An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Tissue bridges predict recovery after traumatic and ischemic thoracic spinal cord injury

OBJECTIVE To investigate the spatiotemporal evolution and predictive properties of intramedullary damage and midsagittal tissue bridges at the epicenter of a thoracic spinal cord injury (SCI) using MRI. METHODS We retrospectively assessed midsagittal T2-weighted scans from 25 patients with thoracic SCI (14 traumatic, 11 ischemic) at 1 month post-SCI. In 12 patients with SCI, linear mixed-effects models on serial MRI explored temporal trajectories of quantifiable lesion markers (area, length, and width) and tissue bridges. Using partial correlation analysis, we assessed associations between structural lesion characteristics at 1 month post-SCI and recovery at 1 year postinjury, adjusting for baseline clinical status, age, and sex. RESULTS Lesion area decreased by 5.68 mm ( = 0.005), lesion length by 2.14 mm ( = 0.004), and lesion width by 0.13 mm ( = 0.004) per month. Width of tissue bridges increased by 0.06 mm ( = 0.019) per month, being similar in traumatic and ischemic SCI ( = 0.576). Smaller lesion area, length, width, and wider tissue bridges at 1 month post-SCI predicted better recovery at 1-year follow-up. CONCLUSIONS Over time, the immediate area of cord damage shrunk while the cystic cavity became demarcated. Adjacent to the cyst, midsagittal tissue bridges became visible. The width of tissue bridges at 1 month post-SCI predicted recovery at 1 year follow-up. Measures of lesion area and tissue bridges early after traumatic and ischemic thoracic SCI therefore allow characterizing the evolution of focal cord damage and are predictive of recovery in thoracic SCI. Thus, lesion extent and tissue bridges hold potential to improve diagnosis and patient stratification in interventional trials

Width and neurophysiologic properties of tissue bridges predict recovery after cervical injury

OBJECTIVE To assess whether preserved dorsal and ventral midsagittal tissue bridges after traumatic cervical spinal cord injury (SCI) encode tract-specific electrophysiologic properties and are predictive of appropriate recovery. METHODS In this longitudinal study, we retrospectively assessed MRI scans at 1 month after SCI that provided data on width and location (dorsal vs ventral) of midsagittal tissue bridges in 28 tetraplegic patients. Regression analysis assessed associations between midsagittal tissue bridges and motor- and sensory-specific electrophysiologic recordings and appropriate outcome measures at 12 months after SCI. RESULTS Greater width of dorsal midsagittal tissue bridges at 1 month after SCI identified patients who were classified as being sensory incomplete at 12 months after SCI ( = 0.025), had shorter sensory evoked potential (SEP) latencies ( = -0.57, = 0.016), and had greater SEP amplitudes ( = 0.61, = 0.001). Greater width of dorsal tissue bridges predicted better light-touch score at 12 months ( = 0.40, = 0.045) independently of baseline clinical score and ventral tissue bridges. Greater width of ventral midsagittal tissue bridges at 1 month identified patients who were classified as being motor incomplete at 12 months ( = 0.002), revealed shorter motor evoked potential (MEP) latencies (r = -0.54, = 0.044), and had greater ratios of MEP amplitude to compound muscle action potential amplitude ( = 0.56, = 0.005). Greater width of ventral tissue bridges predicted better lower extremity motor scores at 12 months ( = 0.41, = 0.035) independently of baseline clinical score and dorsal tissue bridges. CONCLUSION Midsagittal tissue bridges, detectable early after SCI, underwrite tract-specific electrophysiologic communication and are predictors of appropriate sensorimotor recovery. Neuroimaging biomarkers of midsagittal tissue bridges may be integrated into the diagnostic workup, prediction of recovery, and patients' stratification in clinical trials

Success rate 1 year after apical surgery: a retrospective analysis

PURPOSE The aim of the current study was the retrospective analysis of the outcomes of teeth treated with apical surgery after a 1-year follow-up period. Furthermore, potential factors associated with the success rate were investigated. METHODS All patients were treated at the Clinic of Cranio-Maxillofacial and Oral Surgery at the University of Zurich between 2010 and 2017. To be eligible for inclusion, all patients were required to have undergone apical surgery with a retrograde root-end filling, and a 1-year follow-up examination at the University of Zurich. Treatment success at the 1-year follow-up time-point was defined as an absence of clinical complaints and radiographically determined healing. Parameters that were analysed included tooth localisation, periapical index of the preoperative lesion, administration of antibiotics, smoker status, histopathology of the apical lesion, radiographically determined sufficiency of root canal treatment pain and clinical signs of inflammation at the initial examination. RESULTS A total of 81 teeth fulfilled all the inclusion criteria. At the 1-year follow-up, 91.4% of the teeth exhibited successful clinical and radiographic healing. The type of tooth was significantly associated with the success of the surgery (p = 0.006), but radiological severity of periapical inflammation, lesion histopathology, administration of antibiotics, smoker status, the quality of the root canal treatment, and preoperative pain and clinical signs of inflammation were not. CONCLUSION The results of the present study suggest that apical surgery with retrograde root-end filling is a reliable therapy for the preservation of teeth. Furthermore, there are limited factors that affect the treatment outcome

Entscheidungsfindung und Therapie nach Eröffnung der Kieferhöhle

Der Umgang mit der akzidentiell, pathologisch oder therapeutisch eröffneten Kieferhöhle ist ein zentrales Thema in der dentoalveolären Chirurgie. Dennoch liegt derzeit keine einheitliche Leitlinie zur Therapie vor, an welcher sich die Behandler orientieren könnten. Der Beitrag stellt den aktuellen Leitfaden der Züricher Poliklinik für Oralchirurgie zum Management der eröffneten Kieferhöhle vor und bietet dem allgemeinzahnmedizinisch tätigen Praktiker eine Orientierungshilfe

CO2 laser application in stomatology

Der CO2-Laser bietet vielfältige stomatologische Einsatzmöglichkeiten im modernen zahnärztlichen Praxisalltag. Die nachfolgende Arbeit soll eine kompakte Übersicht über den CO2-Laser zeigen und so den Einstieg in die Anwendung erleichtern.The CO2 laser has found great acceptance in the stomatologic field of dentistry. This article gives an overview of the most important benefits. The absorption of the laser light produces photothermal effects such as coagulation, vaporization and photoablation. The main indications in stomatology are pain alleviation and prevention of recurences in aphthae and cold sores (minor aphthae, herpes simplex), ablation of benign and irritant tissue excess (stimulus fibroma), lip and tongue band correction and soft tissue hemostasis. One great advantage is the minimal bleeding in the surgical field, which allows for optimal visibility. In addition, the CO2 laser offers high patient comfort since no primary wound closure with sutures are required. However, in suspect of malignancy a sharp excision with a scalpel is still preferred due to possible compromisation of the histopathologic evaluation

Are midsagittal tissue bridges predictive of outcome after cervical spinal cord injury?

T2-weighted scans provided data on the extent and dynamics of neuronal tissue damage and midsagittal tissue bridges at the epicenter of traumatic cervical spinal cord lesions in 24 subacute tetraplegic patients. At one month post-injury, smaller lesion area and midsagittal tissue bridges identified those patients with lower extremity evoked potentials and better clinical recovery. Wider midsagittal tissue bridges and smaller lesions at one month post-injury were associated with neurological and functional recovery at 1 year follow-up. Neuroimaging biomarkers of lesion area and midsagittal tissue bridges are potential outcome predictors and patient stratifiers in both subacute and chronic clinical trials. This article is protected by copyright. All rights reserved

Guided apicoectomy using a CAD/CAM drilling template

AIM Modern microsurgical techniques have increased the success rate of apicoectomy relative to that of traditional approaches. This case report introduces a novel workaround for guided apicoectomy using a patient-specific computer-aided design/computer-aided manufacturing (CAD/CAM) three-dimensional (3D)-printed template. MATERIALS AND METHODS Apicoectomy was performed on the mesial root of tooth 36 using template-guided trephine drilling, followed by retrograde filling with mineral trioxide aggregate (MTA). Initially, a cone beam computed tomography (CBCT) scan and an intraoral surface scan were imported into the planning software. After superimposition, virtual planning was performed to determine the exact localization for root resection. Subsequently, a tooth-supported drilling template was designed and 3D printed. Endodontic microsurgical approaches, including root-end cavity preparation and root-end filling, completed the surgical treatment. RESULT The apical resection was easily feasible. There were no postoperative complications. Radiological assessment after a 6-month period showed signs of reossification. CONCLUSION Guided apicoectomy allowed precise root resection, suggesting that this technique may be advantageous in complex anatomical situations

The operational performance of an oncology day clinic /

Master of Science in Business Engineering: Operations Managemen