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.

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.

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.

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.

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.

Synthesis of new cis-fused tetrahydrochromeno[4,3-b]quinolines and their antiproliferative activity studies against MDA-MB-231 and MCF-7 breast cancer cell lines.

New cis-fused tetrahydrochromeno[4,3-b]quinolines have been synthesized by intramolecular [4+2] imino-Diels-Alder reactions of 2-azadienes derived in situ from aromatic amines and 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones in the presence of 20mol% Yb(OTf)(3) in acetonitrile under reflux conditions in good to excellent yields. The structures were established by spectroscopic data and further confirmed by X-ray diffraction analysis. These compounds were evaluated for their antiproliferative activity against MDA-MB-231 and MCF-7 breast cancer cells. The results showed that compounds 3e, 3f, and 3k exhibit significant antiproliferative activity against MCF-7 breast cancer cells and low inhibitory activity against MDA-MB-231 breast cancer cell lines. Compound 3h displayed activity as comparable to tamoxifen on both the cell lines.

The influence of reduced glutathione on chromosome damage induced by X-rays or heavy ion beams of different LETs and on the interaction of DNA lesions induced by radiations and bleomycin.

It is thought that high linear energy transfer (LET) radiation induces more complex DNA damage than low-LET particles, specifically clustered DNA damage that causes cells to repair DNA double strand breaks (DSB) more slowly and leads to severe biological consequences. The present study aimed to investigate the role of exogenously added glutathione (GSH) on (12)C-beam (287keV/mum) and (7)Li-beam (60keV/mum) induced chromosome aberration (CA) formation, particularly on exchange aberration formation. In order to characterize the role of GSH in the joining of DNA DSBs, we induced DNA lesions with bleomycin (Blem) in conjunction with either high- or low-LET radiation (X-rays) since the chemistry of the free DNA ends created by Blem and X-rays is similar. CHO cells were exposed to reduced GSH at a concentration of 2mM for 3h before radiation. Treatment with Blem (20mug/ml) was carried out for 2h before the cells were exposed to radiation. Our results show that the frequency of chromosomal aberration increases with increased LET. Heavy ion exposed cells show a higher frequency of CA over time than do X-irradiated cells. An analysis of the first post-irradiation mitosis of exposed CHO cells shows that high-LET radiation induces more breaks than exchange-type aberrations and exogenous GSH has no influence on high-LET radiation-induced DNA damage. The DNA lesions induced by low-LET radiation interact relatively strongly with Blem-induced lesions whereas interaction between Blem and high-LET radiations was poor. This could be attributed to differences in repair kinetics and qualitative differences in the DNA lesions induced by Blem and high-LET radiation.

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.

Oleanane-type isomeric triterpenoids from Barringtonia racemosa.

Two new isomeric acylated oleanane-type triterpenoids along with three known compounds were isolated from the MeOH extract of the dried fruits of Barringtonia racemosa. On the basis of spectroscopic methods, with special emphasis on 1D and 2D NMR techniques as well as chemical methods, the structures were characterized as racemosol A (1) [22alpha-acetoxy-3beta,15alpha,16alpha,21beta-tetrahydroxy-28-(2-methylbutyryl)olean-12-ene] and isoracemosol A (2) [21beta-acetoxy-3beta,15alpha,16alpha,28-tetrahydroxy-22alpha-(2-methylbutyryl)olean-12-ene]. The isolated compounds (1-5) were not active against HeLa and P388 D1 carcinoma cell lines.

SUBTLE CONTROL IN SOLUTION AND CRYSTAL STRUCTURES WITH WEAK HYDROGEN BONDS: THE UNUSUAL PROFILE OF DIMETHYL 3, 12-DIOXO-7, 8 DITHIA 4, 11-DIAZABICYCLO[12.2.2]OCTADECA-1(16), 14, 17-TRIENE 5, 10-DICARBOXYLATE (TDA1).

The structural features of the title compound were determined or examined by three diverse procedures: single crystal X-ray diffraction analysis, solution spectroscopic procedures and Quantum mechanical theoretical calculations. The conformational asymmetry of the macrocycle provides the opportunity to form one strong NH···OC intermolecular hydrogen bond, as well as, a number of weak CH···OC bonds. The interior of the macrocycle has short approaches for NH(...)π and NH···S. The many weak hydrogen bonds cooperate to form a very hard, robust crystal. Crystal parameters: C(18)H(22)N(2)O(6)S(2), P2(1)2(1)2(1), a = 5.108(1) Å, b = 18.948(4) Å, c = 21.029(3) Å, α = ß = γ = 90°. Quantum chemical calculations have provided a strong foundation for weak hydrogen bonds. Contrary to popular belief the present work has conclusively proved that the importance of weak hydrogen bonds are perhaps underestimated since calculations show that the energy of duplex are significantly lower then estimated from the identified hydrogen bonding.

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.

Pharmacophore modeling and virtual screening studies to design some potential histone deacetylase inhibitors as new leads.

Histone deacetylase is one of the important targets in the treatment of solid tumors and hematological cancers. A total of 20 well-defined inhibitors were used to generate Pharmacophore models using and HypoGen module of Catalyst. These 20 molecules broadly represent 3 different chemotypes. The best HypoGen model consists of four-pharmacophore features--one hydrogen bond acceptor, one hydrophobic aliphatic and two ring aromatic centers. This model was validated against 378 known HDAC inhibitors with a correlation of 0.897 as well as enrichment factor of 2.68 against a maximum value of 3. This model was further used to retrieve molecules from NCI database with 238,819 molecules. A total of 4638 molecules from a pool of 238,819 molecules were identified as hits while 297 molecules were indicated as highly active. Also, a Similarity analysis has been carried out for set of 4638 hits with respect to most active molecule of each chemotypes which validated not only the Virtual Screening potential of the model but also identified the possible new Chemotypes. This type of Similarity analysis would prove to be efficient not only for lead generation but also for lead optimization.

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.

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.

Infection control and management of MRSA: assessing the knowledge of staff in an acute hospital setting.

Much of the recent work in tackling meticillin-resistant Staphylococcus aureus (MRSA) has focused on hygiene in hospitals, but it is unclear how much hospital staff know about the treatment and management of patients who are colonized or infected with MRSA. The aim of this study was to assess the knowledge and perceived practice of staff regarding MRSA and its management in an acute hospital setting. A further aim was to determine what staff felt was needed in terms of information or education on the risks, management and treatment of MRSA. A questionnaire survey was carried out through group administration during a study day and by face-to-face interviews. Subjects included in the questionnaire were infection and colonization, treatment, and the availability of local support and advice. There were 174 responses, divided equally between doctors and nurses. Knowledge on many aspects of MRSA and its management was deficient, although the majority of participants who felt that they required additional information about MRSA acknowledged this. The survey confirmed that assumptions should not be made about adequate knowledge and expertise of staff in relation to MRSA. Gaps in awareness of aspects of care and management were highlighted and information and educational needs identified.

Response to high LET radiation 12C (LET, 295 keV/microm) in M5 cells, a radio resistant cell strain derived from Chinese hamster V79 cells.

PURPOSE: To study the effects of 12C-beam of 295 keV/microm (57.24 MeV) on M5 and Chinese hamster V79 cells by using cytogenetic assays like micronuclei (MN) induction, chromosomal aberrations (CA) and apoptosis. Additionally, the relative survival of these two cell lines was tested by the colony forming ability of the cells, with a view to understanding the mechanism of cellular damages that lead to difference in cell survival. MATERIALS AND METHODS: Confluent cells were irradiated with 12C-beam at various doses using 15UD Pelletron accelerator. Cell survival was studied by the colony forming ability of cells. MN assay was done by fluorescent staining. Different types of chromosomal aberrations in metaphase cells were scored at 12 h after irradiation. Apoptosis was measured at different post irradiation times as detected by nuclear fragmentation and DNA ladder was prepared after 48 h of incubation. RESULTS: Dose-dependent decrease in surviving fractions was found in both the cell lines. However, the surviving fractions were higher in M5 cells in comparison to V79 cells when exposed to the same radiation doses. On the other hand, induced MN frequencies, CA frequencies and apoptosis percentages were less in M5 cells than V79 cells. Very good correlations between surviving fractions and induced MN frequencies or induced total CA or induced apoptosis percentages were obtained in this study. CONCLUSIONS: The cell strain M5 showed relatively more radio-resistance to 12C-beam compared to Chinese hamster V79 cells in this study. As the MN formation, CA and apoptosis induction were less in M5 cells as compared to parental V79 cells, the higher cell survival in the former could possibly be attributed to their better repairing ability leading to higher cell survival.