In-vitro antiviral activity of Carica papaya formulations against dengue virus type 2 and chikungunya viruses.

Dengue and chikungunya are diseases of global health significance and currently, no antivirals are available to treat these arboviral diseases. Carica papaya leaves extract is traditionally used to treat thrombocytopenia in patients infected with the dengue virus. The current study was undertaken to study the antiviral activity of commercially available Carica papaya leaves extract (CPLE) based products and CPLE prepared in four formulations against dengue virus type 2 (DENV-2) and chikungunya virus (CHIKV). Maximum nontoxic concentrations of the commercially available CPLE based products and CPLE based formulations (Carica papaya leaves in powder form, Carica papaya leaves in lyophilized form, Carica papaya leaves based silver nanoparticles and supercritical fluid extract of Carica papaya leaves) were used for screening the antiviral activity. The antiviral activity against DENV-2 and CHIKV were assessed post infection using focus forming unit assay. Effective formulations were tested under different conditions i.e. pretreatment, cotreatment and posttreatment. The virus output after treatment was assessed by real-time RT-PCR, immunofluorescence assay and focus forming unit assay. The results revealed Carica papaya leaves based silver nanoparticles and supercritical fluid extract of Carica papaya leaves formulations showed significant inhibition in case of DENV while papaya leaves in powder form showed significant reduction in case of CHIKV. This study demonstrates the antiviral activity of CPLE formulations against DENV-2 and CHIKV infection in in-vitro system and needs further validation in in-vivo models.

An Unusual Case of Pulmonary Mucormycosis.

Invasive fungal infections in solid organ transplant recipients are associated with significant morbidity and mortality. Of these fungal infections, mucormycosis presents as an aggressive, frequently fatal angioinvasive infection. Immunocompromised hosts and diabetes are important risk factors. These infections are frequently difficult to diagnose. A high index of suspicion in the appropriate setting and early, aggressive treatment with the newer antifungal agents have altered the previously grave prognosis. We present the first reported case of cavitating pulmonary mucormycosis in a renal transplant recipient caused by an unusual species of Mucorales. The patient was treated with a combination of lobectomy and antifungal treatment comprising of amphotericin B and posaconazole. He remains free of disease recurrence on monotherapy with posaconazole.

Comparative Neuropathology of Major Indian Bluetongue Virus Serotypes in a Neonatal BALB/c Mouse Model.

Bluetongue virus (BTV) is neurotropic in nature, especially in ruminant fetuses and in-utero infection results in abortion and congenital brain malformations. The aim of the present study was to compare the neuropathogenicity of major Indian BTV serotypes 1, 2, 10, 16 and 23 by gross and histopathological lesions and virus distribution in experimentally infected neonatal BALB/c mice. Each BTV serotype (20 µl of inoculum containing 1 × 105 tissue culture infectious dose [TCID]50/ml of virus) was inoculated intracerebrally into 3-day-old mice, while a control group was inoculated with mock-infected cell culture medium. Infection with BTV serotypes 1, 2 and 23 led to 65-70% mortality at 7-9 days post infection (dpi) and caused severe necrotizing encephalitis with neurodegenerative changes in neurons, swelling and proliferation of vascular endothelial cells in the cerebral cortex, cerebellum, midbrain and brainstem. In contrast, infection with BTV serotypes 10 and 16 led to 25-30% mortality at 9-11 dpi and caused mild neuropathological lesions. BTV antigen was detected by immunohistochemistry, direct fluorescence antibody technique and confocal microscopy in the cytoplasm of neuronal cells of the hippocampus, grey matter of the cerebral cortex and vascular endothelial cells in the midbrain and brainstem of BTV-1, -2, -10, -16 and -23 infected groups from 3 to 20 dpi. BTV nucleic acid was detected in the infected brain tissues from as early as 24 h up to 20 dpi by VP7 gene segment-based one-step reverse transcriptase polymerase chain reaction. This study of the relative neurovirulence of BTV serotypes is likely to help design suitable vaccination and control strategies for the disease.

Genetic characterization of the glycoprotein G of Chandipura viruses in India with emphasis on an outbreak of 2015.

Chandipura virus (CHPV) is found to be associated with sporadic encephalitis outbreaks in humans in India since 1965. We report here, the investigation of CHPV activity during the period of June-August 2015 in the state of Gujarat, which revealed 24.44% positivity among 45 referred encephalitis cases. Phylogenetic study of the G gene sequences of strains from Gujarat 2015 along with available sequences of additional strains from different geographical locations and isolation years (1965-2015), indicated the relatedness of the 2015 strain to a group of the CHPV prototype strain of 1965 and the earliest outbreak strains of 2003. Analyses of selection pressure in the G gene revealed positively selected sites within the signal peptide region and a putative CHPV epitope. These results indicate a probable role of G protein-based immune selection and underline the need for continued surveillance to monitor genetic and antigenic variations in the CHPV.

The Impact of Combined Radiation and Chemotherapy on Outcome in Uterine Clear Cell Carcinoma Compared with Chemotherapy Alone.

AIMS: To investigate the impact of pelvic radiation on survival in patients with uterine clear cell carcinoma (UCC) who received adjuvant chemotherapy. MATERIALS AND METHODS: Patients with stage I-IV UCC who had undergone surgery and chemotherapy were identified from the Surveillance, Epidemiology, and End Results (SEER) programm 2000-2009. Patients were divided into those who received only chemotherapy and those who received both chemotherapy and radiation therapy. Kaplan-Meier curves and Cox regression models were used for analysis. RESULTS: Of the 317 patients included, 195 (62%) were in the chemotherapy only group and 122 (38%) were in the chemotherapy and radiation therapy group. Pelvic radiation was associated with significant improvement in overall survival (median 88 versus 25 months, 5 year survival: 58% versus 33%, P<0.001) in the chemotherapy and radiation therapy group compared with the chemotherapy only group for the entire cohort. On subset analysis, chemotherapy and radiation therapy was associated with improved overall survival in late stage disease (III-IV) (5 year 54% versus 22%, P<0.001) compared with the chemotherapy only group, whereas in stage I-II UCC, there was no difference in overall survival between the chemotherapy and radiotherapy group and the chemotherapy only group (5 year 65% versus 67%, P=0.69). In multivariable analysis, pelvic radiation was associated with improved survival in patients with late stage disease (hazard ratio 0.57, 95% confidence interval 0.35-0.94, P=0.03) but not for early stage disease (hazard ratio 0.81, 95% confidence interval 0.33-2.0, P=0.65). Other significant predictors were advanced stage, positive cytology and extensive lymphadenectomy. CONCLUSIONS: Radiation was associated with significant improvement in survival in advanced stage UCC, but not in early stage UCC. These data support the beneficial role of radiation therapy in UCC, especially in patients with advanced stage disease.

Caries burden and efficacy of a referral pathway in a cohort of preschool refugee children.

BACKGROUND: This study aimed to assess the early caries experience and the efficacy of a community based dental referral pathway in preschool refugees in Western Australia. METHODS: Preschool refugee children referred to the Western Australian paediatric hospital Refugee Health Clinic were prospectively screened for caries by a paediatric dentist before being referred to community dental clinics. Dental forms and medical records were audited to assess decayed, missing and filled teeth (dmft), medical data and dental services engagement. Poisson regression analysis determined the contribution of count variables to the final model. RESULTS: Among the 105 screened children (54% male, median age 3.2 years, 41% Burmese), community dental clinic engagement was low (46%, n=48). Of the 62% with caries (n=65/105, mean dmft 5.2, SD 4.1), 45% were recommended for specialist dental services and 48% were treated. After adjustment for age, gender and total number of teeth, caries incidence was significantly associated with BMI-for-age Z score (p=0.02). CONCLUSIONS: Preschool refugee caries burden was high. The community dental referral pathway was ineffective compared to co-located intersectorial dental screening. Specialist dental service needs are high in this cohort and require a targeted approach.

Consistency of maternal cognitions and principles across the first five months following preterm and term deliveries.

The aims of this study were to examine and compare the development of parenting cognitions and principles in mothers following preterm and term deliveries. Parenting cognitions about child development, including thinking that is restricted to single causes and single outcomes (categorical thinking) and thinking that takes into account multiple perspectives (perspectivist thinking), have been shown to relate to child outcomes. Parenting principles about using routines (structure) or infant cues (attunement) to guide daily caregiving have been shown to relate to caregiving practices. We investigated the continuity and stability of parenting cognitions and principles in the days following birth to 5 months postpartum for mothers of infants born term and preterm. All parenting cognitions were stable across time. Categorical thinking increased at a group level across time in mothers of preterm, but not term, infants. Perspectivist thinking increased at a group level for first-time mothers (regardless of birth status) and tended to be lower in mothers of preterm infants. Structure at birth did not predict later structure (and so was unstable) in mothers of preterm, but not term, infants and neither group changed in mean level across time. Attunement was consistent across time in both groups of mothers. These results indicate that prematurity has multiple, diverse effects on parenting beliefs, which may in turn influence maternal behavior and child outcomes.

Congenital hypothyroidism presenting as pseudo-obstruction in preterm infants.

Congenital hypothyroidism (CH) presenting as acute pseudo-obstruction is uncommon. We report two premature infants presenting with acute bowel obstruction subsequently diagnosed to have CH. Both responded well to medical management with thyroid supplementation.

Estradiol rapidly modulates odor responses in mouse vomeronasal sensory neurons.

In rodents, many social behaviors are driven by the sense of smell. The vomeronasal organ (VNO), part of the accessory olfactory system mediates many of these chemically driven behaviors. The VNO is heavily vascularized, and is readily accessible to circulating peptide or steroid hormones. Potentially, this allows circulating hormones to alter behavior through modulating the output of the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs). Based on this, we hypothesized that steroid hormones, in particular 17ß-estradiol, would modulate activity of VSNs. In this paper, we show that the estrogen receptors, GPR30 and ERα, were present in VSNs and that estradiol may be synthesized locally in the VNO. Our results also showed that 17ß-estradiol decreased responses of isolated VSNs to dilute urine, a potent natural stimulus, with respect to current amplitudes and depolarization. Further, 17ß-estradiol increased the latency of the first action potential (AP) and the AP amplitude. Additionally, calcium responses to sulfated steroids (present in the low molecular weight fraction of urine) that act as ligands for apical vomeronasal receptors were decreased by 17ß-estradiol. In conclusion, we show that estradiol modulates odorant responses mediated by VSNs and hence paves the way for future studies to better understand the mechanisms by which odorant mediated behavior is altered by endocrine status of the animal.

Oxygen therapy in preterm infants.

Despite being the most widely used and vital therapy in neonatology, optimal strategies for the use of oxygen in preterm infants remain controversial. Achieving the balance between attaining adequate tissue oxygenation and avoiding oxygen toxicity is challenging. There remains a paucity of clear evidence based guidance for clinicians on safe oxygen saturation targets. What does seem apparent is that these targets vary over time in the life of a preterm infant. This article summarises the evidence behind current practice of oxygen monitoring and administration from the first few minutes after birth, through to the acute neonatal and later convalescent periods. Finally, we review the use of home oxygen for preterm infants with bronchopulmonary dysplasia including administration and weaning from domically home oxygen.

Influence of evolutionary events on the Indian subcontinent on the phylogeography of dengue type 3 and 4 viruses.

During 1960-80 dengue disease profile in India was mild despite circulation of all four serotypes of dengue virus (DENV). Increase in disease severity with a concomitant change in the population of DENV-1 and 2 have been reported since then. To determine population dynamics of DENV-3 and 4, the envelope (E) gene sequence was determined for 16 Indian isolates of DENV-3 and 11 of DENV-4 and analyzed together with 97 DENV-3 and 43 DENV-4 global sequences. All Indian DENV-3 isolates belonged to genotype III, lineages C, D, E and F. Lineage F was newly identified and represented non-circulating viruses. Three non-conservative amino acid changes in domain I, II & III were identified during the transition from lineages F/E, associated with mild disease, to A-D, associated with severe disease. For DENV-4, the current viruses clustered in genotype I, lineage C, whilst the isolates from 1960s formed the new genotype V. A 1979 Indian isolate of DENV-4 was found to be an inter-genotypic recombinant of Sri Lankan isolate (1978) of genotype I and Indian isolate (1961) of genotype V. The rates of nucleotide substitution and time to the most recent common ancestor (tMRCA) estimated for DENV-3 (1782-1934) and DENV-4 (1719-1931) were similar to earlier reports. However, the divergence time for genotype III of DENV-3, 1938-1963, was a more accurate estimate with the inclusion of Indian isolates from the 1960s. By phylogeographical analysis it was revealed that DENV-3 GIII viruses emerged from India and evolved through Sri Lanka whilst DENV-4 emerged and dispersed from India. The present study demonstrates the crucial role that India/Sri Lanka have played in the evolution and dispersion of the major genotypes, GIII of DENV-3 and GI of DENV-4 which are more virulent and show higher dissemination potential.