Changes in environmental exposures over decades may influence the genetic architecture of severe spermatogenic failure.

STUDY QUESTION: Do the genetic determinants of idiopathic severe spermatogenic failure (SPGF) differ between generations? SUMMARY ANSWER: Our data support that the genetic component of idiopathic SPGF is impacted by dynamic changes in environmental exposures over decades. WHAT IS KNOWN ALREADY: The idiopathic form of SPGF has a multifactorial etiology wherein an interaction between genetic, epigenetic, and environmental factors leads to the disease onset and progression. At the genetic level, genome-wide association studies (GWASs) allow the analysis of millions of genetic variants across the genome in a hypothesis-free manner, as a valuable tool for identifying susceptibility risk loci. However, little is known about the specific role of non-genetic factors and their influence on the genetic determinants in this type of conditions. STUDY DESIGN, SIZE, DURATION: Case-control genetic association analyses were performed including a total of 912 SPGF cases and 1360 unaffected controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants had European ancestry (Iberian and German). SPGF cases were diagnosed during the last decade either with idiopathic non-obstructive azoospermia (n = 547) or with idiopathic non-obstructive oligozoospermia (n = 365). Case-control genetic association analyses were performed by logistic regression models considering the generation as a covariate and by in silico functional characterization of the susceptibility genomic regions. MAIN RESULTS AND THE ROLE OF CHANCE: This analysis revealed 13 novel genetic association signals with SPGF, with eight of them being independent. The observed associations were mostly explained by the interaction between each lead variant and the age-group. Additionally, we established links between these loci and diverse non-genetic factors, such as toxic or dietary habits, respiratory disorders, and autoimmune diseases, which might potentially influence the genetic architecture of idiopathic SPGF. LARGE SCALE DATA: GWAS data are available from the authors upon reasonable request. LIMITATIONS, REASONS FOR CAUTION: Additional independent studies involving large cohorts in ethnically diverse populations are warranted to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Overall, this study proposes an innovative strategy to achieve a more precise understanding of conditions such as SPGF by considering the interactions between a variable exposome through different generations and genetic predisposition to complex diseases. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the "Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020)" (ref. PY20_00212, P20_00583), the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. PID2020-120157RB-I00 funded by MCIN/ AEI/10.13039/501100011033), and the 'Proyectos I+D+i del Programa Operativo FEDER 2020' (ref. B-CTS-584-UGR20). ToxOmics-Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, is also partially supported by the Portuguese Foundation for Science and Technology (Projects: UIDB/00009/2020; UIDP/00009/2020). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

C4BP(ß-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients.

The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed. The minor isoform of the complement inhibitor C4b-binding protein, C4BP(ß-), has been shown to confer a robust anti-inflammatory and immunomodulatory phenotype over inflammatory myeloid cells. Here we show that C4BP(ß-)-mediated immunomodulation can significantly attenuate the histopathological traits and preserve the intestinal epithelial integrity in dextran sulfate sodium (DSS)-induced murine colitis. C4BP(ß-) downregulated inflammatory transcripts, notably those related to neutrophil activity, mitigated circulating inflammatory effector cytokines and chemokines such as CXCL13, key in generating ectopic lymphoid structures, and, overall, prevented inflammatory immune cell infiltration in the colon of colitic mice. PRP6-HO7, a recombinant curtailed analogue with only immunomodulatory activity, achieved a similar outcome as C4BP(ß-), indicating that the therapeutic effect is not due to the complement inhibitory activity. Furthermore, both C4BP(ß-) and PRP6-HO7 significantly reduced, with comparable efficacy, the intrinsic and TLR-induced inflammatory markers in myeloid cells from both ulcerative colitis and Crohn's disease patients, regardless of their medication. Thus, the pleiotropic anti-inflammatory and immunomodulatory activity of PRP6-HO7, able to "reprogram" myeloid cells from the complex inflammatory bowel environment and to restore immune homeostasis, might constitute a promising therapeutic option for IBD.

Is prophylactic mesh closure effective to decrease the incidence of incisional hernia after laparotomy in colorectal surgery?

BACKGROUND: few studies have studied prophylactic mesh closure after laparotomy for colorectal surgery. METHODS: a retrospective cohort study was performed to compare patients with and without prophylactic mesh closure after open colorectal surgery. RESULTS: 309 patients were included from January 2014 to December 2016. Prophylactic mesh closure was performed in 98 patients (31.7%). After a mean follow-up of 21.7 months, incisional hernia was developed in 9 and 54 patients in the group with and without mesh respectively (9.2% vs. 25.7%, OR = 0.3, p = 0.001). In the multivariate Cox model prophylactic mesh closure was associated with a protective effect on incisional hernia development with a Hazard Ratio of 0.46 (p = 0.033). Surgical site infection was more frequent in the mesh group (19.4% vs. 9.5%, OR = 2.3, p = 0.015). CONCLUSIONS: prophylactic mesh closure is effective to decrease the incidence of incisional hernia after colorectal surgery.

Complement components as promoters of immunological tolerance in dendritic cells.

Complement and dendritic cells (DCs) share many functional features that drive the outcome of immune-inflammatory processes. Both have a sentinel function, acting as danger sensors specialized for a rapid, comprehensive and selective action against potential threats without damaging the healthy host cells. But while complement has been considered as a "master alarm" system poised for direct pathogen killing, DCs are regarded as "master regulators" or orchestrators of a vast range of effector immune cells for an effective immune response against threatening insults. The original definition of the complement system, coined to denote its auxiliary function to enhance or assist in the role of antibodies or phagocytes to clear microbes or damaged cells, envisaged an important crosstalk between the complement and the mononuclear phagocyte systems. More recent studies have shown that, depending on the microenvironmental conditions, several complement effectors are competent to influence the differentiation and/or function of different DC subsets toward immunogenicity or tolerance. In this review we will infer about the capability of complement activators and inhibitors to "condition" a tolerogenic and anti-inflammatory immune response by direct interaction with DC surface receptors, and about the implications of this knowledge to devise new complement-based therapeutic approaches for autoimmune pathologies.

Noncanonical immunomodulatory activity of complement regulator C4BP(ß-) limits the development of lupus nephritis.

Lupus nephritis is a chronic autoimmune-inflammatory condition that can lead to end-stage kidney disease. Presently available immunosuppressive treatments for lupus nephritis are suboptimal and can induce significant side effects. Recently, we characterized a novel immunomodulatory activity of the minor isoform of the classical pathway complement inhibitor, C4BP(ß-). We show here that C4BP(ß-) treatment prevented the development of proteinuria and albuminuria, decreased significantly the formation of anti-dsDNA antibodies and, locally, mitigated renal glomerular IgG and C3 deposition and generation of apoptotic cells. There was a consequent histological improvement and increased survival in lupus-prone mice. The therapeutic efficacy of C4BP(ß-) was analogous to that of the broad-acting immunosuppressant cyclophosphamide. Remarkably, a comparative transcriptional profiling analysis revealed that the kidney gene expression signature resulting from C4BP(ß-) treatment turned out to be 10 times smaller than that induced by cyclophosphamide treatment. C4BP(ß-) immunomodulation induced significant downregulation of transcripts relevant to lupus nephritis indicating immunopathogenic cell infiltration, including activated T cells (Lat), B cells (Cd19, Ms4a1, Tnfrsf13c), inflammatory phagocytes (Irf7) and neutrophils (Prtn3, S100a8, S100a9). Furthermore, cytokine profiling and immunohistochemistry confirmed that C4BP(ß-), through systemic and local CXCL13 downregulation, was able to prevent ectopic lymphoid structures neogenesis in aged mice with lupus nephritis. Thus, due to its anti-inflammatory and immunomodulatory activities and high specificity, C4BP(ß-) could be considered for further clinical development in patients with systemic lupus erythematosus.

Extraction-site incisional hernia after laparoscopic colorectal surgery: should we carry out a study about prophylactic mesh closure?

BACKGROUND: Prophylactic mesh closure has only scarcely been studied to avoid extraction-site incisional hernia after laparoscopic colorectal surgery. The aim was to analyze extraction-site incisional hernia incidence after laparoscopic colorectal surgery to assess if prophylactic mesh closure should be studied. METHODS: A retrospective analytic cohort study was conducted in patients who had undergone laparoscopic colorectal surgery with an extraction-site incision. Extraction-site incisional hernia was diagnosed during clinical examination or imaging. Risk factors for extraction-site incisional hernia were analyzed. RESULTS: Two hundred and twenty-five patients were included. More than 80% of the patients had a malignant disease. Ninety-two patients (40.9%) underwent right colectomy. Midline extraction-site incision was used in 86 (38.2%) patients. After a mean follow-up of 2.4 years, 39 (17.3%) patients developed an extraction-site incisional hernia. Midline extraction-site incision was associated with incisional hernia when compared to transverse and Pfannenstiel incision (39.5% vs. 3.6%, OR 17.5, p < 0.001). Surgery to repair an extraction-site incisional hernia was also more frequent in the group of patients with a midline incision (10.5% vs. 1.4%, OR 8.0, p = 0.002). In the multivariate analysis, incisional hernia was associated with body mass index, high blood pressure, and midline incision. CONCLUSIONS: Extraction-site incisional hernia was mainly related to midline incisions; therefore, midline incision should be avoided whenever possible. Studying prophylactic mesh closure for Pfannesnstiel or transverse incisions is needless, as these incisions have a low incisional hernia risk.

Transform-Based Multiresolution Decomposition for Degradation Detection in Cellular Networks.

Anomaly detection in the performance of the huge number of elements that are part of cellular networks (base stations, core entities, and user equipment) is one of the most time consuming and key activities for supporting failure management procedures and ensuring the required performance of the telecommunication services. This activity originally relied on direct human inspection of cellular metrics (counters, key performance indicators, etc.). Currently, degradation detection procedures have experienced an evolution towards the use of automatic mechanisms of statistical analysis and machine learning. However, pre-existent solutions typically rely on the manual definition of the values to be considered abnormal or on large sets of labeled data, highly reducing their performance in the presence of long-term trends in the metrics or previously unknown patterns of degradation. In this field, the present work proposes a novel application of transform-based analysis, using wavelet transform, for the detection and study of network degradations. The proposed system is tested using cell-level metrics obtained from a real-world LTE cellular network, showing its capabilities to detect and characterize anomalies of different patterns and in the presence of varied temporal trends. This is performed without the need for manually establishing normality thresholds and taking advantage of wavelet transform capabilities to separate the metrics in multiple time-frequency components. Our results show how direct statistical analysis of these components allows for a successful detection of anomalies beyond the capabilities of detection of previous methods.

Asymmetric organocatalytic synthesis of tertiary azomethyl alcohols: key intermediates towards azoxy compounds and α-hydroxy-ß-amino esters.

A series of peracylated glycosamine-derived thioureas have been synthesized and their behavior as bifunctional organocatalysts has been tested in the enantioselective nucleophilic addition of formaldehyde tert-butyl hydrazone to aliphatic α-keto esters for the synthesis of tertiary azomethyl alcohols. Using the 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-ß-d-glucosamine derived 3,5-bis-(trifluoromethyl)phenyl thiourea the reaction could be accomplished with high yields (75-98%) and moderate enantioselectivities (50-64% ee). Subsequent high-yielding and racemization-free tranformations of both aromatic- and aliphatic-substituted diazene products in a one pot fashion provide a direct entry to valuable azoxy compounds and α-hydroxy-ß-amino esters.

Mapping chemical disorder and ferroelectric distortions in the double perovskite compound Sr 2-x Gd x MnTiO6 by atomic resolution electron microscopy and spectroscopy.

In this work we report a study of the chemical and structural order of the double perovskite compound Sr 2-x Gd x MnTiO6 for compositions x=0, 0.25, 0.5, 0.75, and 1. A noticeable disorder at the B-site in the Mn and Ti sublattice is detected at the atomic scale by electron energy-loss spectroscopy for all x values, resulting in Mn-rich and Ti-rich regions. For x ≥ 0.75, the cubic unit cell doubles and lowers its symmetry because of structural rearrangements associated with a giant ferroelectric displacement of the perovskite B-site cation. We discuss this finding in the light of the large electroresistance observed in Sr 2-x Gd x MnTiO6, x ≥ 0.75.

Structural Characterization and Magnetic Behavior Due to the Cationic Substitution of Lanthanides on Ferrite Nanoparticles.

A new series of [Fe3-xLnx]O4 nanoparticles, with Ln = Gd; Dy; Lu and x = 0.05; 0.1; 0.15, was synthesized using the coprecipitation method. Analyses by X-ray diffraction (XRD), Rietveld refinement, and high-resolution transmission electron microscopy (HRTEM) indicate that all phases crystallized in space group Fd3¯m, characteristic of spinels. The XRD patterns, HRTEM, scanning electron microscopy analysis (SEM-EDS), and Raman spectra showed single phases. Transmission electron microscopy (TEM), Rietveld analysis, and Scherrer's calculations confirm that these materials are nanoparticles with sizes in the range of ~6 nm to ~13 nm. Magnetic measurements reveal that the saturation magnetization (Ms) of the as-prepared ferrites increases with lanthanide chemical substitution (x), while the coercivity (Hc) has low values. The Raman analysis confirms that the compounds are ferrites and the Ms behavior can be explained by the relationship between the areas of the signals. The magnetic measurements indicate superparamagnetic behavior. The blocking temperatures (TB) were estimated from ZFC-FC measurements, and the use of the Néel equation enabled the magnetic anisotropy to be estimated.

Gut Microbiota Signatures with Potential Clinical Usefulness in Colorectal and Non-Small Cell Lung Cancers.

The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.

Aortic injury during laparoscopic esophageal hiatoplasty.

A 75-year-old female patient with a type III hiatal hernia was submitted to laparoscopic mesh hiatoplasty. Soon after the last suture fixed the mesh to the left crura, a hemorrhage was observed. Conversion to open surgery was not performed. The most common sources of bleeding (liver, phrenic arteries, crura, spleen, and short gastric vessels) were discarded as the cause of the hemorrhage. The mesh was set free in order to explore the lower mediastinum. The source of the hemorrhage was identified: it was the last suture fixing the mesh to the left crura, which was found passing through the aortic wall. The hemorrhage stopped as soon as the suture was removed. When facing a hemorrhage during this kind of surgery, it is essential to be methodical to discover the source of the bleeding. First of all, the most common sources of bleeding must be checked out. Injury of the inferior vena cava must also be ruled out, because it is an uncommon but potentially lethal complication. Afterwards, the lower mediastinum must be explored. Conversion to an open approach is needed if the patient becomes unstable or the surgeon does not have enough laparoscopic skills to find and solve the bleeding. Most of the reported cases of aortic injury during laparoscopic hiatoplasty are secondary to vascular injuries during port insertion. When a suture is the cause of bleeding, the removal of the stitch should be enough to stop the bleeding. If there is a tear of the aortic wall, a patch should be employed for the repair. In conclusion, left crura and thoracic aorta are very close to one another. The surgeon must be very careful when working near the left crura, mostly in old patients with a dilated and aneurysmatic aorta.

Commercially Accessible High-Performance Aluminum-Air Battery Cathodes through Electrodeposition of Mn and Ni Species on Fuel Cell Cathodes.

This study presents a cost-effective method for producing high-performance cathodes for aluminum-air batteries. Commercial fuel cell cathodes are modified through electrodeposition of nickel and manganese species. The optimal conditions for electrodeposition are determined using a combination of structural (Raman, SEM, TEM) and electrochemical (LSV, EI, discharge curves) characterization techniques. The structural analysis confirms successful incorporation of nickel and manganese species onto the cathode surface. Electrochemical tests demonstrate enhanced electrochemical activity compared to unmodified cathodes. By combining the favorable properties of electrodeposited manganese species with nickel species, a high-performance cathode is obtained. The developed cathode exhibits capacities of 50 mA h cm-2 in aluminum-air batteries across a wide range of current densities. The electrodeposition method proves effective in improving electrochemical performance. A key advantage of this method is its simplicity and cost-effectiveness. The use of commercially available materials and well-established electrodeposition techniques allows for easy scalability and commercialization. This makes it a viable option for large-scale production of high-performance cathodes for the next-generation energy storage devices.

Structural Characterization and Thermoelectric Properties of Br-Doped AgSnm[Sb0.8Bi0.2]Te2+m Systems.

Herein, we report the synthesis, structural and microstructural characterization, and thermoelectric properties of AgSnm[Sb0.8Bi0.2]Te2+m and Br-doped telluride systems. These compounds were prepared by solid-state reaction at high temperature. Powder X-ray diffraction data reveal that these samples exhibit crystal structures related to the NaCl-type lattice. The microstructures and morphologies are investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy (EDS), and high-resolution transmission electron microscopy (HRTEM). Positive values of the Seebeck coefficient (S) indicate that the transport properties are dominated by holes. The S of undoped AgSnm[Sb0.8Bi0.2]Te2+m ranges from +40 to 57 µV·K-1. Br-doped samples with m = 2 show S values of +74 µV·K-1 at RT, and the Seebeck coefficient increases almost linearly with increasing temperature. The total thermal conductivity (κtot) monotonically increases with increasing temperature (10-300 K). The κtot values of undoped AgSnm[Sb0.8Bi0.2]Te2+m are ~1.8 W m-1 K-1 (m = 4) and ~1.0 W m-1 K-1 (m = 2) at 300 K. The electrical conductivity (σ) decreases almost linearly with increasing temperature, indicating metal-like behavior. The ZT value increases as a function of temperature. A maximum ZT value of ~0.07 is achieved at room temperature for the Br-doped phase with m = 4.

Expression Analysis of hsa-miR-181a-5p, hsa-miR-143-3p, hsa-miR-132-3p and hsa-miR-23a-3p as Biomarkers in Colorectal Cancer-Relationship to the Body Mass Index.

This work aims to investigate the expression levels of four preselected miRNAs previously linked to cancer and/or obesity, with the purpose of finding potential biomarkers in the clinical management of CRC developed by patients showing different BMI values. We analyzed samples from a total of 65 subjects: 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were investigated, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (hsa-miR-181a-5p, hsa-miR-143-3p, has-miR-132-3p and hsa-miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC, serum levels of hsa-miR-143-3p clearly correlated with their levels in both SAT and OAT, independently of the BMI group. Moreover, hsa-miR-181a-5p could be considered as a biomarker in CRC patients with BMI ≥ 25 Kg/m2 and emerges as a tumor location marker. We conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, and hsa-miR-143-3p and hsa-miR-181a-5p expression analysis could be useful in the clinical management of CRC.

Gut microbiota profiles in feces and paired tumor and non-tumor tissues from Colorectal Cancer patients. Relationship to the Body Mass Index.

Colorectal Cancer (CRC) and Obesity constitute two of the most common malignancies in the western world, and previously have been associated with intestinal microbial composition alterations. Our main aim in this study is to provide molecular data on intestinal microbiota patterns in subjects with CRC, as well as to establish possible associations with their Body Mass Index (BMI). A total of 113 samples from 45 subjects were collected and submitted to metagenomics analysis for gut microbiota. This study was performed by 16S ribosomal RNA bacterial gene amplification and sequencing using the Ion Torrent™ technology. The same dominant phyla were observed in feces and colorectal tissues, although a greater proportion of Fusobacteriota was found in tumor samples. Moreover, at the genus level, LEfSe analysis allowed us to detect a significant increase in Fusobacterium and Streptococcus in colorectal tissues with respect to fecal samples, with a significant preponderance of Fusobacterium in tumor tissues. Also, our data revealed relevant associations between gut microbiota composition and tumor location. When comparing bacterial profiles between right and left colon cancers, those from the left-sided colon showed a significant preponderance, among others, of the order Staphylococcales. Moreover, phyla Firmicutes and Spirochaetota were more abundant in the group of right-sided CRCs and phylum Proteobacteria was increased in rectal cancers. In relation to BMI of patients, we detected significant differences in beta diversity between the normal weight and the obese groups of cases. Microbiota from obese patients was significantly enriched, among others, in Bacteroidales. Therefore, our results are useful in the molecular characterization of CRC in obese and non-obese patients, with a clear impact on the establishment of diagnostic and prognosis of CRC.

The Hidden Side of Complement Regulator C4BP: Dissection and Evaluation of Its Immunomodulatory Activity.

C4b-binding protein (C4BP) is a well-known regulator of the complement system that holds additional and important activities unrelated to complement inhibition. Recently, we have described a novel immunomodulatory activity in the minor C4BP(ß-) isoform directly acting over inflammatory phagocytes. Here we show that incorporation of the ß-chain to the C4BP α-chain oligomer interferes with this immunomodulatory activity of C4BP. Moreover, an oligomeric form including only the complement control protein 6 (CCP6) domain of the C4BP α-chain (PRP6-HO7) is sufficient to "reprogram" monocyte-derived DCs (Mo-DCs) from a pro-inflammatory and immunogenic phenotype to an anti-inflammatory and tolerogenic state. PRP6-HO7 lacks complement regulatory activity but retains full immunomodulatory activity over inflammatory Mo-DCs induced by TLRs, characterized by downregulation of relevant surface markers such as CD83, HLA-DR, co-stimulatory molecules such as CD86, CD80 and CD40, and pro-inflammatory cytokines such as IL-12 and TNF-α. Furthermore, PRP6-HO7-treated Mo-DCs shows increased endocytosis, significantly reduced CCR7 expression and CCL21-mediated chemotaxis, and prevents T cell alloproliferation. Finally, PRP6-HO7 shows also full immunomodulatory activity over Mo-DCs isolated from lupus nephritis patients with active disease, even without further pro-inflammatory stimulation. Therefore PRP6-HO7, retaining the immunomodulatory activity of C4BP(ß-) and lacking its complement regulatory activity, might represent a promising and novel alternative to treat autoimmune diseases.

Telomere Length and Telomerase Activity in Subcutaneous and Visceral Adipose Tissues from Obese and Non-Obese Patients with and without Colorectal Cancer.

To investigate the molecular mechanisms that link obesity and colorectal cancer (CRC), we analyzed parameters related to telomere function in subcutaneous and visceral adipose tissues (SAT and VAT), including subjects with and without CRC, who were classified according to their body mass index (BMI). Adipose tissues were obtained from 147 patients who had undergone surgery. A total of 66 cases corresponded to CRC patients, and 81 subjects were not affected by cancer. Relative telomere length was established by qPCR, and telomerase activity was determined by a method based on the telomeric repeat amplification protocol. Our results indicated longer telomeres in patients affected by CRC, both in SAT and VAT, when compared to the group of subjects without CRC. Tumor local invasion was associated with telomere length (TL) in SAT. Considering the BMI values, significant differences were found in the TL of both adipose tissues between subjects affected by CRC and those without cancer. Overweight subjects showed the greatest differences, with longer telomeres in the group of CRC patients, and a higher number of cases with telomerase reactivation in the VAT of subjects without cancer. In conclusion, parameters related to telomere function in adipose tissue could be considered as potential biomarkers in the evaluation of CRC and obesity.

[Potential usefulness of CT as a marker of persistence of positive PCR in patients with COVID-19.] / Potencial utilidad del CT como marcador de persistencia de PCR positiva en pacientes con COVID-19.

OBJECTIVE: One of the problems associated to SARS-CoV-2 was its persistence in nasopharyngeal tract. The existence of markers that help to predict this situation could be useful to management of the patients. The objective of this paper was to determine the relationship between the CT value from the initial PCR of patients with COVID-19 and the persistence of the infection. METHODS: It was performed an observational retrospective study of patients with positive PCR to SARS-CoV-2 attended in emergency department of a general hospital. Data about compatible symptoms, radiological findings and the CT value obtained with each PCR kit were collected. The control group (G0) included patients with a positive PCR followed by two negative PCR results (P-N-N), while problem group (G1) included patients with at least three consecutive positive PCR results (P-P-P). Chronic infections were discarded selecting only patients with negative serology, and only were included those whose PCR were separated by a minimum of five and maximum of twenty days. The comparison between the study groups was carried out using the t-student test for quantitative variables and the χ2 test for qualitative variables. RESULTS: The mean CT value were 30.8 and 21.5 (p<0.001) on G0 and G1, respectively. G0 reported higher CT values than G1, regardless of symptoms, radiological pattern and the PCR kit utilized. CONCLUSIONS: The CT value from the SARS-CoV-2 initial PCR is related to the persistence of its positivity, regardless of the patient´s symptoms or radiological pattern. Thus, low CT values could be related to persistent infections.

OBJETIVO: Uno de los problemas asociados al SARS-CoV-2 es su persistencia en el tracto nasofaríngeo. La existencia de marcadores que ayuden a predecir este fenómeno podría ser útil en el manejo del paciente. El objetivo de este trabajo fue determinar la relación entre el valor CT (umbral de ciclo) de la PCR inicial de pacientes con COVID-19 y la persistencia de la infección. METODOS: Se realizó un estudio observacional retrospectivo de pacientes con PCR positiva para SARS-CoV-2 atendidos en las Urgencias de un hospital general. Se recogieron datos sobre sintomatología compatible y patrón radiológico de cada paciente, así como el CT obtenido en la PCR con cada equipo utilizado. El grupo control (G0) incluyó pacientes con una PCR positiva seguida de dos negativas (patrón P-N-N), mientras que el grupo problema (G1) incluyó pacientes con al menos tres PCR positivas consecutivas (patrón P-P-P). Se descartaron las infecciones crónicas, considerando únicamente a pacientes con serología negativa, y solo se incluyeron aquellos cuyas tres PCR estuvieron separadas un mínimo de cinco días y un máximo de veinte. La comparación entre los grupos de estudio se realizó mediante el test t-student para variables cuantitativas y el test de χ2 para variables cualitativas. RESULTADOS: La media del valor CT fue de 30,8 en G0 y 21,5 en G1 (p<0,001). G0 reportó CT superiores a G1, independientemente de la sintomatología, el patrón radiológico o el equipo de PCR utilizado. CONCLUSIONES: El valor CT de la PCR inicial de SARS-CoV-2 podría relacionase con la persistencia de su positividad, independientemente de la sintomatología o el patrón radiológico del paciente. Valores bajos de CT en la primera PCR podrían relacionarse con infecciones persistentes.

The antecedents of well-being in first-generation migrant children: A systematic review.

Migrant children's well-being has emerged into the spotlight of academic literature and policy-makers in recent times. This systematic review is aimed at analysing the publication trends on the topic and at synthesising the available evidence on the antecedents of well-being of first-generation international migrant children. Systematic searches of primary studies were conducted in 18 databases using search terms related to migration, childhood and well-being. Three rounds of screening and data extraction, researchers' full agreement and the inclusion criteria produced 39 eligible studies. Critical appraisal of results revealed a fragmentation in the literature, the evidence available being mostly descriptive and focused on involuntary migrants settled in Western countries. A bias across publications overlooking younger migrant children was unveiled. The compartmentalisation of the evidence hindered an understanding of the magnitude of the different effects of migration on well-being. Antecedents of well-being have been documented as factors fostering and hindering well-being. Important gaps in literature and key antecedents of well-being have been uncovered for voluntary and involuntary migrant children. These findings show limitations in the available evidence pointing to specific suggestions for future research that should help improve interventions at the social and individual levels.