Self-blaming as a barrier to lung cancer screening and smoking cessation programs in Italy. A qualitative study.

Background: Lung cancer screening (LCS) combined with smoking cessation programs is a critical strategy for reducing lung cancer mortality. Understanding the perspectives of cigarette users and former ones on these interventions is essential for enhancing their acceptability and effectiveness. This study aimed to explore, in Italy, the perceptions and experiences of individuals eligible for LCS within the context of a smoking cessation program.

Evaluating no fixation, endoscopic suture fixation, and an over-the-scope clip for anchoring fully covered self-expandable metal stents in benign upper GI conditions: a comparative multicenter international study (with video).

Background And Aims: Fully covered self-expandable metal stents (FCSEMSs) are widely used in benign upper GI conditions, but stent migration remains a limitation. An over-the-scope clip (OTSC) device (Stentfix {SF], Ovesco Endoscopy) for stent anchoring has recently been developed. The aim of this study was to evaluate the effect of OTSC fixation on FCSEMS migration rate.

Activities Carried Out during the First COVID-19 Lockdown by Italian Citizens.

The SARS-CoV-2 pandemic has altered how citizens engage in activities. This study describes the new activities citizens engaged in during the first lockdown, factors that helped them cope with the confinement, the supports they used the most, and which supports they would have liked to receive. This cross-sectional study consists of an online survey made of 49 questions that was completed by the citizens of the province of Reggio Emilia (Italy) from 4 May until 15 June 2020.

Role and challenges to digital technologies in community health promotion programs in Italy during the COVID-19 pandemic: a multiple embedded case study protocol.

Background And Aim: Due to the COVID-19 pandemics, The Italian League Against Cancer (LILT), a national federation of local associations promoting cancer prevention, had to face the challenge to find new ways and technologies to promote health in their territories. This study aims to explore how LILT associations led their health promotion interventions during the COVID-19 pandemic and to understand which interventions had a greater impact, for which population group, and why.

Methods: In this descriptive multiple embedded case study, each case will focus on the activities of a local LILT association and their collaborators on the perception and experience of the use of digital technology for health promotion and prevention, through interviews, observations, and a study of products and artifacts.

Deconstructing cold-induced brown adipocyte neogenesis in mice.

Cold exposure triggers neogenesis in classic interscapular brown adipose tissue (iBAT) that involves activation of β1-adrenergic receptors, proliferation of PDGFRA+ adipose tissue stromal cells (ASCs), and recruitment of immune cells whose phenotypes are presently unknown. Single-cell RNA-sequencing (scRNA-seq) in mice identified three ASC subpopulations that occupied distinct tissue locations. Of these, interstitial ASC1 were found to be direct precursors of new brown adipocytes (BAs).

Lipolysis regulates major transcriptional programs in brown adipocytes.

β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. We have used pharmacological inhibitors and a direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in cultured brown adipocytes. Here we show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals.

REEP6 knockout leads to defective β-adrenergic signaling in adipocytes and promotes obesity-related metabolic dysfunction.

Introduction: The mobilization and catabolism of lipid energy is a central function of adipocytes that is under the control of the β-adrenergic signaling pathway, and defects in β-adrenergic signaling in adipocytes have been linked to obesity and obesity-related metabolic diseases. Receptor expression-enhancing proteins (REEPs) are endoplasmic reticulum (ER) proteins that play critical roles in subcellular targeting of receptor signaling complexes. Examination of gene expression profiles indicates that, among REEPs expressed in adipocytes, REEP6 expression is uniquely upregulated by sympathetic nervous system activation, suggesting involvement in regulating adrenergic signal transduction.

Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development.

Objective: The current study addresses the cellular complexity and plasticity of subcutaneous (inguinal) white adipose tissue (iWAT) in mice during the critical periods of perinatal growth and establishment.

Methods: We performed a large-scale single cell transcriptomic (scRNA-seq) and epigenomic (snATAC-seq) characterization of cellular subtypes (adipose stromal cells (ASC) and adipocyte nuclei) during inguinal WAT (subcutaneous; iWAT) development in mice, capturing the early postnatal period (postnatal days (PND) 06 and 18) through adulthood (PND56).

Results: Perinatal and adult iWAT contain 3 major ASC subtypes that can be independently identified by RNA expression profiles and DNA transposase accessibility.

Persistent Response and Prolonged Survival Following Pembrolizumab Discontinuation Due to Long-Lasting Autoimmune Colitis in Advanced NSCLC: A Case Report.

Pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor that has been approved for treatment of a wide variety of malignancies including non-small-cell lung cancer (NSCLC). Immune-mediated colitis is a known adverse effect of pembrolizumab which can lead to the treatment interruption, although not compromising the control of the oncological disease. Herein, we report the case of a 59-year-old woman on pembrolizumab for advanced NSCLC which developed a severe and persistent colitis treated with infliximab for several months following anti-PD-1 antibody discontinuation.

Stereotypies in the Autism Spectrum Disorder: Can We Rely on an Ethological Model?

Background: Stereotypic behaviour can be defined as a clear behavioural pattern where a specific function or target cannot be identified, although it delays on time. Nonetheless, repetitive and stereotypical behaviours play a key role in both animal and human behaviour. Similar behaviours are observed across species, in typical human developmental phases, and in some neuropsychiatric conditions, such as Autism Spectrum Disorder (ASD) and Intellectual Disability.

Activity and Safety of NAB-FOLFIRI and NAB-FOLFOX as First-Line Treatment for metastatic Pancreatic Cancer (NabucCO Study).

Background: Relevant improvement in first-line treatment of metastatic pancreatic cancer (mPC) was provided by FOLFIRINOX and by gemcitabine (gem) plus nab-paclitaxel (Nab-p) regimens. Regardless of the first-line treatment survival benefit, most patients survive less than 1 year.

Aim: The objectives of this multicenter phase I/II study were to evaluate as first-line chemotherapy (CT) two modified regimens of FOLFIRINOX, replacing either oxaliplatin (Oxa) or irinotecan with Nab-p, in patients with mPC.

Beyond Lockdown: The Potential Side Effects of the SARS-CoV-2 Pandemic on Public Health.

Lockdowns to contain the spread of the SARS-CoV-2 have disrupted routines and behaviors, which could lead to a worsening of lifestyle and an increase in the burden of non-communicable diseases. This study aimed to describe the changes in physical activity, diet, alcohol drinking, and cigarette smoking during lockdown. A self-administered online survey addressing adults living in a province in northern Italy was advertised through websites and social media.

Negative Regulation of Human Hepatic Constitutive Androstane Receptor by Cholesterol Synthesis Inhibition: Role of Sterol Regulatory Element Binding Proteins.

The squalene synthase inhibitor squalestatin 1 (Squal1) is a potent and efficacious inducer of CYP2B expression in primary cultured rat hepatocytes and rat liver. To determine whether Squal1 is also an inducer of human CYP2B, the effects of Squal1 treatment were evaluated in primary cultured human hepatocytes, differentiated HepaRG cells, and humanized mouse livers. Squal1 treatment did not increase CYP2B6 mRNA levels in human hepatocytes or HepaRG cells and only slightly and inconsistently increased CYP2B6 mRNA content in humanized mouse liver.

Single cell approaches to address adipose tissue stromal cell heterogeneity.

A central function of adipose tissue is in the management of systemic energy homeostasis that is achieved through the co-ordinated regulation of energy storage and mobilization, adipokine release, and immune functions. With the dramatic increase in the prevalence of obesity and obesity-related metabolic disease over the past 30 years, there has been extensive interest in targeting adipose tissue for therapeutic benefit. However, in order for this goal to be achieved it is essential to establish a comprehensive atlas of adipose tissue cellular composition and define mechanisms of intercellular communication that mediate pathologic and therapeutic responses.

The Relationship Between Spiritual Life and Quality of Life in People with Intellectual Disability and/or Low-Functioning Autism Spectrum Disorders.

Spirituality seems to represent a relevant domain in the person-centred care planning and outcome assessment for persons with intellectual disability and low-functioning autism spectrum disorder. Despite this, the impact of spirituality on subjective well-being and quality of life (QoL) has been scarcely investigated. The aim of the present study was to map the international scientific literature in order to identify the reasons of such misconsideration and the key points for future research and practice implementation.

Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells.

Non-alcoholic fatty liver disease is manifested by hepatic accumulation of triglycerides (TG) and is commonly associated with metabolic syndrome. The isoprenoid farnesol (FOH) modulates lipid metabolism and reduces hepatic TG content in rodents. This effect involves activation of at least two nuclear receptors, peroxisome proliferator-activated receptor α (PPARα) and farnesoid X receptor.

Deconstructing Adipogenesis Induced by β3-Adrenergic Receptor Activation with Single-Cell Expression Profiling.

Recruitment of brown/beige adipocytes (BAs) in white adipose tissue (WAT) involves proliferation and differentiation of adipocyte stem cells (ASCs) in concert with close interactions with resident immune cells. To deconvolve stromal cell heterogeneity in a comprehensive and unbiased fashion, we performed single-cell RNA sequencing (scRNA-seq) of >33,000 stromal/vascular cells from epididymal WAT (eWAT) and inguinal WAT (iWAT) under control conditions and during β3-adrenergic receptor (ADRB3) activation. scRNA-seq identified distinct ASC subpopulations in eWAT and iWAT that appeared to be differentially poised to enter the adipogenic pathway.

Toll-like receptor expression in human non-small cell lung carcinoma: potential prognostic indicators of disease.

Introduction: Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients.

Is early integration of palliative care feasible and acceptable for advanced respiratory and gastrointestinal cancer patients? A phase 2 mixed-methods study.

Background: There is evidence that early integration of palliative care improves quality of life, lowers spending and helps clarify preferences and goals for advanced cancer patients. Little is known about the feasibility and acceptability of early integration.

Aim: Assessing feasibility of early integration of palliative care, and exploring concerns perceived and problems encountered by patients, relatives and oncologists.

Novel Pharmacological Probes Reveal ABHD5 as a Locus of Lipolysis Control in White and Brown Adipocytes.

Current knowledge regarding acute regulation of adipocyte lipolysis is largely based on receptor-mediated activation or inhibition of pathways that influence intracellular levels of cAMP, thereby affecting protein kinase A (PKA) activity. We recently identified synthetic ligands of --hydrolase domain containing 5 (ABHD5) that directly activate adipose triglyceride lipase (ATGL) by dissociating ABHD5 from its inhibitory regulator, perilipin-1 (PLIN1). In the current study, we used these novel ligands to determine the direct contribution of ABHD5 to various aspects of lipolysis control in white (3T3-L1) and brown adipocytes.

Real-life clinical practice results with vinflunine in patients with relapsed platinum-treated metastatic urothelial carcinoma: an Italian multicenter study (MOVIE-GOIRC 01-2014).

Background: Vinflunine is the only chemotherapeutic agent shown to improve survival in platinum-refractory patients with metastatic transitional cell carcinoma of the urothelium (TCCU) in a phase III clinical trial, which led to product registration for this indication in Europe. The aim of this study was to assess the efficacy of vinflunine and to evaluate the prognostic significance of risk factors in a large, unselected cohort of patients with metastatic TCCU treated according to routine clinical practice.

Methods: This was a retrospective multicenter study.

Severe Rhabdomyolysis during Treatment with Trabectedin in Combination with a Herbal Drug in a Patient with Metastatic Synovial Sarcoma: A Case Report.

Rhabdomyolysis is defined as dissolution of striped muscle characterized by leakage of intracellular muscle components into the circulation, which can ultimately lead to renal failure with a possible fatal outcome. This is an uncommon side effect of trabectedin which is used in second-line therapy of metastatic sarcoma after anthracycline and ifosfamide failure. Here, we describe a case of reversible rhabdomyolysis in a male patient with recurrent metastatic synovial sarcoma of the hand, with marked F-FDG uptake into his skeletal muscles, after 4 cycles of trabectedin, and who at the same time was taking an alternative medicine (bioflavonoids) suspected of triggering this adverse event.

Characteristics of the case mix, organisation and delivery in cancer palliative care: a challenge for good-quality research.

Objectives: Palliative care (PC) services and patients differ across countries. Data on PC delivery paired with medical and self-reported data are seldom reported. Aims were to describe (1) PC organisation and services in participating centres and (2) characteristics of patients in PC programmes.

Differential Regulation of Gene Expression by Cholesterol Biosynthesis Inhibitors That Reduce (Pravastatin) or Enhance (Squalestatin 1) Nonsterol Isoprenoid Levels in Primary Cultured Mouse and Rat Hepatocytes.

Squalene synthase inhibitors (SSIs), such as squalestatin 1 (SQ1), reduce cholesterol biosynthesis but cause the accumulation of isoprenoids derived from farnesyl pyrophosphate (FPP), which can modulate the activity of nuclear receptors, including the constitutive androstane receptor (CAR), farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs). In comparison, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (e.g.

Acupuncture As an Integrative Approach for the Treatment of Hot Flashes in Women With Breast Cancer: A Prospective Multicenter Randomized Controlled Trial (AcCliMaT).

Purpose: To determine the effectiveness of acupuncture for the management of hot flashes in women with breast cancer.

Patients And Methods: We conducted a pragmatic, randomized controlled trial comparing acupuncture plus enhanced self-care versus enhanced self-care alone. A total of 190 women with breast cancer were randomly assigned.