Molecular and phylogenetic analysis of the dengue strains circulating in Odisha, India.

Dengue has emerged as a major public health challenge in terms of both changing clinical pattern and epidemiological features. The state of Odisha reported first dengue epidemic in the year 2010 and this continued each year in epidemic form during post monsoon period gradually becoming an endemic phenomenon. Present study depicts the changing epidemiological and clinical pattern of dengue with reference to its serotypes and genotypes. The study included 5320 suspected dengue cases from different health facilities of the state during 2010-2017. Dengue NS1 antigen and IgM antibody was done through ELISA. Serotyping was done through RTPCR by amplifying a part of core-pre-membrane gene (CprM) followed by sequencing and phylogenetic analysis. Dengue IgM antibody in 17.7% cases and NS1 antigen in 53.20% cases was detected. Dengue serotype 2 (DEN-2) was the only serotype detected in 2010 and 2011 where as all four serotypes 1, 2, 3, 4 were detected in 2012-2017, DEN-2 being dominant but in 2017 DEN-3 was found to be dominant. Phylogenetic analysis revealed genotype IV of DEN-2 and genotype III of DEN-1 and DEN-3 circulating in this region. In 6 cases involvement of DEN-2 in clinically evident encephalitis cases is an important observation in this region and needs public health attention. High prevalence of dengue was observed without any previous reported outbreaks in the state with increased number of cases from 2010 to 2012 affecting both urban and rural areas. High incidence in 2012 was due to co-circulation of more than one serotype which continued in the following years. Severity in some cases was associated with mixed infection but in most cases it was mild indicating the endemic nature of the virus in most parts of Odisha.

Epidemiological and clinical profile of Influenza A(H1N1) pdm09 in Odisha, eastern India.

Epidemic of flu is highly contagious and it spreads through air. In 2009 H1N1 influenza virus emerged after reassortment of North American TRIG and Eurasia Avian like virus of swine and started epidemic in Mexico. The first cases were reported from Hyderabad city on 16th May 2009 in India that spread rapidly within a short span of time. During this period large population of Odisha situated at the eastern side of India was also affected and incidences of H1N1 cases were recorded through state Government surveillance system. In this study real time RT-PCR based diagnosis was conducted for the throat swabs collected from suspected H1N1 cases in Odisha during 2009-2017. A total of 2872 throat swabs were received from 23 different Government and private hospitals and 21.1% positivity was confirmed. The disease affected mostly 46-60 years age group, males (50.6%) being more affected. The clinical features had shown that fever with cough (89.6%) was the most common symptom followed by shortness of breath (72.7%). Post monsoon was the peak season in which most of the cases were reported. Neurological signs, pregnancy, diabetes and hypertension were found to be risk factors for H1N1. The case fatality rate (CFR) was 15%.

Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score.

BACKGROUND: Results of endovascular interventions in hepatic venous outflow tract obstruction (HVOTO) have been reported from limited studies. Treatment outcomes and prognostic scores need further validation. AIM: To evaluate treatment outcomes and prognostic scores for hepatic venous outflow tract obstruction in an Indian population. METHODS: Consecutive patients with hepatic venous outflow tract obstruction diagnosed at a tertiary centre were included. Technical success and clinical response after endovascular interventional therapy were documented. Predictors of survival were assessed with Cox-proportional model. A new score was derived from the factors significant on multivariate analysis and compared with Child-Turcotte-Pugh, model for end-stage liver disease (MELD), Rotterdam prognostic index (PI) and Budd-Chiari syndrome-transjugular intrahepatic portosystemic shunt ( BCS-TIPSS) PI. RESULTS: Three hundred and thirty-four patients (56.6% males), median age 24 (3-62) years were included. Hepatic vein was the commonest site of block-isolated hepatic vonous block in 48%, combined hepatic venous-inferior vena cava block in 46%. Endovascular interventional therapy was performed in 233/334 (70%) with 90% technical success. Clinical response was complete in 166 (71.2%), partial in 58 (24.9%) and no response in nine (3.9%). Majority of cases with HV block did not require TIPSS and could be treated with angioplasty (with/without stenting). On Cox-proportional multivariate analysis, Child class C and response to intervention were independent predictors of outcome and used to derive the All India Institute of Medical Sciences (AIIMS) hepatic venous outflow tract obstruction score. The 5-year survival was 92% (95% CI, 81-97%) for score ≤3, 79% (95%CI, 63-88%) for score >3 and ≤4, and 39% (95% CI, 21-57%) for score >4. The performance of AIIMS hepatic venous outflow obstruction score was superior to other prognostic indices. CONCLUSIONS: Advanced Child class and no response to intervention are associated with poor outcomes. The All India Institute of Medical Sciences hepatic venous outflow tract obstruction score predicts survival better than other prognostic scores.

GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling.

PGE2, the major product of cyclooxygenases implicated in carcinogenesis, is significantly upregulated in cervical cancer. PGE2 via prostanoid receptor EP4 stimulates proliferation and motility while inhibiting apoptosis and immune surveillance. It promotes angiogenesis by stimulating the production of pro-angiogenic factors. The present study demonstrates GW627368X, a highly selective competitive EP4 antagonist, which hinders cervical cancer progression by inhibiting EP4/epithelial growth factor receptor (EGFR) interactive signaling. GW627368X reduced protein kinase A (PKA) phosphorylation which in turn leads to decreased cAMP response element-binding protein (CREB) activation. Decreased PKA phosphorylation also directly enhanced Bax activity and in part reduced glycogen synthase kinase 3 (GSK3)ß phosphorylation. Owing to the interactive signaling between EP4 and EGFR, GW627368X lowered EGFR phosphorylation in turn reducing Akt, mitogen-activated protein kinase (MAPK) and GSK3ß activity significantly. Sublethal dose of GW627368X was found to reduce the nuclear translocation of ß-catenin in a time dependent manner along with time-dependent decrease in cytoplasmic as well as whole-cell ß-catenin. Decreased CREB and ß-catenin transcriptional activity restricts the aberrant transcription of key genes like EP4, cyclooxygenase (COX)-2, vascular endothelial growth factor and c-myc, which ultimately control cell survival, proliferation and angiogenesis. Reduced activity of EGFR resulted in enhanced expression of 15-hydroxyprostaglandin dehydrogenase increasing PGE2 degradation thereby blocking a positive feedback loop. In xenograft model, dose-dependent decrease in cancer proliferation was observed characterized by reduction in tumor mass and volume and a marked decrease in Ki67 expression. A diminished CD31 specific staining signified decreased tumor angiogenesis. Reduced expression of pAkt, pMAPK, pEGFR and COX-2 validated in vitro results. GW627368X therefore effectively inhibits tumor survival, motility, proliferation and angiogenesis by blocking EP4/EGFR interactive signaling. EP4 is a potent therapeutic target in cervical cancer and can be explored in combination with conventional therapies to attain superior outcomes and to overcome complications associated with organ toxicities, therapeutic resistance and disease relapse.

Lichenoid drug reaction to isoniazid presenting as exfoliative dermatitis in a patient with acquired immunodeficiency syndrome.

Human immunodeficiency virus-infected patients are at increased risk of drug reactions because of immune dysregulation and multiple drug intake. Lichenoid drug reactions to isoniazid have been reported previously in the literature. However, for lichenoid drug reaction to isoniazid to be so extensive to present as exfoliative dermatitis is rare. We report here a rare case of lichenoid drug reaction to isoniazid presenting as exfoliative dermatitis in a patient with acquired immunodeficiency syndrome.

Histopathological study of placentae in low birth weight babies in India.

BACKGROUND: The antenatal health-care given to pregnant women has great influence on the rates of perinatal death and morbidity. Amongst the different causes of perinatal mortality, low birth weight (LBW) is the single most significant factor therefore placenta from all the LBW babies (LBWB) should be examined routinely to find out the likely cause. AIMS: The aims of this study were to assess the pathological changes in the placenta in association with LBWB. MATERIALS AND METHODS: This is a Case control study performed at Medical College Allahabad,(MLN) India. In this study, 90 placentae were included. 30 placentae from full-term vaginally delivered babies, weighing more than 2500 g were included as the control group. 60 placentae belonged to babies whose birth weight was less than 2500 g (LBW). Weight of the baby was taken within the 1(st) h of birth and Apgar score was noted. Gross and microscopic examination of placentae was done. Statistical correlation of was carried out between them by using SPSS 18 version. Chi-square test with or without yate's correction was used as and when required. P < 0.05 was taken as critical level of significance. RESULTS: Placenta was circum-marginal in both groups. Attachment of cord was mainly central in the control group 90% (27/30), whereas eccentric attachment was prominent in patient group 66.67% (40/60). The difference was statistically significant (P < 0.001). Calcification and sub-chorionic fibrin deposition was seen in significantly higher numbers of placentae from patients than controls (P < 0.01) infarction and meconium staining were seen in placentae from patients only. Histologically placental ischemia, infarction and calcification were seen in significantly higher number of patients (P < 0.001, P < 0.001 and < 0.01 respectively). Fibrinoid necrosis, stromal fibrosis, placental dysmaturity and obstructive vasculopathy were seen in placentae from patients only. CONCLUSION: Placental pathology among LBW infants was high in comparison to control group. The findings suggest that chronic ischemia and associated secondary changes probably lead to improper perfusion and LBWB.

Surgical Results of Non-small Cell Lung Cancer in Nepal.

INTRODUCTION: Surgery remains the only curative modality for early stage of Non small cell lung caner (NSCLC). We reviewed overall scenario of lung cancer and surgical results in Nepal. METHODS: 1000 patients with the pathological diagnosis of lung cancer were analyzed to summarize the overall scenario of lung cancer. 157 NSCLC patients underwent pulmonary resection. cIA, IB, IIA, IIB, IIIA (N1) underwent surgery as initial modality of treatment. cIIIA (N2) patients were taken for surgery after neoadjuvant chemo/ chemoradiation. RESULTS: Analysis of 1000 patients showed squamous cell carcinoma in 41.3%, incurable stage (IIIB/ IV) in 66.8% and rate of curative resection in 6.7% cases. Surgery as a single modality of treatment was used in 38%. Neoadjuvant Chemo/ chemoradiation/ radiation followed by surgery and surgery followed by chemo/ chemoradiation/ radiation was done in 12% and 50%, respectively. In-hospital mortality was 2% (post pneumonectomy: 5.5%; post lobectomy: 1.5%; post sublobar resection: 0%). R0 resction was achieved in 91% cases. Median survival and 5-year overall survival were 36 months and 18%, respectively. Better survival was achieved in pI-II vs pIII/ IV, pN0-1 vs pN2 and pR0 vs pR+ (p <0.05). CONCLUSIONS: Earlier stage (pI-II), R0 resection and pathological pNo-1 has the best five year overall survival in Nepalese patients with NSCLC as well.

Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy.

Histone deacetylase (HDAC) inhibitors (HDACis) are well-characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant cells while sparing normal cells. Gene expression-based chemical genomics identified HDACis as being particularly potent against Down syndrome-associated myeloid leukemia (DS-AMKL) blasts. Investigating the antileukemic function of HDACis revealed their transcriptional and post-translational regulation of key autophagic proteins, including ATG7. This leads to suppression of autophagy, a lysosomal degradation process that can protect cells against damaged or unnecessary organelles and protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mammalian target of rapamycin (mTOR) activation. Consequently, HDAC inhibition repressed autophagy below a critical threshold, which resulted in accumulation of mitochondria, production of reactive oxygen species, DNA damage and apoptosis. Those HDACi-mediated effects could be reverted upon autophagy activation or aggravated upon further pharmacological or genetic inhibition. Our findings were further extended to other major acute myeloid leukemia subgroups with low basal level autophagy. The constitutive suppression of autophagy due to mTOR activation represents an inherent difference between cancer and normal cells. Thus, via autophagy suppression, HDACis deprive cells of an essential pro-survival mechanism, which translates into an attractive strategy to specifically target cancer cells.

Polymeric nanoparticle formulation of octapeptide (NP-OP): in vitro release and in vivo effect in common marmosets, Callithrix jacchus Linn.

Octapeptide (OP)/FSH-Receptor Binding Inhibitor-8 (FRBI-8), is a synthetic peptide corresponding to N-terminal sequence of purified fraction of Follicle Stimulating Hormone Binding-Inhibitor (FSHBI), isolated earlier from human ovarian follicular-fluid. In order to avoid the repeated drug-administration, OP-loaded, polymeric polylactide (PLA) nanoparticle formulation (NP-OP), was developed using multiple-emulsion technique. This yielded an average particle size of 120 nm with 70% encapsulation-efficiency. In vitro release profile of NP-OP showed sustained release of OP for 21 days. In vivo anti-fertility studies were conducted in marmosets. Results indicated that control animals conceived in the same cycle while two of three treated animals failed to conceive in treatment cycle. The in vivo studies thus corroborate with in vitro release of OP, demonstrating its anti-fertility activity in 66% of animals.

Frequency of T cell expressing Th1 and Th2 associated chemokine receptor in patients with renal allograft dysfunction.

Acute rejection of human renal allografts is a frequent, serious posttransplantation complication, occurring in up to 50% of recipients. Leukocyte recruitment is a central feature of acute allograft rejection. Chemokine receptors are expressed on leukocytes in a cell type-specific manner. Recently CCR5+ and CXCR3+ cells have been observed in allograft biopsy specimens of patients undergoing acute cellular rejection (ACR). Herein we investigated the expression of Th1 (CCR5, CXCR3, and CCR2) and Th2 (CCR4, CCR3, and CCR8)-associated chemokine receptors on CD4 and CD8 T-cell populations. We sought to correlate chemokine receptor expression in peripheral blood T-cell subsets with the types of graft dysfunction (biopsy-proven rejections). In the peripheral blood CD4+ and CD8+ T-cell populations of patients with graft dysfunction, we observed a high frequency of Th1-associated chemokine receptors CCR5+ and CCR2+ but not CXCR3.

Orthotopic neobladder urinary diversion for carcinoma of urinary bladder.

BACKGROUND: Invasive cancers of urinary bladder need radical cystectomy as an optimal treatment. Urinary diversions of different types are available after the procedure. Orthotopic neo-bladder reconstruction is an emerging technique of diversion in suitable patients. The aim of this study was to see the outcome of this procedure in our set up. METHODS: The patient with carcinoma of urinary bladder who underwent radical cystectomy and orthotopic neo- bladder reconstruction during five year period were included in the study from department of surgical oncology in a hospital. Studer type ileal pouches were made in all the patients and their outcomes were studied. RESULTS: There were 30 patients among which 28 were male and 2 female. Age ranged from 38-60 years with mean age of 49.6 years. Average operative time was 330 minutes. Average hospital stay was 16 days (range 14-30 days). Majority of patients were transitional cell carcinoma 26 (86.7%) in histology. Majority of cases presented in stage II (53.3%). Post-operative complications were ileus in 30%, urinary leak in 26.6% and pneumonia in 13.3% of patients. Mortality was 1 (3.3%) on 29th postoperative day. Patients were able to micturate with satisfactory stream postoperatively. CONCLUSIONS: Orthotopic neobladder has similar complication rates compared with other forms of continent diversions. This method gives less psychological trauma to the patients with higher acceptance. So we recommend transforming the technique from ileal conduits to neobladder in well-established pelvic reconstruction set ups.

Eight-year experience in esophageal cancer surgery.

AIM: Esophageal cancer remains a major and lethal health problem. In Nepal, not much has been explored about its management. The aim of this study was to conduct a retrospective review of esophageal cancer patients undergoing surgery or combined modality treatment at a cancer hospital in Nepal. MATERIALS AND METHODS: Resectable cases were treated primarily with surgery. Locally advanced cases with doubtful or obviously unresectability underwent preoperative chemo/radiation or chemoradiation followed by surgery. RESULTS: Among 900 patients, 103 were treated with curative intent. Mean age of patients was 54 years, and 100% of the patients presented with complaint of dysphagia. Surgery as a single modality of treatment was done in 57% of cases, and the remaining underwent combined modality treatment. Transthoracic and transhiatal approaches were used in 95% and 5% of cases, respectively. Nodal sampling, two-field (2-FD), and three-field lymphadenectomy (3-FD) were done in 18%, 59%, and 20% of cases, respectively. A majority of patients had pathological stage III disease (46.6%). In-hospitality mortality was 5%, and anastomotic leakage rate was 14%. In 87% of patients, R0 resection was achieved. Overall, 4-year survival was 20%. A R0 resection, early-stage disease and 3-FD favored the survival advantage (P < 0.05). CONCLUSION: The mortality, complication, and survival results were in the acceptable range. R0 resection and radical nodal dissection should be standard practice.

Clinical evaluation of detomidine-butorphanol-guaifenesin-ketamine as short term TIVA in Spiti ponies.

Veterinarians working under remote field conditions are routinely presented with variety of surgical interventions in equines like castrations, management of wound, traumatic and congenital hernias and musculoskeletal disorders thus necessitating the use of general anaesthesia for management of these conditions. The present study was carried out to evaluate and recommend the suitable short term anaesthetic technique for Spiti ponies under field conditions. Seven clinically healthy male Spiti ponies presented for castration were evaluated for short term Total Intravenous Anaesthesia (TIVA) using detomidine (0.02 mg kg(-1)), butorphanol (0.01 mg kg(-1)), 5% guaifenesin (20 mg kg(-1)) and ketamine (2.0 mg kg(-1)). The studies conducted were open label trials and all the animals received same treatment. After proper tetanus prophylaxis and preanesthetic fasting, detomidine was administered intravenously. Subsequently at head down position the animals received butorphanol intravenously. Thereafter, guaifenesin was administered intravenously. As soon as the signs of ataxia developed, the induction of surgical anaesthesia was achieved by intravenous administration of ketamine hydrochloride. The onset of sedation was observed in 2.43 +/- 0.53 min following detomidine administration and the animals were ataxic in 1.43 +/- 0.43 min after butorphanol and guaifenesin administration when ketamine was injected. The ponies were in surgical plane of anaesthesia within 2.28 +/- 0.42 min following ketamine administration. During recovery the limb/head movement and sternal recumbency were attained in 18.71 +/- 1.98 and 26.14 +/- 1.62 min, respectively whereas standing ataxia and normal gait were seen at 29.42 +/- 3.21 and 71.14 +/- 4.74 min, respectively. There was excellent to good muscle relaxation. The surgical anaesthesia remained for 22.57 +/- 1.48 min. The recovery was smooth. Moderate to good suppression of palpebral and corneal reflexes were observed immediately after induction and during anaesthesia. The analgesia was excellent. A highly significant (p < 0.01) to significant (p < 0.05) decrease in respiration rate was observed after induction, during anaesthesia and after recovery. The mean SpO2 value in equines of this group was 76.50 +/- 4.14 and 83.33 +/- 4.18% after induction and during anaesthesia, respectively. Some of the blood biochemical parameters like plasma alanine amino transferase (ALT), total proteins and glucose showed significant increase without clinical consequence. It was concluded that detomidine (0.02 mg kg(-1)), butorphanol (0.01 mg kg(-1)), guaifenesin 5% (20 mg kg(-1)) and ketamine (2.0 mg kg(-1)) combination can safely be used for short term total intravenous anaesthesia in equines under field conditions where the monitoring facilities are meager.

Transnasal trans-sphenoidal endoscopic repair of CSF leak secondary to invasive pituitary tumours using a nasoseptal flap.

Cerebrospinal fluid (CSF) leak following initiation of Dopamine agonist therapy for macroprolactinomas, although uncommon, has been described previously in the literature. Traditional management includes primary repair of the defect using either fat or fascia lata in conjunction with lumbar drain insertion. In this case series we outline two cases of CSF leak secondary to invasive pituitary tumour that were repaired successfully using a nasoseptal flap. We believe that this form of repair is effective and associated with minimal morbidity.

Heterogeneity of reporting standards in randomised clinical trials of endovenous interventions for varicose veins.

AIMS: The efficacy of endovenous treatments for venous reflux has been demonstrated in numerous randomised clinical trials, although significant heterogeneity may exist between studies. The aim of this study was to assess the heterogeneity in reporting between randomised clinical trials investigating endovenous treatments for patients with varicose veins. METHODS: A literature search of the Pubmed, Cochrane and Google Scholar databases was performed using appropriate search terms. Randomised clinical trials published between January 1968 and June 2009 evaluating endovenous interventions for varicose veins were included and relevant abstracts and full text articles were reviewed. Published study reports were evaluated against recommended reporting standards published by the American Venous Forum in 2007. RESULTS: Twenty-eight randomised trials fulfilled the inclusion criteria. Median patient age (reported in 20/28 studies) ranged from 33 to 54 years. The CEAP classification was presented in 17/28 studies and the proportion of patients with C2 disease ranged from 6.3% to 83.5%. A total of 31 different outcome measures were utilised. This included 13 different questionnaires, varicose vein recurrence at 38 time points and 30 categories of complications. Duplex ultrasonography was used in 21/28 trials to assess recurrence. Quality of life was only evaluated in 11 studies and the follow-up period ranged from 3 weeks to 10 years. CONCLUSIONS: Meaningful comparison across randomised studies of endovenous treatments is made difficult by considerable variations in study populations and outcome measures between trials. This highlights the need for the use of prospectively agreed population selection, and reporting standards for outcome measures in randomised clinical assessments of new treatments.

Giant cell tumor arising from anterior arc of first rib: a rare presentation.

We report a case of Giant Cell Tumor (GCT) arising from anterior are of first rib along with literature review which was treated with excision of rib through its normal margin along with tumor mass. GCT of rib is rare and if found mostly arises from the posterior aspect. However, GCT should be considered as differential diagnosis when bony mass is present in the anterior are of rib. It poses surgical challenge for excision because of the delicate and vital neurovascular structures passing above it between clavicle and first rib.

Evidence of late Palaeocene-early Eocene equatorial rain forest refugia in southern Western Ghats, India.

Equatorial rain forests that maintain a balance between speciation and extinction are hot-spots for studies of biodiversity. Western Ghats in southern India have gained attention due to high tropical biodiversity and endemism in their southern most area. We attempted to track the affinities of the pollen fl ora of the endemic plants of Western Ghat area within the fossil palynoflora of late Palaeocene-early Eocene (approximately 55-50 Ma) sedimentary deposits of western and northeastern Indian region. The study shows striking similarity of extant pollen with twenty eight most common fossil pollen taxa of the early Palaeogene. Widespread occurrences of coal and lignite deposits during early Palaeogene provide evidence of existence of well diversified rain forest community and swampy vegetation in the coastal low lying areas all along the western and northeastern margins of the Indian subcontinent. Prevalence of excessive humid climate during this period has been seen as a result of equatorial positioning of Indian subcontinent, superimposed by a long term global warming phase (PETM and EECO) during the early Palaeogene. The study presents clear evidence that highly diversifi ed equatorial rain forest vegetation once widespread in the Indian subcontinent during early Palaeogene times, are now restricted in a small area as a refugia in the southernmost part of the Western Ghat area. High precipitation and shorter periods of dry months seem to have provided suitable environment to sustain lineages of ancient tropical vegetation in this area of Western Ghats in spite of dramatic climatic changes subsequent to the post India-Asia collision and during the Quaternary and Recent times.