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.

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.
Animals ; Bone Density ; Bone Regeneration ; Cautery ; Mandible ; Rabbits ; Radiography ; Regeneration ; Transplants

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.

OBJECTIVES: To validate a critical-size mandibular bone defect model in miniature pigs. MATERIALS AND METHODS: Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks. RESULTS: In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. CONCLUSION: The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.
Autografts ; Bone Regeneration ; Bone Remodeling ; Dental Implants ; Hand ; Mandible ; Swine*

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Humans ; Kallikreins ; genetics ; Male ; Membrane Proteins ; genetics ; Prostatic Neoplasms ; diagnosis ; genetics ; Prostatic Secretory Proteins ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Risk Factors