Detection of human cytomegalovirus in transbronchial biopsies from lung transplant recipients

The role of human cytomegalovirus (HCMV) in lung transplantation (LT) and drawbacks related to viral quantification in bronchoalveolar lavage (BAL) underline the potential usefulness of investigating other specimens. Thirty-three LT recipients were prospectively studied by HCMV quantitative real time PCR on matched transbronchial biopsy (TBB), BAL, and whole blood specimens. Overall, 27/33 patients turned out HCMV-positive in at least one specimen: 7.1 %, 37.1 %, and 13.5 % of TBB, BAL, and blood samples, respectively. No significant association between HCMV on all types of specimens and acute rejection, lymphocytic bronchiolitis, bronchiolitis obliterans and bronchiolitis obliterans syndrome was found. HCMV pneumonia was associated to HCMV detection on TBB (p = 0.003) and whole blood (p = 0.008), not on BAL (p = 0.47). The highest mean viral load was detected in TBB from cases with HCMV pneumonia in comparison to all other cases, suggesting the potential use of HCMV investigation in TBB for evaluating posttransplant complications.     

Inhibition of aquaporin-1 dependent angiogenesis impairs tumour growth in a mouse model of melanoma

Prohibiting angiogenesis is an important therapeutic approach for fighting cancer and other angiogenic related diseases. Research focused on proteins that regulate abnormal angiogenesis has attracted intense interest in both academia and industry. Such proteins are able to target several angiogenic factors concurrently, thereby increasing the possibility of therapeutic success. Aquaporin-1 (AQP1) is a water channel membrane protein that promotes tumour angiogenesis by allowing faster endothelial cell migration. In this study we test the hypothesis that AQP1 inhibition impairs tumour growth in a mouse model of melanoma. After validating the inhibitor efficacy of two different AQP1 specific siRNAs in cell cultures, RNA interference experiments were performed by intratumoural injections of AQP1 siRNAs in mice. After 6 days of treatment, AQP1 siRNA treated tumours showed a 75 % reduction in volume when compared to controls. AQP1 protein level, in AQP1 knockdown tumours, was around 75 % that of the controls and was associated with a significant 40 % reduced expression of the endothelial marker, Factor VIII. Immunofluorescence analysis of AQP1 siRNA treated tumours showed a significantly lower microvessel density. Time course experiments demontrated that repeated injections of AQP1 siRNA over time are effective in sustaining the inhibition of tumour growth. Finally, we have confirmed the role of AQP1 in sustaining an active endothelium during angiogenesis and we have shown that AQP1 reduction causes an increase in VEGF levels. In conclusion, this study validates AQP1 as a pro-angiogenic protein, relevant for the therapy of cancer and other angiogenic-related diseases such as psoriasis, endometriosis, arthritis and atherosclerosis.     

Family climate in children living with parents who harmfully consume alcohol

The family climate has notable impact on cognitive, emotional, behavioural, social and physical development of children and adolescents and can be influenced by parents' health status. The present study aimed at evaluating whether living with a parent with alcohol use disorder negatively influences the perceived emotional family climate, parental attitudes and internal representations of family relationships. Forty-five children living with a parent with alcohol use disorder and 45 controls, matched for sex and age, completed the Level of Expressed Emotion Scale and the Family Attitudes Questionnaire. Their significant parent completed the Parental Attitudes Scale. The results suggested that living with a parent with an alcohol use disorder increased the risk of having perceived higher levels of emotional response, attitude towards illness and expectations from their parents; it also increased the probability of being exposed to lower parental pleasure and of having represented worse family relationships. Emotion regulation interventions might be useful to protect children living with a parent with alcohol use disorder from a potential chaotic and unpredictable family environment.     

The influence of small field output factors simulated uncertainties on the calculated dose in VMAT plans for brain metastases: a multicentre study

Objectives:This multicentric study was carried out to investigate the impact of small field output factors (OFs) inaccuracies on the calculated dose in volumetric arctherapy (VMAT) radiosurgery brain plans.Methods:Nine centres, realised the same five VMAT plans with common planning rules and their specific clinical equipment Linac/treatment planning system commissioned with their OFs measured values (OFbaseline). In order to simulate OFs errors, two new OFs sets were generated for each centre by changing only the OFs values of the smallest field sizes (from 3.2 × 3.2 cm² to 1 × 1 cm²) with well-defined amounts (positive and negative). Consequently, two virtual machines for each centre were recommissioned using the new OFs and the percentage dose differences ΔD (%) between the baseline plans and the same plans recalculated using the incremented (OFup) and decremented (OFdown) values were evaluated. The ΔD (%) were analysed in terms of planning target volume (PTV) coverage and organs at risk (OARs) sparing at selected dose/volume points.Results:The plans recalculated with OFdown sets resulted in higher variation of doses than baseline within 1.6 and 3.4% to PTVs and OARs respectively; while the plans with OFup sets resulted in lower variation within 1.3% to both PTVs and OARs. Our analysis highlights that OFs variations affect calculated dose depending on the algorithm and on the delivery mode (field jaw/MLC‐defined). The Monte Carlo (MC) algorithm resulted significantly more sensitive to OFs variations than all of the other algorithms.Conclusion:The aim of our study was to evaluate how small fields OFs inaccuracies can affect the dose calculation in VMAT brain radiosurgery treatments plans. It was observed that simulated OFs errors, return dosimetric calculation accuracies within the 3% between concurrent plans analysed in terms of percentage dose differences at selected dose/volume points of the PTV coverage and OARs sparing.Advances in knowledge:First multicentre study involving different Planning/Linacs about undetectable errors in commissioning output factor for small fields.     

Assessment of condylar volume and ramus height in JIA patients with unilateral and bilateral TMJ involvement: retrospective case-control study

The objectives of the study are to analyze volumetric differences of condylar volumes in patients with unilateral and bilateral JIA and to compare results     

High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis

PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.     

The impact of SARS-CoV-2 on skeletal muscles

In 2019-2020, the SARS-CoV-2 pandemic has shocked the world and most health care systems, and a “second wave” of the viral spread is ongoing in Europe and in Italy too. While, at the initial outbreak, the treatment of patients had focused on the respiratory symptoms, many diverse clinical manifestations of the disease have to date been reported. However, the complete course of the disease has not yet been fully clarified. In particular, several reports from the real-world clinical practice have highlighted the noxious effects of SARS-CoV-2 on skeletal muscles. In this brief review, we summarized the main current findings about muscular and neuromuscular damages that may be triggered by the virus or by the drugs used to treat COVID-19. Moreover, we underlined the need of attentive care and vigilance for patients with neuro-muscular disorders, who may be particularly susceptible to infection and at increased risk for severe COVID-19.Key words: SARS-CoV-2, COVID-19, skeletal muscles     

Simplified PESI score and sex difference in prognosis of acute pulmonary embolism: a brief report from a real life study

Prognostic stratification of acute pulmonary embolism (PE) remains a challenge in clinical practice. Simplified PESI (sPESI) score is a practical validated score aimed to stratify 30-day mortality risk in acute PE. Whether prognostic value of sPESI score differs according to sex has not been previously investigated. Therefore the aim of our study was to provide information about it. Data records of 452 patients, 180 males (39.8 %) and 272 females (60.2 %) discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. sPESI was retrospectively calculated. Variables enclosed in sPESI score, all cause in-hospital mortality and overall bleedings were compared between sexes. Moreover, predictive ability of sPESI score as prognosticator of all cause in-hospital mortality was tested and compared between sexes. sPESI score 0 (low risk) was found in 17.7 % of males and 13.6 % of females (p = 0.2323). We didn’t find significant difference in sPESI scoring distribution. Age ≥80 years (51.4 vs. 33.8 %, p = 0.0003) and heart rate ≥110 bpm (23.5 vs. 14.4 %, p = 0.0219) were found significantly more prevalent in females, whereas active cancer (23.8 vs. 39.4 %, p = 0.0004) and cardio-respiratory diseases (19.8 vs. 27.7 %, p = 0.0416) were in males. All cause in-hospital mortality was 0 % in both genders for sPESI score 0, whereas it was 5.4 % in females and 13.6 % in males with sPESI score 1–2 (p = 0.0208) and 22 % in females and 19.3 % in males with sPESI score ≥3 (p = 0.7776). Overall bleedings were significantly more frequent in females compared with males (4.77 vs. 0.55 %, p = 0.0189). In females overall bleedings ranged from 2.7 % in sPESI score 0 to 6 % in sPESI score ≥3. Predictive ability of sPESI score as prognosticator of all cause in-hospital mortality was higher in females compared to males (AUC 0.72 vs. 0.67, respectively). In real life different co-morbidity burdens in females compared to males. Females seems to be at lower risk of all cause in-hospital mortality for sPESI score ≤2 but at higher risk of bleeding, irrespective from sPESI scoring. Predictive ability of sPESI score seems better in females.     

Wound repair during arm regeneration in the red starfish Echinaster sepositus

Starfish can regenerate entire arms following their loss by both autotomic and traumatic amputation. Although the overall regenerative process has been studied several times in different asteroid species, there is still a considerable gap of knowledge as far as the detailed aspects of the repair phase at tissue and cellular level are concerned, particularly in post‐traumatic regeneration. The present work is focused on the arm regeneration model in the Mediterranean red starfish Echinaster sepositus; to describe the early cellular mechanisms of arm regeneration following traumatic amputation, different microscopy techniques were employed. In E. sepositus, the repair phase was characterized by prompt wound healing by a syncytial network of phagocytes and re‐epithelialisation followed by a localized subepidermal oedematous area formation. Scattered and apparently undifferentiated cells, intermixed with numerous phagocytes, were frequently found in the wound area during these first stages of regeneration and extensive dedifferentiation phenomena were seen at the level of the stump, particularly in the muscle bundles. A true localized blastema did not form. Our results confirm that regeneration in asteroids mainly relies on morphallactic processes, consisting in extensive rearrangement of the existing tissues which contribute to the new tissues through cell dedifferentiation, redifferentiation, and/or migration.