Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.

Plasma pTau181 Reveals a Pathological Signature that Predicts Cognitive Outcomes in Lewy Body Disease.

OBJECTIVE: To determine whether plasma phosphorylated-Tau181 (pTau181) could be used as a diagnostic biomarker of concurrent Alzheimer's disease neuropathologic change (ADNC) or amyloidosis alone, as well as a prognostic, monitoring, and susceptibility/risk biomarker for clinical outcomes in Lewy body disease (LBD). METHODS: We studied 565 participants: 94 LBD with normal cognition, 83 LBD with abnormal cognition, 114 with Alzheimer's disease, and 274 cognitively normal. Plasma pTau181 levels were measured with the Lumipulse G platform. Diagnostic accuracy for concurrent ADNC and amyloidosis was assessed with Receiver Operating Characteristic curves in a subset of participants with CSF pTau181/Aß42, and CSF Aß42/Aß40 or amyloid-ß PET, respectively. Linear mixed effects models were used to examine the associations between baseline and longitudinal plasma pTau181 levels and clinical outcomes. RESULTS: Plasma pTau181 predicted concurrent ADNC and amyloidosis in LBD with abnormal cognition with 87% and 72% accuracy, respectively. In LBD patients with abnormal cognition, higher baseline plasma pTau181 was associated with worse baseline MoCA and CDR-SB, as well as accelerated decline in CDR-SB. Additionally, in this group, rapid increases in plasma pTau181 over 3 years predicted a faster decline in CDR-SB and memory. In LBD patients with normal cognition, there was no association between baseline or longitudinal plasma pTau181 levels and clinical outcomes; however, elevated pTau181 at baseline increased the risk of conversion to cognitive impairment. INTERPRETATION: Our findings suggest that plasma pTau181 is a promising biomarker for concurrent ADNC and amyloidosis in LBD. Furthermore, plasma pTau181 holds potential as a prognostic, monitoring, and susceptibility/risk biomarker, predicting disease progression in LBD. ANN NEUROL 2024;96:526-538.

Ventral temporal and posteromedial sulcal morphology in autism spectrum disorder.

Two parallel research tracks link the morphology of small and shallow indentations, or sulci, of the cerebral cortex with functional features of the cortex and human cognition, respectively. The first track identified a relationship between the mid-fusiform sulcus (MFS) in ventral temporal cortex (VTC) and cognition in individuals with Autism Spectrum Disorder (ASD). The second track identified a new sulcus, the inframarginal sulcus (IFRMS), that serves as a tripartite landmark within the posteromedial cortex (PMC). As VTC and PMC are structurally and functionally different in ASD, here, we integrated these two tracks and tested if there are morphological differences in VTC and PMC sulci in a sample of young (5-17 years old) male participants (50 participants with ASD and 50 neurotypical controls). Our approach replicates and extends recent findings in four ways. First, regarding replication, the standard deviation (STD) of MFS cortical thickness (CT) was increased in ASD. Second, MFS length was shorter in ASD. Third, the CT STD effect extended to other VTC and to PMC sulci. Fourth, additional morphological features of VTC sulci (depth, surface area, gray matter volume) and PMC sulci (mean CT) were decreased in ASD, including putative tertiary sulci, which emerge last in gestation and continue to develop after birth. To our knowledge, this study is the most extensive comparison of the sulcal landscape (including putative tertiary sulci) in multiple cortical expanses between individuals with ASD and NTs based on manually defined sulci at the level of individual hemispheres, providing novel targets for future studies of neurodevelopmental disorders more broadly.

TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease mouse models.

Human genetics implicate defective myeloid responses in the development of late-onset Alzheimer disease. A decline in peripheral and brain myeloid metabolism, triggering maladaptive immune responses, is a feature of aging. The role of TREM1, a pro-inflammatory factor, in neurodegenerative diseases is unclear. Here we show that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation and hippocampal memory function in mice. Trem1 deficiency rescues age-associated declines in ribose 5-phosphate. In vitro, Trem1-deficient microglia are resistant to amyloid-ß42 oligomer-induced bioenergetic changes, suggesting that amyloid-ß42 oligomer stimulation disrupts homeostatic microglial metabolism and immune function via TREM1. In the 5XFAD mouse model, Trem1 haploinsufficiency prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy and changes in the disease-associated microglial transcriptomic signature. In aging APPSwe mice, Trem1 deficiency prevents hippocampal memory decline while restoring synaptic mitochondrial function and cerebral glucose uptake. In postmortem Alzheimer disease brain, TREM1 colocalizes with Iba1+ cells around amyloid plaques and its expression is associated with Alzheimer disease clinical and neuropathological severity. Our results suggest that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology.

Manejo de quiste odontogénico glandular con rehabilitación implantológica guiada. Reporte de un caso / Management of glandular odontogenic cyst with guided implantologic rehabilitation. Case report

Resumen Objetivo: Describir el manejo de un caso de quiste odontogénico glandular, con tratamiento conservador, terapias adyuvantes y rehabilitación implantoasistida a los 7 años de seguimiento. Caso clínico: Se presenta un caso clínico de un paciente masculino con una lesión mandibular con diagnóstico de quiste odontogénico glandular. El tratamiento que se realizó fue una enucleación con tratamiento de superficie con solución de Carnoy y ostectomía periférica. Se realizó seguimiento clínico y radiográfico durante 7 años verificando ausencia de recidiva, momento en cual se realizó mediante planificación virtual la colocación de implantes con guías quirúrgicas de precisión para rehabilitación implanto asistida.

Abstract Aim: To describe the management of a case with a glandular odontogenic cyst, treated with a conservative treatment, adyuvant therapy and guided implantologic rehabilitation at 7 years of follow up. Clinical case: A case report of a male patient with a mandibular lesion with a diagnose of glandular odontogenic cyst is presented. The treatment that was performed was an enucleation with surface treatment with Carnoy's solution and peripheral ostectomy. Clinical and radiographic follow up was carried out for 7 years, verifying the absence of recurrence. At that time, it was done placement of implants with virtual planning and precision surgical guides for implant-assisted rehabilitation.

Abordaje intraoral con asistencia endoscópica para las fracturas de cóndilo mandibular: descripción de una serie de casos / Intraoral approach with endoscopic assistance for mandibular condyle fractures: a case series

Objetivo: Describir una serie de casos de fracturas de cóndilo mandibular resueltas por abordaje intraoral y asistencia video-endoscópica. Casos clínicos: Se presentan 3 casos de pacientes con fracturas de cóndilo mandibular unilateral. Dos casos presen- tan un segundo trazo de fractura parasinfisiaria asociada. El tratamiento realizado fue la reducción abierta y la fijación in- terna de todas las fracturas por abordaje oral. Se realizaron controles clínicos y tomográficos mediatos y a distancia (AU)

Aim: To present the experience with a series of cases re- solved by an intraoral approach and video-endoscopic assis- tance for the management of mandibular condyle fractures. Clinical cases: Three cases of patients with unilater- al mandibular condyle fractures are presented. Two of the cases presented a second line of associated parasymphyseal fracture. The treatment performed was open reduction and internal fixation of all fractures by oral approach. Mid-term and long-term clinical and tomographic follow-ups were per- formed, with favorable results (AU)

Factores de riesgo de contagio de la Covid-19 en personal sanitario / Risk Factors for COVID-19 transmission among healthcare workers

Objetivos: El personal sanitario se sitúa en la primera barrera en la lucha contra la Covid-19, constituyendo un colectivo con una alto riesgo de infección. El objetivo del presente estudio es describir los factores de riesgo asociados en una población de profesionales que trabajan en un consorcio sanitario que incluye diferentes centros relacionados con la atención a la salud. Métodos: Estudio observacional analítico retrospectivo; población 2.620 trabajadores sanitarios; desde el inicio del Estado de Alarma en España (15/03/20) hasta 21/06/2020. Se calcula la asociación entre las variables independientes sexo, edad, años de antigüedad, categoría profesional y lugar de trabajo con la presencia de Covid-19 mediante la prueba Chi-Cuadrado y el cálculo de la Odds Ratio (OR) e intervalo de confianza al 95% (IC95%) simple y ajustado mediante Regresión Logística Múltiple. Límite de significación aceptado ≤0,05. Resultados: El personal sanitario, en todas las categorías, presenta siempre más riesgo respecto al no sanitario. Enfermería mostró los riesgos más altos -OR:14,03 (3,19-61,66)-. En el lugar de trabajo, Hospitalización-Médico-Quirúrgica -OR:13,43 (1,7-106,12)- y Sociosanitario -OR:17,77 (2,19-144,04)- presentaron más riesgo respecto a los que no tienen contacto con pacientes. Conclusión: El riesgo más elevado de contagio se presentó entre los profesionales que tienen mayor contacto con pacientes y en los lugares en los que se detectaron por PCR positivos para Covid-19 entre los pacientes ingresados por otras patologías, teniendo un riesgo mayor los profesionales que atienden estos pacientes que aquellos que atienden zonas destinadas a Covid-19 (AU)

Objective: Frontline healthcare workers are the first line of defense against Covid-19, resulting in a higher risk of infection. The objective of this study was to describe the impact of the SARS-CoV-2 infection and its associated risk factors among professionals working in a healthcare consortium that includes different centers. Methods: This was a retrospective analytical observational study of 2620 healthcare workers; the project period began with the declaration of the state of alarm in Spain (March 15, 2020) and ended on June 21, 2020. We estimated associations between the independent variables sex, age, seniority, professional category and work location and confirmed COVID-19 as the outcome variable. Bivariate study analysis was based on chi-square test and simple logistic regression with calculation of the odds ratio (OR) and 95% confidence interval (95%CI). Multivariate analysis was performed using multiple logistic regression. Statistical significance was set at p ≤0.05. Results: All frontline healthcare worker categories were at higher risk than non-patient-facing personnel. Nurses had the highest risk [OR, 14.03 (3.19-61.66)]. With respect to work location, and as compared to non-patient-facing personnel, working in the surgical-medical-hospitalization-clinic [OR 13.43 (1.7-106.12)] and socio-health center [OR 17.77 (2.19-144.04) posed the greatest risks. Conclusions: The greatest risk of acquiring COVID-19 was among patient-facing healthcare professionals working in areas where COVID-19 was detected among patients admitted for other pathologies. This risk was higher than in those areas designated for the care of COVID-19 patients, possibly due to differences in the use of personal protective equipment (AU)

Odontoma complejo: resolución de un caso con utilización de osteosíntesis rígida por riesgo de fractura mandibular / Complex odontoma: case resolution with the use of rigid osteosynthesis for risk of mandibular fracture

Objetivo: Describir la resolución de un caso un odontoma complejo de gran tamaño con utilización de osteosíntesis rígida. Caso clínico: Una paciente de 13 años de edad se presentó a la consulta por aumento de volumen en hemifacia izquierda, de 4 meses de evolución. Mediante biopsia incisional, se diagnosticó odontoma complejo. Se realizó tratamiento quirúrgico con utilización de osteosíntesis rígida. Se decidió retirar la placa de osteosíntesis a los 6 meses posoperatorios para evitar alterar el crecimiento y el desarrollo mandibular. Se indicó control posoperatorio durante 5 años. Conclusión: La utilización de osteosíntesis rígida fue adecuada para reforzar el defecto óseo mandibular producido durante el tratamiento quirúrgico de un odontoma complejo de gran tamaño (AU)

Aim: To describe the resolution of a case of a large complex odontoma with the use of rigid osteosynthesis. Clinical case: A 13-year-old patient presented with a swelling in left jaw of 4 months of evolution. Complex odontoma was diagnosed by incisional biopsy. Surgical treatment was performed with the use of rigid osteosynthesis. Removal of osteosynthesis plate was decided 6 months postoperatively to avoid alteration of mandibular growth and development. Postoperative control was indicated for 5 years. Conclusion: The use of rigid osteosynthesis was adequate to reinforce the mandibular bone defect produced during the surgical treatment of large complex odontoma (AU)

Análisis evolutivo de morbimortalidad en cirugía de urgencias durante la pandemia: comparación retrospectiva entre primera y segunda ola de COVID-19 / Evolutionary analysis of patient's morbidity and mortality in emergency surgical care during the pandemic: Retrospective comparison between first and second wave of COVID-19

Introducción: Desde el comienzo de la pandemia, la morbimortalidad en la atención urgente al paciente quirúrgico ha sido objeto de estudio. Sin embargo, la mayoría de los estudios compararon dicha variable con la propia de la época pre-COVID, obviando la evolución de la misma durante la propia pandemia. Con el objetivo de analizar este posible cambio, realizamos un estudio comparativo de morbimortalidad en cirugía de urgencias entre la primera y segunda ola de la pandemia en nuestro centro. Material y métodos: Estudio retrospectivo longitudinal que incluyó a todos los pacientes mayores de 18 años ingresados y/o intervenidos quirúrgicamente de forma urgente en los dos periodos de máxima incidencia (PMI) de infección por COVID-19 (1.er: 22/03/2020-31/05/2020; 2.° PMI: 26/08/2020-30/11/2020). Se analizó la incidencia de infección por SARS-CoV-2, el tratamiento recibido, la morbimortalidad precoz y los posibles factores de riesgo de complicaciones. Resultados: Se analizaron 173 pacientes (1.er: 66; 2.° PMI: 107). La incidencia de COVID-19 fue mayor en el segundo periodo (14,95% vs. 4,54%). La infección por SARS-CoV-2 se asoció a una mayor tasa de complicaciones, sin embargo, no se observaron diferencias estadísticamente significativas en la morbimortalidad general (p = 0,746) ni en la de los pacientes COVID positivos (p = 0,582) entre ambos periodos. El tratamiento quirúrgico se asoció con una menor tasa de complicaciones tanto en la primera (p = 0,006) como en la segunda ola (p = 0,014). Dicho tratamiento quirúrgico fue más frecuente en el segundo PMI (70,1 vs. 57,6%) aunque no se alcanzó la significación estadística al respecto de esta afirmación (p = 0,065).(AU)

Introduction: Since the beginning of the pandemic, morbidity and mortality in emergency care of surgical patients have been the subject of several studies. However, most of these have compared this variable with that of the pre-COVID period, ignoring its evolution during the pandemic itself. In order to analyze this possible change, we performed a comparative study of morbidity and mortality in emergency surgery between the first and second waves of the pandemic in our center. Material and methods: Retrospective longitudinal study including all patients over the age of 18 admitted and/or operated in the emergency setting in the two maximum incidence periods (MIP) of COVID-19 infection (1st MIP: 22/03/2020–31/05/2020; 2nd MIP: 26/08/2020–30/11/2020). The incidence of SARS-CoV-2 infection, treatment received, early morbidity and mortality and possible risk factors for complications were analyzed. Results: A total of 173 patients were analyzed (1st MIP: 66; 2nd MIP: 107). The incidence of COVID-19 was higher in the second period (14.95% vs. 4.54%). SARS-CoV-2 infection was associated with a higher rate of complications, however, no statistically significant differences were observed in morbimortality rate, either in the total sample (p = 0.746) or in patients with a positive COVID-19 test (p = 0.582) between both periods. Surgical treatment was found to be associated with a lower complication rate in both the first (p = 0.006) and second wave (p = 0.014), and it was more frequent in the second PMI (70.1 vs. 57.6%) although statistical significance was not reached (p = 0.065). (AU)

Síndrome confusional agudo en pacientes posquirúrgicos de cirugía de revascularización miocárdica / Acute confusional state in postoperative surgical patients myocardial revascularization

Se realizó un estudio de investigación con un diseño cuantitativo, analítico, retrospectivo, transversal, conmetodología de Casos y Controles, seleccionando una muestra de 90 pacientes, a través de un muestreo aleatorio simple de un total de 246 pacientes posquirúrgicos de revascularización miocárdica, los cuales fueron distribuidos en grupo de casos y grupo de controles. En el grupo casos se incluyeron 30 pacientes, mientras que en el grupo control se incluyeron 60 pacientes. Esto fue realizado en el Instituto de Cardiología de Juana Francisca Cabral, de la ciudad de Corrientes, capital. Las operaciones estadísticas utilizadas fueron porcentajes, promedios; y para establecer las asociaciones, OddsRatio, el nivel de significación fue de p< 0,05, se utilizó el programa “SPPS, versión 17.0”. Cuando se analizó la CEC (Circulación Extracorpórea), en relación al Síndrome Confusional Agudo, se encontró que los pacientes que requirieron CEC tienen 1,75 veces más de probabilidades de desarrollar S.C.A. que los pacientes que no requirieron CEC, con Intervalo de Confianza = 0,71 – 4,17 y P= 0,162 (NS= no significativo). Al analizar el antecedente de tabaquismo, se observó que los pacientes con antecedente de tabaquismo, tienen 1,83 veces más de probabilidades de desarrollar S.C.A. en el posoperatorio de cirugía de revascularización miocárdica con circulación extracorpórea, que de los pacientes sin antecedente de tabaquismo, con un Intervalo de Confianza = 0,58 – 3,36 y P= 0,3 (NS= no significativo). Por último, al analizar la variable sexo, se encontró que el grupo de mujeres tienen 2,11 veces más de probabilidades de desarrollar S.C.A., en el posoperatorio de cirugía de revascularización miocárdica con circulación extracorpórea, que los pacientes del sexo masculino, con Intervalo de Confianza = 0,78 – 7,09 y P= 0,10 (NS= no significativo...

A research study was conducted with quantitative, analytical, retrospective, cross-sectional design with CaseControlmethodology, selecting a sample of 90 patients, through simple random sampling a total of 246 patientspostoperative myocardial revascularization, the which were distributed in the case group and control group. In the case group included 30 patients, whereas in the control group 60 patients were included. This was done at the Institute of Cardiology of Juana Francisca Cabral, city of Corrientes, capital. The statistics operations were used percentages, averages; and to establish partnerships, Odds Ratio, the level ofsignificance was p <0.05, the program was used "SPPS, version 17.0."When the CEC was analyzed in relation to acute confusional syndrome, found that patients who required CPB are1.75 times more likely to develop SCA Patients who required NO CEC, with confidence interval = 0.71 to 4.17 and P= 0.162 (NS = not significant).When analyzing the History of Smoking, it was observed that patients with a history of Tobacco, have 1.83 timesmore likely to develop SCA in the postoperative CABG with cardiopulmonary bypass patients without a history of smoking, a confidence interval = 0.58 to 3.36 and P = 0.3 (NS = not significant). Finally when analyzing the gender variable, it was found that in the group of women, are 2.11 times more likely to develop SCA in the postoperative CABG with cardiopulmonary bypass, that male patients with confidence interval = 0.78 to 7.09 and P = 0.10 (NS = not significant)...

Condromatosis sinovial en la articulación temporomandibular: presentación de caso clínico / Synovial chondromatosis of the temporomandibular joint: clinical case presentation

Objetivo: presentar las características clínicas y por imágenes de un paciente con condromatosis sinovial en la articulación temporomandibular izquierda y el tratamiento realizado. Caso clínico: la condromatosis sinovial es una artropatía benigna crónica, progresiva y proliferativa, que suele afectar las articulaciones largas y, con poca frecuencia, la articulación temporomandibular. En este último caso, la enfermedad se caracteriza por el desarrollo de nódulo cartilaginosos en el espacio articular. Los síntomas clínicos de condromatosis sinovial en la ATM son dolor, inflamación, crepitación, maloclusión y disfunción. Esta sintomatología es común a la de otras patologías en la misma articulación, por lo que la sospecha y el diagnóstico de condromatosis sinovial son en sí un desafío. Conclusión: la condromatosis sinovial es una patología poco frecuente en la articulación temporomandibular. Una vez diagnosticada, yta sea en estadíos tempranos o avanzados, se puede optar por diversos tratamientos, con excelentes pronósticos.

Cariotipo espectral multicolor (SKY). Las ventajas de una segunda opinión en el diagnóstico citogenético de tumores

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