Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors.

Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca2+ influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity.

Could strain echocardiography help to assess systolic function in critically ill COVID-19 patients?

Strain echocardiography enables the automatic quantification of the global longitudinal strain (GLS), which is a direct measure of ventricular shortening during systole. In the current context of overwhelmed ICUs and clinician shortage, GLS has the advantage to be quick and easy to measure by non-experts. However, little is known regarding its value to assess bi-ventricular systolic function in critically ill COVID-19 patients. Therefore, we designed a study to compare right and left ventricular GLS with classic echo-Doppler indices of systolic function, namely the ejection fraction for the left ventricle (LVEF) and the fractional area change (FAC), the tricuspid annular plane systolic excursion (TAPSE), and the tissue Doppler velocity of the basal free lateral wall (S') for the right ventricle. Eighty transthoracic echocardiographic evaluations done in 30 ICU patients with COVID-19 were analyzed. We observed a fair relationship (r = 0.73, p < 0.01) between LVEF and left ventricular GLS. The GLS cut-off value of - 22% identified a LVEF < 50% with a sensitivity of 63% and a specificity of 80%. All patients with a GLS > - 17% had a LVEF < 50%. Although statistically significant, relationships between FAC (r = 0.41, p < 0.01), TAPSE (r = 0.26, p < 0.05) and right ventricular GLS were weak. S' was not correlated with right ventricular GLS. In conclusion, left ventricular GLS was useful to assess left ventricular systolic function. However, right ventricular GLS was poorly correlated with FAC, TAPSE and S'. Further studies are needed to clarify what is the best method to assess right ventricular systolic function in ICU patients with COVID-19.

Impairment of adenosinergic system in Rett syndrome: Novel therapeutic target to boost BDNF signalling.

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.

Numerical investigation of parametric resonance due to hydrodynamic coupling in a realistic wave energy converter.

Representative models of the nonlinear behavior of floating platforms are essential for their successful design, especially in the emerging field of wave energy conversion where nonlinear dynamics can have substantially detrimental effects on the converter efficiency. The spar buoy, commonly used for deep-water drilling, oil and natural gas extraction and storage, as well as offshore wind and wave energy generation, is known to be prone to experience parametric resonance. In the vast majority of cases, parametric resonance is studied by means of simplified analytical models, considering only two degrees of freedom (DoFs) of archetypical geometries, while neglecting collateral complexity of ancillary systems. On the contrary, this paper implements a representative 7-DoF nonlinear hydrodynamic model of the full complexity of a realistic spar buoy wave energy converter, which is used to verify the likelihood of parametric instability, quantify the severity of the parametrically excited response and evaluate its consequences on power conversion efficiency. It is found that the numerical model agrees with expected conditions for parametric instability from simplified analytical models. The model is then used as a design tool to determine the best ballast configuration, limiting detrimental effects of parametric resonance while maximizing power conversion efficiency.

Adenosine A2A Receptors Modulate α-Synuclein Aggregation and Toxicity.

Abnormal accumulation of aggregated α-synuclein (aSyn) is a hallmark of sporadic and familial Parkinson's disease (PD) and related synucleinopathies. Recent studies suggest a neuroprotective role of adenosine A2A receptor (A2AR) antagonists in PD. Nevertheless, the precise molecular mechanisms underlying this neuroprotection remain unclear. We assessed the impact of A2AR blockade or genetic deletion (A2AR KO) on synaptic plasticity and neuronal cell death induced by aSyn oligomers. We found that impairment of LTP associated with aSyn exposure was rescued in A2AR KO mice or upon A2AR blockade, through an NMDA receptor-dependent mechanism. The mechanisms underlying these effects were evaluated in SH-SY5Y cells overexpressing aSyn and rat primary neuronal cultures exposed to aSyn. Cell death in both conditions was prevented by selective A2AR antagonists. Interestingly, blockade of these receptors did not interfere with aSyn oligomerization but, instead, reduced the percentage of cells displaying aSyn inclusions. Altogether, our data raise the possibility that the well-documented effects of A2AR antagonists involve the control of the latter stages of aSyn aggregation, thereby preventing the associated neurotoxicity. These findings suggest that A2AR represent an important target for the development of effective drugs for the treatment of PD and related synucleinopathies.

Burnout and occupational stress in the medical residents of Oncology, Haematology and Radiotherapy: a prevalence and predictors study in Portugal.

Burnout is a professional syndrome associated with stress caused by overwork. Our aim was to calculate the prevalence of burnout and stress on medical residents of Oncology, Haematology and Radiotherapy in Portugal, as well as to determine predictors of burnout and stress. An anonymous questionnaire was applied (n = 118). Statistical analysis consisted of a descriptive and inferential analysis. The prevalence of burnout and stress was calculated to be 45.2 and 50%, respectively. The dimensions that generated higher levels of stress were 'dealing with patients' and 'overwork'. Burnout was directly related with stress dimension 'overwork'. The prevalence of burnout in Portuguese oncological residents is high as in other European countries and in the U.S. Therefore, interventional strategies can be designed.

How immunogenetically different are domestic pigs from wild boars: a perspective from single-nucleotide polymorphisms of 19 immunity-related candidate genes.

The coexistence of wild boars and domestic pigs across Eurasia makes it feasible to conduct comparative genetic or genomic analyses for addressing how genetically different a domestic species is from its wild ancestor. To test whether there are differences in patterns of genetic variability between wild and domestic pigs at immunity-related genes and to detect outlier loci putatively under selection that may underlie differences in immune responses, here we analyzed 54 single-nucleotide polymorphisms (SNPs) of 19 immunity-related candidate genes on 11 autosomes in three pairs of wild boar and domestic pig populations from China, Iberian Peninsula, and Hungary. Our results showed no statistically significant differences in allele frequency and heterozygosity across SNPs between three pairs of wild and domestic populations. This observation was more likely due to the widespread and long-lasting gene flow between wild boars and domestic pigs across Eurasia. In addition, we detected eight coding SNPs from six genes as outliers being under selection consistently by three outlier tests (BayeScan2.1, FDIST2, and Arlequin3.5). Among four non-synonymous outlier SNPs, one from TLR4 gene was identified as being subject to positive (diversifying) selection and three each from CD36, IFNW1, and IL1B genes were suggested as under balancing selection. All of these four non-synonymous variants were predicted as being benign by PolyPhen-2. Our results were supported by other independent lines of evidence for positive selection or balancing selection acting on these four immune genes (CD36, IFNW1, IL1B, and TLR4). Our study showed an example applying a candidate gene approach to identify functionally important mutations (i.e., outlier loci) in wild and domestic pigs for subsequent functional experiments.

Percutaneous left ventricular assistance in cardiogenic shock due to Takotsubo cardiomyopathy secondary to status epilepticus.

Takotsubo syndrome is an acute reversible cardiomyopathy with left ventricular dysfunction and a clinical presentation similar to an acute coronary syndrome. Emotional or physical triggers can cause it, including neurological conditions such as seizures. We describe a case of a woman in her 50s with Takotsubo syndrome secondary to status epilepticus, presenting with cardiac arrest and cardiogenic shock. We excluded acute coronary syndrome with coronary angiography. Despite inotropic support, she remained haemodynamically unstable and a percutaneous left ventricular assistance with an Impella CP catheter was initiated. This resulted in a quick weaning of haemodynamic support and recovery of left ventricle systolic function in 2 weeks. This case illustrates the importance of a high index of suspicion to make this diagnosis and link it to neurological triggers, as well as to consider mechanical circulatory support in managing cardiogenic shock due to this cardiomyopathy.

Left atrial strain is associated with distinct inflammatory and immune profile in patients with COVID-19 pneumonia.

INTRODUCTION: SARS-CoV-2 infection is associated with multiple cardiac manifestations. Left atrial strain (LA-S) by speckle tracking echocardiography (STE) is a novel transthoracic echocardiography (TTE) measure of LA myocardial deformation and diastolic dysfunction, which could lead to early recognition of cardiac injury in severe COVID-19 patients with possible implications on clinical management, organ dysfunction, and mortality. Cardiac injury may occur by direct viral cytopathic effects or virus-driven immune activation, resulting in heart infiltration by inflammatory cells, despite limited and conflicting data are available on myocardial histology. PURPOSE: We aimed to explore LA-S and immune profiles in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. METHODS: We enrolled 30 patients > 18 years with positive SARS-CoV-2 RT-PCR, admitted to ICU. Acute myocardial infarction and pulmonary embolism were exclusion criteria. On days D1, D3, and D7 after ICU admission, patients performed TTE, hemogram, cardiac (pro-BNP; troponin) and inflammatory biomarkers (ESR; ferritin; IL1ß; IL6; CRP; d-dimer; fibrinogen; PCT; adrenomedullin, ADM), and immunophenotyping by flow cytometry. RESULTS: Patient's mean age was 60.7 y, with 63% males. Hypertension was the most common risk factor (73%; with 50% of patients under ACEi or ARA), followed by obesity (40%, mean BMI = 31 kg/m2). Cardiac dysfunction was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. Mortality, hospitalization days, remdesivir use, organ dysfunction, cardiac and serum biomarkers were not different between patients with (DYS) and without cardiac dysfunction (nDYS), except for ADM (increased in nDYS group at D7). From the 77 TTE, there was a striking difference between diastolic dysfunction evaluation by classic criteria compared to STE (28.6% vs. 57.1%, p = 0.0006). Lower reservoir (Ɛ) and contraction (ƐCT) LA-S correlated with IL-6 (Ɛ, p = 0.009, r = - 0.47; ƐCT, p = 0.0002, r = - 0.63) and central memory CD4 T-cells (ƐCT, p = 0.049, r = - 0.24). Along all timepoints, DYS patients showed persistent low lymphocyte counts that recovered at D7 in nDYS patients. DYS patients had lower platelets at D3 and showed a slower recovery in platelet counts and CRP levels; the latter significantly decreased at D7 in nDYS patients (p = 0.009). Overall, patients recovered with an increasing P/F ratio, though to a lesser extent in DYS patients. DISCUSSION: Our study shows that LA-S may be a more sensitive marker for diastolic dysfunction in severe COVID-19, which could identify patients at risk for a protracted inflammatory state. A differential immune trait in DYS patients at ICU admission, with persistent lymphopenia, enriched CM T-cells, and higher IL-6 may suggest distinct inflammatory states or migration patterns in patients that develop cardiac injury.

Development of a novel electrochemical biosensor based on plastic antibodies for detection of STEAP1 biomarker in cancer.

STEAP1 is a cell surface protein of the STEAP family whose main function focuses on intercellular communication and cell growth. STEAP1 is considered a promising putative biomarker and a candidate target for prostate cancer treatment. For specific and selective detection of STEAP1, a molecularly imprinted polymers (MIP) was developed on a screen-printed electrode (C-SPE) whose surface was modified with a nanocomposite based on carbon nanotubes decorated with dendritic platinum nanoparticles (CNTs- PAH /Pt). Then, the MIPs were produced on the modified C-SPE by electropolymerization of a mixture of STEAP1 and a monomer (pyrrole-2-carboxylic acid). Then, the protein was removed from the polymeric network by enzymatic treatment with trypsin, which created the specific template cavities for further STEAP1 detection. Electrochemical techniques such as EIS and CV were used to follow the chemical modification steps of C-SPE. The analytical performance of the biosensor was evaluated by SWV in PBS buffer and in lysates of neoplastic prostate cancer cells (LNCaP) extracts. The MIP material showing a linear range from 130 pg/ml to 13 µg/ml. Overall, the biosensor exhibits essential properties such as selectivity, sensitivity and reproducibility for its application in medical and clinical research diagnosis and/or prognosis of prostate cancer.

Neuroprotection afforded by adenosine A2A receptor blockade is modulated by corticotrophin-releasing factor (CRF) in glutamate injured cortical neurons.

In situations of hypoxia, glutamate excitotoxicity induces neuronal death. The release of extracellular adenosine is also triggered and is accompanied by an increase of the stress mediator, corticotrophin-releasing factor (CRF). Adenosine A(2A) receptors contribute to glutamate excitoxicity and their blockade is effective in stress-induced neuronal deficits, but the involvement of CRF on this effect was never explored. We now evaluated the interaction between A(2A) and CRF receptors (CRFR) function, upon glutamate insult. Primary rat cortical neuronal cultures (9 days in vitro) expressing both CRF(1)R and CRF(2)R were challenged with glutamate (20-1000 µM, 24 h). CRF(1)R was found to co-localize with neuronal markers and CRF(2)R to be present in both neuronal and glial cells. The effects of the CRF and A(2A) receptors ligands on cell viability were measured using propidium iodide and Syto-13 fluorescence staining. Glutamate decreased cell viability in a concentration-dependent manner. Urocortin (10 pM), an agonist of CRF receptors, increased cell survival in the presence of glutamate. This neuroprotective effect was abolished by blocking either CRF(1)R or CRF(2)R with antalarmin (10 nM) or anti-Sauvagine-30 (10 nM), respectively. The blockade of A(2A) receptors with a selective antagonist SCH 58261 (50 nM) improved cell viability against the glutamate insult. This effect was dependent on CRF(2)R, but not on CRF(1)R activation. Overall, these data show a protective role of CRF in cortical neurons, against glutamate-induced death. The neuroprotection achieved by A(2A) receptors blockade requires CRF(2)R activation. This interaction between the adenosine and CRF receptors can explain the beneficial effects of using A(2A) receptor antagonists against stress-induced noxious effects.

Population screening for chronic kidney disease: a survey involving 38,721 Brazilians.

BACKGROUND: It is known that chronic kidney disease (CKD) is continuously increasing all over the world, but the available numbers of affected subjects are mostly collected from renal replacement therapy services and they correspond to individuals with end-stage renal disease. The aim of the present study was to diagnose CKD in its earliest stages in the general population based on detection of proteinuria. METHODS: In public prevention campaigns, from 2005 to 2010, 38 721 inhabitants were evaluated in the state of Sao Paulo (Brazil). Screening procedures included a dipstick test, blood pressure measurement and application of a medical questionnaire. RESULTS: In the whole population, urine samples of 37 771 individuals (mean age: 44.59 + 21.70, 55.74% females) were evaluated, 7.3% presented proteinuria (1+ or more) in the screening test and 85.5% of them had no previous knowledge of this urinary abnormality. Those individuals were referred for further clinical evaluation in order to confirm the detected alterations. Considering being diabetic and/or hypertensive as important risk factors for CKD, it was observed that they corresponded to 9.7 and 28.4% of the population screened for proteinuria, respectively. Newly detected cases of possible CKD, diabetes and hypertension corresponded to 6.2, 0.3 and 6.5%, respectively. CONCLUSIONS: This initiative provided information on proteinuria and possible cases of CKD based on a large sampling of the Brazilian population. Proteinuria was detected in 7.3% of these individuals, and such prevalence is similar to that previously described in developed countries.

Characteristic Immune Dynamics in COVID-19 Patients with Cardiac Dysfunction.

Background: We aimed to explore immune parameters in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. Methods: A total of 30 COVID-19 patients >18 years admitted to the ICU were studied on days D1, D3 and D7 after admission. Cardiac function was assessed using speckle-tracking echocardiography (STE). Peripheral blood immunophenotyping, cardiac (pro-BNP; troponin) and inflammatory biomarkers were simultaneously evaluated. Results: Cardiac dysfunction (DYS) was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. High-sensitivity cardiac troponin (hs-cTn) was detectable in 43.3% of the patients with a median value of 13.00 ng/L. There were no significant differences between DYS and nDYS patients regarding mortality, organ dysfunction, cardiac (including hs-cTn) or inflammatory biomarkers. Patients with DYS showed persistently lower lymphocyte counts (median 896 [661−1837] cells/µL vs. 2141 [924−3306] cells/µL, p = 0.058), activated CD3 (median 85 [66−170] cells/µL vs. 186 [142−259] cells/µL, p = 0.047) and CD4 T cells (median 33 [28−40] cells/µL vs. 63 [48−79] cells/µL, p = 0.005), and higher effector memory T cells (TEM) at baseline (CD4%: 10.9 [6.4−19.2] vs. 5.9 [4.2−12.8], p = 0.025; CD8%: 15.7 [7.9−22.8] vs. 8.1 [7.7−13.7], p = 0.035; CD8 counts: 40 cells/µL [17−61] vs. 10 cells/µL [7−17], p = 0.011) than patients without cardiac dysfunction. Conclusion: Our study suggests an association between the immunological trait and cardiac dysfunction in severe COVID-19 patients.

Plastic Antibody of Polypyrrole/Multiwall Carbon Nanotubes on Screen-Printed Electrodes for Cystatin C Detection.

This work reports the design of a novel plastic antibody for cystatin C (Cys-C), an acute kidney injury biomarker, and its application in point-of-care (PoC) testing. The synthetic antibody was obtained by tailoring a molecularly imprinted polymer (MIP) on a carbon screen-printed electrode (SPE). The MIP was obtained by electropolymerizing pyrrole (Py) with carboxylated Py (Py-COOH) in the presence of Cys-C and multiwall carbon nanotubes (MWCNTs). Cys-C was removed from the molecularly imprinted poly(Py) matrix (MPPy) by urea treatment. As a control, a non-imprinted poly(Py) matrix (NPPy) was obtained by the same procedure, but without Cys-C. The assembly of the MIP material was evaluated in situ by Raman spectroscopy and the binding ability of Cys-C was evaluated by the cyclic voltammetry (CV) and differential pulse voltammetry (DPV) electrochemical techniques. The MIP sensor responses were measured by the DPV anodic peaks obtained in the presence of ferro/ferricyanide. The peak currents decreased linearly from 0.5 to 20.0 ng/mL of Cys-C at each 20 min successive incubation and a limit of detection below 0.5 ng/mL was obtained at pH 6.0. The MPPy/SPE was used to analyze Cys-C in spiked serum samples, showing recoveries <3%. This device showed promising features in terms of simplicity, cost and sensitivity for acute kidney injury diagnosis at the point of care.

IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer's disease.

Neuroinflammation in patients with Alzheimer's disease (AD) and related mouse models has been recognized for decades, but the contribution of the recently described meningeal immune population to AD pathogenesis remains to be addressed. Here, using the 3xTg-AD model, we report an accumulation of interleukin-17 (IL-17)-producing cells, mostly γδ T cells, in the brain and the meninges of female, but not male, mice, concomitant with the onset of cognitive decline. Critically, IL-17 neutralization into the ventricles is sufficient to prevent short-term memory and synaptic plasticity deficits at early stages of disease. These effects precede blood-brain barrier disruption and amyloid-beta or tau pathology, implying an early involvement of IL-17 in AD pathology. When IL-17 is neutralized at later stages of disease, the onset of short-memory deficits and amyloidosis-related splenomegaly is delayed. Altogether, our data support the idea that cognition relies on a finely regulated balance of "inflammatory" cytokines derived from the meningeal immune system.

Modeling human age-associated increase in Gadd45γ expression leads to spatial recognition memory impairments in young adult mice.

Aging is associated with the progressive decay of cognitive function. Hippocampus-dependent processes, such as the formation of spatial memory, are particularly vulnerable to aging. Currently, the molecular mechanisms responsible for age-dependent cognitive decline are largely unknown. Here, we investigated the expression and function of the growth arrest DNA damage gamma (Gadd45γ) during aging and cognition. We report that Gadd45γ expression is increased in the hippocampus of aged humans and that Gadd45γ overexpression in the young adult mouse hippocampus compromises cognition. Moreover, Gadd45γ overexpression in hippocampal neurons disrupted cAMP response element-binding protein signaling and the expression of well-established activity-regulated genes. This work shows that Gadd45γ expression is tightly controlled in the hippocampus and its disruption may be a mechanism contributing to age-related cognitive impairments observed in humans.

ITIL Assessment in a healthcare environment: the role of IT governance at Hospital São Sebastião.

This paper addresses the role of IT Governance in a Hospital Information System (HIS) management. ITIL is introduced as a best practice for supporting HIS development. Since IT Governance is extensive, we focused our study on an ITIL Assessment. The assessment was centred on IT Service Management, and which, according to our findings, is being carried inefficiently in Hospital São Sebastião. Although the literature quotes the many benefits brought by ITIL to the organizations, they all depend on how good the planning and implementing processes are. The implementation process itself is very complex and we focused our study on the assessment step. The ITIL assessment was crucial to identify IT Governance weakness; and it is a way for the organization to become consciousness about IT improvement priorities. The results were used to rethink HIS strategy in order to properly address the next challenges.

The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding.

There is a growing consensus that Alzheimer's disease (AD) involves failure of the homeostatic machinery, which underlies the firing stability of neural circuits. What are the culprits leading to neuron firing instability? The amyloid precursor protein (APP) is central to AD pathogenesis, and we recently showed that its intracellular domain (AICD) could modify synaptic signal integration. We now hypothesize that AICD modifies neuron firing activity, thus contributing to the disruption of memory processes. Using cellular, electrophysiological, and behavioral techniques, we show that pathological AICD levels weaken CA1 neuron firing activity through a gene-transcription-dependent mechanism. Furthermore, increased AICD production in hippocampal neurons modifies oscillatory activity, specifically in the γ-frequency range, and disrupts spatial memory task. Collectively, our data suggest that AICD pathological levels, observed in AD mouse models and in human patients, might contribute to progressive neuron homeostatic failure, driving the shift from normal aging to AD.

The adoption of IT security standards in a healthcare environment.

Security is a vital part of daily life to Hospitals that need to ensure that the information is adequately secured. In Portugal, more CIOs are seeking that their hospital IS departments are properly protecting information assets from security threats. It is imperative to take necessary measures to ensure risk management and business continuity. Security management certification provides just such a guarantee, increasing patient and partner confidence. This paper introduces one best practice for implementing four security controls in a hospital datacenter infrastructure (ISO27002), and describes the security assessment for implementing such controls.

Left Paraduodenal Hernia.

Left paraduodenal hernia is an entrapment of the small bowel into the Landzert fossa, an unusual congenital peritoneal defect behind the descending mesocolon that results from failure of part of the descending mesocolon to fuse with the posterior parietal peritoneum (Doishita et al. in Radiographics, 36(1): 88-106, 2016). This fossa is reported to be present in approximately 2% of autopsy bodies. The authors present a case of a left paraduodenal hernia in a young woman.