Adiposity Predicts Cognitive Decline in Older Persons with Diabetes: A 2-Year Follow-Up

BACKGROUND: The mechanisms related to cognitive impairment in older persons with Type 2 diabetes (DM) remains unclear. We tested if adiposity parameters and body fat distribution could predict cognitive decline in older persons with DM vs. normal glucose tolerance (NGT). METHODOLOGY: 693 older persons with no dementia were enrolled: 253 with DM in good metabolic control; 440 with NGT (age range:65-85 years). Longitudinal study comparing DM and NGT individuals according to the association of baseline adiposity parameters (body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC) and total body fat mass) to cognitive change (Mini Mental State Examination (MMSE), a composite score of executive and attention functioning (CCS) over time. FINDINGS: At baseline, in DM participants, MMSE correlated with WHR (beta = -0.240; p = 0.043), WC (beta = -0.264; p = 0.041) while CCS correlated with WHR (beta = -0.238; p = 0.041), WC (beta = -0.326; p = 0.013) after adjusting for confounders. In NGT subjects, no significant correlations were found among any adiposity parameters and MMSE, while CCS was associated with WHR (beta = -0.194; p = 0.036) and WC (beta = -0.210; p = 0.024). Participants with DM in the 3(rd) tertile of total fat mass showed the greatest decline in cognitive performance compared to those in 1(st) tertile (tests for trend: MMSE(p = 0.007), CCS(p = 0.003)). Logistic regression models showed that 3(rd) vs. 1(st) tertile of total fat mass, WHR, and WC predicted an almost two-fold decline in cognitive function in DM subjects at 2(nd) yr (OR 1.68, 95%IC 1.08-3.52). CONCLUSIONS: Total fat mass and central adiposity predict an increased risk for cognitive decline in older person with DM

Melatonin regulates mesenchymal stem cells differentiation : a review

none10Among the numerous functions of melatonin, the control of survival and differentiation of mesenchymal stem cells (MSCs) has been recently proposed. MSCs are a heterogeneous population of multipotent elements resident in tissues such as bone marrow, muscle, and adipose tissue, which are primarily involved in developmental and regeneration processes, gaining thus increasing interest for tissue repair and restoration therapeutic protocols. Receptor-dependent and receptor-independent responses to melatonin are suggested to occur in these cells. These involve antioxidant or redox-dependent functions of this indolamine as well as secondary effects resulting from autocrine and paracrine responses. Inflammatory cytokines and adipokines, proangiogenic/mitogenic stimuli, and other mediators that influence the differentiation processes may affect the survival and functional integrity of these mesenchymal precursor cells. In this scenario, melatonin seems to regulate signaling pathways that drive commitment and differentiation of MSC into osteogenic, chondrogenic, adipogenic, or myogenic lineages. Common pathways suggested to be involved as master regulators of these processes are the Wnt/b-catenin pathway, the MAPKs and the, TGF-b signaling. In this respect melatonin emerges a novel and potential modulator of MSC lineage commitment and adipogenic differentiation. These and other aspects of the physiological and pharmacological effects of melatonin as regulator of MSC are discussed in this review.openLuchetti, Francesca; Canonico, Barbara; Bartolini, Desiree; Arcangeletti, Marcella; Ciffolilli, Silvia; Murdolo, Giuseppe; Piroddi, Marta; Papa, Stefano; Reiter, Russel J.; Galli, FrancescoLuchetti, Francesca; Canonico, Barbara; Bartolini, Desiree; Arcangeletti, Marcella; Ciffolilli, Silvia; Murdolo, Giuseppe; Piroddi, Marta; Papa, Stefano; Reiter, Russel J.; Galli, Francesc

Autonomic dysfunction in Alzheimer's disease: tools for assessment and review of the literature

Autonomic dysfunction is very common in patients with dementia, and its presence might also help in differential diagnosis among dementia subtypes. Various central nervous system structures affected in Alzheimer's disease are also implicated in autonomic nervous system regulation, and it has been hypothesized that the deficit in central cholinergic function observed in Alzheimer's disease could likely lead to autonomic dysfunction. Several feasible tests can be used in clinical practice for the assessment of parasympathetic and sympathetic functions, especially in terms of cardiovascular autonomic modulation. In this review, we describe the different tests available and the evidence from the literature which indicate a definite presence of autonomic dysfunction in dementia at various degrees. Importantly, the recognition of dysautonomia, besides possibly being an early marker of dementia, would help prevent the disabling complications which increase the risk of morbidity, institutionalization, and mortality in these individuals

Relatives of Crohn's disease patients and breast cancer: An overlooked condition

AbstractRecent data suggest that patients suffering from Crohn’s disease (CD) may be at higher risk of developing extra-intestinal malignancies. This is attributed to inflammation and immunodepression due to medications. However, a genetic predisposition cannot ruled out. In the present study we investigated the prevalence of breast cancer in first-degree female relatives of CD patients compared with relatives of patients without evidence of gastrointestinal diseases. A total of 1302 female first-degree relatives of CD patients and 1294 relatives of controls were included. We found that CD was an independent risk factor for breast cancer development (OR = 2.76, 95% CI = 1.2–6.2; p = 0.017), and this is particularly evident in mothers (3.6% vs 1%, p = 0.009 − OR = 3.7, 95% CI 1.4–10). Among CD group, smoking habit of CD patients was associated with increased risk of cancer compared with relatives of non-smokers (7.7% vs 2.9%, p = 0.01 – OR = 2.8 95% CI 1.2–6.6). Intriguingly, stage at diagnosis was significantly higher in CD relatives (p = 0.04). Our findings suggest that first-degree female relatives of CD patients are at higher risk of developing breast cancer but receive diagnosis at more advanced stages, therefore advocating the need of more active screening protocol in this population

A new humanized antibody is effective against pathogenic fungi in vitro

Invasive fungal infections mainly affect patients undergoing transplantation, surgery, neoplastic disease, immunocompromised subjects and premature infants, and cause over 1.5 million deaths every year. The most common fungi isolated in invasive diseases are Candida spp., Cryptococcus spp., and Aspergillus spp. and even if four classes of antifungals are available (Azoles, Echinocandins, Polyenes and Pyrimidine analogues), the side effects of drugs and fungal acquired and innate resistance represent the major hurdles to be overcome. Monoclonal antibodies are powerful tools currently used as diagnostic and therapeutic agents in different clinical contexts but not yet developed for the treatment of invasive fungal infections. In this paper we report the development of the first humanized monoclonal antibody specific for β-1,3 glucans, a vital component of several pathogenic fungi. H5K1 has been tested on C. auris, one of the most urgent threats and resulted efficient both alone and in combination with Caspofungin and Amphotericin B showing an enhancement effect. Our results support further preclinical and clinical developments for the use of H5K1 in the treatment of patients in need

Clinical Study Functional Outcomes and Quality of Life after Restorative Proctocolectomy in Paediatric Patients: A Case-Control Study

Background. Restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) has some peculiarities in paediatric ulcerative colitis (UC). Aims. The primary aim was to compare the bowel function of patients undergoing IPAA between those operated on in childhood and adulthood. The secondary aim was to compare the quality of life (QoL) and outcomes for children between medical and surgical therapies. Method. Children undergoing IPAA were compared with adult patients undergoing IPAA between 2007 and 2012. Function was assessed 1 year after ileostomy closure. Function and QoL of medically managed paediatric patients were compared with their surgical counterparts. Results. Twelve paediatric IPAA patients were compared with 24 adult ones. Acute presentation was common in the former, usually after failed biological treatment. Recurrent pouchitis was more frequent in children. Younger patients exhibited a trend toward better discrimination and continence. QoL was excellent in both groups. Twelve medically treated children were enrolled for secondary aim. Functioning was similar in IPAA-and medically managed children, but the former had a better QoL, confirmed by parents' perception. Conclusions. Similar function is achieved by IPAA in childhood or adulthood. IPAA may offer a better QoL compared to prolonged medical management. The beneficial effects of IPAA experienced by children were similarly observed by their parents

Ultrastructural detection of environmental nanoparticles in circulating blood

The increase in the incidence of acute myeloid leukemia (AML) may suggest a possible environmental etiology. PM2.5 was declared by the International Agency for Research on Cancer (WHO organ) a Class I carcinogen. To date, no reports have focused on particulate environmental pollution together with AML. The study investigated the presence and composition of particulate matter in circulating blood with a Environmental Scanning Electron Microscope coupled with an Energy Dispersive Spectroscope for the elemental analysis of the samples. 38 peripheral blood samples, 19 AML cases and 19 healthy controls, were analysed. A significant overload of particulate matter-derived nanoparticles linked or aggregated to blood components was found in AML patients, while almost absent in matched healthy controls. Two tailed Student’s t-test, MANOVA and Principal Component Analysis indicated that the total numbers of aggregates and particles were statistically different between cases and controls (MANOVA,

The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015"

Backround: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium. Aim: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients. Methods: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age > 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment). Results: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia. Discussion: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents. Conclusion: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence