Atomically Precise Ni-Pd Alloy Carbonyl Nanoclusters: Synthesis, Total Structure, Electrochemistry, Spectroelectrochemistry, and Electrochemical Impedance Spectroscopy

The molecular nanocluster [Ni36-xPd5+x(CO)46]6- (x = 0.41) (16-) was obtained from the reaction of [NMe3(CH2Ph)]2[Ni6(CO)12] with 0.8 molar equivalent of [Pd(CH3CN)4][BF4]2 in tetrahydrofuran (thf). In contrast, [Ni37-xPd7+x(CO)48]6- (x = 0.69) (26-) and [HNi37-xPd7+x(CO)48]5- (x = 0.53) (35-) were obtained from the reactions of [NBu4]2[Ni6(CO)12] with 0.9-1.0 molar equivalent of [Pd(CH3CN)4][BF4]2 in thf. After workup, 35- was extracted in acetone, whereas 26- was soluble in CH3CN. The total structures of 16-, 26-, and 35- were determined with atomic precision by single-crystal X-ray diffraction. Their metal cores adopted cubic close packed structures and displayed both substitutional and compositional disorder, in light of the fact that some positions could be occupied by either Ni or Pd. The redox behavior of these new Ni-Pd molecular alloy nanoclusters was investigated by cyclic voltammetry and in situ infrared spectroelectrochemistry. All three compounds 16-, 26-, and 35- displayed several reversible redox processes and behaved as electron sinks and molecular nanocapacitors. Moreover, to gain insight into the factors that affect the current-potential profiles, cyclic voltammograms were recorded at both Pt and glassy carbon working electrodes and electrochemical impedance spectroscopy experiments performed for the first time on molecular carbonyl nanoclusters

Exosome determinants of physiological aging and age-related neurodegenerative diseases

Aging is consistently reported as the most important independent risk factor for neurodegenerative diseases. As life expectancy has significantly increased during the last decades, neurodegenerative diseases became one of the most critical public health problem in our society. The most investigated neurodegenerative diseases during aging are Alzheimer disease (AD), Frontotemporal Dementia (FTD) and Parkinson disease (PD). The search for biomarkers has been focused so far on cerebrospinal fluid (CSF) and blood. Recently, exosomes emerged as novel biological source with increasing interest for age-related neurodegenerative disease biomarkers. Exosomes are tiny Extracellular vesicles (EVs; 30\u2013100 nm in size) released by all cell types which originate from the endosomal compartment. They constitute important vesicles for the release and transfer of multiple (signaling, toxic, and regulatory) molecules among cells. Initially considered with merely waste disposal function, instead exosomes have been recently recognized as fundamental mediators of intercellular communication. They can move from the site of release by diffusion and be retrieved in several body fluids, where they may dynamically reflect pathological changes of cells present in inaccessible sites such as the brain. Multiple evidence has implicated exosomes in age-associated neurodegenerative processes, which lead to cognitive impairment in later life. Critically, consolidated evidence indicates that pathological protein aggregates, including A\u3b2, tau, and \u3b1-synuclein are released from brain cells in association with exosomes. Importantly, exosomes act as vehicles between cells not only of proteins but also of nucleic acids [DNA, mRNA transcripts, miRNA, and non-coding RNAs (ncRNAs)] thus potentially influencing gene expression in target cells. In this framework, exosomes could contribute to elucidate the molecular mechanisms underneath neurodegenerative diseases and could represent a promising source of biomarkers. Despite the involvement of exosomes in age-associated neurodegeneration, the study of exosomes and their genetic cargo in physiological aging and in neurodegenerative diseases is still in its infancy. Here, we review, the current knowledge on protein and ncRNAs cargo of exosomes in normal aging and in age-related neurodegenerative diseases

Efficacy of Nutritional Interventions as Stand-Alone or Synergistic Treatments with Exercise for the Management of Sarcopenia

Sarcopenia is an age-related and accelerated process characterized by a progressive loss of muscle mass and strength/function. It is a multifactorial process associated with several adverse outcomes including falls, frailty, functional decline, hospitalization, and mortality. Hence, sarcopenia represents a major public health problem and has become the focus of intense research. Unfortunately, no pharmacological treatments are yet available to prevent or treat this age-related condition. At present, the only strategies for the management of sarcopenia are mainly based on nutritional and physical exercise interventions. The purpose of this review is, thus, to provide an overview on the role of proteins and other key nutrients, alone or in combination with physical exercise, on muscle parameters

Frailty Index and incident mortality, hospitalization and institutionalization in Alzheimer's disease: data from the ICTUS study.

BACKGROUND: The identification of an objective evaluation of frailty capable of predicting adverse outcomes in Alzheimer's disease is increasingly discussed. The purpose of this study was to investigate whether the Frailty Index (FI) predicts hospitalization, institutionalization, and mortality in Alzheimer's disease patients. METHODS: A prospective multicenter cohort study (follow-up = 2 years) that included 1,191 participants with Alzheimer's disease was carried out. The outcomes of interest were incident hospitalization, institutionalization, and mortality. The FI was calculated as the ratio of actual to thirty potential deficits, that is, deficits presented by the participant divided by 30. Severity of dementia was assessed using the Clinical Dementia Rating score. Cox proportional hazard models were performed. RESULTS: Mean age of the study sample was 76.2 (SD = 7.6) years. A quadratic relationship of the FI with age was reported at baseline (R 2 = .045, p < .001). The FI showed a statistically significant association with mortality (age- and gender-adjusted hazard ratio [HR] = 1.019, 95% confidence interval [CI] = 1.002-1.037, p = .031) and hospitalization (age- and gender-adjusted HR = 1.017, 95% CI = 1.006-1.029, p = .004) and a borderline significance with institutionalization. When the Clinical Dementia Rating score was simultaneously included in the age- and gender-adjusted models, the FI confirmed its predictive capacity for hospitalization (HR = 1.019, 95% CI = 1.006-1.032, p = .004), whereas the Clinical Dementia Rating score was the strongest predictor for mortality (HR = 1.922, 95% CI = 1.256-2.941, p = .003) and institutionalization (HR = 1.955, 95%CI = 1.427-2.679, p < .001). CONCLUSIONS: The FI is a robust predictor of adverse outcomes even after the stage of the underlying dementia is considered. Future work should evaluate the clinical implementation of the FI in the assessment of demented individuals in order to improve the personalization of care

Mean first passage time analysis reveals rate-limiting steps, parallel pathways and dead ends in a simple model of protein folding

We have analyzed dynamics on the complex free energy landscape of protein folding in the FOLD-X model, by calculating for each state of the system the mean first passage time to the folded state. The resulting kinetic map of the folding process shows that it proceeds in jumps between well-defined, local free energy minima. Closer analysis of the different local minima allows us to reveal secondary, parallel pathways as well as dead ends.Comment: 7 page

Ultrasound Evaluation of Diaphragmatic Mobility and Contractility After Osteopathic Manipulative Techniques in Healthy Volunteers : A Prospective, Randomized, Double-Blinded Clinical Trial

Objective: The purpose of this study was to investigate the effect of a session of osteopathic manipulative techniques on diaphragmatic motion and thickness in healthy participants. Methods: This was a prospective, randomized, double-blinded, case vs sham vs control clinical trial performed in an outpatient osteopathic clinic in Rome, Italy. Sixty-seven healthy participants, mean age 40.4 \ub1 14.5 years, received an ultrasound evaluation of diaphragmatic motion and thickness, followed by a systematic osteopathic evaluation. After randomization, the experimental group (n = 22) received osteopathic manipulation, whereas the sham (n = 22) and the control (n = 22) groups had a light touch approach and simple observation, respectively. After a 1-session intervention, new osteopathic and ultrasound assessments were repeated in all participants. Results: A statistically significant increase in diaphragmatic mobility was observed in the experimental group after the osteopathic manipulation (\u394 = 14.5 mm, P &lt; .001; analysis of variance P &lt; .001 vs both sham: \u394 = -0.22 mm, and control: \u394 = -2.09 mm groups). A strong linear relationship was observed between the diaphragmatic motion gradient, measured with ultrasonography, and the score assigned by the operator evaluating the change of diaphragm mobility after intervention. Conclusion: Osteopathic techniques used in this study improved the diaphragmatic motion (but not the muscle thickness) in healthy participants. Further studies are needed to confirm our findings and eventually identify the clinical conditions that may benefit from osteopathic manipulative treatment of the diaphragm

Morphology and taxonomy of the genus Ramazzottius (Eutardigrada; Ramazzottiidae) with the integrative description of Ramazzottius kretschmanni sp. nov

The species of the genus Ramazzottius (Ramazzottiidae, Eutardigrada) are among the most common and widespread tardigrade species in the world. Most of the 28 Ramazzottius species have been described only with morphological characters which were most of the time represented only with drawings. The discovery of a new species of this genus in the Black Forest (Germany) provided the opportunity to compare this species with the type specimens of ten Ramazzottius species, to propose the status of species dubia for Ramazzottius edmondabouti, and through new photographs to elucidate the anatomy of animals and eggs (in particular of the head sensory regions, eye spots, buccal tube, ornamentations of the dorsal posterior cuticle, and morphology of egg processes). These thorough observations led to a better understanding of the diversity and evolution, not only of this cosmopolitan genus, but also of other eutardigrade genera. The new species Ramazzottius kretschmanni is described with an integrative approach integrating morphological (light and electron microscopy observations and morphometric data) and molecular (cox1 and ITS2 genes) data. The PTP and ASAP analyses confirmed the validity of the new species from a molecular point of view. The new species is morphologically similar to Ramazzottius oberhaeuseri, but is distinguishable by the smooth cuticle, the presence of a “cheek-like” area on the head, and the size of egg processes as well as different sequences of the molecular markers

Optimal control strategies for tuberculosis treatment: a case study in Angola

We apply optimal control theory to a tuberculosis model given by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions. Numerical simulations are given using data from Angola.Comment: This is a preprint of a paper whose final and definite form will appear in the international journal Numerical Algebra, Control and Optimization (NACO). Paper accepted for publication 15-March-201