The diseases we cause: Iatrogenic illness in a department of internal medicine

BACKGROUND: The aim of this study was to estimate the incidence, main causes, and risk factors of iatrogenic disease occurring in a department of internal medicine. METHODS: Over a 1-year period, physicians systematically filled out a 2-page questionnaire for all patients admitted to the ward. A database was created and the data were statistically analyzed. Patients undergoing immunosuppressive, chemo-, or radiation therapy were excluded. Missing data were completed by reviewing the patients' charts. The patients were then divided into two groups: those with and those without iatrogenic disease. The groups were compared using several parameters including gender, age, social features, days of hospitalization, associated illness, functional status, medical impression, prognosis, associated renal or liver function impairment, drugs taken daily, and outcome. In the group with iatrogenic disease, the type, severity, and predictability were also analyzed. RESULTS: Of the 879 patients admitted to the ward, 445 completed questionnaires and were included in the study. A total of 102 patients (22.9%) developed 121 iatrogenic events. Forty-four patients (43.1%) were admitted for iatrogenic illness, 10 (9.8%) developed life-threatening events, and in 3 (6.8%) it was the cause of death. Fifty-eight patients (56.8%) registered 77 episodes of iatrogenic disease during their hospital stay, 20 (19.6%) developed life-threatening events, and 9 (11.7%) died, 4 (5.2%) of an iatrogenic cause (nosocomial infections). Significant differences were found in 20 out of 26 parameters studied (p<0.005 for all cases; 95% confidence interval). Eighteen percent of all iatrogenic disease was severe, 61.9% predictable, 54.5% avoidable, and 59% drug-related, 80% of which was due to side effects or adverse reactions. Infection and metabolic and electrolyte disorders were the most frequent effects. CONCLUSIONS: It is possible to identify risk factors for iatrogenic events. Chronically ill elderly inpatients are the main target of iatrogenic events

Markedly Divergent Tree Assemblage Responses to Tropical Forest Loss and Fragmentation across a Strong Seasonality Gradient

We examine the effects of forest fragmentation on the structure and composition of tree assemblages within three seasonal and aseasonal forest types of southern Brazil, including evergreen, Araucaria, and deciduous forests. We sampled three southernmost Atlantic Forest landscapes, including the largest continuous forest protected areas within each forest type. Tree assemblages in each forest type were sampled within 10 plots of 0.1 ha in both continuous forests and 10 adjacent forest fragments. All trees within each plot were assigned to trait categories describing their regeneration strategy, vertical stratification, seed-dispersal mode, seed size, and wood density. We detected differences among both forest types and landscape contexts in terms of overall tree species richness, and the density and species richness of different functional groups in terms of regeneration strategy, seed dispersal mode and woody density. Overall, evergreen forest fragments exhibited the largest deviations from continuous forest plots in assemblage structure. Evergreen, Araucaria and deciduous forests diverge in the functional composition of tree floras, particularly in relation to regeneration strategy and stress tolerance. By supporting a more diversified light-demanding and stress-tolerant flora with reduced richness and abundance of shade-tolerant, old-growth species, both deciduous and Araucaria forest tree assemblages are more intrinsically resilient to contemporary human-disturbances, including fragmentation-induced edge effects, in terms of species erosion and functional shifts. We suggest that these intrinsic differences in the direction and magnitude of responses to changes in landscape structure between forest types should guide a wide range of conservation strategies in restoring fragmented tropical forest landscapes worldwide

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Serum biomarkers associated with SARS-CoV-2 severity

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio