Schizophrenia-derived hiPSC brain microvascular endothelial-like cells show impairments in angiogenesis and blood-brain barrier function.

Schizophrenia (SZ) is a complex neuropsychiatric disorder, affecting 1% of the world population. Long-standing clinical observations and molecular data have pointed to a possible vascular deficiency that could be acting synergistically with neuronal dysfunction in SZ. As SZ is a neurodevelopmental disease, the use of human-induced pluripotent stem cells (hiPSC) allows disease biology modeling while retaining the patient's unique genetic signature. Previously, we reported a VEGFA signaling impairment in SZ-hiPSC-derived neural lineages leading to decreased angiogenesis. Here, we present a functional characterization of SZ-derived brain microvascular endothelial-like cells (BEC), the counterpart of the neurovascular crosstalk, revealing an intrinsically defective blood-brain barrier (BBB) phenotype. Transcriptomic assessment of genes related to endothelial function among three control (Ctrl BEC) and five schizophrenia patients derived BEC (SZP BEC), revealed that SZP BEC have a distinctive expression pattern of angiogenic and BBB-associated genes. Functionally, SZP BEC showed a decreased angiogenic response in vitro and higher transpermeability than Ctrl BEC. Immunofluorescence staining revealed less expression and altered distribution of tight junction proteins in SZP BEC. Moreover, SZP BEC's conditioned media reduced barrier capacities in the brain microvascular endothelial cell line HCMEC/D3 and in an in vivo permeability assay in mice. Overall, our results describe an intrinsic failure of SZP BEC for proper barrier function. These findings are consistent with the hypothesis tracing schizophrenia origins to brain development and BBB dysfunction.

Retinal layers and symptoms and inflammation in schizophrenia.

Schizophrenia is a neurodevelopmental disorder that affects brain structure and function. The retina, as well as the brain, consists of neuronal and glial cells packed in layers. Cortical volume and brain thickness are associated with inflammatory biomarkers, however, no study has been performed associating inflammatory biomarkers and retina in schizophrenia. our study aims to compare the retinal macular thickness and volume and peripapillary thickness in patients with schizophrenia and controls, and associate it to symptoms of schizophrenia, to interleukin-6 (IL-6) and C Reactive Protein (CRP) levels. Optical coherence tomography was performed to assess retinal layer thickness and volume, and CRP and IL-6 levels were measured in patients with schizophrenia and controls. Positive, negative, and general symptoms of schizophrenia were measured with the Positive and Negative Syndrome Scale (PANSS). A linear regression controlling for confounding factors was performed. 70 subjects were included, 35 patients, and 35 controls matched for sex and age. Patients with schizophrenia presented a significantly lower macular volume (p < 0.05) and thickness (< 0.05) than controls. PANSS positive, general and total scores were associated with retinal nerve fiber layer (RNFL) thickness (p < 0.05). There was no association between inflammatory markers (CRP and IL-6) levels and the retinal layer. A reduction in macular volume and thickness was found in patients with schizophrenia. The severity of schizophrenia symptoms was associated with RNFL thickness. CRP and IL-6 are not associated with retinal thickness/volume in schizophrenia or controls.

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19.

BACKGROUND: Current approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity. METHODS: SARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19. RESULTS: Daclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 µM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans. CONCLUSIONS: Daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy.

KPC-2-producing Enterobacterales from ready-to-eat food to hospitalized patients.

Foodstuffs are a well-documented source of multidrug-resistant bacteria, and hospitalized patients are usually susceptible to hospital infections owing to their immune status. Therefore, this study aimed to investigate the presence of beta-lactamase-producing Enterobacterales in ready-to-eat foods consumed by hospitalized patients. For this purpose, 51 vegetable and meat samples were collected over 2 months and analyzed. Enterobacterales isolates were identified and subjected to antimicrobial susceptibility testing, followed by beta-lactamase gene screening, pH tolerance assays, and whole-genome sequencing (WGS). Isolates harboring genes encoding extended-spectrum beta-lactamases, cephalosporinases, or carbapenemases were detected, and all isolates tolerated pH levels similar to those in the human gastrointestinal tract. The blaKPC-2 carriers were characterized by WGS and lineages closely related to those causing human infections were identified. These results showed that dietary intake is an alternative route for the transmission of antimicrobial-resistant bacteria, which must be considered when designing effective strategies for infection control.

Modeling Alzheimer's Disease Using Human Brain Organoids.

Alzheimer's disease (AD) is the primary cause of dementia, to date. The urgent need to understand the biological and biochemical processes related to this condition, as well as the demand for reliable in vitro models for drug screening, has led to the development of novel techniques, among which stem cell methods are of utmost relevance for AD research, particularly the development of human brain organoids. Brain organoids are three-dimensional cellular aggregates derived from induced pluripotent stem cells (iPSCs) that recreate different neural cell interactions and tissue characteristics in culture. Here, we describe the protocol for the generation of brain organoids derived from AD patients and for the analysis of AD-derived pathology. AD organoids can recapitulate beta-amyloid and tau pathological features, making them a promising model for studying the molecular mechanisms underlying disease and for in vitro drug testing.

Endoscopic or Microscopic Tympanoplasty Advantages and Disadvantages: A Theory Domain Systematic Review.

Introduction Tympanoplasty is a reparative surgery that has multiple indications. The aid of a microscope or an endoscope is necessary to carry out the procedure. The classic method utilizes the microscope; however, in the recent decades, the endoscope has been popular. Although many articles try to compare these two techniques, there is still no robust evidence that confirms the superiority of either technique. In the present work, we seek to perform a systematic review contribute with this. Objectives The present systematic review attempted to compare endoscopic and microscopic surgery techniques and to discover whether there would be superiority in the results of any of them, based on data currently available in the literature. Data Synthesis The objectives of the present review were organized according to the PICO planning and strategy adapted for systematic reviews. The inclusion and exclusion criteria were established aiming to select only select primary data. The main medical databases were searched using an optimized search string with appropriate descriptors. The searched databases were MEDLINE, LILACS, SciELO, and EMBASE. A total of 99 studies were selected and 38 were fully assessed after the inclusion criteria were applied. All included articles were reviewed by all authors and their results were discussed and summarized. Conclusion The endoscopic technique was shown to be a safer technique comparable in effectiveness to the use of microscopy. In addition, it provides possible advantages such as shortening the surgical time and better postoperative pain outcomes.

Oligomeric α-Synuclein induces skin degeneration in reconstructed human epidermis.

Aged and photoaged skin exhibit fine wrinkles that are signs of epidermal inflammation and degeneration. It has been shown that healthy elderly skin expresses amyloidogenic proteins, including α-Synuclein, which are known to oligomerize and trigger inflammation and neurodegeneration. However, little is known about their putative role in skin physiology and sensitivity. To unravel this possible role, we investigated the impact of oligomeric α-Synuclein (Oα-Syn) in 2D and 3D keratinocyte human models. Exogenous Oα-Syn caused degeneration of reconstructed human epidermis (RHE) by diminishing proliferation and thickness of the stratum basale. Oα-Syn also increased NF-kB nuclear translocation in keratinocytes and triggered inflammation in the RHE, by increasing expression of interleukin-1ß and tumor necrosis factor-alpha, and the release of tumor necrosis factor-alpha in a time-dependent manner. Dexamethasone and an IL-1ß inhibitor partially diminished RHE degeneration caused by Oα-Syn. These findings suggest that Oα-Syn induces epidermal inflammation and decreases keratinocyte proliferation, and therefore might contribute to epidermal degeneration observed in human skin aging.

Age-linked suppression of lipoxin A4 associates with cognitive deficits in mice and humans.

Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system. We demonstrate that genetic suppression of 5-lipoxygenase (5-LOX), the enzyme mediating LXA4 synthesis, promotes learning impairment in mice. Conversely, administration of exogenous LXA4 attenuated cytokine production and memory loss induced by inflammation in mice. We further show that cerebrospinal fluid LXA4 is reduced in patients with dementia and positively associated with cognitive performance, brain-derived neurotrophic factor (BDNF), and AD-linked amyloid-ß. Our findings suggest that reduced LXA4 levels may lead to vulnerability to age-related cognitive disorders and that promoting LXA4 signaling may comprise an effective strategy to prevent early cognitive decline in AD.

Quantitative profiling of axonal guidance proteins during the differentiation of human neurospheres.

Axon guidance is required for the establishment of brain circuits. Whether much of the molecular basis of axon guidance is known from animal models, the molecular machinery coordinating axon growth and pathfinding in humans remains to be elucidated. The use of induced pluripotent stem cells (iPSC) from human donors has revolutionized in vitro studies of the human brain. iPSC can be differentiated into neuronal stem cells which can be used to generate neural tissue-like cultures, known as neurospheres, that reproduce, in many aspects, the cell types and molecules present in the brain. Here, we analyzed quantitative changes in the proteome of neurospheres during differentiation. Relative quantification was performed at early time points during differentiation using iTRAQ-based labeling and LC-MS/MS analysis. We identified 6438 proteins, from which 433 were downregulated and 479 were upregulated during differentiation. We show that human neurospheres have a molecular profile that correlates to the fetal brain. During differentiation, upregulated pathways are related to neuronal development and differentiation, cell adhesion, and axonal guidance whereas cell proliferation pathways were downregulated. We developed a functional assay to check for neurite outgrowth in neurospheres and confirmed that neurite outgrowth potential is increased after 10 days of differentiation and is enhanced by increasing cyclic AMP levels. The proteins identified here represent a resource to monitor neurosphere differentiation and coupled to the neurite outgrowth assay can be used to functionally explore neurological disorders using human neurospheres as a model.

Non-permissive SARS-CoV-2 infection in human neurospheres.

Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.

WIN 55,212-2 shows anti-inflammatory and survival properties in human iPSC-derived cardiomyocytes infected with SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that lead to damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the "cytokine storm", strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins six, eight, 18 and tumor necrosis factor-alpha (TNF-α) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.

Non-permissive SARS-CoV-2 infection in human neurospheres.

Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.

Inhibition of SARS-CoV-2 infection in human iPSC-derived cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoarchitecture and beating.

SARS-CoV-2 infects cardiac cells and causes heart dysfunction. Conditions such as myocarditis and arrhythmia have been reported in COVID-19 patients. The Sigma-1 receptor (S1R) is a ubiquitously expressed chaperone that plays a central role in cardiomyocyte function. S1R has been proposed as a therapeutic target because it may affect SARS-CoV-2 replication; however, the impact of the inhibition of S1R in human cardiomyocytes remains to be described. In this study, we investigated the consequences of S1R inhibition in iPSC-derived human cardiomyocytes (hiPSC-CM). SARS-CoV-2 infection in hiPSC-CM was productive and reduced cell survival. S1R inhibition decreased both the number of infected cells and viral particles after 48 hours. S1R inhibition also prevented the release of pro-inflammatory cytokines and cell death. Although the S1R antagonist NE-100 triggered those protective effects, it compromised cytoskeleton integrity by downregulating the expression of structural-related genes and reducing beating frequency. Our findings suggest that the detrimental effects of S1R inhibition in human cardiomyocytes' integrity may abrogate its therapeutic potential against COVID and should be carefully considered.

hiPSC-derived neural stem cells from patients with schizophrenia induce an impaired angiogenesis.

Schizophrenia is a neurodevelopmental disease characterized by cerebral connectivity impairment and loss of gray matter. It was described in adult schizophrenia patients (SZP) that concentration of VEGFA, a master angiogenic factor, is decreased. Recent evidence suggests cerebral hypoperfusion related to a dysfunctional Blood Brain Barrier (BBB) in SZP. Since neurogenesis and blood-vessel formation occur in a coincident and coordinated fashion, a defect in neurovascular development could result in increased vascular permeability and, therefore, in poor functionality of the SZP's neurons. Here, we characterized the conditioned media (CM) of human induced Pluripotent Stem Cells (hiPSC)-derived Neural Stem Cells of SZP (SZP NSC) versus healthy subjects (Ctrl NSC), and its impact on angiogenesis. Our results reveal that SZP NSC have an imbalance in the secretion and expression of several angiogenic factors, among them non-canonical neuro-angiogenic guidance factors. SZP NSC migrated less and their CM was less effective in inducing migration and angiogenesis both in vitro and in vivo. Since SZP originates during embryonic brain development, our findings suggest a defective crosstalk between NSC and endothelial cells (EC) during the formation of the neuro-angiogenic niche.

Endoscopic or Microscopic Tympanoplasty Advantages and Disadvantages: A Theory Domain Systematic Review

Abstract Introduction Tympanoplasty is a reparative surgery that has multiple indications. The aid of a microscope or an endoscope is necessary to carry out the procedure. The classic method utilizes the microscope; however, in the recent decades, the endoscope has been popular. Although many articles try to compare these two techniques, there is still no robust evidence that confirms the superiority of either technique. In the present work, we seek to perform a systematic review contribute with this discussion. Objectives The present systematic review attempted to compare endoscopic and microscopic surgery techniques and to discover whether there would be superiority in the results of any of them, based on data currently available in the literature. Data Synthesis The objectives of the present review were organized according to the PICO planning and strategy adapted for systematic reviews. The inclusion and exclusion criteria were established aiming to select only select primary data. The main medical databases were searched usingan optimized search string with appropriate descriptors. The searched databases were MEDLINE, LILACS, SciELO, and EMBASE. A total of 99 studies were selected and 38 were fully assessed after the inclusion criteria were applied. All included articles were reviewed by all authors and their results were discussed and summarized. Conclusion The endoscopic technique was shown to be a safer technique comparable in effectiveness to the use of microscopy. In addition, it provides possible advantages such as shortening the surgical time and better postoperative pain outcomes.

Generation of iPSC-Derived Human Peripheral Sensory Neurons Releasing Substance P Elicited by TRPV1 Agonists.

Neural crest stem cells (NCPCs) have been shown to differentiate into various cell types and tissues during embryonic development, including sensory neurons. The few studies addressing the generation of NCPCs and peripheral sensory neurons (PSNs) from human induced pluripotent stem cells (hiPSCs), generated sensory cells without displaying robust activity. Here, we describe an efficient strategy for hiPSCs differentiation into NCPCs and functional PSNs using chemically defined media and factors to achieve efficient differentiation, confirmed by the expression of specific markers. After 10 days hiPSCs differentiated into NCPCs, cells were then maintained in neural induction medium containing defined growth factors for PSNs differentiation, followed by 10 days in neonatal human epidermal keratinocytes- (HEKn-) conditioned medium (CM). We observed a further increase in PSN markers expression and neurites length after CM treatment. The resulting neurons elicited action potentials after current injection and released substance P (SP) in response to nociceptive agents such as anandamide and resiniferatoxin. Anandamide induced substance P release via activation of TRPV1 and not CB1. Transcriptomic analysis of the PSNs revealed the main dorsal root ganglia neuronal markers and a transcriptional profile compatible with C fiber-low threshold mechanoreceptors. TRPV1 was detected by immunofluorescence and RNA-Seq in multiple experiments. In conclusion, the developed strategy generated PSNs useful for drug screening that could be applied to patient-derived hiPSCs, consisting in a powerful tool to model human diseases in vitro.

Síndrome pós-covid: diagnósticos de enfermagem segundo nanda-i versus cipesc / Post covid syndrome: nursing diagnoses according to nanda-i versus cipesc / Síndrome post covid: diagnósticos de enfermería según nanda-i versus cipesc

Introdução: Diagnósticos de enfermagem são instrumentos utilizados mundialmente na sistematização dos cuidados de enfermagem. Objetivo: Identificar e comparar os títulos diagnósticos de enfermagem entre as taxonomias NANDA-I e a Classificação Internacional das Práticas de Enfermagem em Saúde Coletiva (CIPESC) em indivíduos que desenvolveram Síndrome Pós-Covid após período de hospitalização, com alta responsável em acompanhamento no Projeto Terapêutico Singular (PTS) na Atenção Primária a Saúde. Material e Método: Estudo exploratório, descritivo, transversal com abordagem quantitativautilizando a técnica de mapeamento cruzado para identificar e comparar os diagnósticos de enfermagem da NANDA-I e da CIPESC. Estudo realizado no município de Catanduva-SP, com inclusão de 17 pacientes, cuja coleta de dados ocorreu de junho a agosto de 2022 e os resultados analisados utilizaram estatística descritiva. Resultados: Participaram 53% de pessoas do sexo masculino, com idades entre 56 e 85 anos, sendo que 88,2% ficaram hospitalizados em enfermarias e 11,8% necessitaram de tratamento em Unidade de Terapia Intensiva. Prevaleceu como principal comorbidade a Hipertensão Arterial Sistêmica (94%) e a dispnéia aos mínimo esforços (24%). Tiveram edema em MMII, 41%, 24% referiram oligúria, 12% apresentaram diminuição dos murmúrios broncovesiculares e 6% referiram períodos de esquecimento. Em relação aos diagnósticos de enfermagem, na NANDA-I evidenciou-se troca gasosa prejudicada (35%), medo (24%), na CIPESC os DE predominantes foram: respiração alterada (35%) e adaptação/enfrentamento ausente (24%). Conclusão: Tanto a taxonomia NANDA-I como a CIPESC, mostramse adequadas para identificar diagnósticos de enfermagem em pacientes no pós-covid, atendidos na atenção primária a saúde

Introduction: Nursing diagnoses are instruments used worldwide in the systematization of nursing care: Identify and compare the nursing diagnostic titles among the NANDA-taxonomiesI and the International Classification of Nursing Practices in Collective Health (CIPESC) in individuals who developed Post-Covid Syndrome after hospitalization period, with discharge in monitoring in the Singular Therapeutic Project (PTS) in Primary Health Care. Material and Method: Exploratory, descriptive, cross-sectional study with a quantitative approach using the cross-mapping technique to identify and compare the nursing diagnoses of NANDA-I and CIPESC. A study conducted in the city of Catanduva-SP, including 17 patients, whose data collection occurred from June to August 2022 and the results analyzed used descriptive statistics. Results: 53% of males participated, aged between 56 and 85 years, and 88.2% were hospitalized in wards and 11.8% needed treatment in the Intensive Care Unit. Hypertension (94%) and dyspnea at minimum effort (24%) prevailed as the main comorbidity. They had edema in MMII, 41%, 24% reported oliguria, 12% had decreased broncovesicular murmurs and 6% reported periods of forgetfulness. Regarding nursing diagnoses, in NANDA-I there was impaired gas exchange (35%), fear (24%), in CIPESC the predominant ED were: altered breathing (35%) and adaptation/coping absent (24%). Conclusion: Both NANDA-I and CIPESC taxonomy are adequate to identify nursing diagnoses in patients in the post-covid, attended in primary health care.

Introducción: Los diagnósticos de enfermería son instrumentos utilizados a nivel mundial en la sistematización de la atención de enfermería. Objetivo: Identificar y comparar los títulos de los diagnósticos de enfermería entre las taxonomías de la NANDA-I y la Clasificación Internacional de Prácticas de Enfermería en Salud Colectiva (CIPESC) en individuos que desarrollaron Síndrome Postnatal - Covid tras un periodo de hospitalización, con alta a cargo en seguimiento en el Proyecto Terapéutico Singular (PTS) en Atención Primaria de Salud. Material y Método: Estudio exploratorio, descriptivo, transversal con enfoque cuantitativo utilizando la técnica de mapeo cruzado para identificar y comparar los diagnósticos de enfermería de NANDA-I y CIPESC. Estudio realizado en la ciudad de Catanduva-SP, con inclusión de 17 pacientes, cuya recolección de datos ocurrió de junio a agosto de 2022 y los resultados analizados utilizaron estadística descriptiva. Resultados: Los participantes fueron 53% del sexo masculino, con edad entre 56 y 85 años, siendo el 88,2% internados en sala y el 11,8% requiriendo tratamiento en Unidad de Cuidados Intensivos. Predominó como principal comorbilidad la Hipertensión Arterial Sistémica (94%) y la disnea de mínimos esfuerzos (24%). Tenían edema en LL, el 41%, el 24% referían oliguria, el 12% tenían soplos broncovesiculares disminuidos y el 6% referían periodos de olvido. En cuanto a los diagnósticos de enfermería, en NANDA-I se evidenció alteración del intercambio gaseoso (35%), miedo (24%), en CIPESC los DE predominantes fueron: respiración alterada (35%) y ausencia de adaptación/afrontamiento (24%). Conclusión: Tanto la taxonomía NANDA-I como CIPESC son adecuadas para identificar diagnósticos de enfermería en pacientes post-covid, atendidos en atención primaria de salud.

Zika virus disrupts molecular fingerprinting of human neurospheres.

Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.