Accelerating Solutions for the Overdose Crisis: an Effectiveness-Implementation Hybrid Protocol for the HEAL Prevention Cooperative.

Given increasing opioid overdose mortality rates in the USA over the past 20 years, accelerating the implementation of prevention interventions found to be effective is critical. The Helping End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is a consortium of research projects funded to implement and test interventions designed to prevent the onset or escalation of opioid misuse among youth and young adults. The HPC offers a unique opportunity to synthesize and share lessons learned from participating research projects' varied implementation experiences, which can facilitate quicker integration of effective prevention interventions into practice. This protocol paper describes our hybrid approach to collecting and analyzing information about the implementation experiences of nine of the HPC research projects while they maintain their focus on assessing the effectiveness and cost-effectiveness of prevention interventions. To better understand implementation within this context, we will address five research questions: (1) What were the context and approach for implementing the prevention interventions, and how was the overall implementation experience? (2) How representative of the target population are the participants who were enrolled and retained in the research projects' effectiveness trials? (3) For what purposes and how were stakeholders engaged by the research projects? (4) What are the adaptable components of the prevention interventions? And finally, (5) how might implementation of the prevention interventions vary for non-trial implementation? This work will result in intervention-specific and general practical dissemination resources that can help potential adopters and deliverers of opioid misuse prevention make adoption decisions and prepare for successful implementation.

Rapid diagnostic tests for common infection syndromes: less haste, more speed.

Rapid diagnostic tests, which accurately distinguish bacterial from viral infections, are being heralded as the solution to antibiotic overuse, which is a key driver of antimicrobial resistance. We have concerns that this approach is oversimplistic. Rapid diagnostic tests are complex interventions, with clinical context, patient flow, access and timing affecting their impact. There is little robust evidence that they reduce antibiotic prescribing in real-world settings. We suggest that prior to introducing these costly tests, emphasis should be placed on optimizing the implementation of efficient evidence-based antimicrobial stewardship interventions, such as increasing the use of proven automated clinical infection syndrome prediction tools by clinicians, supporting patients to self-care by providing them with high-quality safety-netting resources, providing front-line clinicians with individual prescribing data to facilitate peer benchmarking and setting specific and purposeful antibiotic prescribing targets to improve the quality of antimicrobial prescribing. The stakes are high and time is running out; let's start by getting the basics right.

Spin in articles about minimally invasive transanal total mesorectal excision: an assessment of the current literature.

AIM: Minimally invasive transanal total mesorectal excision (TaTME) is a new approach for treating rectal cancer. 'Spin' can be defined as 'reporting strategies to highlight that the experimental treatment is beneficial' despite limitations in study design. The aim of this study was to assess spin within publications about TaTME. METHOD: EMBASE and MEDLINE (2009-2017) were searched for publications assessing TaTME in rectal cancer. All papers published between 2009 and 2017 were eligible for inclusion. Study titles and abstracts were assessed for evidence of spin, as previously defined. RESULTS: A total of 1202 studies were identified through our search, and 73 were included. The majority were case series (n = 48, 66%). A total of 55 publications (75%) had evidence of spin within at least one domain. The most common type of spin was claiming safety without describing how this was defined or tested (56%). Other strategies included claiming superiority without support (33%) and reporting nonsignificance as equivalence (42%). We did not find that year of publication (P = 0.61), study design (P = 0.60), number of patients (P = 0.85) or declared conflict of interest (P = 0.43) were associated with spin. CONCLUSION: We have shown that spin is common within studies assessing TaTME for rectal cancer. Despite a lack of support from study results, in the majority of studies authors concluded that TaTME is safe for use in rectal cancer. Readers of study abstracts describing new techniques need to be cautious about accepting the authors' conclusions, especially in case series and observational studies.

A systematic review of outcomes after salvage abdominoperineal resection for persistent or recurrent anal squamous cell cancer.

AIM: Up to 30% of patients with squamous cell cancer of the anus (SCCA) will require a salvage abdominoperineal resection (APR) for either persistent or recurrent disease. The objective of this study was to assess cancer-related outcomes in patients with (i) persistent or (ii) recurrent SCCA. METHOD: Embase and MEDLINE were searched. Publications were included if they assessed overall survival (OS), disease-free survival (DFS) and locoregional recurrence or metastatic disease after salvage APR for persistent or recurrent SCCA. RESULTS: A total of 28 retrospective case series (study size ranged from nine to 111) met our inclusion criteria. The median time to salvage APR was 2.6 months [interquartile range (IQR) 2.6-5.0 months, six studies] for persistent disease and 27.6 months (IQR 15.0-32.7 months, five studies) for recurrent disease. The median 5-year OS from the time of salvage APR was 45.0% (IQR 32.0%-52.3%, 10 studies) for persistent disease and 51.0% (IQR 36.0%-60.9%, 11 studies) for recurrent disease. The median 5-year DFS following salvage APR was 44.0% (IQR 29.5%-53.0%, 10 studies) for all patients. Following salvage APR, the median locoregional recurrence rate was 23.5% (IQR 15.8%- 46.9%, 19 studies) and 9.0% (IQR 6.4%-13.3%, 16 studies) of patients developed metastatic disease after salvage APR. CONCLUSION: Our review characterizes the best evidence for outcomes following salvage APR for patients with persistent or recurrent SCCA. The evidence is limited by the quality of included studies, as many were single centre case series.

Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics.

Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality, and treatment choices are often complex. With increased accessibility of next-generation sequencing (NGS), the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre-implantation diagnostics. We investigated a NGS PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. Twenty-seven participants were recruited, and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study shows the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.

Nutritional profile and molecular fingerprints of indigenous black jamun (Syzygium cumini L.) landraces.

The indigenous black jamun landraces (Syzygium Cumini L.), found in western Gujarat of Gir forest region (India), produced fruits with different size and shape. Fruit morphology like shape, volume, weight, length, girth were examined and black jamun categorized into six landraces viz., BJLR 1 (big fruit, > 11 g); BJLR 2 (medium to big fruit, 8-11 g); BJLR 3 (medium fruit, 6-8 g); BJLR 4 (medium to small fruit, 5-6 g); BJLR 5 (small fruit, 3-5 g) and BJLR 6 (very small fruit, < 3 g fruit weight). The landraces (BJLR 1 and 2) with larger size fruits were accumulated higher amount of moisture, total fat content, sugars, total protein, starch, free amino acid contents. Smaller fruits (BJLR 6) contained higher amount of ascorbic acid-137 and 132 mg%; anthocynin-47.7 and 2.35 mg%; crude fibre 3.05 and 10.5 g%; and total phenol-21.7 and 45.0 mg g-1 in their fruit pulp and seed part, respectively with better nutritional profile compared with big and moderate fruited landraces. Nutritional profile of six landraces indicated that fruit pulp accumulated higher amount of soluble sugars (6.51-17.6 mg g-1), anthocyanins (29.7-47.7 mg%) and free amino acids (7.54-18.9 mg%) while that of seeds exhibited higher amount of crude fibre (6017-10.5 g%), ascorbic acid (90-137 mg%), starch (22.8-29.4 g%), total protein (4.72-7.17 mg%), phenols (45-56.7 mg g-1). The black jamun landraces were subjected to ISSR based polymorphic finger prints and genetic diversity analysis. Total 144 bands were amplified across six landraces by 18 UBC primers, of which 94 were polymorphic with 64.2% average polymorphism. Cluster analysis demonstrates the BJLR 6 landraces distinguished from other landraces with 53% similarity.

Prophylactic mesh to prevent parastomal hernia: a meta-analysis of randomized controlled studies.

The aim of the present meta-analysis was to determine whether prophylactic mesh decreases the odds of parastomal hernia formation. Randomized controlled trials referenced in MEDLINE or EMBASE between 1946 and 2016 comparing prophylactic mesh to standard stoma formation were included. The primary outcome was occurrence of parastomal hernia. Secondary outcomes were parastomal hernia requiring surgical intervention and complications. Odds ratios were calculated for the primary and secondary outcomes. Subgroup analyses were conducted based on mesh type, mesh location, laparoscopic versus open, and method of hernia diagnosis. Nine randomized controlled trials with 569 participants were included. There was a significant decrease in the odds of developing a parastomal hernia in the prophylactic mesh group [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.11-0.38, p < 0.00001, I 2 = 36%], as well as decreased odds of requiring surgical repair (OR 0.36, 95% CI 0.15-0.87, p = 0.02, I 2 = 0%). There was no evidence that prophylactic mesh increased the odds of surgical complications (seven studies, OR 1.34, 95% CI 0.73-2.46, p = 0.34, I 2 = 34%) or stoma-specific complications (eight studies, OR 0.65, 95% CI 0.40-1.05, p = 0.08, I 2 = 0%). There was a subgroup effect with synthetic mesh associated with a lower incidence of parastomal hernias which was not appreciated in the biologic mesh group (test of subgroup effect p = 0.01). Five studies had a high risk of bias. The Grades of Recommendation, Assessment, Development and Evaluation quality of evidence was moderate. Prophylactic mesh is associated with decreased odds of parastomal hernia formation and the need for surgical repair. There is no evidence that mesh placement increases the odds of complications.

Antidiabetic and antioxidant functionality associated with phenolic constituents from fruit parts of indigenous black jamun (Syzygium cumini L.) landraces.

ABSTRACT: Fruit phenolics are important dietary antioxidant and antidiabetic constituents. The fruit parts (pulp, seed, seed coat, kernel) of underutilized indigenous six black jamun landraces (Syzygium cumini L.), found in Gir forest region of India and differed in their fruit size, shape and weight, are evaluated and correlated with antidiabetic, DPPH radical scavenging and phenolic constituents. The α-amylase inhibitors propose an efficient antidiabetic strategy and the levels of postprandial hyperglycemia were lowered by restraining starch breakdown. The sequential solvent systems with ascending polarity-petroleum ether, ethyl acetate, methanol and water were performed for soxhlet extraction by hot percolation method and extractive yield was found maximum with methanolic fruit part extracts of six landraces. The methanolic extracts of fruit parts also evidenced higher antidiabetic activity and hence utilized for further characterization. Among the six landraces, pulp and kernel of BJLR-6 (very small, oblong fruits) evidenced maximum 53.8 and 98.2% inhibition of α-amylase activity, respectively. The seed attained inhibitory activity mostly contributed by the kernel fraction. The inhibition of DPPH radical scavenging activity was positively correlated with phenol constituents. An HPLC-PDA technique was used to quantify the seven individual phenolics. The seed and kernel of BJLR-6 exhibited higher individual phenolics-gallic, catechin, ellagic, ferulic acids and quercetin, whereas pulp evidenced higher with gallic acid and catechin as α-amylase inhibitors. The IC50 value indicates concentration of fruit extracts exhibiting ≥50% inhibition on porcine pancreatic α-amylase (PPA) activity. The kernel fraction of BJLR6 evidenced lowest (8.3 µg ml-1) IC50 value followed by seed (12.9 µg ml-1), seed coat (50.8 µg ml-1) and pulp (270 µg ml-1). The seed and kernel of BJLR-6 inhibited PPA at much lower concentrations than standard acarbose (24.7 µg ml-1) considering good candidates for antidiabetic herbal formulations.

Antioxidant defense response induced by Trichoderma viride against Aspergillus niger Van Tieghem causing collar rot in groundnut (Arachis hypogaea L.).

The study was conducted to examine the antioxidant enzymes induced by Trichoderma viride JAU60 as initial defense response during invasion of rot pathogen Aspergillus niger Van Tieghem in five groundnut varieties under pot culture. Seed treatment of T. viride JAU60 reduced 51-58% collar rot disease incidence in different groundnut varieties under pathogen infected soil culture. The activities of the antioxidant enzymes, viz., superoxide dismutase (SOD, EC 1.15.1.1), guaiacol peroxidase (GPX, EC 1.11.1.7) and ascorbate peroxidase (APX, EC 1.11.1.11), elevated in response to pathogen infection, in higher rate by tolerant varieties (J-11 and GG-2) compared with susceptible (GAUG-10, GG-13, GG-20) and further induced by T. viride treatment. Trichoderma treatment remarkably increased the 2.3 fold SOD, 5 fold GPX and 2.5 fold APX activities during disease development in tolerant varieties and the same was found about 1.2, 1.5 and 2.0 folds, respectively, in susceptible varieties. Overall, T. viride JAU60 treated seedlings (T3) witnessed higher activities of SOD (1.5 fold), GPX (3.25 fold) and APX (1.25 fold) than pathogen treatment (T2) possibly suggest the induction of antioxidant defense response by Trichoderma bio-controller to combat oxidative burst produced by invading pathogen.

Translation and validation of the Visual Function and Corneal Health Status (V-FUCHS) questionnaire into Spanish language.

PURPOSE: To translate and validate the V-FUCHS questionnaire into Spanish in a population of patients with Fuchs endothelial dystrophy (DEF). METHODS: The V-FUCHS consists of 15 short, easily understandable questions that assess visual aspects of quality of life in patients with DEF, which can be gathered into a group of seven that assess the "Visual Difficulty" factor and another group of eight that assess the "Glare Factor". For the translation and cultural adaptation, the standardized norms for this process were followed, among other phases, a translation, a back-translation and an application in patients with DEF. RESULTS: In the first phase, consensus was reached on the Spanish translation of the V-FUCHS. Subsequently, 25 patients were included to carry out the pre-test phase with the aim of assessing the applicability and feasibility of the test. The score obtained a minimum value of -0.88 and a maximum value of +2.44, according to the Rasch probabilistic scale. The mean value obtained from the Visual Difficulty factor was 0.61 (±0.71), while the mean for the Glare Factor was 0.41 (±0.51). CONCLUSION: The validation of the V-FUCHS questionnaire, after its translation and adaptation into Spanish, proved to be a useful tool for assessing the visual quality of patients with DEF. Patients with a more advanced stage of the disease presented a greater severity in the test result. Likewise, the Glare Factor (Glare) correlates better with the pachymetric increase than with the visual acuity of the patient.

Acute minocycline treatment inhibits microglia activation, reduces infarct volume, and has domain-specific effects on post-ischemic stroke cognition in rats.

Ischemic stroke affects millions of individuals worldwide and a high prevalence of survivors experience cognitive deficits. At present, the underlying mechanisms that drive post-stroke cognitive decline are not well understood. Microglia play a critical role in the post-stroke inflammatory response, but experimental studies show that an accumulation of chronically activated microglia can be harmful and associates with cognitive impairment. This study assessed the effect of acute post-stroke minocycline treatment on chronic microglia and astrocyte expression within the infarct and remote white matter regions, as well as its effect on various domains of cognitive function post-stroke. Nine-month-old male rats received an injection of endothelin-1 into the right dorsal striatum to induce transient focal ischemia, and then were treated with minocycline or saline for 4 days post-stroke. Rats were tested using a series of lever-pressing tasks and the Morris water maze to assess striatal-based learning, cognitive flexibility, and spatial learning and reference memory. We found that minocycline-treated rats had smaller stroke-induced infarcts and less microglia activation in the infarct area and remote white matter regions compared to saline-treated rats at 28 days post-stroke. The behavioural testing results differed according to the cognitive domain; whereas minocycline-treated rats trended towards improved striatal-based learning in a lever-pressing task, but cognitive flexibility was unaffected during the subsequent set-shifting task. Furthermore, minocycline treatment unexpectedly impaired spatial learning, yet it did not alter reference memory. Collectively, we show that post-stroke minocycline treatment can reduce chronic microglia activation even in remote brain regions, with domain-specific effects on cognitive function.

Prevalence of dental fluorosis & dental caries in association with high levels of drinking water fluoride content in a district of Gujarat, India.

BACKGROUND & OBJECTIVES: Endemic fluorosis resulting from high fluoride concentration in groundwater is a major public health problem in India. This study was carried out to measure and compare the prevalence of dental fluorosis and dental caries in the population residing in high and normal level of fluoride in their drinking water in Vadodara district, Gujarat, India. METHODS: A cross-sectional study was conducted in Vadodara district, six of the 261 villages with high fluoride level and five of 1490 with normal fluoride level in drinking water were selected. The data collection was made by house-to-house visits twice during the study period. RESULTS: The dental fluorosis prevalence in high fluoride area was 59.31 per cent while in normal fluoride area it was 39.21 per cent. The prevalence of dental caries in high fluoride area was 39.53 per cent and in normal fluoride area was 48.21 per cent with CI 6.16 to 11.18. Dental fluorosis prevalence was more among males as compared to females. Highest prevalence of dental fluorosis was seen in 12-24 yr age group. INTERPRETATION & CONCLUSIONS: The risk of dental fluorosis was higher in the areas showing more fluoride content in drinking water and to a lesser degree of dental caries in the same area. High fluoride content is a risk factor for dental fluorosis and problem of dental fluorosis increased with passage of time suggesting that the fluoride content in the water has perhaps increased over time. Longitudinal studies should be conducted to confirm the findings.

Effectiveness of Trastuzumab in Routine Clinical Practice: A Population-based Study of Patients with HER-2-positive Oesophageal, Gastroesophageal and Gastric Cancer.

AIMS: In the pivotal Trastuzumab for Gastric Cancer (ToGA) trial, trastuzumab improved median survival in patients with advanced HER-2-positive gastric and gastroesophageal cancer from 11.1 to 13.8 months; however, its effectiveness in routine clinical practice has not been evaluated. Our objective was to evaluate the uptake and outcomes of trastuzumab in a population-based cohort of patients with oesophageal, gastroesophageal and gastric cancer in Ontario, Canada. MATERIALS AND METHODS: The Ontario Cancer Registry and linked treatment records were used to identify all patients with oesophageal, gastroesophageal and gastric cancer treated with trastuzumab during 2012-2017. Outcomes were analysed from the time of first trastuzumab cycle and included a primary outcome (survival) and secondary outcomes (uptake, delivery, 30-day hospital admission and 30-day mortality). Trends over the study period and survival were evaluated. RESULTS: In total, 476 patients with oesophageal, gastroesophageal and gastric cancer received trastuzumab during the study period. The mean age was 62 years, 78% (370/476) were male, and 65% (312/476) had gastric cancer. The annual number of patients receiving trastuzumab increased over the study period (53 in 2012 and 101 in 2017). The median number of cycles of trastuzumab delivered was six. Thirty-day hospital admission and mortality rates were 17% and 4%, respectively. The median overall survival was 282 days (9.3 months). CONCLUSIONS: The median survival of patients treated with trastuzumab for advanced oesophageal, gastroesophageal and gastric cancer in routine practice is substantially less than that observed in the pivotal clinical trial. Studies of comparative effectiveness using real-world data offer insight into outcomes achieved in routine practice.

Improving paediatric antimicrobial stewardship in hospital-based settings: why, where and how?

BACKGROUND: Antimicrobial resistance (AMR) is being recognized as a priority by healthcare organizations across the world. However, many children are managed on IV antimicrobials in hospital with very little consideration of antimicrobial stewardship issues. OBJECTIVES: A nurse-led paediatric ambulatory outpatient parenteral antimicrobial therapy (OPAT) service, managing children with common infections being ambulated on short courses of IV antimicrobials, was introduced within Southampton Children's Hospital in January 2018. We evaluated the impact of this service in terms of the quality of antimicrobial prescribing and timing of ambulation in children presenting with common infections. METHODS: All cases managed within the service were reviewed in two separate 2 month time periods: prior to introduction of the service (September-October 2016) and then prospectively after its introduction (September-October 2018). RESULTS: A total of 96% of IV antibiotic management decisions at 48 h were deemed appropriate in 2018, compared with 75% in 2016. A total of 64% of patients were ambulated on IV antibiotics at some point during their treatment course in 2018, compared with 19% in 2016. However, a significant proportion of antimicrobial decisions made at the point of presentation to hospital remained suboptimal in 2018. CONCLUSIONS: Children are commonly managed with IV antibiotics in hospital. We demonstrate marked improvements in appropriate antimicrobial use through the introduction of a nurse-led ambulatory OPAT service. In addition, such a service can promote a greater proportion of children being ambulated from hospital, freeing up valuable inpatient beds and potentially delivering cost savings that can be used to fund such services.

Incidence of incisional hernias following single-incision versus traditional laparoscopic surgery: a meta-analysis.

PURPOSE: To compare, using a meta-analysis of randomized controlled trials, the risk of incisional hernia in patients undergoing single-incision laparoscopic surgery to those undergoing traditional laparoscopic surgery. METHODS: MEDLINE and EMBASE databases were searched. Randomized controlled trials comparing single-incision laparoscopic surgery to traditional laparoscopic surgery and which reported incisional hernias over a minimum 6-month follow-up period were eligible. Risk of bias was assessed as outlined in the Cochrane Handbook. Pooled odds ratios were calculated using RevMan. RESULTS: Of 309 identified studies, 22 were included in this meta-analysis. Pooled results showed higher odds of incisional hernia following single-incision laparoscopic surgery relative to traditional laparoscopic surgery (odds ratio 2.83, 95% CI 1.34-5.98, p = 0.006, I2 = 0%). There was no difference in the odds of incisional hernias requiring surgical repair (p = 0.10). Subgroup analysis found no difference in the odds of incisional hernias based on procedure type (p = 0.69) or method of follow-up (p = 0.85). The quality of evidence was determined to be moderate. CONCLUSION: Single-incision laparoscopic surgery is associated with a threefold increase in the odds of incisional hernia compared with traditional laparoscopic surgery.

Is early cardioversion for atrial fibrillation safe in patients with spontaneous echocardiographic contrast?

The 2006 American Heart Association guidelines for management of patients with atrial fibrillation state "For patients with no identifiable thrombus in the left atrium (LA) or left atrial appendage (LAA), cardioversion (CV) is reasonable immediately after anticoagulation with unfractionated heparin. Thereafter, continuation of oral anticoagulation is reasonable for an anticoagulation period of at least 4 weeks". For patients with thrombus identified by transesophageal echocardiography, guidelines recommend therapeutic oral anticoagulation for 3 weeks prior to and 4 weeks after elective cardioversion. Patients with spontaneous echo contrast (SEC) identified by TEE have a high risk of thromboembolic events,1-8 however, the guidelines do not address whether patients with SEC without thrombus can be safely cardioverted. This paper reviews the literature describing the pathogenesis of SEC, how it is detected, and whether elective cardioversion is safe. On the basis of our review, we believe that the risk of cardioembolic stroke after cardioversion of a patient with SEC is low, regardless of anticoagulation. The safe conclusion is that patients with SEC on TEE should receive therapeutic anticoagulation prior to cardioversion if possible and early cardioversion is not contraindicated.

Identification of downstream-initiated c-Myc proteins which are dominant-negative inhibitors of transactivation by full-length c-Myc proteins.

The c-myc gene has been implicated in multiple cellular processes including proliferation, differentiation, and apoptosis. In addition to the full-length c-Myc 1 and 2 proteins, we have found that human, murine, and avian cells express smaller c-Myc proteins arising from translational initiation at conserved downstream AUG codons. These c-Myc short (c-Myc S) proteins lack most of the N-terminal transactivation domain but retain the C-terminal protein dimerization and DNA binding domains. As with full-length c-Myc proteins, the c-Myc S proteins appear to be localized to the nucleus, are relatively unstable, and are phosphorylated. Significant levels of c-Myc S, often approaching the levels of full-length c-Myc, are transiently observed during the rapid growth phase of several different types of cells. Optimization of the upstream initiation codons resulted in greatly reduced synthesis of the c-Myc S proteins, suggesting that a "leaky scanning" mechanism leads to the translation of these proteins. In some hematopoietic tumor cell lines having altered c-myc genes, the c-Myc S proteins are constitutively expressed at levels equivalent to that of full-length c-Myc. As predicted, the c-Myc S proteins are unable to activate transcription and inhibited transactivation by full-length c-Myc proteins, suggesting a dominant-negative inhibitory function. While these transcriptional inhibitors would not be expected to function as full-length c-Myc, the occurrence of tumors which express constitutive high levels of c-Myc S and their transient synthesis during rapid cell growth suggest that these proteins do not interfere with the growth-promoting functions of full-length c-Myc.

Molecular evolution and phylogenetic analysis of biocontrol genes acquired from SCoT polymorphism of mycoparasitic Trichoderma koningii inhibiting phytopathogen Rhizoctonia solani Kuhn.

The biocontrol agent Trichoderma (T. harzianum, T. viride, T. virens, T. hamantum, T. koningii, T. pseudokoningii and Trichoderma species) inhibited variably (15.32 - 88.12%) the in vitro growth of Rhizoctonia solani causing root rot in cotton. The T. koningii MTCC 796 evidenced highest (88.12%) growth inhibition of test pathogen followed by T. viride NBAII Tv23 (85.34%). Scanning electron microscopic study confirmed mycoparasitism for MTCC 796 and Tv23 which were capable of completely overgrowing on R. solani by degrading mycelia, coiling around the hyphae with hook-like structures. The antagonists T. harzianum NBAII Th1 and, T. virens NBAII Tvs12 exhibited strong antibiosis and formed 2-4 mm zone of inhibition for 70.28% and 46.62%, respectively growth inhibition of test pathogen. Mycoparasitism is a strong mode of action for biocontrol activity compared with antibiosis. The antagonists Trichoderma strains were performed for start codon targeted (SCoT) polymorphism to acquire biocontrol genes from potent antagonist. The six unique SCoT fragments amplified by genomic DNA of best mycoparasitic antagonist MTCC 796 strain are subjected to DNA sequencing resulted to confirm two functional sequences for activity related to biocontrol genes. The phylogenetic and molecular evolution of functional 824 bp of SCoT-3(920) and 776 bp of SCoT-6(806) fragments signify sequence homology with biocontrol genes endochitinase (partial cds of 203 amino acids) and novel hmgR genes (partial cds of 239 amino acids), respectively and the same were annotated and deposited in NCBI GenBank database. The hmgR gene is liable to be express hmg - CoA reductase which is a key enzyme for regulation of terpene biosynthesis and mycoparasitic strains produced triterpenes during antagonism to inhibit growth of fungal pathogen as evidenced with GC-MS profile. The biocontrol genes are found in best antagonist T. koningii MTCC 796 for mycoparasitic activity to restrain the growth of test pathogen R. solani.

Trichoderma viride induces pathogenesis related defense response against rot pathogen infection in groundnut (Arachis hypogaea L.).

The study examine induction of defense enzymes involved in phenylpropanoid pathway and accumulation of pathogenesis related proteins in rot pathogen (Aspergillus niger Van Tieghem) challenged groundnut seedlings in response to Trichoderma viride JAU60. Seeds of five groundnut varieties differing in collar rot susceptibility were sown under non-infested, pathogen infested and pathogen+T. viride JAU60 seed treatment. Collar rot disease evident between 31.0% (J-11, GG-2) and 67.4% (GG-20) in different groundnut varieties under pathogen infested which was significantly reduced from 58.1% (J-11, GG-2) to 51.6% (GG-20) by Trichoderma treatment. The specific activities of polyphenol oxidase (EC 1.14.18.1) and ß-1,3 glucanase (EC 3.2.1.6) elevated 3.5 and 2.3-fold, respectively, at 3 days; phenylalanine ammonia lyase (EC 4.3.1.5) evident 1.6-fold higher at 6 days; and chitinase (EC 3.2.1.14) sustained 2.3-2.8 folds up to 9 days in Trichoderma treated+pathogen infested seedlings of tolerant varieties (J-11, GG-2) compared with moderate and susceptible (GAUG-10, GG-13, GG-20). T. viride JAU60 induces defense enzymes in a different way for tolerant and susceptible varieties to combat the disease. This study indicates the synergism activation of defense enzymes under the pathogenic conditions or induced resistance by T. viride JAU60 in a different groundnut varieties susceptible to collar rot disease.

An association between sebaceous carcinoma and microsatellite instability in immunosuppressed organ transplant recipients.

Sebaceous carcinomas are rare cutaneous appendageal tumors that may occur sporadically or in association with an internal malignancy in Muir-Torre syndrome. In Muir-Torre syndrome microsatellite instability can often be demonstrated in tumor DNA as a result of an inherited mutation in one of several known mismatch repair genes; however, the role of microsatellite instability in sporadic sebaceous carcinomas has not been previously studied. In this report we describe the clinicopathologic characteristics of a series of unselected sebaceous carcinomas and examine them for the presence of microsatellite instability. Of 10 consecutive tumors identified over a 10 y period, only one was from a patient known to have Muir-Torre syndrome. Of the nine presumed sporadic cases, five were from four renal transplant recipients and four from otherwise healthy individuals. Microsatellite instability was demonstrable in three cases: in the Muir-Torre syndrome-associated tumor and in two tumors from transplant patients. Microsatellite instability was subsequently also found in a sebaceous carcinoma from a further transplant patient prospectively sought from another institution. The presence of microsatellite instability in post-transplant sebaceous carcinomas was associated with loss of expression of the mismatch repair protein hMSH2. In summary, sebaceous gland carcinomas, while characteristic of Muir-Torre syndrome, are commonly found outside this context. Among presumed sporadic cases, our data suggest they may be over-represented in immunosuppressed renal transplant recipients. The presence of microsatellite instability in transplant-associated lesions, together with loss of hMSH2 expression suggests that immunosuppression might unmask a previously silent Muir-Torre syndrome phenotype in some cases. Alternatively, there is experimental evidence to suggest that immunosuppressive drugs, most plausibly azathioprine, could select for the emergence of a mutator phenotype and thus predispose to the development of sebaceous carcinomas. The role of mismatch repair defects in other post-transplant skin malignancies remains to be established.