High-resolution MR vessel wall imaging in determining the stroke aetiology and risk stratification in isolated middle cerebral artery disease.

PURPOSE: High-resolution MR vessel wall imaging (HRVWI) can characterise vessel wall pathology affecting intracranial circulation and helps in differentiating intracranial vasculopathies. The aim was to differentiate intracranial pathologies involving middle cerebral artery (MCA) in patients with ischemic stroke and characterise the high-risk plaques in intracranial atherosclerotic disease (ICAD) using HRVWI. METHODS: Patients with ischemic stroke with isolated MCA disease with ≥ 50% luminal narrowing by vascular imaging were enrolled within 2 weeks of onset and underwent high-resolution (3 T) intracranial vessel wall imaging (VWI). The pattern of vessel wall thickening, high signal on T1-weighted images, juxtaluminal hyperintensity, pattern and grade of enhancement were studied. The TOAST classification before and after HRVWI and the correlation of the recurrence of ischemic events at 3 months with imaging characteristics were analysed. RESULTS: Of the 36 patients, the mean age was 49.53 ± 15.61 years. After luminal imaging, by TOAST classification, 12 of 36 patients had stroke of undetermined aetiology. After vessel wall imaging, lesions in MCA were analysed. Of them, 23 patients had ICAD, 8 had vasculitis, and 2 had partially occlusive thrombus in MCA. The ability of HRVWI to bring a change in diagnosis was significant (p = 0.031). Of the 23 patients with ICAD, 12 patients had recurrent strokes within 3 months. The presence of grade 2 contrast enhancement (p = 0.02) and type 2 wall thickening (p = 0.03) showed a statistically significant association with recurrent ischemic events. CONCLUSION: High-resolution MRVWI can help in identifying the aetiology of stroke. The HRVWI characteristics in ICAD can help in risk stratification.

Incidence of thrombosis in perioperative and non-operative myocardial infarction.

BACKGROUND: The contribution of thrombosis to the aetiology of perioperative myocardial infarction (MI) is uncertain. We used optical coherence tomography (OCT) to determine the presence of thrombus and plaque morphology in patients experiencing a perioperative MI and matched patients experiencing a non-operative MI using OCT. METHODS: We conducted a single-centre, prospective, cohort study. Thirty patients experiencing a perioperative MI and 30 matched patients experiencing a non-operative MI, without ST elevation, underwent OCT to determine the presence of thrombus and culprit lesion plaque morphology. Angiography and OCT were performed a mean of 1.93(1.09) days and 1.53(0.68) days after the onset of perioperative and non-operative MI, respectively. OCT images were evaluated by an independent core laboratory without knowledge of whether the patient had suffered a perioperative or non-operative MI. RESULTS: We identified thrombus at the culprit lesion in four of 30 patients (13.3%) who experienced a perioperative MI and in 20 of 30 patients (66.7%) who experienced a non-operative MI, P<0.01. The only non-culprit lesion with thrombus was in a perioperative MI patient who also had a culprit lesion thrombus. Perioperative and non-operative MI culprit lesions demonstrated fibroatheroma in 18 patients (60.0%) us 20 patients (66.7%), respectively (P=0.52) and thin cap fibroatheroma in one patient (3.3%) us five patients (16.7%), respectively (P=0.11). One perioperative MI patient (3.3%) suffered a cardiac death and no non-operative MI patient died during the 30-day follow-up. CONCLUSIONS: Thrombosis was less common in perioperative than non-operative MI, despite similar underlying plaque morphology.

Autologous bone marrow cell transplantation in acute spinal cord injury--an Indian pilot study.

STUDY DESIGN: Phase- I/II, prospective, randomized, single-blind, controlled pilot study. PRIMARY OBJECTIVE: To determine the safety and feasibility of autologous bone marrow transplantation in patients with acute spinal cord injury (SCI) via two routes of transplantation as compared with controls. SETTING: Indian Spinal Injuries Center, New Delhi. METHODS: Twenty-one subjects with acute, American Spinal Injury Association Impairment Scale (AIS) A (complete), traumatic SCI with neurological level T1-T12, were recruited and randomized into three groups of seven subjects each. Two groups underwent cell transplantation through the intrathecal or intralesional route, whereas the third served as control. Participants were assessed at baseline and followed up at 6 months and 12-months post enrollment. Safety and tolerability were evaluated by monitoring for any adverse events. Efficacy was assessed through neurological, functional and psychological evaluation, as well as through electrophysiological studies and urodynamics. RESULTS: Surgery was tolerated well by all participants. There were no significant adverse events attributable to the procedure. There was no significant improvement in the neurological, electrophysiological or urodynamic efficacy variables. A statistically significant improvement in functional scores as evaluated by the Spinal Cord Independence Measure and International Spinal Cord Injury Scale was observed in all groups. CONCLUSIONS: The procedure is safe and feasible in AIS A participants with thoracic-level injuries at 12-months follow-up. No efficacy could be demonstrated that could be attributed to the procedure.

Molecular characterization of Opisthorchis noverca (Digenea: Opisthorchiidae) based on nuclear ribosomal ITS2 and mitochondrial COI genes.

Opisthorchiasis is a public health problem in South-East Asian countries and Eastern Europe. The infection implicates mainly two species of Opisthorchis, namely O. viverrini and O. felineus, that occur mostly in fish-eating mammals and humans, although there are rare reports of human cases involving two other species, O. noverca and O. guayaquilensis. Opisthorchis noverca has been reported frequently in dogs and pigs from the Indian subcontinent, with rare reports from cattle and human subjects. With a view to supplementing morphology-based identification of this species, the present study aimed to provide molecular characterization of O. noverca, using rDNA internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome oxidase I (mt COI) markers so as to determine its genetic correlation with other species of Opisthorchiidae, and also to generate a taxon-specific molecular marker based on the ITS2 region. The phylogenetic relationship between O. noverca and other species of the genus was determined using molecular sequence data. To strengthen the result, secondary structure sequence analyses of ITS2 with hemi-compensatory base changes (hCBCs), and amino acid sequence analyses, were also evaluated. Our results confirm that O. noverca is a distinct and valid species.

Retrospective analysis of spinal trauma in patients with ankylosing spondylitis: a descriptive study in Indian population.

OBJECTIVE: This study aims to understand the demographics, mode of trauma, hospital stay, complications, neurological improvement, mortality and expenditure incurred by Indian patients with spinal trauma and ankylosing spondylitis (AS). METHODS: Retrospective analysis of the patient data admitted to a tertiary referral hospital from 2008 to 2013 with the diagnosis of AS and spinal trauma was carried out. The variables studied were demographics, mode of trauma, neurological status, neurological improvement, involved vertebral level, duration of hospital stay, comorbid factors, expenditure and complications during the stay. RESULTS: Forty-six patients with diagnosis of AS with spine trauma were admitted over the last 5 years with a total of 52 fractures. All were male patients; 58.6% had injury because of trivial trauma and 78.2% patients presented with neurological injury. C5 C6, C6 C7, C7 D1 and D12 were the most common injured level. Fractures through intervertebral disc were most common in cervical spine. Of the patients, 52.7% had shown neurological improvement of at least grade 1(AIS). Mean expenditure of patient admitted with spinal cord injury (SCI) with AS is 7957 USD (United States dollar), which is around five times the per capita income in India (as per year 2013). CONCLUSION: Males with AS are much more prone to spinal fractures than females and its incidence may be higher than previously reported. Domestic falls are the most common mechanism of spinal trauma in this population. High velocity injuries are associated with complete SCI. The study reinforces the need for development of subsidized spinal care services for SCI management.

Purification and characterization of phosphoenolpyruvate carboxykinase from Raillietina echinobothrida, a cestode parasite of the domestic fowl.

Phosphoenolpyruvate carboxykinase (PEPCK, EC 4.1.1.32) is an essential regulatory enzyme of glycolysis in helminths in contrast to its role in gluconeogenesis in their host. Previously we have reported that phytochemicals from Flemingia vestita (Family: Fabaceae), genistein in particular, have vermifugal action and are known to affect carbohydrate metabolism in the cestode, Raillietina echinobothrida. In order to determine the functional differences of PEPCK from the parasite and its avian host (Gallus domesticus), we purified the parasite enzyme apparently to homogeneity, and characterized it. The native PEPCK is a monomer with a subunit molecular weight of 65 kDa. The purified enzyme displayed standard Michaelis-Menten kinetics with Km value of 42·52 µM for its substrate PEP. The Ki for the competitive inhibitors GTP, GMP, ITP and IMP for the carboxylation reaction were determined and discussed. In order to identify putative modulators from plant sources, phytochemicals from F. vestita and Stephania glabra were tested on the purified PEPCK, which resulted in alteration of its activity. From our results, we hypothesize that PEPCK may be a potential target site for anthelmintic action.

Crustacean-borne infections with microphallid metacercariae (Digenea: Microphallidae) from focal areas in Meghalaya, north-east India.

During a survey of edible Crustacea for recovery of infective stages (metacercariae) of potential helminthozoonoses of trematode origin in north-east India, the crab species Barytelphusa lugubris mansoniana, collected from suspected foci of lungfluke infection in Meghalaya and Assam, was found to harbour metacercarial cysts that were different from the earlier reported infection, in which the lungfluke Paragonimus was confirmed to be implicated. Using morphological criteria, this metacercaria was identified as Microphallus indicus Mukherjee & Ghosh, 1967 of the trematode family Microphallidae. The present study extends the previous work by providing molecular characterization of this parasite using ribosomal internal transcribed spacer regions (rDNA ITS1 and ITS2) and the partial large ribosomal subunit DNA, lsr. These target regions were amplified by polymerase chain reaction (PCR) using trematode universal primers and sequenced. In BLAST analysis the query sequences were found close to members of Microphallidae and closest to the genus Microphallus.

Molecular characterization of pouched amphistome parasites (Trematoda: Gastrothylacidae) using ribosomal ITS2 sequence and secondary structures.

Members of the family Gastrothylacidae (Trematoda: Digenea: Paramphistomata) are parasitic in ruminants throughout Africa and Asia. In north-east India, five species of pouched amphistomes, namely Fischoederius cobboldi, F. elongatus, Gastrothylax crumenifer, Carmyerius spatiosus and Velasquezotrema tripurensis, belonging to this family have been reported so far. In the present study, the molecular phylogeny of these five gastrothylacid species is derived using the second internal transcribed spacer (ITS2) sequence and secondary structure analyses. ITS2 sequence analysis was carried out to see the occurrence of interspecific variations among the species. Phylogenetic analyses were performed for primary sequence data alone as well as the combined sequence-structure information using neighbour-joining and Bayesian approaches. The sequence analysis revealed that there exist considerable interspecific variations among the various gastrothylacid fluke species. In contrast, the inferred secondary structures for the five species using minimum free energy modelling showed structural identities, in conformity with the core four-helix domain structure that has been recently identified as common to almost all eukaryotic taxa. The phylogenetic tree reconstructed using combined sequence-structure data showed a better resolution, as compared to the one using sequence data alone, with the gastrothylacid species forming a monophyletic group that is well separated from members of the other family, Paramphistomidae, of the amphistomid flukes group. The study provides the molecular characterization based on primary sequence data of the rDNA ITS2 region of the gastrothylacid amphistome flukes. Results also demonstrate the phylogenetic utility of the ITS2 sequence-secondary structure data for inferences at higher taxonomic levels.

High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows.

Drug development suffers from a lack of predictive and human-relevant in vitro models. Organ-on-chip (OOC) technology provides advanced culture capabilities to generate physiologically appropriate, human-based tissue in vitro, therefore providing a route to a predictive in vitro model. However, OOC technologies are often created at the expense of throughput, industry-standard form factors, and compatibility with state-of-the-art data collection tools. Here we present an OOC platform with advanced culture capabilities supporting a variety of human tissue models including liver, vascular, gastrointestinal, and kidney. The platform has 96 devices per industry standard plate and compatibility with contemporary high-throughput data collection tools. Specifically, we demonstrate programmable flow control over two physiologically relevant flow regimes: perfusion flow that enhances hepatic tissue function and high-shear stress flow that aligns endothelial monolayers. In addition, we integrate electrical sensors, demonstrating quantification of barrier function of primary gut colon tissue in real-time. We utilize optical access to the tissues to directly quantify renal active transport and oxygen consumption via integrated oxygen sensors. Finally, we leverage the compatibility and throughput of the platform to screen all 96 devices using high content screening (HCS) and evaluate gene expression using RNA sequencing (RNA-seq). By combining these capabilities in one platform, physiologically-relevant tissues can be generated and measured, accelerating optimization of an in vitro model, and ultimately increasing predictive accuracy of in vitro drug screening.

Neoriojatrema mokokchungensis n. g., n. sp. (Monogenea: Polystomatidae: Polystomatinae) from the urinary bladder of a megophryid frog, Xenophrys glandulosa, in Nagaland, north-eastern India.

A new monogenean fluke, collected from the urinary bladder of a megophryid frog, Xenophrys glandulosa Fei, Ye & Huang, 1991 from Mokokchung and Tuensang districts of Nagaland, north-eastern India is described. Of the six genera under the subfamily Polystomatinae (Polystomatidae) known so far, the present form comes closer to Eupolystoma Kaw, 1950; Pseudopolystoma Yamaguti, 1963 and Riojatrema Lamothe-Argumedo, 1964, in all of which the opisthaptor lacks large hooks. However, a combination of characters, namely, shape of the body, rounded or bulbous pharynx, intestinal caeca not joining posteriorly in the opisthaptoral region, ovary located in the anterior third of the body and presence of vaginal apertures, sets the present form apart from all these genera, and also from the known species of Riojatrema. These differences warrant the establishment of a new species and a new genus to accommodate the present form. The validity of this new monogenean, named as Neoriojatrema mokokchungensis after the type locality of the fluke, is discussed.

Evaluation of the activity of 16 medicinal plants against Neisseria gonorrhoeae.

50% Ethanolic extracts of various parts of 16 medicinal plants were evaluated for potential activity against clinical isolates and WHO strains of Neisseria gonorrhoeae, including multidrug-resistant (MDR) strains. Activity was calculated as percentage inhibition in comparison with penicillin and ciprofloxacin and strains were categorised as less sensitive, sensitive or highly sensitive to the extracts. The extracts caused differential inhibition of N. gonorrhoeae, with greater inhibition of the MDR strains. Among the extracts tested, 60% exhibited high activity whereas 20% showed moderate activity and 20% had little activity against N. gonorrhoeae.

Molecular characterization of Gastrodiscoides hominis (Platyhelminthes: Trematoda: Digenea) inferred from ITS rDNA sequence analysis.

Gastrodiscoides hominis (Digenea: Paramphistomata: Gastrodiscidae) is an amphistomid intestinal fluke of pigs causing gastrodiscoidiosis. With the use of molecular tools assisting the conventional diagnostic procedures, we aimed at finding out molecular characterization of G. hominis using PCR amplifications of rDNA ITS (1, 2) sequences. The sequences obtained (GenBank accession numbers EF027096, EF027097, EF027098, EU887294, and EU887295) were compared with available sequences of other digenean parasites, particularly those having a zoonotic potential in the northeastern region of India. The BLAST search revealed a close similarity with members of the family Paramphistomidae, showing maximum similarity with the amphistome, Homalogaster paloniae (subfamily Paramphistominae). Based on various tree construction methods, phylogeny of G. hominis is discussed.

In vitro activity of eugenol, an active component from Ocimum sanctum, against multiresistant and susceptible strains of Neisseria gonorrhoeae.

In view of the widespread emergence of resistant isolates, an attempt was made to isolate and characterise the component(s) of Ocimum sanctum with activity against Neisseria gonorrhoeae. Bioassay-guided purification of the hexane extract of leaves of O. sanctum was carried out, which yielded H12c as the active compound. H12c was characterised and was determined to be eugenol, with a minimum inhibitory concentration of 85-256 mg/L. The antigonorrhoeal efficacy of H12c was better against multiresistant strains. The 50% lethal dose (LD50) of H12c was found to be 2g/kg body weight in rats. In view of its efficacy and lower toxicity, eugenol may be a potentially suitable molecule to be developed clinically in response to emerging resistant isolates of N. gonorrhoeae.

Genistein: is the multifarious botanical a natural anthelmintic too?

Genistein (4',5,7-trihydroxyisoflavone) is naturally present in plants of the soy family and is known to have various pharmacological activities, such as anti-cancer, anti-diabetic, anti-oxidant, etc. The phytoestrogen is one of the major isoflavones found in some medicinal plants having anthelmintic properties. This review describes the putative role of genistein as an anthelmintic, which has been tested on some helminth parasites in vitro. Genistein has been shown to cause paralysis and alterations in the tegument and tegumental enzymes (acid phosphatase, alkaline phosphatase, adenosine triphosphatase, and 5'-nucleotidase) of helminth parasites. Alterations in the activities of several enzymes associated with the coordination system (specifically non-specific esterases, acetylcholine esterase, and nitric oxide synthase), and changes in the concentration of nitric oxide, cGMP, free amino acid pool, and tissue ammonia are observed in helminth parasites treated with genistein. The phytoestrogen also affects the carbohydrate metabolism by altering the activities of key enzymes involved in glycogen- and glucose-metabolism of a cestode parasite. Considering the significance of phosphoenolpyruvate carboxykinase (PEPCK) in glycolysis of the cestode parasite, Ki of the phytoestrogen for PEPCK in the parasite has been determined, and molecular docking of genistein into the active site of the enzyme has also been described. The potential beneficial role of genistein as a natural alternative in management of helminth parasites needs to be further explored, particularly considering its in vivo efficacy and pharmacokinetics.

Long-term effects of Terminalia chebula Retz. on hyperglycemia and associated hyperlipidemia, tissue glycogen content and in vitro release of insulin in streptozotocin induced diabetic rats.

The aqueous extract of the fruits of Terminalia chebula Retz. has been evaluated for its antidiabetic activity in streptozotocin (STZ) induced mild diabetic rats and compared with a known drug, tolbutamide. The oral effective dose (ED) of the extract was observed to be 200 mg/kg body weight, which produced a fall of 55.6% (p<0.01) in the oral glucose tolerance test. Oral administration of ED of aqueous extract of T.chebula (AETC) daily once for two months reduced the elevated blood glucose by 43.2% (p<0.01) and significantly reduced the increase in glycosylated hemoglobin (HbA1c) (p<0.01). The same dose also showed a marked improvement in controlling the elevated blood lipids as well as decreased serum insulin levels in contrast to the untreated diabetic animals. Hepatic and skeletal muscle glycogen content decreased by 75% and 62.9% respectively in diabetic controls, these alterations were partly prevented (34.9% and 21.17%) in AETC treated group when compared to the healthy controls. The in vitro studies with pancreatic islets showed that the insulin release was nearly two times more than that in untreated diabetic animals. The treatment did not have any unfavorable effect on other blood parameters of liver and kidney function tests. LD 50 was found to be above 3 g/kg bw i.e. 15 times of ED, because there were no deaths of animals even at this dose indicating high margin of safety. These findings suggest further investigations for the possible use of the aqueous extract of fruits of T.chebula for the treatment of diabetes.

Surface fine topography and PCR-based determination of metacercaria of Paragonimus sp. from edible crabs in Arunachal Pradesh, Northeast India.

In several mountainous regions of Northeastern India, foci of Paragonimus infection reportedly involving species that are known to prevail in China have been identified. The present study was undertaken to demonstrate the surface fine topography and sequence analysis of the ribosomal deoxyribonucleic acid (rDNA; second internal transcribed spacer, ITS2) of the metacercarial stages of the lung fluke collected from a mountain stream of the area (Miao, Changlang District in Arunachal Pradesh). The encysted metacercariae were oval in shape and had a smooth surface. The newly excysted metacercaria had a ventral sucker larger than the oral; the body surface was covered with numerous single-pointed and thorn-like tegumentary spines, of which those on the anterior part of the body were bigger in size and showed a gradual reduction in length and number towards the posterior end; dome-shaped papillae in variable numbers were seen around the rim of the oral sucker and were sparsely distributed all over the body surface. The polymerase chain reaction-amplified rDNA ITS2 sequences of the metacercariae were aligned with known sequences for the various species of Paragonimus, and the expectation value was found to be most significant with P. westermani, revealing an absolute match. The surface topography including the number and distribution of papillae and spination patterns and the ITS2 sequences of the metacercariae strongly suggest that the Paragonimus species, prevalent in the region of India, is in fact P. westermani.

Effects of tamoxifen therapy on plasma lipid profile in patients of breast cancer.

AIM: To evaluate the effects of tamoxifen therapy on plasma lipid profile in patients of breast cancer. METHOD: A total of 55 postoperative patients of breast cancer were given tablet tamoxifen 20mg orally daily for 6 months. Estimation of plasma lipid by standard method was carried out in both pre-menopausal and postmenopausal new patients of early stage breast cancer at 0 day, 3rd month and 6th months of therapy. RESULTS: Suggested that in pre-menopausal and postmenopausal patient's TC and LDL-c levels were reduced significantly, whereas, TG, VLDL-c and HDL-c were not altered. Comparison of the effects of tamoxifen in pre-menopausal and postmenopausal patients on lipid profile revealed that fall in TC and LDL-c was significantly higher at both 3 and 6 months in postmenopausal patients. CONCLUSION: The study demonstrates that tamoxifen to favorably alter the markers of cardiovascular risk in both pre-menopausal and postmenopausal patients of breast cancer.

Erratum: Management of neglected sacral fracture with cauda equina syndrome: report of two cases with review of literature.

[This corrects the article DOI: 10.1038/scsandc.2015.20.][This corrects the article DOI: 10.1038/scsandc.2015.20.].

Infections due to Elizabethkingia meningoseptica in critically injured trauma patients: a seven-year study.

Elizabethkingia meningoseptica is an infrequent cause of hospital-acquired infections. The clinical and microbiological profiles of infections due to E. meningoseptica over a seven-year period at a Level-I trauma centre are reported in this study. Medical records of patients from whose clinical samples E. meningoseptica was isolated on more than one occasion were reviewed. A total of 21 cases were observed during the study, 16 (76.2%) of which exhibited multidrug resistance. The observed in-hospital mortality rate was 47.6%. A high index of clinical suspicion and effective detection of E. meningoseptica in clinical samples are requisite for improved clinical outcome.