First report of Burkholderia pseudomallei ST412 and ST734 clones harbouring blaOXA-57 but susceptible to imipenem in India.

Melioidosis caused by Burkholderia pseudomallei has become an important clinical threat, especially in Northern Australia and Southeast Asia. However, the genome information on this pathogen is limited. B. pseudomallei isolates identified from bloodstream infections from inpatients were subjected to whole-genome sequencing by IonTorrent PGM and MinION Oxford Nanopore sequencing technologies. Highly accurate complete genomes of two strains, VB3253 and VB2514, were obtained by a hybrid genome assembly method using both short and long DNA reads. Both isolates carried blaPenI and carbapenemase-encoding blaOXA-57 genes, although the isolates were susceptible to imipenem by E-test method with MIC 1 µg/mL. Multiple IS family transposases specific for all non-fermenting Gram-negative bacteria (NFGNBs)-especially IS3 and IS5, which facilitate mobilization of extended-spectrum ß-lactamase (ESBL) and carbapenemase genes-were carried in these genomes. This further adds to the complexity of gene transmission. These IS families were identified only upon hybrid genome assembly and would otherwise be missed.

Age increases the risk of immediate postoperative dysphagia and pneumonia after odontoid screw fixation.

INTRODUCTION: Type II odontoid fractures are the most common spinal fracture in the elderly population and may be managed with halo immobilization, posterior fusion, and anterior odontoid screw fixation. Anterior odontoid screw fixation has several advantages over posterior fusion, including: reduced surgical time, decreased post-operative pain, preserved range of motion, earlier mobilization, and decreased postoperative narcotic requirement. We review our experience using anterior odontoid screw fixation in type II odontoid fractures in the elderly and non-elderly populations. METHODS: Demographic and outcome data were retrospectively collected in 30 consecutive patients with type II odontoid fractures treated with anterior odontoid screw fixation. RESULTS: Mean patient age was 70.7 (range 20-92); 18 of the patients were male and 12 were female. All patients had successful placement of a single anterior odontoid screw without intra-operative complication. Complications included pneumonia in nine patients (30%), gastrostomy tube placement due to patient failing swallow evaluation in 13 patients (43%), and vocal cord paralysis in one patient (3.3%). Patients over the age of 75 accounted for 12 of the 13 (92%) gastrostomy tube placements and eight of the nine (88.9%) pneumonias, respectively. The difference in rates of gastrostomy tube placement and pneumonia for the older patients were both found to be statistically significant with P<.0001 for gastrostomy tubes and P<.02 for pneumonias. CONCLUSIONS: Anterior odontoid screw fixation is an effective treatment option for patients with Type II odontoid fractures. In the elderly population, however, the benefits of the procedure must be weighed against the risks of postoperative dysphagia requiring gastrostomy and pneumonia.

Antibiotic treatment of pregnant non-obese diabetic mice leads to altered gut microbiota and intestinal immunological changes in the offspring.

The intestinal microbiota is important for tolerance induction through mucosal immunological responses. The composition of the gut microbiota of an infant is affected by environmental factors such as diet, disease and antibiotic treatment. However, already in utero, these environmental factors can affect the immunological development of the foetus and influence the future gut microbiota of the infant. To investigate the effects of antibiotic treatment of pregnant mothers on the offspring's gut microbiome and diabetes development, we treated non-obese diabetic (NOD) mice with a cocktail of antibiotics during gestation and the composition of the gut microbiota, diabetes incidence and major gut-related T lymphocyte populations were investigated in the offspring. We observed a persistent reduction in the general diversity of the gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. In addition, by clustering the present bacterial taxa with principal component analysis, we found a differential clustering of gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. Offspring from NOD mothers treated with antibiotics during gestation also showed some immunological alterations in the gut immune system, which could be related to the diversity of the gut microbiome and influence modulation of diabetes development at 20 weeks. Our data point out maternal derangement of the intestinal microbiota as a potential environmental risk factor for T1D development.

Uptake of HIV testing and HIV positivity among presumptive tuberculosis patients at Puducherry, South India.

SETTING: Puducherry, a district in South India with a low prevalence of human immunodeficiency virus (HIV) infection (<1% among antenatal women). OBJECTIVES: 1) To estimate the proportion of patients with known HIV status who were HIV-positive, 2) to describe the demographic and clinical characteristics of patients with unknown HIV status among presumptive TB patients, and 3) to assess the additional workload at HIV testing centres. DESIGN: In this cross-sectional study, consecutive presumptive TB patients attending microscopy centres for diagnosis during March-May 2013 were asked if they knew their HIV status. Patients with unknown HIV status were offered voluntary counselling and HIV testing. RESULTS: Of 1886 presumptive TB patients, HIV status was ascertained for 842 (44.6%); 28 (3.3%) were HIV-positive. The uptake of HIV testing was significantly higher in younger age groups, males, residents of Puducherry and smear-positive TB patients. The median increase in the number of clients tested for HIV per day per testing centre was 1 (range 0-6). CONCLUSION: The uptake of HIV testing was low. HIV prevalence was higher among presumptive TB patients than in antenatal women, and as high as in TB patients. With minimal increase in workload at HIV testing centres, HIV testing could be implemented using existing resources.

Anti-cell proliferative efficacy of ferulic acid against 7, 12-dimethylbenz(a) anthracene induced hamster buccal pouch carcinogenesis.

The present study was designed to explore the anti-cell proliferative efficacy of ferulic acid by analysing the expression pattern of cell proliferative markers, proliferating cellular nuclear antigen (PCNA) and cyclin D1, in the buccal mucosa of golden Syrian hamsters treated with 7,12-dimethylbenz(a)anthracene (DMBA). Oral squamous cell carcinomas developed in the buccal pouch of hamsters using topical application of 0.5% DMBA three times a week for 14 weeks. Immunohistochemical (PCNA) and RT-PCR (Cyclin D1) analysis revealed over expression of PCNA and cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone (tumor bearing hamsters). Oral administration of ferulic acid at a dose of 40 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also down regulated the expression of PCNA and cyclin D1. The results of the present study thus suggests that ferulic acid might have inhibited tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative potential as evidenced by decreased expression of PCNA and cyclin D1.

In vitro fertility rate of 129 strain is improved by buserelin (gonadotropin-releasing hormone) administration prior to superovulation.

The 129 mice are well recognized for their low fertility and it is speculated that this lack of fertility may be due to the oocyte condition. In this study we investigated superovulation regimens for the 129S1/SvImJ mouse strain to improve the oocyte quality and fertility rate of in vitro fertilization (IVF). Female mice were divided into four groups based on hormone and timing of injection. Group 1 received pregnant mare serum gonadotropin (PMSG) and 48 h later human chorionic gonadotropin (hCG); using the same dose, group 2 received hCG 52 h post-PMSG and group 3, 55 h post-PMSG. Group 4 received buserelin (gonadotropin-releasing hormone agonist [GnRH]) followed 24 h later by PMSG and then hCG 55 h post-PMSG. IVF was performed using 129S1/SvImJ oocytes and sperm; C57BL/6J sperm with 129S1/SvImJ oocytes was used as fertility control. The IVF fertility rate was 1% (Groups 1 and 2), 17% (Group 3) and 55% (Group 4) for 129 oocytes fertilized with 129 sperm. For 129 oocytes fertilized with C57BL/6J sperm, the fertility rate was 5% (Group 1), 10% (Group 2), 40% (Group 3) and 59% (Group 4). These results suggest that extending the interval time between PMSG and hCG and giving GnRH in addition to the standard PMSG and hCG treatments can improve IVF fertility rate of 129S1/SvImJ mouse strains significantly.

Major liver resection without preoperative biliary drainage in jaundiced patients with hilar biliary obstruction.

BACKGROUND: The need for routine use of preoperative biliary drainage (PBD) for major liver resection in jaundiced patients has recently been questioned. METHODS: We present our experience of 22 consecutive patients with hilar biliary obstruction who underwent major liver resection without PBD between January 2007 and January 2011. RESULTS: Twenty-two patients with hilar biliary obstruction underwent major liver resection without PBD over a 4-year period; nineteen had malignant and 3 benign hilar strictures. Fifteen patients underwent right hepatectomy (7) or right trisectionectomy (8) and seven underwent left hepatectomy. Segment 4a was spared in all patients who underwent right trisectionectomy. Six patients had concomitant portal vein resection. Fourteen patients had varying degrees of lobar atrophy. The median preoperative bilirubin was 18 mg % (range 9.1 to 27 mg %). The median blood transfusion requirement was 2 units (range 1-6). There was one postoperative death from portal vein thrombosis. Three patients who underwent greater than 50 % resection developed postoperative ascites. CONCLUSIONS: Major liver resection leaving a liver remnant of 50 % is safe in jaundiced patients without PBD even when portal vein reconstruction is necessary. PBD should be used selectively.

Adenomatoid odontogenic tumor, an uncommon tumor.

Here we report a case of adenomatoid odontogenic tumor (AOT) in the maxilla in a young girl aged 14 years and its surgical management. We also review the literature and variations in the nomenclature and classifications of this interesting tumor. The review of literature gives an interesting picture regarding terminologies in the past and dilemma in classifying this tumor. The introduction of the name adenomatoid odontogenic tumour has resulted in the simpler and fruitful surgical management like enucleation and curettage with no reports of recurrences. In the past, similar lesion with the terminology like adeno ameloblastoma has resulted in unnecessary mutilating surgery. The conflicting views whether the lesion is being neoplasm or an anomalous hamartomatous growth is also being discussed.

Anti-tumor initiating potential of andrographolide in 7,12-dimethylbenz[a]anthracene induced hamster buccal pouch carcinogenesis.

The aim of the study was to investigate the chemopreventive potential of andrographolide in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors developed in the buccal pouch of golden Syrian hamsters at a 100% incidence on painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Marked abnormalities in the status of detoxification enzymes, lipid perxodiation and antioxidants were noticed in hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/ kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also restored the status of the above mentioned biomarkers. The present study thus demonstrates the chemopreventive potential of andrographolide in DMBA-induced hamster buccal pouch carcinogenesis, which is probably due to its antioxidant potential as well as modulating effect on xenobiotic metabolising enzymes during DMBA-induced oral carcinogenesis.

Quantum chemistry calculations of 3-Phenoxyphthalonitrile dye sensitizer for solar cells.

The geometries, electronic structures, polarizabilities, and hyperpolarizabilities of organic dye sensitizer 3-Phenoxyphthalonitrile were studied based on Hartree-Fock (HF) and density functional theory (DFT) using the hybrid functional B3LYP. Ultraviolet-visible (UV-vis) spectrum was investigated by time dependent DFT (TD-DFT). Features of the electronic absorption spectrum in the visible and near-UV regions were assigned based on TD-DFT calculations. The absorption bands are assigned to pi-->pi* transitions. Calculated results suggest that the three excited states with the lowest excited energies in 3-Phenoxyphthalonitrile is due to photoinduced electron transfer processes. The interfacial electron transfer between semiconductor TiO(2) electrode and dye sensitizer 3-Phenoxyphthalonitrile is due to an electron injection process from excited dye to the semiconductor's conduction band. The role of phenoxy group in 3-Phenoxyphthalonitrile in geometries, electronic structures, and spectral properties were analyzed.

Antiatherogenic effect of taurine in high fat diet fed rats.

The role of taurine on atherogenesis induced by high fat diet in rats, a species which depends entirely on taurine for conjugation of bile acids has been investigated. Wistar male rats were fed on (p.o.) taurine in addition to high fat diet (11% coconut oil w/w) for 6 months. High fat diet caused significant increase of serum total cholesterol (2 fold), serum triglycerides (92.6%), LDL cholesterol (92.3%) and body weight gain (2.8 fold). Taurine administration significantly reduced serum cholesterol (37%), triglycerides (94.5%), LDL cholesterol (34%), body weight (46%). It also significantly reduced aortic cholesterol and thiobarbituric acid reactive substances and there was a significant increase of reduced glutathione. Taurine significantly increased fecal bile acids which may have resulted in significant decrease of serum cholesterol. Aortic lesion index was significantly decreased in the taurine administered group suggesting the antiatherogenic effect of taurine. It is concluded that taurine attenuated the atherogenesis possibly by its hypocholesterolemic and antioxidant property.

Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer cell apoptosis and tumor regression.

Prostate cancer cells are generally resistant to apoptosis by conventional therapy. During a search for molecules that may overcome prostate cancer cell survival mechanisms, we identified the prostate apoptosis response-4 (Par-4) gene. Par-4 induced apoptosis of selective prostate cancer cells PC-3, DU-145, and TSU-Pr and caused tumor regression by inhibition of NF-kappaB activity and cell membrane trafficking of Fas and FasL that leads to the activation of the Fas-Fas-associated death domain-caspase-8 pro-death pathway. Neither Fas pathway activation alone nor inhibition of NF-kappaB activity with IkappaB-super repressor was sufficient to induce apoptosis of prostate cancer cells. Coregulation of these two pathways was essential and sufficient for Par-4 to induce apoptosis. On the other hand, prostate cancer cells LNCaP or normal prostatic epithelial cells that were resistant to apoptosis by Par-4 did not show Fas or FasL trafficking. These findings identify a mechanism of apoptosis by Par-4 and suggest that Par-4 may have therapeutic potential.

Regulation of apoptosis in prostate cancer.

Transformation and malignant progression of prostate cancer is regulated by the inability of prostatic epithelial cells to undergo apoptosis rather than by increased cell proliferation. The basic apoptotic machinery of most prostate cancer cells is intact and the inability to undergo apoptosis is due to molecular alterations that result in failure to initiate or execute apoptotic pathways. This review discusses the role of anti-apoptotic proteins such as Bcl-2/BclXL, NF-kappaB, IGF, caveolin, and Akt, and pro-apoptotic molecules such as PTEN, p53, Bin1, TGF-beta, and Par-4 that can regulate progression of prostate cancer. In addition to highlighting the salient features of these molecules and their relevance in apoptosis, this review provides an appraisal of their therapeutic potential in prostate cancer. Molecular targeting of these proteins and/or their innate pro- or anti-apoptotic pathways, either singly or in combination, may be explored in conjunction with conventional and currently available experimental strategies for the treatment of both hormone-sensitive and hormone-resistant prostate cancer.

Influence of intragastric perfusion of aqueous spice extracts on acid secretion in anesthetized albino rats.

BACKGROUND: The effect of spices on gastric acid secretion is variable. Their mechanism of action is also not well established. AIM: To study the effect of spices on gastric acid secretion in anesthetized rats. METHODS: Aqueous extracts (10% w/v) of red pepper (Capsicum annuum), fennel (Foeniculum vulgare), omum/ajwan (Carum copticum), cardamom (Elettaria cardamomum), black pepper (Piper nigrum), cumin (Cuminum cyminum) and coriander (Coriandrum sativum) were prepared. The stomach of pentobarbitone-anesthetized rats was perfused at 0.15 mL/min with aqueous extracts of spice or acetylcholine (1 microgram/mL or 10 micrograms/mL solutions, in 40 min blocks, twice in each experiment bracketed by saline perfusions. The acid content in the samples was estimated by titration with 0.1N NaOH with phenolphthalein as indicator. Atropine 1 microgram/mL was added to the perfusion fluid in 28 experiments. In 32, acute gastric mucosal injury was induced by leaving aspirin 125 mg/Kg in the stomach for 2 h before perfusion. RESULTS: All the spices tested increased acid secretion in the following declining order: red pepper, fennel, omum, cardamom, black pepper, cumin, coriander. Red pepper increased acid secretion (mean [SEM] 0.93 [0.16] mL 0.1N HCl) to about 7 times the basal secretion (0.14 [0.05]; p < 0.005). The increase in acid secretion by the other spices was as follows: fennel 0.42 (0.11) mL 0.1 N HCl from basal secretion (0.12 [0.03]) (p < 0.02); omum 0.33 (0.05) from 0.09 (0.02) (p < 0.01); cardamom 0.28 (0.04) from 0.10 (0.03) (p < 0.005); black pepper 0.19 (0.03) from 0.04 (0.01) (p < 0.005); cumin 0.12 (0.02) from 0.08 (0.01) (p < 0.05); coriander 0.18 (0.03) from 0.09 (0.02) (p < 0.005). Atropine abolished the acid secretion induced by acetylcholine and significantly reduced acid induction by red pepper, omum and coriander, but not that by fennel. In experiments with aspirin-induced mucosal injury the basal acid secretion was low; acid secretion by red pepper and fennel was reduced significantly, but not that by acetylcholine. Cumin and coriander increased acid secretion in injured stomachs. CONCLUSION: The spices tested increased gastric acid secretion, in some by a cholinergic mechanism but by other mechanism(s) as well. Red pepper produced maximum increase in acid secretion, but this was significantly reduced in injured stomachs. Cumin and coriander increased gastric secretion in injured stomachs.

The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses.

Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of their cognate tyrosine kinase receptors, ErbB 1-4. The subcellular distribution and mechanisms that regulate the localization of ErbB receptors are unknown. We have found that ErbB receptors are present in brain subcellular fractions enriched for postsynaptic densities (PSD). The ErbB-4 receptor is unique among the ErbB proteins because its C-terminal tail (T-V-V) conforms to a sequence that binds to a protein motif known as the PDZ domain. Using the yeast two-hybrid system, we found that the C-terminal region of ErbB-4 interacts with the three related membrane-associated guanylate kinases (MAGUKs) PSD-95/SAP90, PSD-93/chapsyn-110, and SAP 102, which harbor three PDZ domains, as well as with beta(2)-syntrophin, which has a single PDZ domain. As with N-methyl-D-aspartate (NMDA) receptors, ErbB4 interacts with the first two PDZ domains of PSD-95. Using coimmunoprecipitation assays, we confirmed the direct interactions between ErbB-4 and PSD-95 in transfected heterologous cells, as well as in vivo, where both proteins are coimmunoprecipitated from brain lysates. Moreover, evidence for colocalization of these proteins was also observed by immunofluorescence in cultured hippocampal neurons. ErbB-4 colocalizes with PSD-95 and NMDA receptors at a subset of excitatory synapses apposed to synaptophysin-positive presynaptic terminals. The capacity of ErbB receptors to interact with PDZ-domain proteins at cell junctions is conserved from invertebrates to mammals. As discussed, the interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity.

Developmental brain injury associated with abnormal play behavior in neonatally Borna disease virus-infected Lewis rats: a model of autism.

Play behavior, nonsocial exploratory activity, and nonplay social interaction were observed in male juvenile Lewis rats with brain developmental injury following neonatal infection with Borna disease virus (BDV). These behaviors were tested using the 'intruder-resident' paradigm, with social isolation of residents for six days prior to testing. Four experimental pairings of infected (BDV) and uninfected (NL) rats were studied as follows: NL-NL; NL BDV; BDV NL; and BDV-BDV (the first member is the resident, the second member is the intruder). Observation of social activities was carried out for 10 min on two consecutive days. Nonsocial exploratory activity (e.g. ambulation and rearing) was similar in BDV and NL residents. Duration of nonplay social investigation (e.g. sniffing, approach, and follow) was higher in BDV residents as compared to NL residents when tested on the first test day. On the second day, all rats showed similar level of nonplay social interaction. When confronted with NL intruders, NL residents exhibited significantly more play behavior compared to the NL-BDV, BDV NL and BDV-BDV pairs, when play behavior was measured by the number of 'pins'. Moreover, irrespective of a type of intruder, NL residents demonstrated higher play soliciting behavior than BDV residents, indicating attenuated readiness to play in BDV-infected rats. The number of pins and play solicitations in BDV-NL pairs significantly increased over the two days of testing, while play activity in NL-BDV pairs declined on the second test day. This pattern suggests that the degree of social reinforcement on the first day of testing affected the level of play on the second day. These data demonstrate deficits in play behavior and other social interactions following BDV-associated developmental brain injury, thus supporting the value of the neonatally BDV-infected rat as an animal model of autism.

Use of rat jejunum for assay of acetylcholine.

Experiments were carried out to determine the advantage in using isolated rat jejunum in the assay of acetylcholine (ACh) in preference to other tissues. Rat jejunum was found to be sensitive to ACh 0.01 micrograms, 5-hydroxytryptamine (5HT) 0.2 to 0.5 microgram and least sensitive to histamine. (Ach greater than 5HT greater than histamine).