Association of gallstone disease with risk of colorectal cancer: a systematic review and meta-analysis of observational studies.

BACKGROUND: Numerous studies have assessed the association of gallstones or cholecystectomy (CE) with risk of colorectal cancer (CRC). However, the findings are mixed. OBJECTIVE: To systematically review and meta-analyse the association between the presence of gallstone disease (GD), or CE and the incidence of CRC. Secondary endpoints were the risk based on type of exposure, study design, tumour subsites and sex. METHODS: PubMed and EMBASE were searched from September 2020 to May 2021. The protocol was registered on the Open Science Foundation Platform. We identified and classified studies according to their design into prospective cohort, population-based case-control, hospital-based case-control and necropsy studies reporting CRC incidence among individuals with diagnosed GD or after CE (or both). Among 2157 retrieved studies, 65 (3%) met the inclusion criteria. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by two independent reviewers. We evaluated the quality of the study according to the Newcastle-Ottawa Scale and only studies with a score of 6 and above were included in the final analyses. We pooled log-transformed odds ratios/risk ratios from the available adjusted models to estimate a summary relative risk (RR) and 95% confidence interval (CI) in a random-effects model. The primary outcome was overall CRC incidence. We also conducted secondary analyses according to sex and CRC subsites (proximal colon, distal colon and rectum). The outcome was measured by RRs with 95% CIs. RESULTS: The overall association of GD and/or CE with CRC was RR = 1.15 (1.08; 1.24), primarily driven by hospital-based case-control studies [RR = 1.61 (1.29; 2.01)], whereas a more modest association was found in population-based case-control and cohort studies [RR = 1.10 (1.02; 1.19)]. Most hospital-based case-control and necropsy studies reported estimates that were adjusted for age and sex only, leaving room for residual confounding; therefore we restricted to population-based case-control and cohort studies for our subsequent analyses. Similar associations were found for women [RR = 1.21 (1.05; 1.4) and men (RR = 1.24 (1.06; 1.44)]. When assessed by CRC subsites, GD and CE were primarily associated with higher risk of proximal colon cancer [RR = 1.16 (1.07; 1.26)] but not distal colon cancer [RR = 0.99 (0.96; 1.03)] or rectal cancer [RR = 0.94 (0.89; 1.00)]. CONCLUSIONS: Gallstones are associated with a modestly increased risk of colon cancer, primarily in the proximal colon.

Impact of the COVID-19 pandemic on knowledge, perceptions, and effects of telemedicine among the general population of Pakistan: A national survey.

Background: Telemedicine is the provision of healthcare services through information and communication technology with the potential to mobilize all facets of the health sector to prevent the spread of COVID-19, provide quality healthcare, protect patients, doctors, and the public from exposure to disease, and reduce the burden on the healthcare system. This study aims to identify knowledge, perceptions, willingness to use, and the impact of the COVID-19 pandemic on telemedicine awareness. Methods: A cross-sectional study was conducted from 27 May 2020 to 17 June 2020 using the convenient sampling technique in the general population of Pakistan. Data were collected by designing an online questionnaire consisting of demographic information, knowledge, attitude perceptions, barriers, utilization, and the impact of the COVID-19 pandemic on telemedicine. Results: Of the 602 participants included in the study, 70.1% had heard about telemedicine, 54.3% had a good understanding of the definition of "telemedicine," 81.4% had not used telemedicine in the past, 29.9% did not know that telemedicine was available before the COVID-19 pandemic, and 70.4% responded that the COVID-19 pandemic had changed their attitudes toward telemedicine. Gender (p = 0.017) and family income (p = 0.027) had a significant association with the perception of the benefits of telemedicine. Conclusion: The knowledge and usage of telemedicine are lacking due to inadequate awareness and technology. The need of the hour is to maximize the application of telemedicine to overcome the deficiencies of the healthcare system. Hence, it is essential to increase awareness through various means and develop an appropriate infrastructure to attain maximum benefits from telehealth services.

Pathophysiology of Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic ß-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.

Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights.

Statins are the gold-standard treatment for the prevention of primary and secondary cardiovascular disease, which is the leading cause of mortality worldwide. Despite the safety and relative tolerability of statins, observational studies, clinical trials and meta-analyses indicate an increased risk of developing new-onset type 2 diabetes mellitus (T2DM) after long-term statin treatment. It has been shown that statins can impair insulin sensitivity and secretion by pancreatic ß-cells and increase insulin resistance in peripheral tissues. The mechanisms involved in these processes include, among others, impaired Ca2+ signaling in pancreatic ß-cells, down-regulation of GLUT-4 in adipocytes and compromised insulin signaling. In addition, it has also been described that statins' impact on epigenetics may also contribute to statin-induced T2DM via differential expression of microRNAs. This review focuses on the evidence and mechanisms by which statin therapy is associated with the development of T2DM. This review describes the multifactorial combination of effects that most likely contributes to the diabetogenic effects of statins. Clinically, these findings should encourage clinicians to consider diabetes monitoring in patients receiving statin therapy in order to ensure early diagnosis and appropriate management.

Research Techniques Made Simple: CAR T-Cell Therapy.

Chimeric antigen receptor (CAR) and chimeric autoantibody receptor T-cell therapy hold great promise in the treatment of cancer and autoimmune disease, respectively. This powerful technique involves genetically engineering T lymphocytes to enable selective destruction of disease-causing cells. In the current approach, a patient's T cells are genetically engineered to express an antigen-specific antibody fragment fused to activating cytoplasmic T-cell signaling domains. After ex vivo activation and genetic modification of a patient's own T cells, the individually tailored CAR T cells are then infused into the patient for the selective destruction of cells bearing the targeted antigen. CAR T cells directed against the CD19 antigen expressed on B lymphoma cells have shown remarkable clinical efficacy in the treatment of refractory lymphoma, with two anti-CD19 CAR-T products recently gaining approval from the US Food and Drug Administration. For dermatological disease, preliminary studies have shown efficacy of CAR T cells in targeting melanoma cells and the pathogenic B cells in pemphigus vulgaris. Despite its great promise, current clinical CAR T-cell (or CAR-T) therapy carries a high risk of cytokine release syndrome, a potentially fatal systemic inflammatory response that can be manifest in cutaneous findings. For the dermatologist, the rapid clinical emergence of CAR-T therapy promises to treat and cure a variety of dermatological conditions, but it also requires an astute awareness of potential cutaneous complications in the increasing number of patients undergoing CAR-T therapy.

Natural variation in stochastic photoreceptor specification and color preference in Drosophila.

Each individual perceives the world in a unique way, but little is known about the genetic basis of variation in sensory perception. In the fly eye, the random mosaic of color-detecting R7 photoreceptor subtypes is determined by stochastic on/off expression of the transcription factor Spineless (Ss). In a genome-wide association study, we identified a naturally occurring insertion in a regulatory DNA element in ss that lowers the ratio of SsON to SsOFF cells. This change in photoreceptor fates shifts the innate color preference of flies from green to blue. The genetic variant increases the binding affinity for Klumpfuss (Klu), a zinc finger transcriptional repressor that regulates ss expression. Klu is expressed at intermediate levels to determine the normal ratio of SsON to SsOFF cells. Thus, binding site affinity and transcription factor levels are finely tuned to regulate stochastic expression, setting the ratio of alternative fates and ultimately determining color preference.