Exposure to Light at Night and Risk of Cancer: A Systematic Review, Meta-Analysis, and Data Synthesis.

BACKGROUND: Emerging interest surrounds the role of environmental factors, notably exposure to light at night (LAN), as a potential cause of cancer. The aim of this study was to conduct a systematic review and, if possible, meta-analysis of observational studies on LAN and cancer risk of multiple types. METHODS: A systematic literature search in PubMed, Web of Science, and Embase, spanning from inception to May 2023, was conducted. Studies focusing on the association between LAN exposure and cancer risk in adult populations were included. We used random effects models to calculate pooled risk estimates (RR) and 95% confidence intervals (CI). We assessed study quality using the Risk of Bias in Non-randomized Studies of Interventions. RESULTS: Among 8492 initially identified studies, 26 met the inclusion criteria (13 were case-control and 13 were cohort studies). These studies were published from 2001 to 2023 and assessed diverse cancer types in North America, Asia, Europe, and Australia. Except for breast cancer, there was a paucity of site-specific cancer studies. In the meta-analysis of 19 breast cancer studies, higher exposure to indoor (summary RR, 1.08; 95% CI 1.01-1.15) and outdoor (summary RR, 1.10; 95% CI, 1.04-1.15) LAN were associated with increased risk. After excluding one low-quality study, the results were unchanged. CONCLUSIONS: We found a positive association between LAN exposure and breast cancer risk in women. However, data are lacking for other cancer types, and further studies are required to better understand the role of LAN on cancer.

Crohn's Disease-Associated Granulomatous Pancreatitis With Exocrine Pancreatic Insufficiency.

Extraintestinal manifestations of inflammatory bowel disease occur commonly and can lead to considerable morbidity. Pancreatic manifestations of inflammatory bowel disease have been reported to be more common in Crohn's disease (CD) than ulcerative colitis. We report a case of granulomatous inflammation in the body of the pancreas with exocrine pancreatic insufficiency, which prompted a diagnosis switch from ulcerative colitis to CD. This is of interest to readers to remind them that pancreatic manifestations can occur and are more common in CD.

Trends and Variations in Pancreatic Cancer Mortality Among US Metro and Nonmetro Adults, 1999-2020.

BACKGROUND: Pancreatic cancer is the third leading cause of cancer deaths in the United States. Despite decreasing cancer mortality rates as a whole, pancreatic cancer death rates in the United States remain steady and demonstrate racial/ethnic disparities. Divergent cancer mortality trends have also been observed between metro and nonmetro populations. We therefore aimed to compare metro and nonmetro trends in pancreatic cancer mortality rates in the United States from 1999 to 2020 and investigate potential sex and racial/ethnic differences. METHODS: We analyzed National Center for Health Statistics data for all pancreatic cancer deaths among individuals aged 25 years or older in the United States. We estimated the average annual percent change (AAPC) in age-standardized pancreatic cancer mortality rates in metro versus nonmetro areas by sex and race/ethnicity. RESULTS: Of the total 810,425 pancreatic cancer-related deaths identified from 1999 to 2020, 668,547 occurred in metro areas and 141,878 in nonmetro areas. Non-Hispanic Black individuals had the highest rates of pancreatic cancer mortality regardless of metropolitan status. In both metro and nonmetro areas, pancreatic cancer mortality rates among non-Hispanic White individuals increased over the study period (AAPC: metro, males, 0.32%; females, 0.27%; nonmetro, males, 0.77%; females, 0.62%). Non-Hispanic Black individuals in metro areas had a decrease in pancreatic cancer mortality (AAPC: males, -0.25%; females, -0.29%), but rates among non-Hispanic Black women in nonmetro areas increased (AAPC, 0.49%). CONCLUSIONS: There are variations not only in pancreatic cancer mortality by metro and nonmetro status but also by sex and race/ethnicity within these areas. Individuals who live in nonmetro areas have higher pancreatic cancer mortality rates and increasing death rates compared with their metro counterparts. These findings highlight the need for targeted cancer prevention strategies that are specific to metro or nonmetro populations.

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

SOX9 is an essential transcriptional regulator of cartilage development and homeostasis. In humans, dysregulation of SOX9 is associated with a wide spectrum of skeletal disorders, including campomelic and acampomelic dysplasia, and scoliosis. The mechanism of how SOX9 variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four novel pathogenic variants of SOX9 identified in a large cohort of patients with congenital vertebral malformations. Three of these heterozygous variants are in the HMG and DIM domains, and for the first time, we report a pathogenic variant within the transactivation middle (TAM) domain of SOX9 . Probands with these variants exhibit variable skeletal dysplasia, ranging from isolated vertebral malformation to acampomelic dysplasia. We also generated a Sox9 hypomorphic mutant mouse model bearing a microdeletion within the TAM domain ( Sox9 Asp272del ). We demonstrated that disturbance of the TAM domain with missense mutation or microdeletion results in reduced protein stability but does not affect the transcriptional activity of SOX9. Homozygous Sox9 Asp272del mice exhibited axial skeletal dysplasia including kinked tails, ribcage anomalies, and scoliosis, recapitulating phenotypes observed in human, while heterozygous mutants display a milder phenotype. Analysis of primary chondrocytes and the intervertebral discs in Sox9 Asp272del mutant mice revealed dysregulation of a panel of genes with major contributions of the extracellular matrix, angiogenesis, and ossification-related processes. In summary, our work identified the first pathologic variant of SOX9 within the TAM domain and demonstrated that this variant is associated with reduced SOX9 protein stability. Our finding suggests that reduced SOX9 stability caused by variants in the TAM domain may be responsible for the milder forms of axial skeleton dysplasia in humans.

Understanding parental knowledge, attitudes and self-efficacy in professional help-seeking for child anxiety.

BACKGROUND: Child anxiety disorders are highly prevalent yet undertreated. As parents are often 'gatekeepers' to children receiving treatment and support, this study aimed to investigate modifiable parental factors affecting professional help-seeking for their children from general practitioners (GPs), psychologists, and paediatricians. METHODS: In this study, 257 Australian parents of children aged 5-12 years with elevated anxiety symptoms completed a cross-sectional online survey. The survey assessed help-seeking from a GP, psychologist, and paediatrician (General Help Seeking Questionnaire), as well as anxiety knowledge (Anxiety Literacy Scale), help-seeking attitudes (Attitudes Toward Seeking Professional Psychological Help), personal stigma (Generalised Anxiety Stigma Scale) and self-efficacy (Self-Efficacy in Seeking Mental Health Care). RESULTS: 66.9% of participants had sought help from a GP, 61.1% from a psychologist, and 33.9% from a paediatrician. Help-seeking from a GP or psychologist was associated with lower personal stigma (p = .02 and p = .03 respectively). Participants who sought help from a psychologist also had more positive attitudes toward seeking professional support (p = .01). Conversely, knowledge of anxiety disorders and self-efficacy were not associated with help-seeking from any source. LIMITATIONS: Limitations of the study include the representativeness of our sample (female gender, higher education level); unexplained variance potentially accounted for by other factors (e.g., structural barriers); lack of prior validation of measures in a parent sample. CONCLUSIONS: This research will inform the development of public health policy and psychoeducation interventions for parents, to reduce personal stigma and increase positive attitudes towards professional help-seeking, in turn improving help-seeking for child anxiety.