Relationships between leisure-time physical activity, obesity and disability in elderly men

BACKGROUND AND AIMS: Relationships have already been shown between leisure-time physical activity, obesity and body composition in young adults. However, this association needs to be confirmed in the elderly. The aim of this study was to investigate the relationship between leisure-time physical activity, obesity, preservation of muscle mass and disability in elderly men. METHODS: Cross-sectional analysis of a sample of 85 community-dwelling men, 68 to 79 years of age. Body mass index (BMI) was used to quantify obesity. Body composition was evaluated using Dual Energy X-ray Absorptiometry. Disability was measured using a modified version of the Activities of Daily Living scale. Leisure-time physical activity was evaluated by a validated self-administered questionnaire. RESULTS: A negative relation between obesity and weekly walking was observed. Walking less than 30 minutes per day was associated with a 2.7 greater probability of being obese (95% CI 1.1-6.7). High-intensity exercise, such as brisk walking or gardening, was inversely correlated with body fat (R = -0.296, p < 0.01) and directly correlated with appendicular skeletal mass (R = 0.238, p < 0.05). The prevalence of disability was the highest (58%) among overweight elderly subjects at the lowest tertile of exercise. Multiple logistic regression selected BMI as a positive predictor and high-intensity exercise as a negative predictor of disability. CONCLUSIONS: Our study shows that, in elderly men, leisure-time physical activity is inversely associated with body fat, BMI, and reported disability, but positively associated with appendicular fat-free mass. The highest prevalence of reported disability was observed in sedentary subjects with BMI higher than 25 kg/m2.     

The identification of a small but significant subset of patients still targetable with anti-HER2 inhibitors when affected by triple negative breast carcinoma

Purpose

Triple (ER-, PR-, HER2-) negative breast carcinoma lack targeted therapies, making this group of tumors difficult to treat. By definition, the lack of HER2 expression means a case scoring 0 or 1+ after immunophenotypical analysis and makes the patients avoiding therapeutical chances with anti-HER2 inhibitors. We sought to recruit from a group of triple negative breast carcinoma, patients eligible for effective personalized targeted therapy with anti-HER therapies on the basis of their HER2 gene status.

Methods

135 patients diagnosed with IHC triple negative breast carcinoma were studied. Whole tissue sections were used for in situ hybridization analysis.

Results

8/100 (8 %) of ductal-type triple negative breast carcinoma presented Her-2/neu gene amplification versus 2/35 (5.7 %) non-ductal triple negative breast carcinoma. Three cases showed a ratio 2.5. One case showed Her-2/neu heterogeneous gene amplification, ratio 2.3. The other six showed from 7 to 8 absolute Her-2/neu gene copy number. Two cases staged pT1c, and eight cases staged pT2. Eight cases graded G3 and two cases G2.

Conclusion

(1) Eight percentage of ductal and 5.7 % non-ductal-type triple negative breast carcinoma present Her-2/neu gene amplification, (2) the standard diagnostic flowchart “do not FISH in 0–1+ (HER2-) breast carcinoma” should be replaced by “do FISH in triple (ER-, PR-, HER2-) negative breast carcinoma,” to avoid loss of therapeutical chances in a cohort of such a patients, (3) we demonstrated the identification of a small but significant subset of patients targetable with anti-HER2 inhibitors, giving patients affected by (ex)triple negative breast carcinoma new personalized therapeutical chances.     

Plasma homocysteine, methylenetetrahydrofolate reductase mutation and carotid damage in elderly healthy women.

Plasma homocysteine (Hcy) is an independent vascular risk factor. Its remethylation to methionine is regulated by the activity of the enzyme 5,10-methylene tetrahydrofolate reductase (MTHFR). A C-to-T substitution at nucleotide 677 of the MTHFR gene is frequently associated to hyperhomocysteinemia. In this study, we evaluated the relationship among MTHFR C677T polymorphism, Hcy and some ultrasonographic parameters at the level of carotid arteries in 120 elderly women with normal ECG, normal blood pressure values, total cholesterol <250 mg/dl, normal glucose tolerance, normal albumin excretion rate. In all subjects, we measured Hcy by HPLC, MTHFR mutation by polymerase chain reaction followed by HinfI digestion and intima-media thickness (IMT), peak velocity of the systolic flow (SP(V)), end-diastolic velocity (ED(V)) and resistance and pulsatility indexes of intracranial circulation (RI and PI) by ultrasound imaging. Twenty-eight women were homozygotes for the wild type allele (Ala/Ala), 72 were heterozygotes (Ala/Val) and 20 were homozygotes for the mutation (Val/Val). Groups were comparable for age, blood pressure values and plasma lipid levels. Hcy was higher in Val/Val group; moreover, after adjustment for confounding factors, Val/Val had significantly greater IMT and ED(V) (P<0.001 and P<0.05, respectively). Logistic analysis revealed that Val/Val genotype was the strongest risk factor for IMT (OR 30.8, 95% CI 2.82-335.6). Our results show that, in elderly healthy women, Val/Val homozygosity for C677T mutation in MTHFR gene could identify subjects at risk for asymptomatic carotid atherosclerotic impairment.     

NALP3: a key player in caspase-1 activation

The NLR (NACHT-LRR) family of proteins have been implicated in the regulation of immune responses and cell death pathways. Some NLR family members can form multiprotein complexes, called inflammasomes, involved in the activation of pro-inflammatory caspases. Mutations in the NALP3/CIAS1/cryopyrin gene, a member of the NLR family, are linked to three auto-inflammatory disorders: Muckle-Wells syndrome, familial cold auto-inflammatory syndrome and neonatal-onset multisystem inflammatory disease. NALP3 along with the adaptor molecule ASC activates caspase-1 in response to a wide variety of stimuli. Here we review recent findings on the biology of NALP3 suggesting that it has functions beyond that of pathogen recognition.     

Resting metabolic rate, body-fat distribution, and visceral fat in obese women.

Resting metabolic rate (RMR) was evaluated in 27 obese women aged 16-49 y [body mass index (in kg/m2) 27-51] by indirect calorimetry. Visceral and subcutaneous adipose tissue areas, body fat, and fat-free mass (FFM) were measured by a single scan with computed tomography (CT); the waist-hip circumference ratio (W/H) was also used. Comparison between the lowest and the highest RMR quartiles--adjusted for age and FFM--revealed a higher W/H in the highest quartile (0.78 +/- 0.08 vs 0.88 +/- 0.08; P < 0.05). No difference was observed in CT indexes. No differences in W/H were observed after RMR was adjusted for age, FFM, and body fat. Our results point out that RMR, adjusted for FFM and age, correlates with body-fat distribution as evaluated by W/H, but not with visceral fat, as evaluated by CT. Correlations disappeared after RMR was adjusted for body fat as well.     

Pancreatic undifferentiated carcinoma with osteoclast‐like giant cells is genetically similar to,but clinically distinct from,conventional ductal adenocarcinoma

Undifferentiated carcinoma of the pancreas with osteoclast‐like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well‐defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.