The Functional Ability of MCI and Alzheimer’s Patients Predicts Caregiver Burden

Research shows that caregivers of dementia patients experience burden and psychological distress, but it is unclear whether or not caregivers of individuals with cognitive impairments that do not meet a diagnosis for dementia also experience similar burdens and psychological problems. Sixty patients and their caregivers participated in this study designed to examine caregiver burden. The patients completed activities-of-daily-living tasks and several neuropsychological tests assessing memory, abstract reasoning, and language. Caregivers completed self-report measures assessing caregiver burden and psychological distress. Results revealed that the caregivers of patients with mild Alzheimer’s disease (mAD) reported greater physical burden and feelings of missing out on life compared to individuals with mild cognitive impairment (MCI) caregivers. The mAD caregivers indicated greater depression and anxiety relative to MCI caregivers. Stepwise regression found that patient neuropsychological scores were worse predictors of caregiver burden than patients’ daily functioning. The conclusions of this study suggest that (1) caregivers of mAD are likely to experience more severe types of burden and psychological distress relative to caregivers of MCI patients, and that (2) patients’ daily functional abilities better predict caregivers’ burden and psychological distress than patients’ neuropsychological functioning. Study findings suggest that caregivers of those in the early stages of dementia, even in persons not yet meeting a diagnosis, experience psychological symptoms and burden, and that these caregivers’ experiences can be best predicted by the patients daily functional ability than by patients’ neuropsychological test scores

Probing the gravitational wave background from cosmic strings with LISA

Cosmic string networks offer one of the best prospects for detection of cosmological gravitational waves (GWs). The combined incoherent GW emission of a large number of string loops leads to a stochastic GW background (SGWB), which encodes the properties of the string network. In this paper we analyze the ability of the Laser Interferometer Space Antenna (LISA) to measure this background, considering leading models of the string networks. We find that LISA will be able to probe cosmic strings with tensions Gμ ≳ (10), improving by about 6 orders of magnitude current pulsar timing arrays (PTA) constraints, and potentially 3 orders of magnitude with respect to expected constraints from next generation PTA observatories. We include in our analysis possible modifications of the SGWB spectrum due to different hypotheses regarding cosmic history and the underlying physics of the string network. These include possible modifications in the SGWB spectrum due to changes in the number of relativistic degrees of freedom in the early Universe, the presence of a non-standard equation of state before the onset of radiation domination, or changes to the network dynamics due to a string inter-commutation probability less than unity. In the event of a detection, LISA's frequency band is well-positioned to probe such cosmic events. Our results constitute a thorough exploration of the cosmic string science that will be accessible to LISA

Zwitterionic nanofibers of super-glue for transparent and biocompatible multi-purpose coatings

Here we show that macrozwitterions of poly(ethyl 2-cyanoacrylate), commonly called Super Glue, can easily assemble into long and well defined fibers by electrospinning. The resulting fibrous networks are thermally treated on glass in order to create transparent coatings whose superficial morphology recalls the organization of the initial electrospun mats. These textured coatings are characterized by low liquid adhesion and anti-staining performance. Furthermore, the low friction coefficient and excellent scratch resistance make them attractive as solid lubricants. The inherent texture of the coatings positively affects their biocompatibility. In fact, they are able to promote the proliferation and differentiation of myoblast stem cells. Optically-transparent and biocompatible coatings that simultaneously possess characteristics of low water contact angle hysteresis, low friction and mechanical robustness can find application in a wide range of technological sectors, from the construction and automotive industries to electronic and biomedical devices

ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation

Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.Fil: Wolin, Ingrid A. V.. Universidade Federal de Santa Catarina; BrasilFil: Heinrich, Isabella A.. Universidade Federal de Santa Catarina; BrasilFil: Nascimento, Ana Paula M.. Universidade Federal de Santa Catarina; BrasilFil: Welter, Priscilla G.. Universidade Federal de Santa Catarina; BrasilFil: Sosa, Liliana del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Zanotto Filho, Alfeu. Universidade Federal de Santa Catarina; BrasilFil: Nedel, Cláudia Beatriz. Universidade Federal de Santa Catarina; BrasilFil: Lima, Lara Dias. Universidade Estadual do Ceará; BrasilFil: Osterne, Vinicius Jose Silva. Universidade Estadual do Ceará; BrasilFil: Pinto Junior, Vanir Reis. Universidade Estadual do Ceará; BrasilFil: Nascimento, Kyria S.. Universidade Estadual do Ceará; BrasilFil: Cavada, Benildo S.. Universidade Estadual do Ceará; BrasilFil: Leal, Rodrigo B.. Universidade Federal de Santa Catarina; Brasi

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Epidemiological and clinical characteristics of Streptococcus tigurinus endocarditis

Background: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. Methods: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. Results: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. Conclusions: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.JMM received a personal 80:20 research grant from the Institut d’InvestigacionsBiomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain during 2017–19. Nofunding entity played any role in the design of the study and data collection,analysis, and interpretation of data and in writing the manuscript

Non-productive angiogenesis disassembles Aß plaque-associated blood vessels

The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD

Impact of N on the atomic-scale Sb distribution in quaternary GaAsSbN-capped InAs quantum dots

The use of GaAsSbN capping layers on InAs/GaAs quantum dots (QDs) has recently been proposed for micro- and optoelectronic applications for their ability to independently tailor electron and hole confinement potentials. However, there is a lack of knowledge about the structural and compositional changes associated with the process of simultaneous Sb and N incorporation. In the present work, we have characterized using transmission electron microscopy techniques the effects of adding N in the GaAsSb/InAs/GaAs QD system. Firstly, strain maps of the regions away from the InAs QDs had revealed a huge reduction of the strain fields with the N incorporation but a higher inhomogeneity, which points to a composition modulation enhancement with the presence of Sb-rich and Sb-poor regions in the range of a few nanometers. On the other hand, the average strain in the QDs and surroundings is also similar in both cases. It could be explained by the accumulation of Sb above the QDs, compensating the tensile strain induced by the N incorporation together with an In-Ga intermixing inhibition. Indeed, compositional maps of column resolution from aberration-corrected Z-contrast images confirmed that the addition of N enhances the preferential deposition of Sb above the InAs QD, giving rise to an undulation of the growth front. As an outcome, the strong redshift in the photoluminescence spectrum of the GaAsSbN sample cannot be attributed only to the N-related reduction of the conduction band offset but also to an enhancement of the effect of Sb on the QD band structure