Analysis of Geographic and Environmental Factors and Their Association with Cutaneous Melanoma Incidence in Canada.

BACKGROUND: Over 90% of skin cancers including cutaneous melanoma (CM) are related directly to sun exposure. Despite extensive knowledge on ultraviolet radiation's (UVR) detrimental impact, many still fail to implement sun protection/sun avoidance. Human behavior, attitudes, and cultural norms of individuals and communities heavily depend on the surrounding climate/environment. In many instances, the climate shapes the culture/norms of the society. Canada has vast geographic/environmental differences. METHODS: In the current ecological study, we sought to examine the relationship between various geographic and environmental factors and the distribution of CM incidence by Forward Sortation Area (FSA) postal code across Canada. CM incidence data were extracted from the Canadian Cancer Registry, while environmental data were extracted from the Canadian Urban Environmental Health Research Consortium (greenspace, as measured by the normalized difference vegetation index; annual highest temperature; absolute number and average length of yearly heat events; annual total precipitation [rain and snow]; absolute number and average length of events with precipitation [rain and snow]; and summer UVR index). The above geographic/environmental data by FSA were correlated with the respective CM incidence employing negative binomial regression model. RESULTS: Our analysis highlights that increases in annual average temperature, summer UVR, and greenspace were associated with higher expected incidence of CM cases, while higher number of annual heat events together with highest annual temperature and higher average number of annual rain events were associated with a decrease in CM incidence rate. This study also highlights regional variation in environmental CM risk factors in Canada. CONCLUSIONS: This national population-based study presents clinically relevant conclusions on weather/geographic variations associated with CM incidence in Canada and will help refine targeted CM prevention campaigns by understanding unique weather/geographic variations in high-risk regions.

Tools used to assay genomic instability in cancers and cancer meiomitosis.

Genomic instability is a defining characteristic of cancer and the analysis of DNA damage at the chromosome level is a crucial part of the study of carcinogenesis and genotoxicity. Chromosomal instability (CIN), the most common level of genomic instability in cancers, is defined as the rate of loss or gain of chromosomes through successive divisions. As such, DNA in cancer cells is highly unstable. However, the underlying mechanisms remain elusive. There is a debate as to whether instability succeeds transformation, or if it is a by-product of cancer, and therefore, studying potential molecular and cellular contributors of genomic instability is of high importance. Recent work has suggested an important role for ectopic expression of meiosis genes in driving genomic instability via a process called meiomitosis. Improving understanding of these mechanisms can contribute to the development of targeted therapies that exploit DNA damage and repair mechanisms. Here, we discuss a workflow of novel and established techniques used to assess chromosomal instability as well as the nature of genomic instability such as double strand breaks, micronuclei, and chromatin bridges. For each technique, we discuss their advantages and limitations in a lab setting. Lastly, we provide detailed protocols for the discussed techniques.

Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD). Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD. Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021. Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib. Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time. Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.

Efficacy and Effectiveness of the PCV-10 and PCV-13 Vaccines Against Invasive Pneumococcal Disease.

CONTEXT: Pneumococcal conjugate vaccines (PCVs) (pneumococcal 13-valent conjugate vaccine [PCV-13] and pneumococcal 10-valent conjugate vaccine [PCV-10]) are available for prevention of pneumococcal infections in children. OBJECTIVE: To determine the vaccine effectiveness (VE) of PCV-13 and PCV-10 in preventing invasive pneumococcal disease (IPD) and acute otitis media (AOM) in children <5 years. DATA SOURCES: Systematic searches of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Cochrane. STUDY SELECTION: Eligible studies examined the direct effectiveness and/or efficacy of PCV-10 and PCV-13 in reducing the incidence of disease in healthy children <5 years. DATA EXTRACTION: Two reviewers independently conducted data extraction and methodologic quality assessment. RESULTS: Significant effectiveness against vaccine-type IPD in children ≤5 years was reported for ≥1 dose of PCV-13 in the 3 + 1 (86%-96%) and 2 + 1 schedule (67.2%-86%) and for PCV-10 for the 3 + 1 (72.8%-100%) and 2 + 1 schedules (92%-97%). In children <12 months of age, PCV-13 VE against serotype 19A post-primary series was significant for the 3 + 1 but not the 2 + 1 schedule. PCV-10 crossprotection against 19A was significant in children ≤5 years with ≥1 dose (82.2% and 71%). Neither PCVs were found effective against serotype 3. PCV-13 was effective against AOM (86%; 95% confidence interval [CI]: 61 to 94). PCV-10 was effective against clinically defined (26.9%; 95% CI: 5.9 to 43.3) and bacteriologically confirmed AOM (43.3%; 95% CI: 1.7 to 67.3). LIMITATIONS: Because of the large heterogeneity in studies, a meta-analysis for pooled estimates was not done. CONCLUSIONS: Both PCVs afford protection against pneumococcal infections, with PCV-10 protecting against 19A IPD, but this VE has not been verified in the youngest age groups.