Background::The prevalence of type 2 diabetes has been growing among younger and middle-aged adults in the United States. A portion of this increase for this age group may be attributable to shared type 2 diabetes risks with family members. How family history of type 2 diabetes history is associated with type 2 diabetes risk among younger and middle-aged adults is not well understood.Methods::This population-based retrospective cohort study uses administrative, genealogical, and electronic medical records from the Utah Population Database. The study population comprises offspring born between 1970 and 1990 and living in the four urban Utah counties in the United States between 1990 and 2015. The sample comprises 360,907 individuals without a type 2 diabetes diagnosis and 14,817 with a diagnosis. Using multivariate logistic regressions, we estimate the relative risk (RR) of type 2 diabetes associated with the number of affected first- (FDRs), second- (SDRs), and third-degree (first cousin) relatives for the full sample and for Hispanic-specific and sex-specific subsets.Results::Individuals with 2+ FDRs with type 2 diabetes have a significant risk of type 2 diabetes in relation to those with no affected FDRs (RR = 3.31 [3.16, 3.48]). Individuals with 2+ versus no SDRs with type 2 diabetes have significant but lower risks (RR = 1.32 [1.25, 1.39]). Those with 2+ versus no affected first cousins have a similarly low risk (RR= 1.28 [1.21, 1.35]). Larger RRs are experienced by males (2+ vs. 0 FDRs, RR = 3.55) than females (2+ vs. 0 FDRs, RR = 3.18) ( p < 0.05 for the interaction). These familial associations are partly mediated by the individual's own obesity. Conclusions::The risks of type 2 diabetes are significantly associated with having affected first-, second-, and third-degree relatives, especially for men. One of the forces contributing to the rising patterns of type 2 diabetes among young and middle-aged adults is their connection to affected, often older, kin.

Background::The prevalence of type 2 diabetes has been growing among younger and middle-aged adults in the United States. A portion of this increase for this age group may be attributable to shared type 2 diabetes risks with family members. How family history of type 2 diabetes history is associated with type 2 diabetes risk among younger and middle-aged adults is not well understood.Methods::This population-based retrospective cohort study uses administrative, genealogical, and electronic medical records from the Utah Population Database. The study population comprises offspring born between 1970 and 1990 and living in the four urban Utah counties in the United States between 1990 and 2015. The sample comprises 360,907 individuals without a type 2 diabetes diagnosis and 14,817 with a diagnosis. Using multivariate logistic regressions, we estimate the relative risk (RR) of type 2 diabetes associated with the number of affected first- (FDRs), second- (SDRs), and third-degree (first cousin) relatives for the full sample and for Hispanic-specific and sex-specific subsets.Results::Individuals with 2+ FDRs with type 2 diabetes have a significant risk of type 2 diabetes in relation to those with no affected FDRs (RR = 3.31 [3.16, 3.48]). Individuals with 2+ versus no SDRs with type 2 diabetes have significant but lower risks (RR = 1.32 [1.25, 1.39]). Those with 2+ versus no affected first cousins have a similarly low risk (RR= 1.28 [1.21, 1.35]). Larger RRs are experienced by males (2+ vs. 0 FDRs, RR = 3.55) than females (2+ vs. 0 FDRs, RR = 3.18) ( p < 0.05 for the interaction). These familial associations are partly mediated by the individual's own obesity. Conclusions::The risks of type 2 diabetes are significantly associated with having affected first-, second-, and third-degree relatives, especially for men. One of the forces contributing to the rising patterns of type 2 diabetes among young and middle-aged adults is their connection to affected, often older, kin.

Purpose: The estimation of the risk posed by malignant polyps for residual or lymphatic disease plays a central role. This study investigated colorectal surgeons’ assessment of these risks associated with malignant polyps. Methods: A cross-sectional questionnaire was electronically administered to colorectal surgeons in Australia and New Zealand in October 2022. The questionnaire contained 17 questions on demographics, when surgeons consider colorectal resection appropriate, and the risk assessment for 5 hypothetical malignant polyps. Results: The mean risk of residual or lymphatic disease that would prompt surgeons to recommend colonic resection was 5%. However, this increased to a mean risk of 10% if the malignant polyp was located in the rectum, and the only resection option was abdominoperineal resection with end-colostomy. There was high concordance between the estimated risk of residual or lymphatic disease by colorectal surgeons and the Association of Coloproctology of Great Britain and Ireland (ACPGBI) guidelines for the 5 hypothetical malignant polyps, with the ACPGBI estimated risk lying within the 95% confidence interval for 4 of the 5 malignant polyps. Nonetheless, 96.6% of surgeons felt that an online risk calculator would improve clinical practice. Conclusion Colorectal surgeons in Australia and New Zealand accurately estimated the risk posed by malignant polyps. An online risk calculator may assist in better conveying risk to patients.

Objective: The real-world INFORM study analyzed sociodemographics, treatment patterns and clinical outcomes for patients with newly diagnosed advanced epithelial ovarian cancer (EOC) in Australia, South Korea (S.Korea) and Taiwan preceding incorporation of poly(ADP-ribose) polymerase inhibitors into clinical practice. Methods: Retrospective data from patients diagnosed with EOC (high-grade serous EOC for Taiwan) between January 2014 and December 2018 with ≥12 months follow-up from diagnosis were analyzed descriptively. Survival was evaluated by Kaplan-Meier with two-sided 95% confidence interval (CI). Results: Of the 987 patients (Australia, 223; S.Korea, 513; Taiwan, 251), 98% received platinum-based chemotherapy (CT). In S.Korea and Taiwan 76.0% and 78.9% respectively underwent primary cytoreductive surgery; in Australia, 56.5% had interval debulking surgery. Bevacizumab was included in primary/maintenance therapy for 22.4%, 14.6% and 6.8% of patients in Australia, S.Korea and Taiwan, respectively. Patients receiving bevacizumab were high-risk (reimbursement policy) and achieved similar real-world progression-free survival (PFS) compared with CT only. Overall, the median real-world PFS (months; 95% CI) was similar across Australia (16.0 [14.63–18.08]), S.Korea (17.7 [16.18–19.27]) and Taiwan (19.1 [17.56–22.29]). Conclusion This study reveals poor prognosis despite differences in demographics and treatment patterns for patients with EOC across Asia-Pacific suggesting the need for biomarker-driven novel therapies to improve outcomes.

Purpose: Medical schools have faced various challenges in preparing their clinical students for the frontlines of a pandemic. This study investigated medical students’ satisfaction with their institutions during the coronavirus disease 2019 (COVID-19) pandemic with the intention of guiding educators in future public health crises. Methods: In this cross-sectional study surveying students in clinical rotations, the primary outcome was overall satisfaction regarding medical schools’ responses to the pandemic, and the four secondary outcomes were school communication, exposure to COVID-19, availability of personal protective equipment, and access to COVID-19 testing. Results: The survey was distributed to ten medical schools, of which 430 students responded for a response rate of 13.0%. While most students were satisfied (61.9%, n=266) with their schools’ response, more than one in five (21.9%, n=94) were dissatisfied. Among the four secondary outcomes, communication with students was most predictive of overall satisfaction. Conclusion In future crises, schools can best improve student satisfaction by prioritizing timely communication.

OBJECTIVES: Small animal maxillofacial models, such as non-segmental critical size defects (CSDs) in the rabbit mandible, need to be standardized for use as preclinical models of bone regeneration to mimic clinical conditions such as maxillofacial trauma. The objective of this study is the establishment of a mechanically competent CSD model in the rabbit mandible to allow standardized evaluation of bone regeneration therapies. MATERIALS AND METHODS: Three sizes of bony defect were generated in the mandibular body of rabbit hemi-mandibles: 12 mm×5 mm, 12 mm×8 mm, and 15 mm×10 mm. The hemi-mandibles were tested to failure in 3-point flexure. The 12 mm×5 mm defect was then chosen for the defect size created in the mandibles of 26 rabbits with or without cautery of the defect margins and bone regeneration was assessed after 6 and 12 weeks. Regenerated bone density and volume were evaluated using radiography, micro-computed tomography, and histology. RESULTS: Flexural strength of the 12 mm×5 mm defect was similar to its contralateral; whereas the 12 mm×8 mm and 15 mm×10 mm groups carried significantly less load than their respective contralaterals (P<0.05). This demonstrated that the 12 mm×5 mm defect did not significantly compromise mandibular mechanical integrity. Significantly less (P<0.05) bone was regenerated at 6 weeks in cauterized defect margins compared to controls without cautery. After 12 weeks, the bone volume of the group with cautery increased to that of the control without cautery after 6 weeks. CONCLUSION: An empty defect size of 12 mm×5 mm in the rabbit mandibular model maintains sufficient mechanical stability to not require additional stabilization. However, this defect size allows for bone regeneration across the defect. Cautery of the defect only delays regeneration by 6 weeks suggesting that the performance of bone graft materials in mandibular defects of this size should be considered with caution.
Animals ; Bone Density ; Bone Regeneration ; Cautery ; Mandible ; Rabbits ; Radiography ; Regeneration ; Transplants

No abstract available.
Carotid Stenosis ; Cerebral Hemorrhage ; Endarterectomy ; Humans ; Stents

OBJECTIVES: Small animal maxillofacial models, such as non-segmental critical size defects (CSDs) in the rabbit mandible, need to be standardized for use as preclinical models of bone regeneration to mimic clinical conditions such as maxillofacial trauma. The objective of this study is the establishment of a mechanically competent CSD model in the rabbit mandible to allow standardized evaluation of bone regeneration therapies. MATERIALS AND METHODS: Three sizes of bony defect were generated in the mandibular body of rabbit hemi-mandibles: 12 mm×5 mm, 12 mm×8 mm, and 15 mm×10 mm. The hemi-mandibles were tested to failure in 3-point flexure. The 12 mm×5 mm defect was then chosen for the defect size created in the mandibles of 26 rabbits with or without cautery of the defect margins and bone regeneration was assessed after 6 and 12 weeks. Regenerated bone density and volume were evaluated using radiography, micro-computed tomography, and histology. RESULTS: Flexural strength of the 12 mm×5 mm defect was similar to its contralateral; whereas the 12 mm×8 mm and 15 mm×10 mm groups carried significantly less load than their respective contralaterals (P<0.05). This demonstrated that the 12 mm×5 mm defect did not significantly compromise mandibular mechanical integrity. Significantly less (P<0.05) bone was regenerated at 6 weeks in cauterized defect margins compared to controls without cautery. After 12 weeks, the bone volume of the group with cautery increased to that of the control without cautery after 6 weeks. CONCLUSION An empty defect size of 12 mm×5 mm in the rabbit mandibular model maintains sufficient mechanical stability to not require additional stabilization. However, this defect size allows for bone regeneration across the defect. Cautery of the defect only delays regeneration by 6 weeks suggesting that the performance of bone graft materials in mandibular defects of this size should be considered with caution.

BACKGROUND: Transforming growth factor beta (TGF-β) signaling has been shown to control a large number of critical cellular actions such as cell death, differentiation, and development and has been implicated as a major regulator of placental function. SM10 cells are a mouse placental progenitor cell line, which has been previously shown to differentiate into nutrient transporting, labyrinthine-like cells upon treatment with TGF-β. However, the signal transduction pathway activated by TGF-β to induce SM10 progenitor differentiation has yet to be fully investigated. MATERIALS AND METHODS: In this study the SM10 labyrinthine progenitor cell line was used to investigate TGF-β induced differentiation. Activation of the TGF-β pathway and the ability of TGF-β to induce differentiation were investigated by light microscopy, luciferase assays, and Western blot analysis. RESULTS AND CONCLUSIONS: In this report, we show that three isoforms of TGF-β have the ability to terminally differentiate SM10 cells, whereas other predominant members of the TGF-β superfamily, Nodal and Activin A, do not. Additionally, we have determined that TGF-β induced Smad2 phosphorylation can be mediated via the ALK-5 receptor with subsequent transactivation of the Activin response element. Our studies identify an important regulatory signaling pathway in SM10 progenitor cells that is involved in labyrinthine trophoblast differentiation.
Activins ; Animals ; Blotting, Western ; Cell Death ; Luciferases ; Mice ; Microscopy ; Phosphorylation ; Placenta ; Protein Isoforms ; Response Elements ; Signal Transduction ; Stem Cells ; Transcriptional Activation ; Transforming Growth Factor beta ; Trophoblasts

Cryopreserved human hepatocytes were used to investigate the role of arylamine-acetyltransferase 2 (NAT2; EC 2.3.1.5) polymorphism on the-acetylation of isoniazid (INH).genotype was determined by Taqman allelic discrimination assay and INH-acetylation was measured by high performance liquid chromatography. INH-acetylation ratesexhibited a robust and highly significant (<0.005) NAT2 phenotype-dependent metabolism.-acetylation rateswere INH concentration- and time-dependent. Following incubation for 24 h with 12.5 or 100 µmol/L INH, acetyl-INH concentrations varied significantly (= 0.0023 and= 0.0002) across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. The clear association betweengenotype and phenotype supports use ofgenotype to guide INH dosing strategies in the treatment and prevention of tuberculosis.