhibitor of HMG-CoA reductase, alone or accompanied by another medication, in epilepsy. Information Sources: A systematic literature search was performed in PubMed, Embase, Ebsco Host, Scopus, Science Direct, Medline, and LILACS. Risk of Bias: It was evaluated with the Newcastle–Ottawa Scale and the experimental studies were evaluated using the GRADE tool. Results: Twenty articles of the 183 evaluated were included. Sixteen studies were conducted in animal models and four studies in humans. Most studies in mice reported a reduction in epileptiform activity and reduction in systemic inflammation with the treatment of statins, potentially influencing epilepsy control. Few studies in humans were performed in the geriatric population with variable results (neuroinflammation, seizure prevention, cell death, prevention of kindling, increase in convulsive threshold, increase in latency, decrease in frequency of crisis, and reduction in mortality) related to reduction in the rate of hospitalizations, mortality, and prevention of epilepsy. Studies in mice found a decrease in interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha and an increase in IL-10 and endothelial nitric oxide synthase. Conclusions: The possible antiepileptic mechanism of statins may be related to the reduction in neuroinflammation mediated by a decrease in pro-inflammatory cytokines and action in the nitrergic system. Further studies evaluating the impact of statins on seizure control are necessary.
Magnetic Resonance Imaging Findings in Viral Encephalitis: A Pictorial Essay
Authors: Jayaraman Kalaivani , Rangasami Rajeswaran , Chandrasekharan Anupama 
Published: August 2018

ABSTRACTViral encephalitis by definition is the result of human virus affecting the brain and sparing the meninges. The other nervous system manifestations are meningitis, meningoencephalitis, encephalomyelitis, and encephalomyeloradiculitis. Encephalitis can involve any age group from children to old people. The severity of the disease depends on the viral agent and the host immune system. The patient can present with fever, headache, seizure, neurological deficit, or altered sensorium. Laboratory investigations, imaging, and cerebrospinal fluid analysis are crucial in the diagnosis of encephalitis. Magnetic resonance imaging (MRI) findings may be nonspecific or specific and plays a major role in the diagnosis of encephalitis and predicting the possible cause. This pictorial essay reviews the MRI findings of common types of viral encephalitis.
Impact on Cognitive Improvement Following Burr Hole Evacuation of Chronic Subdural Hematoma: A Prospective Observational Study
Authors: Gill Maneet , Maheshwari Vikas , Narang Amit , Lingaraju T. S. 
Published: August 2018

ABSTRACT
Objective: Patients of Chronic subdural haematoma can present with only subtle cognitive impairment without any motor deficit. It is hence imperative for the treating clinician to be aware of this entity. The aim of the study was to identify any statistically significant improvement of cognitive functions following burr hole evacuation of Chronic SDH especially in the elderly patients. Methods and Material: A Prospective observational study of 30 patients of CSDH, from Jan 2015 to Dec 2016 was done at a tertiary level Armed Forces Hospital. The study had 23 male, 07 female, with age ranging from 7-85 years. The cognitive function of each patient was assessed at admission and 24 hours after surgery by MMSE. Radiological confirmation was done by CT head. Standard two burr holes were made and hematoma evacuated. The clinical, cognitive assessment and radiological data were collected and analysed. Results: There was no statistical significance preoperatively between age and pre operative cognitive impairment, headache, hemiparesis, dysarthria (P>0.05). We however found a statistically significant improvement postoperatively in cognitive impairment, headache (P=0.00), motor deficit (P=0.01) and dysarthria (P=0.046) Conclusion: The clinical features of dementia and other neurodegenerative disorders simulate CSDH in the geriatric population. These patients should have early neuroimaging and prompt surgical intervention to alleviate cognitive deficits.
Neurobrucellosis Presenting as Acute Psychosis
Authors: Shah Irfan Ahmad , Kawoos Yuman , Sanai Bashir Ahmad , Rabyang Stanzen , Banday Dawood 
Published: August 2018

ABSTRACTA 45-year-old female without any past or family history of psychiatric illness presented to the emergency department with complaints of abnormal behavior, irrelevant talking, restlessness, episodic crying, and decreased sleep of 2-day duration. On detailed interview, the attendants gave a history of an intermittent headache of 6-month duration and hearing impairment of 4-month duration. On investigation, her cerebrospinal fluid was reactive, and brucella titers were positive. She received appropriate treatment for 6 months and a short course of antipsychotics. Her symptoms settled, but she had persistent hearing loss. Psychosis as well as hearing loss is a very rare presentation of brucellosis. The case highlights the importance of considering neurobrucellosis as a differential diagnosis in patients with any unexplained neuropsychiatric symptoms such as acute psychosis or hearing loss.
A Short Weight Loss Intervention in a Neurosurgical Subspecialist Clinical Setting
Authors: Sedney Cara L. , Haggerty Treah , N. Patricia Dekeseredy R. 
Published: August 2018

ABSTRACT
Context: The relationship between back pain and obesity is well characterized; therefore, the neurosurgical consultant visit for back pain may be a key interventional opportunity for weight loss. Aims: The aim of this project was to evaluate efficacy of an educational intervention for back pain. Methods: A retrospective study was undertaken to evaluate effectiveness of an educational intervention (Show patient's own MRI, Explain degenerative disc disease, Relate to weight issues, Reference other weight-related comorbidities, and Encourage a plan of action for weight loss [SERRE]). This has been performed since 2014 for patients presenting to the first author's neurosurgical spine clinic with nonsurgical back pain and body mass index (BMI) over 35. Results: The average BMI was 50.7. Fifty-five percent of patients had additional weight-related comorbidities. After SERRE intervention, 82% of patients were open to weight loss interventions. However, only 22% of patients went on to follow-up with a formal weight management program and only 9% of patients went on to have a documented weight loss. The lack of success was largely attributed to social issues and severe medical comorbidities within the specific population. Conclusions: Incorporation of patient education regarding the relationship of weight loss to back pain and other weight-related comorbidities is well received in a rural specialist consultation setting. Improved communication with primary care physicians regarding this message and further supportive actions may improve follow-through, and therefore success of ultimate weight loss interventions.
Cervical Intramedullary Cystic Teratoma with Dermal Sinus Tract: A Case Report and Review of Literature
Authors: Diyora Batuk , Kukreja Sanjay , Mulla Mazhar , Bhende Bhagyashri , Nayak Naren 
Published: August 2018

ABSTRACTIntramedullary spinal teratomas are rare. We report a case in a 40-year-male who presented with progressive weakness over the right side of the body and gait imbalance. He had dermal sinus with hair patch over nape of the neck. Magnetic resonance imaging revealed cervical (C4–C7) intramedullary tumor with dermal sinus tract. C3–C7 laminectomy was performed and tumor excised along with the sinus tract. Histopathological examination revealed mature cystic teratoma. Gait ataxia was improved immediately while near complete recovery in motor power was achieved over a period of 2–3 weeks.
Perception and Attitude toward Mental Illness in Antenatal Mothers in Rural Population of Southern India: A Cross-Sectional Study
Authors: Manjrekar Shivani , Patil Sandeep 
Published: August 2018

ABSTRACT
Background: Mental health disorders globally are on a rise due to various reasons. Gender differences have been one of the reasons. Pregnancy is a stressful event in mothers and it can either exacerbate preexisting mental illness or can give rise to other mental health disorders. Studies have shown that women residing in rural areas are at higher risk of developing mental health problems. Mental health problems have detrimental effects in post-partum period. Most of the complications can be prevented if psychiatric symptoms are detected in early part of pregnancy and if women are aware of these symptoms. Aim: To find the awareness, attitude and perception towards mental illness in antenatal mothers residing in rural area of India. Setting and Design: It's a descriptive cross sectional study conducted at primary health care centers. Methods and Materials: Total of 300 antenatal mothers attending primary health care centers were recruited into the study after a written informed consent was obtained. Statistical Analysis: Basic socio demographic data were collected and a semi structured questionnaire was designed. The participants were interviewed according to the questionnaire. Data collected was analyzed using SPSS software. Results and Conclusion: The mean age of the study participants was 24+5. Of the 300 study participants more than 90% were unaware that mental illness can occur during pregnancy and only around 07% could agree say that it can occur in pregnancy. There is poor awareness of mental health problems amongst pregnant women residing in rural part of southern India. The reasons for the same are lack of awareness, low levels of education, lower socio economic status, cultural beliefs and practices, lack of mental health services and stigma associated with mental illness. There is no routine screening for mental health problems during antenatal visits. If done otherwise could bring down adverse maternal outcome.