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Hypothesis The absorption capacity and kinetics of nanocellulose foams are controlled by the surface charge of the fibers, which affects swelling and determine the porosity and structure of the network. Experiments Absorption kinetics were quantified at time scales ranging from fractions of a second to minutes. The mass absorption rate as well as the area profile for the liquid stains were simultaneously measured. Findings The absorption profile followed a three-stage mechanism: wicking, transition and fiber swelling. Absorption of fluids differing in ionic strength revealed the critical role played by electrostatic forces. Nanocellulose foam absorption capacity is 25% higher for water than for 0.9 wt% NaCl solution. The absorption kinetics of nanocellulose foam are also tuneable by modulating the surface charge. High surface charge nanocellulose foams have slower absorption in water than their low surface charged analogues. This behaviour is driven by the lower pore sizes developed in high surface charge foams, as determined by X-ray CT. Small Angle X-ray Scattering revealed structural homogeneity of high surface charge foams upon absorption of water due to high fibrillation and fiber swelling.

Exposure to metals has been hypothesized as possible cause of chronic kidney disease of unknown cause (CKDu) in Sri Lanka; however, evidence is inconclusive. We measured the concentrations of nephrotoxic metals (As, Pb, and Cd), as well as Se in rice (a staple grain in Sri Lanka) and other grains consumed in CKDu endemic and non-endemic regions using Inductively Coupled Mass Spectrometry (ICP-MS). Our results showed comparable mean concentrations (in µg/kg) of 24.5 ± 18, 7.3 ± 6.4, and 14.2 ± 15 for As, Pb, and Cd, respectively, in rice from endemic regions and 17.7 ± 4.7, 12.7 ± 6.8, and 17.8 ± 16 in rice from non-endemic regions. Selenium concentrations (in mg/kg) were 0.05 ± 0.02 in rice cultivated in both endemic and non-endemic regions. Arsenic and Cd concentrations were significantly higher in rice compared to other grains, which themselves had higher Se than rice. All samples were below the Codex standards established for Cd (400 µg/kg for rice; 100 µg/kg for cereal grains), Pb (200 µg/kg) and inorganic As (200 µg/kg) for white rice. Our findings show that dietary exposure to low levels of As, Pb, Cd, and inadequate Se in staple grains cannot be clearly linked to CKDu, suggesting that the disease could be multifactorial. Additional research is needed to determine the contribution of other risk factors such as lifestyle habits and heat stress to plan preventive strategies for reducing CKDu health cases in Sri Lanka.

Preeclampsia (PE) is a pregnancy-related disorder characterized by hypertension and proteinuria that affects 3-10% of all pregnancies. Although its pathophysiology remains obscure, placental hypoxia-induced oxidative stress and alterations in vascular function, morphology, and endothelial barrier integrity are considered to play a key role in the development of preeclampsia. In this study, placental villous explants of noncomplicated placentae and BeWo cells were subjected to hypoxia. The effect of placental hypoxic-conditioned medium (HCM) on intraluminal-induced contraction and endothelial barrier integrity in chorionic arteries was investigated using pressure myography. The impact of BeWo cell HCM on endothelial cell viability, reactive oxygen species formation and inflammation was also determined. Alterations in arterial morphology and contractile responsiveness to the thromboxane A2 analog (U46619) after exposure to placental HCM were examined immunohistochemically and by wire myography, respectively. Intraluminal administration of placental HCM induced vasoconstriction and increased the endothelial permeability for KCl, which was concentration-dependently prevented by quercetin. Placental and BeWo cell HCMs decreased endothelial cell viability, increased the production of reactive oxygen species and enhanced the secretion of IL-6 and IL-8. The cross-sectional area of the arterial media was increased upon exposure to placental HCM, which was associated with increased vascular proliferation and contractile responsiveness to U46619, and all of these effects were prevented by the antioxidants quercetin and RRR-alpha-tocopherol. This study is the first to comprehensively demonstrate the link between factors secreted by placental cells in response to hypoxia and vascular abnormalities and paves the way for new diagnostic approaches and therapies to better protect the maternal vasculature during and after a preeclampsia-complicated pregnancy.

Over half a century since the description of the first antiviral drug, “old” re‐emerging viruses and “new” emerging viruses still represent a serious threat to global health. Their high mutation rate and rapid selection of resistance toward common antiviral drugs, together with the increasing number of co‐infections, make the war against viruses quite challenging. Herein we report a host‐targeted approach, based on the inhibition of the lipid kinase PI4KIIIβ, as a promising strategy for inhibiting the replication of multiple viruses hijacking this protein. We show that bithiazole inhibitors of PI4KIIIβ block the replication of human rhinoviruses (hRV), Zika virus (ZIKV) and SARS‐CoV‐2 at low micromolar and sub‐micromolar concentrations. However, while the anti‐hRV/ZIKV activity can be directly linked to PI4KIIIβ inhibition, the role of PI4KIIIβ in SARS‐CoV‐2 entry/replication is debated., Host targeting is a promising approach for the development of broad‐spectrum antiviral agents (BSAAs) endowed with a high genetic barrier to resistance and efficacy against viral mutants resistant to conventional antiviral drugs. We show that bithiazole inhibitors of the host lipid kinase PI4KIIIβ block the replication of human rhinoviruses (hRV), Zika virus (ZIKV) and SARS‐CoV‐2 at low micromolar and sub‐micromolar concentrations. Moreover, inhibition of SARS‐CoV‐2 entry seems to be connected with an additional unknown target.

Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.

BACKGROUND AND AIM: Minority communities, especially African Americans are disproportionately impacted by COVID-19 in the United States (US). In Louisiana, African Americans account 32.2% (1.5 mill...

BACKGROUND:There is an increasing concern about age-related frailty because of the growing number of elderly people in the general population. The Longevity-Associated Variant (LAV) of the human BPIFB4 gene was found to correct endothelial dysfunction, one of the mechanisms underlying frailty, in aging mice whereas the RV-BPIFB4 variant induced opposite effects. Thus, we newly hypothesize that, besides being associated with life expectancy, BPIFB4 polymorphisms can predict frailty.Aim and Results: Here we investigated if the BPIFB4 haplotypes, LAV, wild-type (WT) and RV, differentially associate with frailty in a cohort of 237 elderly subjects from Calabria region in Southern Italy. Moreover, we studied the effect of systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer on the progression of frailty in aging mice. We found an inverse correlation of the homozygous LAV-BPIFB4 haplotype with frailty in elderly subjects. Conversely, carriers of the RV-BPIFB4 haplotype showed an increase in the frailty status and risk of death. Moreover, in old mice, LAV-BPIFB4 gene transfer delayed frailty progression.CONCLUSIONS:These data indicate that specific BPIFB4 haplotypes could represent useful genetic markers of frailty. In addition, horizontal transfer of a healthy gene variant can attenuate frailty in aging organisms.

Si113, a pyrazolo[3,4-d]pyrimidine derivative, gained more attention as an anticancer agent due to its potent anticancer activity on both in vitro and in vivo hepatocellular carcinomas (HCC) and ovarian carcinoma models. But the drawback is the low water solubility which prevents its further development. In this context, we successfully overcame this limitation by synthesizing two novel prodrugs introducing the amino acid sequence D-Ala-Leu-Lys (TP). Moreover, TP sequence has a high affinity with plasmin, a protease recognized as overexpressed in many solid cancers, including HCC and ovarian carcinoma. The prodrugs were synthesized and fully characterized in terms of in vitro ADME properties, plasma stability and plasmin-induced release of the parent drug. The inhibitory activity against Sgk1 was evaluated and in vitro growth inhibition was evaluated on ovarian carcinoma and HCC cell lines in the presence and absence of human plasmin. In vivo pharmacokinetic properties and preliminary tissue distribution confirmed a better profile highlighting the importance of the prodrug approach. Finally, the prodrug antitumor efficacy was evaluated in an HCC xenografted murine model, where a significant reduction (around 90%) in tumor growth was observed. Treatment with ProSi113-TP in combination with paclitaxel in a paclitaxel-resistant ovarian carcinoma xenografted murine model, resulted in an impressive reduction of tumor volume greater than 95%. Our results revealed a promising activity of Si113 prodrugs and pave the way for their further development against resistant cancer.

OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in both adults and children. Along with obesity and metabolic syndrome, genetic predisposition influences the progression of NAFLD. Here, we investigated the effect of lifespan/healthspan-related single nucleotide polymorphisms (SNPs) on metabolically associated fatty liver disease in children. METHODS We evaluated the impact of 10 SNPs involved in both human liver/metabolic diseases and healthspan (interleukin-6 [IL-6] rs1800795, antisense non coding RNA in the INK4 locus (ANRIL) rs1556516, SH2B3/ATXN2 rs7137828, FURIN rs17514846, TP53 rs1042522, APOC3 rs2542052, KL rs9536314, KL rs9527025, SIRT6 rs107251, FOXO3 rs2802292) on NAFLD-related metabolic and liver features in 177 pediatric patients with biopsy-proven NAFLD, by comparing them to 146 healthy controls. We then applied a multidimensional reduction (MDR) case-control analysis of SNP-SNP interactions, to identify the joint effect of analyzed SNPs in predicting NAFLD and associated features. RESULTS Discrete SNPs were significantly associated with individual metabolic NAFLD features, but none of them significantly associated with NAFLD diagnosis. By testing potential synergies using the MDR approach, the best combination to diagnose NAFLD (P = 0.0011) resulted in the one encompassing IL-6 rs1800795 and ANRIL rs1556516. Consistently, the risk combinations suggested by SNP-SNP analysis strongly associated with a higher level of fasting plasma blood glucose level (P = 0.024). CONCLUSION In conclusion, here we demonstrated a synergic interaction between IL-6 rs1800795 and ANRIL rs1556516 in the diagnosis of NAFLD, and NAFLD-associated hyperglycemia in children. Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, hospitals rapidly ran out of intensive care beds. Because minimally invasive surgery and general anaesthesia are both aerosol-generating procedures, their use has become controversial. We report a case series of awake undelayable colorectal surgeries which, innovatively, took advantage of intraoperative pain distraction. Moreover, we describe our frugal solution to social distancing in psychological support of inpatients.Methods: Between October 2020 and February 2021, five patients underwent acute-care colorectal surgery under locoregional anaesthesia in our department. A 3D mobile theatre (3DMT) was used during the operation to distract the patients from pain. Vital signs, pain intensity, ergonomic comfort/discomfort, sense of presence and distress were intraoperatively monitored. A postoperative “cuddle delivery” service was instituted: video messages from relatives and close friends were delivered daily to the patient through the 3DMT. Emotional effects were investigated through clinical interviews conducted by a psychologist at our hospital.Results: Both intraoperative and postoperative pain were always well controlled. Conversion to general anaesthesia and postoperative intensive support/monitoring were never necessary. The “cuddle delivery” initiative helped patients fill the emotional gap created by the strict containment measures implemented inside the hospital, distracting them from emotional anxiety and physical pain.Conclusions: During the next phase of the COVID-19 pandemic and even after the COVID-19 era, awake laparotomy under locoregional anaesthesia may be a crucial option for delivering acute-care surgery to selected patients when intensive care beds are unavailable and postponing surgery is unacceptable. We also introduce a new modality for the provision of emotional support during postoperative inpatient care as a countermeasure to the restrictions imposed by social distancing measures.

Contains fulltext : 244253.pdf (Publisher’s version ) (Open Access) BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (d(max) = -0.20, d(min) = -0.09). The bilateral putamen (d(left) = -0.14, d(right) = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Several studies reported that genetic variants predisposing to neurodegeneration were at higher frequencies in centenarians than in younger controls, suggesting they might favor also longevity. IP6K3 and IPMK regulate many crucial biological functions by mediating synthesis of inositol poly- and pyrophosphates and by acting non-enzymatically via protein-protein interactions. Our previous studies suggested they affect Late Onset Alzheimer Disease (LOAD) and longevity, respectively. Here, in the same sample groups, we investigated whether variants of IP6K3 also affect longevity, and variants of IPMK also influence LOAD susceptibility. We found that: i) a SNP of IP6K3 previously associated with increased risk of LOAD increased the chance to become long-lived, ii) SNPs of IPMK, previously associated with decreased longevity, were protective factors for LOAD, as previously observed for UCP4. SNP-SNP interaction analysis, including our previous data, highlighted phenotype-specific interactions between sets of alleles. Moreover, linkage disequilibrium and eQTL data associated to analyzed variants suggested mitochondria as crossroad of interconnected pathways crucial for susceptibility to neurodegeneration and/or longevity. Overall, data support the view that in these traits interactions may be more important than single polymorphisms. This phenomenon may contribute to the non-additive heritability of neurodegeneration and longevity and be part of the missing heritability of these traits.

Prolonged exposure to higher concentrations of fluoride (> 1.5 mg/L) is associated with dental and skeletal fluorosis. The effects of fluoride on dental and skeletal system have been studied extensively; however, the neurological consequences of fluoride in population-based studies are limited. The study aims to assess the epidemiology of neurological and other manifestations of fluorosis among rural populations living in the Main Ethiopian Rift valley. In this cross-sectional study, we enrolled 316 individuals from 23 rural communities in the Main Ethiopian Rift valley. Fluoride concentration was measured in drinking water samples collected from 23 community wells. Association between fluoride concentrations and clinical features of fluorosis was assessed using student t test, chi square, multivariable regression using adjusted odds ratio (OR). The mean fluoride concentration in the drinking water was 6.8 ± 4.3 mg/L (range: 0.3–15.5 mg/L). At least one clinical sign of skeletal fluorosis was observed in 54.4% (n = 175) of the study participants. Headache and joint pain reported by 67.1% and 56.3% of the participants as the most common neurological manifestation, and skeletal fluorosis symptom, respectively. The mean fluoride level was higher for those individuals who reported paresthesia compared to those with no-paresthesia. Loss of appetite, constipation, and fatigue were reported by 48.0%, 45.6%, and 56.6% of the participants, respectively. Signs of crippling fluorosis were observed in small proportion (1.6%) of the participants. Individuals who reported headache are most likely exposed to higher fluoride concentrations in drinking water compared to those reported no-headache (p

BackgroundBrain structure abnormalities throughout the course of Parkinson’s disease (PD) have yet to be fully elucidated. Inconsistent findings across studies may be partly due to small sample sizes and heterogeneous analysis methods. Using a multicenter approach and harmonized analysis methods, we aimed to overcome these limitations and shed light on disease stage-specific profiles of PD pathology as suggested by in vivo neuroimaging.MethodsIndividual brain MRI and clinical data from 2,367 PD patients and 1,183 healthy controls were collected from 19 sites, deriving from 20 countries. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effect linear models. Patients were grouped according to the Hoehn & Yahr (HY) disease stages and compared to age- and sex-matched controls. Within the PD sample, we investigated associations between Montreal Cognitive Assessment (MoCA) scores and brain morphology.FindingsThe main analysis showed a thinner cortex in 38 of 68 regions in PD patients compared to controls (dmax = −0·25, dmin = −0·13). The bilateral putamen (left: d = −0·16, right: d = −0·16) and left amygdala (d = −0·15) were smaller in patients, while the left thalamus was larger (d = 0·17). HY staging indicated that a thinner cortex initially presents in the occipital, parietal and temporal cortex, and extends towards caudally located brain regions with increased disease severity. From HY stage 2 and onwards the bilateral putamen and amygdala were consistently smaller with larger effects denoting each increment. Finally, we found that poorer cognitive performance was associated with widespread cortical thinning as well as lower volumes of core limbic structures.InterpretationOur findings offer robust and novel imaging signatures that are specific to the disease severity stages and in line with an ongoing neurodegenerative process, highlighting the importance of such multicenter collaborations.FundingNIH Big Data to Knowledge program, ENIGMA World Aging Center, and ENIGMA Sex Differences Initiative, and other international agencies (listed in full in the Acknowledgments).

[Image: see text] Gold-nanoparticle (AuNP)-conjugated drugs represent a promising and innovative antitumor therapeutic approach. In our study, we describe the design, the synthesis, the preparation, and the characterization of AuNPs conjugated with the pyrazolo[3,4-d]pyrimidine derivative SI306, a c-Src inhibitor. AuNPs–SI306 showed a good loading efficacy (65%), optimal stability in polar media and in human plasma, and a suitable morphological profile: a ζ-potential of −43.9 mV, a nanoparticle diameter of 48.6 nm, and a 0.441 PDI value. The antitumoral activity of AuNPs–SI306 was evaluated in vitro in the glioblastoma model, by the low-density growth assay, and also in combination with radiotherapy (RT). Results demonstrated that AuNPs had a basal radiosensitization ability and that AuNPs–SI306, when used in combination with RT, were more effective in inhibiting tumor cell growth with respect to AuNPs and free SI306.

Parkinson’s disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. Phosphorus magnetic resonance spectroscopy (31P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered 10 31P-MRS studies in order to highlight the main findings about brain energetic compounds in patients affected by idiopathic PD and genetic PD. The studies investigated several brain areas such as frontal lobes, occipital lobes, temporoparietal cortex, visual cortex, midbrain, and basal ganglia. Resting-state studies reported contrasting results showing decreased as well as normal or increased HEPs levels in PD patients. Functional studies revealed abnormal PCr + βATP levels in PD subjects during the recovery phase and abnormal values at rest, during activation and recovery in one PD subject with PINK1 gene mutation suggesting that mitochondrial machinery is more impaired in PD patients with PINK1 gene mutation. PD is characterized by energetics impairment both in idiopathic PD as well as in genetic PD, suggesting that mitochondrial dysfunction underlies the disease. Studies are still sparse and sometimes contrasting, maybe due to different methodological approaches. Further studies are needed to better assess the role of mitochondria in the PD development.

Background: Guidelines on the management of orally anticoagulated patients are continuously evolving, leading to an increased need for pharmacists to be fully integrated in care provision. Objective: To identify self-reported gaps in confidence among practicing pharmacists in the area of anticoagulation. Setting Pharmacists in different work settings in different countries. Method: Cross-sectional international survey from October 2015 till November 2016 among pharmacists working in different settings to assess their level of confidence when delivering anticoagulants as well as to identify possible educational needs regarding this medication class. Validation of the survey was ensured. Results: Responses from 4212 pharmacists originating from 18 countries were obtained. Pharmacists’ level of confidence was significantly higher (p < 0.001) when advising patients on vitamin K antagonists (VKAs) versus non-vitamin K antagonists (NOACs). In general, hospital pharmacists displayed higher confidence levels compared to community pharmacists when advising patients on anticoagulation (p < 0.001). Two distinct patterns of confidence levels emerged relating to basic and advanced pharmaceutical care. Confidence levels when providing advanced pharmaceutical care were significantly higher for Oceania and lower for South America (p < 0.005). Conclusions: Pharmacists felt more confident in supporting patients receiving VKAs compared to the more recently introduced NOACs. With the increasing use of NOACs and the risks pertaining to anticoagulation therapy, it is essential to invest in education for pharmacists to address their knowledge gaps enabling them to confidently support patients receiving oral anticoagulants. The project was funded by the Davie-Ratnoff-Macfarlane (DRM) foundation. info:eu-repo/semantics/publishedVersion

Item does not contain fulltext The reduction of childhood obesity through the promotion of a healthy lifestyle is one of the most important public health challenges at the moment. It is known that the unhealthy habits of children can cause unavoidable side effects in their early stage of life, including both physical and mental consequences. This work considers that the physical activity level of children is a behaviour that can be spread throughout the social relations of children in their daily life at school. Therefore, the aim of this work is to define what the best strategy is to find 'targets' (i.e., influential children that can initiate behavioural change) for physical activity (PA) interventions that would affect the average PA of a population of Dutch school classes. We tuned a model based on the influence of the children’s peers in their social network, based on the data set from the MyMovez project - Phase I. Five intervention strategies were implemented, and their efficacy was compared. Once the targets were chosen, an increase of 17% was applied to their initial PA. Then, the diffusion model was run to verify the improvement on the PA of the whole network after one year. We discuss implications of the simulation results on which strategies may be used to make informed choices about the setup of social network interventions and future model improvements. Our results show that targeting more vulnerable children (i.e. in a worse environment) and applying a network optimization algorithm are the best solutions for this data set indicating that future interventions should aim for these two strategies. 8th International Conference on Simulation and Modeling Methodologies, Technologies and Applications (SIMULTECH 2018), Porto, Portugal , 29-31 July 2018

Despite the increased consideration of student mental health and the ongoing efforts of bettering intervention systems, one aspect remains relatively underexplored: the role of the instructor. The purpose of this paper is to propose and discuss a (re)conceptualized understanding of the postsecondary instructor – as one who not only creates, delivers, and/or facilitates academic curriculum, but who can also support the well-being of students. Instructors can carry a central place in supplementing or facilitating a number of initiatives available in higher education settings to support the mental health of students, whether this entails recognizing a concern, rendering a type of support, or redirecting a student elsewhere for further intervention.ᅟ

The benefit of statin therapy in patients with advanced chronic kidney disease remains uncertain. Randomized trials have questioned the efficacy of the drug in improving outcomes for on-dialysis populations, and many patients with end-stage renal disease are not currently taking statins. This study aimed to investigate the impact of statin use on survival of patients with vascular access performed at a vascular center for chronic dialysis. Consecutive end-stage renal disease patients admitted for vascular access surgery in 2006 to 2013 were reviewed. Information on therapy was retrieved and patients on statins were compared to those who were not on statins. Primary endpoint was 5-year survival. Independent predictors of mortality were assessed with Cox regression analysis adjusting for covariates (ie, age, sex, hyperlipidemia, hypertension, cardiac disease, cerebrovascular disease, chronic obstructive pulmonary disease, obesity, diabetes, and statins). Three hundred fifty-nine patients (230 males; mean age 68.9 ± 13.7 years) receiving 554 vascular accesses were analyzed: 127 (35.4%) were on statins. Use of statins was more frequent in patients with hypertension (89.8% v 81%; P = .034), hyperlipidemia (52.4% v 6.2%; P < .0001), coronary disease (54.1% v 42.6%; P = .043), diabetes (39.4% v 21.6%; P = .001), and obesity (11.6% v 2.0%; P < .0001). Mean follow-up was 35 months. Kaplan-Meier survival rates at 3 and 5 years were 84.4% and 75.9% for patients taking statins and 77.0% and 65.1% for those not taking statins (P = .18). Cox regression analysis selected statins therapy as the only independent negative predictor (odds ratio = 0.55; 95% confidence interval = 0.32-0.95; P = .032) of mortality, while age was an independent positive predictor (odds ratio = 1.05; 95% confidence interval = 1.03-1.08; P < .0001). Vascular access patency was comparable in statin takers and those not taking statins (P = .60). Use of statins might halve the risk of all-cause mortality at 5 years in adult patients with vascular access for chronic dialysis. Statins therapy should be considered in end-stage renal disease populations requiring dialysis access placement.

BACKGROUND PINK1 mutations are likely to affect mitochondrial function. The objective of this study was to study brain mitochondrial function in patients with early-onset Parkinson's disease, with or without PINK1 mutations. METHODS We investigated brain intracellular pH, mitochondrial activity, and energetics with functional magnetic resonance spectroscopy in patients with early-onset Parkinson's disease with PINK1 mutations (n = 10), early-onset Parkinson's disease without PINK1 mutations (n = 10), and healthy sex- and age-matched subjects (n = 20). We measured peak areas of phosphocreatine and beta adenosine triphosphate. RESULTS The EOPD- group had normal PCr + βATP contents at rest (P = NS) and under activation (P = NS), but reduced contents during recovery (P < 0.001). The EOPD+ group had abnormal PCr + βATP contents at rest (P < 0.001) and during activation (P < 0.001); during recovery, the contents only partially recovered (P < 0.001). Brain intracellular pH alterations were more severe with EOPD+ than with EOPD-. CONCLUSIONS Brain mitochondrial impairments were similar in early-onset Parkinson's disease without PINK1 mutations and late-onset Parkinson's disease. However, mitochondrial impairments were more severe in early-onset Parkinson's disease with PINK1 mutations. © 2020 International Parkinson and Movement Disorder Society.

The volume expansion, which occurs during the storage of hydrogen by metal hydrides, is a phenomenon linked to the lattice swelling or structural transition some samples. An experimental study realized out in order to characterize the progressive swelling and shrinking observed during the hydrogen absorption and desorption cycles by the compacted LaNi5 powder. The sample LaNi5 compacted has been submitted to 30 hydrogen absorption/desorption cycles, at the same cooling temperature equal 40 °C, under pressure 0.2 bar for the description state and 6 bars for absorption. As expected, the experimental results clearly indicate that the cyclic hydrogenation causes pellet volume changes, i.e. an almost reversible swelling/shrinking in the radial direction. However, this phenomenon can generate major mechanical stresses on the cell containing the pellet. The deformations react on the tank wall tantamount to the initial pressure of hydrogen. The values of the amplitude of the displacement increase progressively up to the 30th cycle, then, the phenomenon is stabilized up to 35 cycles, and this is explained that the relaxation of the metal limited the radial expansion.

Quantifying global international mobility patterns can improve migration governance. Despite decades of calls by the international community to improve international migration statistics, the availability of timely and disaggregated data about long-term and short-term migration at the global level is still very limited. In this study, we investigate the feasibility of using non-traditional data sources to fill existing gaps in migration statistics. To this end, we use anonymised and publicly available data provided by Facebook’s advertising platform. Facebook’s advertising platform classifies its users as “lived in country X” if they previously lived in country X, and now live in a different country. Drawing on statistics about Facebook Network users (Facebook, Instagram, Messenger, and the Audience Network) who have lived abroad and applying a sample bias correction method, we estimate the number of Facebook Network (FN) “migrants” in 119 countries of residence and in two time periods by age, gender, and country of previous residence. The correction method estimates the probability of a person being a FN user based on age, sex, and country of current and previous residence. We further estimate the correlation between FN-derived migration estimates and reference official migration statistics. By comparing FN-derived migration estimates in two different time periods, January-February and August-September 2018, we successfully capture the increase in Venezuelan migrants in Colombia and Spain in 2018. FN-derived migration estimates cannot replace official migration statistics, as they are not representative, and the exact methods the FN uses for classifying its users are not known, and might change over time. However, after carefully assessing the validity of the FN-derived estimates by comparing them with data from reliable sources, we conclude that these estimates can be used for trend analysis and early-warning purposes.

Objective Elderly patients are often turned down from receiving treatment for descending thoracic aortic diseases (DTADs) because of the uncertain benefits, especially in acute settings. This study investigated the impact of old age and timing of thoracic endovascular aortic repair (TEVAR) on outcomes of DTAD in patients older than 75 years of age. Methods Patients from a prospective TEVAR database were dichotomized by age (75 and 80 years of age). Older and young patients were compared in three timing scenarios: (1) elective procedures, (2) any emergency (within 15 days from onset), and (3) acute ruptures (any emergency subgroup). Primary outcome was perioperative mortality assessed at 30 and 90 days. Results Between 2003 and 2015, 141 consecutive TEVARs (71.6% men) were performed. Fifty-seven patients (40.4%) were older than 75 years of age; 28 were octogenarians. Eighty-three TEVARs were performed electively and 58 emergently. Among overall emergencies, 42 TEVARs were for acute ruptures. In the elective scenario, the 30-day mortality rate was 5.0% vs 0 (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.98-1.1; P = .23), and 90-day mortality was 7.5% vs 0, for patients older than 75 years of age vs those who were younger than 75, respectively ( P = .11). No octogenarian died. In the emergency scenario, 30-day mortality was 41.2% vs 9.8%, for patients older than 75 years of age vs those who were younger than 75, respectively (OR, 6.5; 95% CI, 1.6-26.6; P = .01) with unchanged rates at 90 days. The mortality rate was 50% for octogenarians. In the acute rupture scenario, 30-day mortality was 40% vs 11.1% (OR, 5.3; 95% CI, 1.10-25.99; P = .05) for patients older than 75 years of age vs those younger than 75 years of age and 46% vs 10% (OR, 7.5; 95% CI, 1.47-37.46; P = .016) for octogenarians vs younger patients. Rates remained unchanged at 90 days. Patients older than age 75 survived for a mean of 53.98 ± 7.7 months after TEVAR. Conclusions In the elderly patient population with DTAD, mortality risks from TEVAR are strongly related to timing and age. When compared to younger patients, those older than 75 years of age have three to five times the risk of mortality after urgent or emergent TEVAR. However, older patients should still be considered for emergent life-saving treatment, given that the majority survives.

The concept of risk assessment and the identification of surgical unfitness for vascular intervention is a particularly controversial issue today as the minimally invasive surgical population has increased not only in volume but also in complexity (comorbidity profile) and age, requiring an improved pre-operative selection and definition of high risk. A practical step by step (three steps, two points for each) approach for surgical risk assessment is suggested in this review. As a general rule, the identification of a "high risk" patient for vascular surgery follows a step by step process where the risk is clearly defined, quantified (when too "high"?), and thereby stratified based on the procedure, the patient, and the hospital, with the aid of predictive risk scores. However, there is no standardized, updated, and objective definition for surgical unfitness today. The major gap in the current literature on the definition of high risk in vascular patients explains the lack of sound validated predictive systems and limited generalizability of risk scores in vascular surgery. In addition, the concept of fitness is an evolving tool and many traditional high risk criteria and definitions are no longer valid. Given the preventive purpose of most vascular procedures performed in elderly asymptomatic patients, the decision to pursue or withhold surgery requires realistic estimates not only regarding individual peri-operative mortality, but also life expectancy, healthcare priorities, and the patient's primary goals, such as prolongation of life versus maintenance of independence or symptom relief. The overall "frailty" and geriatric risk burden, such as cognitive, functional, social, and nutritional status, are variables that should be also included in the analyses for stratification of surgical risk in elderly vascular patients.

The aging phenotype is quite heterogeneous, being the result of the capability of each individual to successfully or unsuccessfully response to stressors. The reduction of homeostatic reserve characterizing aging is accompanied by a remodeling of the endocrine system. Frailty has been indicated as a promising way for capturing the physiological decline as well as the biological aging of the individuals. In particular, the Frailty Index (FI), based on the assumption that health deficits tend to accumulate with aging, represents a quantitative measure of extreme interest.The study aims to correlate the thyroid hormone levels with FI in a population of centenarians and their offspring to capture the effects of thyroid remodeling in extreme longevity.The study described 593 well-characterized Italian subjects, including 180 centenarians, as well as 276 centenarian's offspring and 137 age-matched controls.FT3 levels and FT3/FT4 ratio were significantly lower (p 0.001) and TSH levels higher (p 0.001) in centenarians compared to the other groups, analysing both overall subjects and excluding subjects with hormone levels out of the normal ranges. In overall centenarians, we observed a negative correlation between FI and FT3 (ρ: -0.281, p 0.001), FT3/FT4 (ρ: -0.344, p 0.001) and TSH (ρ: -0.223, p 0.003) and a positive association between FI and FT4 (ρ: 0.189, p = 0.001). In centenarians with hormone levels within the normal ranges, similar negative correlations were observed between FI and FT3 (ρ: -0.201, p = 0.02) and FT3/FT4 (ρ: -0.264, p = 0.002). In this sub-analysis, FI positively correlated with FT4 and age (ρ: 0.167, p = 0.05; ρ: 0.219, p = 0.005, respectively). Conversely, no significant correlations were observed between hormone levels and FI in offspring and controls.We found an association between thyroid hormone levels and frailty in centenarians, underlying the significant role of thyroid in the aging process and longevity.

Background Various studies, mostly with animals, have provided evidence of adverse impacts of fluoride (F-) on bone density, collagen and microstructure, yet its effects on overall bone quality (strength) has not been clearly or extensively characterized in human populations. Objective In this observational study, we assessed variation in an integrated measures of bone quality in a population exposed to wide-ranging F- levels (0.3 to 15.5 mg/L) in drinking water, using a novel application of non-ionizing ultrasonic method. Method We collected 871 speed of sound (SOS) measurements from 341 subjects residing in 25 communities, aged 10–70 years (188 males and 153 females). All subjects received scans of the cortical radius and tibia, and adults over the age of 19 received an additional scan of the phalanx. Associations between F- in drinking water and 24-h urine samples, and SOS as a measure of bone quality, were evaluated in bivariate and multivariable regressions adjusting for age, sex, BMI, smoking, and toothpaste use. Results We found negative associations between F- exposure and bone quality at all three bones. Adult tibial SOS showed the strongest inverse association with F- exposure, which accounted for 20% of the variance in SOS measures (r = 0.45; n = 199; p, Highlights • A novel ultrasonic bone quality biomarker was tested in a population with low to high exposure to F.- • Negative associations were found between F- exposure and bone quality • Decreased bone quality reflects net bone loss, abnormal mineralization and altered collagen. • The finding highlights that F- exposure has complex effects on bone quality that go beyond changes in bone density alone.

Amino acid (AA) availability is a rate-limiting factor in the regulation of muscle protein metabolism and, consequently, a risk factor for age-related decline in muscle performance. AA transporters are emerging as sensors of AA availability and activators of mTORC1 signalling, acting as transceptors. Here, we evaluated the association of 58 single nucleotide polymorphisms (SNPs) in 10 selected AA transporter genes with parameters of physical performance (Hand Grip, Activity of Daily Living, Walking time). By analysing a sample of 475 subjects aged 50-89 years, we found significant associations with SLC7A5/LAT1, SLC7A8/LAT2, SLC36A1/PAT1, SLC38A2/SNAT2, SLC3A2/CD98, SLC38A7/SNAT7 genes. Further investigation of the SNPs in a cross-sectional study including 290 subjects aged 90-107 years revealed associations of SLC3A2/CD98, SLC38A2/SNAT2, SLC38A3/SNAT3, SLC38A9/SNAT9 variability with longevity. Finally, a longitudinal study examining the survival rate over 10 years showed age-dependent complexity due to possible antagonistic pleiotropic effects for a SNP in SLC38A9/SNAT9, conferring a survival advantage before 90 years of age and a disadvantage later, probably due to the remodelling of AA metabolism. On the whole, our findings support the hypothesis that AA transporters may impact on the age-related physical decline and survival at old age in a complex way, likely through a mechanism involving mTORC1 signalling.

Background Guidelines on the management of orally anticoagulated patients are continuously evolving, leading to an increased need for pharmacists to be fully integrated in care provision. Objective To identify self-reported gaps in confidence among practicing pharmacists in the area of anticoagulation. Setting Pharmacists in different work settings in different countries. Method Cross-sectional international survey from October 2015 till November 2016 among pharmacists working in different settings to assess their level of confidence when delivering anticoagulants as well as to identify possible educational needs regarding this medication class. Validation of the survey was ensured. Results Responses from 4212 pharmacists originating from 18 countries were obtained. Pharmacists’ level of confidence was significantly higher (p

Evidences from model systems and humans have suggested that genetic alterations in cell-ECM interactions and matrix-mediated cellular signaling cascades impact different aspects of metabolism and thereby life span. In this frame, a genetic variant (rs1981429) in the SDC4 gene encoding for syndecan-4, a central mediator of cell adhesion, has been associated with body composition in children and coronary artery disease in middle-age subjects. In order to test the hypothesis that syndecans might affect life span by affecting metabolic endophenotypes, 11 SNPs within the SDC4 gene were tested for association with longevity in a cohort of 64-107 aged individuals. We then determined whether the longevity-associated SNPs were correlated with metabolic parameters in the age group 64-85 years. RobustSNP association tests showed that rs1981429 was negatively associated with longevity (Theop=0.028), but also with high levels of triglyceride (Theop=0.028) and low levels of low-density lipoprotein-cholesterol (LDL-C) (Theop=0.009). On the other hand, rs2251252 was found to be positively correlated with longevity (Theop=0.018) and high LDL-C (Theop=0.022). On the whole, our results suggest that SDC4 alleles affect lipid profile in elderly subjects and may in part mediate the link between LDL-C and longevity.

Resumen Introduccion La encefalitis limbica puede presentarse con sintomas psiquiatricos, reversibles con el tratamiento. Caso clinico Adolescente previamente sana, que desarrollo sucesivamente agresividad, desinhibicion, hipersexualidad, deterioro cognitivo e intentos de suicidio y fue tratada con neurolepticos y benzodiacepinas. Dos meses mas tarde se le solicito resonancia magnetica cerebral, que mostro cambios indicativos de encefalitis limbica. Los estudios bioquimicos y radiologicos no evidenciaron causas tumorales, inflamatorias o infecciosas. Se le realizo tratamiento inmunomodulador, con marcada mejoria sintomatica y radiologica. Conclusion La consideracion diagnostica y el tratamiento apropiado de la encefalitis limbica pueden cambiar radicalmente el pronostico en pacientes con manifestaciones psiquiatricas.

Objective The aim of this study was to investigate outcomes of patients treated with endovascular repair (ER) with the use of fenestrated and branched stent grafts or open surgery (OS) for thoracoabdominal aortic aneurysm (TAAA) in a current series of patients. Methods All TAAA patients undergoing repair at three centers between January 2007 and December 2014 were included in a prospective database. Patients were stratified according to treatment by ER or OS, and outcomes were compared using propensity score matching (1:1). Covariates included age, sex, aneurysm extent, hypertension, coronary disease, chronic pulmonary disease, diabetes, and renal function. The primary end points were mortality and paraplegia. Secondary end points included any spinal cord ischemia (SCI), renal and respiratory insufficiency, and a composite of these complications or death at 30 days. All-cause survival and freedom from reintervention were compared in the two groups. Results Of 341 patients, 84 (25%) underwent ER and 257 underwent OS (75%). After propensity score matching (65 patients per group), no significant differences were observed in rates of 30-day mortality (7.7% in ER and 6.2% in OS; P = 1) and paraplegia (9.2% and 10.8%; P = 1). Any SCI, renal insufficiency, and respiratory insufficiency were 12.3% and 20% ( P = .34), 9.2% and 12.3% ( P = .78), and 0% and 12.3% ( P = .006) in ER and OS, respectively. The incidence of the composite end point was significantly lower in ER patients (18.5% in ER vs 36.0% in OS; P =.03). According to Kaplan-Meier estimates, all-cause survival at 24 months was 82.8% in ER and 84.9% in OS, with rates unchanged at 42 months ( P = .9). Rates of freedom from reintervention were 91.0% vs 89.7% at 24 months and 80.0% vs 79.9% at 42 months in ER vs OS, respectively ( P = .3). Conclusions A propensity score analysis in patients with TAAA undergoing repair suggests an early benefit from ER compared with OS with regard to the composite end point because of reduced 30-day respiratory complications. No significant differences were found in SCI and renal insufficiency at 30 days and in survival and reintervention rates at midterm.

Background Decompression sickness (DCS) is a potential danger and risk for both divers and aircrew alike. DCS is also a potential side effect of altitude (hypobaric) chamber training as well and can present long after training occurs. Literature review shows that altitude chamber induced DCS has approximately a 0.25% incidence. Case report A 32-yr-old, active duty military member developed symptoms of DCS 3 h after his hypobaric chamber training. Unfortunately, he did not seek treatment for DCS until 48 h after the exposure. His initial treatment included ground level oxygen therapy for 30 min at 12 L of oxygen per minute using a nonrebreathing mask. He achieved complete symptom resolution and was returned to duty. However, 12 d after his initial Flight Medicine evaluation, the patient returned complaining of a right temporal headache, multijoint pains, and fatigue. He was treated in the hyperbaric chamber and had complete resolution of symptoms. He was returned to flying status and 5 mo later denied any return of symptoms. Discussion Hypobaric chamber familiarity training is a requirement for all military aircrew personnel to allow them assess their ability to identify symptoms of hypoxia. This training method is not only costly to maintain, but it also places aircrew and chamber technicians at risk for potential long-term side effects from failed recompression treatment of DCS. We are presenting a case of recurrent DCS symptoms 12 d after initial ground level oxygen therapy.Gentry J, Rango J, Zhang J, Biedermann S. Latent presentation of decompression sickness after altitude chamber training in an active duty flier. Aerosp Med Hum Perform. 2017; 88(4):427-430.

Background and aims Non-alcoholic fatty liver disease is recognized not only as part of the metabolic syndrome but also as an independent predictor of cardiovascular disease. Methods In this study, NMR spectroscopy method, together with perfusion techniques, was used to detect subclinical brain vascular damage in subjects with NAFLD without overt atherosclerosis risk factors (i.e. hypertension, diabetes, hypercholesterolemia, obesity). Results The results suggest that subjects with histologically proven NAFLD have a reduced cerebral perfusion (CBFr) confined to limited brain areas, i.e., left semioval center and posterior cingulate cortex. No statistically significant differences in CBFr values were found, dividing the NAFLD cohort into subgroups, considering NAS score, presence/absence of NASH/fibrosis, and degree of steatosis. Conclusions Our data suggest that NAFLD per se may be involved in cerebral atherosclerotic disease. It will be interesting to draw longitudinal studies to determine whether these changes could evolve in more serious cerebral injury.

Background The International Pharmacists for Anticoagulation Care Taskforce (iPACT) is an expert group committed to enhancing the key role that pharmacists play in anticoagulation management. Pharmacists are ideally suited to monitor patients in this therapeutic area, but an assessment of their knowledge in providing consultations has not been formally evaluated. Purpose The purpose of this needs assessment survey was to identify self-reported gaps in competences and confidence among practising pharmacists in the area of anticoagulation; to identify variances in confidence levels between community and hospital pharmacists; and to examine areas of anticoagulation with varying needs. Material and methods An electronic link to the needs assessment survey was distributed to the pharmacists in the participating countries via their respective professional organisations or colleges. Countries with adequate response rates included in the preliminary statistical analysis were Canada, France, Portugal, Croatia, Brazil, Ireland, Hungary, New Zealand and the UK. Results 1692 pharmacists completed the survey. The distribution of respondents were Canada 357 (21.1%), France 304 (18.0%), New Zealand 237 (14.0%), Portugal 180 (10.6%), Croatia 180 (10.6%), Hungary 171 (10.1%), Brazil 76 (4.5%), Ireland 68 (4.0%) and the UK 60 (3.5%). Community pharmacists had the highest participation 759 (44.9%) while outpatient hospital pharmacists, inpatient hospital pharmacists working on wards and other practice sites represented 133 (7.9%), 339 (20.0%) and 461 (27.2%) of the population, respectively. Overall, pharmacists were less confident in providing information on DOACs compared with VKA (83.4% vs 55.5%; p 0.005) but significantly higher when comparing those pharmacists working on inpatient hospital wards (mean score=24.0 vs 26.0; p 0.005). More than 90% of pharmacists reported they would like additional education in anticoagulation with personalised e-learning as the preferred source. Conclusion These results highlight the apparent lack of confidence by both community and hospital pharmacists when discussing anticoagulation, particularly DOACs. Future continuing education programmes should be developed on electronic platforms focusing on practical clinical themes that apply across all settings. No conflict of interest

This study examined the relation between fluoride (F-) concentrations in fingernail clippings and urine and the prevalence and severity of enamel fluorosis (EF) among Ethiopian Rift Valley populations exposed to high levels of F- in drinking water. The utility of fingernail clippings as a biomarker for F- exposure and EF was also assessed for the first time in a high-F- region. The study recorded the EF status of 386 individuals (10 to 50years old), who consume naturally contaminated groundwater with widely varying F- concentration (0.6-15mg/L). The mean F- concentrations among residents of communities with primary reliance on groundwater were 5.1mg/kg (range: 0.5-34mg/kg) in fingernails and 8.9mg/L (range: 0.44-34mg/L) in urine. We show strong positive correlations between F- in drinking water and 12-hour urinary excretion (r=0.74, p 25years old) (p

The evolution of technology and introduction of new generation devices has resulted in increasing utilization of iliac branch graft (IBG) for endovascular treatment of iliac aneurysms. The indications of total endovascular repair have been expanded to more complex and bilateral iliac aneurysms. Technical success for IBGs is high, ranging from 86 to 100 % in most recent series. With the introduction of newer generation devices, the occlusion rates have declined and IBG patency of 81–100 % is achieved at variable follow-up lengths. Nevertheless, the risk of iliac occlusions, frequently associated with buttock claudication, and endoleak still remain possible concerns that require carefully pre-implant assessment and patient selection. This chapter summarizes the current results of IBGs.