Outlier admissions of medical patients: Prognostic implications of outlying patients. The experience of the Hospital of Mestre

ABSTRACT The admission of a patient in wards other than the appropriate ones, known as the patient outlying phenomenon, involves both Medicine and Geriatric Units of many Hospitals. The aims were to learn more about the prognosis of the outlying patients, we investigated 3828 consecutive patients hospitalized in Medicine and Geriatrics of our hub Hospital during the year 2012. We compared patients\u2019 mean hospital length of stay, survival, and early readmission according to their outlying status. The mean hospital length of stay did not significantly differ between the two groups, either for Medicine (9.8 days for outliers and 10.0 for in-ward) or Geriatrics (13.0 days for both). However, after adjustment for age and sex, the risk of death was about twice as high for outlier patients admitted into surgical compared to medical areas (hazard ratio 1.8, 1.2-2.5 95% confidence interval). Readmission within 90 days from the first discharge was more frequent for patients admitted as outliers (26.1% vs 14.2%, P<0.0001). We highlight some critical aspects of an overcrowded hospital, as the shortage of beds in Medicine and Geriatrics and the potential increased clinical risk denoted by deaths or early readmission for medical outlier patients when assigned to inappropriate wards. There is the need to reorganize beds allocation involving community services, improve in-hospital bed management, an extent diagnostic procedures for outlier patients admitted in nonmedical wards

Self-regulated ligand-metal charge transfer upon lithium ion de-intercalation process from LiCoO2 to CoO2

Understanding the role of metal and oxygen in the redox process of layered 3d transition metal oxides is crucial to build high density and stable next generation Li-ion batteries. We combine hard X-ray photoelectron spectroscopy and ab-initio-based cluster model simulations to study the electronic structure of prototypical end-members LiCoO2 and CoO2. The role of cobalt and oxygen in the redox process is analyzed by optimizing the values of d-d electron repulsion and ligand-metal p-d charge transfer to the Co 2p spectra. We clarify the nature of oxidized cobalt ions by highlighting the transition from positive to negative ligand-to-metal charge transfer upon Li+ de-intercalation.Comment: Using X-ray photoelectron spectroscopy and ab-initio simulations, this study reveals the changes in electronic structure upon discharge for LixCoO2, an archetypal cathode material for lithium-ion batterie

Depth-resolving the redox compensation mechanism in LixNiO2

The performances of lithium-ion batteries are set by the electrodes materials capacity to exchange lithium ions and electrons faster and reversibly. To this goal Ni-rich layered metal oxides, especially LiNiO2, are attractive electrode candidate to achieve both high voltage and capacities. Despite its attractiveness, several drawbacks for its industrialization are related to different form of surface and bulk instabilities. These instabilities are due to redox process involving the charge transfer between cations and anions. Therefore, a fundamental understanding based on further experimental evidence is required to resolve of charge transfer between the cation and anion from the surface to the bulk in LiNiO2. Herein, we resolve the role of nickel and oxygen in the charge compensation process in LixNiO2 electrodes from the extreme surface down to 30 nm by energy-dependent core-level HAXPES supported by ab initio simulation. We emphasize the central role of oxygen in the bulk charge compensation mechanism from LiNiO2 to NiO2 due to the negative charge transfer and bond/charge-disproportionation characters of LiNiO2. This bulk behavior is in turn responsible for surface deoxygenation and nickel reduction upon delithiation

HS6ST1 Insufficiency Causes Self-Limited Delayed Puberty in Contrast With Other GnRH Deficiency Genes

Context: Self-limited delayed puberty (DP) segregates in an autosomal-dominant pattern, but the genetic basis is largely unknown. Although DP is sometimes seen in relatives of patients with hypogonadotropic hypogonadism (HH), mutations in genes known to cause HH that segregate with the trait of familial self-limited DP have not yet been identified. Objective: To assess the contribution of mutations in genes known to cause HH to the phenotype of self-limited DP. Design, Patients, and Setting: We performed whole-exome sequencing in 67 probands and 93 relatives from a large cohort of familial self-limited DP, validated the pathogenicity of the identified gene variant in vitro, and examined the tissue expression and functional requirement of the mouse homolog in vivo. Results: A potentially pathogenic gene variant segregating with DP was identified in 1 of 28 known HH genes examined. This pathogenic variant occurred in HS6ST1 in one pedigree and segregated with the trait in the six affected members with heterozygous transmission (P = 3.01 x 10 -5 ). Biochemical analysis showed that this mutation reduced sulfotransferase activity in vitro. Hs6st1 mRNA was expressed in peripubertal wild-type mouse hypothalamus. GnRH neuron counts were similar in Hs6st1 (+/-) and Hs6st1(+/+) mice, but vaginal opening was delayed in Hs6st1(+/-) mice despite normal postnatal growth. Conclusions: We have linked a deleterious mutation in HS6ST1 to familial self-limited DP and show that heterozygous Hs6st1 loss causes DP in mice. In this study, the observed overlap in potentially pathogenic mutations contributing to the phenotypes of self-limited DP and HH was limited to this one gene.Peer reviewe

SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability

Innervation of the hypothalamic median eminence by Gonadotropin-Releasing Hormone (GnRH) neurons is vital to ensure puberty onset and successful reproduction. However, the molecular and cellular mechanisms underlying median eminence development and pubertal timing are incompletely understood. Here we show that Semaphorin-6A is strongly expressed by median eminence-resident oligodendrocytes positioned adjacent to GnRH neuron projections and fenestrated capillaries, and that Semaphorin-6A is required for GnRH neuron innervation and puberty onset. In vitro and in vivo experiments reveal an unexpected function for Semaphorin-6A, via its receptor Plexin-A2, in the control of median eminence vascular permeability to maintain neuroendocrine homeostasis. To support the significance of these findings in humans, we identify patients with delayed puberty carrying a novel pathogenic variant of SEMA6A. In all, our data reveal a role for Semaphorin-6A in regulating GnRH neuron patterning by tuning the median eminence vascular barrier and thereby controlling puberty onset

Comparative genomics of European Avian Pathogenic E. coli (APEC)

Background Avian pathogenic Escherichia coli (APEC) causes colibacillosis, which results in significant economic losses to the poultry industry worldwide. However, the diversity between isolates remains poorly understood. Here, a total of 272 APEC isolates collected from the United Kingdom (UK), Italy and Germany were characterised using multiplex polymerase chain reactions (PCRs) targeting 22 equally weighted factors covering virulence genes, R-type and phylogroup. Following these analysis, 95 of the selected strains were further analysed using Whole Genome Sequencing (WGS). Results The most prevalent phylogroups were B2 (47%) and A1 (22%), although there were national differences with Germany presenting group B2 (35.3%), Italy presenting group A1 (53.3%) and UK presenting group B2 (56.1%) as the most prevalent. R-type R1 was the most frequent type (55%) among APEC, but multiple R-types were also frequent (26.8%). Following compilation of all the PCR data which covered a total of 15 virulence genes, it was possible to build a similarity tree using each PCR result unweighted to produce 9 distinct groups. The average number of virulence genes was 6-8 per isolate, but no positive association was found between phylogroup and number or type of virulence genes. A total of 95 isolates representing each of these 9 groupings were genome sequenced and analysed for in silico serotype, Multilocus Sequence Typing (MLST), and antimicrobial resistance (AMR). The UK isolates showed the greatest variability in terms of serotype and MLST compared with German and Italian isolates, whereas the lowest prevalence of AMR was found for German isolates. Similarity trees were compiled using sequencing data and notably single nucleotide polymorphism data generated ten distinct geno-groups. The frequency of geno-groups across Europe comprised 26.3% belonging to Group 8 representing serogroups O2, O4, O18 and MLST types ST95, ST140, ST141, ST428, ST1618 and others, 18.9% belonging to Group 1 (serogroups O78 and MLST types ST23, ST2230), 15.8% belonging to Group 10 (serogroups O8, O45, O91, O125ab and variable MLST types), 14.7% belonging to Group 7 (serogroups O4, O24, O35, O53, O161 and MLST type ST117) and 13.7% belonging to Group 9 (serogroups O1, O16, O181 and others and MLST types ST10, ST48 and others). The other groups (2, 3, 4, 5 and 6) each contained relatively few strains. However, for some of the genogroups (e.g. groups 6 and 7) partial overlap with SNPs grouping and PCR grouping (matching PCR groups 8 (13 isolates on 22) and 1 (14 isolates on 16) were observable). However, it was not possible to obtain a clear correlation between genogroups and unweighted PCR groupings. This may be due to the genome plasticity of E. coli that enables strains to carry the same virulence factors even if the overall genotype is substantially different. Conclusions The conclusion to be drawn from the lack of correlations is that firstly, APEC are very diverse and secondly, it is not possible to rely on any one or more basic molecular or phenotypic tests to define APEC with clarity, reaffirming the need for whole genome analysis approaches which we describe here. This study highlights the presence of previously unreported serotypes and MLSTs for APEC in Europe. Moreover, it is a first step on a cautious reconsideration of the merits of classical identification criteria such as R typing, phylogrouping and serotyping

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference