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There is active crosstalk between tumor cells and the tumor microenvironment during metastatic progression, a process that is significantly affected by obesity, particularly in breast cancer. Here we analyze the impact of a high fat diet (HFD) on metastasis, focusing on the role of platelets in the formation of premetastatic niches (PMNs). We find that a HFD provokes pre-activation of platelets and endothelial cells, promoting the formation of PMNs in the lung. These niches are characterized by increased vascular leakiness, platelet activation and overexpression of fibronectin in both platelets and endothelial cells. A HFD promotes interactions between platelets, tumor cells and endothelial cells within PMNs, enhancing tumor cell homing and metastasis. Importantly, therapeutic interventions like anti-platelet antibody administration or a dietary switch reduce metastatic cell homing and outgrowth. Moreover, blocking fibronectin reduces the interaction of tumor cells with endothelial cells. Importantly, when coagulation parameters prior to neoadjuvant treatment are considered, triple negative breast cancer (TNBC) female patients with reduced Partial Thromboplastin time (aPTT) had a significantly shorter time to relapse. These findings highlight how diet and platelet activation in pre-metastatic niches affect tumor cell homing and metastasis, suggesting potential therapeutic interventions and prognostic markers for TNBC patients. Previous work has identified a link between obesity and breast cancer metastasis. Here, using preclinical mouse models, the authors show that high-fat diet promotes platelet and endothelial cell activation in the lungs resulting in the development premetastatic niches, enhancing tumor cell homing and metastasis.

BOB.1, encoded by POU2AF1 , is one of many factors regulating physiological B-cell maturation in the germinal center. Recently, several studies have described recurrent mutations in a three-nucleotide region in the POU2AF1 splice site in the two most common B-cell non-Hodgkin lymphomas: diffuse large B-cell lymphoma and, more frequently, follicular lymphoma. In this study, we introduced a C→G mutation at the + 1 position of the POU2AF1 splice site in two B-cell lymphoma cell lines (WSU-NHL and SUDHL4) using CRISPR/Cas9 gene editing. Our results demonstrate how point mutations in the POU2AF1 splice site decreased BOB.1 expression levels. The mutation did not produce significant changes in cell proliferation, migration, or invasiveness, but did affect cell morphology, aggregation, and cell survival in a cell-line-dependent manner. Lastly, we found that the POU2AF1 mutation c.16 + 1G > C increased BCR activation, especially in SUDHL4 cells, downregulated oxidative phosphorylation (OxPhos) metabolism, and modified therapy sensitivities in both cell lines. Mutated B-cells were more sensitive to the BTK inhibitor ibrutinib. In conclusion, mutations in the POU2AF1 splice site impact B-cell lymphomagenesis at multiple levels and represent a potential therapeutic target for patients with tumors harboring this mutation.

The emerging chikungunya virus (CHIKV), is an arbovirus causing intense outbreaks in North America. The situation in Mexico is alarming, and CHIKV threatens to spread further throughout North America. Clinical and biological features of CHIKF outbreaks in Mexico have not been well described; thus, we conducted a cross sectional study of a CHIKV outbreak in Chiapas, Southern Mexico to further characterize these features. We collected blood samples from patients suspected of having chikungunya fever (CHIKF) who presented to Clinical Hospital ISSSTE Dr. Roberto Nettel in Tapachula, Chiapas, Mexico. In addition to the clinical examination, real-time polymerase chain reaction (PCR) standardized for the Asian Chikungunya lineage and/or enzyme-linked immunosorbent assay for immunoglobulin M (IgM) were used to confirm CHIKV diagnosis. Of a total of 850 patients who presented with probably CHIKV at Hospital \"Dr. Roberto Nettel\", 112 probable CHIKF cases were enrolled in this study from November 2014- June 2015, of which 95 patients (84.8%) were CHIKV positive and 17 were negative (15.2%). Of these 95 CHIKV positive patients, 62 were positive by real-time reverse transcriptase PCR (+qRT-PCR); and 33 were seropositive to +IgM with a negative qRT-PCR. The most frequent symptoms reported were fever (100%), headache (82.3%), polyarthralgia (72.1%), and exanthem (82.3%). Biological abnormalities observed during CHIKV infection were lymphopenia (41.1%), leukopenia (51.6%), elevated transaminases (30.5%-46.3%) and high LDH (46.3%) and CRP (60.0%). Clinical and biological data obtained from this study is providing more useful information for benchmarking purposes with outbreaks from different parts of the world and would be helpful for better patient care and treatment.

Background: Many advances have been made in hip labral repair and reconstruction and in the restoration of the suction seal. Purpose/Hypothesis: The purpose of this study was to evaluate the biomechanical effects of segmental labral reconstruction with a synthetic polyurethane scaffold (PS) in comparison with segmental labrectomy. Our hypothesis was that reconstruction with a icroporous polyurethane implant would normalize joint kinetics of the hip and restore the suction seal. Study Design: Controlled laboratory study. Methods: We used 10 hips from 5 fresh-frozen pelvises with an intact acetabular labrum without osteoarthritis. Using an intra-articular pressure measurement system, the contact area, contact pressure, and peak force were assessed for the following conditions: intact labrum, partial anterosuperior labrectomy, and PS reconstruction. For each condition, all specimens were analyzed in 4 positions (90° of flexion, 90° of flexion and internal rotation, 90° of flexion and external rotation, and 20° of extension) and underwent a labral seal test. The relative change from the intact condition was determined for all conditions and positions. Results: Compared with the intact labrum, labrectomy resulted in a significant decrease in the contact area (P < .001) and a significant increase in the peak force (P < .001) and contact pressure (P < .001) across all positions. Compared with labrectomy, PS reconstruction resulted in a significant increase in the contact area (P < .001) and a significant decrease in the contact pressure (P ≤ .02) and peak force (P < .001) across all positions. Compared with the intact labrum, PS reconstruction restored the contact area and peak force to normal values in all positions (P > .05), whereas the contact pressure was significantly decreased compared with labrectomy (P < .05) but did not return to normal values. The labral seal was lost in all specimens after labrectomy but was restored in 80% of the specimens after PS reconstruction. Conclusion: Femoroacetabular contact biomechanics significantly worsened after partial labrectomy; reconstruction using a PS restored the contact area and peak force to the intact state and improved the contact pressure increases seen after partial labrectomy. The contact area and peak force were normalized, and the labral seal was re-established in most cases. Clinical Relevance: This study provides biomechanical evidence for the use of a scaffold for labral reconstruction.

This research is focused on the influence of carbonate minerals on the properties of ceramic blocks as a replacement for commercial stabilizers, using three types of clays and sawdust as raw materials extracted from Chiapas, Mexico, for their application in thermal insulation on lightweight construction systems of local buildings. The effective thermal conductivity of each sample was tested by the guarded hot plate method in a permanent state, and their physical and chemical properties were determined by water absorption, X-ray powder diffraction, and X-ray fluorescence spectroscopy techniques. The results directed attention toward the knowledge of the role of the parameters in improving the thermal insulation properties, highlighting calcite as a favorable stabilizer in the manufacture of such blocks. Furthermore, the parameter affecting the thermal conductivity of the samples is the mass percentage of magnesium oxide (MgO) in a positive linear trend. Finally, the volumetric proportions of the sawdust as a pore-forming aggregate influence the decrease in the bulk density in the ceramic blocks and, thus, the reduction in the thermal conductivity.

Background: The integrity of the acetabular labrum is critical in providing normal function and minimizing hip degeneration and is considered key for success in today’s hip preservation algorithm. Many advances have been made in labral repair and reconstruction to restore the suction seal. Purpose/Hypothesis: To compare the biomechanical effects of segmental labral reconstruction between the synthetic polyurethane scaffold (PS) and fascia lata autograft (FLA). Our hypothesis was that reconstruction with a macroporous polyurethane implant and autograft reconstruction of fascia lata would normalize hip joint kinetics and restore the suction seal. Study Design: Controlled laboratory study. Methods: Ten cadaveric hips from 5 fresh-frozen pelvises underwent biomechanical testing with a dynamic intra-articular pressure measurement system under 3 conditions: (1) intact labrum, (2) reconstruction with PS after a 3-cm segmental labrectomy, then (3) reconstruction with FLA. Contact area, contact pressure, and peak force were evaluated in 4 positions: 90º of flexion in neutral, 90º of flexion plus internal rotation, 90º of flexion plus external rotation, and 20º of extension. A labral seal test was performed for both reconstruction techniques. The relative change from the intact condition (value = 1) was determined for all conditions and positions. Results: PS restored contact area to at least 96% of intact (≥0.96; range, 0.96-0.98) in all 4 positions, and FLA restored contact area to at least 97% (≥0.97; range, 0.97-1.19). Contact pressure was restored to ≥1.08 (range, 1.08-1.11) with the PS and ≥1.08 (range, 1.08-1.10) with the FLA technique. Peak force returned to ≥1.02 (range, 1.02-1.05) with PS and ≥1.02 (range, 1.02-1.07) with FLA. No significant differences were found between the reconstruction techniques in contact area in any position (P > .06), with the exception that FLA presented greater contact area in flexion plus internal rotation as compared with PS (P = .003). Suction seal was confirmed in 80% of PSs and 70% of FLAs (P = .62). Conclusion: Segmental hip labral reconstruction using PS and FLA reapproximated femoroacetabular contact biomechanics close to the intact state. Clinical Relevance: These findings provide preclinical evidence supporting the use of a synthetic scaffold as an alternative to FLA and therefore avoiding donor site morbidity.

Diabetic foot is associated with a low quality of life since physical disabilities, mood disturbances and psychological disorders are frequent. One of the most important biological processes to ensure quality of life is sleep. Sleep disorders can impair glycemic control in patients with diabetes mellitus or even cause long-term type 2 diabetes mellitus. The aim of this study is to carry out a scoping review about the association between sleep cycle disorders and diabetic foot. PubMed, Scopus, CINAHL, PEDro, Cochrane Library, SCIELO and EMBASE databases were chosen for the search and the following terms were used: “diabetic foot”,“sleep*”,“rest-activity”,“mood” and“behavior”. All the studies should include outcome variables about sleep and diabetic foot. Finally, 12 articles were selected, all of whichwere observational. The most frequent variables were those regarding diabetic foot ulcer aspects and diabetic neuropathy on one side, and obstructive sleep apnea, sleep duration and sleep quality on the other side. The results suggest that there is a possible association between obstructive sleep apnea and the presence or history of diabetic foot ulcers. No direct associations between sleep quality or sleep duration and diabetic foot or diabetic foot ulcer variables have been found.

Purpose To determine whether the bathing of an anterior cruciate ligament (ACL) autograft in vancomycin reduces the rate of infection following an ACL reconstruction. Methods Retrospective analysis of all ACL reconstructions over an 8-year period in two University Hospitals. In the initial 4-year period, all patients were operated on under classical antibiotic intravenous prophylaxis (group 1). Over the last 4-year period, this prophylaxis was supplemented with presoaking of the autograft (group 2). Presoaking was performed with sterile gauze previously saturated with a vancomycin solution (5 mg/ml). Results There were 810 and 734 patients in group 1 and 2, respectively. Fifteen cases of knee joint infections were identified in the series (0.97 %). All of these infections occurred in group 1, representing a rate of infection of 1.85 % in comparison with 0 % in group 2 ( p  < 0.001). Conclusions Autograft presoaking with vancomycin in combination with classical intravenous antibiotic prophylaxis reduced the rate of knee joint infection following an ACLR in comparison with antibiotic prophylaxis alone. This technique could be of relevance in daily clinical practice to prevent infection after ACLR. Level of evidence Case control study, retrospective comparative study, Level III.

Background Mutations in the coding region of FOXP2 are known to cause speech and language impairment. However, it is not clear how dysregulation of the gene contributes to language deficit. Interestingly, microdeletions of the region downstream the gene have been associated with cognitive deficits. Methods Here, we investigate changes in FOXP2 expression in the SK-N-MC neuroblastoma human cell line after deletion by CRISPR-Cas9 of two enhancers located downstream of the gene. Results Deletion of any of these two functional enhancers downregulates FOXP2 , but also upregulates the closest 3′ gene MDFIC . Because this effect is not statistically significant in a HEK 293 cell line, derived from the human kidney, both enhancers might confer a tissue specific regulation to both genes. We have also found that the deletion of any of these enhancers downregulates six well-known FOXP2 target genes in the SK-N-MC cell line. Conclusions We expect these findings contribute to a deeper understanding of how FOXP2 and MDFIC are regulated to pace neuronal development supporting cognition, speech and language.

Autoimmune polyendocrine syndrome (APS) is assumed to involve an immune system malfunction and entails several autoimmune diseases co-occurring in different tissues of the same patient; however, they are orphans of its accurate diagnosis, as its genetic basis and pathogenic mechanism are not understood. Our previous studies uncovered alterations in the ATPase H+/K+ Transporting Subunit Alpha (ATP4A) proton pump that triggered an internal cell acid–base imbalance, offering an autoimmune scenario for atrophic gastritis and gastric neuroendocrine tumors with secondary autoimmune pathologies. Here, we propose the genetic exploration of APS involving gastric disease to understand the underlying pathogenic mechanism of the polyautoimmune scenario. The whole exome sequencing (WES) study of five autoimmune thyrogastric families uncovered different pathogenic variants in SLC4A2, SLC26A7 and SLC26A9, which cotransport together with ATP4A. Exploratory in vitro studies suggested that the uncovered genes were involved in a pathogenic mechanism based on the alteration of the acid–base balance. Thus, we built a custom gene panel with 12 genes based on the suggested mechanism to evaluate a new series of 69 APS patients. In total, 64 filtered putatively damaging variants in the 12 genes of the panel were found in 54.17% of the studied patients and none of the healthy controls. Our studies reveal a constellation of solute carriers that co-express in the tissues affected with different autoimmune diseases, proposing a unique genetic origin for co-occurring pathologies. These results settle a new-fangled genetics-based mechanism for polyautoimmunity that explains not only gastric disease, but also thyrogastric pathology and disease co-occurrence in APS that are different from clinical incidental findings. This opens a new window leading to the prediction and diagnosis of co-occurring autoimmune diseases and clinical management of patients.