Unusual outcome of in utero infection and subsequent postnatal super-infection with different PCV2b strains

VC2002, isolated from postweaning multisystemic wasting syndrome (PMWS)-affected pig, is a mixture of two porcine circovirus genotype 2b (PCV2b) viruses, K2 and K39. Preliminary experiments disclosed short-term adverse effects of K39, but not K2, on porcine foetuses. These findings led to the hypothesis that infection of immuno-incompetent foetuses with K2 confers a status of immunotolerance, and postnatal super-infection with K39 triggers PMWS. To explore this hypothesis, nine 55-day-old foetuses were inoculated in utero (three with K2-10^4.3TCID₅₀, three with K39-10^4.3TCID₅₀ and three with medium), and foeto-pathogenicity examined. At 21 days post-inoculation (dpi), K2 did not induce pathology, whereas pathological effects of K39 were evident. Twenty-four 45-day-old foetuses were subsequently inoculated to examine the long-term effect of K2, including six with K2-high dose-10^4.3TCID₅₀, six with K2-low dose-10^2.3TCID₅₀ and 12 mock-inoculated controls. Both doses resulted in five mummified foetuses and one live-born piglet each (69dpi). K2 was recovered from all mummies. K2 and K2-specific antibodies were not detected in serum of the two live-born piglets at birth, indicating full control of K2 infection. The K2-low dose-infected piglet was immunostimulated at day 2, but not the K2-high dose-infected piglet. Both non-stimulated and stimulated K2-infected piglets were super-inoculated with K39 at day 6 or 8 (taken as 0 days post super-inoculation). Low viral replication was observed in the non-stimulated K2-K39 piglet (up to 10^3.3TCID₅₀/g; identified as K39). In contrast, viral replication was extremely high in the stimulated K2-K39 piglet (up to 10^5.6TCID₅₀/g) and identified as K2, indicating that K2 infection is controlled during foetal life, but emerges after birth upon immunostimulation. However, none of the piglets showed any signs of PMWS.     

A Five-Year Experience of Carbapenem Resistance in Enterobacteriaceae Causing Neonatal Septicaemia: Predominance of NDM-1

Treatment of neonatal sepsis has become a challenge with the emergence of carbapenemase-producing bacteria. This study documents the trend of carbapenem susceptibility in Enterobacteriaceae that caused septicaemia in neonates over a five year period (2007–2011) and the molecular characterisation of Enterobacteriaceae resistant to carbapenems and cephalosporins. Hundred and five Enterobacteriaceae including Escherichia coli (n = 27), Klebsiella pneumoniae (n = 68) and Enterobacter spp. (n = 10) were isolated from blood of septicaemic neonates followed by antibiotic susceptibility tests, determination of MIC values, phenotypic and genotypic detection of β-lactamases. Carbapenem was the most active antimicrobial tested after tigecycline. CTX-M type was the most prevalent ESBL throughout the period (82%). New Delhi Metallo-β-lactamase-1 (NDM-1), which is a recent addition to the carbapenemase list, was the only carbapenemase identified in our setting. Fourteen percent of the isolates possessed bla_NDM-1. Carbapenem non-susceptibility was first observed in 2007 and it was due to loss of Omp F/Ompk36 in combination with the presence of ESBLs/AmpCs. NDM-1 first emerged in E. coli during 2008; later in 2010, the resistance was detected in K. pneumoniae and E. cloacae isolates. NDM-1-producing isolates were resistant to other broad-spectrum antibiotics and possessed ESBLs, AmpCs, 16S-rRNA methylases, AAC(6′)-Ib-cr, bleomycin resistant gene and class 1 integron. Pulsed field gel electrophoresis of the NDM-1-producing isolates indicated that the isolates were clonally diverse. The study also showed that there was a significantly higher incidence of sepsis caused by NDM-1-harbouring isolates in the male sex, in neonates with low birth weight and neonates born at an extramural centre. However, sepsis with NDM-1-harbouring isolates did not result in a higher mortality rate. The study is the first to review the carbapenem resistance patterns in neonatal sepsis over an extended period of time. The study highlights the persistence of ESBLs (CTX-Ms) and the emergence of NDM-1 in Enterobacteriaceae in the unit.     

Role of Ferulic Acid in the Amelioration of Ionizing Radiation Induced Inflammation: A Murine Model

Ionizing radiation is responsible for oxidative stress by generating reactive oxygen species (ROS), which alters the cellular redox potential. This change activates several redox sensitive enzymes which are crucial in activating signaling pathways at molecular level and can lead to oxidative stress induced inflammation. Therefore, the present study was intended to assess the anti-inflammatory role of ferulic acid (FA), a plant flavonoid, against radiation-induced oxidative stress with a novel mechanistic viewpoint. FA was administered (50 mg/kg body wt) to Swiss albino mice for five consecutive days prior to exposing them to a single dose of 10 Gy ⁶⁰Co γ-irradiation. The dose of FA was optimized from the survival experiment and 50 mg/kg body wt dose showed optimum effect. FA significantly ameliorated the radiation induced inflammatory response such as phosphorylation of IKKα/β and IκBα and consequent nuclear translocation of nuclear factor kappa B (NF-κB). FA also prevented the increase of cycloxygenase-2 (Cox-2) protein, inducible nitric oxide synthase-2 (iNOS-2) gene expression, lipid peroxidation in liver and the increase of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum. It was observed that exposure to radiation results in decreased activity of superoxide dismutase (SOD), catalase (CAT) and the pool of reduced glutathione (GSH) content. However, FA treatment prior to irradiation increased the activities of the same endogenous antioxidants. Thus, pretreatment with FA offers protection against gamma radiation induced inflammation.     

Predicting Early Mortality in Adult Trauma Patients Admitted to Three Public University Hospitals in Urban India: A Prospective Multicentre Cohort Study

BackgroundIn India alone, more than one million people die yearly due to trauma. Identification of patients at risk of early mortality is crucial to guide clinical management and explain prognosis. Prediction models can support clinical judgement, but existing models have methodological limitations. The aim of this study was to derive a vital sign based prediction model for early mortality among adult trauma patients admitted to three public university hospitals in urban India.MethodsWe conducted a prospective cohort study of adult trauma patients admitted to three urban university hospitals in India between October 2013 and January 2014. The outcome measure was mortality within 24 hours. We used logistic regression with restricted cubic splines to derive our model. We assessed model performance in terms of discrimination, calibration, and optimism.ResultsA total of 1629 patients were included. Median age was 35, 80% were males. Mortality between admission and 24 hours was 6%. Our final model included systolic blood pressure, heart rate, and Glasgow coma scale. Our model displayed good discrimination, with an area under the receiver operating characteristics curve (AUROCC) of 0.85. Predicted mortality corresponded well with observed mortality, indicating good calibration.ConclusionThis study showed that routinely recorded systolic blood pressure, heart rate, and Glasgow coma scale predicted early hospital mortality in trauma patients admitted to three public university hospitals in urban India. Our model needs to be externally validated before it can be applied in the clinical setting.     

Vegetation Response and Landscape Dynamics of Indian Summer Monsoon Variations during Holocene: An Eco-Geomorphological Appraisal of Tropical Evergreen Forest Subfossil Logs

The high rainfall and low sea level during Early Holocene had a significant impact on the development and sustenance of dense forest and swamp-marsh cover along the southwest coast of India. This heavy rainfall flooded the coastal plains, forest flourishing in the abandoned river channels and other low-lying areas in midland.The coastline and other areas in lowland of southwestern India supply sufficient evidence of tree trunks of wet evergreen forests getting buried during the Holocene period under varying thickness of clay, silty-clay and even in sand sequences. This preserved subfossil log assemblage forms an excellent proxy for eco-geomorphological and palaeoclimate appraisal reported hitherto from Indian subcontinent, and complements the available palynological data. The bulk of the subfossil logs and partially carbonized wood remains have yielded age prior to the Holocene transgression of 6.5 k yrs BP, suggesting therein that flooding due to heavy rainfall drowned the forest cover, even extending to parts of the present shelf. These preserved logs represent a unique palaeoenvironmental database as they contain observable cellular structure. Some of them can even be compared to modern analogues. As these woods belong to the Late Pleistocene and Holocene, they form a valuable source of climate data that alleviates the lack of contemporaneous meteorological records. These palaeoforests along with pollen proxies depict the warmer environment in this region, which is consistent with a Mid Holocene Thermal Maximum often referred to as Holocene Climate Optimum. Thus, the subfossil logs of tropical evergreen forests constitute new indices of Asian palaeomonsoon, while their occurrence and preservation are attributed to eco-geomorphology and hydrological regimes associated with the intensified Asian Summer Monsoon, as recorded elsewhere.     

Outcome of Central Nervous System Relapses In Childhood Acute Lymphoblastic Leukaemia – Prospective Open Cohort Analyses of the ALLR3 Trial

The outcomes of Central Nervous System (CNS) relapses in children with acute lymphoblastic leukaemia (ALL) treated in the ALL R3 trial, between January 2003 and March 2011 were analysed. Patients were risk stratified, to receive a matched donor allogeneic transplant or fractionated cranial irradiation with continued treatment for two years. A randomisation of Idarubicin with Mitoxantrone closed in December 2007 in favour of Mitoxantrone. The estimated 3-year progression free survival for combined and isolated CNS disease were 40.6% (25·1, 55·6) and 38.0% (26.2, 49.7) respectively. Univariate analysis showed a significantly better survival for age <10 years, progenitor-B cell disease, good-risk cytogenetics and those receiving Mitoxantrone. Adjusting for these variables (age, time to relapse, cytogenetics, treatment drug and gender) a multivariate analysis, showed a poorer outcome for those with combined CNS relapse (HR 2·64, 95% CI 1·32, 5·31, p = 0·006 for OS). ALL R3 showed an improvement in outcome for CNS relapses treated with Mitoxantrone compared to Idarubicin; a potential benefit for matched donor transplant for those with very early and early isolated-CNS relapses.

Trial Registration

Controlled-Trials.com ISRCTN45724312     

Dynamic Modularity of Host Protein Interaction Networks in Salmonella Typhi Infection

Background

Salmonella Typhi is a human-restricted pathogen, which causes typhoid fever and remains a global health problem in the developing countries. Although previously reported host expression datasets had identified putative biomarkers and therapeutic targets of typhoid fever, the underlying molecular mechanism of pathogenesis remains incompletely understood.

Methods

We used five gene expression datasets of human peripheral blood from patients suffering from S. Typhi or other bacteremic infections or non-infectious disease like leukemia. The expression datasets were merged into human protein interaction network (PIN) and the expression correlation between the hubs and their interacting proteins was measured by calculating Pearson Correlation Coefficient (PCC) values. The differences in the average PCC for each hub between the disease states and their respective controls were calculated for studied datasets. The individual hubs and their interactors with expression, PCC and average PCC values were treated as dynamic subnetworks. The hubs that showed unique trends of alterations specific to S. Typhi infection were identified.

Results

We identified S. Typhi infection-specific dynamic subnetworks of the host, which involve 81 hubs and 1343 interactions. The major enriched GO biological process terms in the identified subnetworks were regulation of apoptosis and biological adhesions, while the enriched pathways include cytokine signalling in the immune system and downstream TCR signalling. The dynamic nature of the hubs CCR1, IRS2 and PRKCA with their interactors was studied in detail. The difference in the dynamics of the subnetworks specific to S. Typhi infection suggests a potential molecular model of typhoid fever.

Conclusions

Hubs and their interactors of the S. Typhi infection-specific dynamic subnetworks carrying distinct PCC values compared with the non-typhoid and other disease conditions reveal new insight into the pathogenesis of S. Typhi.     

Treatment of phenolics containing synthetic wastewater in an internal loop airlift bioreactor (ILALR) using indigenous mixed strain of Pseudomonas sp. under continuous mode of operation

The scope of this study is to evaluate the performance of internal loop airlift bioreactor (ILALR) in treating synthetic wastewater containing phenol and m-cresol, in single and multi component systems. The microbe utilized in the process was an indigenous mixed strain of Pseudomonas sp. isolated from a wastewater treatment plant. The reactor was operated at both lower and higher hydraulic retention times (HRTs) i.e., 4.1 and 8.3 h, respectively, by providing an inlet feed flow rate of 5 and 10 mL/min. Shock loading experiments were also performed up to a maximum concentration of 800 mg/L for phenol at 8.3 h HRT and 500 mg/L for m-cresol at 4.1 h HRT. The study showed complete degradation of both phenol and m-cresol, when they were degraded individually at a HRT of 8.3 h. Experiments with both phenol and m-cresol present as mixtures were performed based on the 2² full factorial design of experiments.