Regulation of embryonic haematopoietic multipotency by EZH1.

All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential. Ultimately, 'definitive' HSCs with long-term, multilineage potential and the ability to engraft irradiated adults emerge at 10.5 days post-coitum from arterial endothelium in the aorta-gonad-mesonephros and other haemogenic vasculature. The molecular mechanisms of this reverse progression of haematopoietic ontogeny remain unexplained. We hypothesized that the definitive haematopoietic program might be actively repressed in early embryogenesis through epigenetic silencing, and that alleviating this repression would elicit multipotency in otherwise lineage-restricted haematopoietic progenitors. Here we show that reduced expression of the Polycomb group protein EZH1 enhances multi-lymphoid output from human pluripotent stem cells. In addition, Ezh1 deficiency in mouse embryos results in precocious emergence of functional definitive HSCs in vivo. Thus, we identify EZH1 as a repressor of haematopoietic multipotency in the early mammalian embryo.

Bilateral same-day myringoplasty: a feasible option?

PURPOSE: Retrospective evaluation of bilateral same-day myringoplasty outcomes. METHODS: Patients who underwent bilateral same-day myringoplasty from 2005 to 2019. RESULTS: Thirty-eight patients underwent bilateral myringoplasty. Mean age was 44.5 years and 55.3% patients were male. Tragal perichondrium-cartilage composite graft was the most frequently used graft material (82.9%). Perforation closure was achieved in 78.9%. Postoperative Pure Tone Average and Air-Bone Gap decreased significantly (p < 0.05), except for the Air-Bone Gap of the right ear (p = 0.058). The complications were cholesteatoma (1.3%), otorrhea (6.6%) and tympanic membrane retraction (1.3%). CONCLUSIONS: Bilateral same-day myringoplasty is a feasible procedure in selected patients. Good anatomic and functional outcomes, as well as a low rate of complications, are achieved with this procedure, improving patient comfort and allowing for a reduction in operation time and costs.

Strategies for nursing care of critically ill multicultural patients: A scoping review.

BACKGROUND: In society, people live in a social reality where multiculturalism is an increasingly relevant and prevalent topic in their contexts. Facing this, caring for multicultural patients in an emergency service or intensive care unit setting requires a high level of cultural competence due to the complexity, vulnerability of the patient, rapid changes in hemodynamic status, involvement of the family, their informational needs. OBJECTIVE: To map the strategies for nursing care of critically ill multicultural patients. METHOD: A Scoping Review was conducted following the Joanna Briggs Institute's recommendations, with the research question: What are the strategies for nursing care of critically ill multicultural patients? The study was guided by PRISMA. The research was conducted through the EBSCOHost platform, SciELO, Portugal's Open Access Scientific Repository, the Virtual Health Library and a search in grey literature. This was achieved by combining the descriptors DECS/MESH: cultural competence; critical care; emergency room; intensive care; and natural words: cultural care; nurs* interventions; nurs* strategies; within the time frame from 2012 to 2024. The study screening was performed by three independent reviewers through the reading of titles, abstracts and full texts, applying exclusion criteria. The study results were then subjected to content analysis, from which categories emerged. RESULTS: The selected articles highlight various strategies that contribute to the improvement of nursing care for critically ill multicultural patients, focusing on care practice and cultural diversity training for both nurses and nursing students. CONCLUSION: Nurses with cultural competence possess more knowledge and strategies to provide tailored care for multicultural critically ill patients, thereby enhancing the quality of care delivered and contributing to the humanization of healthcare. RELEVANCE TO CLINICAL PRACTICE: Nurses need to have knowledge of existing strategies for caring for multicultural critically ill patients. PATIENT OR PUBLIC CONTRIBUTION: No direct patient or public contribution to the review.

Seasonal variations in gonadosomatic index and seminal quality of squirrel monkeys (Saimiri collinsi).

BACKGROUND: We hypothesized that seasonal variations in testicular biometry in Saimiri collinsi are influenced by body mass and that testicular enlargement is related to improved seminal quality. Therefore, the gonadosomatic index (GSI) can be a tool to determine reproductive seasons and the predictors of seminal quality. METHODS: Body mass, testicular biometry, and semen samples were obtained from eight adult males monthly and evaluated. RESULTS: In the non-fattening/non-reproductive season, the body mass and GSI decreased and increased, respectively, in the fattening. A positive correlation was only observed between the GSI and seminal volume. During fattening, high seminal volume and normal morphology were observed, but sperm concentrations were low. CONCLUSION: The GSI cannot be used as a predictor of seminal quality, but selective pressure to improve seminal quality may increase the chances of fertilization at fattening. The GSI provides new information on seasonality and can be used to identify reproductive seasons in squirrel monkeys.

Haematopoietic stem and progenitor cells from human pluripotent stem cells.

A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders.

Skene's Gland Cyst - Case Report of a 2-Year-Old Girl.

BACKGROUND: Skene's glands are the two largest paraurethral glands and the female homologue to the prostate glands. When their ducts become obstructed, cysts may be formed. This usually occurs in adult women. Most cases reported in pediatrics are neonatal, with a single report in a prepubertal girl. CASE REPORT: We present a 25-month-old girl with a 7 mm nontender, solid, oval, pink-orange paraurethral mass, with no change over a five-month period. Histopathology revealed the cyst to be lined with transitional epithelium consistent with a Skene's gland cyst. The child did well with no sequalae. CONCLUSION: We describe a Skene's gland cyst found in a prepubertal child.

Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport.

Posttranslational modifications of tubulin are emerging regulators of microtubule functions. We have shown earlier that upregulated polyglutamylation is linked to rapid degeneration of Purkinje cells in mice with a mutation in the deglutamylating enzyme CCP1. How polyglutamylation leads to degeneration, whether it affects multiple neuron types, or which physiological processes it regulates in healthy neurons has remained unknown. Here, we demonstrate that excessive polyglutamylation induces neurodegeneration in a cell-autonomous manner and can occur in many parts of the central nervous system. Degeneration of selected neurons in CCP1-deficient mice can be fully rescued by simultaneous knockout of the counteracting polyglutamylase TTLL1. Excessive polyglutamylation reduces the efficiency of neuronal transport in cultured hippocampal neurons, suggesting that impaired cargo transport plays an important role in the observed degenerative phenotypes. We thus establish polyglutamylation as a cell-autonomous mechanism for neurodegeneration that might be therapeutically accessible through manipulation of the enzymes that control this posttranslational modification.

Male fattening is related to increased seminal quality of squirrel monkeys (Saimiri collinsi): Implications for sperm competition.

Saimiri are neotropical primates with seasonal reproduction, males develop a seasonal fattening condition that has been suggested as a pre-copulatory sexual selection strategy. Furthermore, females mate with multiple males in the same season. This could also favor the evolution of a postcopulatory sexual strategy by sperm competition. In this study, we tested the hypothesis that there is a relationship between the fatted condition and advantageous seminal characteristics in Saimiri collinsi and evaluated its implications for sperm competition. Adult males (N = 10), aged 5-15 years, housed in mixed or only-male groups, were analyzed from June, 2015 to July, 2016. Measurements of weight, axilla, and arm skinfold, and testicular volume were taken monthly, and semen was collected by electroejaculation. A fattening index was developed to quantify and identify fatted males, biometrics, and seminal parameters were compared between the non-fatted and fatted conditions. The fatted males present a larger testicular volume. This is related to the increase in spermatogenic activity necessary to sustain a high ejaculation frequency during the mating season. An increase in seminal volume and in frequency of semen coagulation were detected in fatted males, advantages related to sperm protection in the female reproductive tract. Age and social context were not significant sources of variation for both morphological and seminal traits. A decrease in response from the fatted males in obtaining semen and an increase in the frequency of azoospermic ejaculates were observed. These unexpected results may be due to intense reproductive activities in a short period. The fattening phenomenon has many implications in the sexual selection of squirrel monkeys, and they are still not entirely unveiled. Our results corroborate the idea that, in S. collinsi, the fatted male condition is related to sexual selection, and we found evidence suggesting it may be also expressed by a post-copulatory component, sperm competition.

Structural Health Monitoring of Dams Based on Acoustic Monitoring, Deep Neural Networks, Fuzzy Logic and a CUSUM Control Algorithm.

Internal erosion is the most important failure mechanism of earth and rockfill dams. Since this type of erosion develops internally and silently, methodologies of data acquisition and processing for dam monitoring are crucial to guarantee a safe operation during the lifespan of these structures. In this context, artificial intelligence techniques show up as tools that can simplify the analysis and verification process not of the internal erosion itself, but of the effects that this pathology causes in the response of the dam to external stimuli. Therefore, within the scope of this paper, a methodological framework for monitoring internal erosion in the body of earth and rockfill dams will be proposed. For that, artificial intelligence methods, especially deep neural autoencoders, will be used to treat the acoustic data collected by geophones installed on a dam. The sensor data is processed to identify patterns and anomalies as well as to classify the dam's structural health status. In short, the acoustic dataset is preprocessed to reduce its dimensionality. In this process, for each second of acquired data, three parameters are calculated (Hjorth parameters). For each parameter, the data from all the available sensors are used to calibrate an autoencoder. Then, the reconstruction error of each autoencoder is used to monitor how far from the original (normal) state the acoustic signature of the dam is. The time series of reconstruction errors are combined with a cumulative sum (CUSUM) algorithm, which indicates changes in the sequential data collected. Additionally, the outputs of the CUSUM algorithms are treated by a fuzzy logic framework to predict the status of the structure. A scale model is built and monitored to check the effectiveness of the methodology hereby developed, showing that the existence of anomalies is promptly detected by the algorithm. The framework introduced in the present paper aims to detect internal erosion inside dams by combining different techniques in a novel context and methodological workflow. Therefore, this paper seeks to close gaps in prior studies, which mostly treated just parts of the data acquisition-processing workflow.

Peripheral Nerve Injury Treatments and Advances: One Health Perspective.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

Gamma Irradiation Processing on 3D PCL Devices-A Preliminary Biocompatibility Assessment.

Additive manufacturing or 3D printing applying polycaprolactone (PCL)-based medical devices represents an important branch of tissue engineering, where the sterilization method is a key process for further safe application in vitro and in vivo. In this study, the authors intend to access the most suitable gamma radiation conditions to sterilize PCL-based scaffolds in a preliminary biocompatibility assessment, envisioning future studies for airway obstruction conditions. Three radiation levels were considered, 25 kGy, 35 kGy and 45 kGy, and evaluated as regards their cyto- and biocompatibility. All three groups presented biocompatible properties, indicating an adequate sterility condition. As for the cytocompatibility analysis, devices sterilized with 35 kGy and 45 kGy showed better results, with the 45 kGy showing overall improved outcomes. This study allowed the selection of the most suitable sterilization condition for PCL-based scaffolds, aiming at immediate future assays, by applying 3D-customized printing techniques to specific airway obstruction lesions of the trachea.

The use of anogenital distance as a non-invasive predictor of seminal quality in captive squirrel monkey (Saimiri collinsi Osgood 1961).

BACKGROUND: Anogenital distance is considered a non-invasive measure to assess the development and functionality of sexual organs in different animal species. Hence, this measurement could potentially be used during the selection of non-human primates for reproductive biotechnology programs. The aim of this study was to assess the correlation between anogenital distance and reproductive parameters in captive Saimiri collinsi. METHODS: Eight mature S. collinsi males were evaluated. Body weight, reproductive hormone levels, testicular volume, and seminal parameters were determined, and their relationship with anogenital distance measurements was assessed. RESULTS: Anogenital distance was correlated with seminal volume, sperm motility, vigor, and plasma membrane integrity, but not with body weight, reproductive hormones, and testicular volume. CONCLUSION: The determination of anogenital distance is a non-invasive method to predict seminal quality. This procedure has the advantage of providing andrologic information without a negative impact on animal welfare.

Gross Motor Function in Children with Congenital Zika Syndrome.

BACKGROUND: Little information on gross motor function of congenital Zika syndrome (CZS) children is available. OBJECTIVES: To evaluate gross motor function in CZS children aged up to 3 years, and its associated factors and changes in a minimum interval of 6 months. METHODS: One hundred children with CZS and cerebral palsy (36 with confirmed and 64 with presumed CZS) were evaluated with the Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM-88/GMFM-66). Forty-six were reevaluated. Wilcoxon tests, Wilcoxon tests for paired samples, percentile scores, and score changes were performed. RESULTS: Clinical and socioeconomic characteristics (except maternal age), GMFM scores and GMFCS classification of confirmed and probable cases, which were analyzed together, were similar. The mean age was 25.6 months (±5.5); the median GMFM-88 score was 8.0 (5.4-10.8); and the median GMFM-66 score was 20.5 (14.8-23.1); 89% were classified as GMFCS level V. Low economic class, microcephaly at birth, epilepsy, and brain parenchymal volume loss were associated with low GMFM-66 scores. The median GMFM-66 percentile score was 40 (20-55). On the second assessment, the GMFM-66 scores in two GMFCS level I children and one GMFCS level IV child improved significantly. In one GMFCS level III child, one GMFCS level IV child, and the group of GMFCS level V children, no significant changes were observed. CONCLUSIONS: Almost all CZS children had severe cerebral palsy; in the third year of life, most presented no improvement in gross motor function and were likely approaching their maximal gross motor function potential.

Activation of Mechanoreflex, but not Central Command, Delays Heart Rate Recovery after Exercise in Healthy Men.

This study tested the hypotheses that activation of central command and muscle mechanoreflex during post-exercise recovery delays fast-phase heart rate recovery with little influence on the slow phase. Twenty-five healthy men underwent three submaximal cycling bouts, each followed by a different 5-min recovery protocol: active (cycling generated by the own subject), passive (cycling generated by external force) and inactive (no-cycling). Heart rate recovery was assessed by the heart rate decay from peak exercise to 30 s and 60 s of recovery (HRR30s, HRR60s fast phase) and from 60 s-to-300 s of recovery (HRR60-300s slow phase). The effect of central command was examined by comparing active and passive recoveries (with and without central command activation) and the effect of mechanoreflex was assessed by comparing passive and inactive recoveries (with and without mechanoreflex activation). Heart rate recovery was similar between active and passive recoveries, regardless of the phase. Heart rate recovery was slower in the passive than inactive recovery in the fast phase (HRR60s=20±8vs.27 ±10 bpm, p<0.01), but not in the slow phase (HRR60-300s=13±8vs.10±8 bpm, p=0.11). In conclusion, activation of mechanoreflex, but not central command, during recovery delays fast-phase heart rate recovery. These results elucidate important neural mechanisms behind heart rate recovery regulation.

Provisioning, Authentication and Secure Communications for IoT Devices on FIWARE.

The increasing pervasiveness of the Internet of Things is resulting in a steady increase of cyberattacks in all of its facets. One of the most predominant attack vectors is related to its identity management, as it grants the ability to impersonate and circumvent current trust mechanisms. Given that identity is paramount to every security mechanism, such as authentication and access control, any vulnerable identity management mechanism undermines any attempt to build secure systems. While digital certificates are one of the most prevalent ways to establish identity and perform authentication, their provision at scale remains open. This provisioning process is usually an arduous task that encompasses device configuration, including identity and key provisioning. Human configuration errors are often the source of many security and privacy issues, so this task should be semi-autonomous to minimize erroneous configurations during this process. In this paper, we propose an identity management (IdM) and authentication method called YubiAuthIoT. The overall provisioning has an average runtime of 1137.8 ms ±65.11+δ. We integrate this method with the FIWARE platform, as a way to provision and authenticate IoT devices.

Delirium in adult patients in intensive care: nursing interventions.

BACKGROUND: Delirium is a neuropsychiatric syndrome of high incidence in the critically ill patient. It is characterised by changes in acute attention and cognition, has a multifactorial aetiology and has a negative impact on the patient's clinical situation and future quality of life. Prevention of delirium and early identification can reduce associated morbidity and mortality. Consequently, it is vital that intensive care unit (ICU) nurses perform targeted patient monitoring to identify acute cognitive changes. OBJECTIVE: To identify nursing interventions directed at the prevention and management of delirium in adult patients in ICU. METHOD: A scoping review was undertaken based on the principles recommended by the Joanna Briggs Institute. RESULTS: Seven studies were selected for inclusion. Non-pharmacological and pharmacological nursing interventions were identified. CONCLUSION: The interventions identified were predominantly aimed at the prevention of delirium. The training of nurses and wider clinical team in preventing and identifying this syndrome is crucial.

Organ-on-a-Chip: A Preclinical Microfluidic Platform for the Progress of Nanomedicine.

Despite the progress achieved in nanomedicine during the last decade, the translation of new nanotechnology-based therapeutic systems into clinical applications has been slow, especially due to the lack of robust preclinical tissue culture platforms able to mimic the in vivo conditions found in the human body and to predict the performance and biotoxicity of the developed nanomaterials. Organ-on-a-chip (OoC) platforms are novel microfluidic tools that mimic complex human organ functions at the microscale level. These integrated microfluidic networks, with 3D tissue engineered models, have been shown high potential to reduce the discrepancies between the results derived from preclinical and clinical trials. However, there are many challenges that still need to be addressed, such as the integration of biosensor modules for long-time monitoring of different physicochemical and biochemical parameters. In this review, recent advances on OoC platforms, particularly on the preclinical validation of nanomaterials designed for cancer, as well as the current challenges and possible future directions for an end-use perspective are discussed.

Micromorphological and ultrastructural description of spermatozoa from squirrel monkeys (Saimiri collinsi Osgood, 1916).

Saimiri collinsi is used as an animal model in biotechnology research for conservation of species from the genus Saimiri. However, the development of biotechnologies depends on a proper knowledge of the sperm morphology to understand the basic aspects of sperm physiology, as potential male fertility depends on different cellular sperm structures. With this purpose, this study characterized the micromorphological and ultrastructural characteristics of squirrel monkeys (Saimiri collinsi) sperm using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM electromyography revealed that a normal Saimiri collinsi sperm measures 71.7 ± 0.7 µm with lateral tail insertion, a paddle-shaped flattened head and an acrosome occupying most of the head. TEM also showed that the middle piece is characterized by a central 9 + 2 microtubule axoneme surrounded by nine dense fibres, and that the mitochondria were juxtaposed, forming the mitochondrial sheath. Here we provide the first micromorphological and ultrastructure description of S. collinsi sperm.

Alterations in the balance of tubulin glycylation and glutamylation in photoreceptors leads to retinal degeneration.

Tubulin is subject to a wide variety of posttranslational modifications, which, as part of the tubulin code, are involved in the regulation of microtubule functions. Glycylation has so far predominantly been found in motile cilia and flagella, and absence of this modification leads to ciliary disassembly. Here, we demonstrate that the correct functioning of connecting cilia of photoreceptors, which are non-motile sensory cilia, is also dependent on glycylation. In contrast to many other tissues, only one glycylase, TTLL3, is expressed in retina. Ttll3-/- mice lack glycylation in photoreceptors, which results in shortening of connecting cilia and slow retinal degeneration. Moreover, absence of glycylation results in increased levels of tubulin glutamylation in photoreceptors, and inversely, the hyperglutamylation observed in the Purkinje cell degeneration (pcd) mouse abolishes glycylation. This suggests that both posttranslational modifications compete for modification sites, and that unbalancing the glutamylation-glycylation equilibrium on axonemes of connecting cilia, regardless of the enzymatic mechanism, invariably leads to retinal degeneration.

Identification of Hypsarrhythmia in Children with Microcephaly Infected by Zika Virus.

Hypsarrhythmia is an electroencephalographic pattern specific to some epileptic syndromes that affect children under one year of age. The identification of this pattern, in some cases, causes disagreements between experts, which is worrisome since an inaccurate diagnosis can bring complications to the infant. Despite the difficulties in visually identifying hypsarrhythmia, options of computerized assistance are scarce. Aiming to collaborate with the recognition of this electropathological pattern, we propose in this paper a mathematical index that can help electroencephalography experts to identify hypsarrhythmia. We performed hypothesis tests that indicated significant differences in the groups under analysis, where the p-values were found to be extremely small.