Radio-miRs: a comprehensive view of radioresistance-related microRNAs.

Radiotherapy is a key treatment option for a wide variety of human tumors, employed either alone or alongside with other therapeutic interventions. Radiotherapy uses high-energy particles to destroy tumor cells, blocking their ability to divide and proliferate. The effectiveness of radiotherapy is due to genetic and epigenetic factors that determine how tumor cells respond to ionizing radiation. These factors contribute to the establishment of resistance to radiotherapy, which increases the risk of poor clinical prognosis of patients. Although the mechanisms by which tumor cells induce radioresistance are unclear, evidence points out several contributing factors including the overexpression of DNA repair systems, increased levels of reactive oxygen species, alterations in the tumor microenvironment, and enrichment of cancer stem cell populations. In this context, dysregulation of microRNAs or miRNAs, critical regulators of gene expression, may influence how tumors respond to radiation. There is increasing evidence that miRNAs may act as sensitizers or enhancers of radioresistance, regulating key processes such as the DNA damage response and the cell death signaling pathway. Furthermore, expression and activity of miRNAs have shown informative value in overcoming radiotherapy and long-term radiotoxicity, revealing their potential as biomarkers. In this review, we will discuss the molecular mechanisms associated with the response to radiotherapy and highlight the central role of miRNAs in regulating the molecular mechanisms responsible for cellular radioresistance. We will also review radio-miRs, radiotherapy-related miRNAs, either as sensitizers or enhancers of radioresistance that hold promise as biomarkers or pharmacological targets to sensitize radioresistant cells.

A Molecular Characterization of the Allelic Expression of the BRCA1 Founder Δ9-12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer.

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9-12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9-12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT-qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9-12 alleles using nanopore long-sequencing. Using the Kruskal-Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9-12 and identifying which of them has developed cancer.

Prevalence of pathogenic or likely pathogenic germline variants in cancer predisposition genes among selected patients with lung adenocarcinoma: The GERMLUNG study.

INTRODUCTION: Pathogenic or likely pathogenic germline variants (PGVs) in cancer predisposition genes may play a role in lung cancer (LC) susceptibility. However, determining an eligible population for genetic testing remains uncertain. This study aimed to assess the prevalence of PGVs in a selected cohort of individuals with lung adenocarcinoma. METHODS: A cross-sectional cohort study was conducted to assess the PGVs rate in lung adenocarcinoma patients with a family history of LC, young-onset presentation, history of never/light smoking, or actionable genomic alterations (AGAs). Sequencing was performed using Sophia Hereditary Cancer Solution panel F, including 144 cancer predisposition genes. Variants classified as pathogenic or likely pathogenic were included for further analysis. RESULTS: Of 201 patients, 43 (21.4 %) exhibited PGVs, among which 64.5 % were DNA damage repair genes, and 86.1 % were clinically actionable. The main PGVs were in ATM (9.3 %), TP53 (6.9 %), BRCA2 (6.9 %), and CHEK2 (6.9 %) genes. PGVs were associated with male sex (adjusted odds ratio [aOR] 2.46, 95 % CI 1.15-5.32, p = 0.021), along with a trend toward association with AGAs (aOR 6.04, 95 % CI 0.77-49.74, p = 0.094). CONCLUSIONS: In this study, a high PGVs prevalence was identified based on our selection criteria, which represents an effective strategy to identify candidates for germline genomic testing, potential screening strategies in close relatives, and personalized therapeutic modalities. Our results warrant further exploration in other populations to confirm them.

An analysis of the association between breast density and body mass index with breast cancer molecular subtypes in early breast cancer: data from a Spanish population.

PURPOSE: Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes. METHODS: This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis. RESULTS: The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52 years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D. CONCLUSIONS: This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

Double Myelomeningocele Repair by Fetal Surgery with a Single Micro-Hysterotomy.

INTRODUCTION: Open spina bifida (OSB) is the most common congenital anomaly of the central nervous system. It is associated with severe neurodevelopmental delay, motor impairment, hydrocephalus, and bowel and bladder dysfunction. In selected cases, intrauterine spina bifida repair has been shown to improve neonatal outcomes. Rarely, the spine can have a double defect compromising two different segments and there is a lack of evidence on the feasibility and benefits of intrauterine repair in these cases. CASE PRESENTATION: We present a case with both cervicothoracic and lumbosacral myelomeningocele, Arnold-Chiari malformation type II and bilateral ventriculomegaly, that was treated successfully at 25 weeks with open micro-neurosurgery. Double myelomeningocele was successfully treated through a single 2-cm micro-hysterotomy, by performing external versions to sequentially expose and repair both defects. Weekly postoperative follow-up showed no progression of ventriculomegaly or complications attributable to the procedure. Preterm rupture of membranes prompted a conventional cesarean delivery at 32 weeks of gestation. Neurodevelopmental outcome at 20 months was within normal ranges, having achieved ambulation without orthopedic support and with no need for ventriculoperitoneal shunting. CONCLUSION: This report demonstrates for the first time the feasibility of double OSB repair through a single 2-cm micro-hysterotomy, suggesting that selected isolated cases of double myelomeningocele could be candidates for fetal intervention. Further prospective studies should be carried out to assess the potential benefit of double OSB intrauterine open repair.

Addressing the C/N imbalance in the treatment of irrigated agricultural water by using a hybrid constructed wetland at field-scale.

To mitigate excess of nitrate-N (NO3--N) derived from agricultural activity, constructed wetlands (CWs) are created to simulate natural removal mechanisms. Irrigated agricultural drainage water is commonly characterized by an organic carbon/nitrogen (C/N) imbalance, thus, C limitation constrains heterotrophic denitrification, the main biotic process implicated in NO3--N removal in wetlands. We studied a pilot plant with three series (169 m2) of hybrid CWs over the first two years of functioning to examine: i) the effect of adding different C-rich substrates (natural soil vs. biochar) to gravel on NO3--N removal in a subsurface flow (Phase I), ii) the role of a second phase with a horizontal surface flow (Phase II) as a source of dissolved organic C (DOC), and its effect in a consecutive horizontal subsurface flow (Phase III) on NO3--N removal, and iii) the contribution of each phase to global NO3--N removal. Our results showed that the addition of a C-rich substrate to gravel had a positive effect on NO3--N removal in Phase I, with mean efficiencies of 40% and 17% for soil and biochar addition, respectively, compared to only gravel (0.75%). In Phase II, the algae growth turned into a DOC concentration increase, but it did not enhance NO3--N removal in Phase III. In series with C-rich substrate addition, the largest contribution to NO3--N removal was found in Phase I. However, in series with only gravel, Phase II was the most effective on NO3--N removal. Contribution of Phase III to NO3--N removal was almost negligible.

Evidencia psicométrica del Cuestionario sobre la Salud del Paciente (PHQ-9) y Escala de Ansiedad Generalizada (GAD-7) en pacientes con asesoramiento genético en Oncología / Psychometric evidence of the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Scale (GAD-7) in patients with genetic counseling in Oncology

Introducción: Los síntomas de depresión y ansiedad en pacientes que reciben Asesoramiento Genético en Oncología (AGO), se encuentran dentro de las afectaciones psicológicas más prevalentes, por lo que su identificación de forma oportuna, valida y confiable es prioritaria. Objetivo: Determinar las propiedades psicométricas del Cuestionario sobre la Salud del Paciente, PHQ-9, y de la Escala de Ansiedad Generalizada, GAD-7, en pacientes con cáncer portadores de variantes patogénicas germinales en genes de alta susceptibilidad. Método: Se empleó un diseño instrumental, transversal con un muestreo no probabilístico. Se incluyeron 163 participantes con variantes patogénicas en BRCA1/BRCA2, asociadas a cáncer hereditario, entre 19 y 79 años, (48,2 ± 11,2 años). Resultados: La validez de constructo de cada instrumento se probó a través de un análisis factorial exploratorio y confirmatorio. La GAD-7 obtuvo un α = 0,899 y 62,3 % de la varianza explicada, por otro lado, el PHQ- 9 obtuvo un α = 0,896 y 54,8 % de la varianza explicada. El análisis factorial confirmatorio sugiere que los modelos teóricos de ambos instrumentos se ajustan a un solo factor, con una consistencia e índices de validez adecuados. Discusión y conclusión: El PHQ-9 y la GAD-7 son instrumentos parsimoniosos, breves, válidos y confiables para la detección de síntomas de depresión y ansiedad en pacientes que reciben AGO, en población mexicana. Se recomienda su uso en la atención clínica (al inicio, y durante el seguimiento), así como en investigaciones futuras (AU)

Introduction: The symptoms of depression and anxiety in patients receiving Genetic Counseling in Oncology (AGO) are among the most prevalent psychological affectations, so their timely, valid, and reliable identification is a priority. Objective: To determine the psychometric properties of the Patient Health Questionnaire, PHQ-9, and the Generalized Anxiety Scale, GAD-7, in cancer patients carrying germinal pathogenic variants in high susceptibility genes. Method: An instrumental, cross-sectional design was used with a non-probabilistic sampling. 163 participants with pathogenic variants in BRCA1/BRCA2, associated with hereditary cancer, between 19 and 79 years (48.2 ± 11.2 years) were included. Statistical analysis: The construct validity of each instrument was tested through an exploratory and confirmatory factor analysis. Results: The GAD-7 obtained α = 0.899 and 62.3% of the explained variance, on the other hand, the PHQ-9 obtained α = 0.896 and 54.8% of the explained variance. Confirmatory factor analysis suggests that the theoretical models of both instruments fit a single factor, with adequate consistency and validity indices. Discussion and conclusion: The PHQ-9 and the GAD-7 are parsimonious, brief, valid and reliable instruments for the detection of symptoms of depression and anxiety in patients receiving AGO, in the Mexican population. Its use is recommended in clinical care (at baseline, and during follow-up), as well as in future research (AU)

Reduction of NrF2 as coadjuvant during the development of persistent periapical lesions

Background: Persistent periapical lesions (PPL) are the result of pulpar necrosis induced by bacterial infection resulting in bone degradation and culminating with the loss of dental piece. Pathological changes in the peripapice are associated with the presence of free radicals. The transcription factor Nrf2 is the main regulator of the endogenous antioxidant response against oxidative stress and has been implicated in the regulation of osteoclastogenesis.The aim is to determine the oxidative condition in samples from patients with Persistent Periapical Injuries as a detonating factor of tissue damage. Material and methods: An observational, descriptive, cross-sectional study was carried out in samples with PPL (cases) and samples by removal of third molars (controls) obtained in the clinic of the specialty in endodontics, University of Guadalajara. Samples were submitted to histological staining with Hematoxylin-Eosin, lipoperoxide analysis, Superoxide Dismutase (SOD), Glutathione-Peroxidase (GPx) and Catalase (CAT) activities were determined by immunoenzymatic assays and NrF2 by Western Blot analysis. Results: Samples from PPL patients histologically showed an increased presence of lymphocytes, plasma cells, and eosinophils, as well as a decrease in extracellular matrix proteins and fibroblast cells. There was a rise in lipid peroxidation, GPx and SOD activities, but an important decline (36%) in Catalase activity was observed (p<0.005); finally, NrF2-protein was diminished at 10.41%. All comparisons were between cases vs controls. Conclusions: The alterations in antioxidants endogenous NrF2-controlled are related to osseous destruction in patients with PPL. (AU)

Fetal Laryngoscopy and Endoscopic Tracheal Intubation to Avoid ex utero Intrapartum Treatment in the Management of Fetuses with Suspected Airway Obstruction.

INTRODUCTION: Large congenital neck tumors can cause neonatal death due to airway obstruction. The aim of this study was to report outcomes of the first cohort of fetuses with neck masses and suspected airway obstruction managed with fetal laryngoscopy (FL) and fetal endoscopic tracheal intubation (FETI) to secure fetal airways and avoid ex utero intrapartum treatment (EXIT) procedure. METHODS: A prospective observational cohort of consecutive fetuses with neck masses that were candidates for an EXIT procedure due to suspicion of laryngeal and/or tracheal occlusion on ultrasonographic (US) or magnetic resonance imaging (MRI) examination were recruited for FL in a tertiary referral center in Queretaro, Mexico. FETI was performed if the obstruction was confirmed by FL. Maternal and perinatal outcomes were evaluated. RESULTS: Between January 2012 and March 2023, 35 cases with neck masses were evaluated. Airway obstruction was suspected in 12/35 (34.3%), either by US in 10/35 (28.6%) or by fetal MRI in 2/35 (5.7%). In all cases, FL was successfully performed at the first attempt at a median gestational age (GA) of 36+5 (range, 33+5-39+6) weeks+days, with a median surgical time of 22.5 (12-35) min. In 4 cases, airway patency was confirmed during FL and an EXIT procedure was avoided. In 8/12 cases (66.7%), airway obstruction was confirmed during fetoscopy and FETI was successfully performed at a median GA of 36+3 (33+2-38+5) weeks+days, with a median surgical time of 25.0 (range, 12-45) min. No case required an EXIT procedure. All patients underwent conventional cesarean delivery with no maternal complications and all neonates were admitted to the neonatal intensive care unit with a correctly positioned endotracheal tube (ETT) immediately after delivery. Three neonatal deaths (37.5%) were reported due to postnatal unplanned extubation, failed ETT replacement, and tumoral bleeding. CONCLUSION: In fetuses with neck masses and suspected airway obstruction, FL and FETI are feasible and could replace EXIT procedures with good maternal and perinatal outcomes.

Management of Late Twin-to-Twin Transfusion Syndrome beyond 26 Weeks: Comparison between Fetoscopic Laser Therapy versus Traditional Management.

INTRODUCTION: A proportion of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) can present after 26 weeks of gestation. The aim of this study was to compare perinatal outcomes of late TTTS treated by fetoscopic laser coagulation versus traditional management with amniodrainage and/or emergency preterm cesarean delivery (CD). METHODS: Retrospective cohort from January 2012 to January 2023 of consecutive MCDA twin pregnancies complicated by TTTS after 26 weeks and evaluated in our referring centers. We analyzed perinatal outcomes of cases treated with fetoscopic laser surgery at our national referral fetal surgery center in Queretaro, Mexico, and compared them with those managed with traditional management (amniodrainage and/or emergency preterm CD). The primary outcome was survival at discharge and the secondary outcome was gestational age (GA) at birth. RESULTS: Among the study population, 46 TTTS cases were treated by fetoscopy at 27+6 (26+0-31+0) weeks+days and were compared with a group of 39 cases who underwent emergency preterm CD. In comparison to the group who underwent traditional management, the group treated by laser fetoscopy showed a significantly higher GA at birth (32+3 vs. 29+1 weeks+days, p < 0.001), lower frequency of preterm delivery below 37 weeks (91.3% vs. 100%, p = 0.06), 34 weeks (63.0% vs. 100%, p < 0.001), 32 weeks (50% vs. 74.4%, p = 0.02), or 30 weeks (28.3% vs. 53.8%, p = 0.01), and significantly higher perinatal survival (89.1% vs. 71.8%, p < 0.05 of at least one twin; and 65.2% vs. 38.5%, p = 0.01 of both twins, respectively). CONCLUSION: MCDA twins complicated with TTTS can be treated with fetoscopic laser surgery between 26 and 31 weeks of gestation, which is a feasible and safe option, and such cases are associated with a higher GA at birth and better perinatal survival than those managed with amniodrainage and/or emergency preterm CD.

Responsabilidad social universitaria en Latinoamérica: Revisión sistemática

Introducción : La responsabilidad social universitaria está presente en los discursos de los académicos, mas no logra permear en las acciones, que conlleven a la transformación de la universidad, por lo que es necesario un cambio de paradigma. En la actualidad, existen confusiones conceptuales que hacen muy difícil su promoción y práctica transformadora; en muchas universidades, se la confunde con proyección social, lo cual reduce su dimensión transversal. Objetivo : Analizar la evidencia científica relacionada con la responsabilidad social universitaria en Latinoamérica. Métodos : Revisión sistemática de la literatura; entre los meses de agosto a diciembre de 2021, se realizó la búsqueda de artículos en las bases de datos: Scopus, Scielo, Doaj, Lilacs Y Redalyc; se aplicó el uso de los descriptores en ciencias de la salud (DECS) y la combinación de los operadores booleanos OR y AND. Se consideraron textos completos en español, entre los años 2015 a 2021. Resultados : Se obtuvo 508 artículos, los cuales fueron sometidos a la metodología prisma y se seleccionaron 20 artículos, agrupados en cuatro categorías, según el manual de responsabilidad social del modelo ÚRSUla: gestión, formación, cognitivo, y participación social. Conclusión : La RSU es un compromiso moral irrenunciable, es importante en la gestión universitaria para promover el desarrollo sostenible, con ética y respeto de los derechos humanos, es necesario la participación de actores comprometidos y se debe considerar que, actualmente, tiene un enfoque asistencialista y reduccionista, escaso apoyo, socialización e implementación y falta unificar criterios en su conceptualización.

Introduction: University social responsibility is present in the discourses of academics, but it fails to permeate the actions that lead to the transformation of the university, requiring a paradigm shift. At present there are conceptual confusions that make its promotion and transformative practice very difficult, in many universities it is confused with social projection, which reduces its transversal dimension. Objective: To analyze the scientific evidence related to university social responsibility in latin america. Methods: Systematic review of the literature, between the months of August to December 2021; the search for articles was carried out in the databases: Scopus, Scielo, Doaj, Lilacs and Redalyc; the use of Descriptors in Health Sciences (DeCS) and the combination of the Boolean operators OR and AND were applied. Full texts in Spanish between the years 2015 and 2021 were considered. Results: 508 articles were obtained, which were submitted to the PRISMA methodology, selecting 20 articles, grouped into four categories according to the Social Responsibility Manual of the Úrsula Model: management, training, cognitive, and social participation. Conclusions: USR is an inalienable moral commitment, it is important in university management to promote sustainable development, with ethics and respect for human rights, the participation of committed actors is necessary, considering that it currently has a welfare and reductionist approach, scarce support, socialization and implementation and there is a need to unify criteria.

Flexible Video Fetoscopy: Feasibility and Outcomes of a Novel Modality for Laser Therapy in Twin-to-Twin Transfusion Syndrome Presenting with Inaccessible Anterior Placenta.

INTRODUCTION: Identification of intertwin anastomosis may be challenging during fetoscopy in cases with complete anterior placenta. The aim of this study was to describe the technique, feasibility, and outcomes of flexible video fetoscopy for laser coagulation in monochorionic (MC) twin pregnancies with twin-to-twin transfusion syndrome (TTTS) presenting with inaccessible anterior placenta. METHODS: From April 2021 to March 2022, a prospective cohort of consecutive MC twin pregnancies complicated with TTTS presenting with anterior placenta after 20 weeks was recruited. Cases with inaccessible anterior placenta during standard technique were converted into flexible video fetoscopy for completion of laser coagulation of placental anastomoses using a 270° flexible video endoscope through the same uterine port. Descriptive analysis includes feasibility, remaining anastomoses requiring laser photocoagulation, and perinatal outcomes. RESULTS: A total of 45 pregnancies with TTTS were treated with fetoscopic laser therapy during the 1-year study period. Twenty-one pregnancies presented with anterior placenta after 20 weeks, in which an inaccessible vascular equator was observed in 33.3% (7/21). Flexible video fetoscopy was successfully performed in all 7 cases at a median gestational age of 22+2 (20+0-27+1) weeks+days. Visualization of the entire placental surface, coagulation of selected vessels, and exploration of the entire vascular equator were achieved in all cases. Six cases (85.7%) required additional laser coagulation due to either vascular patency despite initial coagulation with conventional fetoscopy (1/6, 16.7%) and/or remaining noncoagulated anastomoses (5/6, 83.3%). Perinatal survival of at least one twin and both twins was achieved in 85.7% and 57.1%, respectively. DISCUSSION: Flexible video fetoscopy for completion of laser coagulation of placental anastomoses is feasible and represents a good option for TTTS cases presenting after 20 weeks with inaccessible anterior placenta.

A Pathogenic Variant Reclassified to the Pseudogene PMS2P1 in a Patient with Suspected Hereditary Cancer.

The PMS2 gene is involved in DNA repair by the mismatch repair pathway. Deficiencies in this mechanism have been associated with Lynch Syndrome (LS), which is characterized by a high risk for colorectal, endometrial, ovarian, breast, and other cancers. Germinal pathogenic variants of PMS2 are associated with up to 5% of all cases of LS. The prevalence is overestimated for the existence of multiple homologous pseudogenes. We report the case of a 44-year-old woman diagnosed with breast cancer at 34 years without a relevant cancer family history. The presence of pathogenic variant NM_000535.7:c.1A > T, (p.Met1Leu) in PMS2 was determined by next-generation sequencing analysis with a panel of 322 cancer-associated genes and confirmed by capillary sequencing in the patient. The variant was determined in six family members (brothers, sisters, and a son) and seven non-cancerous unrelated individuals. Analysis of the amplified region showed high homology of PMS2 with five of its pseudogenes. We determined that the variant is associated with the PMS2P1 pseudogene following sequence alignment analysis. We propose considering the variant c.1A > T, (p.Met1Leu) in PMS2 for reclassification as not hereditary cancer-related, given the impact on the diagnosis and treatment of cancer patients and families carrying this variant.

Seroprevalence of SARS-CoV2 Infections in Health Care Personnel in a Long-Term Care Institution After the First Wave of the Pandemic: A Cross-Sectional Study.

BACKGROUND: At the time of our study, occupational health evidence specific for long-term care employees was mostly lacking. The purpose of this study was to determine the proportion of positive cases in employees after the first COVID-19 wave in May 2020. We also determined the prevalence of asymptomatic cases. METHOD: The study population included all health care workers (HCW) employed at one mid-size long-term hospital in Spain (May 2020). A cross-sectional study design included an interviewer-administered self-reported questionnaire (including sociodemographic questions, risk factors for COVID-19 complications such as hypertension or diabetes, and previous polymerase chain reaction [PCR] results) and antibody determination (Biozek rapid test). Data were analyzed using Student's t, Fisher, and chi-square tests. Two multivariate logistic models were created to evaluate exposure factors and symptoms separately on the outcome of having had COVID-19. FINDINGS: Of the 97% of workers who participated (580/596), 300 (51.7%) suffered symptoms of COVID-19, 161 (27.8%) of the rapid antibody tests were positive for IgM and/or IgG, 160 (27.6%) workers had at least one risk factor, and 32 (19.0%) of the 168 SARS-CoV-2-positive cases were asymptomatic. The proportion of negative or unavailable PCRs, with positive antibody, was 11.7% (56/477). Casual contact without protection (odds ratio [OR]: 1.9, 95% confidence interval [CI]: 1.1-3.4), doctor occupation (OR 3.3, 95% CI: 1.1-10.2), and nursing assistant occupation (OR 2.5, 95% CI: 1.2-5.8) were independently associated with SARS-CoV-2 infection. CONCLUSION: Physicians and nursing assistants in a long-term care setting were at a higher risk of SARS-COV-2 infection over other occupations in the first wave of the pandemic, especially when in contact with patients without protection. Almost one-fifth of the workers with a positive PCR test for SARS-COV-2 were asymptomatic and seroprevalence (27.8%) was well below the approximated herd immunity cutoff (60-70%). Essential workers in long-term care must be monitored frequently by Employee Health Service and should be required to wear personal protective equipment including a fit-tested N-95 while in close contact with patients and coworkers.

Deep DNA sequencing of MGMT, TP53 and AGT in Mexican astrocytoma patients identifies an excess of genetic variants in women and a predictive biomarker.

PURPOSE: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. METHODS: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). RESULTS: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. CONCLUSIONS: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.

Transcriptomics and RNA-Based Therapeutics as Potential Approaches to Manage SARS-CoV-2 Infection.

SARS-CoV-2 is a coronavirus family member that appeared in China in December 2019 and caused the disease called COVID-19, which was declared a pandemic in 2020 by the World Health Organization. In recent months, great efforts have been made in the field of basic and clinical research to understand the biology and infection processes of SARS-CoV-2. In particular, transcriptome analysis has contributed to generating new knowledge of the viral sequences and intracellular signaling pathways that regulate the infection and pathogenesis of SARS-CoV-2, generating new information about its biology. Furthermore, transcriptomics approaches including spatial transcriptomics, single-cell transcriptomics and direct RNA sequencing have been used for clinical applications in monitoring, detection, diagnosis, and treatment to generate new clinical predictive models for SARS-CoV-2. Consequently, RNA-based therapeutics and their relationship with SARS-CoV-2 have emerged as promising strategies to battle the SARS-CoV-2 pandemic with the assistance of novel approaches such as CRISPR-CAS, ASOs, and siRNA systems. Lastly, we discuss the importance of precision public health in the management of patients infected with SARS-CoV-2 and establish that the fusion of transcriptomics, RNA-based therapeutics, and precision public health will allow a linkage for developing health systems that facilitate the acquisition of relevant clinical strategies for rapid decision making to assist in the management and treatment of the SARS-CoV-2-infected population to combat this global public health problem.

A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population.

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies.

Clinical Benefits of Olaparib in Mexican Ovarian Cancer Patients With Founder Mutation BRCA1-Del ex9-12.

Background: Ovarian cancer (OC) is gynecologic cancer with the highest mortality rate. It is estimated that 13-17% of ovarian cancers are due to heritable mutations in BRCA1 and BRCA2. The BRCA1 (BRCA1-Del ex9-12) Mexican founder mutation is responsible for 28-35% of the cases with ovarian cancer. The aim was to describe the PFS of OC patients treated with olaparib, emphasizing patients carrying the Mexican founder mutation (BRCA1-Del ex9-12). Methods: In this observational study, of 107 patients with BRCAm, 35 patients were treated with olaparib from November 2016 to May 2021 at the Ovarian Cancer Program (COE) of Mexico; patient information was extracted from electronic medical records. Results: Of 311 patients, 107 (34.4%) were with BRCAm; 71.9% (77/107) were with BRCA1, of which 27.3% (21/77) were with BRCA1-Del ex9-12, and 28.1% (30/107) were with BRCA2 mutations. Only 35 patients received olaparib treatment, and the median follow-up was 12.87 months. The PFS of BRCA1-Del ex9-12 was NR (non-reach); however, 73% of the patients received the treatment at 36 vs. 11.59 months (95% CI; 10.43-12.75) in patients with other BRCAm (p = 0.008). Almost 50% of patients required dose reduction due to toxicity; the most frequent adverse events were hematological in 76.5% and gastrointestinal in 4%. Conclusion: Mexican OC BRCA1-Del ex9-12 patients treated with olaparib had a significant increase in PFS regardless of the line of treatment compared to other mutations in BRCA.

Quistes y hamartomas biliares, no siempre son asintomáticos / Biliary cysts and hamartomas are not always asymptomatic

In daily clinical practice, we can find consultation reasons and exploratoryfindings that can guide us to a certain pathology. However, to avoid mistakes,we must remember that there are fewer common diseases, which could leadto an unexpected final diagnosis.Hepatic cystic lesions are usually found incidentally, having a wide differentialdiagnosis. Among them are biliary cysts and hamartomas, rare lesions, butwith not inconsiderable importance, as we will see in the case that is exposedbelow. (AU)

En la práctica clínica habitual nos podemos encontrar motivos de consulta yhallazgos exploratorios que nos pueden guiar a una determinada patología.Sin embargo, para no caer en errores, debemos recordar que existen enfermedades menos habituales, que podrían llevarnos a un diagnóstico finalinesperado.Las lesiones quísticas hepáticas se hallan generalmente de forma incidental, teniendo un amplio diagnóstico diferencial. Entre ellas se encuentranlos quistes y hamartomas biliares, lesiones poco frecuentes, pero con unaimportancia no desdeñable, como veremos en el caso que se expone a continuación. (AU)

Compromiso en el cuidado de enfermería / Commitment in Nursing Care

Introducción: La sobrecarga laboral, los recursos insuficientes y las condiciones precarias obligan a la enfermera brindar cuidados a la carrera en muchas ocasiones, debido a que debe distribuir su tiempo en las múltiples actividades del servicio. Promover el compromiso en las enfermeras implica un alto sentido de conexión física, cognitiva y emocional con la calidad del cuidado al paciente y contribuye con el logro de los objetivos institucionales. Objetivo: Analizar la evidencia científica relacionada con el compromiso en el cuidado de enfermería. Métodos: Revisión sistemática de la literatura entre los meses de julio a setiembre del 2020. Se realizó la búsqueda de artículos en las siguientes bases de datos: Wiley Online Library, Pubmed, DOAJ, SciELO, Eselvier, Sage Journals, Proquest y Lilacs; se aplicó el uso de los Descriptores en Ciencias de la Salud (DeCS), Descriptores MeSH y la combinación de los operadores booleanos OR y AND. Se consideraron textos completos en inglés, portugués y español entre los años del 2010 al 2020, los cuales fueron sometidos a la metodología PRISMA. Se seleccionaron 27 artículos. Conclusiones: El compromiso surge en la enfermera como resultado de varios factores, entre ellos la vocación, la autonomía, la confianza, el apoyo social, la edad, el entorno laboral, el tipo de horario y la reflexión crítica, estos influyen de forma positiva o negativa en el desempeño, la capacidad laboral, la satisfacción y, sobretodo, en la calidad de los cuidados que se brindan(AU)

Introduction: Work overload, insufficient resources and precarious conditions force the nurse to provide care in a hurry on many occasions, due to the fact that she or he must distribute their time among the multiple activities of the service. Promoting commitment among nurses implies a high sense of physical, cognitive and emotional connection with the quality of patient care and contribute to the achievement of institutional objectives. Objective: To analyze the scientific evidence related to commitment in nursing care. Methods: Systematic review of the literature from July to September 2020. Articles were searched in the following databases: Wiley Online Library, Pubmed, DOAJ, SciELO, Elsevier, Sage Journals, Proquest and Lilacs. Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH), as well as the combination of the Boolean operators OR and, were used. Full texts published in English, Portuguese and Spanish between 2010 and 2020 were considered and processed using the Preferred Reporting Items for Systematic Review and Meta-Analyses methodology. Twenty-seven articles were selected. Conclusions: Commitment appears in the nurse as a result of several factors, including vocation, autonomy, confidence, social support, age, work environment, type of schedule, and critical reflection; these influence, positively or negatively, performance, work capacity, satisfaction and, above all, the quality of provided care(AU)