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

Ceramic Total Knee Arthroplasty: Ready to Go?

Total knee arthroplasty (TKA) is a well-established surgical procedure in the late stages of knee osteoarthritis. Nevertheless, this procedure is associated with a percentage of unsatisfactory results and biomechanical failures, with aseptic loosening being the most common cause of revision. Beside these problems, cutaneous and systemic hypersensitivity reactions to metals have arisen as an increasing concern after joint arthroplasties, even if allergies against implant materials are still a quite rare and not well-known problem. Ceramic composites have been recently used in prosthetic components, showing minimum wear and excellent long-term results in total hip replacement, due to their high resistance to scratching and their better wettability with respect to cobalt-chromium alloy. Furthermore, the biologic response to debris generated from these bearings is less aggressive. Knee joint simulator tests and clinical results demonstrate promising results of TKAs with ceramic components that should led to benefit for the patients

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

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

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

Long term durability of protected silver coating for the mirrors of Ariel mission telescope

Ariel (Atmospheric Remote-sensing Infrared Exoplanet Large survey) is the fourth medium-size mission in ESA “Cosmic Vision” program. It is scheduled to launch in 2029. Ariel will conduct spectroscopic and photometric observations of a large sample of known exoplanets to survey their atmospheres with the transit method. Ariel is based on a 1 m class telescope designed for the visible and near infrared spectrum, but optimized specifically for spectroscopy in the waveband between 1.95 and 7.8 μm. Telescope and instruments will be operating in cryogenic conditions in the range 40-50 K. The telescope mirrors will be manufactured in aluminum 6061, with a protected silver coating deposited onto the optical surface to enhance reflectivity and prevent oxidation and corrosion. During the preliminary definition phase of the development work, leading to mission adoption, a silver coating with space heritage was selected and underwent a qualification process on disc-shaped samples of the mirrors substrate material. The samples were deposited through magnetron sputtering and then subjected to a battery of tests, including environmental durability tests, accelerated aging, cryogenic tests and mechanical resistance tests. Further to the qualification, the samples have been stored in cleanroom conditions and periodically re-examined and measured to detect any sign of coating degradation. The test program, still ongoing at the time of writing this article, consists of visual inspection with a high intensity lamp, spectral reflectance measurements and Atomic Force Microscopy (AFM) evaluation of nanometric surface features. The goal is to ensure stability of the optical performance, in terms of coating reflectance, during a time span comparable to the period that the actual mirrors of the telescope will spend in average cleanroom conditions. This study presents the interim results after three years of storage

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

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