Clinicopathological comparison of VHL expression as a prognostic tumor marker in renal cell carcinoma: A single center experience.

AIM: To assess the VHL gene expression as a prognostic marker in Renal Cell Carcinoma (RCC) and compare it with clinicopathologic features. MATERIALS AND METHODS: This retrospective observational study was conducted in the department of Urology and Renal Transplantation in Sri Ramachandra Institute of Higher Education and Research, Chennai from August 2016 to August 2018. Thirty patients who have undergone a radical/partial nephrectomy with biopsy proven histological diagnosis of RCC during the study period were included in the study. Data was analyzed using Statistical package for Social Sciences version 17. RESULTS: A complete loss and retained VHL expression were noted in 60% and 40% of the RCC specimens. Association between smoking and VHL expression was found to be statistically significant. There was no statistical significance found between age group, sex, chief complaints, BMI. ECOG score, hypertension, family history, location of tumor, calcification, venous system or lymphnode involvement. However, rT staging, nature of lesion and cut surface, HPE type, pT staging, HPE grade, necrosis and lympho-vascular invasion were also found to be statistically significant. CONCLUSION: Complete loss of VHL expression was noted in majority of the specimens that leads to the development of RCC. Smoking has been found to be statistically significant in tumors that retain VHL expression which may contributes to more aggressive form of tumor. Association between rT staging, nature of lesion and cut surface, HPE type, pT staging, HPE grade, necrosis and lympho-vascular invasion were also found to be statistically significant.

Attitudes towards risk-reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study.

OBJECTIVE: To determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. DESIGN: Multicentre, cohort, questionnaire study (IRSCTN:12310993). SETTING: United Kingdom (UK). POPULATION: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. METHODS: Participants completed a 39-item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. MAIN OUTCOMES: RRESDO acceptability, menopausal sequelae, satisfaction/regret. RESULTS: In all, 346 of 683 participants underwent risk-reducing salpingo-oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2-7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2-27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2-0.9, P = 0.025). CONCLUSION: Data show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness. TWEETABLE ABSTRACT: RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.

Translation Approach for Dentine Regeneration Using GSK-3 Antagonists.

The canonical Wnt/ß-catenin signaling pathway is crucial for reparative dentinogenesis following tooth damage, and the modulation of this pathway affects the rate and extent of reparative dentine formation in damaged mice molars by triggering the natural process of dentinogenesis. Pharmacological stimulation of Wnt/ß-catenin signaling activity by small-molecule GSK-3 inhibitor drugs following pulp exposure in mouse molars results in reparative dentinogenesis. The creation of similar but larger lesions in rat molars shows that the adenosine triphosphate (ATP)-competitive GSK-3 inhibitor, CHIR99021 (CHIR), and the ATP noncompetitive inhibitor, Tideglusib (TG), can equally enhance reparative dentine formation to fully repair an area of dentine damage up to 10 times larger, mimicking the size of small lesions in humans. To assess the chemical composition of this newly formed dentine and to compare its structure with surrounding native dentine and alveolar bone, Raman microspectroscopy analysis is used. We show that the newly formed dentine comprises equal carbonate to phosphate ratios and mineral to matrix ratios to that of native dentine, both being significantly different from bone. For an effective dentine repair, the activity of the drugs needs to be restricted to the region of damage. To investigate the range of drug-induced Wnt-activity within the dental pulp, RNA of short-term induced (24-h) molars is extracted from separated roots and crowns, and quantitative Axin2 expression is assayed. We show that the activation of Wnt/ß-catenin signaling is highly restricted to pulp cells in the immediate location of the damage in the coronal pulp tissue with no drug action detected in the root pulp. These results provide further evidence that this simple method of enhancement of natural reparative dentinogenesis has the potential to be translated into a clinical direct capping approach.

A Mouse Model to Study Reparative Dentinogenesis.

Different animal models have been introduced recently to study the process of reparative dentinogenesis in response to injury-induced pulp exposure. Using a mouse model is advantageous over other animal models since mice can be genetically manipulated to examine specific cellular pathways and lineage trace the progeny of a single cell. However, enabling a standardized molar damage in mice is demanding due to the small size of the teeth compared to the available dental instruments. Here we describe a reproducible and reliable in vivo model that allows us to study dentinogenesis in the first maxillary mouse molar.

Prevalence of enteropathogens and their antibiotic sensitivity pattern in puppies with hemorrhagic gastroenteritis.

AIM: Hemorrhagic gastroenteritis (HGE) ranging from mild to severe forms is commonly encountered in puppies. The aim of the study was to identify the prevalence of common enteropathogens and the antibiotic sensitivity pattern in puppies reported with HGE. MATERIALS AND METHODS: The canine HGE activity index, with little modification, was adopted to identify Grade III/severely affected puppies below 6 months of age. Fecal polymerase chain reaction (PCR) assay was employed to screen and compare the enteropathogens in puppies with hemorrhagic diarrhea and healthy control. RESULTS: Canine parvovirus 2b was identified in 90.3% of the diarrheic and 10% of the non-diarrheic healthy puppies. Clostridium difficile was identified in all the diarrheic puppies and in 80% of the healthy puppies. Among the diarrheic puppies, 17.7% were positive for Clostridium perfringens enterotoxin, 9.7% were positive for C. perfringens alpha toxin, 6.4% were positive for Escherichia coli shiga toxin, 6.4% were positive for E. coli enterotoxin (LT), and 3.2% were positive for canine distemper virus. Whereas, none of the healthy puppies were positive for these bacteria and toxins. Fecal antibiotic sensitivity test pattern revealed gentamicin to be sensitive in 95% of the cases, azithromycin in 50%, enrofloxacin in 25%, cefotaxime in 20%, and tetracycline in 5% of the cases. CONCLUSION: Parvoviral enteritis is predominant among puppies. Yet, bacteria and their toxins also play an important role in HGE. Gentamicin has higher sensitivity against the enteropathogens associated with the condition.

Effect of coenzyme Q10 supplementation on serum protein, mineral status, blood picture and immune status in broilers.

In poultry, coenzyme Q10 (CoQ10) is widely used as a feed additive to control mortality due to ascites in broilers. Apart from its use the treatment of a variety of disorders viz., ischemic heart disease, diabetes mellitus, Parkinson's disease, muscle fatigue and muscle weakness, its supplementation has been reported to be beneficial for cardiovascular disease, chronic heart failure, cancer, migraine, asthma and hypertension. In this study, we investigated the effect of CoQ10 supplementation on serum protein, serum minerals, blood parameters, ascites susceptibility and humoral immune status in broilers fed with different energy levels which influence their productivity, biochemical profile and ascites incidences. The treatment had three levels of CoQ10, namely 0, 20 and 40 mg/kg at normal (NE), low (LE) and high (HE) energy levels in which 2X3 factorial design was followed. The haemoglobin and packed cell volume were not affected (P >0.05) by either energy or CoQ10 levels but the erythrocyte osmotic fragility per cent (EOF %) and blood glucose levels were decreased by CoQ10 supplementation at both 20 and 40 mg/kg. The serum calcium level had significantly (P <0.01) increased with CoQ10 at 40 mg/kg (12.70 vs. 11.58 and 11.98 mg/dL) in NE diet group over the unsupplemented and 20 mg/kg supplemented birds. Compared to the respective unsupplemented groups, CoQ10 @40 mg/kg reduced (P <0.01) the serum total protein (4.69 vs. 5.23 g/dL) and serum albumin (2.46 vs. 2.78 g/dL) in NE group but increased (P <0.01) (4.70 vs. 4.08 g/dL) and (2.59 vs. 2.04 g/dL), respectively in LE group. High energy birds showed significantly (P <0.01) increased serum albumin (2.74 vs. 2.24 g/dL). The humoral immunity against Newcastle Disease (ND titre) was significantly (P <0.01) higher in 21 days of growth period at both the levels of supplementation but on 42 days no significant difference among the groups were observed. It can be concluded that CoQ10 supplementation at 20 mg/kg decreased blood glucose level and increased erythrocytes osmotic stability and hence, could reduce bird's susceptibility to ascites.

Seasonal variations in composting process of dead poultry birds.

Composting of dead birds with caged layer manure (CLM) and farm yard manure (FYM) was carried out to study the feasibility of composting as an alternative for disposal in Tamil Nadu State, India. The dead birds were sequentially layered with manure substrate and carbon source as per recipes formulated in mini-compost bins (4 x 4 x 4 feet). The temperature profile of both CLM and FYM group reached the peak by second week of composting and started declining steadily. The temperature profile was better during summer and monsoon and bins were able to maintain temperature above 60 degrees C (thermophilic) for 3-4 weeks. Season had no influence on attainment of peak temperature and it ranged between 51.8 and 70.4 degrees C. The persistency of thermophilic temperature (above 55 degrees C) was prolonged during summer (17.5-65 days) followed by monsoon (24-39 days) and winter (15.5-21.5 days). No putrefied or obnoxious odour or fly menace was observed during all the seasons of composting. The composting process took 107-127.5 days to finish during summer, 84.5-91 days in monsoon and 61.5-73.5 days in winter. The FYM was able to retain moisture higher (41-54% at the end of primary stage and 27.5-48.2% at the end of secondary stage) than CLM group (17.5-39.3% at primary stage and 20.4-33.5% in secondary stage). Weight reduction was more in FYM group (31.8-58.7%) than CLM group (19.3-48.6%). The volume reduction was uniform in all the seasons, it ranged between 39% and 59.3%.

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.

BACKGROUND: Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. OBJECTIVES: To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer. METHODS: By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. RESULTS: HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. CONCLUSIONS: Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.

Comparison of in vitro characteristics of and experimental lesions produced by a clinical and an environmental isolate of Aspergillus flavus.

In the present study, two strains of Aspergillus flavus (one from a human corneal ulcer and one from the environment) were found to be strikingly similar in vitro in terms of thermotolerance, inability to grow in an anaerobic environment and in secreting proteinases; however, one obvious difference was that the clinical isolate produced 120 ppb of aflatoxin B1 in glucose salt medium while the environmental isolate did not produce this toxic metabolite. Alterations in the activities of acid phosphatase (ACP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and glutathione-S-transferase were observed in the liver, kidney and serum in an experimental rat model, irrespective of whether the animal had been challenged with the clinical isolate or the environmental isolate of A. flavus. In rats that had been challenged with the clinical isolate, a significant decrease in the activity of kidney ALP was noted, whereas in rats that had been challenged with the environmental isolate, the reverse was observed. While these differential alterations may have occurred due to differences in the toxin-producing ability of the two isolates, further investigation is warranted to clarify whether other phenotypic, or genotypic, differences are also involved.