Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion

The mechanism of skeletal myoblast fusion is not well understood. We show that endogenous nitric oxide (NO) generation is required for myoblast fusion both in embryonic myoblasts and in satellite cells. The effect of NO is concentration and time dependent, being evident only at the onset of differentiation, and direct on the fusion process itself. The action of NO is mediated through a tightly regulated activation of guanylate cyclase and generation of cyclic guanosine monophosphate (cGMP), so much so that deregulation of cGMP signaling leads to a fusion-induced hypertrophy of satellite-derived myotubes and embryonic muscles, and to the acquisition of fusion competence by myogenic precursors in the presomitic mesoderm. NO and cGMP induce expression of follistatin, and this secreted protein mediates their action in myogenesis. These results establish a hitherto unappreciated role of NO and cGMP in regulating myoblast fusion and elucidate their mechanism of action, providing a direct link with follistatin, which is a key player in myogenesis

Association between Type-D Personality and Affective (Anxiety, Depression, Post-traumatic Stress) Symptoms and Maladaptive Coping in Breast Cancer Patients: A Longitudinal Study

Background: Type-D (distressed) personality has not been prospectively explored for its association with psychosocial distress symptoms in breast cancer patients. Objective: The objective of the study was to test the hypothesis that Type-D personality can be associated with psychosocial distress variables in cancer over a 2-point period (6 month-follow-up). Aims: The aim of the study was to analyze the role of Type-D personality in relation to anxiety, depression, post-traumatic stress symptoms, general distress, and maladaptive coping among cancer patients. Methods: 145 breast cancer patients were assessed within 6 months from diagnosis (T0) and again 6 months later (T1). The Type-D personality Scale, the Hospital Anxiety and Depression Scale, Depression subscale (HAD-D), the Brief Symptom Inventory (BSI-18) Anxiety subscale, the Distress Thermometer (DT), the Post-traumatic Symptoms (PTS) Impact of Event Scale (IES), and the Mini Mental Adjustment to Cancer (Mini-MAC) Anxious Preoccupation and Hopelessness scales were individually administered at T0 and T1. Results: One-quarter of cancer patients met the criteria for Type-D personality, which was stable over the follow-up time. The two main constructs of TypeD personality, namely social inhibition (SI) and negative affectivity (NA), were related to anxiety, depression, PTS, BSI-general distress and maladaptive coping (Mini-MAC anxious preoccupation and hopelessness). In regression analysis, Type-D SI was the most significant factor associated with the above-mentioned psychosocial variables, both at T0 and T1. Conclusion: Likewise other medical disorders (especially cardiology), Type-D personality has been confirmed to be a construct significantly related to psychosocial distress conditions and maladaptive coping that are usually part of assessment and intervention in cancer care. More attention to personality issues is important in oncology

Psychosocial Issues in Long-Term Survivors of Testicular Cancer

Testicular cancer is the most frequent tumor in young males aged 15–39 years. As cure rates are currently around 90%, the prevalence of survivors is increasing. However, a disease-free condition does not necessarily correspond to a life free of physical and psychosocial health problems. The aim of this review was to explore psychosocial morbidity among testicular cancer survivors. A literature search was conducted in three electronic databases (PubMed, Medline, and Embase). The results of the search on cancer survivors were then combined with those of the search on psychosocial concerns and work performance. Eighty-four publications met the inclusion criteria. Physical, psychological, work-related problems and changing perspectives about work and life in general influenced life and career decisions among testicular cancer survivors. Individual health, sexual relationships and work problems, affect several important aspects of survival and significantly influence the QoL of long-term survivors

Retrospective observational multicenter study on patients treated with a non-animal origin cross-linked hyaluronic acid with different molecular weights for nasolabial folds

Background: According to the American Academy of Aesthetic Plastic Surgeons, more than 11 million cosmetic surgical and nonsurgical procedures were performed by board-certified plastic surgeons, dermatologists and otolaryngologists in the United States, totaling more than 12 billion dollars. Of that total, more than 7 billion was spent on surgical procedures and more than 5 billion was spent on nonsurgical procedures. More than 1,872,172 people received Hyaluronic Acid (HA) injections in 2013. Moreover, filler treatments are the most popular procedures performed by dermatologists. Objective: Evaluate, with a new imaging system, durability, efficacy and safety of a nasolabial fold treatment with a cross-linked HA of non-animal origin with different molecular weights. Material and methods: A cross-linked HA (25 mg/ml, 1000-2000 kDa, 23 ± 3 Newton [N] extrusion force, 1,4-Butanediol Diglycidyl Ether (BDDE) content < 0.1 ppm) was used in order to perform the treatment. The product is commercially available with the trademark Aliaxin®GP (Global Performance) and distributed by IBSA Farmaceutici Italia Srl. 25 female subjects aged 40 and 60 years with a photoageing level III according Rubin or type III according Glogau were recruited for the treatment and 0.5 ml of the product were injected for single nasolabial fold. The aesthetic result and the duration of the aesthetic correction were evaluated by the analysis of the skin microreliefs through confocal microscopy and by Glogau's Scale. Additionally, pictures of each patient were collected by Canon PowerShot G10 Digital Camera (14.7 megapixels) before and after treatment. Below the description of the experimental schedule: T0: Baseline, evaluation and treatment; T1: second visit, 4 months after the treatment; T2: third visit, 6 months after the treatment. Results: From 25 patients, 150 silicone casts were obtained: 75 casts of the right nasolabial fold and 75 casts of the left nasolabial fold. Roughness arithmetical average (Ra) was assessed by profilometry. This parameter represents the arithmetic mean deviation of the profile points compared to the average value. The Ra of the right fold at T2 decreased by 50% versus T0 and by 40% compared to T1; Ra of the left fold at T2 decreased by the 45% versus T0 and by 35% compared to T1. No side effects were reported during the observation period beyond mild symptoms (pain, sensation of heat, reddening in the injection site) also described by the product technical sheet. Conclusion: The results proved the efficacy and safety of the nasolabial folds treatment with the tested product and the durability of the aesthetic correction

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register

Abstract COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p &lt; 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p &lt; 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

Hostility in cancer patients as an underexplored facet of distress

ObjectiveIn the present study, we aimed to assess hostility and to examine its association with formal psychiatric diagnosis, coping, cancer worries, and quality of life in cancer patients.MethodsThe World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) to make an ICD‐10 (International Classification of Disease) psychiatric diagnosis was applied to 516 cancer outpatients. The patients also completed the Brief Symptom Inventory‐53 to assess hostility (BSI‐HOS), and the Mini‐Mental Adjustment to cancer scale (Mini‐MAC). A subset of patients completed the Cancer Worries Inventory (CWI), the Openness Scale, and the Quality of Life Index.ResultsBy analyzing the distribution of the responses 25% of the patients had moderate and 11% high levels of hostility, with about 20% being BSI‐HOS “cases.” Hostility was higher in patients with a formal ICD‐10 psychiatric diagnosis (mainly major depression, other depressive disorders, anxiety disorders) than patients without ICD‐10 diagnosis. However, about 25% of ICD‐10‐non cases also had moderate‐to‐high hostility levels. Hostility was associated with Mini‐MAC hopelessness and anxious preoccupation, poorer quality of life, worries (mainly problems sin interpersonal relationships), and inability to openly discuss these problems within the family.ConclusionsHostility and its components should be considered as dimensions to be more carefully explored in screening for distress in cancer clinical settings for its implications in negatively impacting on quality of life, coping and relationships with the family, and possibly the health care system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167492/1/pon5594_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167492/2/pon5594.pd