Changes in oxidative stress in response to different levels of energy restriction in obese ponies

The present study evaluated the effect of different levels of energy restriction on metabolic parameters in obese ponies. Relative weight changes, markers of lipid metabolism, and oxidant/antioxidant balance were monitored. Eighteen obese (body condition score≥7/9) Shetland ponies were studied over a 23.5 week trial, divided into 3 periods. First a 4 week adaptation period in which each animal was fed 100% of their maintenance energy requirements needed to maintain stable obese body weight (MERob). Then a 16.5 weeks weight loss period in which ponies were assigned to receive either 100% (control group, CONTROL), 80% (slow weight loss group, SLOW) or 60% (rapid weight loss group, RAPID) of their MERob. During the 3 week end phase period all animals were again fed 100% of their MERob. Relative weight loss was higher in RAPID (P<0.001) compared to SLOW. No linear relationship was found as a doubling in caloric restriction was accompanied with a tripling in weight loss. Relative weight gain afterwards in the end phase period was higher in RAPID (P<0.001) compared to SLOW and CONTROL. During the weight loss period, triacylglycerol and non-esterified fatty acids levels were highest in RAPID, as were α-tocopherol and ferric reducing ability of plasma. After 8 weeks of weight loss, advanced oxidation protein products were higher in RAPID compared to SLOW and CONTROL (P<0.001). In conclusion, the level of energy restriction influences the extent of changes in oxidant/antioxidant balance. Practically, more severe energy restriction regimens may be associated with a greater regain of weight post restriction

Safety and tolerability of intravenous ferric carboxymaltose in the oldest old patients: a prospective cohort study in a University Italian Geriatrics Department

Background & aims. Anemia is common in older adults and it is associated with relevant complications. Although anemia is often multifactorial in origin and iron deficiency is considered a key relevant causative factor. The first therapeutic option is oral iron supplementation, but it is frequently characterized by adverse effects and overall poor efficacy. So far, intravenous (i.v.) iron formulations may serve as alternative treatment options and, in particular, Ferric carboxymaltose (FCM), showed to be safe and effective in older patients. We aimed to assess the safety and tolerability of FCM in real world hospitalized frail oldest old patients. Methods.This is an observational prospective study on 25 old age patients with iron deficiency anemia (IDA), admitted between July 2019 and November 2019 to the Geriatric Clinical ward of the IRCCS Policlinico San Martino, Genoa, Italy and treated with i.v. FCM. The incidence, probability and severity of adverse drug reactions (ADR) were reported along with the clinical response in term of mean Haemoglobin (Hb) increase after one week from the drug administration. Results. 72% of patients were oldest old with IDA and the clinical phenotype was characterized by multimorbidity and disability. The mean dose of i.v. FCM was 1160.0 ± 313.6 mg. FCM resulted safe therapeutic option with overall good tolerability. Additionally, a significant clinical improvement in the mean Hb level was observed. Conclusions. These findings moved a step in the recommendation of i.v. iron supplementation as a preferable route in oldest old, serving as a potential platform for future randomized clinical studies

Predictive values of two frailty screening tools in older patients with solid cancer: a comparison of SAOP2 and G8

Objectives: Comprehensive Geriatric Assessment (CGA), the gold standard for detecting frailty in elderly cancer patients, is time-consuming and hard to apply in routine clinical practice. Here we compared the performance of two screening tools for frailty, G8 and SAOP2 for their accuracy in identifying vulnerable patients. Material and Methods: We tested G8 and SAOP2 in 282 patients aged 65 or older with a diagnosis of solid cancer and candidate to undergo surgical, medical and/or radiotherapy treatment. CGA, including functional and cognitive status, depression, nutrition, comorbidity, social status and quality of life was used as reference. ROC curves were used to compare two screening tools. Results: Mean patient age was 79 years and 54% were female. Colorectal and breast cancer were the most common types cancer (49% and 24%). Impaired CGA, G8, and SAOP2 were found in 62%, 89%, and 94% of the patients, respectively. SAOP2 had a better sensitivity (AUC 0.85, p&lt;0.032) than G8 (AUC 0.79), with higher performance in breast cancer patients (AUC 0.93) and in patients aged 70-80 years (AUC 0.87). Conclusions: G8 and SAOP2 both showed good screening capacity for frailty in the cancer patient population we examined with SAOP2 showing a slightly better performance than G8

Pectin-honey hydrogel: Characterization, antimicrobial activity and biocompatibility

BACKGROUND: Novel pectin-honey hydrogels have been developed and characterized as medical device. Ideally, a wound dressing should maintain optimal fluid affinity, permit moisture evaporation, protect the wound from microbes, and have shape-conformability, biocompatibility, and antibacterial activity. OBJECTIVE: A novel, simple and fast method to produce pectin-honey wound dressings is described. METHODS: The properties of these pectin-honey hydrogels were investigated, including swelling ability, water vapour transmission rate, hydrogen peroxide production, methylglyoxal content and antibacterial activity. Biocompatibility was assessed by proliferation assays using cultured fibroblast cells and by in vivo study with subcutaneous and intraperitoneal implantation in rats. RESULTS: Hydrogel showed a good water vapour transmission rate, fluid uptake and were not cytotoxic for fibroblasts. The hydrogel demonstrated good antibacterial activity toward clinically relevant pathogens, including S. aureus and E. coli. Biocompatibility was confirmed by the measurement of plasma levels of interleukin (IL)1 beta, IL-6, tumour necrosis factor (TNF) alpha, and prostaglandin (PG)E2. No histological changes were observed. CONCLUSIONS: The presence of a natural active component, conformability, and complete resorbability are the main characteristics of this new biocompatible biomaterial that is well tolerated by the body, possibly improves healing, may be used for surgical complications prevention, with a simple and inexpensive production process. \ua9 2018 - IOS Press and the authors. All rights reserve

Nicotinic acid phosphoribosyltransferase regulates cancer cell metabolism, susceptibility to NAMPT inhibitors and DNA repair.

In the last decade, substantial efforts have been made to identify NAD(+) biosynthesis inhibitors, specifically against nicotinamide phosphoribosyltransferase (NAMPT), as preclinical studies indicate their potential efficacy as cancer drugs. However, the clinical activity of NAMPT inhibitors has proven limited, suggesting that alternative NAD(+) production routes exploited by tumors confer resistance. Here, we show the gene encoding nicotinic acid phosphoribosyltransferase (NAPRT), a second NAD(+)-producing enzyme, is amplified and overexpressed in a subset of common types of cancer, including ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression signature. Both NAPRT and NAMPT increased intracellular NAD(+) levels. NAPRT silencing reduced energy status, protein synthesis, and cell size in ovarian and pancreatic cancer cells. NAPRT silencing sensitized cells to NAMPT inhibitors both in vitro and in vivo; similar results were obtained with the NAPRT inhibitor 2-hydroxynicotinic acid. Reducing NAPRT levels in a BRCA2-deficient cancer cell line exacerbated DNA damage in response to chemotherapeutics. In conclusion, NAPRT-dependent NAD(+) biosynthesis contributes to cell metabolism and to the DNA repair process in a subset of tumors. This knowledge could be used to increase the efficacy of NAMPT inhibitors and chemotherapy. Cancer Res; 77(14); 3857-69. ©2017 AACR

Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models

The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain

&quot;Delirium Day&quot;: A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys