Excitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption and the storage of long-term information, spines need to be ...plastic and stable at the same time. Here, we advanced in vivo STED nanoscopy to superresolve distinct features of spines (head size and neck length/width) in mouse neocortex for up to 1 month. While LTP-dependent changes predict highly correlated modifications of spine geometry, we find both, uncorrelated and correlated dynamics, indicating multiple independent drivers of spine remodeling. The magnitude of this remodeling suggests substantial fluctuations in synaptic strength. Despite this high degree of volatility, all spine features exhibit persistent components that are maintained over long periods of time. Furthermore, chronic nanoscopy uncovers structural alterations in the cortex of a mouse model of neurodegeneration. Thus, at the nanoscale, stable dendritic spines exhibit a delicate balance of stability and volatility.
Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator-prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process ...using the predator
and the bacterial prey
which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to
at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of
secrete dodecanoic acid, which is sensed by SRB-6. This behavioral adaptation represents an important strategy for the nematode, which utilizes specialized sensory organs and a chemoreceptor that is tuned to recognize the bacteria. These findings provide a window into the molecules and organs used in the coevolutionary arms race between predator and potential prey.
Background
Emotional distress is common in dialysis patients, but its role on clinical outcomes for patients on peritoneal dialysis (PD) is uncertain.
Purpose
To evaluate the effect of depression and ...anxiety on 1-year prognosis in PD patients.
Methods
A total of
N
= 201 PD patients (58.9 ± 12.59 years) completed the Hospital Anxiety Depression Scale and measures of social support at baseline and were followed up for CC technique and actuarial patient survival.
Results
Mortality and technique failure rates were 9.9 and 5.97 %, respectively. Carer-assisted PD, anxiety, comorbid burden and albumin were significant univariate predictors. Multivariate proportional hazard model to adjust for confounders indicated that anxiety remained significant with HR of 2.145 95 % CI 1.03, 4.49,
p
= 0.043 for death/technique failure.
Conclusion
Anxiety is an important predictor of actuarial and technique survival in PD. Effective treatment for symptoms of anxiety may represent an easily achievable means of improving the clinical outcome of PD patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hepatocyte transplantation has the potential to cure inherited liver diseases, but its application is impeded by a scarcity of donor livers. Therefore, we explored whether transplantation of ...hepatocyte-like cells (iHeps) differentiated from human induced pluripotent stem cells (iPSCs) could ameliorate inherited liver diseases. iPSCs reprogrammed from human skin fibroblasts were differentiated to iHeps, which were transplanted into livers of uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-deficient Gunn rats, a model of Crigler-Najjar syndrome 1 (CN1), where elevated unconjugated bilirubin causes brain injury and death. To promote iHep proliferation, 30% of the recipient liver was X-irradiated before transplantation, and hepatocyte growth factor was expressed. After transplantation, UGT1A1+ iHep clusters constituted 2.5%–7.5% of the preconditioned liver lobe. A decline of serum bilirubin by 30%–60% and biliary excretion of bilirubin glucuronides indicated that transplanted iHeps expressed UGT1A1 activity, a postnatal function of hepatocytes. Therefore, iHeps warrant further exploration as a renewable source of hepatocytes for treating inherited liver diseases.
•Human skin fibroblast-derived iPSCs were differentiated to hepatocyte-like iHeps•iHeps were transplanted into Gunn rats, a model of Crigler-Najjar syndrome 1•Engraftment of the iHeps in Gunn rat livers reduced serum bilirubin levels•iHeps may be potentially useful in treating liver-based metabolic disorders
Roy-Chowdhury and colleagues show that human iPSCs differentiated to hepatocyte-like iHep cells engraft into the liver of UGT1A1-deficient Gunn rats, a model of Crigler-Najjar syndrome 1, where hyperbilirubinemia causes brain injury and death. After iHep transplantation, serum bilirubin declined by 30%–60% and bilirubin glucuronides appeared in bile, indicating that the engrafted iHeps expressed UGT1A1, a postnatal hepatocyte function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Can a core outcome set to standardize outcome selection, collection, and reporting across future infertility research be developed?
A minimum data set, known as a core outcome set, has been developed ...for randomized controlled trials (RCT) and systematic reviews evaluating potential treatments for infertility.
Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret.
A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries).
Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods.
The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable.
We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition, and an arbitrary consensus threshold.
Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Ferility and Sterility, and Human Reproduction, have committed to implementing this core outcome set.
This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. Hans Evers reports being the Editor Emeritus of Human Reproduction. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Annika Strandell reports consultancy fees from Guerbet. Ernest Ng reports research sponsorship from Merck. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form.
Core Outcome Measures in Effectiveness Trials Initiative: 1023.
Desarrollar un conjunto de resultados básicos para futura investigación sobre infertilidad: un estudio de desarrollo de consenso internacional.
¿Se puede establecer y desarrollar un conjunto de resultados básicos para estandarizar la selección, recopilación y presentación de informes de resultados en futuras investigaciones sobre infertilidad?
se ha desarrollado un conjunto mínimo de datos, conocido como conjunto de resultados básicos, para ensayos controlados aleatorios (ECA) y revisiones sistemáticas que evalúan posibles tratamientos para la infertilidad.
los problemas son complejos, incluido el hecho de no tener en cuenta las perspectivas de las personas con problemas de fertilidad al seleccionar los resultados, las variaciones en las definiciones de los resultados y el informe selectivo de los resultados sobre la base del análisis estadístico, lo que hacen que los resultados de la investigación sobre infertilidad sean difíciles de interpretar.
una encuesta Delphi de tres rondas (372 participantes de 41 países) y un taller de desarrollo de consenso (30 participantes de 27 países).
se contó con profesionales de la salud, investigadores y personas con problemas de fertilidad en un proceso abierto y transparente utilizando métodos científicos formales de consenso.
el conjunto de los resultados básicos consiste en: embarazo intrauterino viable confirmado por ecografía (contando los embarazos únicos, gemelares y múltiples superiores); pérdida del embarazo (que incluya el embarazo ectópico, el aborto espontáneo, la muerte fetal, y la interrupción del embarazo); recién nacido vivo; edad gestacional en el momento del parto; peso al nacer; mortalidad neonatal; y anomalía congénita mayor. Cuando corresponda, se debe informar el tiempo transcurrido hasta el embarazo que conduce a un nacimiento vivo.
utilizamos métodos de desarrollo de consenso que tienen limitaciones inherentes, incluida la representatividad de la muestra de participantes, deserción de la encuesta Delphi y un umbral de consenso arbitrario.
la integración del conjunto de resultados centrales en los ECA y las revisiones sistemáticas debe garantizar la selección, recopilación e informe de resultados básicos. Los Organismos de financiación de la investigación, El Protocolo Estándar: recomendaciones for Interventional Trials (SPIRIT) y más de 80 revistas especializadas, incluido el Grupo Cochrane de Ginecología y Fertilidad, Fertility & Sterility, y Human Reproduction, se han comprometido a implementar este conjunto de resultados básicos.
Esta investigación fue financiada por Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund y Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya informa que es el editor en jefe de Human Reproduction Open y editor del grupo Cochrane de Ginecología y Fertilidad. Hans Evers informa ser el editor emérito de Human Reproduction. Jose Knijnenburg informa del patrocinio de investigación de Ferring y Theramex. Richard Legro informa de honorarios en consultoría de Abbvie, Bayer, Ferring, Fractyl, Insud Pharma y Kindex y patrocinio de investigación de Guerbet y Hass Avocado Tablero. Ben Mol informa los honorarios de consultoría de Guerbet, iGenomix, Merck, Merck KGaA y ObsEva. Craig Niederberger informa que es el Coeditor en Jefe de Fertility & Sterility y editor de sección del Journal of Urology, patrocinio de investigación de Ferring, y conserva un interés financiero en NexHand. Annika Strandell informa de los honorarios de consultoría de Guerbet. Ernest Ng informa del patrocinio en investigación de Merck. Lan Vuong informa los honorarios de consultoría y conferencias de Ferring, Merck y Merck Sharp and Dohme. Los autores restantes declaran no tener intereses contrapuestos en relación con el trabajo presentado. Todos los autores han completado el formulario de divulgación.
Medidas de resultado básicas en la Iniciativa de ensayos de eficacia: 1023
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Absorbable inferior vena cava filters (IVCFs) offer a promising alternative to metallic retrievable filters in providing protection against pulmonary embolism (PE) for patients contraindicated for ...anticoagulant therapy. However, because absorbable filters are not radiopaque, monitoring of the filter using conventional X-ray imaging modalities (e.g. plain film radiographs, computed tomography CT and fluoroscopy) during deployment and follow-up is not possible and represents a potential obstacle to widespread clinical integration of the device. Here, we demonstrate that gold nanoparticles (AuNPs) infused into biodegradable filters made up of poly-p-dioxanone (PPDO) may improve device radiopacity without untoward effects on device efficacy and safety, as assessed in swine models for 12 weeks. The absorbable AuNP-infused filters demonstrated significantly improved visualization using CT without affecting tensile strength, in vitro degradation, in vivo resorption, or thrombus-capturing efficacy, as compared to similar non-AuNPs infused resorbable IVCFs. This study presents a significant advancement to the development of imaging enhancers for absorbable IVCFs.
The savanna complex is a highly diverse global biome that occurs within the seasonally dry tropical to sub-tropical equatorial latitudes and are structurally and functionally distinct from grasslands ...and forests. Savannas are open-canopy environments that encompass a broad demographic continuum, often characterised by a changing dominance between C3-tree and C4-grass vegetation, where frequent environmental disturbances such as fire modulates the balance between ephemeral and perennial life forms. Climate change is projected to result in significant changes to the savanna floristic structure, with increases to woody biomass expected through CO2 fertilisation in mesic savannas and increased tree mortality expected through increased rainfall interannual variability in xeric savannas. The complex interaction between vegetation and climate that occurs in savannas has traditionally challenged terrestrial biosphere models (TBMs), which aim to simulate the interaction between the atmosphere and the land surface to predict responses of vegetation to changing in environmental forcing. In this review, we examine whether TBMs are able to adequately represent savanna fluxes and what implications potential deficiencies may have for climate change projection scenarios that rely on these models. We start by highlighting the defining characteristic traits and behaviours of savannas, how these differ across continents and how this information is (or is not) represented in the structural framework of many TBMs. We highlight three dynamic processes that we believe directly affect the water use and productivity of the savanna system: phenology, root-water access and fire dynamics. Following this, we discuss how these processes are represented in many current-generation TBMs and whether they are suitable for simulating savanna fluxes.Finally, we give an overview of how eddy-covariance observations in combination with other data sources can be used in model benchmarking and intercomparison frameworks to diagnose the performance of TBMs in this environment and formulate road maps for future development. Our investigation reveals that many TBMs systematically misrepresent phenology, the effects of fire and root-water access (if they are considered at all) and that these should be critical areas for future development. Furthermore, such processes must not be static (i.e. prescribed behaviour) but be capable of responding to the changing environmental conditions in order to emulate the dynamic behaviour of savannas. Without such developments, however, TBMs will have limited predictive capability in making the critical projections needed to understand how savannas will respond to future global change.
Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients.
This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 ...patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16).
Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against ...COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines (from December 2020 through August 2021) were matched with 30 naturally infected women (from March 2020 through January 2021) by gestational age of exposure. Neutralization activity against the 5 SARS-CoV-2 spike sequences was measured by a SARS-CoV-2-pseudotyped spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared with WT spike protein, these nAbs were less effective against the Delta and Mu spike variants. Vaccination during the third trimester induced higher cord-nAb levels at delivery than did infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared with infection during the first trimester. The transfer ratio (cord nAb level divided by maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicits effective nAbs with differing neutralization kinetics that are influenced by gestational time of exposure.
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