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Background: Empirical evidence shows that life satisfaction is positively related to character strengths, and although this association has been observed in different populations, it is scarce in breast cancer patients. This study analyzes the relationship between character strengths and life satisfaction in Spanish women diagnosed with breast cancer. Methods: A sample of 117 women completed the Satisfaction with Life Scale (SWLS) and the Spanish version of the VIA Inventory of Strengths (VIA-IS). Correlation analysis and regression modeling were performed to determine which strengths predict life satisfaction. Results: The results of the correlation analysis showed that 15 strengths were positively and significantly associated with life satisfaction, with the highest correlations corresponding to zest, hope, curiosity, social intelligence, love, gratitude, and judgment. Regression modeling indicated that of these, zest and hope were key strengths for predicting life satisfaction. Conclusions: These findings suggest that intervention programs based on the development of zest and hope could help to improve life satisfaction and, therefore, the psychological well-being of women with breast cancer.

Background: In pediatric electrocardiography (ECG), the correct classification of segments in the medical record is subjected to various components. A conventional analysis based either on the cardiologist's skills or a quick reference to a standard normality table may lead to mistakes and to an incorrect final medical diagnosis. In this study, the evaluation of 12 specific ECG segments (ES) is defined as segmental analysis (SA). We hypothesized that a computer-aided SA can provide better results for a correct classification of pediatric ECGs, compared to the conventional analysis. This study aims to evaluate the accuracy of a computer-aided SA ECG diagnosis of pediatric patients by cardiologists.Methods: To validate the software, we selected four normal and one altered ECG as references, all with concordant reports given by two cardiologists using manual planimetry. Nineteen cardiology experts independently examined each of the five standard pediatric ECGs twice. First, the ECG was analyzed in the conventional form. Subsequently, the participants evaluated ECGs with our proposed computer-aided AS, by measuring the 12 specific ES in the grid paper and having their values entered into a custom-made software, in order to compare them with normality standards.Results: The computer-aided SA reduced ECG misreading or ECG misinterpretation errors by 83%. It also showed a more uniform, high-quality analysis of all ES (minimum of 92% correctly reviewed segments from normal pediatric ECGs) by all the participant cardiologists.Conclusions: We consider the computer-aided SA for ECG evaluation in pediatric cardiology an efficient and safe complementary method. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the progression of coronary artery calcification (CAC) and associated risk factors in a systemic lupus erythematosus (SLE) cohort., Methods: We reassessed the presence of CAC in patients with SLE who were screened 9 years before, using multidetector computed tomography. Clinical variables (cumulated disease activity and damage accrual), antiphospholipid syndrome and SLE serology, and cardiovascular (CV) risk factors (hypertension, BMI [kg/m 2 ], modified Framingham risk score, lipid profile, menopausal status) were assessed longitudinally., Results: We included 104 patients from the parent study. Most of them were women (94.2%), with a mean age of 41.0 (SD 8.3) years and mean disease duration of 14.8 (SD 2.9) years. We documented CAC in 17 patients (16.3%). Seven cases were from the parent study and 10 were incident cases. The cumulative incidence of CAC was 9% and the incidence density was 1 per 100 person-years. CAC occurred more frequently in the age groups 30-39 years and 40-44 years. All patients with previous CAC had worsening of their calcium indexes, and none developed clinical CV events. When comparing prevalent CAC cases (n = 17) vs patients without calcification (n = 87), both groups were similar in traditional CV risk factors, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) area under the curve (AUC), and Systemic Lupus International Collaborating Clinics (SLICC) score, but were more likely to be postmenopausal and have higher apolipoprotein B (apoB) levels. Patients with previous CAC had higher apoB levels, SLEDAI-2K AUC scores, and anticardiolipin IgG antibodies than incident cases., Conclusion: CAC in patients with SLE progressed over time but was not associated with adverse CV events during the first 9 years of follow-up. ApoB levels and postmenopausal status might be associated with this progression., (Copyright © 2024 by the Journal of Rheumatology.)

The immediate precursor to murine type 1 conventional DCs (cDC1s) has recently been established and named "pre-cDC1s". Mature CD8α+ cDC1s are recognized for suppressing graft-versus-host disease (GvHD) while promoting graft-versus-leukemia (GvL), however pre-cDC1s have not previously been investigated in the context of alloreactivity or anti-tumor responses. Characterization of pre-cDC1s, compared to CD8α+ cDC1s, found that a lower percentage of pre-cDC1s express PD-L1, yet express greater PD-L1 by MFI and a greater percent PIR-B, a GvHD-suppressing molecule. Functional assays were performed ex vivo following in vivo depletion of CD8α+ DCs to examine whether pre-cDC1s play a redundant role in alloreactivity. Proliferation assays revealed less allogeneic T-cell proliferation in the absence of CD8α+ cDC1s, with slightly greater CD8+ T-cell proliferation. Further, in the absence of CD8α+ cDC1s, stimulated CD8+ T-cells exhibited significantly less PD-1 expression compared to CD4+ T-cells, and alloreactive T-cell death was significantly lower, driven by reduced CD4+ T-cell death. Tumor-killing assays revealed that T-cells primed with CD8α-depleted DCs ex vivo induce greater killing of A20 B-cell leukemia cells, particularly when antigen (Ag) is limited. Bulk RNA sequencing revealed distinct transcriptional programs of these DCs, with pre-cDC1s exhibiting activated PD-1/PD-L1 signaling compared to CD8α+ cDC1s. These results indicate distinct T-cell-priming capabilities of murine pre-cDC1s compared to CD8α+ cDC1s ex vivo, with potentially clinically relevant implications in suppressing GvHD while promoting GvL responses, highlighting the need for greater investigation of murine pre-cDC1s., Competing Interests: The authors have declared that no competing interests exist.

Aims: Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure, and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure., Methods and Results: Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and five control samples were analysed by RNA-Seq (discovery group). These cases presented with cardiac arrhythmias and had a normal right ventricular function. The RNA-Seq analysis identified ∼5000 differentially expressed genes (DEGs), which predicted suppression of the Hippo and canonical WNT pathways, among others. Dysregulated genes and pathways, identified by RNA-Seq, were tested for validation in the right and left ventricular tissues from five independent autopsy-confirmed ACM cases with defined mutations (validation group), who were victims of SCD and had no history of heart failure. Protein levels and nuclear localization of the cWNT and Hippo pathway transcriptional regulators were reduced in the right and left ventricular validation samples. In contrast, levels of acetyltransferase EP300, known to suppress the Hippo and canonical WNT pathways, were increased and its bona fide target TP53 was acetylated. RNA-Seq data identified apical junction, reflective of cell-cell attachment, as the most disrupted biological pathway, which were corroborated by disrupted desmosomes and intermediate filament structures. Moreover, the DEGs also predicted dysregulation of over a dozen canonical signal transduction pathways, including the Tec kinase and integrin signalling pathways. The changes were associated with increased apoptosis and fibro-adipogenesis in the ACM hearts., Conclusion: Altered apical junction structures are associated with activation of the EP300-TP53 and suppression of the Hippo/cWNT pathways in human ACM caused by defined mutations in the absence of an overt heart failure. The findings implicate altered mechanotransduction in the pathogenesis of ACM., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Tocopherols and sterols are minor components of virgin olive oils that contribute to oil quality. Based on observations at different geographical locations, it has been suggested that environmental temperature during fruit growth affects tocopherol and sterol oil concentrations in olive fruit. However, controlled experiments have not been conducted to directly assess their responses to temperature. In this study, a manipulative experiment using open-top chambers (OTCs) was performed in the field to evaluate the responses of these oil components to a moderate air temperature increase during oil accumulation in young trees of two olive cultivars (Arbequina, Coratina). The two temperature levels in the OTCs were a control about 1 °C above ambient temperature (T0) and a heated treatment (T+) with a target temperature of 4 °C above T0., Results: Total tocopherol and sterol oil concentrations in olive fruit were generally higher in the T+ temperature treatment than in the control at the end of the oil accumulation period. The increase in total tocopherols in T+ appeared to be related to a decrease in fruit oil concentration with heating. Individual sterols showed both significant increases and decreases due to T+, and some differences in response occurred between the two cultivars., Conclusion: These findings provide evidence that growth temperature affects tocopherol and sterol oil concentrations in olive fruit at the end of the oil accumulation period. Cultivars should be carefully chosen for new olive-growing regions, and the results could be relevant for global warming scenarios in existing growing regions. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na V 1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na V 1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

For some cancer subtypes, such as triple-negative breast cancer, there are no specific therapies, which leads to a poor prognosis associated with invasion and metastases. Ruthenium complexes have been developed to act in all steps of tumor growth and its progression. In this study, we investigated the effects of Ruthenium (II) complexes coupled to the amino acids methionine (RuMet) and tryptophan (RuTrp) on the induction of cell death, clonogenic survival ability, inhibition of angiogenesis, and migration of MDA-MB-231 cells (human triple-negative breast cancer). The study also demonstrated that the RuMet and RuTrp complexes induce cell cycle blockage and apoptosis of MDA-MB-231 cells, as evidenced by an increase in the number of Annexin V-positive cells, p53 phosphorylation, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Moreover, morphological changes and loss of mitochondrial membrane potential were detected. The RuMet and RuTrp complexes induced DNA damage probably due to reactive oxygen species production related to mitochondrial membrane depolarization. Therefore, the RuMet and RuTrp complexes acted directly on breast tumor cells, leading to cell death and inhibiting their metastatic potential; this reveals the potential therapeutic action of these drugs., (Published by Elsevier Inc.)

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Variants in MYBPC3, the gene encoding cardiac myosin-binding protein C (cMyBP-C), are the leading cause of HCM. However, the pathogenicity status of hundreds of MYBPC3 variants found in patients remains unknown, as a consequence of our incomplete understanding of the pathomechanisms triggered by HCM-causing variants. Here, we examined 44 nontruncating MYBPC3 variants that we classified as HCM-linked or nonpathogenic according to cosegregation and population genetics criteria. We found that around half of the HCM-linked variants showed alterations in RNA splicing or protein stability, both of which can lead to cMyBP-C haploinsufficiency. These protein haploinsufficiency drivers associated with HCM pathogenicity with 100% and 94% specificity, respectively. Furthermore, we uncovered that 11% of nontruncating MYBPC3 variants currently classified as of uncertain significance in ClinVar induced one of these molecular phenotypes. Our strategy, which can be applied to other conditions induced by protein loss of function, supports the idea that cMyBP-C haploinsufficiency is a fundamental pathomechanism in HCM., Competing Interests: Conflict of interest L. M. holds share in Health in Code. All other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The growth factor Flt3 ligand (Flt3L) is central to dendritic cell (DC) homeostasis and development, controlling survival and expansion by binding to Flt3 receptor tyrosine kinase on the surface of DCs. In the context of hematopoietic cell transplantation, Flt3L has been found to suppress graft-versus-host disease (GvHD), specifically via host DCs. We previously reported that the pre-transplant conditioning regimen consisting of bendamustine (BEN) and total body irradiation (TBI) results in significantly reduced GvHD compared to cyclophosphamide (CY)+TBI. Pre-transplant BEN+TBI conditioning was also associated with greater Flt3 expression among host DCs and an accumulation of pre-cDC1s. Here, we demonstrate that exposure to BEN increases Flt3 expression on both murine bone marrow-derived DCs (BMDCs) and human monocyte-derived DCs (moDCs). BEN favors development of murine plasmacytoid DCs, pre-cDC1s, and cDC2s. While humans do not have an identifiable equivalent to murine pre-cDC1s, exposure to BEN resulted in decreased plasmacytoid DCs and increased cDC2s. BEN exposure and heightened Flt3 signaling are associated with a distinct regulatory phenotype, with increased PD-L1 expression and decreased ICOS-L expression. BMDCs exposed to BEN exhibit diminished pro-inflammatory cytokine response to LPS and induce robust proliferation of alloreactive T-cells. These proliferative alloreactive T-cells expressed greater levels of PD-1 and underwent increased programmed cell death as the concentration of BEN exposure increased. Alloreactive CD4 + T-cell death may be attributable to pre-cDC1s and provides a potential mechanism by which BEN+TBI conditioning limits GvHD and yields T-cells tolerant to host antigen., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Molina, Hoffman, Stokes, Kummet, Smith, Baker, Zúñiga, Simpson and Katsanis.)

Background: Arrhythmogenic cardiomyopathy is a hereditary cause of ventricular arrhythmias and sudden death. Identifying the healthy genetic carriers who will develop the disease remains a challenge. A novel approach to the analysis of the digital electrocardiograms of mutation carriers through signal processing may identify early electrocardiographic abnormalities. Methods: A retrospective case-control study included a population of healthy genetics carriers and their wild-type relatives. Genotype-positive/phenotype-negative individuals bore mutations associated with the development of arrhythmogenic cardiomyopathy. The relatives included had a non-pathological 12-lead electrocardiogram, echocardiogram, and a cardiac magnetic resonance. Automatic digital electrocardiographic analyses comprised QRS and terminal activation delay duration, the number of QRS fragmentations, ST slope, and T-wave voltage. Results: Digital 12-lead electrocardiograms from 41 genotype-positive/ phenotype-negative (29 simple carriers and 12 double mutation carriers) and 73 wild-type relatives were analyzed. No differences in the QRS length, the number of QRS fragmentations, and the voltage of the T-wave were observed. After adjusting for potential confounders, double carriers showed an average ST-slope flatter than those of the simple carriers and wild type [5.18° (0.73-8.01), 7.15° (5.14-11.05), and 11.46° (3.94-17.49), respectively, p = 0.005]. There was a significant negative correlation between the ST slope and the age in genotype-positive/phenotype-negative relatives ( r = 0.376, p = 0.021) not observed in their wild-type counterparts ( r = 0.074, p = 0.570). Conclusions: A flattened ST segment may be an early sign of electrical remodeling that precedes T-wave inversion in healthy genetic carriers. A thorough analysis of the digital electrocardiographic signal may help identify and measure early electrical abnormalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lopez-Ayala, Gimeno-Blanes, Lopez-Cuenca, Molina and Gimeno-Blanes.)

Bendamustine (BEN) is a unique alkylating agent with efficacy against a broad range of hematological malignancies, although investigations have only recently started to delve into its immunomodulatory effects. These immunomodulatory properties of BEN in the context of hematopoietic cell transplantation (HCT) are reviewed here. Pre- and post-transplant use of BEN in multiple murine models have consistently resulted in reduced GvHD and enhanced GvL, with significant changes to key immunological cell populations, including T-cells, myeloid derived suppressor cells (MDSCs), and dendritic cells (DCs). Further, in vitro studies find that BEN enhances the suppressive function of MDSCs, skews DCs toward cDC1s, enhances Flt3 expression on DCs, increases B-cell production of IL-10, inhibits STAT3 activation, and suppresses proliferation of T- and B-cells. Overall, BEN has a broad range of immunomodulatory effects that, as they are further elucidated, may be exploited to improve clinical outcomes. As such, clinical trials are currently underway investigating new potential applications of BEN in the setting of allogeneic HCT.

Aims: Hypertrophic cardiomyopathy (HCM) is often accompanied by increased trabeculated myocardium (TM)-which clinical relevance is unknown. We aim to measure the left ventricular (LV) mass and proportion of trabeculation in an HCM population and to analyze its clinical implication., Methods and Results: We evaluated 211 patients with HCM (mean age 47.8 ± 16.3 years, 73.0% males) with cardiac magnetic resonance (CMR) studies. LV trabecular and compacted mass were measured using dedicated software for automatic delineation of borders. Mean compacted myocardium (CM) was 160.0 ± 62.0 g and trabecular myocardium (TM) 55.5 ± 18.7 g. The percentage of trabeculated myocardium (TM%) was 26.7% ± 6.4%. Females had significantly increased TM% compared to males (29.7 ± 7.2 vs. 25.6 ± 5.8, p < 0.0001). Patients with LVEF < 50% had significantly higher values of TM% (30.2% ± 6.0% vs. 26.6% ± 6.4%, p = 0.02). Multivariable analysis showed that female gender and neutral pattern of hypertrophy were directly associated with TM%, while dynamic obstruction, maximal wall thickness and LVEF% were inversely associated with TM%. There was no association between TM% with arterial hypertension, physical activity, or symptoms. Atrial fibrillation and severity of hypertrophy were the only variables associated with cardiovascular death. Multivariable analysis failed to demonstrate any correlation between TM% and arrhythmias., Conclusions: Approximately 25% of myocardium appears non-compacted and can automatically be measured in HCM series. Proportion of non-compacted myocardium is increased in female, non-obstructives, and in those with lower contractility. The amount of trabeculation might help to identify HCM patients prone to systolic heart failure.

Graft-versus-host disease (GvHD) remains the second leading cause of death in allogeneic hematopoietic stem cell transplantation recipients, highlighting the need for improved preventative strategies. Our laboratory has previously demonstrated in an experimental bone marrow transplantation (BMT) model that bendamustine combined with total body irradiation (BEN+TBI) is a safer alternative to cyclophosphamide with TBI (CY+TBI). The biological mechanisms of action of BEN have not been fully elucidated and likely involve multiple cell populations. Host dendritic cells (DCs) can prime naïve donor T-cells immediately following transplantation, making host DCs critical for the initiation phase of GvHD. We hypothesized that BEN+TBI conditioning favorably alters host DC composition to reduce GvHD. We demonstrate that host DCs treated with BEN+TBI induce less allogeneic T-cell proliferation than those conditioned with CY+TBI. We further show that BEN+TBI conditioning results in greater total numbers of all host DC subsets but with a more favorable composition compared to CY+TBI with significantly larger proportions of type 1 conventional DCs (cDC1), a highly regulatory DC subset capable of suppressing GvHD. Our studies using recipient Batf3 KO mice indicate that CD8α+ cDC1s are largely dispensable for the reduced GvHD following BEN+TBI conditioning. We found a higher frequency of host pre-cDC1s with BEN+TBI conditioning in both wild-type (WT) and Batf3 KO mice, which was inversely associated with GvHD. Additionally, we observed that BEN treatment results in greater expression of Flt3 receptor (CD135) on host DCs compared to CY, potentially contributing to the skewing of host DCs toward cDC1s. Further, BEN+TBI conditioning results in host cDCs with greater expression of PIR-B, an inhibitory receptor capable of preventing lethal GvHD. We conclude that BEN+TBI is a safer alternative to CY+TBI, resulting in a greater frequency of host pre-cDC1s and limiting GvHD., (Copyright © 2020 Molina, Stokes, Hoffman, Eremija, Zeng, Simpson and Katsanis.)

Graft-versus-host disease (GvHD) remains a significant impediment to allogeneic hematopoietic cell transplantation (HCT) success, necessitating studies focused on alleviating GvHD, while preserving the graft-versus-leukemia (GvL) effect. Based on our previous studies showing bendamustine with total body irradiation (BEN-TBI) conditioning reduces GvHD compared to the current clinical standard of care cyclophosphamide (CY)-TBI in a murine MHC-mismatched bone marrow transplantation (BMT) model, this study aimed to evaluate the role and fate of donor T-cells following BEN-TBI conditioning. We demonstrate that BEN-TBI reduces GvHD compared to CY-TBI independently of T regulatory cells (Tregs). BEN-TBI conditioned mice have a smaller proportion and less activated donor T-cells, with lower CD47 expression, early post-transplant, but no sustained phenotypic differences in T-cells. In BEN-TBI conditioned mice, donor T-cells gain tolerance specific to host MHC antigens. Though these T-cells are tolerant to host antigens, we demonstrate that BEN-TBI preserves a T-cell-dependent GvL effect. These findings indicate that BEN-TBI conditioning reduces GvHD without compromising GvL, warranting its further investigation as a potentially safer and more efficacious clinical alternative to CY-TBI., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Graft-versus-host disease (GVHD) remains a significant challenge in allogeneic hematopoietic cell transplantation (HCT). An underinvestigated strategy to reduce GVHD is the modification of the preparative conditioning regimen. In the present study, we aimed to evaluate GVHD associated with bendamustine (BEN) conditioning in conjunction with total body irradiation (TBI) as an alternative to the standard myeloablative regimen of cyclophosphamide (CY) and TBI. We demonstrate that BEN-TBI conditioning, although facilitating complete donor chimerism, results in significantly less GVHD compared with CY-TBI. In BEN-TBI-conditioned mice, suppressive CD11b + Gr-1 high myeloid cells are increased in the blood, bone marrow, spleen, and intestines. When Gr-1 high cells are depleted before transplantation, the beneficial effects of BEN-TBI are partially lost. Alternatively, administration of granulocyte colony-stimulating factor, which promotes CD11b + Gr-1 + myeloid cell expansion, is associated with a trend toward increased survival in BEN-TBI-conditioned mice. These findings indicate a potential role of myeloid-derived suppressor cells in the mechanism by which BEN allows engraftment with reduced GVHD. BEN-TBI conditioning may present a safer alternative to CY-TBI conditioning for allogeneic HCT., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Staphylococcal species are the most common organisms causing prosthetic mesh infections, however, infections due to rapidly growing mycobacteria are increasing. This study evaluates the resistance of biomaterial for abdominal wall prostheses against the development of postoperative infection in a rat model., Material and Methods: In 75 rats, we intramuscularly implanted three different types of prostheses: (1) low-density polypropylene monofilament mesh (PMM), (2) high-density PMM, and (3) a composite prosthesis composed of low-density PMM and a nonporous hydrophilic film. Meshes were inoculated with a suspension containing 10 8 colony-forming units of Staphylococcus aureus, Staphylococcus epidermidis, Mycobacterium fortuitum, or Mycobacterium abscessus before wound closure. Animals were sacrificed on the eighth day postoperatively for clinical evaluation, and the implants were removed for bacteriologic analyses., Results: Prostheses infected with S aureus showed a higher bacterial viability, worse integration, and clinical outcome compared with infection by other bacteria. Composite prostheses showed a higher number of viable colonies of both M fortuitum and Staphylococcus spp., with poorer integration in host tissue. However, when the composite prosthesis was infected with M abscessus, a lower number of viable bacteria were isolated and a better integration was observed compared with infection by other bacteria., Conclusions: Considering M abscessus, a smaller collagen-free contact surface shows better resistance to infection, however, depending on the type of bacteria, prostheses with a large surface, and covered with collagen shows reduced resistance to infection, worse integration, and worse clinical outcome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Internal mammary chain (IMC) is one of the main local lymph drainages in breast cancer. However, internal mammary chain sentinel lymph node biopsy (IMC-SLNB) is not always performed. The purpose of this research is to evaluate the outcomes of IMC-SLNB in our institution from 2008 to 2014. We analyzed 1346 women with breast cancer. Six-hundred twenty-two sentinel node biopsies were carried out, one out of ten in IMC territory. Adjuvant radiotherapy in this area was added when positive. IMC-SLNB is feasible, it may change tumour stage, modify adjuvant therapy and change prognosis in selected patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: We aimed to evaluate the usefulness of anti-α-fodrin antibodies (AFA) in combination with rheumatoid factor (RF) and/or antinuclear antibodies (ANA) as an alternative immunological criterion for Sjögren syndrome (SS) among patients with negative anti-Ro/La serology., Methods: The study included 350 patients (100 with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, and 50 with primary SS) randomly selected and assessed for SS. All patients were tested for ANA, RF, anti-SSA/SSB, and AFA antibodies. SS diagnosis was made on a clinical basis by 2 rheumatologists based on the 6-item screening questionnaire, Schirmer-I test, nonstimulated whole salivary flow rate, fluorescein staining test, autoantibodies, lip biopsy, and medical chart review. Non-SS was defined as lack of clinical diagnosis and not fulfilling the American-European Consensus Group classification criteria and the American College of Rheumatology (ACR) criteria. The ACR criteria were applied substituting the immunological criteria as follows: (1) RF plus ANA > 1:320, (2) RF plus AFA, (3) ANA > 1:320 plus AFA, (4) RF alone, and (5) 2 positive tests out of RF, ANA > 1:320, or AFA. We estimated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio positivity with 95% CI for each criterion., Results: There were 236 patients (67%) who tested negative for anti-SSA/SSB antibodies, of whom 65 (27.5%) were clinically diagnosed as SS, and 149 (63%) with non-SS. RF + AFA and ANA + AFA performed similarly to RF + ANA > 1:320. The model 2 out of 3 of RF, ANA, or AFA improved the sensitivity from 56.9% to 70.7%, although the specificity decreased., Conclusion: The combination AFA + RF, AFA + ANA > 1:320, or at least 2 out of 3, performed well as a proxy immunological test for patients with SS and negative Ro/La serology.

Introduction: Mammographic density (MD) is one of the strongest determinants of sporadic breast cancer (BC). In this study, we compared MD in BRCA1/2 mutation carriers and non-carriers from BRCA1/2 mutation-positive families and investigated the association between MD and BC among BRCA1/2 mutation carriers per type of mutation and tumor subtype., Methods: The study was carried out in 1039 female members of BRCA1 and BRCA2 mutation-positive families followed at 16 Spanish Genetic Counseling Units. Participants' density was scored retrospectively from available mammograms by a single blinded radiologist using a 5-category scale (<10 %, 10-25 %, 25-50 %, 50-75 %, >75 %). In BC cases, we selected mammograms taken prior to diagnosis or from the contralateral breast, whereas, in non-cases, the last screening mammogram was evaluated. MD distribution in carriers and non-carriers was compared using ordinal logistic models, and the association between MD and BC in BRCA1/2 mutation carriers was studied using logistic regression. Huber-White robust estimators of variance were used to take into account correlations between family members. A similar multinomial model was used to explore this association by BC subtype., Results: We identified and scored mammograms from 341 BRCA1, 350 BRCA2 mutation carriers and 229 non-carriers. Compared to non-carriers, MD was significantly lower among BRCA2 mutation carriers (odds ratio (OR) =0.71; P-value=0.04), but not among BRCA1 carriers (OR=0.84; P-value=0.33). MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48). Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes., Conclusions: Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context.

Objectives: To develop and test a computer program to assist researchers in assigning scores in the application of the Basso, Beattie and Bresnahan (BBB) scale and to compare these scores when doing so in free, targeted and automated computer-assisted modes., Method: To test the program, the participants used the Impactor methodology recommended by the New York University (USA), in which 12 Wistar rats submitted to spinal cord injury were filmed on the 28(th) day after the injury. Eight researchers from the Laboratory of Medical Investigation, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil took part in the study. The two heads of the laboratory, with 15 years of experience in the application of the scale, were considered the gold standard., Results: The results of the scale application were not significantly different in relation to the gold standard, considering the mean of the evaluators in each method: free, targeted and automated form (with the help of the computer)., Conclusions: The application of the BBB scale in the automated mode, using the computer program, did not present any difference in relation to the gold standard for all the evaluators. Level of Evidence II, Diagnostic Studies.

Fasting hypertriglyceridemia relates with high-density lipoprotein (HDL) cholesterol, but it is not known whether low HDL cholesterol is associated with disturbances of chylomicron metabolism. To clarify this issue this metabolism was studied in subjects with low HDL cholesterol together with vascular reactivity and evaluation of no-flush niacin treatment. Thirty men with HDL < 1.04 mmol/L and no other risk factors for coronary artery disease (CAD) and 11 normal controls with HDL > 1.04 mmol/L were studied. The plasma kinetics of a chylomicron-like emulsion labeled with 14C-cholesterol oleate (CO) and 3H-triolein (TG) was determined and the fractional clearance rate (FCR, min(-1)) was calculated. Vascular reactivity was evaluated using high-resolution ultrasonography. CO FCR was markedly reduced in the low HDL group compared to controls (3.6 x 10(-3) +/- 5.1 x 10(-3) min(-1) versus 12.2 x 10(-3) +/- 8.4 x 10(-3) min(-1), p < 0.001) but TG FCR was similar. Flow-mediated dilation (FMD) was diminished in low HDL (7.4 +/- 4.1 versus 12.8 +/- 4.6%, p < 0.001), whereas nitrate-mediated dilation was similar. Twenty-two low HDL subjects with reduced FMD were randomized into two groups, one given 1.5 g/day niacin and a placebo group. After 3-month treatment, plasma lipids and chylomicron kinetics were not changed by niacin treatment but FMD improved to normal values (5.44 +/- 1.89 to 11.13 +/- 3.4%, p < 0.01). In conclusion, isolated low HDL cholesterol subjects may also bear chylomicron remnant accumulation and endothelial dysfunction, which highlight the importance of their preventive treatment.