Reclaiming comprehensive public health

Global and national responses to the COVID-19 pandemic highlight a long-standing tension between biosecurity-focused, authoritarian and sometimes militarised approaches to public health and, in contrast, comprehensive, social determinants, participatory and rights-based approaches. Notwithstanding principles that may limit rights in the interests of public health and the role of central measures in some circumstances, effective public health in a protracted pandemic like COVID-19 requires cooperation, communication, participatory decision-making and action that safeguards the Siracusa principles, respect for people’s dignity and local-level realities and capacities. Yet there is mounting evidence of a dominant response to COVID-19 where decisions are being made and enforced in an overcentralised, non-transparent, top-down manner, often involving military coercion and abuse in communities, even while evidence shows the long-term harm to public health and human rights. In contrast, experiences of comprehensive, equity-focused, participatory public health approaches, which use diverse sources of knowledge, disciplines and capabilities, show the type of public health approach that will be more effective to meet the 21st century challenges of pandemics, climate, food and energy crises, growing social inequality, conflict and other threats to health

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Loss-of-function uORF mutations in human malignancies

Abstract Ribosome profiling revealed widespread translational activity at upstream open reading frames (uORFs) and validated uORF-mediated translational control as a commonly repressive mechanism of gene expression. Translational activation of proto-oncogenes through loss-of-uORF mutations has been demonstrated, yet a systematic search for cancer-associated genetic alterations in uORFs is lacking. Here, we applied a PCR-based, multiplex identifier-tagged deep sequencing approach to screen 404 uORF translation initiation sites of 83 human tyrosine kinases and 49 other proto-oncogenes in 308 human malignancies. We identified loss-of-function uORF mutations in EPHB1 in two samples derived from breast and colon cancer, and in MAP2K6 in a sample of colon adenocarcinoma. Both mutations were associated with enhanced translation, suggesting that loss-of-uORF-mediated translational induction of the downstream main protein coding sequence may have contributed to carcinogenesis. Computational analysis of whole exome sequencing datasets of 464 colon adenocarcinomas subsequently revealed another 53 non-recurrent somatic mutations functionally deleting 22 uORF initiation and 31 uORF termination codons, respectively. These data provide evidence for somatic mutations affecting uORF initiation and termination codons in human cancer. The insufficient coverage of uORF regions in current whole exome sequencing datasets demands for future genome-wide analyses to ultimately define the contribution of uORF-mediated translational deregulation in oncogenesis

Iatrogenic Bile Duct Injuries in Kashmir Valley

Cholecystectomy is one of the commonest operations performed throughout the world and bile duct injury is the worst complication of this procedure. In a prospective and retrospective study 25 patients were seen in a tertiary care hospital over a period of 10 years. 72% of patients were referred from other hospitals. 48% of patients presented within one month of injury. Pain was the commonest presentation (92%) followed by jaundice (80%). Liver functions were deranged in 70% of patients, USG revealed biliary dilatation in 69.6% of patients. ERCP was done in 16 patients and revealed cut off of the common hepatic duct in 43.8% of patients. Intraoperative findings revealed adhesions in 96% of patients. 48% of patients had bile duct stricture. Roux-en-Y hepaticojejunostomy was the commonest procedure performed. All patients showed improvement in liver function after surgery. Wound infection was the commonest complication seen in 32% patients. 3 patients died in our series

Tissue Culture, Genetic Engineering, and Nanotechnology in Bitter Gourd

Bitter gourd (Momordica charantia L.) belongs to the genus Momordica that includes 45 species. It is cultivated extensively in tropical, subtropical, and rarely under temperate climates. The plant is valued in various disciplines of life and natural sciences. It is extensively used for culinary purposes. Its extracts are important for the treatment of a number of diseases and ailments in traditional and modern medicinal systems because of the abundance of insulin-like peptides, a mixture of steroidal sapogenins and alkaloids. It is rarely used as an ornamental plant. There are very few reports on systematic research on agronomic, breeding, and biotechnological aspects that curtail the improvement of this crop plant. This chapter reviews available information on biotechnology in a bitter gourd that will help understand the current scenario and help in making plans for improvement of bitter gourd