Are mast cells implicated in asphyxia?

In a previous immunohistochemical (IHC) study, we documented the reaction of lung tissue vessels to hypoxia through the immunodetection of HIF1-α protein, a key regulator of cellular response to hypoxic conditions. Findings showing that asphyxia deaths are associated with an increase in the number of mast cell (MC)-derived tryptase enzymes in the blood suggests that HIF1-α production may be correlated with MC activation in hypoxic conditions. This hypothesis prompted us to investigate the possible role of pulmonary MC in acute asphyxia deaths. Lung of 47 medico-legal autopsy cases (35 asphyxia/hypoxia deaths, 11 controls, and 1 anaphylactic death) were processed by IHC analysis using anti-CD117 (c-Kit) antibody to investigate peri-airway and perivascular MC together with their counts and features. Results showed a significant increase in peri-vascular c-kit+ MC in some asphyxia deaths, such as hanging, strangulation, and aspiration deaths. A strong activation of MC in peri-airway and peri-vascular areas was also observed in lung samples from the anaphylaxis case, which was used as a positive control. Our study points to the potential role of MC in hypoxia and suggests that an evaluation of MC in the lungs may be a useful parameter when forensic pathologists are required to make a differential diagnosis between acute asphyxia deaths and other kinds of death

Stress management interventions among healthcare workers using mindfulness. A systematic review.

Background: stress among healthcare professionals has gained more and more attention due to the negative consequences on their and patients’ health. As a result of intense working hours, night shifts, responsibilities of care, and emotional contact with patients, healthcare workers experience stressful conditions. Interventions to prevent and manage their wellbeing are needed, in order to reduce the risks of onset of burnout syndrome. Aim: the aim of this systematic review is to analyze how mindfulness courses can improve mental and physical well-being of healthcare workers. Methods: a literature search was conducted in May 2018 using the databases Medline (PubMed), Scopus and Isi Web of Knowledge. Studies were included if they examined mindfulness interventions as possible solutions to manage stress among healthcare workers. Results: fifty-eight articles met the inclusion criteria: 13 of them were clinical trials; 11 were randomized clinical trials; 12 were systematic reviews; 7 were narrative reviews and 15 were observational studies. The studies included showed effectiveness of mindfulness programs in reducing stress, self-compassion, burnout, anxiety and depression. Significant negative association has been observed between MBSR and stress levels (β: −0.60, 95% CI:−5.95 to −4.04, P< 0.001) and mental exhaustion (β:−0.43, 95% CI:−3.30 −1.86, P< 0.001). Clinical trials focused on psychoeducational interventions highlighted decreased burnout scores in intervention group (SDM: -0.38). Conclusion: courses based on mindfulness showed to be effective in improving healthcare workers’ well-being, increasing their quality of life and the productivity outcomes. The evidence derived from this systematic review suggests that these interventions should be included within the work organization in order to be viable tools for promoting self-care and quality of care

Functional assessment of cancer therapy questionnaire for breast cancer (FACT-B+4): Italian version validation

BACKGROUND: Improvements in breast cancer diagnosis and treatment led to an increased incidence of survivors' rate. The healthcare system has to face new problems related not only to the treatment of the disease, but also to the management of the quality of life after the diagnosis. The aim of this study was to validate the Italian version of the Functional Assessment of Cancer Therapy - Breast (FACT-B+4) questionnaire and to evaluate its reliability. METHODS: The questionnaire was administered twice, with an interval of three days between each administration, to a cohort of women of the Breast Surgical Unit, PoliclincoUmberto I. Cronbach's alpha was used as a measure of the internal consistency of the Italian version. RESULTS: The Italian version of the tool was administered to 55 subjects. The Cronbach's alpha for most scores registered values >0.7, both at baseline and at the follow-up analysis, therefore the subscale showed good internal consistency. CONCLUSIONS: The Italian version of FACT-B+4 demonstrated acceptable reliability properties in the Breast Unit patients. The use of this questionnaire seemed to be effective and in line with the results derived from the English and Spanishversions. Internal consistency and validity had similar performance results

CRISPR-Cas9 Multiplex Editing of the α-Amylase/Trypsin Inhibitor Genes to Reduce Allergen Proteins in Durum Wheat

Wheat and its derived foods are widespread, representing one of the main food sources globally. During the last decades, the incidence of disorders related to wheat has become a global issue for the human population, probably linked to the spread of wheat-derived foods. It has been ascertained that structural and metabolic proteins, like \u3b1-amylase/trypsin inhibitors (ATI), are involved in the onset of wheat allergies (bakers' asthma) and probably Non-Coeliac Wheat Sensitivity (NCWS). The ATI are a group of exogenous protease inhibitors, which are encoded by a multigene family dispersed over several chromosomes in durum and bread wheat. WTAI-CM3 and WTAI-CM16 subunits are considered among the main proteins involved in the onset of bakers' asthma and probably NCWS. A CRISPR-Cas9 multiplexing strategy was used to edit the ATI subunits WTAI-CM3 and WTAI-CM16 in the grain of the Italian durum wheat cultivar Svevo with the aim to produce wheat lines with reduced amount of potential allergens involved in adverse reactions. Using a marker gene-free approach, whereby plants are regenerated without selection agents, homozygous mutant plants without the presence of CRISPR vectors were obtained directly from T0 generation. This study demonstrates the capability of CRISPR technology to knock out immunogenic proteins in a reduced time compared to conventional breeding programmes. The editing of the two target genes was confirmed either at molecular (sequencing and gene expression study) or biochemical (immunologic test) level. Noteworthy, as a pleiotropic effect, is the activation of the ATI 0.28 pseudogene in the edited lines

Association between work related stress and health related quality of life: the impact of socio-demographic variables. A cross sectional study in a region of central Italy

The aim of this work is investigate relationship between health-related quality of life and work-related stress and the impact of gender, education level, and age on this relationship. A cross-sectional study was conducted among workers of various setting in Rome and Frosinone. Work-related stress was measured with a demand-control questionnaire and health-related functioning by SF (short form)-12 health survey. There were 611 participants. Men reported high mental composite summary (MCS) and physical composite summary (PCS). In multivariate analysis age, gender (p < 0.001) and job demand (0.045) predicted low PCS. Low MCS predicted poor PCS. Job demand and educational level resulted negatively associated with MCS. In an analysis stratified for age, gender, and educational level, gender and age resulted effect modifier for MCS, gender and education level for PCS. In women increase of decision latitude predict (p = 0.001) an increase in MCS; a low job demand predict high MCS in male (p ≤ 0.001). In younger workers, a lower level of job demand predicted high MCS (<0.001). For PCS, gender and education level resulted effect modifier. In women, high decision latitude predicted higher PCS (p = 0.001) and lower level of job demand results in higher PCS (p ≤ 0.001). Higher educational level resulted predictor of low PCS. Management of risk about work-related stress should consider socio-demographic factors

ICSBP Is Essential for the Development of Mouse Type I Interferon-producing Cells and for the Generation and Activation of CD8α+ Dendritic Cells

Interferon (IFN) consensus sequence-binding protein (ICSBP) is a transcription factor playing a critical role in the regulation of lineage commitment, especially in myeloid cell differentiation. In this study, we have characterized the phenotype and activation pattern of subsets of dendritic cells (DCs) in ICSBP−/− mice. Remarkably, the recently identified mouse IFN-producing cells (mIPCs) were absent in all lymphoid organs from ICSBP−/− mice, as revealed by lack of CD11clowB220+Ly6C+CD11b− cells. In parallel, CD11c+ cells isolated from ICSBP−/− spleens were unable to produce type I IFNs in response to viral stimulation. ICSBP−/− mice also displayed a marked reduction of the DC subset expressing the CD8α marker (CD8α+ DCs) in spleen, lymph nodes, and thymus. Moreover, ICSBP−/− CD8α+ DCs exhibited a markedly impaired phenotype when compared with WT DCs. They expressed very low levels of costimulatory molecules (intercellular adhesion molecule [ICAM]-1, CD40, CD80, CD86) and of the T cell area-homing chemokine receptor CCR7, whereas they showed higher levels of CCR2 and CCR6, as revealed by reverse transcription PCR. In addition, these cells were unable to undergo full phenotypic activation upon in vitro culture in presence of maturation stimuli such as lipopolysaccharide or poly (I:C), which paralleled with lack of Toll-like receptor (TLR)3 mRNA expression. Finally, cytokine expression pattern was also altered in ICSBP−/− DCs, as they did not express interleukin (IL)-12p40 or IL-15, but they displayed detectable IL-4 mRNA levels. On the whole, these results indicate that ICSBP is a crucial factor in the regulation of two possibly linked processes: (a) the development and activity of mIPCs, whose lack in ICSBP−/− mice may explain their high susceptibility to virus infections; (b) the generation and activation of CD8α+ DCs, whose impairment in ICSBP−/− mice can be responsible for the defective generation of a Th1 type of immune response

Proteomic changes and molecular effects associated with Cr(III) and Cr(VI) treatments on germinating kiwifruit pollen

The present study is aimed at identifying molecular changes elicited by Cr(III) and Cr(VI) on germinating kiwifruit pollen. To address this question, comparative proteomic and DNA laddering analyses were performed. While no genotoxic effect was detected, a number of proteins whose accumulation levels were altered by treatments were identified. In particular, the upregulation of some proteins involved in the scavenging response, cell redox homeostasis and lipid synthesis could be interpreted as an oxidative stress response induced by Cr treatment. The strong reduction of two proteins involved in mitochondrial oxidative phosphorylation and a decline in ATP levels were also observed. The decrease of pollen energy availability could be one of the causes of the severe inhibition of the pollen germination observed upon exposure to both Cr(III) and Cr(VI). Finally, proteomic and biochemical data indicate proteasome impairment: the consequential accumulation of misfolded/damaged proteins could be an important molecular mechanism of Cr(III) toxicity in pollen

No effect of creatine supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats

Background: Exacerbated oxidative stress is thought to be a mediator of arterial hypertension. It has been postulated that creatine (Cr) could act as an antioxidant agent preventing increased oxidative stress. The aim of this study was to investigate the effects of nine weeks of Cr or placebo supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR). Findings: Lipid hydroperoxidation, one important oxidative stress marker, remained unchanged in the coronary artery (Cr: 12.6 +/- 1.5 vs. Pl: 12.2 +/- 1.7 nmol.mg(-1); p = 0.87), heart (Cr: 11.5 +/- 1.8 vs. Pl: 14.6 +/- 1.1 nmol.mg(-1); p = 0.15), plasma (Cr: 67.7 +/- 9.1 vs. Pl: 56.0 +/- 3.2 nmol.mg(-1); p = 0.19), plantaris (Cr: 10.0 +/- 0.8 vs. Pl: 9.0 +/- 0.8 nmol.mg(-1); p = 0.40), and EDL muscle (Cr: 14.9 +/- 1.4 vs. Pl: 17.2 +/- 1.5 nmol.mg(-1); p = 0.30). Additionally, Cr supplementation affected neither arterial blood pressure nor heart structure in SHR (p &gt; 0.05). Conclusions: Using a well-known experimental model of systemic arterial hypertension, this study did not confirm the possible therapeutic effects of Cr supplementation on oxidative stress and cardiovascular dysfunction associated with arterial hypertension.FAPES

Hemidesmus indicus induces apoptosis via proteasome inhibition and generation of reactive oxygen species.

Proteasome inhibition represents an important anticancer strategy. Here, we studied the mechanisms at the basis of the pro-apoptotic activity of the standardized decoction of Hemidesmus indicus, a plant evoking a complex anticancer activity, and explored its inhibition of proteasome activity in human leukemia cells. Additionally, we preliminary tested the cytotoxicity of some H. indicus's phytochemicals on leukemia cells and their intestinal absorption on a human intestinal epithelium model consisting of a monolayer of differentiated Caco2 cells. We observed a potent antileukemic effect for H. indicus, imputable to the modulation of different critical targets at protein and mRNA levels and the reduction of the 26S proteasome expression. We found that some phytomarkers of H. indicus decoction passed through the enterocyte monolayer. Overall, our study supports the pharmacological potential of H. indicus, which can represent an interesting botanical drug in the oncological area