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Objectives: To attain an understanding of pachyvein formation seen with central serous chorioretinopathy (CSC) by measuring the choroidal blood flow (CBF) velocity and to apply the findings to existing hydrodynamic theorems. Methods: Nineteen subjects with monocular CSC (mean age 51.8 ± 12.7 years) were included. Laser speckle flowgraphy measured the mean blur rate (MBR) in the foveal and perifoveal regions, and the findings were applied to the Equation of Continuity (Q = AV) and Bernoulli's theorem (1/2V2 + P/ρ = constant). Results: The mean foveal/perifoveal MBRs in the CSC eyes were 6.4 ± 3.2/9.6 ± 3.2 (p < 0.001). The mean MBRs in the non-CSC eyes were 8.3 ± 3.2/7.9 ± 2.4 (p = 0.37). The significant foveal CBF velocity decrease in CSC eyes occurs because of exudation from the hyperpermeable choriocapillaris. The subsequent decrease in blood volume due to the exudation elicits a decrease in the blood flow velocity in the inferior venules in accordance with the Equation of Continuity. The decrease in the blood flow velocity may result in an elevated blood flow pressure in the inferior venules and veins at the exudation site, in accordance with Bernoulli's theorem. Conclusion: A significant decrease in the foveal MBR may result from exudation from the hyperpermeable macular choriocapillaris. This decreased velocity may elicit a blood pressure elevation that can expand the inferior venules and veins at the exudation site, so-called pachyvein and pachychoroid formation. The application of hydrodynamic theorems to the measurement of ocular blood flow can provide new insights into the understanding of the pathogenesis of chorioretinal disease. [ABSTRACT FROM AUTHOR]

In mammals, nitric oxide (NO) is generated either by the nitric oxide synthase (NOS) enzymes from arginine or by the reduction of nitrate to nitrite by tissue xanthine oxidoreductase (XOR) and the microbiome and further reducing nitrite to NO by XOR or several heme proteins. Previously, we reported that skeletal muscle acts as a large nitrate reservoir in mammals, and this nitrate reservoir is systemically, as well as locally, used to generate nitrite and NO. Here, we report identifying two additional nitrate storage organs—bone and skin. We used bolus of ingested 15N-labeled nitrate to trace its short-term fluxes and distribution among organs. At baseline conditions, the nitrate concentration in femur bone samples was 96 ± 63 nmol/g, scalp skin 56 ± 22 nmol/g, with gluteus muscle at 57 ± 39 nmol/g. In comparison, plasma and liver contained 34 ± 19 nmol/g and 15 ± 5 nmol/g of nitrate, respectively. Three hours after 15N-nitrate ingestion, its concentration significantly increased in all organs, exceeding the baseline levels in plasma, skin, bone, skeletal muscle, and in liver 5-, 2.4-, 2.4-, 2.1-, and 2-fold, respectively. As expected, nitrate reduction into nitrite was highest in liver but also substantial in skin and skeletal muscle, followed by the distribution of 15N-labeled nitrite. We believe that these results underline the major roles played by skeletal muscle, skin, and bone, the three largest organs in mammals, in maintaining NO homeostasis, especially via the nitrate–nitrite–NO pathway. [ABSTRACT FROM AUTHOR]

Protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) regulate the level of tyrosine phosphorylation in proteins. PTKs are key enzymes that catalyze the transfer of an ATP phosphoric acid to a tyrosine residue on target protein substrates. Protein tyrosine phosphatases (PTPs) are responsible for the dephosphorylation of tyrosine residues and play a role in countering PTK overactivity. As widespread oncogenes, PTKs were once considered to be promising targets for therapy. However, tyrosine kinase inhibitors (TKIs) now face a number of challenges, including drug resistance and toxic side effects. Treatment strategies now need to be developed from a new perspective. In this review, we assess the current state of TKIs and highlight the role of PTPs in cancer and other diseases. With the advances of allosteric inhibition and the development of multiple alternative proprietary drug strategies, the reputation of PTPs as "undruggable" targets has been overturned, and they are now considered viable therapeutic targets. We also discuss the strategies and prospects of PTP-targeted therapy, as well as its future development. [ABSTRACT FROM AUTHOR]

Erwinia amylovora is a Gram-negative bacterium, responsible for the fire blight disease in Rosaceae plants. Its virulence is correlated with the production of an exopolysaccharide (EPS) called amylovoran, which protects the bacterium from the surrounding environment and helps its diffusion inside the host. Amylovoran biosynthesis relies on the expression of twelve genes clustered in the ams operon. One of these genes, amsI, encodes for a Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) called EaAmsI, which plays a key role in the regulation of the EPS production pathway. For this reason, EaAmsI was chosen in this work as a target for the development of new antibacterial agents against E. amylovora. To achieve this aim, a set of programs (DOCK6, OpenEye FRED) was selected to perform a virtual screening using a database of ca. 700 molecules. The six best-scoring compounds identified were tested in in vitro assays. A complete inhibition kinetic characterization carried out on the most promising molecule (n-Heptyl β-D-glucopyranoside, N7G) showed an inhibition constant of 7.8 ± 0.6 µM. This study represents an initial step towards the development of new EaAmsI inhibitors able to act as antibacterial agents against E. amylovora infections. [ABSTRACT FROM AUTHOR]

Social robots represent a valid opportunity to manage the diagnosis, treatment, care, and support of older people with dementia. The aim of this study is to validate the Mini-Mental State Examination (MMSE) test administered by the Pepper robot equipped with systems to detect psychophysical and emotional states in older patients. Our main result is that the Pepper robot is capable of administering the MMSE and that cognitive status is not a determinant in the effective use of a social robot. People with mild cognitive impairment appreciate the robot, as it interacts with them. Acceptability does not relate strictly to the user experience, but the willingness to interact with the robot is an important variable for engagement. We demonstrate the feasibility of a novel approach that, in the future, could lead to more natural human–machine interaction when delivering cognitive tests with the aid of a social robot and a Computational Psychophysiology Module (CPM). [ABSTRACT FROM AUTHOR]

The structural determination and characterization of molecules, namely proteins and enzymes, is crucial to gaining a better understanding of their role in different chemical and biological processes. The continuous technical developments in the experimental and computational resources of X-ray diffraction (XRD) and, more recently, cryogenic Electron Microscopy (cryo-EM) led to an enormous growth in the number of structures deposited in the Protein Data Bank (PDB). Bioinorganic chemistry arose as a relevant discipline in biology and therapeutics, with a massive number of studies reporting the effects of metal complexes on biological systems, with vanadium complexes being one of the relevant systems addressed. In this review, we focus on the interactions of vanadium compounds (VCs) with proteins. Several types of binding are established between VCs and proteins/enzymes. Considering that the V-species that bind may differ from those initially added, the mentioned structural techniques are pivotal to clarifying the nature and variety of interactions of VCs with proteins and to proposing the mechanisms involved either in enzymatic inhibition or catalysis. As such, we provide an account of the available structural information of VCs bound to proteins obtained by both XRD and/or cryo-EM, mainly exploring the more recent structures, particularly those containing organic-based vanadium complexes. [ABSTRACT FROM AUTHOR]

In clinical practice, self-administered and brief tools to promptly identify older people at risk of frailty are required. The Multidimensional Prognostic Index (MPI), derived from the Comprehensive Geriatric Assessment (CGA) seems reliable enough to serve this purpose, but despite the several versions developed over the past 15 years, it lacks a self-administered and brief version. In this study, we aimed to evaluate the agreement between an abbreviated form of the SELFY-MPI (i.e., SELFY-BRIEF-MPI) and the standard version of the MPI. Four Italian hospitals consecutively enrolled outpatients and inpatients >65 years. The sample included 105 participants (mean age = 78.8 years, 53.3% females). Overall, the two versions showed non-statistically significant differences (Standard-MPI 0.42 ± 0.19 vs.. SELFY-BRIEF-MPI 0.41 ± 0.18; p = 0.104) and a very strong correlation (R = 0.86, p < 0.001). The Bland–Altman Plot revealed that only 5/105 measurements (4.76%) were outside the limits of agreement. The accuracy of the SELFY-BRIEF-MPI in identifying frail people (defined as a Standard-MPI > 0.66) was optimal (area under the curve, AUC = 0.90, p < 0.001). To predict multidimensional frailty, a SELFY-BRIEF-MPI score of 0.60 exhibited the greatest sensitivity/specificity ratio. In conclusion, the SELFY-BRIEF-MPI reported a good agreement with the standard version of the MPI, indicating its application in the screening of multidimensional frailty among older people. [ABSTRACT FROM AUTHOR]

Nowadays, more studies deal with "OrthoGeriatrics", for the co-management of elderly patients suffering fractures, from the admission to the discharge and beyond. For the first time at Cagliari University Hospital, we introduced an orthogeriatric service, in which trained geriatricians stay in orthopedic unit alongside trained orthopedics. The primary aim of the study was to analyze the rate of death and rehospitalization in elderly femur-fractured people of 65 or more years of age, identifying possible predictive factors. The secondary aim of the study was to analyze the recovery of daily living autonomies during the months following surgery. To reach the aim, we designed a prospective study, which is currently ongoing. We evaluated femur-fractured patients aged 65 years or more with a comprehensive geriatric assessment before surgery. The most common fractures were lateral hip ones, treated with osteosynthesis. Cognitive–affective, functional, and nutritional status, mood, and comorbidities were less impaired than in the outpatient service of the same hospital devoted to frail elderly. Pain control was excellent. A significantly low delirium incidence was found. More than a third of the sample were recognized as frail (according to the Survey of Health, Ageing and Retirement in Europe—Frailty Instrument (SHARE-FI)), and over a third of the sample were identified as a moderate-high risk of hospitalization and death (according to Multidimensional Prognostic Index (MPI)). Overall mortality rate was 13.87%, and rehospitalization rate was 11.84%. Frail people were more likely to die than non-frail (HR: 5.64), and pre-frail ones (HR: 3.97); similarly, high-risk patients were more likely to die than low-risk (HR: 8.04), and moderate-risk ones (HR: 5.46). Conversely, neither SHARE-FI nor MPI predicted rehospitalization. Creatinine (OR: 2.66, p = 0.003) and folate (OR: 0.75, p = 0.03) levels were independently associated with death and rehospitalization, respectively. Finally, the patients did recover the lost autonomies later, 6 months after surgery. Our study demonstrated that SHARE-FI and MPI are reliable tools to predict mortality in an orthogeriatric setting, and that creatinine and folate levels should also be measured given their independent association with negative outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present pilot study, we developed and validated a new accurate, quick-to-use screening tool for stratifying frailty and the risk of mortality in oncological geriatric patients. Frailty detection with comprehensive geriatric assessment (CGA) is of pivotal importance in older cancer patients to avoid over- or under-treatment with chemotherapy and to detect those at increased risk for poor outcomes. Several tools have been developed to capture the complexity of frailty, but only a few were explicitly conceived for older patients with cancer. In this study, we consecutively enrolled older patients with breast cancer during the preoperative evaluation as the development cohort. We evaluated seventy patients with different types of cancer admitted to our OncoGeriatric Clinic for the validation cohort. We then evaluated the relationship between MPI and CGA items, and we finally realized a screening tool based on the combination of the significant variables, now called the Multidimensional Oncological Frailty Scale (MOFS). Background: Frailty detection with comprehensive geriatric assessment (CGA) is of pivotal importance in older patients with cancer to avoid over- or under-treatment and to detect those at increased risk for poor outcomes. Several tools have been developed to capture the complexity of frailty, but only a few were explicitly conceived for older adults with cancer. The study aimed at developing and validating a multidimensional, easy-to-use diagnostic tool for early-risk stratification in patients with cancer, called the Multidimensional Oncological Frailty Scale (MOFS). Methods: In this single-center prospective study, we consecutively enrolled 163 older women (age ≥ 75 years) with breast cancer, screened with a G8 score ≤ 14 during the outpatient preoperative evaluation at our breast centre, as the development cohort. Seventy patients with different types of cancer admitted to our OncoGeriatric Clinic served as the validation cohort. Using stepwise linear regression analysis, we evaluated the relationship between Multidimensional Prognostic Index (MPI) and CGA items, and, finally, realized a screening tool based on the combination of the significant variables. Results: The mean age of the study population was 80.4 ± 5.8 years, while the mean age of the validation cohort was 78.6 ± 6.6 years [42 women (60%)]. A composite model of the Clinical Frailty Scale, G8, and hand grip strength test showed a strong correlation with MPI (R= −0.712, p < 0.001). The MOFS accuracy in the prediction of mortality was optimal in both the development and the validation cohorts (AUC 0.82 and 0.87; p < 0.001 and 0.003, respectively). Conclusion: MOFS represents a new, accurate, quick-to-use frailty screening tool for stratifying the risk of mortality in geriatric cancer patients. [ABSTRACT FROM AUTHOR]

Since the heterogeneity of the growing group of older outpatients with cognitive decline, it is challenging to evaluate survival rates in clinical shared decision making. The primary outcome was to determine whether the Multidimensional Prognostic Index (MPI) predicts mortality, whilst assessing the MPI distribution was considered secondary. This retrospective chart review included 311 outpatients aged ≥65 years and diagnosed with dementia or mild cognitive impairment (MCI). The MPI includes several domains of the comprehensive geriatric assessment (CGA). All characteristics and data to calculate the risk score and mortality data were extracted from administrative information in the database of the Alzheimer's Center and medical records. The study population (mean age 76.8 years, men = 51.4%) was divided as follows: 34.1% belonged to MPI category 1, 52.1% to MPI category 2 and 13.8% to MPI category 3. Patients with dementia have a higher mean MPI risk score than patients with MCI (0.47 vs. 0.32; p < 0.001). The HRs and corresponding 95% CIs for mortality in patients in MPI categories 2 and 3 were 1.67 (0.81–3.45) and 3.80 (1.56–9.24) compared with MPI category 1, respectively. This study shows that the MPI predicts mortality in outpatients with cognitive decline. [ABSTRACT FROM AUTHOR]

The negative impact of chronic kidney disease (CKD) on health status and quality of life in older patients has been well documented. However, data on frailty trajectories and long-term outcomes of older CKD patients undergoing structured Comprehensive Geriatric Assessment (CGA) with multidimensional frailty evaluation are sparse. Here, we analysed records from 375 CKD patients admitted to our university hospital (mean age 77.5 (SD 6.1) years, 36% female) who had undergone a CGA-based calculation of the frailty score with the multidimensional prognostic index (MPI) as well as follow-up evaluations at 3, 6 and 12 months after discharge. Based on the MPI score at admission, 21% of the patients were frail and 56% were prefrail. MPI values were significantly associated with KDIGO CKD stages (p = 0.003) and rehospitalisation after 6 months (p = 0.027) and mortality at 3, 6 and 12 months (p = 0.001), independent of chronological age. Kidney transplant recipients (KTR) showed a significantly lower frailty compared to patients with renal replacement therapy (RRT, p = 0.028). The association between frailty and mortality after 12 months appeared particularly strong for KTR (mean MPI 0.43 KTR vs. 0.52 RRT, p < 0.001) and for patients with hypoalbuminemia (p < 0.001). Interestingly, RRT was per se not significantly associated with mortality during follow up. However, compared to patients on RRT those with KTR had a significantly lower grade of care (p = 0.031) and lower rehospitalisation rates at 12 months (p = 0.010). The present analysis shows that the large majority of older CKD inpatients are prefrail or frail and that the risk for CKD-related adverse outcomes on the long term can be accurately stratified by CGA-based instruments. Further studies are needed to explore the prognostic and frailty-related signature of laboratory biomarkers in CKD. [ABSTRACT FROM AUTHOR]

Résumé: Le recueil d'informations pronostiques chez le sujet âgé est primordial. L'objectif principal était de répliquer l'indice pronostique multidimensionnel (MPI), comme instrument prédictif de la mortalité à un an chez des personnes hospitalisées en gériatrie. Les objectifs secondaires étaient d'évaluer si le MPI était prédictif de la durée du séjour hospitalier, et d'une réhospitalisation dans l'année. Méthodes. Étude prospective de février 2015 à novembre 2016 au pôle de gériatrie du CHU de Poitiers. Une évaluation gériatrique standardisée (nombre de médicaments, mode de vie, autonomie, comorbidités, risque d'escarre, statuts nutritionnel et cognitif) était utilisée pour calculer le score MPI et catégoriser les patients en trois groupes : risque de mortalité faible (MPI-1), modéré (MPI-2) et élevé (MPI-3). Résultats. 153 patients inclus, d'âge moyen 85,9 ± 5,4 ans. Vingt-et-un patients (13,7 %) appartenaient au groupe MPI-1, 98 (64,1 %) au groupe MPI-2, 34 (22,2 %) au groupe MPI-3. Le nombre de décès à un an selon le groupe MPI était différent (p < 0,01). L'indice pronostique MPI apparaissait comme performant à un an (AUC de 0,76), et était prédictif de la durée d'hospitalisation (p < 0,05). Conclusion. Le MPI apparaît comme un instrument pronostique pertinent dans la stratification du risque de mortalité à un an chez les personnes hospitalisées en gériatrie. The collection of prognostic information in the elderly is essential. The main objective was to perform a replication of the multidimensional prognostic index (MPI), to predict mortality at one-year in patients hospitalized in geriatric wards. Secondary objectives were to evaluate if the MPI was predictive of the length of hospital stay, and of rehospitalization in the following year. Methods. Prospective study conducted from February 2015 to November 2016 at the University Hospital of Poitiers (Geriatrics department). A comprehensive geriatric assessment (number of treatment, lifestyle, autonomy, comorbidities, risk of pressure sore, nutritional and cognitive status) was used to calculate the MPI score and to categorize patients into three groups: low (MPI-1), moderate (MPI-2) and high (MPI-3) risk of mortality. Results. 153 patients were included, with mean age 85.9 ± 5.4 years. Twenty-one patients (13.7%) belonged to MPI-1 group, 98 (64.1%) to MPI-2 group, and 34 (22.2%) to MPI-3 group. The number of deaths at one-year according to the MPI group was different (p < 0.01). The one-year prognostic performance of MPI was good (AUC at 0.76). MPI was also predictive of hospital length stay (p < 0.05). Conclusion. MPI appears to be a relevant prognostic tool in the stratification of one-year mortality risk in elderly patients hospitalized in geriatrics. [ABSTRACT FROM AUTHOR]

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The article presents research briefs related to medicinal chemistry, as of January 2018. Topics include a study on an allosteric inhibitor with the most complex mode of action to combat tuberculosis; use of selective indazole ether-based glucocorticoid receptor modulators for treating asthma and chronic obstructive pulmonary disease; and developing potent proteolysis-targeting chimeras (protacs) in anticancer drug discovery.

Caspase-1 is involved in inflammatory processes and is overactive in autoimmunity and autoinflammation. Antioxidant small molecules also play a role in the immune response by decreasing inflammation. An 84-membered library of pro- and antioxidant small molecules was screened for potential inhibitors of caspase-1. Thirteen compounds were discovered to reduce the activity of caspase-1 below 30%. The most potent inhibitors were lazaroid antioxidant molecules, U83836E ( B8) and U74389G ( B9), displaying apparent Ki values of 48.0 and 50.0 n m, respectively. Both demonstrated a time-dependent and reversible inhibition. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase receptor gamma (PTPRG) is known to interact with and regulate several tyrosine kinases, exerting a tumor suppressor role in several type of cancers. Its wide expression in human tissues compared to the other component of group 5 of receptor phosphatases, PTPRZ expressed as a chondroitin sulfate proteoglycan in the central nervous system, has raised interest in its role as a possible regulatory switch of cell signaling processes. Indeed, a carbonic anhydrase-like domain (CAH) and a fibronectin type III domain are present in the N-terminal portion and were found to be associated with its role as [HCO3−] sensor in vascular and renal tissues and a possible interaction domain for cell adhesion, respectively. Studies on PTPRG ligands revealed the contactins family (CNTN) as possible interactors. Furthermore, the correlation of PTPRG phosphatase with inflammatory processes in different normal tissues, including cancer, and the increasing amount of its soluble form (sPTPRG) in plasma, suggest a possible role as inflammatory marker. PTPRG has important roles in human diseases; for example, neuropsychiatric and behavioral disorders and various types of cancer such as colon, ovary, lung, breast, central nervous system, and inflammatory disorders. In this review, we sum up our knowledge regarding the latest discoveries in order to appreciate PTPRG function in the various tissues and diseases, along with an interactome map of its relationship with a group of validated molecular interactors. [ABSTRACT FROM AUTHOR]

Traumatic injuries to the nervous system, including the brain and spinal cord, lead to neurological dysfunction depending upon the severity of the injury. Due to the loss of motor (immobility) and sensory function (lack of sensation), spinal cord injury (SCI) and brain injury (TBI) patients may be bed-ridden and immobile for a very long-time. These conditions lead to secondary complications such as bladder/bowel dysfunction, the formation of pressure ulcers (PUs), bacterial infections, etc. PUs are chronic wounds that fail to heal or heal very slowly, may require multiple treatment modalities, and pose a risk to develop further complications, such as sepsis and amputation. This review discusses the role of oxidative stress and reactive oxygen species (ROS) in the formation of PUs in patients with TBI and SCI. Decades of research suggest that ROS may be key players in mediating the formation of PUs. ROS levels are increased due to the accumulation of activated macrophages and neutrophils. Excessive ROS production from these cells overwhelms intrinsic antioxidant mechanisms. While short-term and moderate increases in ROS regulate signal transduction of various bioactive molecules; long-term and excessively elevated ROS can cause secondary tissue damage and further debilitating complications. This review discusses the role of ROS in PU development after SCI and TBI. We also review the completed and ongoing clinical trials in the management of PUs after SCI and TBI using different technologies and treatments, including antioxidants. [ABSTRACT FROM AUTHOR]

Equine metabolic syndrome (EMS) is a cluster of metabolic disorders, such as obesity, hyperinsulinemia, and hyperleptinemia, as well as insulin resistance (IR). In accordance with the theory linking obesity and IR, excessive accumulation of lipids in insulin-sensitive tissues (lipotoxicity), like liver, alters several cellular functions, including insulin signaling. Therefore, the purpose of the study was to isolate equine hepatic progenitor-like cells (HPCs) and assess whether inhibition of low molecular weight protein tyrosine phosphatase (LMPTP) affects the expression of genes involved in macroautophagy, chaperone-mediated autophagy (CMA), endoplasmic reticulum stress, and mitochondrial dynamics in a palmitate-induced IR model. We demonstrated that LMPTP inhibition significantly enhanced expression of heat shock cognate 70 kDa protein (HSC70), lysosome-associated membrane protein 2 (LAMP2), and parkin (PRKN), all master regulators of selective autophagy. We also observed downregulation of C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and binding immunoglobulin protein encoded by the HSPA gene. Moreover, LMPTP inhibition increased alternative splicing of X-box binding protein 1 (XBP1), suggesting high endonuclease activity of inositol-requiring enzyme 1 alpha (IRE1α). Taken together, our data provide convincing evidence that LMPTP inhibition reverses palmitate-induced insulin resistance and lipotoxicity. In conclusion, this study highlights the role of LMPTP in the regulation of CMA, mitophagy, and ER stress, and provides a new in vitro model for studying HPC lipotoxicity in pre-clinical research. [ABSTRACT FROM AUTHOR]

Background and aims: The Multidimensional Prognostic Index (MPI), an objective and quantifiable tool based on the Comprehensive Geriatric Assessment, has been shown to predict adverse outcomes in European cohorts. We conducted a validation study of the original MPI, and of adapted versions that accounted for the use of specific drugs and cultural diversity in the assessment of cognition, in older Australians. Methods: The capacity of the MPI to predict 12-month mortality was assessed in 697 patients (median age: 80 years; interquartile range: 72–86) admitted to a metropolitan teaching hospital between September 2015 and February 2017. Results: In simple logistic regression analysis, the MPI was associated with 12-month mortality (Low risk: OR reference group; moderate risk: OR 2.50, 95% CI: 1.67–3.75; high risk: OR 4.24, 95% CI: 2.28–7.88). The area under the receiver operating characteristic curve (AUC) for the unadjusted MPI was 0.61 (0.57–0.65) and 0.64 (95% CI: 0.59–0.68) with age and sex adjusted. The adapted versions of the MPI did not significantly change the AUC of the original MPI. Conclusion: The original and adapted MPI were strongly associated with 12-month mortality in an Australian cohort. However, the discriminatory performance was lower than that reported in European studies. [ABSTRACT FROM AUTHOR]

Pressure ulcers are one of the most common complications of a spinal cord injury (SCI). Prolonged unrelieved pressure is thought to be the primary causative factor resulting in tissue ischemia and eventually pressure ulcers. Previous studies suggested that local cooling reduces skin ischemia of the compressed soft tissues based on smaller hyperemic responses. However, the effect of local cooling on nonlinear properties of skin blood flow (SBF) during hyperemia is unknown. In this study, 10 wheelchair users with SCI and 10 able-bodied (AB) controls underwent three experimental protocols, each of which included a 10-min period as baseline, a 20-min intervention period, and a 20-min period for recovering SBF. SBF was measured using a laser Doppler flowmetry. During the intervention period, a pressure of 60 mmHg was applied to the sacral skin, while three skin temperature settings were tested, including no temperature change, a decrease by 10 °C, and an increase by 10 °C, respectively. A multiscale entropy (MSE) method was employed to quantify the degree of regularity of blood flow oscillations (BFO) associated with the SBF control mechanisms during baseline and reactive hyperemia. The results showed that under pressure with cooling, skin BFO both in people with SCI and AB controls were more regular at multiple time scales during hyperemia compared to baseline, whereas under pressure with no temperature change and particularly pressure with heating, BFO were more irregular during hyperemia compared to baseline. Moreover, the results of surrogate tests indicated that changes in the degree of regularity of BFO from baseline to hyperemia were only partially attributed to changes in relative amplitudes of endothelial, neurogenic, and myogenic components of BFO. These findings support the use of MSE to assess the efficacy of local cooling on reactive hyperemia and assess the degree of skin ischemia in people with SCI. [ABSTRACT FROM AUTHOR]

Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p < 0.001), and were more likely to be older (p < 0.001), have a significant clear cognitive impairment (MMSE: p < 0.001), show the presence of a depressive mood (HDRS-21: p < 0.001) and have major impairments in ADL (p < 0.001), IADL (p < 0.001), MNA (p < 0.001), and ESS (p < 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Na+: p < 0.001; K+: p < 0.001; Cl−: p < 0.001), risk of dehydration (osmolality p < 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer’s disease (AD) patients showed a major risk for current dehydration (p ≤ 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p < 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p < 0.001) and IADL (p < 0.001), but independently associated with age (r2 = 0.0046, p = 0.77), ESS (r2 = 0.0052, p = 0.54) and MNA (r2 = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65–75 years, p = 0.001; 76–85 years, p = 0.001; ≥86 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage. [ABSTRACT FROM AUTHOR]