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Selection of the appropriate DNA double-strand break (DSB) repair pathway is decisive for genetic stability. It is proposed to act according to two steps: 1-canonical nonhomologous end-joining (C-NHEJ) versus resection that generates single-stranded DNA (ssDNA) stretches; 2-on ssDNA, gene conversion (GC) versus nonconservative single-strand annealing (SSA) or alternative end-joining (A-EJ). Here, we addressed the mechanisms by which RAD51 regulates this second step, preventing nonconservative repair in human cells. Silencing RAD51 or BRCA2 stimulated both SSA and A-EJ, but not C-NHEJ, validating the two-step model. Three different RAD51 dominant-negative forms (DN-RAD51s) repressed GC and stimulated SSA/A-EJ. However, a fourth DN-RAD51 repressed SSA/A-EJ, although it efficiently represses GC. In living cells, the three DN-RAD51s that stimulate SSA/A-EJ failed to load efficiently onto damaged chromatin and inhibited the binding of endogenous RAD51, while the fourth DN-RAD51, which inhibits SSA/A-EJ, efficiently loads on damaged chromatin. Therefore, the binding of RAD51 to DNA, rather than its ability to promote GC, is required for SSA/A-EJ inhibition by RAD51. We showed that RAD51 did not limit resection of endonuclease-induced DSBs, but prevented spontaneous and RAD52-induced annealing of complementary ssDNA in vitro. Therefore, RAD51 controls the selection of the DSB repair pathway, protecting genome integrity from nonconservative DSB repair through ssDNA occupancy, independently of the promotion of CG.

Roux-en-Y gastric bypass (RYGB) is an established surgical treatment for obesity. Variations in limb length during RYGB procedures have been investigated for optimizing weight loss while minimizing nutritional deficiencies. The role of the total alimentary limb length (TALL; Roux limb plus common channel [CC]), however, is poorly defined.Compare TALL in RYGB procedures for weight loss outcomes and malnutrition.Systematic review.Ovid Medline and PubMed databases were searched for entries between 1993 and 2020. Search terms included "gastric bypass" and "TALL." Two independent reviewers screened the results.A total of 21 studies measured TALL in RYGB. Of these, 4 of 6 reported a relationship between TALL and weight loss. Additionally, 11 studies reported that when TALL was ≤400 cm and CC200 cm, 3.4% to 63.6% of patients required limb lengthening for protein malnutrition.The majority of studies on RYGB do not report TALL length. There is some evidence that weight loss is affected by shortening TALL, while a TALL ≤400 cm with CC200 should be avoided due to severe protein malnutrition. More studies on the effect of TALL are needed.

For patients with super obesity (BMI 50 kg/mThe MBSAQIP database was queried for primary and revisional BPD/DS (2015-2018). Inclusion criteria were patients ≥ 18 years of age, BMI 50 kg/mThere were 3,378 primary BPD/DS and 487 revisional BPD/DS patients. Primary BPD/DS patients had higher BMI (56.5 [IQR4.4] versus 54.8 [IQR4] kg/mRevisional BPD/DS is associated with higher morbidity than primary BPD/DS in patients with super obesity. These patients should thus be counselled appropriately when choosing a primary or revisional bariatric procedure.

The obesity rate for the Hispanic population is significantly higher than that of white, non-Hispanic people in the United States, yet Hispanic people undergo disproportionately fewer metabolic and bariatric surgery procedures. This study used the Metabolic Bariatric Surgery Accreditation and Quality Improvement Program data registry to examine potential differences in preoperative co-morbidities and postoperative outcomes in Hispanic adults undergoing sleeve gastrectomy or Roux-en-Y gastric bypass procedures in the United States.To study the presence of the Hispanic paradox in metabolic and bariatric surgery utilizing the MBSAQIP registry.Academic Teaching Institution.Participant User Files from the Metabolic Bariatric Surgery Accreditation and Quality Improvement Program were reviewed for patients undergoing sleeve gastrectomy or Roux-en-Y gastric bypass (2015-2017). Patients were grouped by race (Hispanic versus all other races) and primary procedure performed. Variables for major and minor postoperative complications were combined. A univariate analysis was performed on unmatched and propensity-matched cohorts.After applying exclusions, 53,353 (13.7%) Hispanic patients and 335,299 non-Hispanic patients remained. A univariate analysis demonstrated Hispanic patients had the lowest preoperative co-morbidity profile compared with all other races and decreased rates of major and minor postoperative complications. Using matched-cohort data, when complications were assessed and grouped as major/minor complications, rates of major and minor complications in Hispanic patients were lower in the Roux-en-Y gastric bypass group, despite Hispanic patients having higher leak rates. Similarly, there were no differences between Hispanic/non-Hispanic sleeve gastrectomy patients in overall major/minor complication rates despite Hispanic patients exhibiting higher venous thromboembolism and lower bleeding compared with non-Hispanic patients.Hispanic patients undergo disproportionately low rates of metabolic and bariatric surgery procedures and present with lower incidence of preoperative co-morbidities. Additionally, Hispanic patients have the same or decreased incidence of postoperative complications compared with non-Hispanic patients, thereby corroborating the Hispanic paradox.

Purpose To estimate the incidence of patients presenting to emergency departments (EDs) as a result of facial trauma sustained from skateboarding. Patients and Methods The National Electronic Injury Surveillance System (NEISS) database was queried for skateboard-related head and face fractures, contusions, abrasions, and lacerations from 2009 through 2018. We identified 2,519 reported injuries, extrapolating to a national incidence of 100,201 injuries. Fractures accounted for 14.1% of these visits. There were 355 ED visits for fractures, extrapolating to an estimated 11,893 visits nationally. Entries were tabulated for demographic information, fracture type, mechanism of injury, and disposition. Results Patients sustaining injury to the head and face were aged 16 years, on average, and predominantly male patients (85.9%). Most patients sustaining fractures were male patients (87.9%), with a mean age of 18 years. The most common fracture types included unspecified skull fractures (31%), nasal fractures (29%), and mandibular fractures (18%). The most common mechanism of injury was falling off the skateboard while riding (76.9%). Collisions with motor vehicles also accounted for a substantial proportion of the injuries (7.3%). Conclusions A substantial number of ED visits were a result of skateboarding-related facial trauma. Given the neurologic outcomes of head trauma and functional consequences of facial fractures, especially among adolescents, our findings suggest that injury prevention programs and more aggressive helmet use may be necessary to reduce morbidity and hospitalization.

Background Ladders are a commonly used piece of equipment; however, their use is accompanied by a significant potential for injury. Fractures of the head, face, and neck are potential consequences of ladder use and can be devastating due to potential for severe sequalae. Objectives To describe the frequency and pattern of ladder-related head, face, and neck fractures from 2009–2018. Methods The National Electronic Injury Surveillance System (NEISS) was searched for ladder-related head, face, and neck fractures treated in U.S. emergency departments. Demographics, mechanism of injury, fracture type, setting in which fracture occurred, and patient disposition were analyzed. Results There were 601 total cases (weighted national estimate of 20,450 total cases) of ladder-related head, face, and neck fractures obtained from the NEISS from 2009 to 2018. The mean age of injury was 53 years, and the majority of cases occurred in home settings. Approximately 25% of the cases were patients aged older than 65 years. The majority of fractures in individuals younger than 18 years and older than 46 years of age resulted in admission. The most commonly fractured locations included the face (51.0%), followed by cervical spine (28.3%) and cranial (20.7%) fractures. Conclusions Admission rates for ladder-related head, face, and neck fractures are substantially higher than those previously reported for all types of ladder-related injuries. Injury and admission patterns vary by age. Rigorous safety precautions may be indicated for the high-risk groups identified by this study, especially the elderly.

Efficient brain strain estimation is critical for routine application of a head injury model. Lately, a convolutional neural network (CNN) has been successfully developed to estimate spatially detailed brain strains instantly and accurately in contact sports. Here, we extend its application to automotive head impacts, where impact profiles are typically more complex with longer durations. Head impact kinematics (N=458) from two public databases were used to generate augmented impacts (N=2694). They were simulated using the anisotropic Worcester Head Injury Model (WHIM) V1.0, which provided baseline elementwise peak maximum principal strain (MPS). For each augmented impact, rotational velocity (

Regionalization of emergency general surgery (EGS) has primarily focused on expediting care of high acuity patients through interfacility transfers. In contrast, triaging low-risk patients to a nondesignated trauma facility has not been evaluated. This study evaluates a 16-month experience of a five-surgeon team triaging EGS patients at a tertiary care, Level I trauma center (TC) to an affiliated community hospital 1.3 miles away.All EGS patients who presented to the Level I TC emergency department from January 2020 to April 2021 were analyzed. Patients were screened by EGS surgeons covering both facilities for transfer appropriateness including hemodynamics, resource need, and comorbidities. Patients were retrospectively evaluated for disposition, diagnosis, comorbidities, length of stay, surgical intervention, and 30-day mortality and readmission.Of 987 patients reviewed, 31.5% were transferred to the affiliated community hospital, 16.1% were discharged home from the emergency department, and 52.4% were admitted to the Level I TC. Common diagnoses were biliary disease (16.8%), bowel obstruction (15.7%), and appendicitis (14.3%). Compared with Level I TC admissions, Charlson Comorbidity Index was lower (1.89 vs. 4.45, p0.001) and length of stay was shorter (2.23 days vs. 5.49 days, p0.001) for transfers. Transfers had a higher rate of surgery (67.5% vs. 50.1%, p0.001) and lower readmission and mortality (8.4% vs. 15.3%, p = 0.004; 0.6% vs. 5.0%, p0.001). Reasons not to transfer were emergency evaluation, comorbidity burden, operating room availability, and established care. No transfers required transfer back to higher care (under-triage). Bed days saved at the Level I TC were 693 (591 inpatients). Total operating room minutes saved were 24,008 (16,919, between 7:00 am and 5:00 pm).Transfer of appropriate patients maintains high quality care and outcomes, while improving operating room and bed capacity and resource utilization at a tertiary care, Level I TC. Emergency general surgery regionalization should consider triage of both high-risk and low-risk patients.Prospective comparative cohort study, Level II.

Background Male patients undergoing bariatric surgery have (historically) been considered higher risk than females. The aim of this study was to examine the disparity between genders undergoing laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) procedures and assess gender as an independent risk factor. Methods The MBSAQIP® Data Registry Participant User Files for 2015–2017 was reviewed for patients having primary SG and RYGB. Patients were divided into groups based on gender and procedure. Variables for major complications were grouped together, including but not limited to PE, stroke, and MI. Univariate and propensity matching analyses were performed. Results Of 429,664 cases, 20.58% were male. Univariate analysis demonstrated males were older (46.48 ± 11.96 vs. 43.71 ± 11.89 years, p

Although the US population is becoming increasingly diverse, diversity in medicine is lacking. Our aim was to examine trends in sex, racial, and ethnic diversity of trainees in the field of dermatology. Graduate medical education supplements published annually in the

Marginal ulceration (MU) is a common long-term complication following Roux-en-Y gastric bypass (RYGB). The causes of MU after RYGB are multifactorial and include surgical technique of constructing the gastrojejunal anastomosis (GJA). The purpose of this study is to evaluate the relationship between gastric pouch size in RYGB and MU using CT volumetrics.Patients were retrospectively identified who underwent esophagogastroduodenoscopy (EGD) following RYGB at a tertiary care teaching hospital. Measurement of gastric pouch size was performed using 3-D CT software. Standard statistical methods were used, a univariate comparison was performed between MU and non-MU patients followed by a propensity-matched comparison to control for factors known to affect MU, and a propensity-matched subgroup analysis was also performed.In total, 122 patients met criteria, 57 of which had MU on EGD and 65 who did not. The MU group had more smokers and patients with PPI use than the non-MU group, and the mean time from operation to CT scan was 26.6 months (range: 0-108 months). The MU group had a larger gastric pouch size than the non-MU group (34.1 ± 11.8 versus 20.1 ± 6.8 cmCT volumetric analysis demonstrated that a larger gastric pouch size was associated with MU following RYGB.

Patients undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) are at risk of developing strictures of the gastrojejunal anastomosis (GJA). Several variables can affect this, one of which may be the method of anastomosis. Between 2010 and 2014, our institution utilized three different anastomotic techniques for creating the GJA (25 mm end-to-end circular-stapled (CS), linear-stapled (LS), and robotic hand sewn (HS)). Our objectives were to compare the method of GJA relative to the subsequent development of anastomotic stricture.We queried our electronic health record for all patients who underwent an upper endoscopy (EGD) after RYGB (2010-2014). Patient charts were retrospectively reviewed for type of GJA, weight loss, complications, interventions, and revisions of the GJA.In total, 1112 RYGB were performed at our institute, and 17.4% of patients (194/1112) had an upper endoscopy (EGD). Overall, 3.1% (34/1112) were found to have a stricture of the GJA. Patients undergoing a CS, LS, and HS anastomosis had GJA stricture rates of 4.9%, 0.5%, and 1.2% respectively (CS to LS (p 0.05), p = NS among CS vs. HS, and LS vs. HS). The rate of GJA revision was 1.5%, 0.5%, and 0.1% (p = NS). In patients who had an EGD, excess BMI loss was 57.4%, 64.6%, and 59.2% (p = NS). In patients symptomatic from strictures, excess BMI loss was 69.4%, 83%, and 63.5% respectively (p = NS).The anastomotic technique for creating of the GJA may impact the formation of strictures. Based on our experience, gastrojejunostomies created with a 2-mm EEA-stapling technique are at higher risk of strictures.

The development and survival of cancer cells require adaptive mechanisms to stress. Such adaptations can confer intrinsic vulnerabilities, enabling the selective targeting of cancer cells. Through a pooled in vivo short hairpin RNA (shRNA) screen, we identified the adenosine triphosphatase associated with diverse cellular activities (AAA-ATPase) valosin-containing protein (VCP) as a top stress-related vulnerability in acute myeloid leukemia (AML). We established that AML was the most responsive disease to chemical inhibition of VCP across a panel of 16 cancer types. The sensitivity to VCP inhibition of human AML cell lines, primary patient samples, and syngeneic and xenograft mouse models of AML was validated using VCP-directed shRNAs, overexpression of a dominant-negative VCP mutant, and chemical inhibition. By combining mass spectrometry-based analysis of the VCP interactome and phospho-signaling studies, we determined that VCP is important for ataxia telangiectasia mutated (ATM) kinase activation and subsequent DNA repair through homologous recombination in AML. A second-generation VCP inhibitor, CB-5339, was then developed and characterized. Efficacy and safety of CB-5339 were validated in multiple AML models, including syngeneic and patient-derived xenograft murine models. We further demonstrated that combining DNA-damaging agents, such as anthracyclines, with CB-5339 treatment synergizes to impair leukemic growth in an MLL-AF9-driven AML murine model. These studies support the clinical testing of CB-5339 as a single agent or in combination with standard-of-care DNA-damaging chemotherapy for the treatment of AML.

Brain tissue deformation resulting from head impacts is primarily caused by rotation and can lead to traumatic brain injury. To quantify brain injury risk based on measurements of kinematics on the head, finite element (FE) models and various brain injury criteria based on different factors of these kinematics have been developed, but the contribution of different kinematic factors has not been comprehensively analyzed across different types of head impacts in a data-driven manner. To better design brain injury criteria, the predictive power of rotational kinematics factors, which are different in (1) the derivative order (angular velocity, angular acceleration, angular jerk), (2) the direction and (3) the power (e.g., square-rooted, squared, cubic) of the angular velocity, were analyzed based on different datasets including laboratory impacts, American football, mixed martial arts (MMA), NHTSA automobile crashworthiness tests and NASCAR crash events. Ordinary least squares regressions were built from kinematics factors to the 95% maximum principal strain (MPS95), and we compared zero-order correlation coefficients, structure coefficients, commonality analysis, and dominance analysis. The angular acceleration, the magnitude and the first power factors showed the highest predictive power for the majority of impacts including laboratory impacts, American football impacts, with few exceptions (angular velocity for MMA and NASCAR impacts). The predictive power of rotational kinematics about three directions (x: posterior-to-anterior, y: left-to-right, z: superior-to-inferior) of kinematics varied with different sports and types of head impacts.

Marginal ulceration (MU) and bleeding are possible complications following laparoscopic Roux-en-Y gastric bypass (RYGB). Our institution utilizes three techniques for performing the gastrojejunal anastomosis (GJA), providing a means to compare postoperative MU and bleeding as it relates to GJA technique.We sought to analyze the incidence of MU and bleeding between the 25-mm end-to-end anastomosis (EEA) stapler, linear stapler (LS), and robotic hand-sewn (RHS) GJA techniques.Electronic health records for all patients who had an upper endoscopy (EGD) after RYGB were queried (2010-2014). Charts were retrospectively reviewed for type of GJA, complications, endoscopic interventions, and smoking and NSAID use.Out of 1112 RYGBs, the GJA was created using an EEA, LS, or RHS approach in 58.6%, 33.6%, and 7.7% of patients, respectively. 17.4% had an EGD (19.9% EEA, 13.9% LS, and 14.0% RHS). Incidence of MU was 7.3% (9.3% EEA, 4.8% LS, and 5.8% RHS). Rates of EGD and MU were significantly higher after EEA vs. LS GJA (p0.05). The bleeding rate was 1.5%, [1.1% EEA, 2.1% LS, and 2.3% RHS (p=NS)]. MU within 90 days of RYGB occurred in 4.1%, 0.8%, and 4.7%, respectively (p0.05 for EEA vs LS only). NSAID and cigarette use were identified in 29.3%, 38.9%, and 60% and 17.2%, 22.2%, and 20%, respectively, for the EEA, LS, and RHS GJA (p=NS).The method of GJA has an impact on rate of MU formation. A GJA fashioned with a 25-mm EEA stapler tends to have higher rates of EGD and MU.

Background The incidence of obesity is disproportionally high in African Americans (AA) in the United States. This study compared outcomes for AA patients undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) with non-AA patients. Methods The MBSAQIP database was reviewed for RYGB and SG patients (2015–2017). Patients were identified as AA or non-AA and grouped to RYGB or SG. Combined and univariate analyses were performed on unmatched/propensity matched populations to assess outcomes. Results After applying exclusion criteria, 75,409 AA and 354,305 non-AA patients remained. Univariate analysis identified AA-RYGB and AA-SG patients were heavier and younger than non-AA patients. Overall, AA patients tended to have fewer preoperative comorbidities than non-AA patients with the majority of AA comorbidities related to hypertension and renal disease. Analysis of propensity matched data confirmed AA bariatric surgery patients had increased cardiovascular-related disease incidence compared with non-AA patients. Perioperatively, AA-RYGB patients had longer operative times, increased rates of major complications/ICU admission, and increased incidence of 30-day readmission, re-intervention, and reoperation, concomitant with lower rates of minor complications/superficial surgical site infection (SSI) compared with non-AA patients. For SG, AA patients had longer operative times and higher rates of major complications and 30-day readmission, re-intervention, and mortality, coupled with fewer minor complications, superficial/organ space SSI, and leak. Conclusion African American patients undergoing bariatric surgery are younger and heavier than non-AA patients and present with different comorbidity profiles. Overall, AAs exhibit worse outcomes following RYGB or SG than non-AA patients, including increased mortality rates in AA-SG patients.

Aging leads to a loss of muscle strength and functional capacity likely resulting from a combination of neural and muscle alterations. The aim of this study was to identify possible disparities in muscle strength and force development profiles in high- and low-functioning elderly men and to investigate muscular and neurophysiological factors that could explain the differences.Sixty community-dwelling men in good general health were divided in two groups based on a functional capacity (FC) z-score derived from 6 tests of the Short Physical Performance Battery and Senior Fitness Test (Normal and fast 4m-walk tests, normal and fast Timed-up and go, chair and stair tests). Extensor strength of the lower limbs (LL) was obtained for concentric (CLES) contraction and combined with lean masses of LL (LLLM) to yield concentric (CLES/LLLM) index. Similarly, extensor strength of the right Quadriceps Femoris (IKES) was obtained during maximal voluntary isometric contraction (MVC) and combined with right thigh lean mass (rTLM) to produce an isometric strength (IKES/rTLM) index. A muscular profile was obtained from: ascending and descending force slopes during the MVC; Vastus Lateralis (VL) muscle twitches parameters (amplitude, contraction and ½ relaxation times); the knee joint velocity (KV) as well as integrated EMG (iEMG) were determined for a sit-to-stand functional evaluation; muscle phenotype. A neurophysiological profile was established from: the spinal excitability (Hmax/Mmax ratio); motoneuron conduction velocity (CV); the completeness of muscle activation (% of force reserve), median power frequency (MPF) and mean amplitude (MA) of the VL EMG signal during MVC.Coincidently, age did not differ between groups. Strength and force indices, descending force slopes for MVC, KV and iEMG during the sit-to-stand evaluation and FC parameters were all significantly (p0.05) lower in the LoFC group than in the HiFC group. In contrast, no difference was observed between groups in: LLLM and rTLM, Hmax/Mmax ratio, CV, twitch parameters and muscle phenotype.The lower concentric and isometric strengths found in the LoFC group could not be accounted for by muscular factors. Similarly, peripheral nervous systems alterations could not explain group differences. It can be suggested that modifications within the central nervous system may be responsible for the differences in the functional status of healthy elderly individuals. Finally, more complex and demanding tasks, such as those requiring greater intensity or coordination, may further clarify how healthy elderly individuals with low and high functional capacities differ.

Whole-genome sequencing plays now a leading role in epidemiologic studies of tuberculosis. DNA extraction of Mycobacterium tuberculosis complex (MTBC) requires complete inactivation of the strains, to be handled for further molecular procedures. In this study we compared two chloroform-based denaturation methods (one with a step of heat killing, one without) to a traditional heat inactivation method. Our results showed that 40% of the strains of MTBC treated by the traditional protocol resulted in a positive culture whereas no culture was observed with the two chloroform-based protocols. The DNA extracts obtained with chloroform-based protocols preparation were successfully used for whole-genome sequencing. We recommend inactivation with our rapid and efficient denaturation method using chloroform without heat killing which met our expectations and biosecurity requirements.

Background Previous reports of bariatric surgery outcomes when cases are assisted by residents and/or fellows have been inconclusive. Objective To compare bariatric surgery outcomes for cases with surgical trainees (ST; residents and fellows) versus nonsurgical trainees (nST; all other assistants) using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Registry. Setting Academic teaching. Methods The MBSAQIP Registry was reviewed (2015–2017) for Roux-en-Y gastric bypass, sleeve gastrectomy, and revision surgery based on ST and nST status. Univariate, multivariate logistic regression, and propensity matching analyses were performed. Results Of 477,670 cases, 26.8% were performed with ST. For ST patients 79.9% were female (versus 80.3% nST) and mean body mass index was 45.2 ± 8 kg/m2 (versus 45.0 ± 8.1 kg/m2 nST). Overall, 31.7% of patients underwent Roux-en-Y gastric bypass (versus 25.7% nST), 65.9% underwent sleeve gastrectomy (versus 71.6% nST), and 2.4% of patients had revision surgery (versus 2.7% nST). After matching, no difference in 30-day mortality was observed between groups. However, ST patients had higher incidence of deep vein thrombosis (P = .004), pulmonary embolism (P = .005), superficial surgical site infection (P Conclusion Overall, there was no difference observed in 30-day mortality between the ST and nST groups. However, despite lower 30-day reoperation rates, ST patients exhibited higher rates of postoperative deep vein thrombosis, pulmonary embolism, superficial surgical site infection, postoperative sepsis, blood transfusions, 30-day readmission rates, and longer operative times than nST patients.

BackgroundAlthough women make up a substantial portion of the workforce in emergency medicine, they remain under-represented in academia.MethodsThis study investigates trends in the representation of female speakers at the American College of Emergency Physicians scientific assembly—the largest academic emergency medicine conference in the world. Publication profiles, speaking duration and gender composition of speakers were collected and compared over a 3-year period.ResultsThe authors described increased representation of female speakers at the conference from 2016 to 2018, as well as an upward trend in women’s actual speaking time.ConclusionThis upward trend in women’s representation may translate to more opportunities for female engagement in academic emergency medicine. Despite the increasing representation of women, male speakers outnumbered female speakers all 3 years, demonstrating that a speaker gender gap persists in academic emergency medicine.

Bariatric surgery is the most effective modality to treat obesity and obesity-related comorbidities. This study sought to utilize the MBASQIP® Data Registry to analyze the impact of age at time of surgery on outcomes following sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedures. The MBSAQIP® Data Registry for patients undergoing SG or RYGB procedures between 2015 and 2016 was reviewed. Patients were divided into 4 age groups [18–44; 45–54; 55–64; > 65 years]. Minimal exclusions for revisional and/or emergency surgery were selected and combination variables created to classify complications as major or minor. A comorbidity index was constructed to include diabetes, gastroesophageal reflux disease (GERD), obstructive sleep apnea (OSA), and prior cardiac surgery. Univariate and multivariate logistic regression analyses were performed to compare age stratifications to the young adult (18–45 years) cohort. Of 301,605 cases, 279,419 cases (71.2% SG) remained after applying exclusion criteria (79.2% female, mean BMI 45.5 ± 8.1 kg/m2, 8.9% insulin-dependent diabetics). Mean age was 44.7 ± 12.0 years (51.3% 18–44 years; 26.9% 45–54 years; 16.3% 55–64 years; 5.5% > 65 years). A univariate analysis demonstrated preoperative differences of lower BMI with increasing age concomitant with increasing frequency of RYGB and a higher comorbidity index (p 45 years, major complications and 30-day mortality increased independent of procedure type (p 45 years) increased risk for major complications and mortality. Overall, bariatric surgery (SG or RYGB) remains a low mortality risk procedure for all age groups. However, all age group classifications > 45 years had higher incidence of major complications and mortality compared to patients 18–45 years (despite older individuals having lower preoperative BMI) indicating delaying surgery is detrimental.

Multiple brain injury criteria (BIC) are developed to quickly quantify brain injury risks after head impacts. These BIC originated from different types of head impacts (e.g., sports and car crashes) are widely used in risk evaluation. However, the accuracy of using the BIC on brain injury risk estimation across different types of head impacts has not been evaluated. Physiologically, brain strain is often considered the key parameter of brain injury. To evaluate the BIC's risk estimation accuracy across five datasets comprising different head impact types, linear regression was used to model 95% maximum principal strain, 95% maximum principal strain at the corpus callosum, and cumulative strain damage (15%) on each of 18 BIC respectively. The results show a significant difference in the relationship between BIC and brain strain across datasets, indicating the same BIC value may suggest different brain strain in different head impact types. The accuracy of brain strain regression is generally decreasing if the BIC regression models are fit on a dataset with a different type of head impact rather than on the dataset with the same type. Given this finding, this study raises concerns for applying BIC to estimate the brain injury risks for head impacts different from the head impacts on which the BIC was developed., Comment: 28 pages, 11 figures

Background Usual gait speed (UGS) is recognized as a good indicator of a variety of health conditions as well as a predictor of future disability and mortality. There is evidence that UGS increases with physical activity. Muscle function and body composition changes may mediate these changes. However, we do not know exactly which of these factors contribute to the effect of physical activity on gait speed or the magnitude of their contribution. Methods Data are from 1378 women aged 75 years and older recruited in the Toulouse EPIDemiologie de l'OSteoporose cohort. Body weight and composition (dual energy X-ray absorptiometry), knee extension strength, and physical activity habits were assessed. The INDIRECT macro for SPSS (SPSS Inc, Chicago, IL) was used to determine total and specific indirect effects of physical activity on UGS through body weight (BW) and composition as well as muscle mass and strength. Results Knee extension strength [95% confidence interval (CI) 0.0091, 0.0231] and BW (95% CI 0.0037, 0.0412), but not fat mass or muscle mass, were mediators of the relationship between physical activity and gait speed. However, muscle mass significantly mediated the relationship between physical activity and muscle strength (95% CI −3.0722, −0.6265). Conclusions Results suggest that muscle strength and BW are the most significant mediators of the relationship between physical activity and UGS. Although the specific effect of muscle mass appears negligible at first sight, its role should not be overlooked given its impact on muscle strength.

Background The exact impact of ageing on skeletal muscle phenotype and mitochondrial and lipid content remains controversial, probably because physical activity, which greatly influences muscle physiology, is rarely accounted for. The present study was therefore designed to investigate the effects of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, and mitochondrial and intramyocellular lipid content in men. Methods Recreationally active young adult (20–30 yo; YA); active (ACT) and sedentary (SED) middle‐age (50–65 yo; MA‐ACT and MA‐SED); and older (65 + yo; 65 + ACT and 65 + SED) and pre‐frail older (65 + PF) men were recruited. Muscle biopsies from the vastus lateralis were collected to assess, on muscle cross sections, muscle phenotype (using myosin heavy chain isoforms immunolabelling), the fibre type‐specific content of mitochondria (by quantifying the succinate dehydrogenase stain intensity), and the fibre type‐specific lipid content (by quantifying the Oil Red O stain intensity). Results Only 65 + SED and 65 + PF displayed significantly lower overall and type IIa fibre sizes vs. YA. 65 + SED displayed a lower type IIa fibre proportion vs. YA. MA‐SED and 65 + SED displayed a higher hybrid type IIa/IIx fibre proportion vs. YA. Sedentary and pre‐frail, but not active, men displayed lower mitochondrial content irrespective of fibre type vs. YA. 65 + SED, but not 65 + ACT, displayed a higher lipid content in type I fibres vs. YA. Finally, mitochondrial content, but not lipid content, was positively correlated with indices of muscle function, functional capacity, and insulin sensitivity across all subjects. Conclusions Taken altogether, our results indicate that ageing in sedentary men is associated with (i) complex changes in muscle phenotype preferentially affecting type IIa fibres; (ii) a decline in mitochondrial content affecting all fibre types; and (iii) an increase in lipid content in type I fibres. They also indicate that physical activity partially protects from the effects of ageing on muscle phenotype, mitochondrial content, and lipid accumulation. No skeletal specific muscle phenotype of pre‐frailty was observed.

Background: Phytochemicals are natural compounds synthesized as secondary metabolites in plants and represent an important source of molecules with therapeutic applications. Attention is accorded to their potential in anti-cancer therapies as single agents or adjuvant treatment. Herby, we evaluated the in vitro effects of a panel of natural compounds with focus on caffeic acid phenethyl ester (CAPE) and Kaempferol for the treatment of human colon cancer. Methods: We exposed two human colon cancer cell lines, RKO and HCT-116, followed by functional examination of cell viability, cell proliferation and invasion, cell cycle, apoptosis, and autophagy. Modifications in gene expression were investigated through microarray and detection of existing mutations and finding of new ones was done with the help of Next Generation Sequencing (NGS). Results: Both CAPE and Kaempferol inhibit cell proliferation, motility and invasion, and stimulate apoptosis and autophagy, concomitant with modifications in coding and noncoding genes&rsquo, expression. Moreover, there are pathogenic mutations that are no longer found upon treatment with CAPE and Kaempferol. Conclusions: Our findings indicate that CAPE and Kaempferol have the ability to negatively influence the development and advancement of colon cancer in vitro by specifically altering the cells at the molecular level, this activity can be exploited in possible adjuvant therapies once the optimal dose concentration with minimal side effects but with cancer inhibitory activity is set in vivo.

Traumatic brain injury (TBI) is a complex injury that is hard to predict and diagnose, with many studies focused on associating head kinematics to brain injury risk. Recently, there has been a push towards using computationally expensive finite element (FE) models of the brain to create tissue deformation metrics of brain injury. Here, we developed a 3 degree-of-freedom lumped-parameter brain model, built based on the measured natural frequencies of a FE brain model simulated with live human impact data, to be used to rapidly estimate peak brain strains experienced during head rotational accelerations. On our dataset, the simplified model correlates with peak principal FE strain by an R2 of 0.80. Further, coronal and axial model displacement correlated with fiber-oriented peak strain in the corpus callosum with an R2 of 0.77. Using the maximum displacement predicted by our brain model, we propose an injury criteria and compare it against a number of existing rotational and translational kinematic injury metrics on a dataset of head kinematics from 27 clinically diagnosed injuries and 887 non-injuries. We found that our proposed metric performed comparably to peak angular acceleration, linear acceleration, and angular velocity in classifying injury and non-injury events. Metrics which separated time traces into their directional components had improved deviance to those which combined components into a single time trace magnitude. Our brain model can be used in future work as a computationally efficient alternative to FE models for classifying injuries over a wide range of loading conditions., Comment: 10 figures, 3 tables

peer-reviewed H.D.D., A.J.C., P.J.B. and B.J.H. would like to acknowledge the Dairy Futures Cooperative Research Centre for funding. H.P. and R.F. acknowledge funding from the German Federal Ministry of Education and Research (BMBF) within the AgroClustEr ‘Synbreed—Synergistic Plant and Animal Breeding’ (grant 0315527B). H.P., R.F., R.E. and K.-U.G. acknowledge the Arbeitsgemeinschaft Süddeutscher Rinderzüchter, the Arbeitsgemeinschaft Österreichischer Fleckviehzüchter and ZuchtData EDV Dienstleistungen for providing genotype data. A. Bagnato acknowledges the European Union (EU) Collaborative Project LowInputBreeds (grant agreement 222623) for providing Brown Swiss genotypes. Braunvieh Schweiz is acknowledged for providing Brown Swiss phenotypes. H.P. and R.F. acknowledge the German Holstein Association (DHV) and the Confederación de Asociaciones de Frisona Española (CONCAFE) for sharing genotype data. H.P. was financially supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (DFG) (grant PA 2789/1-1). D.B. and D.C.P. acknowledge funding from the Research Stimulus Fund (11/S/112) and Science Foundation Ireland (14/IA/2576). M.S. and F.S.S. acknowledge the Canadian Dairy Network (CDN) for providing the Holstein genotypes. P.S. acknowledges funding from the Genome Canada project entitled ‘Whole Genome Selection through Genome Wide Imputation in Beef Cattle’ and acknowledges WestGrid and Compute/Calcul Canada for providing computing resources. J.F.T. was supported by the National Institute of Food and Agriculture, US Department of Agriculture, under awards 2013-68004-20364 and 2015-67015-23183. A. Bagnato, F.P., M.D. and J.W. acknowledge EU Collaborative Project Quantomics (grant 516 agreement 222664) for providing Brown Swiss and Finnish Ayrshire sequences and genotypes. A.C.B. and R.F.V. acknowledge funding from the public–private partnership ‘Breed4Food’ (code BO-22.04-011- 001-ASG-LR) and EU FP7 IRSES SEQSEL (grant 317697). A.C.B. and R.F.V. acknowledge CRV (Arnhem, the Netherlands) for providing data on Dutch and New Zealand Holstein and Jersey bulls. Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10−8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP–seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.

International audience; Double strand breaks (DSBs) are one of the most toxic lesions to cells. DSB repair by the canonical non-homologous end-joining (C-EJ) pathway involves minor, if any, processing of the broken DNA-ends, whereas the initiation of DNA resection channels the broken-ends toward DNA repair pathways using various lengths of homology. Mechanisms that control the resection initiation are thus central to the regulation to the choice of DSB repair pathway. Therefore, understanding the mechanisms which regulate the initiation of DNA end-resection is of prime importance. Our findings reveal that poly(ADP-ribose) polymerase 2 (PARP2) is involved in DSBR pathway choice independently of its PAR synthesis activity. We show that PARP2 favors repair by homologous recombination (HR), single strand annealing (SSA) and alternative-end joining (A-EJ) rather than the C-EJ pathway and increases the deletion sizes at A-EJ junctions. We demonstrate that PARP2 specifically limits the accumulation of the resection barrier factor 53BP1 at DNA damage sites, allowing efficient CtIP-dependent DNA end-resection. Collectively, we have identified a new PARP2 function, independent of its PAR synthesis activity, which directs DSBs toward resection-dependent repair pathways.

DNA double-strand breaks (DSBs) are highly toxic lesions that can lead to profound genome rearrangements and/or cell death. They routinely occur in genomes due to endogenous or exogenous stresses. Efficient repair systems, canonical non-homologous end-joining and homologous recombination exist in the cell and not only ensure the maintenance of genome integrity but also, via specific programmed DNA double-strand breaks, permit its diversity and plasticity. However, these repair systems need to be tightly controlled because they can also generate genomic rearrangements. Thus, when DSB repair is not properly regulated, genome integrity is no longer guaranteed. In this review, we will focus on non-programmed genome rearrangements generated by DSB repair, in somatic cells. We first discuss genome rearrangements induced by homologous recombination and end-joining. We then discuss recently described rearrangement mechanisms, driven by microhomologies, that do not involve the joining of DNA ends but rather initiate DNA synthesis (microhomology-mediated break-induced replication, fork stalling and template switching and microhomology-mediated template switching). Finally, we discuss chromothripsis, which is the shattering of a localized region of the genome followed by erratic rejoining.

The repair of toxic double-strand breaks (DSB) is critical for the maintenance of genome integrity. The major mechanisms that cope with DSB are: homologous recombination (HR) and classical or alternative nonhomologous end joining (C-NHEJ versus A-EJ). Because these pathways compete for the repair of DSB, the choice of the appropriate repair pathway is pivotal. Among the mechanisms that influence this choice, deoxyribonucleic acid (DNA) end resection plays a critical role by driving cells to HR, while accurate C-NHEJ is suppressed. Furthermore, end resection promotes error-prone A-EJ. Increasing evidence define Poly(ADP-ribose) polymerase 3 (PARP3, also known as ARTD3) as an important player in cellular response to DSB. In this work, we reveal a specific feature of PARP3 that together with Ku80 limits DNA end resection and thereby helps in making the choice between HR and NHEJ pathways. PARP3 interacts with and PARylates Ku70/Ku80. The depletion of PARP3 impairs the recruitment of YFP-Ku80 to laser-induced DNA damage sites and induces an imbalance between BRCA1 and 53BP1. Both events result in compromised accurate C-NHEJ and a concomitant increase in DNA end resection. Nevertheless, HR is significantly reduced upon PARP3 silencing while the enhanced end resection causes mutagenic deletions during A-EJ. As a result, the absence of PARP3 confers hypersensitivity to anti-tumoral drugs generating DSB.

Mitochondrial dysfunction is implicated in skeletal muscle atrophy and dysfunction with aging, with strong support for an increased mitochondrial-mediated apoptosis in sedentary rodent models. Whether this applies to aged human muscle is unknown, nor is it clear whether these changes are caused by sedentary behavior. Thus, we examined mitochondrial function [respiration, reactive oxygen species (ROS) emission, and calcium retention capacity (CRC)] in permeabilized myofibers obtained from vastus lateralis muscle biopsies of healthy physically active young (23.7±2.7 yr; mean±SD) and older (71.2±4.9 yr) men. Although mitochondrial ROS and maximal respiratory capacity were unaffected, the acceptor control ratio was reduced by 18% with aging, suggesting mild uncoupling of oxidative phosphorylation. CRC was reduced by 50% with aging, indicating sensitization of the mitochondrial permeability transition pore (mPTP) to apoptosis. Consistent with the mPTP sensitization, older muscles showed a 3-fold greater fraction of endonuclease G (a mitochondrial proapoptotic factor)-positive myonuclei. Aged muscles also had lower mitophagic potential, based on a 43% reduction in Parkin to the voltage-dependent anion channel (VDAC) protein ratio. Collectively, these results show that mitochondrial-mediated apoptotic signaling is increased in older human muscle and suggest that accumulation of dysfunctional mitochondria with exaggerated apoptotic sensitivity is due to impaired mitophagy.

The purpose of the present study was to examine the relationship between two different levels of protein intake (0.8 vs.1.2 g/kg body weight/day) with muscle mass and muscle strength.Seventy-two postmenopausal women were recruited. Body composition (bioelectrical impedance analysis), muscle strength (dynamometer), energy metabolism (indirect calorimetry) and dietary intake (dietary journal) were measured. We divided the women into two groups. Women with a protein intake of ≥ 1.2 g/kg body weight/day were placed in the Protein ≥ 1.2 group (n = 35), whereas women with a protein intake of 0.8-1.19 g/kg body weight/day were categorized in the Protein 0.8-1.19 group (n = 32).No significant difference was observed between groups for age, height, skeletal muscle mass, resting energy expenditure, total energy expenditure, carbohydrate and lipid intake. Significant differences between groups were observed for body mass index (p0.001), fat mass (p0.001) and muscle strength (hand grip and knee extensors) (p0.001). More specifically, the Protein ≥ 1.2 group presented a higher muscle strength as well as a lower body mass index and fat mass compared to the Protein 0.8-1.19 group. In addition, the group with a protein intake of ≥ 1.2 g/kg body weight/day presented significantly higher energy intake (p = 0.002), and essential (p0.001) and non-essential (p0.001) amino acid intake. Interestingly, when muscle strength was adjusted for essential or non-essential amino acids, differences in muscle strength persisted.The present study indicates higher levels of muscle strength in postmenopausal women with a protein intake of ≥ 1.2 g/kg body weight/day compared to 0.8-1.19 g/kg body weight/day despite no differences in muscle mass.

SummaryThe choice of the appropriate double-strand break (DSB) repair pathway is essential for the maintenance of genomic stability. Here, we show that the Bloom syndrome gene product, BLM, counteracts CtIP/MRE11-dependent long-range deletions (>200 bp) generated by alternative end-joining (A-EJ). BLM represses A-EJ in an epistatic manner with 53BP1 and RIF1 and is required for ionizing-radiation-induced 53BP1 focus assembly. Conversely, in the absence of 53BP1 or RIF1, BLM promotes formation of A-EJ long deletions, consistent with a role for BLM in DSB end resection. These data highlight a dual role for BLM that influences the DSB repair pathway choice: (1) protection against CtIP/MRE11 long-range deletions associated with A-EJ and (2) promotion of DNA resection. These antagonist roles can be regulated, according to cell-cycle stage, by interacting partners such as 53BP1 and TopIII, to avoid unscheduled resection that might jeopardize genome integrity.

Diabetes is associated with impaired glucose metabolism in the presence of excess insulin. Glucose and fatty acids provide reducing equivalents to mitochondria to generate energy, and studies have reported mitochondrial dysfunction in type II diabetes patients. If mitochondrial dysfunction can cause diabetes, then we hypothesized that increased mitochondrial metabolism should render animals resistant to diabetes. This was confirmed in mice in which the heart-muscle-brain adenine nucleotide translocator isoform 1 (ANT1) was inactivated. ANT1-deficient animals are insulin-hypersensitive, glucose-tolerant, and resistant to high fat diet (HFD)-induced toxicity. In ANT1-deficient skeletal muscle, mitochondrial gene expression is induced in association with the hyperproliferation of mitochondria. The ANT1-deficient muscle mitochondria produce excess reactive oxygen species (ROS) and are partially uncoupled. Hence, the muscle respiration under nonphosphorylating conditions is increased. Muscle transcriptome analysis revealed the induction of mitochondrial biogenesis, down-regulation of diabetes-related genes, and increased expression of the genes encoding the myokines FGF21 and GDF15. However, FGF21 was not elevated in serum, and FGF21 and UCP1 mRNAs were not induced in liver or brown adipose tissue (BAT). Hence, increased oxidation of dietary-reducing equivalents by elevated muscle mitochondrial respiration appears to be the mechanism by which ANT1-deficient mice prevent diabetes, demonstrating that the rate of mitochondrial oxidation of calories is important in the etiology of metabolic disease.

Fundamental physics and numerous field studies have shown a higher injury and fatality risk for occupants in smaller and lighter vehicles when struck by heavier, taller and higher vehicles. The consensus is that the significant parameters influencing compatibility in front-to-side crashes are geometric interaction, vehicle stiffness, and vehicle mass. The objective of this research is to develop a concept of deployable bumper and grille airbags for improved vehicle compatibility in side impact. The external airbags, deployed upon signals from sensors, may help mitigate the effect of weight, geometry and stiffness differences and reduce side intrusions. However, a highly reliable pre-crash sensing system is required to enable the reliable deployment, which is currently not technologically feasible.Analytical and numerical methods and hardware testing were used to help develop the deployable external airbags concept. Various Finite Element (FE) models at different stages were developed and an extensive number of iterations were conducted to help optimize airbag and inflator parameters to achieve desired targets. The concept development was executed and validated in two phases. This paper covers Phase II ONLY, which includes: (1) Re-design of the airbag geometry, pressure, and deployment strategies; (2) Further validation using a Via sled test of a 48 kph perpendicular side impact of an SUV-type impactor against a stationary car with US-SID-H3 crash dummy in the struck side; (3) Design of the reaction surface necessary for the bumper airbag functionality. The concept was demonstrated through live deployment of external airbags with a reaction surface in a full-scale perpendicular side impact of an SUV against a stationary passenger car at 48 kph. This research investigated only the concept of the inflatable devices since pre-crash sensing development was beyond the scope of this research.The concept design parameters of the bumper and grille airbags are presented in this paper. Full vehicle-to-vehicle crash test results, Via sled test, and simulation results are also presented. Head peak acceleration, Head Injury Criteria (HIC), Thoracic Trauma Index (TTI), and Pelvic acceleration for the SID-H3 dummy and structural intrusion profiles were used as performance metrics for the bumper and grille airbags. Results obtained from the Via sled tests and the full vehicle-to-vehicle tests with bumper and grille airbags were compared to those of baseline test results with no external airbags.

DNA double-strand breaks (DSB) are very harmful lesions that can generate genome rearrangements. In this study, we used intrachromosomal reporters to compare both the efficiency and accuracy of end-joining occurring with close (34 bp apart) vs. distant DSBs (3200 bp apart) in human fibroblasts. We showed that a few kb between two intrachromosomal I-SceI-induced DSBs are sufficient to foster deletions and capture/insertions at the junction scar. Captured sequences are mostly coupled to deletions and can be partial duplications of the reporter (i.e., sequences adjacent to the DSB) or insertions of ectopic chromosomal sequences (ECS). Interestingly, silencing 53BP1 stimulates capture/insertions with distant but not with close double-strand ends (DSEs), although deletions were stimulated in both case. This shows that 53BP1 protects both close and distant DSEs from degradation and that the association of unprotection with distance between DSEs favors ECS capture. Reciprocally, silencing CtIP lessens ECS capture both in control and 53BP1-depleted cells. We propose that close ends are immediately/rapidly tethered and ligated, whereas distant ends first require synapsis of the distant DSEs prior to ligation. This "spatio-temporal" gap gives time and space for CtIP to initiate DNA resection, suggesting an involvement of single-stranded DNA tails for ECS capture. We therefore speculate that the resulting single-stranded DNA copies ECS through microhomology-mediated template switching., Author Summary A DNA double-strand break is a very toxic lesion that can be repaired by rejoining DNA ends. This repair process can have deleterious consequences on the genome by joining DNA ends that were not originally fused (translocations) or modifying the DNA sequence with deletions or insertions. Here, we show that rejoining distant ends (only a few kb apart) favors error-prone repair characterized by deletion of the original sequences and also favors insertions of ectopic chromosomal sequences. These insertions are coupled to error-prone repair, i.e., deletion of the original sequence, initiated by the nuclease CtIP. Interestingly, favoring deletions by removal of the protection factor 53BP1 is not sufficient to efficiently promote insertions of ectopic sequences when the DNA ends are close. Therefore, the association of both unprotection and distance between DNA ends favors insertion of ectopic chromosomal sequences. The requirement of CtIP that generates single-strand DNA suggests that the generation of single-strand DNA favors insertions of ectopic sequences by microhomology-mediated template switching.

DNA double-strand break (DSB) repair is essential for genome stability maintenance, but the joining of distant DNA double strand ends (DSEs) inevitably leads to genome rearrangements. Therefore, DSB repair should be tightly controlled to secure genome stability while allowing genetic variability. Tethering of the proximal ends of a 2-ended DSB limits their mobility, protecting thus against their joining with a distant DSE. However, replication stress generates DSBs with only one DSE, on which tethering is impossible. Consistently, we demonstrated that the joining of 2 DSBs only 3.2 kb apart is repressed in the S, but not the G1, phase, revealing an additional mechanism limiting DNA ends mobility in S phase. The cohesin complex, by maintaining the 2 sister chromatids linked, limits DSEs mobility and thus represses the joining of distant DSEs, while allowing that of adjacent DSEs. At the genome scale, the cohesin complex protects against deletions, inversions, translocations and chromosome fusion.

BACKGROUND Muscle mass index has long been used as a useful index to evaluate the risks of developing functional impairments. However, there is evidence that other indexes (particularly muscle strength-based indexes) may be more relevant. Thus, the purpose of this study was to compare the association between different indexes of muscle mass or strength with self-reported and measured functional performance to determine which index would be clinically relevant to detect individuals at risk of functional impairments. METHODS Data are from 1,462 women aged 75 years and older recruited in the Toulouse EPIDemiologie de l'OSteoporose cohort. Body composition (assessed by dual energy x-ray absorptiometry), handgrip, and knee extension strength were assessed. Physical function was measured using the chair stand test as well as the usual and fast gait speed tests. Participants were also asked if they experienced any difficulty at performing functional tasks. RESULTS Results showed that knee extension strength relative to body weight was the strongest correlate of physical function measures (.30 < r < .40). Women in the lowest quartile of knee extension strength relative to body weight were 5.9-, 24.7-, 12.1-, and 20.9-fold, respectively, more likely to present impairments at self-reported activities, chair stand test, and usual and fast gait speed compared with women in the highest quartile, respectively. CONCLUSIONS Knee extension strength relative to body weight appears to be well associated with self-reported difficulties and functional impairments. A threshold between 2.78 and 2.86 (knee extension strength [kPa]/body weight [kg]), determined using receiver operating characteristics curves analysis, may be a potential cut point to discriminate women presenting higher functional impairments.

The purpose of this study was to investigate the relationship between protein intake and dynapenia.A cross-sectional/observational study.Department of Kinanthropology at the University of Quebec at Montreal.Seventy-two non-frail postmenopausal women aged between 50 to 75 years were recruited.Body weight (BW), lean body mass (LBM; %) and skeletal muscle mass (bio-electrical impedancemetry analysis), maximum voluntary handgrip strength (using hand dynamometer), aerobic capacity (VO2peak) and dietary intake were measured. Women were divided according to dynapenia criteria.The strongest correlation between muscle strength and protein intake was observed when we express the amount of protein in g/d/BW. No differences for age, BMI, status of menopause, fat mass and VO2peak were observed between non-dynapenic, type I dynapenic and type II dynapenic women, independently of the criteria used. We observed significant differences in protein intake (g/d/BW) between non-dynapenic and type II dynapenic (p0.01) as well as between type I dynapenic and type II dynapenic (p0.01) when dynapenia was expressed in kg/BW and in kg/LBM, respectively. It should be noted that no differences in LBM between the three groups were observed when dynapenia was expressed in kg/BW and kg/LBM. Protein intake for all groups respected the RDA of 0.8 to 1.2 g/d/BW (non-dynapenic: 1.44/1.38; type I dynapenic: 1.30/1.33; type II dynapenic: 1.05/1.08 g/d/BW).Protein intake seems to play a role in the development of dynapenia particularly at the level of type II dynapenia. Therefore, an increase in the recommended daily allowance for protein intake may be warranted.

The purpose of the present study was to examine the relationship between long sleep duration and functional capacities.We conducted a cross-sectional study at the Department of Kinanthropology at the University of Quebec at Montreal. Forty eight non-frail postmenopausal women aged between 49 to 75 years were recruited using advertisements in local papers. Body weight, body mass index, fat mass, skeletal muscle mass, number of steps per day, SF-36 total (healthy questionnaire), resting metabolic rate, total energy intake, sleep duration, knee extensor strength (dynamometer), chair stand test and balance opened eyes test were measured.WE FOUND A SIGNIFICANT NEGATIVE CORRELATION BETWEEN HOURS OF SLEEP AND FUNCTIONAL CAPACITY: chair stand test (r = -0.33, p = 0.02), balance opened eyes test (r = -0.45, p = 0.001), muscle strength (r = -0.43, p = 0.002) and skeletal muscle mass (r = -0.39, p = 0.007). In addition, long sleepers (9 h) had significantly lower values for skeletal muscle mass (p = 0.03), muscle strength (p = 0.01), chair stand test (p = 0.03), and balance opened eyes test (p = 0.001). Finally, linear regression analysis showed that sleep duration was an independent predictor of the chair stand test (p = 0.024), balance opened eyes test (p = 0.001), and muscle strength (p = 0.035) in our cohort.Long sleepers were associated with lower functional capacities in our cohort of sedentary postmenopausal women.

Obesity has been associated with metabolic complications. However, two subgroups of obese individuals (namely "sarcopenic obese" and "metabolically healthy but obese" individuals) with low muscle mass appear to have a better metabolic profile. Despite having a lower muscle mass, these individuals appear to have higher muscle strength, suggesting higher muscle quality. Studies have reported insulin sensitivity to be related to muscle quality. Therefore, the aim of the present study was to test the hypothesis that low muscle mass was associated with better muscle quality in obese individuals.A total of 112 postmenopausal women aged between 50 and 77 years (means, 61±6 years) were recruited. Body composition (bioelectrical impedancemetry), muscle strength (hand dynamometer), and functional capacity (chair stand test, alternate step test and balance test) were measured.Skeletal muscle mass (SM; kg) was significantly positively correlated with muscle strength (kg) in normal weight (r=0.43; P=0.003) and overweight (r=0.42; P=0.020) women, but not in obese (r=0.28; P=0.13) women. Muscle mass (kg) was significantly negatively correlated with muscle quality (kg/SMkg) in normal weight (r=-0.41, P=0.005), overweight (r=-0.59; P0.001) and obese (r=-0.59; P0.001) individuals. Skeletal muscle mass index (kg/m(2)) was significantly negatively correlated with muscle quality in normal weight (r=-0.33, P=0.025), overweight (r=-0.47, P=0.008), and obese (r=-0.43, P=0.015) women. Finally, type II sarcopenic individuals had higher muscle quality than type I sarcopenic (P=0.002) and nonsarcopenic (P=0.001) individuals.Our results support our hypothesis and showed that muscle quality increased as muscle mass and muscle mass index decreased. Thus, muscle quality may potentially explain the favorable metabolic profile observed in metabolically healthy but obese and sarcopenic obese postmenopausal women. Further studies including metabolic data are needed to confirm our results.

The purpose of the present study was to investigate the effects of a 12-week tai chi program in type I dynapenic and nondynapenic postmenopausal women.Sixty-two postmenopausal women were recruited. Body composition, handgrip strength, functional capacities, cardiorespiratory functions (forced expiratory volume in 1 s and oxygen consumption per unit time peak), and quality of life (36-item Short-Form Health Survey) were measured before and after the intervention.Type I dynapenic postmenopausal women showed a significant decrease in body weight (P = 0.004), fat mass percentage (P = 0.02), and skeletal muscle mass (SM; in kilograms; P = 0.02), whereas handgrip strength (in kilograms per SMkg; P = 0.04), functional capacity test scores (P ≤ 0.050), and general health perception (P = 0.01) significantly increased. In nondynapenic postmenopausal women, we observed a significantly decreased waist circumference (P = 0.04) and a significantly increased chair-stand test (P0.001) and one-leg stance test (P = 0.04) scores. In addition, significantly lower systolic (P ≤ 0.001) and diastolic (P ≤ 0.005) blood pressures were observed in both groups after the intervention. Finally, type I dynapenic women showed a more pronounced general health perception increase compared with nondynapenic individuals (P = 0.03).Tai chi training improved body composition, muscle strength, functional capacities, and general health perception in postmenopausal women, and this last improvement was more pronounced in type I dynapenic individuals. Therefore, tai chi may be considered as an alternative physical training method in preventing the occurrence of disabilities and frailty in postmenopausal women with type I dynapenia.

Genetic stability requires coordination of a network of pathways including DNA repair/recombination and apoptosis. In addition to its canonical anti-apoptotic role, Bcl-2 negatively impacts genome stability. In this study, we identified the breast cancer tumor suppressor BRCA1, which plays an essential role in homologous recombination (HR), as a target for Bcl-2 in the repression of HR. Indeed, ionizing radiation–induced BRCA1 foci assembly was repressed when Bcl-2 was expressed ectopically, in human SV40 fibroblasts, or spontaneously, in lymphoma t(14:18) cells and in HeLa and H460 cancer cell lines. Moreover, we showed that the transmembrane (TM) domain of Bcl-2 was required for both inhibition of BRCA1 foci assembly and the inhibition of HR induced by a double-strand break targeted into an intrachromosomal HR substrate by the meganuclease I-SceI. Fluorescence confocal microscopy, proximity ligation assay, and electron microscopy analyses as well as Western blot analysis of subcellular fractions showed that Bcl-2 and BRCA1 colocalized to mitochondria and endoplasmic reticulum in a process requiring the TM domain of Bcl-2. Targeting BRCA1 to the endomembranes depletes BRCA1 from the nucleus and, thus, accounts for the inhibition of HR. Furthermore, our findings support an apoptosis-stimulatory role for the cytosolic form of BRCA1, suggesting a new tumor suppressor function of BRCA1. Together, our results reveal a new mode of BRCA1 regulation and for HR in the maintenance of genome stability. Cancer Res; 71(10); 3590–602. ©2011 AACR.

Menopause is associated with a decline in estrogen levels, which could lead to an increase in visceral adiposity as well as a decrease in bone density, muscle mass and muscle strength. This decline in muscle mass, known as sarcopenia, is frequently observed in postmenopausal women. Potential causes of sarcopenia include age-related changes in the hormonal status, low levels of physical activity, reduced protein intake and increased oxidative stress. However, the role of sex hormones, specifically estrogens, on the onset of sarcopenia is controversial. Preventing sarcopenia and preserving muscle strength are highly relevant in order to prevent functional impairment and physical disability. To date, resistance training has been shown to be effective in attenuating age-related muscle loss and strength. However, results on the effect of hormonal supplementation to treat or prevent sarcopenia are contradictory. Further research is needed to identify other potential mechanisms of sarcopenia as well as effective interventions for the prevention and treatment of sarcopenia. Therefore, the purpose of this review will be to examine the role of sex hormonal status in the development of sarcopenia. We will also overview the physical as well as metabolic consequences of sarcopenia and the efficiency of different interventions for the prevention and treatment of sarcopenia.

A 65-year-old man with dysphagia underwent placement of a percutaneous endoscopic gastrostomy tube. He was cared for at a nursing facility where the tube became dislodged and was replaced with similar size Foley catheter. Patient was brought to the hospital with dislodged feeding Foley but none was found at the bedside. Diagnostic workup revealed antegrade migration of the catheter into the small bowel. Push enteroscopy was unsuccessful in retrieving the catheter because it was too far distal. Patient was observed for a total of 7 days. Due to lack of progress with conservative measures, a colonoscopy was performed to extract the catheter, thus avoiding the need for more invasive surgical measures. If a Foley catheter is used as a gastrostomy tube, it should be replaced with a dedicated feeding tube as quickly as possible and should always be affixed to the skin to prevent antegrade migration and associated complications.

Small disasters are usually the product of climate variability and climate change. Analysis of them illustrates that they increase difficulties for local development-frequently affecting the livelihoods of poor people and perpetuating their level of poverty and human insecurity-and entail challenges for a country's development. In contrast to extreme events, small disasters are often invisible at the national level and their effects are not considered as relevant from a macroeconomic standpoint. Nevertheless, their accumulated impact causes economic, environmental and social problems. This paper presents the results of an evaluation of the DesInventar database, developed in 1994 by the Network for Social Studies in Disaster Prevention in Latin America. In addition, it proposes a new version of the Local Disaster Index developed in 2005 within the framework of the Disaster Risk and Management Indicators Program for the Americas, with the support of the Inter-American Development Bank.