Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions

Background Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. Methods We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. Results Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. Conclusions Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis

Efeitos da aplicação de prostaglandinas intervaladas de 10 dias sobre características reprodutivas de cabras leiteiras nulíparas cíclicas

Relataram-se os efeitos da aplicação de prostaglandina sobre características reprodutivas de cabras leiteiras nulíparas cíclicas. Cabras Alpinas (n=9) e Saanen (n=9) receberam duas doses de 22,5mg PGF2a com 10 dias de intervalo. A progesterona plasmática (ng/mL) foi determinada a partir de amostras de sangue coletadas nos dias 0 (primeira dose), 5, 10 (segunda dose), 15, 20, 25 e 30. Após início do segundo estro, as fêmeas foram monitoradas por ultrassonografia transretal a cada quatro horas até oito horas após a ovulação. A gestação foi verificada por ultrassonografia transretal nos dias 20, 25, 30, 35 e 90 após a segunda dose. As características estudadas foram semelhantes entre as raças (P>0,05). Animais em estro e o intervalo parto-estro de, respectivamente, 78,9% e 50,6±17,2h e 88,9% e 50,0±14,8h após a primeira e segunda administrações de prostaglandina, não diferiram (P>0,05). Todas as cabras ovularam e registraram-se valores do intervalo parto-ovulação após a segunda aplicação de prostaglandina de 64,5±19,5h e após início do estro de 18,0±9,1h, a taxa de ovulação de 1,3±0,5 e diâmetro do folículo ovulatório de 8,1±1,1mm. Perda embrionária ocorreu antes de 30 dias de gestação. O estro pode ser eficientemente sincronizado em cabras leiteiras núliparas com duas doses de prostaglandina intervaladas de 10 dias. _________________________________________________________________________________________ ABSTRACT: This study reported the effects of prostaglandin (PGF2a) administration 10 days apart on reproductive parameters of cyclic artificial inseminated (AI) nulliparous Alpine (n=9) and Saanen (n=9) goats. Animals received two doses of 22.5mg PGF2a 10 days apart. After 1st and 2nd PGF2a administrations, estrus was monitored at 12 h intervals, with a buck teaser. Plasma progesterone concentration (ng/mL) was determined from blood sampled on day 0 (1st PGF2a) and the following 5, 10 (2nd PGF2a), 15, 20, 25 and 30 days. After the onset of the second estrus, females were transrectally (5 MHz probe) scanned at 4 hour intervals until at least 8h after ovulation. Pregnancy was checked through transrectal ultrasound on days 20, 25, 30, 35 and 90 after insemination. All parameters studied did not differ between breeds (P>0.05). Estrous response and interval to estrus, respectively, after 1st (78.9% and 50.6±17.2h) and 2nd PGF2a (88.9% and 50.0±14.8h) administration did not differ (P>0.05). Overall animals ovulating (100.0%), interval to ovulation after 2nd PGF2a (64.5±19.5h) and after estrous onset (18.0±9.1h), ovulation rate (1.3±0.5), diameter of ovulatory follicle (8.1±1.1mm) were recorded. Embryo loss occurred before day 30 of pregnancy. Estrus can be efficiently synchronized in nulliparous Alpine and Saanen goats with two doses of prostaglandin 10 days apart

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Covid-19 update: Omicron variant − a new emerging threat

A new health threat in the form of a new variant of Covid-19 called Omicron has emerged globally in this holiday season. This new variant has been declared a variant of concern (VOC) by the World Health Organization and experts are expecting another wave of the pandemic. A lot still unknown about this variant and researchers worldwide are conducting studies to find the nature and characteristics of this mutated strain. Cases have begun to rise dramatically around the world and many countries have already imposed travel restrictions again to prevent disease transmission. It is being speculated that this particular variant has got tendency of immune escape and therefore can even infect fully vaccinated individuals. Vaccination and adhering to Covid-19 guidelines and protocols can curtail the spread of the virus. The present paper focuses on what is currently known about this variant, antigen diagnostic tests, importance of getting fully vaccinated and having booster dose etc. If we want to emerge from this pandemic, countries should practice vaccine equality and solidarity for the good of mankind

Identifying monkeypox: do dental professionals have adequate knowledge and awareness?

Background. The emergence of monkeypox has presented a new challenge for health agencies around the globe. There is significant increase in the number of cases that too in non-endemic countries with more than 18000 cases reported worldwide. Objective. The present study was conducted to assess knowledge and awareness regarding monkeypox among dental professionals. Materials and Method. The present cross-sectional study among 410 subjects who were residing in a northern state of the country. Informed consent was obtained from all the subjects. Study sample was selected on the basis of Systematic random sampling methodology. A self-designed close-ended questionnaire written in English and verified by experts was utilized for the study. The questionnaire was delivered personally to study subjects to collect the required information. Chi-square test and ANOVA were used for statistical analysis. Results. One-fourth (24.8%) of the subjects never heard about monkeypox disease. Negative response was given by 44.8% of subjects regarding resemblance of monkeypox with small pox. Only 31.2% of subjects had knowledge regarding oral manifestations of the disease. High knowledge scores were reported by only 28% of subjects. Higher knowledge levels were significantly related to education level and working profile of study subjects. Online media (Internet) was preferred as the main source to obtain more information by 42.2 of subjects. Conclusion. There was low level of knowledge regarding monkeypox among study subjects. There is an urgent need for dental professionals to keep themselves updated with recent knowledge on new emerging infectious diseases