Moving into a new era of periodontal genetic studies: relevance of large case–control samples using severe phenotypes for genome‐wide association studies

Studies to elucidate the role of genetics as a risk factor for periodontal disease have gone through various phases. In the majority of cases, the initial ‘hypothesis‐dependent’ candidate‐gene polymorphism studies did not report valid genetic risk loci. Following a large‐scale replication study, these initially positive results are believed to be caused by type 1 errors. However, susceptibility genes, such as CDKN2BAS (Cyclin Dependend KiNase 2B AntiSense RNA; alias ANRIL [ANtisense Rna In the Ink locus]), glycosyltransferase 6 domain containing 1 (GLT6D1) and cyclooxygenase 2 (COX2), have been reported as conclusive risk loci of periodontitis. The search for genetic risk factors accelerated with the advent of ‘hypothesis‐free’ genome‐wide association studies (GWAS). However, despite many different GWAS being performed for almost all human diseases, only three GWAS on periodontitis have been published – one reported genome‐wide association of GLT6D1 with aggressive periodontitis (a severe phenotype of periodontitis), whereas the remaining two, which were performed on patients with chronic periodontitis, were not able to find significant associations. This review discusses the problems faced and the lessons learned from the search for genetic risk variants of periodontitis. Current and future strategies for identifying genetic variance in periodontitis, and the importance of planning a well‐designed genetic study with large and sufficiently powered case–control samples of severe phenotypes, are also discussed.     

Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background/AimsPosthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model.MethodsA total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model.ResultsPHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (≤3.8 g/dL; OR 15.89, 95% CI 2.41 to 104.82, p=0.004), major hepatic resection (OR 4.16, 95% CI 1.40 to 12.38, p=0.014), higher albumin-bilirubin score (>–0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum α-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF.ConclusionsOur novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF.     

Impact of transcervical resection of endometrium on uterine and ovarian haemodynamics

This study prospectively evaluated the impact of transcervical resection of endometrium (TCRE) on uterine and ovarian haemodynamics. The study group comprised 35 women with abnormal (excessive) uterine bleeding who underwent TCRE. The patients were examined by transvaginal colour Doppler ultrasonography 1-4 days prior to operation, and then 1, 3, 6 and 12 months post-operatively, to measure resistance index (RI) and pulsatility index from uterine, arcuate, radial and ovarian arteries. Thirty-five patients were followed up for 1 year after TCRE. Thirty (85.7%) patients had adequately controlled menorrhagia as defined by the patients subjectively. Nine (25.7%) patients had amenorrhoea, 21 (60%) patients had hypomenorrhoea and five (14.3%) patients had lighter periods initially but the menorrhagia recurred within 1 year after the operation. However, patients who had relapse of menorrhagia at 1 year after TCRE had a lower RI at all levels of uterine arteries compared with those who had persistent improvement. The data suggest that patients who had TCRE per se did not have associated altered uterine and ovarian haemodynamics; however, compared with those who had persistent improvement, those who had relapse in symptoms had an associated lower RI (P < or = 0.01) after TCRE at all levels of uterine arteries.     

Clinical and economic outcomes of a multidisciplinary team approach in a lower extremity amputation prevention programme for diabetic foot ulcer care in an Asian population: A case‐control study

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case‐control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow‐up (33% vs 76%, P < .001), decrease in 1‐year minor amputation rate (14% vs 3%, P = .007), and decrease in 1‐year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.     

Gracilaria changii(Rhodophyta) alleviates bisphenol A-induced adverse reproductive abnormalities in mice

Objective: To evaluate the potential of Gracilaria changii extract in ameliorating the potential adverse effects of bisphenol A. Methods: The antioxidant capacity of Gracilaria changii extracted using different solvents(methanol, ethanol, and aqueous) was studied. The mice were administered by oral gavage with bisphenol A(60 mg/kg body weight) for 6 weeks with or without Gracilaria changii aqueous extract. Thereafter, the mice were either euthanized for histology and immunohistochemistry studies or mated to evaluate the pregnancy rate. Results: Gracilaria changii aqueous extract showed the highest antioxidant properties compared with extract using methanol and ethanol. The aqueous extract of Gracilaria changii improved the uterus index and uterine lipid peroxidation after bisphenol A exposure, although the uterine expressions of estrogen receptors and complement C3 were not improved. Histological evaluation of the uterus during the estrus stage has revealed that the extract could mitigate bisphenol A-induced adverse effects in the uterus as there was a lower percentage of mice showing abnormalities like decreased eosin staining in the myometrium, and decrease in the number of eosinophil and endometrial glands in the endometrium. Besides, Gracilaria changii aqueous extract improved the pregnancy rate of mice administered with bisphenol A. Conclusions: Gracilaria changii extract protects against bisphenol A-induced female reproductive abnormalities in mice which may be mediated via modulation of eosinophil migration, endometrial gland formation, and protein expressions associated with prostaglandins in the myometrium.     

Workload of Healthcare Workers During the COVID-19 Outbreak in Korea: A Nationwide Survey

BackgroundAs the coronavirus disease 2019 (COVID-19) pandemic is ongoing, heavy workload of healthcare workers (HCWs) is a concern. This study investigated the workload of HCWs responding to the COVID-19 outbreak in South Korea.MethodsA nationwide cross-sectional survey was conducted from September 16 to October 15, 2020, involving 16 healthcare facilities (4 public medical centers, 12 tertiary-care hospitals) that provide treatment for COVID-19 patients.ResultsPublic medical centers provided the majority (69.4%) of total hospital beds for COVID-19 patients (n = 611), on the other hand, tertiary care hospitals provided the majority (78.9%) of critical care beds (n = 57). The number of beds per doctor (median [IQR]) in public medical centers was higher than in tertiary care hospitals (20.2 [13.0, 29.4] versus 3.0 [1.3, 6.6], P = 0.006). Infectious Diseases physicians are mostly (80%) involved among attending physicians. The number of nurses per patient (median [interquartile range, IQR]) in tertiary-care hospitals was higher than in public medical centers (4.6 [3.4–5] vs. 1.1 [0.8–2.1], P = 0.089). The median number of nurses per patient for COVID-19 patients was higher than the highest national standard in South Korea (3.8 vs. 2 for critical care). All participating healthcare facilities were also operating screening centers, for which a median of 2 doctors, 5 nurses, and 2 administrating staff were necessary.ConclusionAs the severity of COVID-19 patients increases, the number of HCWs required increases. Because the workload of HCWs responding to the COVID-19 outbreak is much greater than other situations, a workforce management plan regarding this perspective is required to prevent burnout of HCWs.     

Sex differences in rapid nonclassical action of 17β‐oestradiol on intracellular signalling and oestrogen receptor α expression in basal forebrain cholinergic neurones in mouse

Rapid nonclassical effects of 17β‐oestradiol (E₂) on intracellular signalling have been identified in the basal forebrain, although the extent to which these actions may be different in males and females is unknown. Previous work has shown that E₂ rapidly phosphorylates cAMP responsive element binding protein (CREB) via ΕRα in female cholinergic neurones. Using this indicator, the present study examined whether nonclassical actions of E₂ occur in a sexually dimorphic manner within basal forebrain cholinergic neurones in mice. In addition, we investigated the expression and intracellular distribution of oestrogen receptor (ΕR)α in cholinergic neurones in female and male mice. Animals were gonadectomised and treated 2 weeks later with E₂. The number of CREB‐expressing cholinergic neurones was not altered in any of the brain regions after E₂ treatment in both males and females. However, E₂ treatment rapidly (< 15 minutes) increased (P < 0.05) the number of cholinergic neurones expressing phosphorylated CREB (pCREB) in the substantia innominata and medial septum but not in the striatum in female mice. By contrast, E₂ did not change pCREB expression in cholinergic neurones in male mice at any time point (15 minutes, 1 hour, 4 hours), irrespective of the neuroanatomical location. We also observed that, in females, more cholinergic neurones expressed nuclear ΕRα in all regions, whereas males showed more cholinergic neurones with cytoplasmic or both nuclear and cytoplasmic expression of ΕRα. Taken together, these results demonstrate a marked sex difference in the E₂‐induced nonclassical effect and intracellular distribution of ΕRα in basal forebrain cholinergic neurones in vivo.     

Two-year follow-up of the quantitative angiographic and volumetric intravascular ultrasound analysis after nonpolymeric paclitaxel-eluting stent implantation: late "catch-up" phenomenon from ASPECT Study.

OBJECTIVES: This study used serial angiographic and intravascular ultrasound (IVUS) analysis to evaluate the long-term efficacy of a nonpolymeric, paclitaxel-eluting stent coating on intimal hyperplasia (IH) 2 years after implantation. BACKGROUND: Long-term efficacy of patients treated with nonpolymeric paclitaxel-eluting stents beyond 1 year has not been well determined. METHODS: Patients were randomized to placebo or 1 of 2 doses of paclitaxel (low dose, 1.28 microg/mm2; high dose, 3.10 microg/mm2). Complete after-procedure, 6-month, and 2-year angiographic and IVUS data were available in 53 patients (17, 17, and 19 patients, respectively). RESULTS: Baseline characteristics were similar among the 3 groups. Although 6-month minimal luminal diameter (MLD) was significantly smaller in placebo compared with paclitaxel-eluting stent patients (1.9 +/- 0.6 mm in placebo, 2.5 +/- 0.6 mm in low-dose, and 2.6 +/- 0.5 mm in high-dose patients, p = 0.004), the MLDs at 2 years were similar (2.3 +/- 0.6 mm, 2.3 +/- 0.7 mm, and 2.0 +/- 0.8 mm, respectively, p = 0.4). Despite a stepwise reduction in IH accumulation at 6 months (23 +/- 18 mm3 in placebo, 14 +/- 11 mm3 in low-dose, and 10 +/- 12 mm3 in high-dose, p = 0.017), the increase of IH volume from 6 months to 2 years was significantly greater in the high-dose patients (13 +/- 14 mm3 in high-dose vs. 4 +/- 7 mm3 in low-dose patients, p = 0.074; and vs. 1 +/- 13 mm3 in placebo, p = 0.019). Late target lesion revascularization (beyond 1 year) was performed in 2 high-dose patients. CONCLUSIONS: Despite the suppression of IH after non-polymeric paclitaxel-eluting stents compared with bare-metal stents at 6 months, a "late catch-up" IH growth was found in the high-dose patients at 2-year follow-up.