Cancer and Chemotherapy Contribute to Muscle Loss by Activating Common Signaling Pathways

Cachexia represents one of the primary complications of colorectal cancer due to its effects on depletion of muscle and fat. Evidence suggests that chemotherapeutic regimens, such as Folfiri, contribute to cachexia-related symptoms. The purpose of the present study was to investigate the cachexia signature in different conditions associated with severe muscle wasting, namely Colon-26 (C26) and Folfiri-associated cachexia. Using a quantitative LC-MS/MS approach, we identified significant changes in 386 proteins in the quadriceps muscle of Folfiri-treated mice, and 269 proteins differentially expressed in the C26 hosts (p < 0.05; -1.5 ≥ fold change ≥ +1.5). Comparative analysis isolated 240 proteins that were modulated in common, with a large majority (218) that were down-regulated in both experimental settings. Interestingly, metabolic (47.08%) and structural (21.25%) proteins were the most represented. Pathway analysis revealed mitochondrial dysfunctions in both experimental conditions, also consistent with reduced expression of mediators of mitochondrial fusion (OPA-1, mitofusin-2), fission (DRP-1) and biogenesis (Cytochrome C, PGC-1α). Alterations of oxidative phosphorylation within the TCA cycle, fatty acid metabolism, and Ca(2+) signaling were also detected. Overall, the proteomic signature in the presence of both chemotherapy and cancer suggests the activation of mechanisms associated with movement disorders, necrosis, muscle cell death, muscle weakness and muscle damage. Conversely, this is consistent with the inhibition of pathways that regulate nucleotide and fatty acid metabolism, synthesis of ATP, muscle and heart function, as well as ROS scavenging. Interestingly, strong up-regulation of pro-inflammatory acute-phase proteins and a more coordinated modulation of mitochondrial and lipidic metabolisms were observed in the muscle of the C26 hosts that were different from the Folfiri-treated animals. In conclusion, our results suggest that both cancer and chemotherapy contribute to muscle loss by activating common signaling pathways. These data support the undertaking of combination strategies that aim to both counteract tumor growth and reduce chemotherapy side effects

The sustained psychological impact of the COVID-19 pandemic on health care workers one year after the outbreak-a repeated cross-sectional survey in a tertiary hospital of North-East Italy

: This study aimed to evaluate the mental health outcomes of health care workers (HCWs) of the Verona academic hospital trust (Italy) one year after the outbreak of COVID-19 and to identify predicted risk factors. A web-based survey was conducted from mid-April to mid-May 2021 on hospital workers one year after the first evaluation performed during the lock-down phase of the COVID-19 pandemic. Post-traumatic stress, general anxiety, depression, and burnout were assessed by using, respectively, the impact of event scale (IES-R), the self-rating anxiety scale (SAS), the patient health questionnaire (PHQ-9) and the Maslach burnout inventory-general survey (MBI-GS). Multivariate logistic regression analysis was performed to identify factors associated with each of the four mental health outcomes one year after the COVID-19 outbreak. A total of 1033 HCWs participated. The percentage of HCWs scoring above the cut-off increased from 2020 to 2021 in all of the outcome domains (anxiety, 50.1% vs. 55.7, p &lt; 0.05; depression, 26.6% vs. 40.6%, p &lt; 0.001; burnout, 28.6% vs. 40.6%, p &lt; 0.001; chi-square test), with the exception of post-traumatic distress. There was also an increase when stratifying by occupation and workplace, with a greater increase for depression and burnout. Multivariate analysis revealed that, one year after the COVID-19 outbreak, nurses were at the greatest risk of anxiety and depression, whereas residents were at the greatest risk of burnout (in terms of low professional efficacy). Working in intensive care units was associated with an increased risk of developing severe emotional exhaustion and a cynical attitude towards work

Levels of burn-out among healthcare workers during the COVID-19 pandemic and their associated factors: a cross-sectional study in a tertiary hospital of a highly burdened area of north-east Italy

Objective: To determine burn-out levels and associated factors among healthcare personnel working in a tertiary hospital of a highly burdened area of north-east Italy during the COVID-19 pandemic. Design: Observational study conducted from 21 April to 6 May 2020 using a web-based questionnaire. Setting: Research conducted in the Verona University Hospital (Veneto, Italy). Participants: Out of 2195 eligible participants, 1961 healthcare workers with the full range of professional profiles (89.3%) completed the survey. Primary outcome measure: Levels of burn-out, assessed by the Maslach Burnout Inventory-General Survey (MBI-GS). Multivariable logistic regression analysis was performed to identify factors associated with burn-out in each MBI-GS dimension (emotional exhaustion, EX; professional efficacy, EF; cynicism, CY). Results: Overall, 38.3% displayed high EX, 46.5% low EF and 26.5% high CY. Burn-out was frequent among staff working in intensive care units (EX 57.0%; EF 47.8%; CY 40.1%), and among residents (EX 34.9%; EF 63.9%; CY 33.4%) and nurses (EX 49.2%; EF 46.9%; CY 29.7%). Being a resident increased the risk of burn-out (by nearly 2.5 times) in all the three MBI subscales and being a nurse increased the risk of burn-out in the EX dimension in comparison to physicians. Healthcare staff directly engaged with patients with COVID-19 showed more EX and CY than those working in non-COVID wards. Finally, the risk of burn-out was higher in staff showing pre-existing psychological problems, in those having experienced a COVID-related traumatic event and in those having experienced interpersonal avoidance in the workplace and personal life. Conclusions: Burn-out represents a great concern for healthcare staff working in a large tertiary hospital during the COVID-19 pandemic and its impact is more burdensome for front-line junior physicians. This study underlines the need to carefully address psychological well-being of healthcare workers to prevent the increase of burn-out in the event of a new COVID-19 healthcare emergency

Changes in emergency psychiatric consultations in time of COVID-19: a retrospective observational study in the Verona Academic Hospital over the two pandemic years 2020-2021

Background: During the first months of the COVID-19 pandemic, local health authorities in most Italian regions prescribed a reduction of ordinary outpatient and community mental health care. The aim of this study was to assess the impact of the COVID-19 pandemic on access to the emergency departments (ED) for psychiatric consultation in the pandemic years 2020 and 2021 compared to 2019. Methods: This is a retrospective study conducted by using routinely collected administrative data of the two EDs of the Verona Academic Hospital Trust (Verona, Italy). All ED psychiatry consultations registered from 01.01.2020 to 31.12.2021 were compared with those registered in the pre-pandemic year (01.01.2019 to 31.12.2019). The association between each recorded characteristic and the year considered was estimated by chi-square or Fisher's exact test. Results: A significant reduction was observed between 2020 and 2019 (-23.3%) and between 2021 and 2019 (-16.3%). This reduction was most evident in the lockdown period of 2020 (-40.3%) and in the phase corresponding to the second and third pandemic waves (-36.1%). In 2021, young adults and people with diagnosis of psychosis showed an increase in requests for psychiatric consultation. Conclusions: Fear of contagion may have been an important factor in the overall reduction in psychiatric consultations. However, psychiatric consultations for people with psychosis and for young adults increased. This finding underlines the need for mental health services to implement alternative outreach strategies aimed to support, in times of crisis, these vulnerable segments of the population

Energy Efficient Content Distribution in an ISP Network

International audienceWe study the problem of reducing power consump- tion in an Internet Service Provider (ISP) network by designing the content distribution infrastructure managed by the operator. We propose an algorithm to optimally decide where to cache the content inside the ISP network. We evaluate our solution over two case studies driven by operators feedback. Results show that the energy-efficient design of the content infrastructure brings substantial savings, both in terms of energy and in terms of bandwidth required at the peering point of the operator. Moreover, we study the impact of the content characteristics and the power consumption models. Finally, we derive some insights for the design of future energy-aware networks

Patterns of tumor response in canine and feline cancer patients treated with electrochemotherapy: preclinical data for the standardization of this treatment in pets and humans

Electrochemotherapy (ECT) is a novel anticancer therapy that is currently being evaluated in human and pet cancer patients. ECT associates the administration of an anti-tumor agent to the delivery of trains of appropriate waveforms. The increased uptake of chemotherapy leads to apoptotic death of the neoplasm thus resulting in prolonged local control and extended survival. In this paper we describe the histological features of a broad array of spontaneous tumors of companion animals receiving pulse-mediated chemotherapy. Multivariate statistical analysis of the percentage of necrosis and apoptosis in the tumors before and after ECT treatment, shows that only a high percentage of necrosis and apoptosis after the ECT treatment were significantly correlated with longer survivals of the patients (p < 0.0001 and p = 0.004, respectively). Further studies on this topic are warranted in companion animals with spontaneous tumors to identify new molecular targets for electrochemotherapy and to the develop new therapeutical protocols to be translated to humans

Effectiveness of a Mindful Compassion Care Program in reducing burnout and psychological distress amongst frontline hospital nurses during the COVID-19 pandemic: a study protocol for a randomized controlled trial

Background: Recent studies have shown that nurses have been more affected by the COVID-19 pandemic than any other group of hospital workers in terms of anxiety, depression, and burnout. Several clinical studies had previously demonstrated the effectiveness of mindfulness and compassion interventions in reducing burnout and emotional distress amongst healthcare professionals. Methods and analysis: A parallel-group randomized controlled trial will assess the feasibility, acceptability, and efficacy of a mindfulness and compassion-focused programme on frontline nurses who had been working during the COVID-19 pandemic. Seventy-two participants will be recruited from Verona University Hospital Trust (Veneto Region, north-east Italy) and will be divided equally into an intervention group and a control group. Primary outcome will be assessed using the Emotional Exhaustion subscale of the Maslach Burnout Inventory General Survey (MBI-GS). Secondary outcomes will be measured by the Cynicism and Professional Efficacy subscales of the MBI-GS, the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7), the Insomnia Severity Index (ISI), the Impact of Stressful Events (IES-R), the Perceived Stress Scale (PSS), the Five Facet Mindfulness Questionnaire (FFMQ), and the Forms of Self-Criticising/attacking and Self-Reassuring Scale (FSCRS). Discussion: The study aims to fill a gap in the literature and present a scientifically validated intervention for those healthcare professionals most exposed to the stressful conditions of working during the COVID-19 pandemic. Trial registration: ClinicalTrials.gov; Identifier: NCT05308537