The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury.

In addition to the loss of motor function, ~60% of patients develop pain after spinal cord injury. The cellular-molecular mechanisms are not well understood, but the data suggests that plasticity within the rostral, epicenter, and caudal penumbra of the injury site initiates a cellular-molecular interplay that acts as a rewiring mechanism leading to central neuropathic pain. Sprouting can lead to the formation of new connections triggering abnormal sensory transmission. The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity. Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen. In this study, we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury. We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters, leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting. Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control (placebo). We used von Frey monofilaments and the "up-down method" to evaluate mechanical allodynia. Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sex-dependent effect. The expression profile of glutamatergic transporters (excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1) revealed a sexual dimorphism in the rostral, epicenter, and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes. Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents. Analyses of peptidergic (calcitonin gene-related peptide-α) and non-peptidergic (isolectin B4) fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/ isolectin B4 ratio in comparison with sham, suggesting increased receptive fields in the dorsal horn. Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats, this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury. Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord. The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain, an area with a critical need for treatment.

Sacituzumab-govitecan in metastatic triple-negative breast cancer: a multicenter effectiveness and safety study.

Aim: Sacituzumab-govitecan (Sgov) is a new antibody-drug conjugate recently approved for metastatic triple negative breast cancer (mTNBC), so there are still few data published in the real-world setting.Materials & methods: This study was to analyze the effectiveness and safety of Sgov in mTNBC of patients from the three main hospitals of a city and to compare with the pivotal ASCENT-trial. A total of 46 patients were included, all women diagnosed with mTNBC, with a median age of 52 years and Eastern Cooperative Oncology Group performance status 0-1 71.8% of patients.Results: Sgov effectiveness data seem to be slightly inferior than expected. Furthermore, it is observed that patients with an Eastern Cooperative Oncology Group of two or higher benefit significantly less from treatment with the drug. Safety profile of Sgov is acceptable.

What is this article about? Sacituzumab-govitecan (Sgov) is a new drug recently approved for metastatic triple negative breast cancer, so there is still little data on patients receiving treatment outside of a clinical trial.What were the results? At the cut-off date, 33 patients (71.7%) had withdrawn from treatment with Sgov, and 21 patients (45.7%) had died. Disease remained stable or shrank in 23.9% of patients (n = 11). Median time to disease progression was 4.1 months (IC 95%: 2.6­5.6) and median overall survival 11.0 months (95% CI: 6.1­15.9), with a median duration of follow-up of 6.6 months (interquartile range: 2.1­10.5). Patients with ECOG 0­1 (better performance status) show a higher overall survival than patients with higher ECOG (Not reached [95% CI: NR-NR] vs 3.8 [95% CI: 2.7­4.9]; p = 0.009). No patients stopped treatment due to side effects and almost two thirds of patients did not have to have their dose reduced or delayed due to adverse events (AE). Asthenia (71.7%) and anemia (60.9%) were the most frequent AE. No patient characteristics were identified that predicted less or worse toxicity.What do the results of the study mean? This suggests that sacituzumab-govitecan effectiveness data seem to be slightly worse than expected, even more when performance status before starting Sgov is poor (ECOG 2). AE profile of Sgov is acceptable.

Synergistic neuroprotective action of prolactin and 17ß-estradiol on kainic acid-induced hippocampal injury and long-term memory deficit in ovariectomized rats.

PURPOSE: The neuroprotective actions of the ovarian hormone 17ß-estradiol (E2) against different brain lesions have been constantly confirmed in a variety of models including kainic acid (KA) lesions. Similarly, the pituitary hormone prolactin (PRL), traditionally associated with lactogenesis, has recently been linked to a large diversity of functions, including neurogenesis, neuroprotection, and cognitive processes. While the mechanisms of actions of E2 as regards its neuroprotective and behavioral effects have been extensively explored, the molecular mechanisms of PRL related to these roles remain under investigation. The current study aimed to investigate whether the simultaneous administration of PRL and a low dose of E2 prevents the KA-induced cognitive deficit and if this action is associated with changes in hippocampal neuronal density. METHODS: Ovariectomized (OVX) rats were treated with saline, PRL, and/or E2 in the presence or absence of KA. Neuroprotection was assessed by Nissl staining and neuron counting. Memory was evaluated with the novel object recognition test (NOR). RESULTS: On their own, both PRL and E2 prevented short- and long-term memory deficits in lesioned animals and exerted neuroprotection against KA-induced excitotoxicity in the hippocampus. Interestingly, the combined hormonal treatment was superior to either of the treatments administered alone as regards improving both memory and neuronal survival. CONCLUSION: Taken together, these results point to a synergic effect of E2 and PRL in the hippocampus to produce their behavioral, proliferative, and neuroprotective effects.

Tuberculosis among children visiting friends & relatives.

BACKGROUND: Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR. METHODS: We conducted a prospective multicentric observational study in Catalonia (Spain) from June 2017 to December 2019. We enrolled children aged < 15 years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent's birth country for ≥21 days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8-12 weeks post-return. LTBI was defined as a TST ≥5 mm and/or a positive QFT-Plus. RESULTS: Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU, 95%CI = 8.8-28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3-9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU, 95%CI = 3.9-20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1-13.3). CONCLUSIONS: The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions.

Image-Guided Transrectal Drainage of Pelvic Abscesses in Children.

OBJECTIVE: To describe our technique and share our experience with image-guided transrectal drainage (TRD) of pelvic abscesses in children. MATERIALS AND METHODS: Retrospective review and analysis of indications for image-guided TRD and examination of procedural outcomes in pediatric patients with pelvic abscesses over 8 years. RESULTS: A total of 69 patients (33 males and 36 females) with symptomatic pelvic abscesses underwent image-guided TRD. The median age and weight of the patients were 11.5 years (range, 3-18) and 46.8 kg (range, 15.1-118.0), respectively. The etiologies of the pelvic abscesses were perforated appendicitis (72.5%) and post-operative collections (27.5%). All patients presented with abdominal pain. Fever, emesis, and diarrhea were also common symptoms. The size of the pelvic abscesses ranged from 24.0 to 937.1 mL (median, 132.7). Technical success was achieved in 68 of 69 TRD procedures (98.6%). Clinical improvement was observed in all patients with technically successful TRD. The TRD catheter dwell time ranged from 0 to 10 days (median, 4.0). Most patients who underwent TRD for perforated appendicitis subsequently underwent elective appendectomy after the resolution of the pelvic abscess (84.0%). The median time from TRD to elective appendectomy was 2.8 months (range, 0.3-6.1). There were no procedure-related complications. CONCLUSION: Image-guided TRD is a safe and effective procedure with high technical and clinical success rates for the treatment of pelvic abscesses in children.

Implementation of esophageal endoscopic submucosal dissection in Spain: Results from the nationwide registry. / Implementación de la disección endoscópica submucosa esofágica en España: resultados del registro nacional.

INTRODUCTION AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) in the esophagus have not been assessed in our country. Our primary aim was to analyze the effectiveness and safety of the technique. MATERIAL AND METHODS: Analysis of the prospectively maintained national registry of ESD. We included all superficial esophageal lesions removed by ESD in 17 hospitals (20 endoscopists) between January 2016 and December 2021. Subepithelial lesions were excluded. The primary outcome was curative resection. We conducted a survival analysis and used logistic regression analysis to assess predictors of non-curative resection. RESULTS: A total of 102 ESD were performed on 96 patients. The technical success rate was 100% and the percentage of en-bloc resection was 98%. The percentage of R0 and curative resection was 77.5% (n=79; 95%CI: 68%-84%) and 63.7% (n=65; 95%CI: 54%-72%), respectively. The most frequent histology was Barrett-related neoplasia (n=55 [53.9%]). The main reason for non-curative resection was deep submucosal invasion (n=25). The centers with a lower volume of ESD obtained worse results in terms of curative resection. The rate of perforation, delayed bleeding and post-procedural stenosis were 5%, 5% and 15.7%, respectively. No patient died or required surgery due to an adverse effect. After a median follow-up of 14months, 20patients (20.8%) underwent surgery and/or chemoradiotherapy, and 9 patients died (mortality 9.4%). CONCLUSIONS: In Spain, esophageal ESD is curative in approximately two out of three patients, with an acceptable risk of adverse events.

Resultados maternos y fetales en mujeres embarazadas con enfermedad renal crónica basada en la tasa de filtración glomerular / Maternal And Fetal Outcomes In Pregnant Women With Chronic Kidney Disease Based On Glomerular Filtration Rate

Introducción: el embarazo causa adaptaciones en el riñón, tanto en anatomía como en función, para mantener el entorno extracelular, hemodinámico y hormonal. Sin embargo, estos pueden no llevarse a cabo de manera completamente óptima en presencia de enfermedad renal. El objetivo era estudiar la relación entre la enfermedad renal y los resultados maternos de fetal durante el embarazo, asociado con un rechazo por paciente y/o en relación con el tratamiento especializado. Material y métodos: estudio observacional y retrospectivo en una serie de casos, revisando 134 archivos de pacientes embarazadas con cierto grado de enfermedad renal antes del embarazo. Los resultados maternos registrados fueron: enfermedad hipertensiva durante el embarazo, deterioro renal agudo, necesidad de terapia de sustitución renal y en productos: prematuridad, restricción del crecimiento intrauterino, muerte fetal y aborto espontáneo. Resultados: Resultados maternos: tasa media de filtración glomerular (GFR) de 58.23 ml/min, aumento de peso de 7 kg; La preeclampsia fue diagnosticada en 92 mujeres (55 severas). 46 pacientes mostraron lesión renal aguda, 40 se resolvieron conservativamente; 1 requirió diálisis peritoneal y 15 hemodiálisis (con una decisión retrasada un promedio de un mes por rechazo por paciente y/o pariente). La resolución del embarazo fue por cesárea en 111 pacientes; Nacieron 116 productos antes de las 37 semanas de gestación, con un peso promedio de 1910 g, 94 mostraron restricción del crecimiento intrauterino. Conclusión: la enfermedad renal influyó directamente en el mayor número de resultados adversos maternos y fetales cuando se rechazó la atención médica especializada. Existe una correlación entre el ligero estado de Davison con los estados I, II y IIIA de Kdigo en el análisis de correspondencia

Introduction: Pregnancy causes adaptations in the kidney, both in anatomy and function, to maintain the extracellular, hemodynamic and hormonal environment. However, these may not be carried out completely optimally in the presence of kidney disease. The objective was to study the relation between kidney disease and maternal-fetal outcomes during pregnancy, associated with a rejection by patient and/or relative to specialized treatment. Material and Methods: Observational, retrospective study in a series of cases, reviewing 134 files of pregnant patients with some degree of kidney disease prior to pregnancy. Maternal outcomes recorded were: hypertensive disease during pregnancy, acute renal deterioration, need for renal substitution therapy, and in products: prematurity, restriction of intrauterine growth, fetal death and miscarriage. Results: Maternal outcomes: mean glomerular filtration rate (GFR) of 58.23ml/min, weight gain of 7 kg; preeclampsia was diagnosed in 92 women (55 severe). 46 patients showed acute renal lesion, 40 were conservatively resolved; 1 required peritoneal dialysis and 15 hemodialysis (with decision delayed an average of one month by rejection by patient and/or relative). Resolution of pregnancy was by cesarean in 111 patients; 116 products were born before 37 weeks of gestation, with average weight of 1910 g, 94 showed restriction of intrauterine growth. Conclusion: Kidney disease directly influenced the greater number of adverse maternal and fetal outcomes when specialized medical care was rejected. There is a correlation between slight Davison state with states I, II and IIIa of KDIGO in correspondence analysis.

Advances of Nanotechnology in the Diagnosis and Treatment of Hepatocellular Carcinoma.

Nanotechnology has emerged as a promising technology in the field of hepatocellular carcinoma (HCC), specifically in the implementation of diagnosis and treatment strategies. Nanotechnology-based approaches, such as nanoparticle-based contrast agents and nanoscale imaging techniques, have shown great potential for enhancing the sensitivity and specificity of HCC detection. These approaches provide high-resolution imaging and allow for the detection of molecular markers and alterations in cellular morphology associated with HCC. In terms of treatment, nanotechnology has revolutionized HCC therapy by enabling targeted drug delivery, enhancing therapeutic efficacy, and minimizing off-target effects. Nanoparticle-based drug carriers can be functionalized with ligands specific to HCC cells, allowing for selective accumulation of therapeutic agents at the tumor site. Furthermore, nanotechnology can facilitate combination therapy by co-encapsulating multiple drugs within a single nanoparticle, allowing for synergistic effects and overcoming drug resistance. This review aims to provide an overview of recent advances in nanotechnology-based approaches for the diagnosis and treatment of HCC. Further research is needed to optimize the design and functionality of nanoparticles, improve their biocompatibility and stability, and evaluate their long-term safety and efficacy. Nonetheless, the integration of nanotechnology in HCC management holds great promise and may lead to improved patient outcomes in the future.

Epigenetic Factors and ncRNAs in Testicular Cancer.

Testicular cancer is the most prevalent tumor among males aged 15 to 35, resulting in a significant number of newly diagnosed cases and fatalities annually. Non-coding RNAs (ncRNAs) have emerged as key regulators in various cellular processes and pathologies, including testicular cancer. Their involvement in gene regulation, coding, decoding, and overall gene expression control suggests their potential as targets for alternative treatment approaches for this type of cancer. Furthermore, epigenetic modifications, such as histone modifications, DNA methylation, and the regulation by microRNA (miRNA), have been implicated in testicular tumor progression and treatment response. Epigenetics may also offer critical insights for prognostic evaluation and targeted therapies in patients with testicular germ cell tumors (TGCT). This comprehensive review aims to present the latest discoveries regarding the involvement of some proteins and ncRNAs, mainly miRNAs and lncRNA, in the epigenetic aspect of testicular cancer, emphasizing their relevance in pathogenesis and their potential, given the fact that their specific expression holds promise for prognostic evaluation and targeted therapies.

mRNA-1273 SARS-CoV-2 vaccine in recently transplanted allogeneic hematopoietic cell transplant recipients: Dynamics of cellular and humoral immune responses and booster effect.

Allogeneic hematopoietic stem cell transplant (HCT) recipients are at high risk of severe COVID-19 despite vaccination. Little is known about cellular response to SARS-CoV-2 vaccine in this population, especially in recently transplanted patients (RTP). In this single-center study we examined cellular and humoral response to the mRNA-1273 (Spikevax®) vaccine in recently transplanted patients (RTP, n = 49), and compared them to long-term transplanted patients (LTTP, n = 19) and healthy controls (n = 20) at three different timepoints: one and three months after the second dose (T1 and T2, respectively, 28 days apart), and one month after the third dose (T3). Controls did not receive a third dose. RTPs showed lower IgG anti-S1 titers than healthy controls at both T1 (mean 0.50 vs 0.94 arbitrary units -AU-, p < 0.0001) and T2 (0.37 vs 0.79 AU, p < 0.0001). They also presented lower titers than LTTPs at T1 (0.50 vs 0.66, p = 0.01), but no differences at T2 (0.37 vs 0.40 AU, p = 0.55). The rate of positive T-cell responses was lower in RTPs than in controls at both T1 and T2 (61.2 % vs 95 %, p = 0.007; 59.2 % vs 100 %, p = 0.001, respectively), but without statistically significant differences between transplanted groups. At T3 no differences were seen between RTPs and LTTPs as well, neither in IgG antibodies (p = 0.82) nor in cellular responses (p = 0.15), although a third dose increased the rate of positive cellular and humoral responses in approximately 50 % of recently transplanted patients. However, active immunosuppressive treatment severely diminished their chances to produce an adequate response.

DFT Study of Adsorption Behavior of Nitro Species on Carbon-Doped Boron Nitride Nanoribbons for Toxic Gas Sensing.

The modifications of the electronic properties on carbon-doped boron nitride nanoribbons (BNNRs) as a response to the adsorption of different nitro species were investigated in the framework of the density functional theory within the generalized gradient approximation. Calculations were performed using the SIESTA code. We found that the main response involved tuning the original magnetic behavior to a non-magnetic system when the molecule was chemisorbed on the carbon-doped BNNR. It was also revealed that some species could be dissociated through the adsorption process. Furthermore, the nitro species preferred to interact over nanosurfaces where dopants substituted the B sublattice of the carbon-doped BNNRs. Most importantly, the switch on the magnetic behavior offers the opportunity to apply these systems to fit novel technological applications.

Co-Expression Network Analysis Identifies Molecular Determinants of Loneliness Associated with Neuropsychiatric and Neurodegenerative Diseases.

Loneliness and social isolation are detrimental to mental health and may lead to cognitive impairment and neurodegeneration. Although several molecular signatures of loneliness have been identified, the molecular mechanisms by which loneliness impacts the brain remain elusive. Here, we performed a bioinformatics approach to untangle the molecular underpinnings associated with loneliness. Co-expression network analysis identified molecular 'switches' responsible for dramatic transcriptional changes in the nucleus accumbens of individuals with known loneliness. Loneliness-related switch genes were enriched in cell cycle, cancer, TGF-ß, FOXO, and PI3K-AKT signaling pathways. Analysis stratified by sex identified switch genes in males with chronic loneliness. Male-specific switch genes were enriched in infection, innate immunity, and cancer-related pathways. Correlation analysis revealed that loneliness-related switch genes significantly overlapped with 82% and 68% of human studies on Alzheimer's (AD) and Parkinson's diseases (PD), respectively, in gene expression databases. Loneliness-related switch genes, BCAM, NECTIN2, NPAS3, RBM38, PELI1, DPP10, and ASGR2, have been identified as genetic risk factors for AD. Likewise, switch genes HLA-DRB5, ALDOA, and GPNMB are known genetic loci in PD. Similarly, loneliness-related switch genes overlapped in 70% and 64% of human studies on major depressive disorder and schizophrenia, respectively. Nine switch genes, HLA-DRB5, ARHGAP15, COL4A1, RBM38, DMD, LGALS3BP, WSCD2, CYTH4, and CNTRL, overlapped with known genetic variants in depression. Seven switch genes, NPAS3, ARHGAP15, LGALS3BP, DPP10, SMYD3, CPXCR1, and HLA-DRB5 were associated with known risk factors for schizophrenia. Collectively, we identified molecular determinants of loneliness and dysregulated pathways in the brain of non-demented adults. The association of switch genes with known risk factors for neuropsychiatric and neurodegenerative diseases provides a molecular explanation for the observed prevalence of these diseases among lonely individuals.

Genome-wide association study biomarkers in T-cell mediated rejection: selective effect according to the Banff classification.

BACKGROUND: A genome-wide association study (GWAS) in kidney transplant recipients reported the association of two polymorphisms located in the PTPRO gene and upstream of the CCDC67 (DEUP1) gene with increased risk of acute T cell-mediated rejection (TCMR). We aimed at replicating the assessment of mentioned associations and additionally ascertaining the influence of treatment and clinical features of the patients. METHODS: The polymorphisms, PTPRO-rs7976329 and CCDC67-rs10765602 were genotyped by TaqMan chemistry in 641 consecutive kidney transplant recipients. The diagnosis of rejection was confirmed by biopsy and categorized according to the Banff classification. Associations were evaluated by Chi-square test or Fisher's exact test when necessary and multivariate logistic regression. RESULTS: Considering the GWAS study we only replicated the association of the PTPRO-rs7976329*C allele in the Banff grade < II subjects. However, the homozygous mutant genotypes of both polymorphism seemed to increase the risk of TCMR Banff grade < II in the overall cohort and after stratification by Thymoglobulin induction therapy. In the multivariate analysis, we confirmed the association of PTPRO-rs7976329 with TCMR Banff grade < II, independently of the Thymoglobulin induction therapy and of CCDC67-rs10765602 only in the group of patients not receiving Thymoglobulin induction therapy. No association of these polymorphisms with TCMR Banff grade ≥ II was observed in either the overall cohort or in the subgroups stratified by Thymoglobulin therapy. CONCLUSIONS: Our study shows that the increased risk of TCMR related to polymorphisms PTPRO-rs7976329 and CCDC67-rs10765602 previously reported in a GWAS was replicated only in homozygous patients who presented TCMR Banff grade < II and for the minor allele of either polymorphism.

Embarazo gemelar espontáneo en útero bicorpóreo: una contribución a la experiencia / Spontaneous twin pregnancy in a bicorporeal uterus, a contribution to the experience

Resumen ANTECEDENTES: Las anomalías uterinas congénitas son consecuencia de la formación anormal, fusión o reabsorción de los conductos de Müller durante el desarrollo embriológico. El útero bicorne, unicorne y didelfo (U1, U2, U3 ESHRE-ESGE) son defectos en la unificación con una baja prevalencia en la población general y en la que tiene antecedente de aborto e infertilidad; se estima en alrededor de 0.4 a 1.1%, respectivamente. La presentación del caso puede aportar información útil relacionada con la evolución del embarazo y los desenlaces perinatales cuando aparece esta anomalía. CASO CLÍNICO: Paciente de 35 años, con amenorrea secundaria y prueba inmunológica de embarazo positiva, con antecedentes de dismenorrea primaria severa y anomalía uterina congénita compatible con útero bicorpóreo (U3 completo ESHRE-ESGE), bicorne completo (4a-AFS) y didelfo. El embarazo trascurrió sin complicaciones hasta la semana 37, cuando finalizó mediante cesárea, con hipotonía uterina que no ameritó transfusión de hemoderivados. CONCLUSIÓN: Los embarazos gemelares con útero bicorne son excepcionales y casi todos se logran espontáneamente; los que llegan a término finalizan mediante cesárea electiva.

Abstract BACKGROUND: Congenital uterine anomalies are the result of abnormal formation, fusion, or resorption of the Müllerian ducts during embryological development. The bicornuate, unicornuate and didelphic uterus (U1, U2, U3 ESHRE/ESGE), are unification defects with a low prevalence both in the general population and in the population with a history of abortion and infertility, is estimated at around 0.4 to 1.1%, respectively. The presentation of the case can provide useful information related to with the evolution of the pregnancy and the perinatal outcomes when this anomaly appears. CLINICAL CASE: A 35-year-old patient with secondary amenorrhea and a positive immunological pregnancy test with a history of severe primary dysmenorrhea and previous magnetic resonance imaging with a congenital uterine anomaly compatible with a bicorporeal uterus (U3 complete ESHRE-ESGE), complete bicornuate (4a /AFS) , uterus didelphys (ASRM). The pregnancy was uncomplicated until 37 weeks, when it was terminated by cesarean section, with uterine hypotonia that did not require transfusion of blood products. CONCLUSION: Twin pregnancy with bicornuate uterus is a rare entity, most of them have been achieved spontaneously and those that reach term have been resolved by elective cesarean section.

Intervención temprana de dientes supernumerarios en dentición primaria: Reporte y seguimiento de caso clínico / Intervenção precoce de dentes supranumerários na dentição decídua: relato e acompanhamento de um caso clínico / Early intervention of supernumerary teeth in primary dentition: Report and follow-up of clinical case

El mesiodens es un diente supernumerario que se encuentra en la zona de los incisivos centrales superiores, cuyo diagnóstico temprano es fundamental ya que permite la extracción oportuna del mismo previniendo posibles alteraciones a futuro como son: el desarrollo de quistes, malposición de los dientes adyacentes, retraso de erupción, diastema interincisal, reabsorción apical de dientes vecinos. Reporte de caso: Paciente masculino, de 6 años con 11 meses de edad, que presentó mesiodens doble, cuyo hallazgo fue radiológico, mediante una panorámica, requisito de la odontóloga para control odontológico general, en el cual se pudo observar la presencia de dos dientes supernumerarios, los cuales estaban provocando la rotación de los incisivos permanentes superiores. El tratamiento se basó en la extracción quirúrgica temprana de los dientes supernumerarios, para determinar el abordaje fue necesario la realización de un estudio tomográfico, una vez determinada el proceso de extracción, y posteriormente la recuperación del paciente, y seguimiento radiográfico y clínico, se logró la erupción adecuada de los incisivos centrales superiores permanentes, hasta la actualidad se realizan controles periódicos y la colocación de placas de expansión superior e inferior. Conclusión: En este caso el tratamiento es la extracción temprana, y debido al diagnóstico oportuno y las condiciones óptimas del paciente como son: la reabsorción radicular fisiológica de los dientes primarios, la ubicación de los dientes supernumerarios, así como el estadio de Nolla de los incisivos centrales superiores, permite que el tratamiento elegido sea el óptimo y con las condiciones menos traumáticas posibles.

O mesiodens é um dente supranumerário encontrado na região dos incisivos centrais superiores, cuja detecção pode ser acidental. O diagnóstico precoce é fundamental, pois permite a extração oportuna do dente supranumerário, prevenindo possíveis alterações futuras como: desenvolvimento de cistos, má localização dos dentes adjacentes, atraso na erupção, diastema interincisal, reabsorção apical dos dentes vizinhos. Relato de caso: O caso apresentado é de um paciente pediátrico do sexo masculino, 6 anos e 11 meses, que apresentava duplo mesiodens, cujo achado foi radiológico, através de visão panorâmica, uma solicitação do cirurgião-dentista para controle odontológico geral, no qual pôde observar a presença de dois dentes supranumerários, que causavam a rotação dos incisivos permanentes superiores. O tratamento baseou-se na extração cirúrgica precoce dos dentes supranumerários, para determinar a abordagem foi necessário realizar um estudo tomográfico, uma vez determinado o processo de extração, e posteriormente a recuperação do paciente, e acompanhamento radiográfico e clínico , conseguiu-se uma erupção adequada dos incisivos centrais superiores permanentes, até o momento são realizadas verificações periódicas e colocação de placas de expansão superiores e inferiores. Conclusão: Neste caso, o tratamento é a extração precoce e devido ao diagnóstico oportuno e condições ideais do paciente, como: reabsorção radicular fisiológica dos dentes decíduos, localização dos dentes supranumerários, bem como o estágio Nolla dos dentes. incisivos centrais superiores, permite que o tratamento escolhido seja ótimo e com as condições menos traumáticas possíveis

Mesiodens is a supernumerary tooth found in the area of the upper central incisors, the detection of which may be accidental. Early diagnosis is essential since it allows timely extraction of the supernumerary tooth, preventing possible future alterations such as: the development of cysts, poor location of adjacent teeth, delayed eruption, interincisal diastema, apical resorption of neighboring teeth. Case report: The case presented is of a male pediatric patient, 6 years and 11 months old, who presented double mesiodens, whose finding was radiological, through a panoramic view, a requirement of the dentist for general dental control, in which could observe the presence of two supernumerary teeth, which were causing the rotation of the upper permanent incisors. The treatment was based on the early surgical extraction of the supernumerary teeth, to determine the approach it was necessary to carry out a tomographic study, once the extraction process was determined, and later the recovery of the patient, and radiographic and clinical follow-up, it was achieved. proper eruption of the permanent upper central incisors, to date periodic checks and placement of upper and lower expansion plates are performed. Conclusion: In this case, the treatment is early extraction, and due to timely diagnosis and optimal patient conditions such as: physiological root resorption of deciduous teeth, location of supernumerary teeth, as well as the Nolla stage of the teeth. upper central incisors, allows the chosen treatment to be optimal and with the least traumatic conditions possible

Rare association between giant-cell aortitis and giant-cell aortic valvulitis

ABSTRACT Giant cell arteritis (GCA) is a type of chronic vasculitis that affects medium and large-caliber arteries, frequently related to aortic involvement and, consequently, to aneurysm formation. However, associated valvulitis with giant cells is uncommon. We describe the case of a 50-year-old female patient with aortic aneurysm and valvular insufficiency, whose anatomopathological examination revealed giant-cell aortic valvulitis associated with giant cell aortitis.

[Techniques for the treatment of keratocyst, review of the literature and case report]. / Técnicas para el tratamiento del queratoquiste, revisión de la literatura y presentación de un caso.

The odontogenic keratocystic tumor (OKT) or also currently known as odontogenic keratocyst (OK) is a benign pathology derived from the remains of the dental lamina characteristic for possessing variable amounts of desquamated keratin. It usually rises as solitary or with the presence of satellite cysts, the appearance of these satellite cysts is frequently related to the possible recurrence of OK, according to the literature, this recurrence can vary between 0 - 50%. As for the treatment stage of (OKT), it can be mentioned that at present there is a well-defined histological and clinical criterion, which facilitates its recognition and therefore its treatment. According to the literature, there are several treatment procedures that can be classified into non-conservative or radical treatments and conservative treatments accompanied by adjuvant methods. Within the non-conservative or radical treatments, we find en bloc resection, which is the most aggressive way to treat a keratocyst; however, it is the most effective way to avoid recurrence. Within the conservative treatments, marsupialization, decompression, and enucleation with or without adjuvant therapy are described. It is paramount to know how to recognize the different types of treatment for (OKT) since this will be conditioned by multiple factors, such as the location of nearby bone structures and the size of the lesion considering the possible involvement of dental structures. The objective is to seek the lowest-risk treatment possible, which avoids recurrence and finally puts an end to this pathology.

Sex-specific transcriptional rewiring in the brain of Alzheimer's disease patients.

Sex-specific differences may contribute to Alzheimer's disease (AD) development. AD is more prevalent in women worldwide, and female sex has been suggested as a disease risk factor. Nevertheless, the molecular mechanisms underlying sex-biased differences in AD remain poorly characterized. To this end, we analyzed the transcriptional changes in the entorhinal cortex of symptomatic and asymptomatic AD patients stratified by sex. Co-expression network analysis implemented by SWItchMiner software identified sex-specific signatures of switch genes responsible for drastic transcriptional changes in the brain of AD and asymptomatic AD individuals. Pathway analysis of the switch genes revealed that morphine addiction, retrograde endocannabinoid signaling, and autophagy are associated with both females with AD (F-AD) and males with (M-AD). In contrast, nicotine addiction, cell adhesion molecules, oxytocin signaling, adipocytokine signaling, prolactin signaling, and alcoholism are uniquely associated with M-AD. Similarly, some of the unique pathways associated with F-AD switch genes are viral myocarditis, Hippo signaling pathway, endometrial cancer, insulin signaling, and PI3K-AKT signaling. Together these results reveal that there are many sex-specific pathways that may lead to AD. Approximately 20-30% of the elderly have an accumulation of amyloid beta in the brain, but show no cognitive deficit. Asymptomatic females (F-asymAD) and males (M-asymAD) both shared dysregulation of endocytosis. In contrast, pathways uniquely associated with F-asymAD switch genes are insulin secretion, progesterone-mediated oocyte maturation, axon guidance, renal cell carcinoma, and ErbB signaling pathway. Similarly, pathways uniquely associated with M-asymAD switch genes are fluid shear stress and atherosclerosis, FcγR mediated phagocytosis, and proteoglycans in cancer. These results reveal for the first time unique pathways associated with either disease progression or cognitive resilience in asymptomatic individuals. Additionally, we identified numerous sex-specific transcription factors and potential neurotoxic chemicals that may be involved in the pathogenesis of AD. Together these results reveal likely molecular drivers of sex differences in the brain of AD patients. Future molecular studies dissecting the functional role of these switch genes in driving sex differences in AD are warranted.

Surgical correction of the ascending aorta and an aortic root aneurysm associated with coarctation of the descending aorta.

This case report shows how to perform simultaneously an open surgical correction of an aortic root aneurysm and aortic stenosis by interposition of an aortic composite graft and the transdiaphragmatic extra-anatomical correction of an aortic coarctation.

Cambios en las características clínicas y desenlaces de pacientes hospitalizados por COVID-19 durante dos años de pandemia: experiencia en un hospital venezolano / Changes in clinical characteristics and outcomes of patients hospitalized with COVID-19 during two years of the pandemic: experience in a venezuelan hospital

RESUMEN Objetivos. Determinar los cambios en las características clínicas y desenlaces intrahospitalarios de los pacientes hospitalizados por COVID-19 en un hospital privado de Caracas durante dos años de pandemia. Materiales y métodos. Estudio retrospectivo, observacional, de pacientes hospitalizados por COVID-19. Se investigó la correspondencia entre las olas de ingresos hospitalarios con las variantes circulantes del SARS-CoV-2 en la población general del Distrito Capital y estado Miranda. Resultados. Se incluyeron 1025 pacientes (569 hombres y 456 mujeres), con edad promedio de 62,9 DE: 16,2 años. Cuatro olas de ingresos hospitalarios fueron identificadas: primera (marzo-noviembre 2020) 150/1025 (14,6%) casos; segunda (diciembre-2020 a mayo-2021) 415/1025 (40,5%) casos; tercera (junio-diciembre 2021) 344/1025 (33,6%) casos; cuarta (enero-febrero 2022) 116/1025 (11,3%) casos. La edad promedio fue mayor en la cuarta ola (primera 64,0±15,7, segunda 61,4±15,8, tercera 62,1±16,5, y cuarta ola 68,5±16,4), mientras que la proporción de pacientes masculinos (primera 66,7%, segunda 58,8%, tercera 50,3%, y cuarta 44,8%), los pacientes con enfermedad grave-crítica (primera 65,3%, segunda 57%, tercera 51,7% y cuarta 44,8%), la estadía intrahospitalaria (primera 9,1±6,0, segunda 9,0±7,3, tercera 8,8±7,7, y cuarta 6,9±5,0 días), los ingresos a la UCI (primera 23,3%, segunda 15,7%, tercera 14,0%, y cuarta 11,2%; p=0,027) y la mortalidad (primera 21.8%, segunda 10,7%, tercera 9,1%, y cuarta 7,1%; p<0,001) disminuyeron progresivamente con el tiempo. Conclusiones. Los resultados muestran menor frecuencia de casos severos y mejoría de los desenlaces intrahospitalarios en dos años de pandemia. Es probable que los cambios en las variantes circulantes, las mejoras del manejo de la enfermedad y la vacunación hayan influido sobre estos resultados.

ABSTRACT Objectives. To determine changes in the clinical characteristics and in-hospital outcomes of patients hospitalized for COVID-19 in a private hospital in Caracas during two years of the pandemic. Materials and Methods. Retrospective, observational study of patients hospitalized for COVID-19. We evaluated the correspondence between waves of hospital admissions and circulating variants of SARS-CoV-2 in the general population of the Capital District and Miranda state. Results. A total of 1025 patients (569 men and 456 women) were included, with a mean age of 62.9 SD: 16.2 years. Four waves of hospital admissions were identified: first (March-November 2020) 150/1025 (14.6%) cases; second (December 2020 to May 2021) 415/1025 (40.5%) cases; third (June-December 2021) 344/1025 (33.6%) cases; fourth (January-February 2022) 116/1025 (11.3%) cases. The mean age was higher in the fourth wave (first: 64.0±15.7, second: 61.4±15.8, third: 62.1±16.5, and fourth wave: 68.5±16.4), while the proportion of male patients (first: 66.7%, second: 58.8%, third: 50.3%, and fourth wave: 44.8%), patients with severe-critical illness (first: 65.3%, second: 57%, third: 51.7%, and fourth wave: 44.8%), in-hospital stay (first: 9.1±6.0, second: 9.0±7.3, third: 8.8±7.7, and fourth wave: 6.9±5.0 days), ICU admissions (first: 23.3%, second: 15.7%, third: 14.0%, and fourth wave: 11.2%; p=0.027) and mortality (first: 21. 8%, second: 10.7%, third: 9.1%, and fourth wave: 7.1%; p<0.001) progressively decreased over time. Conclusions. The results show lower frequency of severe cases and improvement of in-hospital outcomes in two years of the pandemic. Changes in circulating variants, improvements in disease management and vaccination are likely to have influenced these results.