Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.

Cognitive screening in Parkinson's disease: Comparison of the Parkinson Neuropsychometric Dementia Assessment (PANDA) with 3 other short scales.

Background: Cognitive screening is crucial in Parkinson's disease (PD). However, there is still a lack of short tools in French. In this study, we aimed to compare the Parkinson Neuropsychometric Dementia Assessment (PANDA) with the Mini Mental Parkinson (MMP), the Mini Mental State Examination (MMSE) and the Clock Test in French-speaking patients.

What Goes Wrong with Lon in Ageing?

We have shown previously that the product of the human lon gene, the Lon protease, selectively degrades oxidized mitochondrial proteins, thus preventing their aggregation and cross-linking. We have also shown that lon is a stress-responsive gene, whose protease product is a stress-responsive protein that is induced by multiple stressors, including heat shock, serum starvation, and oxidative stress. Lon induction, by pre-treatment with low-level stress, protects against oxidative protein damage, diminished mitochondrial function, and loss of cell proliferation, induced by toxic levels of hydrogen peroxide.

TGFβ1 rapidly activates Src through a non-canonical redox mechanism.

Transforming growth factor-β (TGF-β1 is involved in multiple cellular processes including epithelial-mesenchymal transition (EMT), and many of them are mediated through activating Src kinase, a non-receptor tyrosine kinase. How TGF-β1activates Src remains largely unknown. In the classic pathway Src activation is initiated by dephosphorylation of pTyr530 followed by a conformational change that permits autophosphorylation at Tyr419 with full activation.

Acute Electrical Pulse Stimulation and Hyperglycemia Regulates RCAN1-4 in C2C12 myotubes through Oxidative Stress.

Regulator of Calcineurin1 (RCAN1) controls the Sr/Thr phosphatase, Calcineurin. RCAN1 has never been studied in-vitro in myotubes following acute Electrical Pulse Stimulation (EPS) which recapitulates the physiological effect of exhaustive exercise and hyperglycemia (HG). 144 h differentiated C2C12 myotubes were treated either with high glucose (HG) at 15mM or kept as control for 48 h.

Dysregulated metabolism contributes to oncogenesis.

Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark.

4-Hydroxynonenal activates Src through a non-canonical pathway that involves EGFR/PTP1B.

Src, a non-receptor protein tyrosine kinase involved in many biological processes, can be activated through both redox-dependent and independent mechanisms. 4-Hydroxy-2-nonenal (HNE) is a lipid peroxidation product that is increased in pathophysiological conditions associated with Src activation. This study examined how HNE activates human c-Src.

Altered moral decision-making in patients with idiopathic Parkinson's disease.

Background: Moral decision-making essentially contributes to social conduct. Although patients with Parkinson's disease (PD) show deficits in (non-moral) decision making and related neuropsychological functions, i.e.

Aging in Poland.

With 38 million residents, Poland has the eighth-largest population in Europe. A successful transition from communism to democracy, which began in 1989, has brought several significant changes to the country's economic development, demographic structure, quality of life, and public policies. As in the other European countries, Poland has been facing a rapid increase in the number of older adults.

Depressive Symptoms, Transitions to Widowhood, and Informal Support From Adult Children Among Older Women and Men in Japan.

This study examines the relationships among depressive symptoms, transitions to widowhood, worsening health, and family support in Japan over 10 years. The analyses focus on availability and receipt as the two primary dimensions of intergenerational support relationships. We used growth curve models to analyze data from the Nihon University Japanese Longitudinal Study of Aging, finding that (1) becoming widowed correlated with increased depressive symptoms and this relationship was weaker among women than men, (2) continuous widowhood was associated with fewer depressive symptoms over time, (3) transitions to coresidence with sons and daughters among the widowed was correlated with reduced depressive symptoms, (4) self-reported health and difficulty with activities of daily living were predictors of depressive symptoms over time.

Possession divestment by sales in later life.

Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers' capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation.

Twentieth century surge of excess adult male mortality.

Using historical data from 1,763 birth cohorts from 1800 to 1935 in 13 developed countries, we show that what is now seen as normal-a large excess of female life expectancy in adulthood-is a demographic phenomenon that emerged among people born in the late 1800s. We show that excess adult male mortality is clearly rooted in specific age groups, 50-70, and that the sex asymmetry emerged in cohorts born after 1880 when male:female mortality ratios increased by as much as 50% from a baseline of about 1.1.

The calcineurin antagonist RCAN1-4 is induced by exhaustive exercise in rat skeletal muscle.

The aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus.

Oxidative stress response and Nrf2 signaling in aging.

Increasing oxidative stress, a major characteristic of aging, has been implicated in a variety of age-related pathologies. In aging, oxidant production from several sources is increased, whereas antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins, also decline.

Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder.

CDKL5 mutation is associated with an atypical Rett syndrome (RTT) variant. Recently, cholesterol homeostasis perturbation and oxidative-mediated loss of the high-density lipoprotein receptor SRB1 in typical RTT have been suggested. Here, we demonstrate an altered lipid serum profile also in CDKL5 patients with decreased levels of SRB1 and impaired activation of the defensive system Nrf2.

The Tres Ventanas Mummies of Peru.

The Tres Ventanas mummies of Peru are thought to be among the oldest mummies in existence, dating to between 8,000 and 10,000 years ago. A preliminary assessment is made of the potential of these mummies for use in future research on mummified remains. Although the Tres Ventanas cave and the four mummies were explored and then excavated by Frederic Engel in 1966-67, and the project is named in his honor as the "Engel Study Group", the importance of both the physical remains and the context in which they were found has only come to light in the last few years.

Sex differences in cognitive training effects of patients with amnestic mild cognitive impairment.

Cognitive training has been shown to be effective in improving cognitive functions in patients with Mild Cognitive Impairment (MCI). However, data on factors that may influence training gains including sociodemographic variables such as sex or age is rare. In this study, the impact of sex on cognitive training effects was examined in N = 32 age- and education-matched female (n = 16) and male (n = 16) amnestic MCI patients (total sample: age M = 74.

The Effects of Antipsychotic Quality Reporting on Antipsychotic and Psychoactive Medication Use.

Objective: The objective of this study is to examine how nursing homes changed their use of antipsychotic and other psychoactive medications in response to Nursing Home Compare's initiation of publicly reporting antipsychotic use in July 2012.

Research Design And Subjects: The study includes all state recertification surveys (n = 40,415) for facilities six quarters prior and post the initiation of public reporting. Using a difference-in-difference framework, the change in use of antipsychotics and other psychoactive medications is compared for facilities subject to public reporting and facilities not subject to reporting.

TGFβ1 rapidly activates Src through a non-canonical redox signaling mechanism.

Transforming growth factor-β1 (TGF-β) is involved in multiple cellular processes through Src activation. In the canonical pathway, Src activation is initiated by pTyr530 dephosphorylation followed by a conformational change allowing Tyr419 auto-phosphorylation. A non-canonical pathway in which oxidation of cysteine allows bypassing of pTyr530 dephosphorylation has been reported.

[The study of general satisfaction in stationary social institutions (Yaroslavl Regional Gerontology Center)].

The article analyzes the satisfaction with social environment of patients of older age groups living in the Yaroslavl Regional Gerontology Center. On the basis of a survey of 118 patients of older age groups the satisfaction with the living conditions in the institution, the provision of socio-medical assistance, catering, leisure activities and social environment were assessed. 92,4 % of patients reported of their satisfaction, in general, with the stay.

Validation and modification of dried blood spot-based glycosylated hemoglobin assay for the longitudinal aging study in India.

Objectives: This study aims to validate a modified dried blood spot (DBS)-based glycosylated hemoglobin (HbA1c) assay protocol, after a pretest in India showed poor correlation between the original DBS-based protocol and venous results.

Methods: The original protocol was tested on different chemistry analyzers and then simplified at the University of Washington (UW). A second pretest was conducted in India to validate the modified assay protocol, using 44 quality control specimens.

Even free radicals should follow some rules: a guide to free radical research terminology and methodology.

Free radicals and oxidants are now implicated in physiological responses and in several diseases. Given the wide range of expertise of free radical researchers, application of the greater understanding of chemistry has not been uniformly applied to biological studies. We suggest that some widely used methodologies and terminologies hamper progress and need to be addressed.

NADPH oxidase activation and 4-hydroxy-2-nonenal/aquaporin-4 adducts as possible new players in oxidative neuronal damage presents in drug-resistant epilepsy.

A correlation between epilepsy and cellular redox imbalance has been suggested, although the mechanism by which oxidative stress (OS) can be implicated in this disorder is not clear. In the present study several oxidative stress markers and enzymes involved in OS have been determined. In particular, we examined the levels of 4-hydroxy-2-nonenal protein adducts (HNE-PA), a by-product of lipid peroxidation, and the activation of NADPH oxidase 2 (NOX2), as cellular source of superoxide (O(2)(-)), in surgically resected epileptic tissue from drug-resistant patients (N=50).

The 'mitoflash' probe cpYFP does not respond to superoxide.

Ageing and lifespan of organisms are determined by complicated interactions between their genetics and the environment, but the cellular mechanisms remain controversial. There have been a number of studies suggesting that cellular energy metabolism and free radical dynamics affect lifespan, implicating mitochondrial function. Recently, Shen provided apparent mechanistic insight by reporting that mitochondrial oscillations of ‘free radical production’, called ‘mitoflashes’, in the pharynx of 3-day old correlated inversely with lifespan.