Effects of granulocyte-macrophage colony-stimulating factor and cyclic AMP interaction on human neutrophil apoptosis.

The current study was undertaken to evaluate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and cyclic AMP (cAMP) signaling interaction on human neutrophil apoptosis, either occurring spontaneously or induced by Fas antigen activation. Results show that GM-CSF, dibutyryl cAMP (a cAMP analog) and forskolin (an adenylate cyclase activator) are all able to suppress spontaneous neutrophil cell death. Of note however, when GM-CSF is used in combination with cAMP-elevating agents, an additive effect on neutrophil survival is observed with dibutyryl cAMP only, whereas supplementation of cell cultures with GM-CSF and forskolin results in a progressive reduction of antiapoptotic effects exerted by the single compounds. Moreover, although dibutyryl cAMP and forskolin do not affect Fas-triggered apoptotic events, they are still able to modulate the GM-CSF capacity to prolong neutrophil survival following anti-Fas IgM cell challenge, with effects similar to those respectively exerted on spontaneous neutrophil apoptosis. The data indicate that GM-CSF may negatively modulate the cAMP-mediated antiapoptotic pathway in human neutrophils, likely via the inhibition of adenylate cyclase activity. This would prevent an abnormal neutrophil survival as a result of cAMP signaling stimulation, which provides a novel insight into the role of GM-CSF as a physiological regulator of myeloid cell turnover

Influence of quality attributes of early, intermediate and late peach varieties on suitability for fresh-convenience products

Fresh convenience products represent a category of minimally processed fruit and vegetables (chunks, mousse, smoothies) that respond to the changes in consumer attitudes. Thanks to the image of convenience (time-saving, snack sizes, no waste, smart packaging) and healthiness their sales are steadily increasing. In this study 26 varieties (including peach, nectarines, and clingstone peaches) from Apulian production were divided into three groups according to harvest dates in early (A), middle (B) and late (C) maturing. Physical, chemical and sensorial analyses were performed in order to select high quality fruits for minimal processing according to the harvesting season. A multivariate Principal Component Analysis was applied to discriminate different varieties for quality attributes. Within Group A, ‘Honey Kist’ showed the lowest acidity and intermediate susceptibility to mechanical damage. For Group B, ‘Stark Red Gold’, ‘Zee Glo’ and ‘Venus’ resulted different in sensorial evaluation, while ‘Loadel’ and ‘Eolia’ were more susceptible to browning. For Group C, ‘Tardi Belle’ and ‘Baby Gold7’, although more sensitive to mechanical damage, were differentiated for flavor. Results of this work confirm the extreme variability among varieties in terms of sensorial quality, susceptibility to browning and to mechanical damage, and the importance of assessing varietal screening for selection of most suitable varieties for minimal processing

Effect of type of fertilization and maturity on quality of fresh-cut red and yellow peppers (Capsicum annuum L.)

The aim of this work was to evaluate the effect of the type of fertilization (mineral and combined fertilization with compost in pre-transplant plus mineral addition during cultivation) and stage of maturity at harvest (mature-green and full-colored) on post-cutting quality of red and yellow ‘Cazzone’ peppers. Peppers were cut into strips, and air-stored for 8 days at 5°C. During storage, color, appearance score, firmness, respiration rate, soluble solids, acidity, pH, vitamin C, total phenols, and antioxidant activity were measured. The maturity stage influenced color parameters and soluble solids, acidity and pH for both yellow and red types. Full-colored peppers showed a lower respiration rate, and higher SSC than mature-green peppers; for the yellow type, a lower firmness value was observed for full-colored fruits compared to the mature-green ones. A lower antioxidant activity was also observed in the yellow type fertilized with the combined treatment, while phenol content in full-colored peppers was higher than in mature-green ones. Fresh-cut yellow peppers showed higher susceptibility to decay compared to red types: after 8 days of storage, the appearance score in mineral fertilized full-colored yellow peppers dramatically decreased below the limit of marketability. The results of this experiment show that the type of fertilization and maturity stage can have varying impact on the quality of yellow and red peppers

Qualitative analysis of the capacity to consent to treatment in patients with a chronic neurodegenerative disease. Alzheimer's Disease.

Objective: Informed consent is an essential element in doctor–patient relationship. In particular, obtaining valid informed consent from patients with neurocognitive diseases is a critical issue at present. For this reason, we decided to conduct research on elderly patients with Alzheimer’s disease (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) to assess their capacity to make treatment decisions. Methods: The experimental group comprised 70 Alzheimer patients who were admitted to the Neurodegenerative Disease Unit of the University of Bari. The control group consisted of 83 elderly patients without neurocognitive disorders who were hospitalized in the Geriatric Unit at the same university. After providing written consent to participate in the research, each subject underwent the following assessments: (a) assessment of comprehension sheet, (b) Neuropsychiatric Inventory (NPI) and Global Functioning Evaluation (GFE), (c) neurological evaluation, (d) neuropsychological assessment with a full battery of tests, (d) The MacArthur Treatment Competence Study (MacArthur Competence Assessment Tool for Treatment (MacCAT-T); understanding, appreciating, reasoning and expressing a choice) and (e) a semi-structured interview administered by the patient’s caregiver. Results/conclusion: The present survey was designed to analyze possible qualitative and quantitative correlations between cognitive functioning and capacity to consent in relation to different degrees of severity of the neurodegenerative disorder. A large portion of the patients in our experimental sample did not appear to have the capacity to provide a valid consent. The authors present initial results of this study and discuss their possible implications

Silymarin, boswellic acid and curcumin enriched dietetic formulation reduces the growth of inherited intestinal polyps in an animal model

BACKGROUND Some substances of plant origin have been reported to exert an effect in reducing intestinal neoplasm development, especially in animal models. Adenomatous polyposis coli multiple intestinal neoplasia-ApcMin/+ is the most studied murine model of genetic intestinal carcinogenesis. AIM To assess whether an enriched nutritional formulation (silymarin, boswellic acid and curcumin) with proven "in vitro" and "in vivo" anti-carcinogenetic properties may prevent inherited intestinal cancer in animal model. METHODS Forty adenomatous polyposis coli multiple intestinal neoplasia-ApcMin/+ mice were used for the study of cancer prevention. They were divided into two groups: 20 assumed standard and 20 enriched diet. At the 110th d animals were sacrificed. In each group, four subgroups received intraperitoneal bromodeoxyuridine injection at different times (24, 48, 72 and 96 h before the sacrifice) in order to assess epithelial turnover. Moreover, we evaluated the following parameters: Intestinal polypoid lesion number and size on autoptic tissue, dysplasia and neoplasia areas by histological examination of the whole small intestine, inflammation by histology and cytokine mRNA expression by real-Time polymerase chain reaction, bromodeoxyuridine and TUNEL immunofluorescence for epithelial turnover and apoptosis, respectively. Additionally, we performed western blotting analysis for the expression of estrogen alpha and beta receptors, cyclin D1 and cleaved caspase 3 in normal and polypoid tissues. RESULTS Compared to standard, enriched diet reduced the total number (203 vs 416) and the mean ± SD/animal (12.6 ± 5.0 vs 26.0 ± 8.8; P< 0.001) of polypoid lesions. In enriched diet group a reduction in polyp size was observed (P< 0.001). Histological inflammation and pro-inflammatory cytokine expression were similar in both groups. Areas of low-grade dysplasia (P< 0.001) and intestinal carcinoma (IC; P< 0.001) were significantly decreased in enriched diet group. IC was observed in 100% in standard and 85% in enriched formulation assuming animals. Enriched diet showed a faster epithelial migration and an increased apoptosis in normal mucosa and low-grade dysplasia areas (P< 0.001). At western blotting, estrogen receptor beta protein was well expressed in normal mucosa of enriched and standard groups, with a more marked trend associated to the first one. Estrogen receptor alpha was similarly expressed in normal and polypoid mucosa of standard and enriched diet group. Cleaved caspase 3 showed in normal mucosa a stronger signal in enriched than in standard diet. Cyclin D1 was more expressed in standard than enriched diet group of both normal and polypoid tissue. CONCLUSION Our results are suggestive of a chemo-preventive synergic effect of the components (silymarin, boswellic acid and curcumin) of an enriched formulation in inherited IC. This effect may be mediated by the reduction of epithelial proliferation, the increase of apoptosis and the acceleration of villous cell renewal due to dietary formulation intake

Helicobacter pylori primary and secondary genotypic resistance to clarithromycin and levofloxacin detection in stools: A 4-year scenario in Southern Italy

Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017-2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains

GeV Photons from Ultra High Energy Cosmic Rays accelerated in Gamma Ray Bursts

Gamma-ray bursts are produced by the dissipation of the kinetic energy of a highly relativistic fireball, via the formation of a collisionless shock. When this happens, Ultra High Energy Cosmic Rays up to 10^20 eV are produced. I show in this paper that these particles produce, via synchrotron emission as they cross the acceleration region, photons up to 300 GeV which carry away a small, ~0.01, but non-negligible fraction of the total burst energy. I show that, when the shock occurs with the interstellar medium, the optical depth to photon-photon scattering, which might cause energy degradation of the photons, is small. The burst thusly produced would be detected at Earth simultaneoulsy with the parent gamma-ray burst, although its duration may differ significantly from that of the lower energy photons. The expected fluences, ~10^{-5}-10^{-6} erg/cm^2 are well within the range of planned detectors. A new explanation for the exceptional burst GRB 940217 is discussed.Comment: Accepted for publication in The Physical Review Letters. 4 pages, RevTeX needed, no figure

Liver fibrosis score, physical frailty, and the risk of dementia in older adults: The Italian longitudinal study on aging

Introduction: Liver fibrosis increases progressively with aging and has been associated with poorer cognitive performance in middle-aged and older adults. We investigated the relationships between a non-invasive score for advanced liver fibrosis (non-alcoholic fatty liver disease [NAFLD] fibrosis score [NFS]) and dementia risk. We also assessed physical frailty, a common geriatric condition which is associated to dementia. We tested the joint effects of physical frailty and fibrosis on dementia incidence. Methods: A total of 1061 older adults (65 to 84 years), from the Italian Longitudinal Study on Aging, were prospectively evaluated for the risk of dementia in a period between 1992 and 2001. Liver fibrosis was defined according to the NFS. Physical frailty was assessed according to the Fried's criteria. Cox proportional hazards models were used to estimate the short- and long-term risk of overall dementia, associated to the NFS, testing the effect modifier of physical frailty status. Results: Older adults with only high NFS (F3-F4) did not exhibit a significant increased risk of overall dementia. Over 8 years of follow-up, frail older adults with high NFS had an increased risk of overall dementia (hazard ratio [HR]: 4.23; 95% confidence interval [CI]: 1.22 to 14.70, P = .023). Finally, physically frail older adults with low albumin serum levels (albumin < 4.3 g/dL) and with advanced liver fibrosis (F3-F4 NFS) compared to those with lower liver fibrosis score (F0-F2 NFS) were more likely to have a higher risk of overall dementia in a long term-period (HR: 16.42; 95% CI: 1.44 to 187.67, P = .024). Discussion: Advanced liver fibrosis (F3-F4 NFS) could be a long-term predictor for overall dementia in people with physical frailty. These findings should encourage a typical geriatric, multidisciplinary assessment which accounts also for the possible co-presence of frail condition in older adults with chronic liver disease and liver fibrosis

Sirtuin 1 regulation of developmental genes during differentiation of stem cells

The longevity-promoting NAD+-dependent class III histone deacetylase Sirtuin 1 (SIRT1) is involved in stem cell function by controlling cell fate decision and/or by regulating the p53-dependent expression of NANOG. We show that SIRT1 is down-regulated precisely during human embryonic stem cell differentiation at both mRNA and protein levels and that the decrease in Sirt1 mRNA is mediated by a molecular pathway that involves the RNA-binding protein HuR and the arginine methyltransferase coactivator-associated arginine methyltransferase 1 (CARM1). SIRT1 down-regulation leads to reactivation of key developmental genes such as the neuroretinal morphogenesis effectors DLL4, TBX3, and PAX6, which are epigenetically repressed by this histone deacetylase in pluripotent human embryonic stem cells. Our results indicate that SIRT1 is regulated during stem cell differentiation in the context of a yet-unknown epigenetic pathway that controls specific developmental genes in embryonic stem cells