Scn1a haploinsufficiency in the prefrontal cortex engages to cognitive impairment and depressive phenotype.

Altered development and function of the prefrontal cortex (PFC) during adolescence is implicated in the origin of mental disorders. Deficits in the GABAergic system prominently contribute to these alterations. Nav1.1 is a voltage-gated Na+ channel critical for normal GABAergic activity. Here, we studied the role of Nav1.1 in PFC function and its potential relationship with the aetiology of mental disorders. Dysfunction of Nav1.1 activity in the medial PFC (mPFC) of adolescent mice enhanced the local excitation/inhibition ratio, resulting in epileptic activity, cognitive deficits and depressive-like behaviour in adulthood, along with a gene expression profile linked to major depressive disorder (MDD). Additionally, it reduced extracellular serotonin concentration in the dorsal raphe nucleus and brain-derived neurotrophic factor expression in the hippocampus, two MDD-related brain areas beyond the PFC. We also observed alterations in oscillatory activity and impaired hippocampal-mPFC coherence during sleep. Finally, we found reduced expression levels of SCN1A, the gene encoding Nav1.1, in post-mortem PFC samples from human MDD subjects. Collectively, our results provide a novel mechanistic framework linking adolescence-specific alterations in Nav1.1 function in the PFC to the pathogenesis of epilepsy and comorbidities such as cognitive impairment and depressive disorders.

CPEB and translational control by cytoplasmic polyadenylation: impact on synaptic plasticity, learning, and memory.

The late 1990s were banner years in molecular neuroscience; seminal studies demonstrated that local protein synthesis, at or near synapses, was necessary for synaptic plasticity, the underlying cellular basis of learning and memory [1, 2]. The newly made proteins were proposed to "tag" the stimulated synapse, distinguishing it from naive synapses, thereby forming a cellular memory [3]. Subsequent studies demonstrated that the transport of mRNAs from soma to dendrite was linked with translational unmasking at synapses upon synaptic stimulation. It soon became apparent that one prevalent mechanism governing these events is cytoplasmic polyadenylation, and that among the proteins that control this process, CPEB, plays a central role in synaptic plasticity, and learning and memory. In vertebrates, CPEB is a family of four proteins, all of which regulate translation in the brain, that have partially overlapping functions, but also have unique characteristics and RNA binding properties that make them control different aspects of higher cognitive function. Biochemical analysis of the vertebrate CPEBs demonstrate them to respond to different signaling pathways whose output leads to specific cellular responses. In addition, the different CPEBs, when their functions go awry, result in pathophysiological phenotypes resembling specific human neurological disorders. In this essay, we review key aspects of the vertebrate CPEB proteins and cytoplasmic polyadenylation within the context of brain function.

Machine Learning Classification of Event-Related Brain Potentials during a Visual Go/NoGo Task.

Machine learning (ML) methods are increasingly being applied to analyze biological signals. For example, ML methods have been successfully applied to the human electroencephalogram (EEG) to classify neural signals as pathological or non-pathological and to predict working memory performance in healthy and psychiatric patients. ML approaches can quickly process large volumes of data to reveal patterns that may be missed by humans. This study investigated the accuracy of ML methods at classifying the brain's electrical activity to cognitive events, i.e., event-related brain potentials (ERPs). ERPs are extracted from the ongoing EEG and represent electrical potentials in response to specific events. ERPs were evoked during a visual Go/NoGo task. The Go/NoGo task requires a button press on Go trials and response withholding on NoGo trials. NoGo trials elicit neural activity associated with inhibitory control processes. We compared the accuracy of six ML algorithms at classifying the ERPs associated with each trial type. The raw electrical signals were fed to all ML algorithms to build predictive models. The same raw data were then truncated in length and fitted to multiple dynamic state space models of order nx using a continuous-time subspace-based system identification algorithm. The 4nx numerator and denominator parameters of the transfer function of the state space model were then used as substitutes for the data. Dimensionality reduction simplifies classification, reduces noise, and may ultimately improve the predictive power of ML models. Our findings revealed that all ML methods correctly classified the electrical signal associated with each trial type with a high degree of accuracy, and accuracy remained high after parameterization was applied. We discuss the models and the usefulness of the parameterization.

Ductular reaction promotes intrahepatic angiogenesis through Slit2-Roundabout 1 signaling.

BACKGROUND AND AIMS: Ductular reaction (DR) expands in chronic liver diseases and correlates with disease severity. Besides its potential role in liver regeneration, DR plays a role in the wound-healing response of the liver, promoting periductular fibrosis and inflammatory cell recruitment. However, there is no information regarding its role in intrahepatic angiogenesis. In the current study we investigated the potential contribution of DR cells to hepatic vascular remodeling during chronic liver disease. APPROACH AND RESULTS: In mouse models of liver injury, DR cells express genes involved in angiogenesis. Among angiogenesis-related genes, the expression of Slit2 and its receptor Roundabout 1 (Robo1) was localized in DR cells and neoangiogenic vessels, respectively. The angiogenic role of the Slit2-Robo1 pathway in chronic liver disease was confirmed in ROBO1/2-/+ mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine, which displayed reduced intrahepatic neovascular density compared to wild-type mice. However, ROBO1/2 deficiency did not affect angiogenesis in partial hepatectomy. In patients with advanced alcohol-associated disease, angiogenesis was associated with DR, and up-regulation of SLIT2-ROBO1 correlated with DR and disease severity. In vitro, human liver-derived organoids produced SLIT2 and induced tube formation of endothelial cells. CONCLUSIONS: Overall, our data indicate that DR expansion promotes angiogenesis through the Slit2-Robo1 pathway and recognize DR cells as key players in the liver wound-healing response.

CPEB4 Increases Expression of PFKFB3 to Induce Glycolysis and Activate Mouse and Human Hepatic Stellate Cells, Promoting Liver Fibrosis.

BACKGROUND & AIMS: We investigated mechanisms of hepatic stellate cell (HSC) activation, which contributes to liver fibrogenesis. We aimed to determine whether activated HSCs increase glycolysis, which is regulated by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and whether this pathway might serve as a therapeutic target. METHODS: We performed studies with primary mouse HSCs, human LX2 HSCs, human cirrhotic liver tissues, rats and mice with liver fibrosis (due to bile duct ligation [BDL] or administration of carbon tetrachloride), and CPEB4-knockout mice. Glycolysis was inhibited in cells and mice by administration of a small molecule antagonist of PFKFB3 (3-[3-pyridinyl]-1-[4-pyridinyl]-2-propen-1-one [3PO]). Cells were transfected with small interfering RNAs that knock down PFKFB3 or CPEB4. RESULTS: Up-regulation of PFKFB3 protein and increased glycolysis were early and sustained events during HSC activation and accompanied by increased expression of markers of fibrogenesis; incubation of HSCs with 3PO or knockdown of PFKFB3 reduced their activation and proliferation. Mice with liver fibrosis after BDL had increased hepatic PFKFB3; injection of 3PO immediately after the surgery prevented HSC activation and reduced the severity of liver fibrosis compared with mice given vehicle. Levels of PFKFB3 protein were increased in fibrotic liver tissues from patients compared with non-fibrotic liver. Up-regulation of PFKFB3 in activated HSCs did not occur via increased transcription, but instead via binding of CPEB4 to cytoplasmic polyadenylation elements within the 3'-untranslated regions of PFKFB3 messenger RNA. Knockdown of CPEB4 in LX2 HSCs prevented PFKFB3 overexpression and cell activation. Livers from CPEB4-knockout had decreased PFKFB3 and fibrosis after BDL or administration of carbon tetrachloride compared with wild-type mice. CONCLUSIONS: Fibrotic liver tissues from patients and rodents (mice and rats) have increased levels of PFKFB3 and glycolysis, which are essential for activation of HSCs. Increased expression of PFKFB3 is mediated by binding of CPEB4 to its untranslated messenger RNA. Inhibition or knockdown of CPEB4 or PFKFB3 prevents HSC activation and fibrogenesis in livers of mice.

Effect of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF v600-mutated metastatic colorectal cancer: a real-world study in Spain.

BACKGROUND: Outcomes are poorer in metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear. This real-world study assessed the effects of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF V600-mutated mCRC. METHODS: This real-world, multicenter, retrospective, observational study included patients with BRAF V600-mutated mCRC treated in eight hospitals in Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS); overall response rate (ORR) and disease control rate (DCR) were also assessed. The effect of first- and second-line treatment type on OS, PFS, ORR, and DCR were evaluated, plus the impact of systemic inflammatory markers on these outcomes. A systemic inflammation score (SIS) of 1-3 was assigned based on one point each for platelet-lymphocyte ratio (PLR) ≥200, neutrophil-lymphocyte ratio (NLR) ≥3, and serum albumin < 3.6 g/dL. RESULTS: Of 72 patients, data from 64 were analyzed. After a median of 69.1 months, median OS was 11.9 months and median first-line PFS was 4.4 months. First-line treatment was triplet chemotherapy-antiangiogenic (12.5%), doublet chemotherapy-antiangiogenic (47.2%), doublet chemotherapy-anti-EGFR (11.1%), or doublet chemotherapy (18.1%). Although first-line treatment showed no significant effect on OS, antiangiogenic-based regimens were associated with prolonged median PFS versus non-antiangiogenic regimens. Negative predictors of survival with antiangiogenic-based treatment were NLR, serum albumin, and SIS 1-3, but not PLR. Patients with SIS 1-3 showed significantly prolonged PFS with antiangiogenic-based treatment versus non-antiangiogenic-based treatment, while those with SIS=0 showed no PFS benefit. CONCLUSIONS: Antiangiogenic-based regimens, SIS, NLR, and albumin were predictors of survival in patients with mCRC, while SIS, NLR and serum albumin may predict response to antiangiogenic-based chemotherapy. TRIAL REGISTRATION: GIT-BRAF-2017-01.

NGF and Endogenous Regeneration: From Embryology Toward Therapies.

The self-repair ability of tissues and organs in case of injury and disease is a fundamental biological mechanism and an important therapeutic target. The tissue plasticity and the presence of adult stem cell niches open a new path in the development of pharmacological and non-pharmacological treatments finalized to improve the intrinsic regeneration.In this context, nerve growth factor (NGF) is widely studied for its capability of driving endogenous regeneration of ectoderm-derived tissues, directly acting on the cell targets and through the regulation of the stem cell niches. In fact, this growth factor is very promising for its key role in the development and multiplicity of the cellular targets.In this chapter, we have traveled across the recent history of NGF pleiotropic role in ectodermal tissue generation and repair, from embryonic development to skin wound healing, axonal regrowth, and remyelination.The better understanding of both the biological mechanisms underlying regeneration and the physiological role of NGF in development and injury response will open new therapeutic strategies, driven by the potential applications of this growth factor as an agent for improving endogenous regeneration processes.

Ascocotyle longa (Digenea: Heterophyidae) infecting dolphins from the Atlantic Ocean.

We report for the first time the infection of dolphins with Ascocotyle longa found in the intestines of three different species, Sotalia guianensis, Steno bredanensis, and Tursiops truncatus gephyreus, which were found washed ashore along the southeastern and southern Brazilian coast. The worms were identified based on morphological and molecular data using the 28S rDNA gene and the COI gene. Specimens of A. longa from the pinniped Otaria flavescens were also analyzed. As the first isolation of A. longa from cetaceans, the present study increases the distribution area and range of definitive hosts of this trematode, and provides new molecular data to complement the phylogeny of the group in future studies, thus contributing to the scientific knowledge of this potentially zoonotic parasite.

Wearable Technology to Detect Motor Fluctuations in Parkinson's Disease Patients: Current State and Challenges.

Monitoring of motor symptom fluctuations in Parkinson's disease (PD) patients is currently performed through the subjective self-assessment of patients. Clinicians require reliable information about a fluctuation's occurrence to enable a precise treatment rescheduling and dosing adjustment. In this review, we analyzed the utilization of sensors for identifying motor fluctuations in PD patients and the application of machine learning techniques to detect fluctuations. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ten studies were included between January 2010 and March 2021, and their main characteristics and results were assessed and documented. Five studies utilized daily activities to collect the data, four used concrete scenarios executing specific activities to gather the data, and only one utilized a combination of both situations. The accuracy for classification was 83.56-96.77%. In the studies evaluated, it was not possible to find a standard cleaning protocol for the signal captured, and there is significant heterogeneity in the models utilized and in the different features introduced in the models (using spatiotemporal characteristics, frequential characteristics, or both). The two most influential factors in the good performance of the classification problem are the type of features utilized and the type of model.

Design of Liposomes Carrying HelixComplex Snail Mucus: Preliminary Studies.

In recent decades liposomes have been used in different field thanks to their ability to act as a vehicle for a wide range of biomolecules, their great versatility and their easy production. The aim of this study was to evaluate liposomes as a vehicle for the actives present in the HelixComplex (HC) snail mucus for topical delivery. Liposomes composed of a mixture of phosphatidylcholine, cholesterol and octadecylamine were prepared with and without HC (empty liposomes) and their biological efficacy was tested by evaluating cell viability and migration. HC-loaded liposomes (LHC) were stable throughout 60 days of observation, and showed interesting effects on wound healing reconstitution. In particular, we observed that 25 µg/mL LHC were already able to induce a higher cell monolayer reconstitution in comparison to the untreated samples and HC treated samples after only 4 h (28% versus 10% and 7%, p = 0.03 and p= 0.003, respectively). The effect was more evident at 24 h in comparison with the untreated control (54% versus 21.2% and 41.6%, p = 0.006 and p = NS, respectively). These results represent a preliminary, but promising, novelty in the delivery strategy of the actives present in the HelixComplex mucus.

Thyroid Hormone Signaling in Embryonic Stem Cells: Crosstalk with the Retinoic Acid Pathway.

While the role of thyroid hormones (THs) during fetal and postnatal life is well-established, their role at preimplantation and during blastocyst development remains unclear. In this study, we used an embryonic stem cell line isolated from rat (RESC) to study the effects of THs and retinoic acid (RA) on early embryonic development during the pre-implantation stage. The results showed that THs play an important role in the differentiation/maturation processes of cells obtained from embryoid bodies (EB), with thyroid hormone nuclear receptors (TR) (TRα and TRß), metabolic enzymes (deiodinases 1, 2, 3) and membrane transporters (Monocarboxylate transporters -MCT- 8 and 10) being expressed throughout in vitro differentiation until the Embryoid body (EB) stage. Moreover, thyroid hormone receptor antagonist TR (1-850) impaired RA-induced neuroectodermal lineage specification. This effect was significantly higher when cells were treated with retinoic acid (RA) to induce neuroectodermal lineage, studied through the gene and protein expression of nestin, an undifferentiated progenitor marker from the neuroectoderm lineage, as established by nestin mRNA and protein regulation. These results demonstrate the contribution of the two nuclear receptors, TR and RA, to the process of neuroectoderm maturation of the in vitro model embryonic stem cells obtained from rat.

Early CSF Biomarkers and Late Functional Outcomes in Spinal Cord Injury. A Pilot Study.

Although, biomarkers are regarded as an important tool for monitoring injury severity and treatment efficacy, and for predicting clinical evolution in many neurological diseases and disorders including spinal cord injury, there is still a lack of reliable biomarkers for the assessment of clinical course and patient outcome. In this study, a biological dataset of 60 cytokines/chemokines, growth factorsm and intracellular and extracellular matrix proteins, analyzed in CSF within 24 h of injury, was used for correlation analysis with the clinical dataset of the same patients. A heat map was generated of positive and negative correlations between biomarkers and clinical rating scale scores at discharge, and between biomarkers and changes in clinical scores during the observation period. Using very stringent statistical criteria, we found 10 molecules which correlated with clinical scores at discharge, and five molecules, which correlated with changes in clinical scores. The proposed methodology may be useful for generating hypotheses regarding "predictive" and "treatment effectiveness" biomarkers, thereby suggesting potential candidates for disease-modifying therapies using a "bed-to-bench" approach.

Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview.

Molecular and cellular research modalities for the study of liver pathologies have been tremendously improved over the recent decades. Advanced technologies offer novel opportunities to establish cell isolation techniques with excellent purity, paving the path for 2D and 3D microscopy and high-throughput assays (e.g., bulk or single-cell RNA sequencing). The use of stem cell and organoid research will help to decipher the pathophysiology of liver diseases and the interaction between various parenchymal and non-parenchymal liver cells. Furthermore, sophisticated animal models of liver disease allow for the in vivo assessment of fibrogenesis, portal hypertension and hepatocellular carcinoma (HCC) and for the preclinical testing of therapeutic strategies. The purpose of this review is to portray in detail novel in vitro and in vivo methods for the study of liver cell biology that had been presented at the workshop of the 8th meeting of the European Club for Liver Cell Biology (ECLCB-8) in October of 2018 in Bonn, Germany.

White Matter and Neuroprotection in Alzheimer's Dementia.

Myelin is the main component of the white matter of the central nervous system (CNS), allowing the proper electrical function of the neurons by ensheathing and insulating the axons. The extensive use of magnetic resonance imaging has highlighted the white matter alterations in Alzheimer's dementia (AD) and other neurodegenerative diseases, alterations which are early, extended, and regionally selective. Given that the white matter turnover is considerable in the adulthood, and that myelin repair is currently recognized as being the only true reparative capability of the mature CNS, oligodendrocyte precursor cells (OPCs), the cells that differentiate in oligodendrocyte, responsible for myelin formation and repair, are regarded as a potential target for neuroprotection. In this review, several aspects of the OPC biology are reviewed. The histology and functional role of OPCs in the neurovascular-neuroglial unit as described in preclinical and clinical studies on AD is discussed, such as the OPC vulnerability to hypoxia-ischemia, neuroinflammation, and amyloid deposition. Finally, the position of OPCs in drug discovery strategies for dementia is discussed.

The taxonomic status of Skrjabinalius guevarai Gallego & Selva, 1979 (Nematoda: Pseudaliidae) and the synonymy of Skrjabinalius Delyamure, 1942 and Halocercus Baylis & Daubney, 1925.

Within the cetacean lungworm family Pseudaliidae Raillet & Henry, 1909, the distinction between the two genera of the subfamily Halocercinae Delamure, 1952, i.e. Halocercus Baylis & Daubney, 1925 and Skrjabinalius Delyamure, 1942, is principally based on the structure and shape of the male copulatory bursa. In species of Halocercus, the bursa is unlobed, whereas in the two species included in Skrjabinalius, S. cryptocephalus Delyamure, 1942 and Skrjabinalius guevarai Gallego & Selva, 1979, the bursa is described as clearly lobed. During a parasitological analysis of cetaceans from the Spanish Mediterranean, we collected a number of specimens of S. guevarai with variable levels of bursal lobulation, including individuals with unlobed bursae. Examination of voucher specimens of the type-species of Halocercus, H. delphini Baylis & Daubney, 1925, collected from cetaceans in the North-East Atlantic revealed the same variations in bursal shape, and the same arrangement of bursal rays and papillae. A morphometric comparison did not reveal substantial differences between both species. Moreover, Maximum Likelihood and Bayesian Inference analyses of the second internal transcribed spacer (ITS2) sequences of 11 specimens of S. guevarai and one of H. delphini grouped both species together, regardless of bursal shape, in a highly supported clade within the Pseudaliidae. Accordingly, we consider S. guevarai as a junior synonym of H. delphini. The great variability found in bursal lobulation in the type-species of Halocercus invalidates the use of this trait as a genus-level diagnostic character and, therefore, Skrjabinalius should also be considered synonymous with Halocercus.

Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat.

BACKGROUND: Hypoxic-ischemic (HI) encephalopathy causes life-long morbidity and premature mortality in term neonates. Therapies in addition to whole-body cooling are under development to treat the neonate at risk for HI encephalopathy, but are not a quickly measured serum inflammatory or neuronal biomarkers to rapidly and accurately identify brain injury in order to follow the efficacy of therapies. METHODS: In order to identify potential biomarkers for early inflammatory and neurodegenerative events after neonatal hypoxia-ischemia, both male and female Wistar rat pups at postnatal day 7 (P7) were used and had their right carotid artery permanently doubly occluded and exposed to 8% oxygen for 90 min. Sensory and cognitive parameters were assessed by open field, rotarod, CatWalk, and Morris water maze (MWM) test. Plasma and CSF biomarkers were investigated on the acute (24 h and 72 h) and chronic phase (4 weeks). Brains were assessed for gene expression analysis by quantitative RT-PCR Array. RESULTS: We found a delay of neurological reflex maturation in HI rats. We observed anxiolytic-like baseline behavior in males more than females following HI injury. HI rats held on the rotarod for a shorter time comparing to sham. HI injury impaired spatial learning ability on MWM test. The CatWalk assessment demonstrated a long-term deficit in gait parameters related to the hind paw. Proinflammatory biomarkers such as IL-6 in plasma and CCL2 and TNF-α in CSF showed an upregulation at 24 h after HI while other cytokines, such as IL-17A and CCL5, were upregulated after 72 h in CSF. At 24 h post-injury, we observed an increase of Edn1, Hif1-α, and Mmp9 mRNA levels in the ipsilateral vs the contralateral hemisphere of HI rats. An upregulation of genes involved with clotting and hematopoietic processes was observed 72 h post-injury. CONCLUSIONS: Our work showed that, in the immature brain, the HI injury induced an early increased production of several proinflammatory mediators detectable in plasma and CSF, followed by tissue damage in the hypoxic hemisphere and short-term as well as long-lasting neurobehavioral deficits.

Constitutive and LPS-stimulated secretome of porcine Vascular Wall-Mesenchymal Stem Cells exerts effects on in vitro endothelial angiogenesis.

BACKGROUND: MSCs secretome is under investigation as an alternative to whole-cell-based therapies, since it is enriched of bioactive molecules: growth factors, cytokines and chemokines. Taking into account the translational value of the pig model, the leading aim of the present paper was to characterize the secretome of porcine Vascular Wall-Mesenchymal Stem Cells (pVW-MSCs) and its change in presence of LPS stimulation. Moreover, considering the importance of angiogenesis in regenerative mechanisms, we analysed the effect of pVW-MSCs secretome on in vitro angiogenesis. RESULTS: Our results demonstrated that conditioned medium from unstimulated pVW-MSCs contained high levels of IL-8, GM-CSF, IFN-γ and other immunomodulatory proteins: IL-6 IL-18 IL-4 IL-2 IL-10. LPS modulates pVW-MSCs gene expression and secretome composition, in particular a significant increase of IL-6 and IL-8 was observed; conversely, the amount of GM-CSF, IFN-γ, IL-2, IL-4, IL-10 and IL-18 showed a significant transient decrease with the LPS stimulation. Conditioned medium from unstimulated pVW-MSCs induced in vitro endothelial angiogenesis, which is more evident when the conditioned medium was from LPS stimulated pVW-MSCs. CONCLUSIONS: The lines of evidence here presented shed a light on possible future application of secretome derived by pVW-MSCs on research studies in translational regenerative medicine.

Pericytes in the Gut.

This review chapter describes the current knowledge about the nature of pericytes in the gut, their interaction with endothelial cells in blood vessels, and their pathophysiological functions in the setting of chronic liver disease. In particular, it focuses on the role of these vascular cell types and related molecular signaling pathways in pathological angiogenesis associated with liver disease and in the establishment of the gut-vascular barrier and the potential implications in liver disease through the gut-liver axis.

Relationship between pressure ulcer risk based on Norton Scale and on the "Eating/Drinking" need assessment.

AIM: To study the relationship between pressure ulcer risk evaluated by the Norton Scale and inadequate fulfilment of Need 2 (Eating/Drinking) from the 14-need classification designed by Virginia Henderson. BACKGROUND: Assessing nutritional status and skin condition to implement preventive measures are important nursing interventions. Our hospital's standard procedure requires recording Norton Scale and Henderson Eating/Drinking Assessment results. METHODS: This was a descriptive cross-sectional study, analysing case histories of 219 patients in medical/surgical wards for >24 hr with nursing care recorded in the GACELA Care computer application. Patient sociodemographic variables and evaluation concepts from the Norton Scale and Eating/Drinking were studied. RESULTS: A statistically significant relationship (p < 0.05; 95% CI: 0.61, 2.83) was seen between inadequate Eating/Drinking need fulfilment and increased pressure ulcer risk. Pressure ulcer risk was generally low in the sample, with mainly no or minimum risk (77.3%); the oldest age group had the highest risk. Self-care autonomy was the most frequently assessed item in Eating/Drinking (42%). CONCLUSIONS: A relationship was found between Norton Scale risk results and Eating/Drinking need assessment results. The greater the pressure ulcer risk, the more likely was inadequate need satisfaction (poor nutritional status). IMPLICATIONS: To help identify pressure ulcer risk, nurses should assess patients' eating independence. Safeguarding nutritional status and preventing pressure ulcers are nursing skills associated with quality nursing care.

Lethal Influenza in Two Related Adults with Inherited GATA2 Deficiency.

The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.