Factors influencing local and distant recurrence following resection of periampullary cancer.

BACKGROUND: Recurrence of periampullary cancer after pancreatoduodenectomy is common. The aim of this study was to investigate patterns of recurrence, incidence, and factors associated with local and distant recurrences. METHODS: This retrospective, single-centre study included consecutive patients with periampullary cancer who underwent resection with curative intent from January 2012 to January 2018. Survival, patterns of recurrence, and factors associated with recurrences were analysed. RESULTS: Median overall survival (OS) and disease-free survival among 398 included patients was 58.4 and 49.5 months respectively. Twenty-three patients (5.8 per cent) developed isolated local recurrences (LR), 50 (12.6 per cent) developed LR along with distant metastasis (DM), and 103 (25.9 per cent) developed isolated DM. Median OS was 40.4 months for patients with isolated LR versus 23 months for those with DM (P < 0.001). Tumour subtype (distal common bile duct (CBD): odds ratio (OR) 6.18, 95 per cent c.i. 2.19 to 17.46) and node-positive status (OR 2.36, 1.26 to 4.43) were independently associated with higher rates of LR. The most common site for isolated LR was along the superior mesenteric artery (12 of 23 patients). Tumour subtype (distal CBD: OR 2.86, 1.09 to 7.52), nodal positivity (OR 2.46, 1.53 to 3.94), and presence of perineural invasion (OR 1.80, 1.02 to 3.18) were independently associated with DM. CONCLUSION: Isolated LR is associated with better survival than DM and occurs most commonly along the superior mesenteric artery.

Predicting the length of stay at admission for emergency general surgery patients a cohort study.

INTRODUCTION: Predicting length of stay (LOS) is beneficial to patients and the health service. When a prolonged LOS is predicted, it gives the opportunity for focused therapies and allocation of resources to reduce this period. In emergency general surgery (EGS) there has been limited investigation of variables that may be important predictors of LOS. This study examines social characteristics alongside measures of severity of acute illness and co-morbidities in an adult EGS population to establish their contribution to LOS. METHODS: Data were collected prospectively from patients at admission including medical variables, demographics, and therapeutic requirements. The length of hospital admission was measured, and multiple regression analysis was used to identify variables which predicted the LOS. RESULTS: Data were collected from 105 patients. The regression model gave an R2 of 0.34, p = 0.0006. Barthal index (measure of independence in activities of daily living) was a significant predictor of LOS [logworth 1.649, p0.02243]. Housing status and Level of social support both correlated in one-way analysis with LOS. CONCLUSION: There are non-surgical variables, measurable at admission which are of significant value in predicting LOS of EGS patients. This warrants further investigation through a larger study to better quantify the contributions of these variables, and establish potential early interventions to reduce the LOS.

Personalized cumulative UV tracking on mobiles & wearables.

Maintaining a balanced Ultra Violet (UV) exposure level is vital for a healthy living as the excess of UV dose can lead to critical diseases such as skin cancer while the absence can cause vitamin D deficiency which has recently been linked to onset of cardiac abnormalities. Here, we propose a personalized cumulative UV dose (CUVD) estimation system for smartwatch and smartphone devices having the following novelty factors; (a) sensor orientation invariant measurement of UV exposure using a bootstrap resampling technique, (b) estimation of UV exposure using only light intensity (lux) sensor (c) optimal UV exposure dose estimation. Our proposed method will eliminate the need for a dedicated UV sensor thus widen the user base of the proposed solution, render it unobtrusive by eliminating the critical requirement of orienting the device in a direction facing the sun. The system is implemented on android mobile platform and validated on 1200 minutes of lux and UV index (UVI) data collected across several days covering morning to evening time frames. The result shows very impressive final UVI estimation accuracy. We believe our proposed solution will enable the future wearable and smartphone users to obtain a seamless personalized UV exposure dose across a day paving a way for simple yet very useful recommendations such as right skin protective measure for reducing risk factors of long term UV exposure related diseases like skin cancer and, cardiac abnormality.

Evaluation of synergistic effects of sulforaphene with photodynamic therapy in human cervical cancer cell line.

Sulforaphene from cruciferous vegetable has shown to modulate various signaling pathways of apoptosis. But it has not yet been studied extensively for the cervical cancer treatment. Previous studies show the promising role of photodynamic therapy for cervical cancer. Here, we confirm that sulforaphene can synergistically enhance the efficacy of photodynamic therapy. Human cervical cancer cells HeLa were treated with a very low dose of sulforaphene (2.0 µg/ml) and photodynamic therapy with radachlorin (0.5 µg/ml) at a fluence of 27 J/cm2 (30 milliwatts/cm2, λmax ∼ 670 ± 3 nm). The combination treatment showed a synergistic effect to induce apoptosis. The mitochondrial apoptotic pathway was activated via caspase 3 and caspase 9. On the other hand, caspase 12 and C/EBP homologous protein (CHOP) were expressed that indicated endoplasmic reticulum stress. This combination treatment also activated death receptor pathway via activation of caspase 8 and inhibited cell proliferation via down-regulation of EGFR. Thus, several apoptotic pathways were simultaneously activated in this combination treatment which results in a synergistic efficacy of sulforaphene with photodynamic therapy. Therefore, this study could be useful in the improvement of therapies for human cervical and other types of cancers.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Utility and impact of early t(15;17) identification by Fluorescence In Situ Hybridization (FISH) in clinical decision making for patients in Acute Promyelocytic Leukemia (APL).

INTRODUCTION: Acute Promyelocytic Leukemia (APL) is a curable malignancy with studies showing above 90% survival. However, population-based studies looking at survival suggest that approximately 30% of patients with APL die during induction. Early demonstration of t(15;17) will lead to accurate decision making regarding treatment. The aim of this project was to validate earlier time frames for the Abbott Molecular Vysis LSI promyelocytic leukemia (PML)/ retinoic acid receptor alpha (RARA) fluorescence in situ hybridization (FISH) probe (ASR 6-16 h). METHODS: Twenty patients (15 APL cases and five non-APL cases) were selected for validating various hybridization times for the FISH probe. Expected normal signal pattern was two red and two green signals (2R2G), and the most common expected abnormal signal pattern was two fusion (yellow) signals, one red and one green (2F1R1G) and/or one fusion, one red and one green (1F1R1G). RESULTS: The specificity of the probe ranged from 84% at 2 h, 86% at 4 h, 84% at 6 h, and 87% for overnight hybridization. The sensitivity increased from 79% at 2 h, 80% at 4 h, 81% at 6 h to 87% for overnight hybridization. CONCLUSION: Based on the validation studies, we recommend reading of FISH results at the 4-h incubation mark for a preliminary diagnosis and confirmation with overnight hybridization.

Efficient removal of arsenic (V) from water using steel-making slag.

This study describes the potential use of steel-making slag as an arsenic-removal medium. Systematic analysis of slag material revealed a composition of oxides of calcium, iron, silicon, and phosphorous. Under the experimental conditions of this study, the equilibrium time was shown to be 2 hours, and the removal capacity to be 99%, with an adsorbent loading capacity of 1.25g/l. The adsorption kinetics were shown to follow a pseudo-second-order rate equation, and the adsorption isotherm closely followed both the Langmuir and Freundlich isothermic models. Variations in solution pH levels demonstrated that with a decrease in the initial solution pH, the adsorption capacity decreases. This is attributed to the leaching of silica and phosphate from the slag to the solution, which imparted a competing effect for adsorption sites. However, with an alkaline pH, such leaching was reduced, and due to formation of calcium carbonate from the leached calcium from the slag material, the arsenic removal efficiency increased as it was co-precipitated with calcium carbonate.

Optimization of fermentation conditions for green pigment production from Bacillus cereus M¹ 16 (MTCC 5521) and its pharmacological application.

UNLABELLED: Optimal culture conditions for the production of green pigment was investigated. The optimal culture condition for the production of an extracellular green pigment by growing Bacillus cereus M(1) 16 (MTCC 5521) in a complex medium containing (g l(-1) ) Peptone-4.0, Beef Extract-9.0, NaCl-7.0, MgSO4 .7H2 O-1.0 and KH2 PO4 -5.0 was as follows pH-7.0 at 30°C for 72 h in a 5 l fermenter. Aeration rate and agitator speed had no effect on the pigment production. Thin layer chromatogram of the pigment extracted from the fermented broth with chloroform on silica gel GF254 using ethyl acetate and hexane (1 : 1) as solvent showed three fractions. The major fraction (C3 ) was separated out and identified as 9-methyl-1, 4, 5, 8-tetra-azaphenanthrene. Acute toxicity test revealed the nontoxic nature upto a dose of 2000 mg kg(-1) , b.wt., of mice. MTT assay showed the cytotoxic nature in HL60 cells having an IC50 of 2.47 mmol. So, this biopigment may have application in food, textile colorant and pharmaceutical industry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the optimum production of a biopigment (9-methyl-1, 4, 5, 8-tetra-azaphenanthrene) by fermentation of a complex medium with Bacillus cereus M(1) 16 (MTCC 5521) in submerged fermentation. This is the first investigation of toxicity and cytotoxicity activities of this biopigment. The study showed that the purified pigment had no toxicity to healthy albino mice but a high cytotoxicity activity in HL60 cancer cell line in vitro. The biopigment had further displayed dyeing capability to both solidified agar and cotton cloth. Therefore, it may represent a nontoxic and natural alternative to chemical dyes and pigments.

Physico-chemical characterization and biological response of Labeo rohita-derived hydroxyapatite scaffold.

The chemically treated Labeo rohita scale is used for synthesizing hydroxyapatite (HAp) biomaterials. Thermogravimetric and differential thermal analyses of fish scale materials reveal the different phase changes with temperature and find out the suitable calcination temperatures. The composition and structures of wet ball-milled calcined HAp powders are characterized by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray analysis (EDX). The EDX as well as chemical analysis of fish scale-derived apatite materials confirms that the Ca/P ratio is 1.71. The compressive stress, hardness and porosity have been evaluated on sintered HAp biomaterials. The cell attachment on HAp surfaces, cytotoxicity evaluation and MTT assay, which are carried out in RAW macrophage-like cell line media demonstrate good biocompatibility. The histological analysis also supports the bioaffinity of processed HAp biomaterials in Wistar rat model for investigating the contact reaction and stability at the artificial or natural prosthesis interface.

Downregulation of splicing factor SRSF3 induces p53ß, an alternatively spliced isoform of p53 that promotes cellular senescence.

Most human pre-mRNA transcripts are alternatively spliced, but the significance and fine-tuning of alternative splicing in different biological processes is only starting to be understood. SRSF3 (SRp20) is a member of a highly conserved family of splicing factors that have critical roles in key biological processes, including tumor progression. Here, we show that SRSF3 regulates cellular senescence, a p53-mediated process to suppress tumorigenesis, through TP53 alternative splicing. Downregulation of SRSF3 was observed in normal human fibroblasts undergoing replicative senescence, and was associated with the upregulation of p53ß, an alternatively spliced isoform of p53 that promotes p53-mediated senescence. Knockdown of SRSF3 by short interfering RNA (siRNA) in early-passage fibroblasts induced senescence, which was associated with elevated expression of p53ß at mRNA and protein levels. Knockdown of p53 partially rescued SRSF3-knockdown-induced senescence, suggesting that SRSF3 acts on p53-mediated cellular senescence. RNA pulldown assays demonstrated that SRSF3 binds to an alternatively spliced exon uniquely included in p53ß mRNA through the consensus SRSF3-binding sequences. RNA crosslinking and immunoprecipitation assays (CLIP) also showed that SRSF3 in vivo binds to endogenous p53 pre-mRNA at the region containing the p53ß-unique exon. Splicing assays using a transfected TP53 minigene in combination with siRNA knockdown of SRSF3 showed that SRSF3 functions to inhibit the inclusion of the p53ß-unique exon in splicing of p53 pre-mRNA. These data suggest that downregulation of SRSF3 represents an endogenous mechanism for cellular senescence that directly regulates the TP53 alternative splicing to generate p53ß. This study uncovers the role for general splicing machinery in tumorigenesis, and suggests that SRSF3 is a direct regulator of p53.

Evaluation of Antitumor and Antioxidant Activity of Melothria heterophylla (Lour.) Cogn.

Melothria heterophylla (Lour.) Cogn., (family-Cucurbitaceae) popularly known as kundari, has been shown to exhibit antioxidant effects. The main objective was to isolate active constituents of the plant extract. In this study, the ability of M. heterophylla to induce apoptosis was studied in Ehrlich ascites carcinoma cells. Treatment of the Ehrlich ascites carcinoma cells with a variety of concentrations of the ethanol extracts of M. heterophylla and gallic acid (100-1000 µM), to determine the sequences of events marked by apoptosis, assayed by the spectrofluorometric method. Gallic acid and rutin were isolated from plant extract which were quantified by high-performance liquid chromatography. Our results indicate that ethanol extracts of M. heterophylla and gallic acid-induced apoptotic cell death in a dose dependent manner could be due to the generation of reactive oxygen species, especially H2O2, which is confirmed by caspase 3 activation. Treatment of Ehrlich ascites carcinoma bearing Swiss albino mice with varied doses (200 and 400 mg/kg, b.w.) of plant extract significantly reduced tumor volume and viable tumor cell count and improved hemoglobin content, RBC count, mean survival time, tumor inhibition, and percentage life span. The enhanced antioxidant status in extract-treated animals were evident from the decline in the levels of lipid peroxidation and increased levels of glutathione, catalase, and superoxide dismutase. The data suggest that M. heterophylla exerts anticancer activity, valuable for application in food and drug products.

Adherence to a Mediterranean diet and Alzheimer's disease risk in an Australian population.

The Mediterranean diet (MeDi), due to its correlation with a low morbidity and mortality for many chronic diseases, has been widely recognised as a healthy eating model. We aimed to investigate, in a cross-sectional study, the association between adherence to a MeDi and risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large, elderly, Australian cohort. Subjects in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing cohort (723 healthy controls (HC), 98 MCI and 149 AD participants) completed the Cancer Council of Victoria Food Frequency Questionnaire. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD and MCI status in multinominal logistic regression models that were adjusted for cohort age, sex, country of birth, education, apolipoprotein E genotype, total caloric intake, current smoking status, body mass index, history of diabetes, hypertension, angina, heart attack and stroke. There was a significant difference in adherence to the MeDi between HC and AD subjects (P < 0.001), and in adherence between HC and MCI subjects (P < 0.05). MeDi is associated with change in Mini-Mental State Examination score over an 18-month time period (P < 0.05) in HCs. We conclude that in this Australian cohort, AD and MCI participants had a lower adherence to the MeDi than HC participants.

17-AAG mediated targeting of Hsp90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry.

AIM: Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific chaperone-clients interaction in the event of peritoneal sarcoma related malignant ascites formation in mouse model at the late stage of malignant growth. METHODS: We administered 17-AAG, an Hsp90 inhibitor, divided doses (330 µg/kg b.w./day for first five days then next ten days with166 µg/kg b.w./day) through intra-peritoneal route of inbred Swiss albino mice bearing full grown peritoneal malignant ascites of sarcoma-180. Our study was evaluated by peripheral blood hemogram analysis, malignant ascitic cytology, cell viability test, survival time and mitotic indexing. Furthermore, flowcytometric HSP90, TERT, CyclinD1, PCNA and GM-CSF expression analysis has been considered for special objective of the study. RESULTS: Our experimental efforts reduced the aggressive proliferation of malignant ascites by drastic downregulation of TERT and cyclin D1 on the verge of cell cycle entry along with DNA replication processivity factor PCNA by directly modulating their folding machinery - heat shock protein 90. Consequently, we observed that malignant ascitic cells became error prone during the event of karyokinesis and produced micronucleus containing malignant cells with low viability. Peripheral neutrophilia due to over-expression of GM-CSF by the peritoneal malignant ascites were also controlled by the treatment with 17-AAG and overall, the treatment modality improved the median survival time. CONCLUSION: Finally we can conclude that 17AAG administration might serve as a prospective pharmacological agent for the management of peritoneal sarcoma related malignant ascites and throws light towards prolonged survival of the patients concerned.

Comparision of F-18 FDG and C-11 Methionine PET/CT for demonstration of subependymal deposit in a treated case of glioblastoma multiforme.

A 10-year-boy post-operative, post-radiotherapy case of left temporal glioblastoma multiforme (GBM) was referred for F-18 Flurodeoxyglucose (FDG) Positron emission tomography/Computed Tomography (PET/CT) to rule out residual/recurrent disease 6 months following completion of therapy. The FDG scan 3 months following therapy had not shown evidence of viable residual or metastatic disease. The present scan showed a tiny focus of abnormal FDG accumulation in the region of the trigone of the left lateral ventricle which was best appreciated on the plain PET image. A correlative C-11 methionine study showed a well defined focus of abnormal tracer accumulation in the region of the left trigone. CECT and MRI done subsequently proved it to be a subependymal deposit. This case therefore demonstrates the possibility of subependymal deposits in GBM and the need for this possibility to be entertained during interpretation of the FDG study. It also highlights the advantage of labelled amino acids like C-11 methionine for clearly delineating subependymal deposits apart from the advantage for unequivocal interpretation of the PET study in recurrent brain tumors.

Total goitre rate in rural primary school children aged 8-12 years and impact of their health education, on consumption of iodised salt among their families.

In the present study, the total goitre rate was assessed in children aged 8-12 years, attending a rural primary school along with a longitudinal, educational intervention study undertaken among them, regarding proper comsumption of iodised salt and percolating this to their families through them. It was carried over a period of four months and 110 children, studying in a rural primary school, were the study population. The total goitre rate among the surveyed school children was found to be 6%, indicating mild Iodine deficiency disorder prevalence, according to accepted recommendations. Before health education was given, 100% salt as collected on first fortnight was iodised, but optimum iodisation was present only in 80.4% of the samples tested. In view of all these, it emerges that the area is in a transitional phase of iodine deficiency to iodine sufficiency. Over the period of study, during which educational input was provided, there was increase in the voluntary participation of the students regarding bringing of salt for iodine estimation (p < 0.05). On analysis the children were very good at percolating the health education to the parents and significant change was observed in their practice as well.

Neo-regeneration of urinary bladder: a desired metaplasia of autologous membrane from rectosigmoid colon containing stem cells of intestinal crypts.

The current management of diseases of urinary bladder requiring resection is by augmentation cystoplasty or transplantation of ureters. Transplantation of ureters is associated with morbidity and mortality. Ideal management will be by regenerating urinary bladder in vivo. Neo-regeneration of tissues and organs like abdominal wall, aponeurosis etc., has been attempted and patented. After neo-regeneration of mesoderm tissues and organs, regeneration of urinary bladder (developed from endoderm) was. In vivo surgical techniques were developed in dogs. It is known that the embryonic morphogenesis of urinary bladder is from uro-genital sinus of hind gut. A membrane, containing endoderm stem cells in crypts of recto-sigmoid colon, was surgically isolated and colonized with remnant of urinary bladder wall after extensive resection. Experimental study was performed in dogs, for 60 days to one and a half year. Regeneration of all the layers of tissues of the wall of urinary bladder was observed. The neo-regeneration phenomenon has been recognized as "desired metaplasia". The regenerated neo tissue/organ on histological examination and cystometry studies was found compatible with normal urinary bladder. The hypothesis, neo-regeneration and desired metaplasia, is discussed.

Occult foreign bodies in the aero digestive tracts in infancy.

Foreign body impaction in aero digestive tract in infancy is difficult to diagnose sometimes. In this review of five unusual cases of occult foreign body impaction in aero digestive tract has been presented and their management discussed.

Paenibacillus assamensis sp. nov., a novel bacterium isolated from a warm spring in Assam, India.

A polyphasic approach was used to characterize a bacterium, GPTSA 11(T), isolated from a warm spring located in a reserve forest in Assam, India. The cells are Gram-variable, strictly aerobic, sporulating motile rods. The major fatty acids of the strain are C(15 : 0) anteiso (48.42 %), C(16 : 0) iso (11.59 %), C(16 : 1)omega11c (6.16 %), C(15 : 0) iso (6.03 %), C(17 : 0) anteiso (5.68 %) and C(16 : 1)omega7c alcohol (5.01 %). The presence of the fatty acid C(16 : 1)omega7c alcohol distinguishes this strain from other closely related species of the genus Paenibacillus. The strain contains MK-7 as the diagnostic menaquinone. The G+C content of the genomic DNA is 41.2 mol%. Analysis of the 16S rRNA gene sequence (1466 nt) revealed the presence of signature sequences PAEN 515F (5'-GAGTAACTGCTCTCGGAATGACGGTACTTGAGAAGAAAGCCCC-3') and PAEN 862F (5'-TCGATACCCTTGGTGCCGAAGT-3'), which were found in the species of the genus Paenibacillus surveyed by Shida et al. [Shida, O., Takagi, H., Kadowaki, K., Nakamura, L. K. & Komagata, K. (1997). Int J Syst Bacteriol 47, 289-298]. The sequence shows closest similarity (95.85 %) to that of Paenibacillus apiarius, followed by Paenibacillus alvei (94.34 %), Paenibacillus cineris (93.87 %), Paenibacillus favisporus (93.80 %), Paenibacillus chibensis (93.47 %) and Paenibacillus azoreducens (93.40 %). Biochemical, physiological, chemotaxonomic and phylogenetic analyses justify placement of the strain in the genus Paenibacillus but not within any existing species. It should, therefore, be considered as representing a novel species, for which the name Paenibacillus assamensis sp. nov. is proposed. The type strain is GPTSA 11T (=MTCC 6934T=JCM 13186T).

Midline cervical cleft: A report of two cases.

Congenital midline cervical cleft is a rare congenital anomaly. The cardinal diagnostic features are-(1). Fistula's opening are located caudally (2) Internuittent serous fluid discharge in the early neonatal period (3). Nipple like appearance of the cleft in the superior aspect (4). Widened scar and mininual neck contracture in later life. Two such cases are reported herewith with briefreview of literature and it's surgical management.