Search

Repair of a DNA double-strand break relies upon a pathway of proteins to identify damage, regulate cell cycle checkpoints, and repair the damage. This process is initiated by a sensor protein complex, the MRN complex, comprised of three proteins-MRE11, RAD50, and NBS1. After a double-stranded break, the MRN complex recruits and activates ATM, in-turn activating other proteins such as BRCA1/2, ATR, CHEK1/2, PALB2 and RAD51. These proteins have been the focus of many studies for their individual roles in hereditary cancer syndromes and are included on several genetic testing panels. These panels have enabled us to acquire large amounts of genetic data, much of which remains a challenge to interpret due to the presence of variants of uncertain significance (VUS). While the primary aim of clinical testing is to accurately and confidently classify variants in order to inform medical management, the presence of VUSs has led to ambiguity in genetic counseling. Pathogenic variants within MRN complex genes have been implicated in breast, ovarian, prostate, colon cancers and gliomas; however, the hundreds of VUSs within MRE11, RAD50, and NBS1 precludes the application of these data in genetic guidance of carriers. In this review, we discuss the MRN complex's role in DNA double-strand break repair, its interactions with other cancer predisposing genes, the variants that can be found within the three MRN complex genes, and the MRN complex's potential as an anti-cancer therapeutic target.

Variants of unknown significance (VUS) remain a constant challenge in the diagnosis of hereditary cancer and the counseling of patients with pedigrees suggestive of such a syndrome. In order to assess some of this limitation, several variants in the DNA repair gene ATM were selected from a cohort of high risk individuals with negative genetic diagnoses. ATM has proven a challenge in the counseling of patients due to its nature as a moderate penetrance gene. In this study, six ATM missense mutations with a high likelihood for pathogenicity were assessed through a battery of experiments to yield high fidelity information on their biochemical effect on ATM activity. We report that several of these variants show signs of reduced ATM function indicative of likely pathogenicity. With further study, this data may be used in clinic, improving diagnosis, surveillance, and outcome for patients carrying these mutations., (Copyright © 2022. Published by Elsevier Inc.)

Aim: To systematically review the comparative differences in the performance and timeliness of conventional orthodontic treatment with that of corticotomy-assisted accelerated orthodontic treatment., Data Sources: The electronic databases PubMed and Google Scholar were searched from January 2007 to January 2018 in English, with manual searches of reference lists and gray literature. Thirty-six articles were included in the study with inclusion criteria as prospective clinical studies of patients treated with fixed conventional appliance and the intervention was the corticotomy-assisted accelerated orthodontic treatment method., Study Selection: Two reviewers assessed independently the eligibility of the included articles. One investigator abstracted study design information, intervention details, and harms data from all included studies into a standardized evidence table. The accuracy of these data was checked by the second investigator. We resolved any disagreements through discussion with other authors., Results: Different aspects of the corticotomy-assisted accelerated orthodontics treatment method were investigated including risk factors, advantages, and disadvantages as compared to that of conventional orthodontic treatment., Conclusion: There is limited available evidence about effectiveness of corticotomy-assisted accelerated orthodontics. Although the current review indicates that the corticotomy-assisted accelerated orthodontic treatment method can fasten the treatment duration by 2.2-3 folds compared to conventional orthodontic treatment, furthermore, the level of evidence needs well-conducted prospective research with big sample size to draw valid conclusions., Clinical Significance: Orthodontic treatment is a time-consuming process and due to noncompliance of patients, research has found different methods to accelerate the treatment, thus reducing the total treatment duration. Use of accelerated orthodontic techniques is expected to help clinicians in better treatment decisions for noncompliant patients.

Fluoride is one of the most abundant elements found in nature. Water is the major dietary source of fluoride. The only known association with low fluoride intake is the risk of dental caries. Initially, fluoride was considered beneficial when given systemically during tooth development, but later research has shown the importance and the advantages of its topical effects in the prevention or treatment of dental caries and tooth decay. Water fluoridation was once heralded as one of the best public health achievements in the twentieth century. Since this practice is not feasible or cost effective in many regions, especially rural areas, researchers and policy makers have explored other methods of introducing fluoride to the general population such as adding fluoride to milk and table salt. Lately, major concerns about excessive fluoride intake and related toxicity were raised worldwide, leading several countries to ban fluoridation. Health-care professionals and the public need guidance regarding the debate around fluoridation. This paper reviews the different aspects of fluoridation, their effectiveness in dental caries prevention and their risks. It was performed in the PubMed and the Google Scholar databases in January 2018 without limitation as to the publication period., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest.

Purpose: We compare oncologic outcomes of minimally invasive and open nephrectomy for locally advanced kidney cancer., Materials and Methods: A retrospective review of a single-institutional, prospectively maintained database from a National Comprehensive Cancer Network-designated center was conducted. All patients who underwent radical nephrectomy at Roswell Park Cancer Institute with diagnosis of pT3 and pT4 renal-cell carcinoma (RCC) between years 1998 and 2015 were reviewed. Patients who underwent partial nephrectomy and nephroureterectomy were excluded., Results: We identified 172 patients with pT3 or pT4 tumors resected by minimally invasive (laparoscopic and robotic) or open radical nephrectomy. Demographic characteristics were similar between the two groups. Patients in the minimally invasive group had a higher mean body mass index (31.9 vs 28.1, p = 0.002), radiologically smaller tumors (7.7 cm vs 9.1 cm, p = 0.008), lower mean estimated blood loss (277 vs 1429, p < 0.001), lower rate of blood transfusion (4.7% vs 45.5%, p < 0.001), and a shorter mean length of stay (3.5 days vs 5.7 days, p < 0.001) compared with patients who underwent open surgery. At a median follow-up of 32.8 months, there was no significant difference in overall survival (p = 0.8) between the two groups., Conclusion: Minimal invasive nephrectomy is a safe approach with similar oncologic outcomes to open nephrectomy for select patients with locally advanced RCC.

Purpose. The surgical expertise to perform robotic partial nephrectomy is heavily dependent on technology. The Da Vinci Xi (XI) is the latest robotic surgical platform with significant advancements compared to its predecessor. We describe our operative technique and experience with the XI system for robotic partial nephrectomy (RPN). Materials and Methods. Patients with clinical T1 renal masses were offered RPN with the XI. We used laser targeting, autopositioning, and a novel "in-line" port placement to perform RPN. Results. 15 patients underwent RPN with the XI. There were no intraoperative complications and no operative conversions. Mean console time was 101.3 minutes (range 44-176 minutes). Mean ischemia time was 17.5 minutes and estimated blood loss was 120 mLs. 12 of 15 patients had renal cell carcinoma. Two patients had oncocytoma and one had benign cystic disease. All patients had negative surgical margins and pathologic T1 disease. Two postoperative complications were encountered, including one patient who developed a pseudoaneurysm and one readmitted for presumed urinary tract infection. Conclusions. RPN with the XI system can be safely performed. Combining our surgical technique with the technological advancements on the XI offers patients acceptable pathologic and perioperative outcomes.

The search continues for optimal markers that can be utilized to improve bladder cancer detection and to predict disease recurrence. Although no single marker has yet replaced the need to perform cystoscopy and urine cytology, many tests have been evaluated and are being developed. In the future, these promising markers may be incorporated into standard practice to address the challenge of screening in addition to long-term surveillance of patients who have or are at risk for developing bladder cancer.

Purpose: Robotic-assisted laparoscopic nephroureterectomy (RALNU) has been previously utilized for management of upper tract urothelial carcinoma. The da Vinci Xi surgical system was released in April of 2014. We describe our operative technique and early experience for RALNU using the da Vinci Xi system highlighting unique features of this surgical platform., Materials and Methods: A total of 10 patients with a diagnosis of upper tract urothelial carcinoma underwent RALNU using the da Vinci Xi system between April and November of 2014. A novel, oblique "in line" robotic trocar configuration was utilized to access the upper abdomen (nephrectomy portion) and pelvis (bladder cuff excision) without undocking. The port hopping feature of da Vinci Xi was utilized to facilitate optimal, multi-quadrant visualization during RALNU., Results: Robotic-assisted laparoscopic nephroureterectomy was successfully completed without open conversion in all 10 patients. Mean operative time was 184 min (range 140-300 min), mean estimated blood loss was 121 cc (range 60-300 cc), and mean hospital stay was 2.4 days. Final pathology demonstrated high grade urothelial carcinoma in all patients. Surgical margins were negative in all patients. No intra-operative complications were encountered. One patient developed a pulmonary embolus after being discharged. No patients required a blood transfusion. Mean patient follow-up was 130 days (range 15-210 days)., Conclusion: The use of da Vinci Xi with a novel, oblique "in line" port configuration and camera port hopping technique allows for an efficient and reproducible method for RALNU without the need for repositioning the patient or the robot during surgery.