Connecting Clinical Capacity and Intervention Sustainability in Resource-Variable Pediatric Oncology Centers in Latin America.

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment.

Trainee Perspectives Regarding the Effect of the Dobbs v. Jackson Women's Health Organization Supreme Court Decision on Obstetrics and Gynecology Training.

Objectives: We aimed to describe obstetrics and gynecology (OBGYN) trainees' anticipation of how the Dobbs v. Jackson Women's Health Organization (Dobbs) U.S. Supreme Court decision may affect their training. Methods: A REDCap survey of OBGYN residents and fellows in the United States from September 19, 2022, to December 1, 2022, queried trainees' anticipated achievement of relevant Accreditation Council for Graduate Medical Education (ACGME) training milestones, their concerns about the ability to provide care and concern about legal repercussions during training, and the importance of OBGYN competence in managing certain clinical situations for residency graduates. The primary outcome was an ACGME program trainee feeling uncertain or unable to obtain the highest level queried for a relevant ACGME milestone, including experiencing 20 abortion procedures in residency. Results: We received 469 eligible responses; the primary outcome was endorsed by 157 respondents (33.5%). After correction for confounders, significant predictors of the primary outcome were state environment (aOR = 3.94 for pending abortion restrictions; aOR = 2.71 for current abortion restrictions), trainee type (aOR = 0.21 for fellow vs. resident), and a present or past Ryan Training Program in residency (aOR = 0.55). Although the vast majority of trainees believed managing relevant clinical situations are key to OBGYN competence, 10%-30% of trainees believed they would have to stop providing the standard of care in clinical situations during training. Conclusions: This survey of OBGYN trainees indicates higher uncertainty about achieving ACGME milestones and procedural competency in clinical situations potentially affected by the Dobbs decision in states with legal restrictions on abortion.

Biogenic Ag2O nanoparticles with "Hoja Santa" (Piper auritum) extract: characterization and biological capabilities.

The 'sacred leaf' or "Hoja Santa" (Piper auritum Kunth) has a great value for Mexican culture and has gained popularity worldwide for its excellent properties from culinary to remedies. To contribute to its heritage, in this project we proposed the green synthesis of silver oxide nanoparticles (Ag2O NPs) using an extract of "Hoja Santa" (Piper auritum) as a reducing and stabilizing agent. The synthesized Ag2O NPs were characterized by UV-Visible spectroscopy (plasmon located at 405 nm), X-ray diffraction (XRD) (particle size diameter of 10 nm), scanning electron microscopy (SEM) (particle size diameter of 13.62 ± 4.61 nm), and Fourier-transform infrared spectroscopy (FTIR) (functional groups from "Hoja Santa" attached to nanoparticles). Antioxidant capacity was evaluated using DPPH, ABTS and FRAP methods. Furthermore, the antimicrobial activity of NPs against a panel of clinically relevant bacterial strains, including both Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Salmonella Enteritidis and Escherichia coli O157:H7), was over 90% at concentrations of 200 µg/mL. Additionally, we assessed the antibiofilm activity of the NPs against Pseudomonas aeruginosa (reaching 98% of biofilm destruction at 800 µg/mL), as biofilm formation plays a crucial role in bacterial resistance and chronic infections. Moreover, we investigated the impact of Ag2O NPs on immune cell viability, respiratory burst, and phagocytic activity to understand their effects on the immune system.

Presence of Saccharomyces eubayanus in fermentative environments reveals a new adaptive scenario in Patagonia.

Patagonia (Argentina and Chile) harbors the highest Saccharomyces eubayanus genomic diversity and its widest predominance in natural environments. In this work, S. eubayanus was isolated for the first time from a fermentative environment. This species was found dominating both a traditional apple chicha fermentation as well as feral apple trees in the Andean region of Aluminé (Argentina). S. eubayanus was the only Saccharomyces species found in the isolation substrates, although it coexisted with other non-Saccharomyces species. The absence of strong fermentative competitors of the Saccharomyces genus (like Saccharomyces uvarum or Saccharomyces cerevisiae) in the feral apples could promote the development and implantation of S. eubayanus in a spontaneous apple must fermentation. Phylogeographic analyses revealed a high intraspecific diversity in S. eubayanus, enabling the characterization of strains belonging to the genomic subpopulations PA1, PA2, and PB1 according to the sequences obtained for the intFR gene region. This result evidence that the studied sampling area represents a natural habitat for the species. Being a novel finding, studying the causes that allowed this species to prosper in a fermentative environment becomes essential. Hence, the physiological profile of the new isolates, including their ability to grow at different temperature, nitrogen, and ethanol concentrations was evaluated in comparison with a set of S. eubayanus strains previously isolated from natural environment and representing different genomic subpopulations. Greater physiological diversity was evidenced when strains isolated from both natural and fermentative environments were analyzed overall. Furthermore, no direct relationship between genomic population and physiological behavior was observed; on the opposite, strains appeared to exhibit similar behavior, primarily grouped by isolation origin.

Traslado no programado de pacientes pediátricos desde una sala de internación general a una unidad de cuidados intensivos / Unplanned transfer of pediatric patients from the general ward to the intensive care unit

Introducción. Durante la internación, los pacientes pueden presentar un deterioro clínico significativo y requerir el ingreso no programado a la unidad de cuidados intensivos pediátricos (UCIP). Esto puede conllevar un aumento de la morbilidad y la mortalidad. Frecuentemente, estos eventos están precedidos por una fase de deterioro que podría pasar desapercibida. Objetivo. Determinar la frecuencia, analizar las causas, describir las características clínicas y los resultados de los traslados no programados en pacientes pediátricos hospitalizados, desde el área de internación general pediátrica (IGP) a la UCIP, y analizar las diferencias entre traslados urgentes y emergentes. Población y métodos. Estudio descriptivo prospectivo; se analizaron todos los traslados no programados desde IGP a la UCIP ocurridos entre el 1 de enero de 2014 y el 31 de diciembre 2019. Resultados. Se constataron 212 traslados no programados (21 traslados cada 1000 ingresos). El 76 % de los pacientes trasladados presentaban una comorbilidad asociada ­la más frecuente fue la patología oncológica (36 %)­ y llevaban más de 24 horas internados en IGP. Las causas más frecuentes de traslado fueron dificultad respiratoria (43 %), sepsis (20 %) y complicaciones neurológicas/neuroquirúrgicas (20 %). La tasa de mortalidad global fue del 8,96 % (19 pacientes). Conclusiones. El análisis de los traslados no programados es un elemento esencial en la evaluación de la calidad de atención y seguridad del paciente de un área, y debe constituir un indicador integrado al tablero de control. La interpretación de los traslados no programados como un evento prevenible constituye un cambio de paradigma clave.

Introduction. During hospitalization, patients may develop significant clinical deterioration and require unplanned admission to the pediatric intensive care unit (PICU). This may result in increased morbidity and mortality. These events are often preceded by a deterioration phase that may go unnoticed. Objective. To determine the frequency, analyze the causes, and describe the clinical characteristics and outcomes of unplanned transfers of hospitalized pediatric patients from the general pediatric ward (GPW) to the PICU, and analyze the differences between urgent and emergent transfers. Population and methods. Prospective, descriptive study; all unplanned transfers from the GPW to the PICU occurring between January 1st, 2014 and December 31st, 2019 were analyzed. Results. There were 212 unplanned transfers (21 transfers per 1000 admissions). An associated comorbidity was present in 76% of transferred patients ­being cancer the most frequent one (36%)­ and they had been hospitalized for more than 24 hours in the GPW. The most frequent causes of transfer were respiratory distress (43%), sepsis (20%), and neurological/neurosurgical complications (20%). The overall mortality rate was 8.96% (19 patients). Conclusions. The analysis of unplanned transfers is a critical component in the assessment of the quality of care and patient safety of an area, and should be an indicator integrated into the control panel. The interpretation of unplanned transfers as a preventable event is a key paradigm shift.

Association Between Enlarged Genital Hiatus and Composite Surgical Failure After Vaginal Hysterectomy With Uterosacral Ligament Suspension.

IMPORTANCE: The impact of a persistently enlarged genital hiatus (GH) after vaginal hysterectomy with uterosacral ligament suspension on prolapse outcomes is currently unclear. OBJECTIVES: This secondary analysis of the Study of Uterine Prolapse Procedures Randomized trial was conducted among participants who underwent vaginal hysterectomy with uterosacral ligament suspension. We hypothesized that women with a persistently enlarged GH size would have a higher proportion of prolapse recurrence. STUDY DESIGN: Women who underwent vaginal hysterectomy with uterosacral ligament suspension as part of the Study of Uterine Prolapse Procedures Randomized trial (NCT01802281) were divided into 3 groups based on change in their preoperative to 4- to 6-week postoperative GH measurements: (1) persistently enlarged GH, 2) improved GH, or (3) stably normal GH. Baseline characteristics and 2-year surgical outcomes were compared across groups. A logistic regression model for composite surgical failure controlling for advanced anterior wall prolapse and GH group was fitted. RESULTS: This secondary analysis included 81 women. The proportion with composite surgical failure was significantly higher among those with a persistently enlarged GH (50%) compared with a stably normal GH (12%) with an unadjusted risk difference of 38% (95% confidence interval, 4%-68%). When adjusted for advanced prolapse in the anterior compartment at baseline, the odds of composite surgical failure was 6 times higher in the persistently enlarged GH group compared with the stably normal group (95% confidence interval, 1.0-37.5; P = 0.06). CONCLUSION: A persistently enlarged GH after vaginal hysterectomy with uterosacral ligament suspension for pelvic organ prolapse may be a risk factor for recurrent prolapse.

Preoperative Simulation of Retropubic Midurethral Sling to Decrease Bladder Perforation Rate Among Obstetrics and Gynecology Residents.

IMPORTANCE: Bladder perforation is an often avoidable complication of retropubic midurethral sling procedures. Bladder injury rates decrease with surgeon experience, but literature on techniques to train novice surgeons is limited. OBJECTIVE: Our objective was to decrease the bladder perforation rate among obstetrics and gynecology residents during retropubic midurethral sling procedures through implementation of an instructional video and low-fidelity simulation. STUDY DESIGN: A baseline bladder perforation rate was determined by retrospective chart review. A prospective educational intervention, consisting of a 10-minute instructional video with preoperative simulation using a simple bony pelvis model, was then implemented among residents on the urogynecology service from December 2017 through March 2020. The primary outcome was the change in the bladder perforation rate. Compliance with the intervention protocol was a secondary outcome. Categorical data were evaluated using the χ 2 or Fisher exact test. Continuous variables were assessed using the Student t test or Mann-Whitney U test as appropriate. RESULTS: Two hundred fifteen retropubic midurethral sling cases were included in analysis. There were no significant demographic differences between the patients undergoing surgery preintervention and postintervention. Resident surgeons were in their second (47.4%) and third (52.6%) years of training. The postintervention bladder perforation rate was 6.5%, which is a 35% reduction from the preintervention perforation rate of 10% ( P = 0.19). The instructional video and preoperative simulation were successfully implemented in 193 of 215 (89.8%) eligible cases. CONCLUSION: Despite high compliance, the combination of the instructional video and preoperative low-fidelity bony pelvis simulation was not effective in reducing tension-free vaginal tape-associated bladder perforations among residents.

Unplanned transfer of pediatric patients from the general ward to the intensive care unit. / Traslado no programado de pacientes pediátricos desde una sala de internación general a una unidad de cuidados intensivos.

Introduction. During hospitalization, patients may develop significant clinical deterioration and require unplanned admission to the pediatric intensive care unit (PICU). This may result in increased morbidity and mortality. These events are often preceded by a deterioration phase that may go unnoticed. Objective. To determine the frequency, analyze the causes, and describe the clinical characteristics and outcomes of unplanned transfers of hospitalized pediatric patients from the general pediatric ward (GPW) to the PICU, and analyze the differences between urgent and emergent transfers. Population and methods. Prospective, descriptive study; all unplanned transfers from the GPW to the PICU occurring between January 1st , 2014 and December 31st, 2019 were analyzed. Results. There were 212 unplanned transfers (21 transfers per 1000 admissions). An associated comorbidity was present in 76% of transferred patients -being cancer the most frequent one (36%)- and they had been hospitalized for more than 24 hours in the GPW. The most frequent causes of transfer were respiratory distress (43%), sepsis (20%), and neurological/neurosurgical complications (20%). The overall mortality rate was 8.96% (19 patients). Conclusions. The analysis of unplanned transfers is a critical component in the assessment of the quality of care and patient safety of an area, and should be an indicator integrated into the control panel. The interpretation of unplanned transfers as a preventable event is a key paradigm shift.

Introducción. Durante la internación, los pacientes pueden presentar un deterioro clínico significativo y requerir el ingreso no programado a la unidad de cuidados intensivos pediátricos (UCIP). Esto puede conllevar un aumento de la morbilidad y la mortalidad. Frecuentemente, estos eventos están precedidos por una fase de deterioro que podría pasar desapercibida. Objetivo. Determinar la frecuencia, analizar las causas, describir las características clínicas y los resultados de los traslados no programados en pacientes pediátricos hospitalizados, desde el área de internación general pediátrica (IGP) a la UCIP, y analizar las diferencias entre traslados urgentes y emergentes. Población y métodos. Estudio descriptivo prospectivo; se analizaron todos los traslados no programados desde IGP a la UCIP ocurridos entre el 1 de enero de 2014 y el 31 de diciembre 2019. Resultados. Se constataron 212 traslados no programados (21 traslados cada 1000 ingresos). El 76 % de los pacientes trasladados presentaban una comorbilidad asociada ­la más frecuente fue la patología oncológica (36 %)­ y llevaban más de 24 horas internados en IGP. Las causas más frecuentes de traslado fueron dificultad respiratoria (43 %), sepsis (20 %) y complicaciones neurológicas/neuroquirúrgicas (20 %). La tasa de mortalidad global fue del 8,96 % (19 pacientes). Conclusiones. El análisis de los traslados no programados es un elemento esencial en la evaluación de la calidad de atención y seguridad del paciente de un área, y debe constituir un indicador integrado al tablero de control. La interpretación de los traslados no programados como un evento prevenible constituye un cambio de paradigma clave.

The International Oryza Map Alignment Project (IOMAP): the Americas-past achievements and future directions.

The wild relatives of rice hold unexplored genetic diversity that can be employed to feed an estimated population of 10 billion by 2050. The Oryza Map Alignment Project (OMAP) initiated in 2003 has provided comprehensive genomic resources for comparative, evolutionary, and functional characterization of the wild relatives of rice, facilitating the cloning of >600 rice genes, including those for grain width (GW5) and submergence tolerance (SUB1A). Following in the footsteps of the original project, the goal of 'IOMAP: the Americas' is to investigate the present and historic genetic diversity of wild Oryza species endemic to the Americas through the sequencing of herbaria and in situ specimens. The generation of a large diversity panel describing past and current genetic status and potential erosion of genetic variation in the populations will provide useful knowledge for the conservation of the biodiversity in these species. The wild relatives of rice in the Americas present a wide range of resistance traits useful for crop improvement and neodomestication approaches. In the race against time for a sustainable food future, the neodomestication of the first cereal species recently accomplished in O. alta opens the door to the potential neodomestication of the other wild Oryza species in Americas.

PCR-tips for rapid diagnosis of bacterial pathogens.

Micropipette tips are currently among the most used disposable devices in bioresearch and development laboratories. Their main application is the fractionation of solutions. New functionalities have recently been added to this device, widening their applications. This paper analyzed disposable micropipette tips as reagent holders of PCR reagents. PCR has become a prevalent and often indispensable technique in biological laboratories for various applications, such as the detection of coronavirus and other infectious diseases. A functional micropipette tip was implemented to simplify PCR analysis and reduce the contamination chances of deoxynucleotides and specific primers. This disposable device is prepared by tip coating processes of reagents, using polyvinyl alcohol polymer and additives. The coated layer is optimized to load and release PCR reagents efficiently. As a proof of concept, we show that the detection of Bordetella pertussis, the etiological agent of whooping cough whose diagnostic relies on PCR, can be quickly done using practical-functional tips. This device is an excellent example of testing the functionality and contribution of molecular diagnostic PCR tips. KEY POINTS: • Functional micropipette tips are prepared by coating with dNTPs and primers. • Functional tips are used to replace dNTPs and primers in the PCR master mix. • PCR diagnostic of Bordetella pertussis is performed using functional tips.

Induction of Cellular Senescence in Rat Vaginal Fibroblasts and Treatment With Senolytics: An in Vitro Model for the Study of Pelvic Organ Prolapse.

OBJECTIVE: The objective of this study was to develop an in vitro model of cellular senescence using rat vaginal fibroblasts and determine the effects of treatment with senolytics. METHODS: Rat vaginal tissue biopsies were collected. Primary vaginal fibroblasts were isolated and characterized by immunofluorescence. To induce cellular senescence, fibroblasts were treated with etoposide at 3, 10, and 20 mM for 24 hours, followed by treatment with the senolytics dasatinib (1 mM) and/or quercetin (20 mM). After treatment, RNA was extracted and the expression of selected genes was quantified. Immunostaining of senescence markers was also performed. RESULTS: Fibroblasts were confirmed by positive immunostaining for α-smooth muscle actin and vimentin, and negative immunostaining for pan-cytokeratin. Treatment with etoposide resulted in a dose-dependent increase in expression of the senescence-associated secretory phenotype markers MMP-7, MMP-9, and IL-b1 (P < 0.05) compared with controls. Immunostaining showed increased expression of γ-H2A and p21 after treatment with etoposide. Cells treated with dasatinib and quercetin after etoposide treatment had decreased expression of p21, MMP-7, MMP-9, and IL-1b compared with cells treated only with etoposide (P < 0.05). CONCLUSIONS: Upregulation of senescence-associated factors provided evidence that senescence can be induced in vaginal fibroblasts in vitro. Furthermore, treatment with the senolytics dasatinib and quercetin abrogated the senescence phenotype induced by etoposide in rat vaginal fibroblasts. Our findings provide a novel model for the study and development of new therapies targeting the disordered extracellular matrix associated with pelvic organ prolapse.

Convergent adaptation of Saccharomyces uvarum to sulfite, an antimicrobial preservative widely used in human-driven fermentations.

Different species can find convergent solutions to adapt their genome to the same evolutionary constraints, although functional convergence promoted by chromosomal rearrangements in different species has not previously been found. In this work, we discovered that two domesticated yeast species, Saccharomyces cerevisiae, and Saccharomyces uvarum, acquired chromosomal rearrangements to convergently adapt to the presence of sulfite in fermentation environments. We found two new heterologous chromosomal translocations in fermentative strains of S. uvarum at the SSU1 locus, involved in sulfite resistance, an antimicrobial additive widely used in food production. These are convergent events that share similarities with other SSU1 locus chromosomal translocations previously described in domesticated S. cerevisiae strains. In S. uvarum, the newly described VIIXVI and XIXVI chromosomal translocations generate an overexpression of the SSU1 gene and confer increased sulfite resistance. This study highlights the relevance of chromosomal rearrangements to promote the adaptation of yeast to anthropic environments.

Impact of vaginal distention on cell senescence in an animal model of pelvic organ prolapse.

OBJECTIVE: Cellular senescence, associated with aging, leads to impaired tissue regeneration. We hypothesize that vaginal injury initiates cell senescence, further propagated during aging resulting in pelvic organ prolapse (POP). Our objective was to employ a mouse model of POP (Fibulin-5 knockout mice, Fbln5-/-) to determine if vaginal distention leads to cellular senescence and POP. METHODS: 6wk old females [wild-type (WT), n = 81; Fbln5-/-, n = 47)] were assigned to control vs vaginal distention, which approximated vaginal delivery. Serial POP measurements were obtained until vagina were harvested from euthanized mice at 24, 48, 72 h and 1wk. Markers of cell senescence were quantified by immunofluorescence. DNA damage was assessed with γ-H2Ax. RESULTS: WT distended mice showed decreased p53 (p = 0.0230) and γ-H2Ax (p = 0.0008) in vaginal stromal cells at 1wk compared to controls. In WT mice, SA-ß-Gal activity increased 1wk after distention (p = 0.05). In Fbln5-/- mice, p53 and γ-H2Ax did not decrease, but p16 decreased 72 h after distention (p = 0.0150). SA-ß-Gal activity also increased in Fbln5-/-, but at earlier time points and 1wk after distention (p < 0.0001). Fbln5-/- mice developed POP after distention earlier than non distended animals (p = 0.0135). CONCLUSIONS: Vaginal distention downregulates p53 and γ-H2Ax in WT mice, thereby promoting cell proliferation 1wk after injury. This was absent among Fbln5-/- distention mice suggesting they do not escape senescence. These findings indicate a failure of cellular protection from senescence in animals predisposed to POP.

Improving safety in paediatric thyroidectomy by PTH measurements.

OBJETIVE: We followed our previously reported algorithm based on intra and postoperative parathyroid hormone (PTH) levels to predict postthyroidectomy hypoparathyroid hypocalcemia. The objective of the study was to assess if this strategy is useful and safe to reduce hypocalcemia, hospitalisation length and postsurgery calcium sampling. DESIGN, PATIENTS, MEASSUREMENTS: We classified our series of 66 patients according to their risk of hypoparathyroidism based on PTH determinations. We treated high-risk patients with calcium and vitamin D1-25 supplementation and obtained routine daily calcium samples to control low-risk patients until 48 h postsurgery. We compared the outcomes and overall results of this new approach with those of a historical control group of patients with equivalent PTH measurements who were treated only if they presented hypocalcemia. RESULTS: In the high-risk subgroup (n = 30), five patients had hypocalcemia within the first 24 h. Compared with the high-risk control subgroup, the incidence of hypocalcemia fell from 100% to 17% (p < .001), and the median hospitalisation length from 6 to 3 days (p < .001). In the low-risk subgroup (n = 36), 28 patients remained normocalcemic with significantly less calcium sampling (p < .001). Eight patients had hypocalcemia; seven of them required neck dissection, which was the only risk factor related to postsurgical hypoparathyroidism (RR: 2.1 [confidence interval 95%: 1.4-3.1]; p < .001). The overall incidence of hypocalcemia decreased by 58% in our patients compared to the control group. CONCLUSIONS: Assessing PTH levels to classify the risk of hypoparathyroidism and to initiate preventive therapy was an effective approach that improved the safety of our paediatric patients by reducing the incidence of hypocalcemia and the length of hospitalisation after thyroidectomy in paediatric patients.

Floodwater Depth Causes Different Physiological Responses During Post-flooding in Willows.

Willows are widely planted in areas under risk of flooding. The physiological responses of willows to flooding have been characterized, but little is known about their responses during the post-flooding period. After the end of the stress episode, plants may modify some traits to compensate for the biomass loss during flooding. The aim of this work was to analyze the post-flooding physiological responses of willow under two different depths of stagnant floodwater. Cuttings of Salix matsudana NZ692 clone were planted in pots in a greenhouse. The experiment started when the plants were 2 months old with the following treatments: Control plants (watered to field capacity); plants partially flooded 10 cm above soil level (F10) and plants partially flooded 40 cm above soil level (F40). The flooding episode lasted 35 days and was followed by a recovery period of 28 days (post-flooding period). After the flooding period, height, diameter and total biomass were higher in F10, while F40 plants showed an increase in plant adventitious root production and leaf nitrogen content. During the post-flooding period, the photosynthetic rate, nitrogen, chlorophyll and soluble sugar contents were significantly higher in leaves of F40 than in Control and F10 treatments. Stomatal conductance and specific leaf area were higher in the previously flooded plants compared to Control treatment. Plants from F10 treatments showed a higher growth in height, root-to-shoot ratio, and carbon isotope discrimination than F40, while the opposite occurred for growth in diameter, vessel size and leaf area. We conclude that depth of floodwater not only causes different responses during flooding, but that its effects are also present in the post-flooding recovery period, affecting the growth and physiology of willows once the stress episode has ended. Even when flooding impacted growth negatively in F40, in the post-flooding period these plants compensated by increasing the photosynthetic rate, plant leaf area and xylem vessel size. Willows endurance to flooding is the result of both responses during flooding, and plastic responses during post-flooding.

Antitumor efficacy and reduced toxicity using an anti-CD137 Probody therapeutic.

Costimulation via CD137 (4-1BB) enhances antitumor immunity mediated by cytotoxic T lymphocytes. Anti-CD137 agonist antibodies elicit mild liver inflammation in mice, and the maximum tolerated dose of Urelumab, an anti-human CD137 agonist monoclonal antibody, in the clinic was defined by liver inflammation-related side effects. A protease-activated prodrug form of the anti-mouse CD137 agonist antibody 1D8 (1D8 Probody therapeutic, Pb-Tx) was constructed and found to be selectively activated in the tumor microenvironment. This construct, which encompasses a protease-cleavable linker holding in place a peptide that masks the antigen binding site, exerted antitumor effects comparable to the unmodified antibody but did not result in liver inflammation. Moreover, it efficaciously synergized with both PD-1 blockade and adoptive T-cell therapy. Surprisingly, minimal active Pb-Tx reached tumor-draining lymph nodes, and regional lymphadenectomy did not abrogate antitumor efficacy. By contrast, S1P receptor-dependent recirculation of T cells was absolutely required for efficacy. The preferential cleavage of the anti-CD137 Pb-Tx by tumor proteases offers multiple therapeutic opportunities, including neoadjuvant therapy, as shown by experiments in which the Pb-Tx is given prior to surgery to avoid spontaneous metastases.

The genomic structure of the highly-conserved dmrt1 gene in Solea senegalensis (Kaup, 1868) shows an unexpected intragenic duplication.

Knowing the factors responsible for sex determination in a species has significant theoretical and practical implications; the dmrt1 gene (Doublesex and Mab-3 (DM)-related Transcription factor 1) plays this role in diverse animal species. Solea senegalensis is a commercially important flat fish in which females grow 30% faster than males. It has 2n = 42 chromosomes and an XX / XY chromosome system for sex determination, without heteromorph chromosomes but with sex proto-chromosome. In the present study, we are providing the genomic structure and nucleotide sequence of dmrt1 gene obtained from cDNA from male and female adult gonads. A cDNA of 2027 containing an open-reading frame (ORF) of 1206 bp and encoding a 402 aa protein it is described for dmrt1 gene of S. senegalensis. Multiple mRNA isoforms indicating a high variable system of alternative splicing in the expression of dmrt1 of the sole in gonads were studied. None isoforms could be related to sex of individuals. The genomic structure of the dmrt1 of S. senegalensis showed a gene of 31400 bp composed of 7 exons and 6 introns. It contains an unexpected duplication of more than 10399 bp, involving part of the exon I, exons II and III and a SINE element found in the sequence that it is proposed as responsible for the duplication. A mature miRNA of 21 bp in length was localized at 336 bp from exon V. Protein-protein interacting networks of the dmrt1 gene showed matches with dmrt1 protein from Cynoglossus semilaevis and a protein interaction network with 11 nodes (dmrt1 plus 10 other proteins). The phylogenetic relationship of the dmrt1 gene in S. senegalensis is consistent with the evolutionary position of its species. The molecular characterization of this gene will enhance its functional analysis and the understanding of sex differentiation in Solea senegalensis and other flatfish.

Gene clusters related to metamorphosis in Solea senegalensis are highly conserved.

The flatfish, Solea senegalensis has considerable scientific interest and commercial value. The metamorphosis in this species occurs between 12 and 19 days after hatching and it takes about 1 week to complete. Eleven Bacterial Artificial Chromosomes (BAC) clones containing the various candidate genes involved in the process of metamorphosis: thyroxine 5 deiodinase 3 (dio3); forkhead box protein E4 (foxe4); melatonin receptor type 1C (mel1c); calsequestrin 1b (casq1b); thyrotropin subunit beta (tshß); thyrotropin-releasing hormone receptor 1, 2, and 3 (trhr1, trhr2, trhr3); thyroid hormone receptor α a and b (thrαa, thrαb); and thyroid hormone receptor beta (thrß) were analyzed by multiple Fluorescence in situ Hybridization (mFISH) and Next Generation Sequencing (NGS) techniques. The mFISH technique localized the 11 BAC clones on 12 different chromosome pairs because three of them, specifically the trhr1a, trhr2 and thrß BAC clones, showed double signals. This signal duplication indicates a duplication of the genomic region inserted within the BAC clone, which provides evidence for the Teleost-Specific Whole Genome Duplication (TS-WGD). Micro-synteny and phylogenetic analysis showed that Cynoglossus semilaevis is the nearest species to S. senegalensis and that Danio rerio is the most distant one. The tshß BAC clone was highly conserved as the genes belonging to this BAC were located on a single chromosome in all the species studied. These genes participate in proliferation, migration and cell-death, which are key processes during metamorphosis. Overall, micro-synteny analysis showed that most candidate genes are found in conserved genomic surroundings.

Does Living With Human Immunodeficiency Virus Increase Pelvic Reconstructive Surgery Perioperative Complication Risk? A Multicenter Retrospective Cohort Study.

OBJECTIVE: To determine if women with human immunodeficiency virus (HIV) undergoing pelvic reconstructive surgery (PRS) have an increased risk of perioperative and postoperative complications compared with HIV-negative controls. STUDY DESIGN: Multicenter, retrospective matched cohort study of patients with and without HIV infection who underwent PRS between 2006 and 2016. Cases were identified using International Classification of Disease, 9th edition Clinical Modification and 10th edition Clinical Modification and current procedural terminology (CPT) codes encompassing HIV diagnoses and pelvic reconstructive surgeries. Controls were identified as patients without HIV who underwent similar procedures, performed by the same surgeon during the same 1-year period as surgeries performed on patients with HIV. Cases were matched to controls at a ratio of 1:3. The primary outcome was composite complication rate within 1 year of surgery. RESULTS: Sixty-three patients with HIV and 187 controls were identified. There was no difference in the composite complication rate between women with HIV and HIV-negative women (36.5% vs 30.0%, P = 0.15) over 1 year. However, 19.1% of patients with HIV compared with 5.4% controls had Clavien Dindo Grade I complications (P = 0.002), and 11.1% of HIV patients had urinary retention within 6 weeks of surgery compared with 3.2% of controls (P = 0.02). After multivariable logistic regression used to adjust for confounders, living with HIV was not associated with an increased risk of complications. CONCLUSIONS: Patients living with HIV are not at an increased risk of complications within 1 year of PRS compared with patients without HIV.