RESUMEN
The plant signaling molecule auxin is present in multiple kingdoms of life. Since its discovery, a century of research has been focused on its action as a phytohormone. In land plants, auxin regulates growth and development through transcriptional and non-transcriptional programs. Some of the molecular mechanisms underlying these responses are well understood, mainly in Arabidopsis. Recently, the availability of genomic and transcriptomic data of green lineages, together with phylogenetic inference, has provided the basis to reconstruct the evolutionary history of some components involved in auxin biology. In this review, we follow the evolutionary trajectory that allowed auxin to become the "giant" of plant biology by focusing on bryophytes and streptophyte algae. We consider auxin biosynthesis, transport, physiological, and molecular responses, as well as evidence supporting the role of auxin as a chemical messenger for communication within ecosystems. Finally, we emphasize that functional validation of predicted orthologs will shed light on the conserved properties of auxin biology among streptophytes.
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Arabidopsis , Ácidos Indolacéticos , Filogenia , Ecosistema , Evolución Molecular , Plantas , Arabidopsis/genéticaRESUMEN
The origin and evolution of hominin mortuary practices are topics of intense interest and debate1-3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1-6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS), a cave site in the tropical upland coast of Kenya7,8. Recent excavations have revealed a pit feature containing a child in a flexed position. Geochemical, granulometric and micromorphological analyses of the burial pit content and encasing archaeological layers indicate that the pit was deliberately excavated. Taphonomical evidence, such as the strict articulation or good anatomical association of the skeletal elements and histological evidence of putrefaction, support the in-place decomposition of the fresh body. The presence of little or no displacement of the unstable joints during decomposition points to an interment in a filled space (grave earth), making the PYS finding the oldest known human burial in Africa. The morphological assessment of the partial skeleton is consistent with its assignment to Homo sapiens, although the preservation of some primitive features in the dentition supports increasing evidence for non-gradual assembly of modern traits during the emergence of our species. The PYS burial sheds light on how MSA populations interacted with the dead.
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Entierro/historia , Fósiles , Esqueleto/anatomía & histología , Animales , Huesos/anatomía & histología , Preescolar , Evolución Cultural/historia , Dentición , Historia Antigua , Hominidae/anatomía & histología , Hominidae/clasificación , Humanos , KeniaRESUMEN
DELLA proteins are negative regulators of the gibberellin response pathway in angiosperms, acting as central hubs that interact with hundreds of transcription factors (TFs) and regulators to modulate their activities. While the mechanism of TF sequestration by DELLAs to prevent DNA binding to downstream targets has been extensively documented, the mechanism that allows them to act as coactivators remains to be understood. Here, we demonstrate that DELLAs directly recruit the Mediator complex to specific loci in Arabidopsis, facilitating transcription. This recruitment involves DELLA amino-terminal domain and the conserved MED15 KIX domain. Accordingly, partial loss of MED15 function mainly disrupted processes known to rely on DELLA coactivation capacity, including cytokinin-dependent regulation of meristem function and skotomorphogenic response, gibberellin metabolism feedback, and flavonol production. We have also found that the single DELLA protein in the liverwort Marchantia polymorpha is capable of recruiting MpMED15 subunits, contributing to transcriptional coactivation. The conservation of Mediator-dependent transcriptional coactivation by DELLA between Arabidopsis and Marchantia implies that this mechanism is intrinsic to the emergence of DELLA in the last common ancestor of land plants.
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Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Marchantia , Complejo Mediador , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Complejo Mediador/metabolismo , Complejo Mediador/genética , Marchantia/genética , Marchantia/metabolismo , Giberelinas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Transcripción Genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genéticaRESUMEN
BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).
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Arenavirus del Nuevo Mundo , Fiebre Hemorrágica Americana , ARN Viral , Roedores , Animales , Arenavirus del Nuevo Mundo/genética , Arenavirus del Nuevo Mundo/aislamiento & purificación , Bolivia/epidemiología , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Transmisión de Enfermedad Infecciosa , Fiebre Hemorrágica Americana/complicaciones , Fiebre Hemorrágica Americana/genética , Fiebre Hemorrágica Americana/transmisión , Fiebre Hemorrágica Americana/virología , Fiebres Hemorrágicas Virales/genética , Fiebres Hemorrágicas Virales/transmisión , Fiebres Hemorrágicas Virales/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Reacción en Cadena de la Polimerasa , ARN Viral/genética , ARN Viral/aislamiento & purificación , Ratas/virología , Roedores/virología , Zoonosis Virales/transmisión , Zoonosis Virales/virologíaRESUMEN
The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5' â 3' exoribonuclease paralogs. In yeast, they are called Xrn1, which shuttles between the nucleus and the cytoplasm, and executes major cytoplasmic messenger RNA (mRNA) decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes to the nucleus. Xrn1 is 30% identical to Rat1 but has an extra ~500 amino acids C-terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes, a process referred to as "cotranslational mRNA decay." The division of labor between the two enzymes is still enigmatic and serves as a paradigm for the subfunctionalization of many other paralogs. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the physical segregation of the two paralogs plays roles in their specific functions. However, reversing segregation is not sufficient to fully complement the Xrn1 function. Specifically, cRat1 can partially restore the cell volume, mRNA stability, the proliferation rate, and 5' â 3' decay alterations that characterize xrn1Δ cells. Nevertheless, cotranslational decay is only slightly complemented by cRat1. The use of the AlphaFold prediction for cRat1 and its subsequent docking with the ribosome complex and the sequence conservation between cRat1 and Xrn1 suggest that the tight interaction with the ribosome observed for Xrn1 is not maintained in cRat1. Adding the Xrn1 C-terminal domain to Rat1 does not improve phenotypes, which indicates that lack of the C-terminal is not responsible for partial complementation. Overall, during evolution, it appears that the two paralogs have acquired specific characteristics to make functional partitioning beneficial.
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Exorribonucleasas , Estabilidad del ARN , ARN Mensajero , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Exorribonucleasas/metabolismo , Exorribonucleasas/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Citoplasma/metabolismo , Biosíntesis de ProteínasRESUMEN
Beer brewing is a well-known process that still faces great challenges, such as the total consumption of sugars present in the fermentation media. Lager-style beer, a major worldwide beer type, is elaborated by Saccharomyces pastorianus (Sp) yeast, which must ferment high maltotriose content worts, but its consumption represents a notable problem, especially among Sp strains belonging to group I. Factors, such as fermentation conditions, presence of maltotriose transporters, transporter copy number variation, and genetic regulation variations contribute to this issue. We assess the factors affecting fermentation in two Sp yeast strains: SpIB1, with limited maltotriose uptake, and SpIB2, known for efficient maltotriose transport. Here, SpIB2 transported significantly more maltose (28%) and maltotriose (32%) compared with SpIB1. Furthermore, SpIB2 expressed all MAL transporters (ScMALx1, SeMALx1, ScAGT1, SeAGT1, MTT1, and MPHx) on the first day of fermentation, whereas SpIB1 only exhibited ScMalx1, ScAGT1, and MPH2/3 genes. Some SpIB2 transporters had polymorphic transmembrane domains (TMD) resembling MTT1, accompanied by higher expression of these transporters and its positive regulator genes, such as MAL63. These findings suggest that, in addition to the factors mentioned above, positive regulators of Mal transporters contribute significantly to phenotypic diversity in maltose and maltotriose consumption among the studied lager yeast strains.IMPORTANCEBeer, the third most popular beverage globally with a 90% market share in the alcoholic beverage industry, relies on Saccharomyces pastorianus (Sp) strains for lager beer production. These strains exhibit phenotypic diversity in maltotriose consumption, a crucial process for the acceptable organoleptic profile in lager beer. This diversity ranges from Sp group II strains with a notable maltotriose-consuming ability to Sp group I strains with limited capacity. Our study highlights that differential gene expression of maltose and maltotriose transporters and its upstream trans-elements, such as MAL gene-positive regulators, adds complexity to this variation. This insight can contribute to a more comprehensive analysis needed to the development of controlled and efficient biotechnological processes in the beer brewing industry.
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Cerveza , Fermentación , Proteínas Fúngicas , Maltosa , Saccharomyces , Trisacáridos , Maltosa/metabolismo , Trisacáridos/metabolismo , Saccharomyces/genética , Saccharomyces/metabolismo , Cerveza/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Transporte Biológico , Proteínas de Transporte de Monosacáridos/genética , Proteínas de Transporte de Monosacáridos/metabolismo , Regulación Fúngica de la Expresión GénicaRESUMEN
OBJECTIVE: To investigate genetic interactions between mitochondrial deoxyribonucleic acid (mtDNA) haplogroups and nuclear single nucleotide polymorphisms (nSNPs) to analyze their impact on the development of the rapid progression of knee osteoarthritis (OA). DESIGN: A total of 1095 subjects from the Osteoarthritis Initiative, with a follow-up time of at least 48-months, were included. Appropriate statistical approaches were performed, including generalized estimating equations adjusting for age, gender, body mass index, contralateral knee OA, Western Ontario and McMaster Universities Osteoarthritis Index pain, previous injury in target knee and the presence of the mtDNA variant m.16519C. Additional genomic data consisted in the genotyping of Caucasian mtDNA haplogroups and eight nSNPs previously associated with the risk of knee OA in robust genome-wide association studies. RESULTS: The simultaneous presence of the G allele of rs12107036 at TP63 and the haplogroup Uk significantly increases the risk of a rapid progression of knee OA (odds ratio = 1.670; 95% confidence interval [CI]: 1.031-2.706; adjusted p-value = 0.027). The assessment of the population attributable fraction showed that the highest proportion of rapid progressors was under the simultaneous presence of the G allele of rs12107036 and the haplogroup Uk (23.4%) (95%CI: 7.89-38.9; p-value < 0.05). The area under the curve of the cross-validation model (0.730) was very similar to the obtained for the predictive model (0.735). A nomogram was constructed to help clinicians to perform clinical trials or epidemiologic studies. CONCLUSIONS: This study demonstrates the existence of a mitonuclear epistasis in OA, providing new mechanisms by which nuclear and mitochondrial variation influence the susceptibility to develop different OA phenotypes.
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Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/epidemiología , Estudio de Asociación del Genoma Completo , Epistasis Genética , Articulación de la Rodilla , ADN Mitocondrial/genética , Progresión de la Enfermedad , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Physiotherapists encounter challenges in diagnosing myofascial trigger points (MTrPs), which are crucial for managing myofascial pain but difficult due to their complex referred pain patterns. We aimed to assess if an interactive software (MyofAPPcial) can enhance the ability of physical therapists specialized in musculoskeletal disorders (as clinicians and as researchers and educators) to identify referred pain patterns associated with specific MTrPs and to explore their opinion about incorporating this technology regularly into their professional setting. METHODS: After developing the app, a descriptive cross-sectional survey study was conducted. Participants were asked about their demographic characteristics, professional experience, two knowledge tests (first without and later with MyofAPPcial support) and the 18-item mHealth app usability questionnaire. RESULTS: Fifty-nine participants completed the survey (47.5% clinicians and 62.5% researchers/educators). Groups were comparable in terms of age, gender and professional experience (p > .05). However, clinicians coursed shorter specific MPS trainings (p = .007) and handle more cases a week (p < .001). In the first knowledge test, participants in both the groups were more accurate in identifying pain maps of highly prevalent MTrPs than those with a moderate or low prevalence (p < .001), with no differences between the groups for individual items (all, p > .05) nor the total score (p > .05). In the second knowledge test, perfect scores were obtained for all items in both the groups. Finally, MyofAPPcial scored high satisfaction and app usefulness, with no difference between clinicians and researchers/educators (except greater convenience of use for researchers/educators p = .02). CONCLUSIONS: MyofAPPcial enhances physiotherapists' ability to accurately identify MTrPs, with a good acceptation among clinicians and researchers/educators.
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BACKGROUND: Tepary bean (Phaseolus acutifolius A. Gray) is one of the five species domesticated from the genus Phaseolus with genetic resistance to biotic and abiotic stress. To understand the mechanisms underlying drought responses in seed storage proteins germinated on water and polyethylene glycol (PEG-6000) at -0.49 MPa, we used a proteomics approach to identify potential molecular target proteins associated with the low water potential stress response. METHODS: Storage proteins from cotyledons of Tepary bean seeds germinated at 24, 48 and 72 h on water and PEG-6000 at -0.49 MPa were analyzed by one-dimensional electrophoresis (DE) with 2-DE analysis and shotgun mass spectrometry. Using computational database searching and bioinformatics analyses, we performed Gene Ontology (GO) and protein interactome (functional protein association network) String analyses. RESULTS: Comparative analysis showed that the effect of PEG-6000 on root growth was parallel to that on germination. Based on the SDSâPAGE protein banding patterns and 2-DE analysis, ten differentially abundant seed storage proteins showed changes in storage proteins, principally in the phaseolin and lectin fractions. We found many proteins that are recognized as drought stress-responsive proteins, and several of them are predicted to be intrinsically related to abiotic stress. The shotgun analysis searched against UniProt's legume database, and Gene Ontology (GO) analysis indicated that most of the seed proteins were cytosolic, with catalytic activity and associated with carbohydrate metabolism. The proteinâprotein interaction networks from functional enrichment analysis showed that phytohemagglutinin interacts with proteins associated with the degradation of storage proteins in the cotyledons of common bean during germination. CONCLUSION: These findings suggest that Tepary bean seed proteins provide valuable information with the potential to be used in genetic improvement and are part of the drought stress response, making our approach a potentially useful strategy for discovering novel drought-responsive proteins in other plant models.
RESUMEN
Through a COVID-19 public health intervention implemented across sequenced research trials, we present a community engagement phased framework that embeds intervention implementation: (1) consultation and preparation, (2) collaboration and implementation, and (3) partnership and sustainment. Intervention effects included mitigation of psychological distress and a 0.28 increase in the Latinx population tested for SARS-CoV-2. We summarize community engagement activities and implementation strategies that took place across the trials to illustrate the value of the framework for public health practice and research. (Am J Public Health. 2024;114(S5):S396-S401. https://doi.org/10.2105/AJPH.2024.307669).
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COVID-19 , Humanos , COVID-19/prevención & control , Participación de la Comunidad/métodos , SARS-CoV-2 , Salud Pública/métodos , Hispánicos o Latinos , Investigación Biomédica Traslacional/métodos , Investigación Biomédica Traslacional/organización & administraciónRESUMEN
BACKGROUND: Robotics has increased rates of minimally invasive surgery, with distinct advantages over open surgery. However, current commercially available robotic platforms have device and system issues that limit robotic-assisted surgery expansion. OBJECTIVE: To demonstrate the safety and efficacy of a novel miniaturized robotic-assisted surgery device in colectomy. DESIGN: Prospective, Investigational Device Exemption clinical study following the idea, development, exploration, assessment, and long-term follow-up framework (stage 2b, exploration). SETTINGS: Three centers with high-volume robotic colorectal cases and surgeons. PATIENTS: Patients scheduled for a right or left colectomy for benign or malignant disease. INTERVENTION: Colectomy with the novel miniaturized robotic-assisted surgery device. MAIN OUTCOME MEASURES: For safety, intraoperative and device-related adverse events and 30-day morbidity. For efficacy, successful completion of predefined procedural steps without conversion. RESULTS: Thirty patients (13 women, 17 men) were analyzed. The mean age was 59.4 (SD 13.4) years. Seventy percent of patients (n = 21) were overweight/obese and 53.3% of patients (n = 16) had prior abdominal surgery. Forty percent of patients had malignant and 60% had benign disease. Cases were 15 right and 15 left colectomies. Overall operative time was a median of 146 (range, 80-309) minutes; console time was 70 (range, 34-174) minutes. There were no conversions to open surgery and no intraoperative or device-related adverse events. In 100% of patients (n = 30), the primary dissection was completed, and hemostasis was maintained with the novel miniaturized robotic-assisted surgery device. The morbidity rate was 26.7% minor and 3.3% major. The median length of stay was 2 days. There were no mortalities. LIMITATIONS: Single-arm study, short-term follow-up. CONCLUSIONS: This first clinical study of a novel miniaturized robotic-assisted surgery device along the IDEAL framework demonstrated that it was safe and effective. Given this success, further assessment and long-term follow-up of the miniaturized robotic-assisted surgery device are planned for comparative clinical and economic effectiveness in colorectal surgery. See Video Abstract . SEGURIDAD Y EFICACIA DE UN NOVEDOSO SISTEMA DE CIRUGA ASISTIDA POR ROBOT MINIATURIZADO EN COLECTOMA UN ESTUDIO CLNICO PROSPECTIVO DE INVESTIGACIN DE EXENCIN DE DISPOSITIVO QUE UTILIZA EL MARCO IDEAL: ANTECEDENTES:La robótica ha aumentado las tasas de cirugía mínimamente invasiva, con claras ventajas sobre la cirugía abierta. Sin embargo, las plataformas robóticas actualmente disponibles comercialmente tienen problemas con los dispositivos y sistemas que limitan la expansión de la cirugía asistida por robot.OBJETIVO:Demostrar la seguridad y eficacia de un novedoso dispositivo de cirugía asistida por robot miniaturizado en colectomía.DISEÑO:Estudio clínico prospectivo de investigación de exención de dispositivo siguiendo el marco IDEAL (Etapa 2b, exploración).ESCENARIO:Tres centros con cirujanos y casos colorrectales robóticos de gran volumen.PACIENTES:Pacientes programados para colectomía derecha o izquierda por enfermedad benigna o maligna.INTERVENCIÓN:Colectomía con el nuevo dispositivo de cirugía asistida por robot miniaturizado.PRINCIPALES MEDIDAS DE RESULTADO:Para la seguridad, eventos adversos intraoperatorios y relacionados con el dispositivo y morbilidad a 30 días. Para la evaluación de la eficacia, la finalización exitosa de los pasos predefinidos sin conversión.RESULTADOS:Se analizaron treinta pacientes (13 mujeres, 17 hombres). La edad media fue 59,4 (DE 13,4) años. El 70% (n=21) tenía sobrepeso/obesidad y el 53,3% (n=16) había tenido cirugía abdominal previa. El 40% tenía enfermedad maligna y el 60% benigna. Los casos fueron 15 colectomías derechas y 15 izquierdas. La mediana del tiempo operatorio general fue de 146 (rango, 80-309) minutos; 70 (rango, 34-174) minutos fue el tiempo de consola. No hubo conversiones a cirugía abierta ni eventos adversos intraoperatorios o relacionados con el dispositivo. En el 100% (n=30), se completó la disección primaria y se mantuvo la hemostasia con el novedoso dispositivo de cirugía asistida por robot miniaturizado. La tasa de morbilidad menor fue de un 26,7% y mayor un 3,3%. La mediana de estadía fue de 2 días. No hubo mortalidad.LIMITACIONES:Estudio de un solo brazo, corto plazo de seguimiento.CONCLUSIONES:Este primer estudio clínico de un novedoso dispositivo de cirugía asistida por robot miniaturizado según el marco IDEAL demostró que era seguro y eficaz. Dado este éxito, se planean evaluaciones adicionales y seguimiento a largo plazo del dispositivo de cirugía asistida por robot miniaturizado para comparar la efectividad clínica y económica en la cirugía colorrectal. (Traducción-Dr. Felipe Bellolio ).
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Colectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Femenino , Procedimientos Quirúrgicos Robotizados/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Colectomía/métodos , Colectomía/instrumentación , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Miniaturización , Adulto , Diseño de Equipo , Tempo Operativo , Enfermedades del Colon/cirugíaRESUMEN
INTRODUCTION: Living donor kidney evaluation has substantial time variations with significant intercenter variation. One-day donor evaluation has shown to be clinically efficient and improve transplant rates. However, patients' perception of 1-day evaluation is unknown. We hypothesized that 1 day LKD evaluation will improve patient satisfaction and improve living donation rates. METHODS: All interested LD candidates from April 2018 to May 2020 were enrolled in the study. Non-directed donors, donors greater than 60 years old, and recipients with more than three donors underwent multi-day evaluation (control group) while the rest underwent 1-day evaluation (intervention group). An anonymous survey was filled by both groups to assess their perceptions on different areas including time, communication, experience, information provided, and their preferences on living donor evaluation. RESULTS: Donor candidates in the 1-day evaluation group selected that the time from the questionnaire to clinic evaluation took "under 1 month" or "less than 3 months" (62.5% vs. 15.8%, p = .002), with "excellent" for both scheduling process (65% vs. 31.6%, p = .03) and communication (82.5% vs. 57.9%, p = .09) when compared to candidates in the multiple-days evaluation group. One-day candidates felt "very satisfied" with the overall experience (95% vs. 68.4%, p = .02) and felt "extremely well" with the information provided regarding the living donor process (87.5% vs. 47.4%, p = .003) when compared to multiple-day evaluation group. Regardless of the group, 53 (89.8%) patients preferred 1-day evaluation. CONCLUSION: We demonstrate 1-day living donor evaluation is efficient, patient preferred, and adds value through improved communication, and better overall patient satisfaction.
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Trasplante de Riñón , Humanos , Persona de Mediana Edad , Donadores Vivos , Riñón , Encuestas y Cuestionarios , Satisfacción del PacienteRESUMEN
BACKGROUND: Gallstone-related conditions affect a significant portion of the population, with varying prevalence among different ethnic groups. Complications such as pancreatitis and cholangitis are associated with the presence of common bile duct (CBD) stones. Existing guidelines for diagnosing choledocholithiasis lack precision, leading to excessive use of invasive procedures like endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A prospective study was conducted at Hospital Central "Dr. Ignacio Morones Prieto," involving 374 patients in the development cohort and 154 patients in the validation cohort. Patients meeting inclusion criteria underwent biochemical testing and ultrasonography. A predictive scoring system was developed using logistic regression and validated in an independent cohort. Clinical and laboratory variables were collected, and model performance was assessed using receiver-operator characteristic (ROC) curves. RESULTS: The predictive model incorporated variables such as age, pancreatitis, cholangitis, bilirubin levels, and CBD stone presence on ultrasound. The model demonstrated an area under the ROC curve (AUC) of 93.81% in the validation dataset. By adjusting the threshold defining high-risk probability to 40%, the model improved specificity and sensitivity compared to existing guidelines. Notably, the model reclassified patients, leading to a more accurate risk assessment. CONCLUSIONS: The developed algorithm accurately predicts choledocholithiasis non-invasively in patients with symptomatic gallstones. This tool has the potential to reduce reliance on costly or invasive procedures like magnetic resonance cholangiopancreatography and ERCP, offering a more efficient and cost-effective approach to patient management. The user-friendly calculator developed in this study could streamline diagnostic procedures, particularly in resource-limited healthcare settings, ultimately improving patient care.
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Coledocolitiasis , Humanos , Coledocolitiasis/diagnóstico por imagen , Coledocolitiasis/diagnóstico , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Medición de Riesgo/métodos , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Curva ROC , Valor Predictivo de las Pruebas , Ultrasonografía , Modelos LogísticosRESUMEN
BACKGROUND: The learning-curve cumulative sum method (LC-CUSUM) and its risk-adjusted form (RA-LC-CUSUM) have been proposed as performance-monitoring methods to assess competency during the learning phase of procedural skills. However, scarce data exist about the method's accuracy. This study aimed to compare the accuracy of LC-CUSUM forms using historical data consisting of sequences of successes and failures in brachial plexus blocks (BPBs) performed by anesthesia residents. METHODS: Using historical data from 1713 BPB performed by 32 anesthesia residents, individual learning curves were constructed using the LC-CUSUM and RA-LC-CUSUM methods. A multilevel logistic regression model predicted the procedure-specific risk of failure incorporated in the RA-LC-CUSUM calculations. Competency was defined as a maximum 15% cumulative failure rate and was used as the reference for determining the accuracy of both methods. RESULTS: According to the LC-CUSUM method, 22 residents (84.61%) attained competency after a median of 18.5 blocks (interquartile range [IQR], 14-23), while the RA-LC-CUSUM assigned competency to 20 residents (76.92%) after a median of 17.5 blocks (IQR, 14-25, P = .001). The median failure rate at reaching competency was 6.5% (4%-9.75%) under the LC-CUSUM and 6.5% (4%-9%) for the RA-LC-CUSUM method ( P = .37). The sensitivity of the LC-CUSUM (85%; 95% confidence interval [CI], 71%-98%) was similar to the RA-LC-CUSUM method (77%; 95% CI, 61%-93%; P = .15). Identical specificity values were found for both methods (67%; 95% CI, 29%-100%, P = 1). CONCLUSIONS: The LC-CUSUM and RA-LC-CUSUM methods were associated with substantial false-positive and false-negative rates. Also, small lower limits for the 95% CIs around the accuracy measures were observed, indicating that the methods may be inaccurate for high-stakes decisions about resident competency at BPBs.
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Bloqueo del Plexo Braquial , Competencia Clínica , Internado y Residencia , Curva de Aprendizaje , Humanos , Bloqueo del Plexo Braquial/métodos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Plexo Braquial , Anestesiología/educación , Anestesiología/normas , Anestesiología/métodos , Educación de Postgrado en Medicina/métodos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To assess the prevalence of anxiety and depression and their associated risk factors throughout the pregnancy and postpartum process using a new screening for the early detection of mental health problems. DESIGN: A prospective cross-sectional descriptive multicentred study. Participants were consecutively enrolled at ≥ 12 weeks' gestation and followed at three different time points: at 12-14 weeks of pregnancy, at 29-30 weeks of pregnancy, and 4-6 weeks postpartum. All women completed a mental screening at week 12-14 of pregnancy consisting of two questions from the Generalised Anxiety Disorder Scale (GAD-2) and the two Whooley questions. If this screening was positive, the woman completed the Edinburgh Postnatal Depression Scale (EPDS). SETTING: Seven primary care centres coordinated by a Gynaecology and Obstetrics Department in the city of Terrassa (Barcelona) in northern Spain. PARTICIPANTS: Pregnant women (N = 335, age 18-45 years), in their first trimester of pregnancy, and receiving prenatal care in the public health system between July 2018 and July 2020. FINDINGS: The most relevant factors associated with positive screening for antenatal depression or anxiety during pregnancy, that appear after the first trimester of pregnancy, are systematically repeated throughout the pregnancy, and are maintained in the postpartum period were: a history of previous depression, previous anxiety, abuse, and marital problems. In weeks 12-14 early risk factors for positive depression and anxiety screening and positive EPDS were: age, smoking, educational level, employment status, previous psychological/psychiatric history and treatment, suicide in the family environment, voluntary termination of pregnancy and current planned pregnancy, living with a partner and partner's income. In weeks 29-30 risk factors were: being a skilled worker, a history of previous depression or anxiety, and marital problems. In weeks 4-6 postpartum, risk factors were: age, a history of previous depression or anxiety or psychological/psychiatric treatment, type of treatment, having been mistreated, and marital problems. CONCLUSIONS: Early screening for anxiety and depression in pregnancy may enable the creation of more effective healthcare pathways, by acting long before mental health problems in pregnant women worsen or by preventing their onset. Assessment of anxiety and depression symptoms before and after childbirth and emotional support needs to be incorporated into routine practice.
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Ansiedad , Depresión , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Adulto , Estudios Transversales , Estudios Prospectivos , Factores de Riesgo , Prevalencia , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Ansiedad/epidemiología , Depresión/epidemiología , Depresión/diagnóstico , Depresión/psicología , Adulto Joven , Periodo Posparto/psicología , España/epidemiología , Adolescente , Depresión Posparto/epidemiología , Depresión Posparto/diagnóstico , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Atención PrenatalRESUMEN
BACKGROUND: Inherited retinal dystrophies are hereditary diseases which have in common the progressive degeneration of photoreceptors. They are a group of diseases with clinical, genetic, and allelic heterogeneity. There is limited information regarding the genetic landscape of inherited retinal diseases in Mexico, therefore, the present study was conducted in the northeast region of the country. METHODS: Patients with inherited retinal dystrophies were included. A complete history, full ophthalmological and medical genetics evaluations, and genetic analysis through a targeted NGS panel for inherited retinal dystrophies comprising at least 293 genes were undertaken. RESULTS: A total of 126 patients were included. Cases were solved in 74.6% of the study's population. Retinitis pigmentosa accounted for the most found inherited retinal disease. Ninety-nine causal variants were found, being USH2A and ABCA4 the most affected genes (26 and 15 cases, respectively). CONCLUSIONS: The present study documents the most prevalent causative genes in IRDs, as USH2A, in northeastern Mexico. This contrasts with previous reports of IRDs in other zones of the country. Further studies, targeting previously unstudied populations in Mexico are important to document the genetic background of inherited retinal dystrophies in the country.
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Distrofias Retinianas , Retinitis Pigmentosa , Síndromes de Usher , Humanos , Mutación , México/epidemiología , Distrofias Retinianas/epidemiología , Distrofias Retinianas/genética , Retinitis Pigmentosa/genética , Linaje , Transportadoras de Casetes de Unión a ATP/genéticaRESUMEN
High uptake of HIV and hepatitis C (HCV) testing in Gay, bisexual, and other men who have sex with men (GBMSM) is needed to interrupt transmission. The objective was to identify subgroups with increased probability of lack of testing among HIV-negative GBMSM in Spain. Cross-sectional study including 3486 HIV-negative GBMSM attending prevention facilities in Madrid and Barcelona, 2018-2020. Data came from self-administered online sociodemographic, health, and risk behaviors questionnaires. Outcomes were lack of HCV (lifetime) and HIV (lifetime, last year) testing. Crude and adjusted prevalences and prevalence ratios were assessed for each outcome using negative binomial regression models. Lifetime lack of HIV and HCV testing prevalence was 6.3% and 35.8%, respectively, while lack of HIV testing in the last year was 22.4%. Prevalences were also substantial in GBMSM with high-risk behaviors. After sociodemographic adjustment, the highest probability of lack of HCV testing (lifetime) and HIV (last year) was among GBMSM with insufficient viral hepatitis knowledge, no history of STI, or HCV (or HIV) testing, aged < 25, non-outness about sex life with men, and less high-risk behaviors. Lack of HCV (lifetime) and HIV testing (last year) among HIV-negative GBMSM in Spain is still high, despite high-risk behaviors.
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Infecciones por VIH , Hepatitis C , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Estudios Transversales , España/epidemiología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Hepacivirus , AntiviralesRESUMEN
Metabolic engineering uses enzymes as parts to build biosystems for specified tasks. Although a part's working life and failure modes are key engineering performance indicators, this is not yet so in metabolic engineering because it is not known how long enzymes remain functional in vivo or whether cumulative deterioration (wear-out), sudden random failure, or other causes drive replacement. Consequently, enzymes cannot be engineered to extend life and cut the high energy costs of replacement. Guided by catalyst engineering, we adopted catalytic cycles until replacement (CCR) as a metric for enzyme functional life span in vivo. CCR is the number of catalytic cycles that an enzyme mediates in vivo before failure or replacement, i.e., metabolic flux rate/protein turnover rate. We used estimated fluxes and measured protein turnover rates to calculate CCRs for â¼100-200 enzymes each from Lactococcus lactis, yeast, and Arabidopsis CCRs in these organisms had similar ranges (<103 to >107) but different median values (3-4 × 104 in L. lactis and yeast versus 4 × 105 in Arabidopsis). In all organisms, enzymes whose substrates, products, or mechanisms can attack reactive amino acid residues had significantly lower median CCR values than other enzymes. Taken with literature on mechanism-based inactivation, the latter finding supports the proposal that 1) random active-site damage by reaction chemistry is an important cause of enzyme failure, and 2) reactive noncatalytic residues in the active-site region are likely contributors to damage susceptibility. Enzyme engineering to raise CCRs and lower replacement costs may thus be both beneficial and feasible.
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Arabidopsis/enzimología , Biocatálisis , Enzimas/química , Lactococcus lactis/enzimología , Ingeniería Metabólica , Saccharomyces cerevisiae/enzimologíaRESUMEN
The Perseverance rover is carrying out an original acoustic experiment on Mars: the SuperCam microphone records the spherical acoustic waves generated by laser sparks at distances from 2 m to more than 8 m. These N-shaped acoustic waves scatter from the multiple local heterogeneities of the turbulent atmosphere. Therefore, large and random fluctuations of sound travel time and intensity develop as the waves cross the medium. The variances of the travel times and the scintillation index (normalized variance of the sound intensity) are studied within the mathematical formalism of the propagation of spherical acoustic waves through thermal turbulence to infer statistical properties of the Mars atmospheric temperature fluctuation field. The comparison with the theory is made by simplifying assumptions that do not include wind fluctuations and diffraction effects. Two Earth years (about one Martian year) of observations acquired during the maximum convective period (10:00-14:00 Mars local time) show a good agreement between the dataset and the formalism: the travel time variance diverges from the linear Chernov solution exactly where the density of occurrence of the first caustic reaches its maximum. Moreover, on average, waves travel faster than the mean speed of sound due to a fast path effect, which is also observed on Earth. To account for the distribution of turbulent eddies, several power spectra are tested and the best match to observation is obtained with a generalized von Karman spectrum with a shallower slope than the Kolmogorov cascade, Ï(k)â(1+k2L2)-4/3. It is associated with an outer scale of turbulence, L, of 11 cm at 2 m above the surface and a standard deviation of 6 K over 9 s for the temperature. These near-surface atmospheric properties are consistent with a weak to moderate wave scattering regime around noon with little saturation. Overall, this study presents an innovative and promising methodology to probe the near-surface atmospheric turbulence on Mars.
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This study shows the results of the analysis of the photogrammetric use of 360-degree cameras in complex heritage-related scenes. The goal is to take advantage of the large field of view provided by these sensors and reduce the number of images used to cover the entire scene compared to those needed using conventional cameras. We also try to minimize problems derived from camera geometry and lens characteristics. In this regard, we used a multi-sensor camera composed of six fisheye lenses, applying photogrammetric procedures to several funerary structures. The methodology includes the analysis of several types of spherical images obtained using different stitching techniques and the comparison of the results of image orientation processes considering these images and the original fisheye images. Subsequently, we analyze the possible use of the fisheye images to model complex scenes by reducing the use of ground control points, thus minimizing the need to apply surveying techniques to determine their coordinates. In this regard, we applied distance constraints based on a previous extrinsic calibration of the camera, obtaining results similar to those obtained using a traditional schema based on points. The results have allowed us to determine the advantages and disadvantages of each type of image and configuration, providing several recommendations regarding their use in complex scenes.