Small vessel childhood primary angiitis of the central nervous system with positive anti-glial fibrillary acidic protein antibodies: a case report and review of literature.

BACKGROUND: Small vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries. CASE PRESENTATION: We report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group. CONCLUSION: We present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.

Appraising the availability of biomass residues in India and their bioenergy potential.

Biomass produced from agriculture at present provides most energy services in developing nations. In India, enormous quantities of biomass are produced for conversion into valuable energy. Bioenergy production from agricultural leftovers, animal manure, and municipal waste has the potential to meet of the rising need sustainable energy. It is a practical and sustainable option since the energy produced from the above mentioned sources can minimise the use of fossil fuels, reduce greenhouse gas emissions, and alleviate the effects of climate change. In addition, it can boost marginal and small farmers in terms of income and job opportunities. Evaluating agricultural leftovers, animal manure, and municipal waste as bioenergy resources can provide a method of tapping renewable energy opportunities. It is possible to minimise constraints for using agricultural leftovers, animal manure, and municipal waste, support investment decisions, and maximise the utilisation of biomass resources available. This study is intended to establish the amount of energy demand in India that can be met by using crop residues, animal manure, logging residues, and municipal waste. The annual energy potential of these biomass waste was quantified and assessed in the study. It has been determined that the technical bioenergy potential of these biomass resources is 1.29 × 103 PJ in 2.31 × 104 Mm3 of biogas and 7.79 × 102 PJ in 3.49 × 104 Ml of cellulosic ethanol. However, the country must overcome techno-economic barriers to handle the projects likely to be initiated soon.

Noncontrast MRI Protocol for Selected Pediatric Pituitary Endocrinopathies: A Procedure with High Diagnostic Yield and Potential to Reduce Anesthesia and Gadolinium-Based Contrast Exposure.

BACKGROUND AND PURPOSE: Although many pediatric neuroradiology practices empirically use noncontrast brain and pituitary MR imaging for evaluation of growth hormone deficiency, central precocious puberty, and short stature, there are currently insufficient published data to support this practice in an evidence-based fashion. Therefore, the use of contrast-enhanced MR imaging for all pediatric pituitary endocrinopathies remains widespread. We evaluated whether noncontrast MR imaging has adequate diagnostic yield for the evaluation of pediatric growth hormone deficiency, central precocious puberty, and short stature. MATERIALS AND METHODS: Pituitary MR imaging studies obtained for growth hormone deficiency, central precocious puberty, or short stature in patients 0-18 years of age from 2010 to 2019 were analyzed. Separate blinded review of noncontrast images in cases with abnormalities on the original radiology report was performed by 2 subspecialty-trained pediatric neuroradiologists, with discrepancies resolved by consensus. RESULTS: Of the 134/442 MR imaging studies obtained for growth hormone deficiency, central precocious puberty, or short stature with hypothalamic-pituitary region abnormalities, there was 70% concordance with the original reports on blinded review of noncontrast images. Twenty-two of 40 discrepancies were deemed unrelated to the indication, and 9 cases originally interpreted as possible microadenoma were read as having normal findings on blinded review. Only 9 of 40 discrepancies required contrast for further characterization. CONCLUSIONS: In our study, most relevant radiologic findings in patients with growth hormone deficiency, central precocious puberty, and short stature were detectable without contrast, providing evidence that contrast can be avoided in routine MR imaging evaluation of these indications. We propose a "rapid noncontrast pituitary" MR imaging protocol for pediatric patients presenting with growth hormone deficiency, central precocious puberty, or short stature, which may increase efficiency and decrease contrast and anesthesia exposure.

Diffuse Leptomeningeal Glioneuronal Tumor of Childhood.

Diffuse leptomeningeal glioneuronal tumor is a newly defined entity under the neuronal and mixed neuronal-glial tumors category in the 2016 World Health Organization classification of brain tumors. In this series, we report clinical, radiologic, and histologic findings in 7 cases of diffuse leptomeningeal glioneuronal tumor. Our cases and literature review indicate that the most characteristic imaging finding is diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement. This is often associated with small cyst-like, nonenhancing lesions. It should be noted that tumors sometimes bear nontypical features, for example, presenting as a solitary spinal cord mass without leptomeningeal involvement or with a dominant intracranial mass. In children with characteristic imaging findings and without clinical features of infection, the radiologist has an opportunity to promptly raise the possibility of diffuse leptomeningeal glioneuronal tumor, and thereby, affect streamlined diagnostic evaluation.

Human Parechovirus Meningoencephalitis: Neuroimaging in the Era of Polymerase Chain Reaction-Based Testing.

Human parechovirus infection is an increasingly recognized cause of neonatal meningoencephalitis. We describe characteristic clinical features and brain MR imaging abnormalities of human parechovirus meningoencephalitis in 6 infants. When corroborated by increasingly available polymerase chain reaction-based testing of the CSF, the distinctive MR imaging appearance may yield a specific diagnosis that obviates costly and time-consuming further clinical evaluation. In our study, infants with human parechovirus presented in the first 35 days of life with seizures, irritability, and sepsis. MR imaging consistently demonstrated low diffusivity within the thalami, corpus callosum, and subcortical white matter with a frontoparietal predominance. T1 and T2 shortening connoting white matter injury along the deep medullary veins suggests venous ischemia as an alternative potential pathogenetic mechanism to direct neuroaxonal injury.

Identification, synthesis and evaluation of CSF1R inhibitors using fragment based drug design.

Colony-stimulating factor 1 receptor is a type III receptor protein tyrosine kinase belonging to PDGFR family. CSF1R signaling is essential for differentiation, proliferation and survival of macrophages. Aberrant expression of CSF1R appears to be an attractive target in several cancer types. Higher expression of CSF1R ligands correlates to tumor progression. CSF1R inhibitors have been shown to suppress cancers. We have attempted an in silico fragment derived drug discovery approach by screening ˜25,000 in-house compounds as potential CSF1R inhibitors. Using FBDD approach we have identified six diverse fragments that exhibit affinity towards hinge region of CSF1R. Some of the fragments 5-nitroindole and 7-azaindole and their derivatives were synthesized for further evaluation. The in silico and in vitro enzyme activity studies reveal moderate inhibition of CSF1R kinase activity by 5-nitroindole and good inhibition by 7-azaindole fragments. Bio and chemiinformatics studies have shown that 7-azaindole compounds have better membrane permeability and enzyme inhibition properties. Molecular docking studies show that the amino acid residues 664-666 in the hinge region of the cytosolic domain of CSF1R to be the preferred region of binding for nitroindole and azaindole derivatives. Further optimization and biological analysis would identify these fragments as potential and promising leads as CSF1R inhibitors.

Synthesis and biological evaluation of Schizandrin derivatives as potential anti-cancer agents.

A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 showed potent activities against tested cell lines. More significantly, compound 5 exhibited most potent cytotoxic activity against DU-145 with an IC50 value of 1.38 µM which is comparable to the standard agent, doxorubicin. Further, flow cytometry analysis indicated that 5 arrested cells in G2/M phase and consequently leading to apoptosis. Molecular docking analysis showed that 5 occupied the colchicine binding pocket of tubulin. Overall, the present study demonstrates that 5, as a mitotic-agent.

Deep Neck Space Infections-A Study in Diabetic Population in a Tertiary Care Centre.

This study is intended to analyze the clinical profile and outcomes of deep neck space infection in diabetic patients in our tertiary care centre. A prospective study of 1 year duration from 30th September 2015 to 30th September 2016 at department of Otorhinolaryngology, Gauhati Medical College and Hospital, Guwahati. A total of 45 diabetic patients who presented with DNSI are included in this study. Their demographic profile, etiology, bacteriology, treatment, duration of hospital stay, complications and outcomes have been analyzed. 45 patients were recorded; 32 (71.11%) were men, and 13 (45%) were women, with a mean age of 63.27 ± 7.55 years. There were 30 patients (66.67%) who had associated systemic diseases apart from diabetes mellitus. The parapharyngeal space in 13 patients (28.89%) was the most commonly involved space. Odontogenic infections in 18 patients (40%) and upper airway infections 9 patients (20%) were the two most common causes. Klebsiella pneumonia in 29 patients (64.44%), was the commonest organism isolated through pus cultures. All the patients except one (97.78%) came with abscess and underwent surgical drainage. One patient (2.22%) with carbuncle underwent regular dressing. Six patients (13.33%) had major complications. Those patients with other underlying systemic diseases or complications tended to have a longer hospital stay and were older. No cases of death has been reported. (mortality rate, 0%). DNSI patients with diabetes have a more severe clinical course. They are likely to have complications more frequently and a longer duration of hospital stay. In clinical practices while dealing with these patients more vigilance is required. On admission empirical antibiotics should cover K. pneumonia. Early surgical drainage remains the main method of treatment. Primary prevention can be achieved by orodental hygiene, regular dental check ups and in this part of the country by avoidance of substance abuse like tobacco chewing.

Ovarian markers and irregular menses among women with type 1 diabetes in the Epidemiology of Diabetes Interventions and Complications study.

OBJECTIVE: Women with type 1 diabetes have increased risk of infertility compared to women without diabetes even after adjustment for irregular menses, but aetiologies are incompletely understood. Our aim was to examine the prevalence of abnormalities in ovarian markers consistent with polycystic ovary syndrome in women with type 1 diabetes and associations with irregular menses and diabetes-specific variables. DESIGN, PATIENTS AND MEASUREMENTS: We conducted a secondary analysis of women in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), a randomized trial and observational follow-up of intensive insulin therapy for type 1 diabetes. We included women with anti-Müllerian hormone (AMH) measurements among women not using oral contraceptives (n = 187). Initial AMH and testosterone measures were performed between EDIC years 1 and 4. History of irregular menses was assessed annually. RESULTS: The median age of women was 35 (interquartile ratio 29, 40) years; 133 (35%) had elevated AMH and 62 (17%) reported irregular menses. Twelve per cent of women had relative elevations in total testosterone. In multivariable models, lower insulin dosages were associated with higher AMH concentrations (P = .0027), but not diabetes duration, glycemic control, body mass index or irregular menses. Neither irregular menses nor diabetes-specific variables were associated with testosterone concentrations. CONCLUSIONS: Among women with type 1 diabetes in their thirties, abnormalities in ovarian markers are common and not associated with irregular menses and thus may partially account for decreased fecundity in women with type 1 diabetes.

Potential of oleaginous yeast Trichosporon sp., for conversion of sugarcane bagasse hydrolysate into biodiesel.

This study reports production of microbial oil from a yeast strain Trichosporon sp., (RW) isolated from decayed wood. Preliminary analysis based on fluorescence microscopy and spectroscopy of Nile red stained yeast cells showed accumulation of lipid globules. The potential of the yeast to produce lipids was evaluated on glucose, glycerol and acid hydrolysate of sugarcane bagasse, where Trichosporon sp. (RW) was found to accumulate 21.45 (59.6%), 18.41 (56%) and 10.25g/l (40.5%) of the lipids after 120h of fermentation at 30°C. FAME analysis of lipids by GC-FID and NMR revealed oleic acid (18:1) as the major constituent, corresponding to 50.05, 46.48 and 54.66% of the accumulated lipids in glucose, glycerol and hydrolysate grown cultures, respectively. Other accumulated lipids included palmitic (16:0), linoleic (18:2) and stearic acids (18:0) in that order. The cetane number of the lipids ranged from 52.39 to 59.57 indicating suitability for biodiesel production.

A comparative study of sheath potential profile measurements with laser-heated and current-heated emissive probes.

Emissive Langmuir probe is one of the most efficient diagnostic tools available for plasma potential measurements. Extensive studies have been carried out in designing different kinds of conventional (electrically heated) emissive probes (CEPs) to estimate the plasma potential. Laser heated emissive probe (LHEP) has been developed with certain advantages over the conventional probes such as low evaporation rate of the probe material, high lifetime, and high emission levels. Most importantly, the LHEP uses laser to heat the probe-tip and does not require electric current to heat the probe-tip like in CEP. The heating current in CEP substantially affects the plasma potential measurements, especially in the regions of plasma where high electric and magnetic field gradients are present. In this paper, we studied the plasma potential structures in sheath-presheath region using both LHEP and CEP in an unmagnetized dc-filament discharge plasma. Measurements of sheath spatial potential profile using laser heated emissive probe are compared with those obtained using conventional emissive probe.

Glycaemic control and risk of incident urinary incontinence in women with Type 1 diabetes: results from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

AIMS: To study the impact of glycaemic control on urinary incontinence in women who participated in the Diabetes Control and Complications Trial (DCCT; 1983-1993) and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC; 1994-present). METHODS: Study participants were women who completed, at both years 10 (2003) and 17 (2010) of the EDIC follow-up, the urological assessment questionnaire (UroEDIC). Urinary incontinence was defined as self-reported involuntary leakage of urine that occurred at least weekly. Incident urinary incontinence was defined as weekly urinary incontinence present at EDIC year 17 but not at EDIC year 10. Multivariable regression models were used to examine the association of incident urinary incontinence with comorbid prevalent conditions and glycaemic control (mean HbA1c over the first 10 years of EDIC). RESULTS: A total of 64 (15.3%) women with Type 1 diabetes (mean age 43.6 ± 6.3 years at EDIC year 10) reported incident urinary incontinence at EDIC year 17. When adjusted for clinical covariates (including age, DCCT cohort assignment, DCCT treatment arm, BMI, insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract infection in the last year), the mean EDIC HbA1c was associated with increased odds of incident urinary incontinence (odds ratio 1.03, 95% CI 1.01-1.06 per mmol/mol increase; odds ratio 1.41, 95% CI 1.07-1.89 per % HbA1c increase). CONCLUSIONS: Incident urinary incontinence was associated with higher HbA1c levels in women with Type 1 diabetes, independent of other recognized risk factors. These results suggest the potential for women to modify their risk of urinary incontinence with improved glycaemic control. (Clinical Trials Registry no: NCT00360815 and NCT00360893).

Tandem Prins/Wagner/Ritter process for the stereoselective synthesis of (3-oxabicyclo[4.2.0]octanyl)amide and (1-(5-aryltetrahydrofuran-3-yl)cyclobutyl)amide derivatives.

Three-component coupling of aldehydes, vinylcyclopropyl carbinols, and nitriles in the presence of 10 mol% TMSOTf at -40 to 0 °C in dichloromethane affords a novel class of (3-oxabicyclo[4.2.0]octanyl)amides in high yields with excellent selectivity, whereas (1-vinylcyclobutyl)methanol provides the corresponding (1-(5-aryltetrahydrofuran-3-yl)cyclobutyl)amides under similar conditions. This is the first report on the synthesis of oxabicycles through a sequential Prins/Wagner/Ritter process.

Effect of deep litter housing and fermented feed on carcass characteristics and meat quality of crossbred Hampshire pigs.

AIM: The objective of the study was to evaluate the effect of deep litter housing and fermented feed on carcass characteristics and meat quality of crossbred Hampshire pigs. MATERIALS AND METHODS: Forty-eight weaned crossbred Hampshire piglets of 2 months age (24 males and 24 females) were selected for the experiment. The piglets were randomly assigned into 4 homogenous experimental groups with 6 males and 6 females each: E1; reared on a conventional housing and fed with a fermented diet, E2; reared on a deep litter housing system and fed with a fermented diet, E3; reared on a deep litter housing system and fed with a conventional diet and C; reared on a conventional housing system and fed with a conventional diet. The study was continued up to 32 weeks of age and at the end of this period, 6 animals (3 males and 3 females) from each experimental group were slaughtered to evaluate carcass traits and meat quality characteristics. RESULTS: Pre-slaughter weight, hot carcass weight, and dressing percentage were significantly (p<0.01) affected by feeding fermented diet and deep litter housing while carcass traits, i.e., carcass length, backfat thickness, and loin eye area were not affected. The edible offal; liver and heart weight (p<0.05) differed significantly while kidney weight showed no difference. The inedible offal; head weight (p<0.01) and lung weight revealed a significant difference (p<0.05) while spleen and stomach weight showed no difference among the experimental groups. The wholesale cuts and meat: bone ratio of pigs also differed significantly among the groups. Morphometry of small and large intestine also showed a significant difference. Chemical composition of pork viz., moisture and total ash content was influenced by the treatment, while crude protein and ether extract content were not affected. Mineral composition of pork also showed no significant difference. Color characteristics of Longissimus dorsi muscle showed a significant difference in L* and a* value while parameter b* was not affected. The tenderness of meat showed significant difference among the groups (p<0.01). CONCLUSION: Crossbred Hampshire pigs being reared on fermented feed and deep litter housing could produce highlygraded carcass and improvement in meat quality.

Annotated chemical patent corpus: a gold standard for text mining.

Exploring the chemical and biological space covered by patent applications is crucial in early-stage medicinal chemistry activities. Patent analysis can provide understanding of compound prior art, novelty checking, validation of biological assays, and identification of new starting points for chemical exploration. Extracting chemical and biological entities from patents through manual extraction by expert curators can take substantial amount of time and resources. Text mining methods can help to ease this process. To validate the performance of such methods, a manually annotated patent corpus is essential. In this study we have produced a large gold standard chemical patent corpus. We developed annotation guidelines and selected 200 full patents from the World Intellectual Property Organization, United States Patent and Trademark Office, and European Patent Office. The patents were pre-annotated automatically and made available to four independent annotator groups each consisting of two to ten annotators. The annotators marked chemicals in different subclasses, diseases, targets, and modes of action. Spelling mistakes and spurious line break due to optical character recognition errors were also annotated. A subset of 47 patents was annotated by at least three annotator groups, from which harmonized annotations and inter-annotator agreement scores were derived. One group annotated the full set. The patent corpus includes 400,125 annotations for the full set and 36,537 annotations for the harmonized set. All patents and annotated entities are publicly available at www.biosemantics.org.

Tandem Prins/pinacol reaction for the synthesis of oxaspiro[4.5]decan-1-one scaffolds.

A novel Lewis acid catalyzed Prins/pinacol cascade process has been developed for the synthesis of 7-substituted-8-oxaspiro[4.5]decan-1-ones in good yields with excellent selectivity. This is the first example of the synthesis of oxaspirocycles from aldehydes and 1-(4-hydroxybut-1-en-2-yl)cyclobutanol through a cascade of Prins/pinacol rearrangement. This method is applicable to a wide range of aldehydes such as aromatic, aliphatic, heteroaromatic, and α,ß-unsaturated aldehydes.

Tracking 20 years of compound-to-target output from literature and patents.

The statistics of drug development output and declining yield of approved medicines has been the subject of many recent reviews. However, assessing research productivity that feeds development is more difficult. Here we utilise an extensive database of structure-activity relationships extracted from papers and patents. We have used this database to analyse published compounds cumulatively linked to nearly 4000 protein target identifiers from multiple species over the last 20 years. The compound output increases up to 2005 followed by a decline that parallels a fall in pharmaceutical patenting. Counts of protein targets have plateaued but not fallen. We extended these results by exploring compounds and targets for one large pharmaceutical company. In addition, we examined collective time course data for six individual protease targets, including average molecular weight of the compounds. We also tracked the PubMed profile of these targets to detect signals related to changes in compound output. Our results show that research compound output had decreased 35% by 2012. The major causative factor is likely to be a contraction in the global research base due to mergers and acquisitions across the pharmaceutical industry. However, this does not rule out an increasing stringency of compound quality filtration and/or patenting cost control. The number of proteins mapped to compounds on a yearly basis shows less decline, indicating the cumulative published target capacity of global research is being sustained in the region of 300 proteins for large companies. The tracking of six individual targets shows uniquely detailed patterns not discernible from cumulative snapshots. These are interpretable in terms of events related to validation and de-risking of targets that produce detectable follow-on surges in patenting. Further analysis of the type we present here can provide unique insights into the process of drug discovery based on the data it actually generates.

GPS and GPRS Based Telemonitoring System for Emergency Patient Transportation.

Telemonitoring during the golden hour of patient transportation helps to improve medical care. Presently there are different physiological data acquisition and transmission systems using cellular network and radio communication links. Location monitoring systems and video transmission systems are also commercially available. The emergency patient transportation systems uniquely require transmission of data pertaining to the patient, vehicle, time of the call, physiological signals (like ECG, blood pressure, a body temperature, and blood oxygen saturation), location information, a snap shot of the patient, and voice. These requirements are presently met by using separate communication systems for voice, physiological data, and location that result in a lot of inconvenience to the technicians, maintenance related issues, in addition to being expensive. This paper presents design, development, and implementation of such a telemonitoring system for emergency patient transportation employing ARM 9 processor module. This system is found to be very useful for the emergency patient transportation being undertaken by organizations like the Emergency Management Research Institute (EMRI).

Virtual screening studies on HIV-1 reverse transcriptase inhibitors to design potent leads.

The purpose of this study is to identify novel and potent inhibitors against HIV-1 reverse transcriptase (RT). The crystal structure of the most active ligand was converted into a feature-shaped query. This query was used to align molecules to generate statistically valid 3D-QSAR (r(2) = 0.873) and Pharmacophore models (HypoGen). The best HypoGen model consists of three Pharmacophore features (one hydrogen bond acceptor, one hydrophobic aliphatic and one ring aromatic) and further validated using known RT inhibitors. The designed novel inhibitors are further subjected to docking studies to reduce the number of false positives. We have identified and proposed some novel and potential lead molecules as reverse transcriptase inhibitors using analog and structure based studies.