A novel estimate of biological aging by multiple fitness tests is associated with risk scores for age-related diseases.

Introduction: Recent research highlights the need for a correct instrument for monitoring the individual health status, especially in the elderly. Different definitions of biological aging have been proposed, with a consistent positive association of physical activity and physical fitness with decelerated aging trajectories. The six-minute walking test is considered the current gold standard for estimating the individual fitness status in the elderly. Methods: In this study, we investigated the possibility of overcoming the main limitations of assessing fitness status based on a single measure. As a result, we developed a novel measure of fitness status based on multiple fitness tests. In 176 Sardinian individuals aged 51-80 years we collected the results of eight fitness tests to measure participants' functional mobility, gait, aerobic condition, endurance, upper and lower limb strength, and static and dynamic balance. In addition, the participants' state of health was estimated through validated risk scores for cardiovascular diseases, diabetes, mortality, and a comorbidity index. Results: Six measures contributing to fitness age were extracted, with TUG showing the largest contribution (beta = 2.23 SDs), followed by handgrip strength (beta = -1.98 SDs) and 6MWT distance (beta = -1.11 SDs). Based on fitness age estimates, we developed a biological aging measure using an elastic net model regression as a linear combination of the results of the fitness tests described above. Our newly developed biomarker was significantly associated with risk scores for cardiovascular events (ACC-AHA: r = 0.61; p = 0.0006; MESA: r = 0.21; p = 0.002) and mortality (Levine mortality score: r = 0.90; p = 0.0002) and outperformed the previous definition of fitness status based on the six-minute walking test in predicting an individual health status. Discussion: Our results indicate that a composite measure of biological age based on multiple fitness tests may be helpful for screening and monitoring strategies in clinical practice. However, additional studies are needed to test standardisation and to calibrate and validate the present results.

Management of a Hypomineralisation of the Enamel by Applying a Remineraliser Based on Zinc Hydroxyapatite (microRepair).

According to our experience, the treatment with remineralising mousse based on biomimetic nanohydroxyapatite has the advantage of being easily implemented by all patients as it is economical and absolutely noninvasive. The following case report reports the results obtained from the use of a mousse based on biomimetic nanohydroxyapatite for the treatment of incisor and molar hypomineralisation. This case report illustrates the case of a 4-year-old patient who was diagnosed with MIH and was subjected to remineralising treatments at home for six months, at alternating periods. Throughout the observation period, the painful perception of the lesions was detected through an assessment scale, and the clinical appearance was documented photographically. One year after the diagnosis, all the elements involved no longer showed any symptoms.

Focal nodular hyperplasia: new findings at Doppler ultrasonography.

OBJECTIVE: The aim of our study was to explore the features of focal nodular hyperplasia (FNH) at Doppler ultrasonography, analyzing specifically the presence of intratumoral venous flow in patients with an established diagnosis of FNH. Previous studies showed that using a venous Doppler spectrum, intratumoral vessels are often depicted in hepatocellular adenoma (HCA) but less frequently in FNH. PATIENTS AND METHODS: Forty-five FNHs from thirty-three consecutive patients (26 female, 7 male; mean±SD age: 40±13) underwent color Doppler ultrasonography and spectral analysis according to a standardized protocol. FNH diagnosis was established by the presence of typical behavior at contrast-enhanced ultrasound (CEUS) associated with another imaging technique (contrast-enhanced computed tomography [ceCT] or contrast-enhanced magnetic resonance [ceMR]). A biopsy was performed when imaging was inconclusive. All data concerning Doppler analysis were reviewed by two more operators, blinded to the final diagnosis, and the interobserver agreement for the presence of venous Doppler signal was determined by Cohen's Kappa. RESULTS: Of the 33 patients, 24 had a single solitary focus, and 9 had multiple foci. Lesion diameter ranged between 1.2 and 8.9 cm (mean ± SD 3.2±1.6 cm). The central feeding artery with the typical arterial spectrum was detected in all 45 lesions, whereas the spoke-wheel sign was observed in 18 cases (40%). A venous Doppler signal was detected in 35 FNHs (77.8%), and in 60% of them, it was identified in the center of the lesion. CONCLUSIONS: Venous Doppler signal located in the center of the lesion suspected to be a hypervascular benign lesion cannot be considered a typical HCA feature since it has been detected in a high percentage of FNH cases.

[Cognitive decline in geriatric oncology: Trends, evaluation and treatment]. / Cancer de la personne âgée : rechercher, évaluer et prendre en charge le déclin cognitif.

Cancer prevalence increases with aging. Prevalent or incident neurocognitive disorders are frequent in geriatric oncology. Cognitive decline associated with cancer increases the risk of under or over-cancer treatment and makes therapeutic decisions complex. In this context, we present tools to optimize cognitive impairment screening, identification of underlying mechanisms and specific treatments. Geriatric specialists intervention can help global care, social services utilization and patient's orientation when ambulatory cares become difficult.

How long does the volumizing effect of a Zingiber officinale-based lip plumper last?

OBJECTIVE: Lip plumpers should enhance lip volume. It has been shown that no noticeable result was obtained after long term use of these products. The present study has been carried out to assess lip plumpers' short term effectiveness within 2 h from application. METHODS: Effectiveness was assessed using non-invasive techniques. The effect on vascularisation was analyzed with the Mexameter MX 16® , and the volume enhancing effect was assessed by anthropometric measures and profilometry analysis from 3D scanning electron microscope (SEM) images using Alicona's MEX software. Sixty female volunteers were recruited for the study and the measurements were taken 15, 30, 60, 90 and 120 min after product application. RESULTS: Product application produced a statistically significant increase of lip vascularisation during the first 15 min, which stayed unchanged until the 30th min, then decreased in intensity. The volumizing effect was revealed by 3D profilometry analysis only, not by anthropological measurements. The use of 3D SEM images showed an increase of 0.50 mm in the protrusion of the lip vermilion (MHP parameter) during the first 15 min from product application. CONCLUSION: Results suggest that the lip plumper temporarily enhances vasodilation and increases lip volume.

Characterization of ankle dorsiflexors performance in healthy subjects following maximal-intensity isokinetic resistance training.

The purpose of this randomized trial was to examine, in healthy subjects, the effect of unilateral isokinetic-concentric training of the dominant ankle dorsiflexors (DF) on the peak moment (PM), mean PM (MPM), maximal work and mean work (meanW). Thirty volunteers (26.7±4.6years old) underwent bilateral isokinetic testing of ankle DF at 45 and 90°/s. Participants were randomly assigned to a control or a training group. The training lasted 4weeks (4-day/week). All dynamometric parameters increased significantly only in the training group for the trained leg (p<0.05), with greater gains in work (32-47% at 45°/s and 31-41% at 90°/s) than moment variables (14-18% at 45°/s and 14-28% at 90°/s). Similar increases in strength were also noted at both angular velocities in the untrained leg (p<0.01) for both work and moment parameters, depicting a cross-training effect. Correlations between 'moments' and 'works' increased in both legs after training from 0.59-0.77 to 0.79-0.95. Principal component analysis indicated that, at baseline, PM showed the highest weight on DF performance; after training, meanW at 90°/s and MPM at 45°/s exhibited the highest loadings. High-intensity training of ankle DF increase the ability in generating energy throughout the entire range of motion rather than maximizing the PM.

Deregulation of DNA-dependent protein kinase catalytic subunit contributes to human hepatocarcinogenesis development and has a putative prognostic value.

BACKGROUND: The DNA-repair gene DNA-dependent kinase catalytic subunit (DNA-PKcs) favours or inhibits carcinogenesis, depending on the cancer type. Its role in human hepatocellular carcinoma (HCC) is unknown. METHODS: DNA-dependent protein kinase catalytic subunit, H2A histone family member X (H2AFX) and heat shock transcription factor-1 (HSF1) levels were assessed by immunohistochemistry and/or immunoblotting and qRT-PCR in a collection of human HCC. Rates of proliferation, apoptosis, microvessel density and genomic instability were also determined. Heat shock factor-1 cDNA or DNA-PKcs-specific siRNA were used to explore the role of both genes in HCC. Activator protein 1 (AP-1) binding to DNA-PKcs promoter was evaluated by chromatin immunoprecipitation. Kaplan-Meier curves and multivariate Cox model were used to study the impact on clinical outcome. RESULTS: Total and phosphorylated DNA-PKcs and H2AFX were upregulated in HCC. Activated DNA-PKcs positively correlated with HCC proliferation, genomic instability and microvessel density, and negatively with apoptosis and patient's survival. Proliferation decline and massive apoptosis followed DNA-PKcs silencing in HCC cell lines. Total and phosphorylated HSF1 protein, mRNA and activity were upregulated in HCC. Mechanistically, we demonstrated that HSF1 induces DNA-PKcs upregulation through the activation of the MAPK/JNK/AP-1 axis. CONCLUSION: DNA-dependent protein kinase catalytic subunit transduces HSF1 effects in HCC cells, and might represent a novel target and prognostic factor in human HCC.

Immunohistohemical expression of the chemokine fractalkine and its receptor in the human brain cortex after severe traumatic brain injury and brain hemorrhage.

AIM: Recent experimental studies have suggested that chemokines, a subclass of chemoattractant cytokines which play an important role in regulating leukocyte migration and intercellular communication, participate in brain responses of traumatic injury. Fractalkine (CX3CL1) is a peculiar chemokine, the only one with a CX3C motif, existing both as a soluble and a membrane-anchored molecule. In the brain, Fractalkine has been suggested to have a role in neuroprotection under experimental conditions of brain injury. METHODS: Eighteen human brain samples were obtained during surgery of decompressive craniotomy for severe traumatic brain injury (TBI) or after spontaneous intracranial haemorrhage (ICH). Five normal brain samples were obtained during surgery for unruptured intracranial aneurysms (standard gyrectomy). Immunohistochemistry of formalin fixed and paraffin embedded tissues was performed in order to verify the expression of fractalkine and its receptor (CX3CR1). The values of chemokine and receptor expression were correlated with the clinical parameters of the patients. RESULTS: The chemokine fractalkine was significantly upregulated in the neural compartment after brain injury, compared to normal brain samples. Intensity scores were significantly higher when the interval between injury and surgery was >5 h, (P=0.015). In the glial compartment, Fractalkine expression was significantly associated with less severe clinical conditions and lower intracranial pressure at surgery (P=0.014). Expression of the receptor CX3CR1 was detected, at low intensity, on both glial and neurons. Higher expression in neurons was associated with better clinical conditions (Glasgow score) of patients at admission (P=0.037). CONCLUSION: The results of this study highlights for the first time that fractalkine and its receptor CX3CR1 are expressed in the human brain after TBI and ICH and may be involved in the limitation of tissue damage.

Molecular pathways linking metabolic inflammation and thermogenesis.

Obesity is caused by chronic positive energy balance because of higher energy intake relative to energy expenditure. Thermogenesis, the capacity of an organism to produce heat, is an important component of energy expenditure. Thus targeting the molecular mechanisms controlling thermogenesis could be an effective strategy for the prevention or treatment of obesity. Thermogenesis is modulated by three major factors: environmental temperature, nutrient quantity and quality, and by systemic inflammation. Obesity is now recognized to be a state of chronic low-grade systemic inflammation, which has been proposed to play a major role in the pathogenesis of obesity and obesity-associated diseases. This review discussed the molecular pathways that are recruited during metabolic inflammation and that are also implicated in the control of thermogenesis and energy balance. It emerges that the complex signalling network recruited during metabolic inflammation exerts a balanced action on the modulation of thermogenesis and energy balance, with some pathways promoting weight gain whereas other pathways have opposite actions. It is thus concluded that immunomodulation of metabolic inflammation, rather than an anti-inflammatory intervention aiming at its suppression, may be a more promising strategy to increase thermogenesis for the treatment or prevention of obesity and its associated diseases.

Body composition phenotypes in pathways to obesity and the metabolic syndrome.

Dynamic changes in body weight have long been recognized as important indicators of risk for debilitating diseases. While weight loss or impaired growth can lead to muscle wastage, as well as to susceptibility to infections and organ dysfunctions, the development of excess fat predisposes to type 2 diabetes and cardiovascular diseases, with insulin resistance as a central feature of the disease entities of the metabolic syndrome. Although widely used as the phenotypic expression of adiposity in population and gene-search studies, body mass index (BMI), that is, weight/height(2) (H(2)), which was developed as an operational definition for classifying both obesity and malnutrition, has considerable limitations in delineating fat mass (FM) from fat-free mass (FFM), in particular at the individual level. After an examination of these limitations within the constraints of the BMI-FM% relationship, this paper reviews recent advances in concepts about health risks related to body composition phenotypes, which center upon (i) the partitioning of BMI into an FM index (FM/H(2)) and an FFM index (FFM/H(2)), (ii) the partitioning of FFM into organ mass and skeletal muscle mass, (iii) the anatomical partitioning of FM into hazardous fat and protective fat and (iv) the interplay between adipose tissue expandability and ectopic fat deposition within or around organs/tissues that constitute the lean body mass. These concepts about body composition phenotypes and health risks are reviewed in the light of race/ethnic variability in metabolic susceptibility to obesity and the metabolic syndrome.