Hyperactive Rac stimulates cannibalism of living target cells and enhances CAR-M-mediated cancer cell killing.

The 21kD GTPase Rac is an evolutionarily ancient regulator of cell shape and behavior. Rac2 is predominantly expressed in hematopoietic cells where it is essential for survival and motility. The hyperactivating mutation Rac2E62K also causes human immunodeficiency, although the mechanism remains unexplained. Here, we report that in Drosophila, hyperactivating Rac stimulates ovarian cells to cannibalize neighboring cells, destroying the tissue. We then show that hyperactive Rac2E62K stimulates human HL60-derived macrophage-like cells to engulf and kill living T cell leukemia cells. Primary mouse Rac2+/E62K bone-marrow-derived macrophages also cannibalize primary Rac2+/E62K T cells due to a combination of macrophage hyperactivity and T cell hypersensitivity to engulfment. Additionally, Rac2+/E62K macrophages non-autonomously stimulate wild-type macrophages to engulf T cells. Rac2E62K also enhances engulfment of target cancer cells by chimeric antigen receptor-expressing macrophages (CAR-M) in a CAR-dependent manner. We propose that Rac-mediated cell cannibalism may contribute to Rac2+/E62K human immunodeficiency and enhance CAR-M cancer immunotherapy.

Immunodeficiency is prevalent in congenital heart disease and associated with increased risk of emergency admissions and death.

AIMS: To provide population-based data on the prevalence and clinical significance of immune deficiency syndromes (IDS) associated with congenital heart disease (CHD). METHODS AND RESULTS: Utilizing administrative German Health System data the prevalence of increased susceptibility to infection (ISI) or confirmed IDS was assessed in CHD patients and compared with an age-matched non-congenital control group. Furthermore, the prognostic significance of IDS was assessed using all-cause mortality and freedom from emergency hospital admission. A total of 54 449 CHD patients were included. Of these 14 998 (27.5%) had ISI and 3034 (5.6%) had a documented IDS (compared with 2.9% of the age-matched general population). During an observation period of 394 289 patient-years, 3824 CHD patients died, and 31 017 patients experienced a combined event of all-cause mortality or emergency admission. On multivariable Cox proportional-hazard analysis, the presence of ISI [hazard ratio (HR): 2.14, P < 0.001] or documented IDS (HR: 1.77, P = 0.035) emerged as independent predictors of all-cause mortality. In addition, ISI and confirmed IDS were associated with a significantly higher risk of emergency hospital admission (P = 0.01 for both on competing risk analysis) during follow-up. CONCLUSION: Limited immune competence is common in CHD patients and associated with an increased risk of morbidity and mortality. This highlights the need for structured IDS screening and collaboration with immunology specialists as immunodeficiency may be amenable to specific therapy. Furthermore, studies are required to assess whether IDS patients might benefit from intensified antibiotic shielding or tailored prophylaxis.

Validity and reliability of the Spanish version of the consultation and relational empathy measure in dental students (Sp-Dent-CARE): A cross-sectional study.

INTRODUCTION: An evaluation was made of the psychometric properties of a Spanish version of the Consultation and Relational Empathy Measure (CARE) to assess relational empathy in undergraduate dental students. In addition, the influence of demographic, socio-economic and consultation-related factors upon the degree of perceived empathy and overall satisfaction was studied. MATERIALS AND METHODS: A cross-sectional study was carried out in patients seen in the Oral Surgery Unit by fourth year dental students. Dentists, specialized translators and psychologists developed the translation of the questionnaire. After a pilot test, a convenience sample of patients was included. Construct validity was tested by factor analysis using principal component analysis with varimax rotation and Kaiser standardization, and internal consistency was assessed by Cronbach's α. RESULTS: Two pilot tests were carried out with a panel of experts until the final version of the questionnaire was established. In the validation stage, 191 patients participated (92 men and 99 women), with a mean age of 52.5 ± 17 years. The mean score of the CARE measure was 47.2 ± 4.4, and 57.6% of the patients (n = 110) reported the maximum score on the questionnaire. The final version showed a 1-factor solution explaining 68.6% of the total variance, with excellent final internal consistency (α = 93.4%). CONCLUSION: The Spanish version of the CARE measure affords high reliability and validity in assessing relational empathy in dental students. Perceived empathy is related to overall satisfaction. Patient demographics and the number of visits do not influence perceived empathy.

Upscaling the effect of traits in response to drought: The relative importance of safety-efficiency and acquisitive-conservation functional axes.

We tested the idea that functional trade-offs that underlie species tolerance to drought-driven shifts in community composition via their effects on demographic processes and subsequently on shifts in species' abundance. Using data from 298 tree species from tropical dry forests during the extreme ENSO-2015, we scaled-up the effects of trait trade-offs from individuals to communities. Conservative wood and leaf traits favoured slow tree growth, increased tree survival and positively impacted species abundance and dominance at the community-level. Safe hydraulic traits, on the other hand, were related to demography but did not affect species abundance and communities. The persistent effects of the conservative-acquisitive trade-off across organizational levels is promising for generalization and predictability of tree communities. However, the safety-efficient trade-off showed more intricate effects on performance. Our results demonstrated the complex pathways in which traits scale up to communities, highlighting the importance of considering a wide range of traits and performance processes.

Reciprocal YAP1 loss and INSM1 expression in neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a rare but aggressive histologic variant of prostate cancer that responds poorly to androgen deprivation therapy. Hybrid NEPC-adenocarcinoma (AdCa) tumors are common, often eluding accurate pathologic diagnosis and requiring ancillary markers for classification. We recently performed an outlier-based meta-analysis across a number of independent gene expression microarray datasets to identify novel markers that differentiate NEPC from AdCa, including up-regulation of insulinoma-associated protein 1 (INSM1) and loss of Yes-associated protein 1 (YAP1). Here, using diverse cancer gene expression datasets, we show that Hippo pathway-related genes, including YAP1, are among the top down-regulated gene sets with expression of the neuroendocrine transcription factors, including INSM1. In prostate cancer cell lines, transgenic mouse models, and human prostate tumor cohorts, we confirm that YAP1 RNA and YAP1 protein expression are silenced in NEPC and demonstrate that the inverse correlation of INSM1 and YAP1 expression helps to distinguish AdCa from NEPC. Mechanistically, we find that YAP1 loss in NEPC may help to maintain INSM1 expression in prostate cancer cell lines and we further demonstrate that YAP1 silencing likely occurs epigenetically, via CpG hypermethylation near its transcriptional start site. Taken together, these data nominate two additional markers to distinguish NEPC from AdCa and add to data from other tumor types suggesting that Hippo signaling is tightly reciprocally regulated with neuroendocrine transcription factor expression. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Maternal and neonatal complications in women with congenital heart disease: a nationwide analysis.

AIMS: The aim of this study was to provide population-based data on maternal and neonatal complications and outcome in the pregnancies of women with congenital heart disease (CHD). METHODS AND RESULTS: Based on administrative data from one of the largest German Health Insurance Companies (BARMER GEK, ∼9 million members representative for Germany), all pregnancies in women with CHD between 2005 and 2018 were analysed. In addition, an age-matched non-CHD control group was included for comparison and the association between adult CHD (ACHD) and maternal or neonatal outcomes investigated. Overall, 7512 pregnancies occurred in 4015 women with CHD. The matched non-CHD control group included 6502 women with 11 225 pregnancies. Caesarean deliveries were more common in CHD patients (40.5% vs. 31.5% in the control group; P < 0.001). There was no excess mortality. Although the maternal complication rate was low in absolute terms, women with CHD had a significantly higher rate of stroke, heart failure and cardiac arrhythmias during pregnancy (P < 0.001 for all). Neonatal mortality was low but also significantly higher in the ACHD group (0.83% vs. 0.22%; P = 0.001) and neonates to CHD mothers had low/extremely low birth weight or extreme immaturity (<0.001) or required resuscitation and mechanical ventilation more often compared to non-CHD offspring (P < 0.001 for both). On multivariate logistic regression maternal defect complexity, arterial hypertension, heart failure, prior fertility treatment, and anticoagulation with vitamin K antagonists emerged as significant predictors of adverse neonatal outcome (P < 0.05 for all). Recurrence of CHD was 6.1 times higher in infants to ACHD mothers compared to controls (P < 0.0001). CONCLUSIONS: This population-based study illustrates a reassuringly low maternal mortality rate in a highly developed healthcare system. Nevertheless, maternal morbidity and neonatal morbidity/mortality were significantly increased in women with ACHD and their offspring compared to non-ACHD controls highlighting the need of specialized care and pre-pregnancy counselling.

Lack of specialist care is associated with increased morbidity and mortality in adult congenital heart disease: a population-based study.

AIMS: The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population. METHODS AND RESULTS: Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (<70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67-0.98; P = 0.03) or major events (HR 0.85, 95% CI 0.78-0.92; P < 0.001) compared to those only followed by PCPs. At 3-year follow-up, the absolute risk difference for mortality was 0.9% higher in ACHD patients with moderate/severe complexity lesions cared by PCPs compared to those under cardiology follow-up. CONCLUSION: Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care.

Diverging functional strategies but high sensitivity to an extreme drought in tropical dry forests.

Extreme drought events have negative effects on forest diversity and functioning. At the species level, however, these effects are still unclear, as species vary in their response to drought through specific functional trait combinations. We used long-term demographic records of 21,821 trees and extensive databases of traits to understand the responses of 338 tropical dry forests tree species to ENSO2015 , the driest event in decades in Northern South America. Functional differences between species were related to the hydraulic safety-efficiency trade-off, but unexpectedly, dominant species were characterised by high investment in leaf and wood tissues regardless of their leaf phenological habit. Despite broad functional trait combinations, tree mortality was more widespread in the functional space than tree growth, where less adapted species showed more negative net biomass balances. Our results suggest that if dry conditions increase in this ecosystem, ecological functionality and biomass gain would be reduced.

Influence of incision on periodontal parameters after apical surgery: a meta-analysis.

INTRODUCTION: The aim of the present meta-analysis was to determine the effect of the different incision designs used in apical surgery on periodontal parameters. METHODS: An electronic search in Cochrane Library, Pubmed (MEDLINE), and Scopus was conducted on April 2020. Two independent investigators included clinical trials and prospective cohort studies comparing the influence of different incision designs used in apical surgery on gingival recession, periodontal probing depth, and clinical attachment level. A pairwise and network meta-analysis was performed in order to meta-analyze the direct and the indirect comparisons among the incision designs. RESULTS: Six articles were included for the qualitative and the quantitative syntheses, involving a total of 401 teeth (372 patients). The pairwise meta-analysis did not reveal statistically significant differences between the incision designs in any of the outcomes evaluated. However, to reduce the amount of buccal gingival recession, the papilla base incision presented the highest probabilities of being ranked the most effective incision (85.7%), followed by submarginal incision (50.0%) and intrasulcular incision (14.3%). CONCLUSION: Regardless of the incision design used, the periodontal parameters did not statistically differ after apical surgery. CLINICAL RELEVANCE: Periodontal parameters did not significantly change despite the incision used in apical surgery. However, based on the results of the present review, the papilla base incision seems to be the best option to reduce the amount of buccal gingival recession.

Afrocolombian Struggles for Food, Land, and Culture: The Case of El Tiple.

El Tiple is one of many marginalized Afrodescendant communities confined within a green desert located in the southwest region of Colombia. This green desert is most widely known as the second-largest sugarcane monoculture field in the Americas. Herein, we describe a transdisciplinary and participatory effort to understand agroindustrial expansion in the region through the lens of the El Tiple community. Using qualitative and quantitative methodologies, we characterized the socioenvironmental context of El Tiple in terms of ethnography, autoethnography, social cartography, and ethnobotany. We implemented a participatory approach to codevelop a technology-assisted strategy for strengthening the community's small-scale farming activities. Our contextual analysis results show systemic food dispossession, which arises from several factors, including dramatic land transformation, rapid depletion and contamination of natural assets, and biodiversity loss. All these factors are associated with the presence of bordering sugarcane plantations. In collaboration with community members, we designed, constructed, and analyzed a greenhouse hydroponic cultivation system as an actionable means to gradually restore local production of food and medicinal plants for the community. Our transdisciplinary and participatory approach demonstrates how academics can partner with vulnerable communities in the coproduction of knowledge and solutions to pressing social needs.

Mechanical complications of implant-supported complete-arch restorations and impact on patient quality of life: A retrospective cohort study.

STATEMENT OF PROBLEM: Mechanical complications (for example, fractures) in implant-supported complete-arch restorations may affect the social and professional activities of the patient. However, most studies seem to overlook patient perceptions and generally do not assess the changes in the quality of life (QoL) of patients who experience these complications. PURPOSE: The purpose of this retrospective cohort study was to assess the influence of technical or mechanical complications of complete-arch implant-supported prostheses on patient perception and QoL by using the Oral Health Impact Profile (OHIP)-14. MATERIAL AND METHODS: A retrospective cohort study was formed of patients treated consecutively at a private clinic with immediately loaded complete-arch prostheses supported by a minimum of 4 implants (Replace Tapered; Nobel Biocare AB) and Multi-Unit conical abutments (Multi-Unit abutments; Nobel Biocare AB). OHIP-14 and questions regarding self-reported satisfaction were used to evaluate the influence of mechanical complications on QoL. RESULTS: Fifty-six participants (26 men and 30 women) with a mean age of 64 ±11.1 years, and 72 restored arches were included. The mean ±standard deviation follow-up time was 52 ±26 months. The prosthetic success rate was 38.8%, and the survival rate was 100% (no failure was registered). The most common complications were abutment screw loosening (43%), chipping or fracture of the veneering material (25%), and screw loosening (21%). The OHIP-14 scores were close to zero, without differences between participants with or without mechanical complications. Overall, the participants reported that the prostheses allowed good oral hygiene (94.6%) and met their expectations (89%) and that they would repeat the treatment (87.5%) and would recommend it to others (93%). CONCLUSIONS: Minor mechanical complications such as screw loosening and chipping or fracture of the veneering material were frequent events but had no impact on the satisfaction and QoL of patients with immediately loaded complete-arch implant-supported prostheses.

Effect of an Informative Video on Anxiety and Hemodynamic Parameters in Patients Requiring Mandibular Third Molar Extraction: A Randomized Clinical Trial.

PURPOSE: The purpose was to determine the effect of watching an informative video about mandibular third molar (M3M) removal on patient anxiety and hemodynamic parameters. PATIENTS AND METHODS: A randomized controlled clinical trial was carried out in healthy patients (aged between 18 and 40 years) requiring M3M extraction under local anesthesia. Patients with previous tooth extractions, psychiatric disorders, or cardiac problems or patients undergoing anxiolytic or antidepressant drug treatment were excluded. Participants were randomized into 2 groups according to whether they watched an informative video about the surgical procedure (video group) or not (control group). The primary outcome variable was the difference between groups regarding patient anxiety assessed with the State-Trait Anxiety Inventory (STAI) and the Modified Dental Anxiety Scale (MDAS). The secondary outcome variables were hemodynamic parameters recorded during different moments of the surgical procedure. Descriptive, bivariate, and multivariate analyses were performed, and a repeated-measures mixed model was generated. Statistical significance was considered for P < .05. RESULTS: Fifty patients referred for M3M extraction met the inclusion criteria. The final data analysis was based on 47 patients: 25 from the video group and 22 controls. The bivariate analysis showed the video group to have a significant decrease in anxiety as measured by the MDAS (P = .006; 95% confidence interval [CI], -4.1 to -0.7) and STAI-State (P = .003; 95% CI, -13.7 to -0.7). A significantly lower heart rate was likewise found in the video group (χ2 = 4.30, df = 1, P = .038). The linear regression analysis adjusting for the STAI-Trait also showed lower dental anxiety measured by the MDAS in the video group (P = .023; 95% CI, 0.32 to 4.14). CONCLUSIONS: Providing preoperative information through an informative video about M3M removal significantly reduces patient anxiety and heart rate during the surgical procedure.

Torsion Resistance of the Ball Head System Screw and Screwdriver for Angled Screw Channels on Implant Prosthetics.

The primary objective of this study was to determine the torsion resistance of the Ball Head System (BHS) screw and screwdriver set at 0°, 20°, and 30° angulations. The secondary objective was to compare the BHS set with the 1.3-mm hexagonal screwdriver system (HexS) at 20° and analyze the condition of the BHS after 10 and 30 iterations with 30 N·cm torque at 30° angulation. A workbench made from type 4 plaster with 6 steel implant replicas (external hexagon, 4.1 mm) inserted at 0°, 20°, and 30° angulation was designed. An analogical torque meter was used. The deformations produced on the whole set were examined by field emission scanning electron microscopy. A descriptive analysis was performed. The maximum torque performance for BHS at 30° angulation was 54 ± 12 N·cm. Most screws could be removed despite the deformations produced. At 20° angulation, the BHS set achieved an average torque resistance of 67 ± 12 N·cm, whereas the HexS failed at 45 ± 2 N·cm. Although the iterations performed at 30 N·cm torque and 20° angulation produced some deformations on BHS sets; these could be tightened and unscrewed. The BHS allows tightening at a torque of up to 54 N·cm. Under the same conditions, BHS showed more torque resistance than HexS. Deformation of BHS sets was directly related to the number of iterations.

Does Mandibular Gonial Angle Predict Difficulty of Mandibular Third Molar Removal?

PURPOSE: Predicting the difficulty of impacted mandibular third molar (IM3M) removal remains a controversial issue because many variables have been associated with increased operation time. Thus, the main objective of this study was to assess the influence of the gonial angle on the surgical difficulty of IM3M extraction. PATIENTS AND METHODS: A prospective cohort study of patients requiring IM3M removal was conducted. The gonial angle measured with a goniometer was considered the primary predictor variable. The primary outcome variable was operation time. Difficulty also was recorded by surgeons using a 100-mm visual analog scale (VAS). Postoperative complications (pain, swelling, and trismus at 48 hours and 7 days) were registered as secondary outcome variables. A descriptive bivariate statistical analysis, Pearson correlations and scatter plots, and an explanatory multiple linear regression model were performed. Significance was set at P < .05. RESULTS: The sample comprised 60 participants (17 men and 43 women) with a mean age of 25.2 years (standard deviation, 7.1 years). No significant correlations were found between the gonial angle and operation time, VAS difficulty score, and postoperative complications. Regression analysis confirmed this lack of effect of the gonial angle. The operation time was significantly affected by surgical experience (P = .016) and patient age (P = .009), whereas the 100-mm VAS difficulty score was only related to surgical experience (P = .001). CONCLUSIONS: The gonial angle is not related to the surgical difficulty of IM3M removal. Moreover, this variable is not associated with the occurrence of postoperative complications. According to the findings in this cohort, surgical experience and patient age are the only variables significantly related to increased operation time.

ETS2 is a prostate basal cell marker and is highly expressed in prostate cancers aberrantly expressing p63.

BACKGROUND: Rare prostate carcinomas aberrantly express p63 and have an immunophenotype intermediate between basal and luminal cells. Here, we performed gene expression profiling on p63-expressing prostatic carcinomas and compared them to usual-type adenocarcinoma. We identify ETS2 as highly expressed in p63-expressing prostatic carcinomas and benign prostate basal cells, with lower expression in luminal cells and primary usual-type adenocarcinomas. METHODS: A total of 8 p63-expressing prostate carcinomas at radical prostatectomy were compared to 358 usual-type adenocarcinomas by gene expression profiling performed on formalin fixed paraffin embedded tumor tissue using Affymetrix 1.0 ST microarrays. Correlation between differentially expressed genes and TP63 expression was performed in 5239 prostate adenocarcinomas available in the Decipher GRID. For validation, ETS2 in situ hybridization was performed on 19 p63-expressing prostate carcinomas and 30 usual-type adenocarcinomas arrayed on tissue microarrays (TMA). RESULTS: By gene expression, p63-expressing prostate carcinomas showed low cell cycle activity and low Decipher prognostic scores, but were predicted to have high Gleason grade compared to usual-type adenocarcinomas by gene expression signatures and morphology. Among the genes over-expressed in p63-expressing carcinoma relative to usual-type adenocarcinoma were known p63-regulated genes, along with ETS2, an ETS family member previously implicated as a prostate cancer tumor suppressor gene. Across several cohorts of prostate samples, ETS2 gene expression was correlated with TP63 expression and was significantly higher in benign prostate compared to usual-type adenocarcinoma. By in situ hybridization, ETS2 gene expression was high in benign basal cells, and low to undetectable in benign luminal cells or usual-type adenocarcinoma. In contrast, ETS2 was highly expressed in 95% (18/19) of p63-expressing prostate carcinomas. CONCLUSIONS: ETS2 is a predominantly basally-expressed gene in the prostate, with low expression in usual-type adenocarcinoma and high expression in p63-expressing carcinomas. Given this pattern, the significance of ETS2 loss by deletion or mutation in usual-type adenocarcinomas is uncertain.

A phase II study of the dual mTOR inhibitor MLN0128 in patients with metastatic castration resistant prostate cancer.

Background MLN0128 is a first-in-class, dual mTOR inhibitor with potential to outperform standard rapalogs through inhibition of TORC1 and TORC2. This phase II study was designed to assess antitumor activity of MLN0128 in metastatic castration-resistant prostate cancer (mCRPC). Methods Eligible patients had mCRPC previously treated with abiraterone acetate and/or enzalutamide. Five patients started MLN0128 at 5 mg once daily, subsequently dose reduced to 4 mg because of toxicity. Four subsequent patients started MLN0128 at 4 mg daily. Primary endpoint was progression-free survival at 6 months. Results Nine patients were enrolled and median time on treatment was 11 weeks (range: 3-30). Best response was stable disease. All patients had a rise in PSA on treatment, with a median 159% increase from baseline (range: 12-620%). Median baseline circulating tumor cell count was 1 cell/mL (range: 0-40); none had a decrease in cell count posttreatment. Grade ≤ 2 adverse events included fatigue, anorexia, and rash. The most common serious adverse events were grade 3 dyspnea and maculopapular rash. Eight patients discontinued treatment early because of radiographic progression (n = 1), grade 3 toxicity (n = 5), or investigator discretion (n = 2). Four patients had immediate PSA decline following drug discontinuation, suggesting MLN0128 could cause compensatory increase of androgen receptor (AR) activity. Correlative studies of pretreatment and posttreatment biopsy specimens revealed limited inhibition of AKT phosphorylation, 4EBP1 phosphorylation, and eIF4E activity. Conclusions Clinical efficacy of MLN0128 in mCRPC was limited likely due to dose reductions secondary to toxicity, PSA kinetics suggesting AR activation resulting from mTOR inhibition, and poor inhibition of mTOR signaling targets.

Effect of implantoplasty on fracture resistance and surface roughness of standard diameter dental implants.

OBJECTIVE: To assess the effect of implantoplasty on the fracture resistance, surface roughness, and macroscopic morphology of standard diameter (4.1 mm) external connection dental implants. MATERIALS AND METHODS: An in vitro study was conducted in 20 screw-shaped titanium dental implants with an external connection. In 10 implants, the threads and surface were removed and polished with high-speed burs (implantoplasty), while the remaining 10 implants were used as controls. The final implant dimensions were recorded. The newly polished surface quality was assessed by scanning electron microscopy (SEM) and by 3D surface roughness analysis using a confocal laser microscope. Finally, all the implants were subjected to a mechanical pressure resistance test. A descriptive analysis of the data was made. Also, Student's t tests were employed to detect differences regarding the compression tests. RESULTS: Implantoplasty was carried out for a mean time of 10 min and 48 s (standard deviation (SD) of 1 min 22 s). Macroscopically, the resulting surface had a smooth appearance, although small titanium shavings and silicon debris were present. The final surface roughness (Sa values 0.1 ± 0.02 µm) was significantly lower than that of the original (0.75 ± 0.08 µm Sa ) (p = .005). There was minimal reduction in the implant's inner body diameter (0.19 ± 0.03 mm), and no statistically significant differences were found between the test and control implants regarding the maximum resistance force (896 vs 880 N, respectively). CONCLUSIONS: Implantoplasty, although technically demanding and time-consuming, does not seem to significantly alter fracture resistance of standard diameter external connection implants. A smooth surface with Sa values below 0.1 µm can be obtained through the use of silicon polishers. A larger sample is required to confirm that implantoplasty does not significantly affect the maximum resistance force of standard diameter external connection implants.

Novel Ball Head Screw and Screwdriver Design for Implant-Supported Prostheses With Angled Channels: A Finite Element Analysis.

The primary objective of this study was to design the optimal geometry of a novel screwdriver, create the grooves on a ball head screw, and demonstrate its resistance to a torque of up to 40 Ncm at angulations of 0°, 15°, and 30° by using nonlinear finite element analysis. A secondary objective was to create a foolproof, easily recognizable system. The grooved ball head screw and geometry of the screwdriver, functioning from an angulation of 0° to 30°, was generated using Pro-ENGINEER Wildfire 5.0 software. Static structural analyses among bodies in contact were performed at different angles of 0°, 15°, and 30° at a torque of 20 Ncm and 40 Ncm using nonlinear finite element simulation by means of ANSYS 12.0. The maximum stress supported by the ball head screw and screwdriver was similar at 20 Ncm and 40 Ncm. Although greater deformations were found at 40 Ncm, these were small and might not affect the performance of the system. Further, the rupture torque value for the M2 connection was 55 Ncm for 0° and 30°, and 47.5 Ncm for 15°. Numerical simulation showed that the ball head system design can achieve the mechanical strength requirements expected for screws used in implant-supported restorations at an angulation of up to 30°. Finite element analysis showed this novel ball head screw and screwdriver system to be a good solution for angled screw channels in implant-supported prostheses.

The spectrum of BRCA1 and BRCA2 alleles in Latin America and the Caribbean: a clinical perspective.

Hereditary cancer predisposition gene testing allows the identification of individuals at high risk of cancer that may benefit from increased surveillance, chemoprevention, and prophylactic surgery. In order to implement clinical genetic strategies adapted to each population's needs and intrinsic genetic characteristic, this review aims to present the current status of knowledge about the spectrum of BRCA pathogenic variants in Latin American populations. We have conducted a comprehensive review of 33 studies published between 1994 and 2015 reporting the prevalence and/or spectrum of BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) variants. The combined sample size for these studies consisted of 4835 individuals from 13 countries in Latin America and the Caribbean, as well as in Hispanics in the United States. A total of 167 unique pathogenic variants have been reported in the existing literature. In unselected breast cancer cases, the prevalence ranged from 1.2 to 27.1%. Some countries presented a few recurrent pathogenic variants, while others were characterized by diverse, non-recurrent variants. The proportion of BRCA pathogenic variants shared between Hispanics in the United States and Latin American populations was estimated at 10.4%. Within Latin America and the Caribbean, 8.2% of the BRCA variants reported were present in more than one country. Countries with high prevalence of BRCA pathogenic variants may benefit from more aggressive testing strategies, while testing of recurrent variant panels might present a cost-effective solution for improving genetic testing in some, but not all, countries.

Utility of intracardiac echocardiography for catheter ablation of complex cardiac arrhythmias in a medium-volume training center.

AIMS AND OBJECTIVES: New electrophysiology tools like intracardiac echocardiography (ICE) might help to minimize and early detect complications during cardiac ablation procedures. The aim of the study was to assess the utility and vascular safety of ICE during catheter ablation of complex cardiac arrhythmias in a medium-volume training center. METHODS: Prospective, observational study consisted of consecutive patients who underwent catheter-based ablation of complex cardiac arrhythmias. All procedures were performed using three-dimensional electro-anatomical mapping and routine cannulation of right and left femoral veins. The ICE probe was initially positioned at the mid-level of the right atrium and properly moved to monitor different steps of the procedure and identify complications. All procedure-related vascular complications were registered. RESULTS: One hundred two patients (age 61.4 ± 13.1 years, 69 male) underwent 110 ablation procedures. Pulmonary vein isolation was the most common ablation substrate (55.4%). Ventricular tachycardia (17.2%) and left atrial flutter procedures (16.4%) were also common. The use of ICE enabled us to early initiate anticoagulation and to optimize the transseptal puncture. It also provided the capability to early detect life-threatening complications such as tamponade (3.6%), along with important information during the procedure such as exact catheter location, lesion formation, and stability during radiofrequency delivery. Such benefits were not associated with a higher number of vascular complications. CONCLUSION: The use of ICE during catheter-based ablation of complex cardiac substrates provides technical features that may decrease complications and increase accuracy while applying radiofrequency, especially in training centers where fellows start to perform complex procedures.