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.     

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.     

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.     

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.     

清开灵与利巴韦林治疗小儿呼吸道合胞病毒肺炎的比较：单盲、随机、平行对照试验

目的:比较清开灵与利巴韦林对呼吸道合胞病毒肺炎患儿治疗效果的差异。方法:选择2005-02/2006-04在北京儿童医院分中心治疗的小儿呼吸道合胞病毒肺炎97例,患儿法定监护人知情同意。采用单盲、随机、平行对照试验的原则,按区组随机化方法分为2组,清开灵注射液组49例,利巴韦林组48例。①清开灵注射液组:清开灵注射液静脉滴注加口服中成药。②利巴韦林组:利巴韦林注射液静脉滴注加口服复方愈创木酚磺酸钾口服液。两组疗程均为10d,比较两组患儿的疗效。结果:清开灵注射液组脱落3例,利巴韦林组脱落1例,进入结果分析清开灵注射液组46例,利巴韦林组47例。①清开灵注射液组发热患儿体温恢复正常时间比利巴韦林组短[(2.72±1.86)d,(6.29±2.41)d(P<0.01)]。②清开灵注射液组患儿咳嗽、痰壅、气促症状积分改善方面优于利巴韦林组(P<0.05～0.01)。③清开灵注射液组的呼吸道合胞病毒转阴时间明显优于利巴韦林组。④咳嗽、痰壅、病毒转阴时间、气促均进入Logistic模型,其中前两个症状的回归系数绝对值较大。结论:清开灵注射液治疗小儿呼吸道合胞病毒肺炎在退热、止咳平喘、呼吸道合胞病毒转阴时间等方面均具有明显优势,咳嗽、痰壅这两个症状更能反映清开灵注射液的疗效优于利巴韦林。     

Managing complications of radiation therapy in head and neck cancer patients: Part II. Management of radiation-induced caries

Head and neck cancer is becoming a more recognizable pathology to the general population and dentists. The modes of treatment include surgery and/or radiation therapy. Where possible, pretreatment dental assessment shall be provided for these patients before they undergo radiation therapy. There are occasions, however, whereby head and neck cancer patients are not prepared optimally for radiation therapy. Because of this, they succumb to complicated oral complications after radiation therapy. The management of xerostomia has been reviewed in Part I of this series. In this article, the management of dental caries, a sequalae of xerostomia following radiation therapy is reviewed.