Factors affecting biochemical pregnancy loss (BPL) in preimplantation genetic testing for aneuploidy (PGT-A) cycles: machine learning-assisted identification.

PURPOSE: To determine the factors influencing the likelihood of biochemical pregnancy loss (BPL) after transfer of a euploid embryo from preimplantation genetic testing for aneuploidy (PGT-A) cycles. METHODS: The study employed an observational, retrospective cohort design, encompassing 6020 embryos from 2879 PGT-A cycles conducted between February 2013 and September 2021. Trophectoderm biopsies in day 5 (D5) or day 6 (D6) blastocysts were analyzed by next generation sequencing (NGS). Only single embryo transfers (SET) were considered, totaling 1161 transfers. Of these, 49.9% resulted in positive pregnancy tests, with 18.3% experiencing BPL. To establish a predictive model for BPL, both classical statistical methods and five different supervised classification machine learning algorithms were used. A total of forty-seven factors were incorporated as predictor variables in the machine learning models. RESULTS: Throughout the optimization process for each model, various performance metrics were computed. Random Forest model emerged as the best model, boasting the highest area under the ROC curve (AUC) value of 0.913, alongside an accuracy of 0.830, positive predictive value of 0.857, and negative predictive value of 0.807. For the selected model, SHAP (SHapley Additive exPlanations) values were determined for each of the variables to establish which had the best predictive ability. Notably, variables pertaining to embryo biopsy demonstrated the greatest predictive capacity, followed by factors associated with ovarian stimulation (COS), maternal age, and paternal age. CONCLUSIONS: The Random Forest model had a higher predictive power for identifying BPL occurrences in PGT-A cycles. Specifically, variables associated with the embryo biopsy procedure (biopsy day, number of biopsied embryos, and number of biopsied cells) and ovarian stimulation (number of oocytes retrieved and duration of stimulation), exhibited the strongest predictive power.

Trefoil Factor 2 Expressed by the Murine Pancreatic Acinar Cells Is Required for the Development of Islets and for ß-Cell Function During Aging.

Exocrine-to-endocrine cross talk in the pancreas is crucial to maintain ß-cell function. However, the molecular mechanisms underlying this cross talk are largely undefined. Trefoil factor 2 (Tff2) is a secreted factor known to promote the proliferation of ß-cells in vitro, but its physiological role in vivo in the pancreas is unknown. Also, it remains unclear which pancreatic cell type expresses Tff2 protein. We therefore created a mouse model with a conditional knockout of Tff2 in the murine pancreas. We find that the Tff2 protein is preferentially expressed in acinar but not ductal or endocrine cells. Tff2 deficiency in the pancreas reduces ß-cell mass on embryonic day 16.5. However, homozygous mutant mice are born without a reduction of ß-cells and with acinar Tff3 compensation by day 7. When mice are aged to 1 year, both male and female homozygous and male heterozygous mutants develop impaired glucose tolerance without affected insulin sensitivity. Perifusion analysis reveals that the second phase of glucose-stimulated insulin secretion from islets is reduced in aged homozygous mutant compared with controls. Collectively, these results demonstrate a previously unknown role of Tff2 as an exocrine acinar cell-derived protein required for maintaining functional endocrine ß-cells in mice.

Exome sequencing in genuine empty follicle syndrome: Novel candidate genes.

OBJECTIVE(S): Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved in an IVF cycle despite apparently normal follicular development and meticulous follicular aspiration following ovulation induction. The EFS is called genuine (gEFS) when the trigger administration is correct. The existence of gEFS is a subject of controversy, and it is quite rare with an undetermined etiology. Genetic defects in specific genes have been demonstrated to be responsible for this condition in some patients. Our objective was to identify novel genetic variants associated with gEFS. STUDY DESIGN: We conducted a prospective observational study including 1,689 egg donors from July 2017 to February 2023. WES were performed in patients suffering gEFS. RESULTS: Only 7 patients (0.41 %) exhibited gEFS after two ovarian stimulation cycles and we subsequently performed whole exome sequencing (WES) on these patients. Following stringent filtering, we identified 6 variants in 5 affected patients as pathogenic in new candidate genes which have not been previously associated with gEFS before, but which are involved in important biological processes related to folliculogenesis. These genetic variants included c.603_618del in HMMR, c.1025_1028del in LMNB1, c.1091-1G > A in TDG, c.607C > T in HABP2, c.100 + 2 T > C in HAPLN1 and c.3592_3593del in JAG2. CONCLUSION: As a conclusion, we identified new candidate genes related to gEFS that expand the mutational spectrum of genes related to gEFS.This study show that WES might be an efficient tool to identify the genetic etiology of gEFS and provide further understanding of the pathogenic mechanism of gEFS.

Chemical sensing of common microorganisms found in biopharmaceutical industries using MIR laser spectroscopy and multivariate analysis.

Mid-infrared laser spectroscopy was used to investigate common bacteria encountered in biopharmaceutical industries. The study involved the detection of bacteria using quantum cascade laser spectroscopy coupled to a grazing angle probe (QCL-GAP). Substrates similar to surfaces commonly used in biopharmaceutical industries were used as support media for the samples. Reflectance measurements were assisted by Multivariate Analysis (MVA) to assemble a powerful spectroscopic technique with classification and identification resources. The species analyzed, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus, were used to challenge the technique's capability to discriminate from microorganisms of the same family. Principal Components Analysis and Partial Least Squares-Discriminant Analysis differentiated between the bacterial species, using QCL-GAP-MVA as the reference. Spectral differences in the bacterial membrane were used to determine if these microorganisms were present in the samples analyzed. Results herein provided effective discrimination for the bacteria under study with high sensitivity and specificity.

Activation of ductal progenitor-like cells from adult human pancreas requires extracellular matrix protein signaling.

Ductal progenitor-like cells are a sub-population of ductal cells in the adult human pancreas that have the potential to contribute to regenerative medicine. However, the microenvironmental cues that regulate their activation are poorly understood. Here, we establish a 3-dimensional suspension culture system containing six defined soluble factors in which primary human ductal progenitor-like and ductal non-progenitor cells survive but do not proliferate. Expansion and polarization occur when suspension cells are provided with a low concentration (5% v/v) of Matrigel, a sarcoma cell product enriched in many extracellular matrix (ECM) proteins. Screening of ECM proteins identified that collagen IV can partially recapitulate the effects of Matrigel. Inhibition of integrin α1ß1, a major collagen IV receptor, negates collagen IV- and Matrigel-stimulated effects. These results demonstrate that collagen IV is a key ECM protein that stimulates the expansion and polarization of human ductal progenitor-like and ductal non-progenitor cells via integrin α1ß1 receptor signaling.

Impact of Group vs Individual Embryo Culture Strategies on Blastocyst and Clinical Outcomes.

Embryo culture is one of the most important steps in an assisted reproduction laboratory. Embryos can be cultured individually, one embryo per media drop, or in groups, culturing several embryos in the same media drop. Due to the controversy generated on this subject, we wondered which embryo culture method would have the best results in terms of quality and blastocyst formation rate. We designed a prospective randomized study comparing two different embryo culture strategies: group and individual embryo culture. The data were obtained from 830 embryos from 103 egg donation treatments. The zygotes were randomized into two groups: individual culture (group 1) or group culture (group 2). The embryos were cultured in 35-µl drops until day 5 when they were classified morphologically. We observed a significant increase in the blastocyst formation rate and in the usable embryo rate in individual culture on day 5 compared to group culture. However, good embryo quality (A/B blastocysts), implantation, and pregnancy rates were similar regardless of the type of embryo-culture. As a conclusion, individual culture may increase blastocyst formation rate and may benefit embryo quality on day 5. Our results support previous reports suggesting that individual culture could improve embryo development.

Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury.

Pancreatic ductal progenitor cells have been proposed to contribute to adult tissue maintenance and regeneration after injury, but the identity of such ductal cells remains elusive. Here, from adult mice, we identify a near homogenous population of ductal progenitor-like clusters, with an average of 8 cells per cluster. They are a rare subpopulation, about 0.1% of the total pancreatic cells, and can be sorted using a fluorescence-activated cell sorter with the CD133highCD71lowFSCmid-high phenotype. They exhibit properties in self-renewal and tri-lineage differentiation (including endocrine-like cells) in a unique 3-dimensional colony assay system. An in vitro lineage tracing experiment, using a novel HprtDsRed/+ mouse model, demonstrates that a single cell from a cluster clonally gives rise to a colony. Droplet RNAseq analysis demonstrates that these ductal clusters express embryonic multipotent progenitor cell markers Sox9, Pdx1, and Nkx6-1, and genes involved in actin cytoskeleton regulation, inflammation responses, organ development, and cancer. Surprisingly, these ductal clusters resist prolonged trypsin digestion in vitro, preferentially survive in vivo after a severe acinar cell injury and become proliferative within 14 days post-injury. Thus, the ductal clusters are the fundamental units of progenitor-like cells in the adult murine pancreas with implications in diabetes treatment and tumorigenicity.

Síndrome metabólico: percepción de enfermedad y falta de adherencia a la prescripción médica / Metabolic syndrome: disease perception and lack of adherence to medical advice

Se presenta el caso de una mujer de 52 años sedentaria y con sobrepeso, índice de masa corporal igual 28.3, que tiene, según ATP-III, las 5 características del síndrome metabólico: diabetes tipo 2, glicemia en ayunas igual 294 mg/dL, trialcilglicerol igual 162 mg/dL, HDL-colesterol igual 44 mg/dL y obesidad central, perímetro de la cintura igual 90 cm. La diabetes tipo 2 le fue diagnosticada hace 17 años, recibe medicamento para la hipertensión desde hace 7 años y presenta hipercolesterolemia, colesterol total igual 283 mg/dL, para lo que no recibe tratamiento farmacológico. A pesar de su condición, la paciente se considera saludable lo cual le impide modificar su estilo de vida y mejorar la calidad de vida lo que aumenta el costo de su tratamiento médico para el sistema de seguridad social.

Efecto de la actividad física en la reducción del riesgo de enfermedad cardiovascular mediante el control del peso corporal / The effect of physical activity over cardiovascular risk reduction by means of weight control

La obesidad es un padecimiento complejo que ha alcanzado niveles de epidemia mundial y constituye un importante riesgo de enfermedad cardiovascular. En el 2005, el 40.5 por ciento de la población adulta estadounidense era físicamente inactiva, sedentaria, un año antes la prevalencia de obesidad, en la misma población, era de 32.1 por ciento, un aumento de 37.8 por ciento en una década. Existen pocos trabajos publicados que valoran el efecto de la actividad física, AF en la pérdida inicial peso y en el mantenimiento del nuevo peso después de un período de seguimiento igual o mayor a 1 año. La evidencia indica que el efecto del gasto de energía por AF incrementa la pérdida de peso, mejora la conservación del nuevo peso durante el período de seguimiento, 2 años, disminuye la pérdida de masa magra que produce la pérdida de peso, mejora el control de la ingesta de energía y no produce un incremento compensatorio en el corto plazo en la ingesta de energía. Los programas exitosos de pérdida de peso y mantenimiento del peso perdido incluyen un aumento en la AF. Es necesario hacer estudios aleatorizados y controlados de pérdida de peso y mantenimiento del nuevo peso que incluyan aumentos en la AF antes, durante y después de la restricción de la ingesta de calorías y sus diferentes combinaciones que permita estimar la magnitud de cada efecto.

Apendicectomía laparoscópica: estudio comparativo / Laparoscopic appendectomy: a comparative study

Objetivo: analizar los resultados de la apendicectomía laparoscópica y la apendicectomía abierta para comparar y evaluar ambos procedimientos realizados por el mismo equipo médico Sede: servicio de cirugía general del Hospital Regional 1§ de octubre y practica privada en la Ciudad de México. Diseño: estudio retrospectivo, observacional, con grupo control y seguimiento longiudinal. Material y métodos: se estudiaron los expedientes clínicos de 150 pacientes intervenidos quirúrgicamente de apendicectomía; todos procedían del servicio de urgencias con diagnóstico de apendicitis aguda y se dividieron en dos grupos: uno de 75 pacientes operados por vía tradicional y otro de 75 sujetos intervenidos por apendicectomía laparoscópica. Se excluyeron del estudio pacientes con operaciones previas en hemiabdomen inferior, con alteraciones que contraindicaban la anestesia general y mujeres embarazadas. Las variables analizadas fueron las siguientes: comienzo del tratamiento por vía oral, analgésico usados, estancia hospitalaria, complicaciones transoperatorias, reintervenciones quirúrgicas, índice de conversión, resultados histopatológicos y días de incapacidad posoperatoria. Resultados: éstos no mostraron diferencias estadísticas significativas en ambos grupos. Con la laparoscopia se obtienen mejores resultados estéticos y la reincorporación a las actividades normales se da en menor tiempo, lo que se traduce en menos días de incapacidad laboral