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Abstract Background The main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, β1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of β1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC). In addition, we compared the expression of β1 integrin in patients with ductal carcinoma in situ (DCIS). Methods Through tissue microarray (TMA) slides containing 225 samples of IDC and 67 samples of DCIS, β1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance. Results β1 integrin was overexpressed in 32.8% of IDC. In IDC, β1 integrin was related with HER-2 (p = 0.019) and VEGF (p = 0.011) expression and it had a significant relationship with metastasis and death (p = 0.001 and p = 0.05, respectively). Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p = 0.002) in specific survival (number of months between diagnosis and death caused by the disease). There were no correlation between IDC and DCIS (p = 0.559) regarding β1 integrin expression. Conclusions Considering that the expression of β1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that β1 integrin can be a marker of poor prognosis in breast cancer. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6652215267393871

Abstract Background Cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of tumor. Stem cells renewal and differentiation can be directly influenced by the oxygen levels of determined tissues, probably by the reduction of oxidative DNA damage in hypoxic regions, thus leading to a friendlier microenvironment, regarding to clonal expansion and for resistance to chemotherapeutic regimens. Furthermore, there have been strong data indicating a pivotal role of hypoxic niche in cancer stem cells development. There are evidence that hypoxia could drive the maintenance of CSC, via HIF-1α expression, but it still to be determined whether hypoxia markers are expressed in breast tumors presenting CD44+CD24-/low immunophenotype. Methods Immunohistochemical analysis of CD44+CD24-/low expression and its relationship with hypoxia markers and clinical outcome were evaluated in 253 samples of breast ductal carcinomas. Double-immunolabeling was performed using EnVision Doublestain System (Dako, Carpinteria, CA, USA). Slides were then scanned into high-resolution images using Aperio ScanScope XT and then, visualized in the software Image Scope (Aperio, Vista, CA, USA). Results In univariate analysis, CD44+CD24-/low expression showed association with death due to breast cancer (p = 0.035). Breast tumors expressing CD44+CD24-/low immunophenotype showed relationship with HIF-1α (p = 0.039) and negativity for HER-2 (p = 0.013). Conclusion Considering that there are strong evidences that the fraction of a tumour considered to be cancer stem cells is plastic depending upon microenvironmental signals, our findings provide further evidence that hypoxia might be related to the worse prognosis found in CD44+CD24-/low positive breast tumors.

Background: Global health diplomacy is the applied practice of foreign affairs to further national goals that focus on health issues requiring international cooperation and collective action. We aimed to determine how international diplomats and health policy-related professionals in the EU understand the concept of health diplomacy, which impacts both diplomatic relations as well as patients' rights., Methods: In a qualitative interview study, we used a heterogeneous stratified purposeful sampling to reach participants from different countries and different practitioners from the Pyramid of Health Diplomacy: core, multi-stakeholder, and informal. Reflexive thematic analysis was used to identify the main themes., Findings: We contacted 131 practitioners of GHD, of which 37 responded, and nine agreed to be interviewed. From 11 interview questions, four main themes emerged from the analysis of the individual interview. The participants reported limited knowledge about the definition of GHD but also that they engaged in daily activities and decisions of inter-governmental bodies. They were not aware of existing special education and training for health attachés and made suggestions for improving the field and practice of GHD. They were not fully familiar with the European Charter of Patients' Rights. There was a consensus from all participants that patient rights need to improve as a fundamental right. They stressed the fact that the hospital lockdown and the right access to healthcare were impaired during the COVID pandemic., Interpretation: The role of health diplomacy in linking public health and foreign affairs is key to respecting patients' rights. Health over other interests is becoming an increasingly critical element in foreign policy. Establishing a clear career path for health attachés is necessary to foster effective global health agreements and coordination across countries., 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 © 2023 Karačić Zanetti, Brown, Viđak and Marušić.)

We developed a genomic surveillance program for real-time monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) in Uruguay. We report on a PCR method for SARS-CoV-2 VOCs, the surveillance workflow, and multiple independent introductions and community transmission of the SARS-CoV-2 P.1 VOC in Uruguay.

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020-February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay's capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest.

Introduction: Multiple stages of carcinogenesis in colon cancer encompass subpopulations of cancer stem cells (CSC), responsible for tumor cell transformation, growth and proliferation. CD44 and CD166 proteins are CSC markers associated with cell signaling, adhesion, migration, metastasis and lymphocytic response. The expression of CSC may be modulated by some factors, such as the KRAS gene mutation., Objective: Correlate the expression of CD44 and CD166 markers in metastatic colon adenocarcinoma and KRAS mutation status (wild-type/mutated) with clinical pathological features and patients' outcome., Material and Methods: Fifty-eight samples of tumor tissue samples of metastatic colon adenocarcinoma were collected from patients treated with CapeOx at the HCFMRP-USP Clinical Oncology Service. Clinical and survival data were collected from medical records. KRAS status was determined by the polymerase chain reaction (PCR) technique, and analysis of immunohistochemical expression of CD44 and CD166 proteins was performed by tissue microarray., Results: The expression of CD44 and CD166 were positive in 41% and 43% of patients, respectively, and mutated KRAS was detected in 48% of patients. A significant association was found between CD166 and CD44 expression (p= 0.016), mainly in the wild-type KRAS group (p= 0.042) and patients over 65 years (p= 0.001). CD44-positive patients had 3.7-fold and 5.3-fold greater risk of liver metastasis and lung metastasis, respectively (p< 0.01), compared with CD44-negative patients. CD166-negative patients had 2.7 greater risk of lymph node involvement (0.03), compared with CD166-positive patients. KRAS mutation increased the risk of liver metastasis by 8 times (p< 0.01), and the risk of lung metastasis by 5 times (p= 0.04) in CD44-positive patients. KRAS mutation increased the risk of lymph node involvement by 8 times in CD166-negative patients (p= 0.0007)., Conclusion: An association between CD44 and CD166 expression was demonstrated in this study. Analysis of KRAS mutation combined with immunohistochemical expression of CD44 and CD166 identified subgroups of patients with colon adenocarcinoma at higher risk of lymph node involvement by the tumor and development of liver and lung metastasis.

In the past decade, there has been a resurgence in the field of unobtrusive cardiomechanical assessment, through advancing methods for measuring and interpreting ballistocardiogram (BCG) and seismocardiogram (SCG) signals. Novel instrumentation solutions have enabled BCG and SCG measurement outside of clinical settings, in the home, in the field, and even in microgravity. Customized signal processing algorithms have led to reduced measurement noise, clinically relevant feature extraction, and signal modeling. Finally, human subjects physiology studies have been conducted using these novel instruments and signal processing tools with promising results. This paper reviews the recent advances in these areas of modern BCG and SCG research.

Context: The reconstruction of evolutionary scenarios for whole genomes in terms of genome rearrangements is a fundamental problem in evolutionary and comparative genomics. The DeCo algorithm, recently introduced by Bérard et al., computes parsimonious evolutionary scenarios for gene adjacencies, from pairs of reconciled gene trees. However, as for many combinatorial optimization algorithms, there can exist many co-optimal, or slightly sub-optimal, evolutionary scenarios that deserve to be considered., Contribution: We extend the DeCo algorithm to sample evolutionary scenarios from the whole solution space under the Boltzmann distribution, and also to compute Boltzmann probabilities for specific ancestral adjacencies., Results: We apply our algorithms to a dataset of mammalian gene trees and adjacencies, and observe a significant reduction of the number of syntenic conflicts observed in the resulting ancestral gene adjacencies.

Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase IIIβ, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase IIIβ in breast cancer and its relationships with clinicopathologic features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase IIIβ, estrogen receptor, progesterone receptor, HER-2, BRCA-1, p53, and Ki67. Immunostaining for topoisomerase IIIβ was found in 33.9% of breast carcinomas, and immunopositivity was correlated with distant metastasis (P = .036) and death (P = .006). Decreased expression of topoisomerase IIIβ correlated with low expression of Ki67 (P < .001) and negativity for HER-2 (P < .001), BRCA-1 (P = .001), and p53 (P < .001). In the multivariate analysis, topoisomerase IIIβ expression was a significant predictor of survival (hazard ratio, 3.006 [95% confidence interval, 1.582-5.715]; P = .001). In conclusion, topoisomerase IIIβ expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Changes due to biventricular pacing have been documented by shortening of QRS duration and echocardiography. Compared to normal ventricular activation, the presence of left bundle branch block (LBBB) results in a significant change in cardiac cycle time intervals. Some of these have been used to quantify the underlying cardiac dyssynchrony, assess the effects of biventricular pacing, and guide programming of ventricular pacing devices. This study evaluates a simple noninvasive method using accelerometers attached to the skin to measure cardiac time intervals in biventricularly paced patients., Methods: Ten patients with biventricular pacemakers previously implanted for congestive heart failure were paced in the AAI mode, then in atrioventricular (AV) sequential mode from the right and left ventricles followed by biventricular pacing. Simultaneous recordings were obtained by 2D, Doppler echocardiography as well as by accelerometers. Similar recordings were obtained from 10 gender, aged matched, normal controls during sinus rhythm., Results: Compared to normals, heart failure patients paced in AAI mode had prolonged isovolumetric contraction time (IVCT), shorter ventricular ejection time (LVET), and prolonged isovolumetric relaxation (IVRT). With biventricular pacing the IVCT decreased, but the LVET and IVRT did not change significantly. There was excellent correlation between the echo and accelerometer-measured intervals., Conclusions: Shortening of the IVCT measured by an accelerometer is a consistent time interval change due to biventricular pacing that probably reflects more rapid acceleration of left ventricular ejection. The accelerometer may be useful to assess immediate efficacy of biventricular pacing during device implantation and optimize programmable time intervals such as AV and interventricular (VV) delays.