Publications by authors named "Chiara Airoldi"

38 Publications

Nursing evaluation during treatment with helmet continuous positive airway pressure in patients with respiratory failure due to COVID-19 pneumonia: A case series.

Aust Crit Care 2021 Oct 23. Epub 2021 Oct 23.

Department of Emergency Medicine, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.

Background: During COVID-19 outbreak, with the increasing number of patients presenting with acute respiratory failure, a large use of non invasive positive pressure ventilation was done in the emergency departments and medical wards despite the lack of recommendations.

Objectives: This study describes the clinical characteristics of patients presenting to the hospital with acute respiratory failure due to COVID-19 related pneumonia undergoing treatment with helmet continuous positive airway pressure (CPAP) with a strict nursing evaluation and monitoring.

Methods: A case series study enrolling adult patients admitted to an emergency department of an Italian hospital with acute respiratory failure due to COVID-19 pneumonia from March 18th to April 18th, 2020, was conducted. Only patients who strictly followed a local CPAP protocol were enrolled.

Results: A total of 52 patients were included in this study. Thirty-eight patients (73%) were judged eligible for endotracheal intubation (ETI). Eighteen (34.6%) were intubated. Sixteen (30.8%) patients died: seven (38.9%) and nine (26.5%) in the eligible-for-ETI and non eligible-for-ETI group, respectively. The median hospital length of stay was different in the ETI and non-ETI group: 26 days (interquartile range [IQR]: 16-37) vs 15 days [IQR 9-17] (p = 0.005). The median invasive mechanical ventilation time was 11 days [IQR 7-21] with an ICU length of stay of 14.5 days [IQR 10-28]. During the CPAP trial, among patients eligible for ETI variations over time for positive end-expiratory pressure (p = 0.003) and respiratory rate (p = 0.059) were found between intubated and non-intubated patients.

Conclusions: A short closed monitored CPAP trial could be considered for acute respiratory failure due to COVID-19 pneumonia before considering ETI. A progressive positive end-expiratory pressure titration should target reduction in a patient's respiratory rate. More studies are needed to evaluate the efficacy and predictors of failure of CPAP and non-invasive positive pressure ventilation in patients with acute respiratory failure due to COVID-19 pneumonia.
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http://dx.doi.org/10.1016/j.aucc.2021.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536817PMC
October 2021

Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis.

Ther Adv Urol 2021 Jan-Dec;13:17562872211053189. Epub 2021 Oct 29.

Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy.

Background: In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC).

Objective: This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups.

Design Setting And Participants: A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed.

Results And Limitations: Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients' characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons.

Conclusions: A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting.
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http://dx.doi.org/10.1177/17562872211053189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558789PMC
October 2021

Magnetic Resonance Accuracy in the Diagnosis of Anterior Talo-Fibular Ligament Acute Injury: A Systematic Review and Meta-Analysis.

Diagnostics (Basel) 2021 Sep 28;11(10). Epub 2021 Sep 28.

Department of Radiodiagnostic and Interventional Radiology, AOU Maggiore della Carità, 28100 Novara, Italy.

Background: The studies about injury to the anterior talo-fibular ligament (ATFL) are focused mainly on chronic symptoms and chronic instability, and the literature about the accuracy of magnetic resonance imaging (MRI) in acute injuries is quite lacking.

Methods: This systematic review with meta-analysis analyzes the diagnostic accuracy of MRI on acute ATFL injury. Relative studies were retrieved after searching three databases (MEDLINE, SCOPUS, and Cochrane Central Register of Controlled Trails). Eligible studies were summarized. The quality of the included articles was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data were extracted to calculate pooled sensitivity and specificity of MRI.

Results: Seven studies met our inclusion and exclusion criteria. For MRI, the pooled sensitivities and specificity in diagnosing acute ATFL injury were respectively 1.0 (95% CI: 0.58-1) and 0.9 (95% CI: 0.79-0.96). Pooled LR+ and LR- were respectively 10.4 (95% CI: 4.6-23) and 0 (95% CI: 0-0.82).

Conclusion: This systematic review with meta-analysis investigated the accuracy of imaging for the diagnosis of acute ATFL injury. Our results demonstrated that MRI shows high diagnostic accuracy in the diagnosis of acute ATFL lesions. These results suggest that routine MRI in the case of suspected ATFL acute injury may be clinically useful, although this is not done in clinical practice due probably to high cost.
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http://dx.doi.org/10.3390/diagnostics11101782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534480PMC
September 2021

4D Electromagnetic Navigation Bronchoscopy for the Sampling of Pulmonary Lesions: First European Real-Life Experience.

Lung 2021 Oct 25;199(5):493-500. Epub 2021 Sep 25.

Respiratory Diseases Unit, Medical Department, AOU Maggiore Della Carità, C.so Mazzini 18, 28100, Novara, Italy.

Purpose: The use of Electromagnetic navigation bronchoscopy (ENB) for the diagnosis of pulmonary peripheral lesions is still debated due to its variable diagnostic yield; a new 4D ENB system, acquiring inspiratory and expiratory computed tomography (CT) scans, overcomes respiratory motion and uses tracked sampling instruments, reaching higher diagnostic yields. We aimed at evaluating diagnostic yield and accuracy of a 4D ENB system in sampling pulmonary lesions and at describing their influencing factors.

Methods: We conducted a three-year retrospective observational study including all patients with pulmonary lesions who underwent 4D ENB with diagnostic purposes; all the factors potentially influencing diagnosis were recorded.

Results: 103 ENB procedures were included; diagnostic yield and accuracy were, respectively, 55.3% and 66.3%. We reported a navigation success rate of 80.6% and a diagnosis with ENB was achieved in 68.3% of cases; sensitivity for malignancy was 61.8%. The majority of lesions had a bronchus sign on CT, but only the size of lesions influenced ENB diagnosis (p < 0.05). Transbronchial needle aspiration biopsy was the most used tool (93.2% of times) with the higher diagnostic rate (70.2%). We reported only one case of pneumothorax.

Conclusion: The diagnostic performance of a 4D ENB system is lower than other previous navigation systems used in research settings. Several factors still influence the reachability of the lesion and therefore diagnostic yield. Patient selection, as well as the multimodality approach of the lesion, is strongly recommended to obtain higher diagnostic yield and accuracy, with a low rate of complications.
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http://dx.doi.org/10.1007/s00408-021-00477-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510943PMC
October 2021

Mechanical buckling can pattern the light-diffracting cuticle of Hibiscus trionum.

Cell Rep 2021 Sep;36(11):109715

Sainsbury Laboratory Cambridge University, Bateman Street, Cambridge, CB2 1LR, UK. Electronic address:

Many species have cuticular striations that play a range of roles, from pollinator attraction to surface wettability. In Hibiscus trionum, the striations span multiple cells at the base of the petal to form a pattern that produces a type of iridescence. It is postulated, using theoretical models, that the pattern of striations could result from mechanical instabilities. By combining the application of mechanical stress with high-resolution imaging, we demonstrate that the cuticle buckles to create a striated pattern. Through mechanical modeling and cryo-SEM fractures, we show that the cuticle behaves like a bilayer system with a stiff film on a compliant substrate. The pattern of buckling aligns with the direction of the stress to create a larger-scale pattern. Our findings contribute to the understanding of the formation of tissue-wide patterns in living organisms.
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http://dx.doi.org/10.1016/j.celrep.2021.109715DOI Listing
September 2021

Mycotic infection prevalence among patients undergoing bronchoalveolar lavage with search of SARS-CoV-2 after two negative nasopharyngeal swabs.

J Breath Res 2021 09 13;15(4). Epub 2021 Sep 13.

Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.

The evidence that severe coronavirus disease 2019 (COVID-19) is a risk factor for development of mycotic respiratory infection with an increased mortality is rising. Immunosuppressed are among the most susceptible patients andspecies is the most feared superinfection. In this study we evaluated mycotic isolation prevalence on bronchoalveolar lavage (BAL) of patients who underwent bronchoscopy in search of severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA. Moreover, we described the clinical characteristics and main outcomes of these patients. We included 118 patients, 35.9% of them were immunosuppressed for different reasons: in 23.7% we isolated SARS-CoV-2 RNA, in 33.1% we identified at least one mycotic agent and both in 15.4%. On BAL we observed in three casesspp, in six casesand in 32spp. The prevalence of significant mold infection was 29.3% and 70.7% of cases were false positive or clinically irrelevant infections. In-hospital mortality of patients with fungal infection was 15.3%. The most frequent computed tomography (CT) pattern, evaluated with the Radiological Society of North America consensus statement, among patients with a mycotic pulmonary infection was the atypical one (< 0.0001). Mycotic isolation on BAL may be interpreted as an innocent bystander, but its identification could influence the prognosis of patients, especially in those who need invasive investigations during the COVID-19 pandemic; BAL plays a fundamental role in resolving clinical complex cases, especially in immunosuppressed patients independently from radiological features, without limiting its role in ruling out SARS-CoV-2 infection.
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http://dx.doi.org/10.1088/1752-7163/ac2290DOI Listing
September 2021

Seroprevalence of SARS-CoV-2 Among Workers in Northern Italy.

Ann Work Expo Health 2021 Aug 8. Epub 2021 Aug 8.

Department of Translation Medicine, Università del Piemonte Orientale, Via Solaroli 17 Novara, 20100, Italy.

Background: The spread of severe acute respiratory coronavirus 2 (SARS-CoV-2) among active workers is poor known. The aim of our study was to evaluate the seroprevalence of immunoglobulin G (IgG) among a convenience sample of workers and to identify high-risk job sectors during the first pandemic way.

Methods: We conducted a cross-sectional study among workers tested for SARS-CoV-2 between 28 March and 7 August 2020, recorded by a private healthcare center located in North-West Italy. Association among seroprevalence and demographic and occupational variables was evaluated using chi square test and the seroprevalence and 95% confidence intervals (CI) were calculated.

Results: We collected the results for 23568 serological tests from a sample of 22708 workers from about 1000 companies. Median age was 45 years and about 60% of subjects were male. The overall seroprevalence was 4.97% [95%CI 4.69-5.25]. No statistical difference was found among gender while seroprevalence was associated with subjects' age, geographical location, and occupational sector. Significantly higher values of positivity were observed for the logistics sector (31.3%), weaving factory (12.6%), nursing homes (9.8%), and chemical industry (6.9%) workers. However, we observed some clusters of cases in single companies independently from the sector.Then, a detailed focus on 940 food workers shown a seroprevalence of 5.21% [95%CI 3.79-6.63] and subjects who self-reported COVID-19 symptoms and who worked during lockdown had a higher probability of being infected (p < 0.001).

Conclusions: Data obtained might be useful for future public health decision; more than occupation sector, it seems that failure on prevention system in single companies increase the SARS-CoV-2 transmission.
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http://dx.doi.org/10.1093/annweh/wxab062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385866PMC
August 2021

Effectiveness and feasibility of smoking counselling: a randomized controlled trial in an Italian emergency department.

Eur J Public Health 2021 Jul 12. Epub 2021 Jul 12.

Department of Translational Medicine, Università degli Studi del Piemonte Orientale, Novara, Italy.

Background: 5A's counselling is recommended for screening and treating patients with smoking addiction. The emergency department (ED) setting might be a suitable environment for conducting interventions for smoking cessation. The present study aims to determine the feasibility and effectiveness on smoking cessation of 5A's counselling administered to ED patients by nurses.

Methods: Parallel group randomized trial assessing 5A's counselling for smoking cessation vs. usual care at a University Hospital in the North of Italy. The primary end-point was prevalence of tobacco-free patients. The secondary outcomes at 6- and 12-month follow-up were (i) consecutive past 30-day smoking abstinence; (ii) past 7-day 50%, or more, decrease in daily tobacco consumption over baseline; and (iii) number of attempts to quit smoking.

Results: A total of 480 patients were randomized to intervention (n = 262) or usual care (n = 218). Intention to treat analysis displayed no differences in primary and secondary outcomes between groups. A slight but not statistically significant enhancement in cessation was recorded in the intervention group [relative risk (RR) = 1.04, 95% confidence interval (CI) = 0.58-1.87] at 6 months, whereas a reversed observation at 12 months (RR = 0.86, 95% CI = 0.50-1.47). Similar results were obtained for the secondary outcomes. Per protocol analysis increased the size of the results. Of the 126 smokers receiving counselling, 18 were visited and treated at the local smoking cessation centre, with 12 of them successfully completing the treatment.

Conclusion: The results of this study indicate that the ED is not a suited environment for 5A's counselling.
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http://dx.doi.org/10.1093/eurpub/ckab114DOI Listing
July 2021

High Seroprevalence of SARS-CoV-2 among Healthcare Workers in a North Italy Hospital.

Int J Environ Res Public Health 2021 03 24;18(7). Epub 2021 Mar 24.

Department of Translational Medicine, Università degli Studi del Piemonte Orientale, 28100 Novara, Italy.

Background: Healthcare workers (HCWs) have been the key players in the fight against the coronavirus disease 2019 (COVID-19) pandemic. The aim of our study was to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG anti-bodies.

Methods: We conducted a cross-sectional study among workers of two hospitals and Territorial Medical and Administrative services in Northern Italy. From 8 May to 3 June 2020, 2252 subjects were tested. Seroprevalence and 95% confidence interval (CI) were calculated for all individuals who were stratified by job title, COVID-19 risk of exposure, direct contact with patients, unit ward, and intensity of care.

Results: Median age was 50 years, and 72% of subjects were female. The overall seroprevalence was 17.11% [95% CI 15.55-18.67]. Around 20% of healthcare assistants were seropositive, followed by physicians and nurses (16.89% and 15.84%, respectively). HCWs with high risk of exposure to COVID-19 were more frequently seropositive (28.52%) with respect to those with medium and low risks (16.71% and 12.76%, respectively). Moreover, personnel in direct contact had higher prevalence (18.32%) compared to those who did not (10.66%). Furthermore, the IgG were more frequently detected among personnel of one hospital (19.43%).

Conclusion: The high seroprevalence observed can be partially explained by the timing and the population seroprevalence; the study was conducted in an area with huge spread of the infection.
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http://dx.doi.org/10.3390/ijerph18073343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037577PMC
March 2021

Ultrasound-guided peripheral intravenous catheters insertion in patient with difficult vascular access: Short axis/out-of-plane versus long axis/in-plane, a randomized controlled trial.

J Vasc Access 2021 Apr 2:11297298211006996. Epub 2021 Apr 2.

Department of Translation Medicine, University of Piemonte Orientale, Novara, Italy.

Purpose: The aim of this study was to evaluate the rate of successful peripheral cannulation between short-axis and long-axis ultrasound guided techniques.

Methods: A single-center, two-arm randomized controlled, intention-to-treat, open-label study was conducted at the Emergency Department, between August and November 2020. Patients requiring a peripheral intravenous catheter insertion and identified as having a difficult intravascular access, were enrolled and followed for up to 96 h.The primary endpoint was the correct placement of the peripheral intravenous catheter. The secondary endpoints were number of venipunctures, intra-procedural pain, local complications, and positive blood return during the follow up.

Results: A total of 283 patients were enrolled: 141 subjects were randomized to the short-axis and 142 to the long-axis group. Success rate was 96.45% (135/141; 95% CI, 91.92%-98.84%) in the short-axis group compared with 92.25% (132/142; 95% CI, 86.56%-96.07%) in the long-axis group ( = 0.126). No significant differences were found in terms of intraprocedural pain and local complications. Higher rate of positive blood return at 72 h [3/17 long-axis, 14/17 short-axis ( = 0.005)] and 96 h [1/10 long-axis, 9/10 short-axis 96 h, ( = 0.022)] was found for the short-axis group.

Conclusions: No differences were found between short-axis and long-axis techniques in terms of success rate, intraprocedural pain, and local complications. Despite this, a slightly higher success rate, a lower number of venipunctures, and a higher rate of positive blood return at 72 and 96 h together with an easier ultrasound technique could suggest a short-axis approach.
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http://dx.doi.org/10.1177/11297298211006996DOI Listing
April 2021

Purse-string suture versus full-thickness skin graft: An efficacy and safety comparison study.

Dermatol Ther 2021 05 4;34(3):e14909. Epub 2021 Mar 4.

Department of Health Science, University of Eastern Piedmont, Novara, Italy.

Purse-string suture (PSS) and full-thickness skin graft (FTSG) are two different approaches to the closure of circular skin defects. In this study, we compare the feasibility and the aesthetic outcome of these two techniques in high operatory risk non-melanoma skin cancer (NMSC) patients. We performed a retrospective study on 65 patients, treated with PSS or FTSG, and evaluated after a minimum follow-up of 6 months. The post-surgery assessment was based on the Vancouver scar scale (VSS) and differences in terms of defect areas, operative and healing times were performed both with parametric and nonparametric tests. Operative times in PSS were significantly lower than those needed for FTSG, without perioperative adverse events; PSS required a waiting time before removing the suture greater than FTSG. After surgery, PSS resulted in a median defect area reduction of 73%. No significant differences were found in the median value for VSS in the two groups. Based on our clinical experience, the PSS advantages in terms of feasibility, rapidity of execution, and mean defect area reduction were confirmed. So, this technique seems to be appropriate for fragile patients affected by NMSC, that cannot hold long surgical sessions.
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http://dx.doi.org/10.1111/dth.14909DOI Listing
May 2021

The Early Detection of Osteoporosis in a Cohort of Healthcare Workers: Is There Room for a Screening Program?

Int J Environ Res Public Health 2021 02 2;18(3). Epub 2021 Feb 2.

Department of Translational Medicine, University of Eastern Piedmont (UPO), 28100 Novara, Italy.

Workforce aging is becoming a significant public health problem due to the resulting emergence of age-related diseases, such as osteoporosis. The prevention and early detection of osteoporosis is important to avoid bone fractures and their socio-economic burden. The aim of this study is to evaluate the sustainability of a screening workplace program able to detect workers with osteoporosis. The screening process included a questionnaire-based risk assessment of 1050 healthcare workers followed by measurement of the bone mass density (BMD) with a pulse-echo ultrasound (PEUS) at the proximal tibia in the at-risk subjects. Workers with a BMD value ≤ 0.783 g/cm² were referred to a specialist visit ensuring a diagnosis and the consequent prescriptions. Any possible association between the outcome variable BMD ≤ 0.783 g/cm² and the risk factors was evaluated. The costs were calculated with a full costing method. We identified 60 pathological subjects. We observed increased risks for women, older ages, and menopause ( < 0.01). The yearly cost of our screening program estimated for this study was 8242 euros, and, considering the fragility bone fracture costs, we hypothesize a considerable economic savings, with a possible positive benefits/cost ratio of 2.07. We can say that the margin between the investment and results leads to a preference for this type of screening program. Osteoporosis is an occupational health problem, and a workplace screening program could be a cost-effective intervention.
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http://dx.doi.org/10.3390/ijerph18031368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908569PMC
February 2021

COVID-19 Diagnosis in Case of Two Negative Nasopharyngeal Swabs: Association between Chest CT and Bronchoalveolar Lavage Results.

Radiology 2021 03 5;298(3):E152-E155. Epub 2021 Jan 5.

From the Medical Department, Respiratory Diseases Unit (F.P., P.E.B.), Department of Diagnosis and Treatment Services, Radiodiagnostics (A.C., Z.F., A.P.), Emergency Medicine Department (F.G.), and Medical Department, Internal Medicine Unit (M.B., P.P.S.), Azienda Ospedaliero Universitaria Maggiore della Carità di Novara, C.so Mazzini 18, 28100 Novara, Italy; Translational Medicine Department, University of Piemonte Orientale Amedeo Avogadro, Novara, Italy (F.P., F.G., C.A., M.B.); and Medical Sciences Department, University of Torino, Turin, Italy (P.S.).

See also the editorial by Little in this issue.
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http://dx.doi.org/10.1148/radiol.2020203776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903987PMC
March 2021

Cellular and humoral cytomegalovirus immunity changes in one-year combined prophylaxis after lung transplantation: suggestions from and for clinical practice.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620981851

Division of Respiratory Medicine, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza di Torino, Torino, Italy.

Background: Immune responses, both cellular and humoral, against cytomegalovirus (CMV) are used to predict CMV manifestations in solid organ recipients. The aim of this study is to evaluate CMV enzyme-linked immunospot (ELISPOT) assay and serology during CMV infections, their concordance and variations after lung transplantation (LTx).

Methods: We retrospectively analysed in one year the follow-up data of 43 patients receiving combined CMV prophylaxis with antiviral agents and CMV-specific immunoglobulin G (IgG). CMV infections were investigated by using molecular analyses on both 167 bronchoalveolar lavage and biopsy specimens and 1134 blood samples. Cellular CMV immunity was assessed with specific ELISPOT whereas the humoral one was assessed by quantifying specific immunoglobulins.

Results: At the first month after LTx the majority of patients were ELISPOT responders (52.3%) and 30.9% were non-responders. ELISPOT responders had a lower incidence of CMV viremia ( = 0.047), whereas neither effects on CMV pulmonary asymptomatic infection nor on acute rejection were observed. Responders had a higher CMV IgG titre ( < 0.0001) in particular at the first month after LTx ( = 0.0001). Concordance among CMV ELISPOT assay and IgG levels was moderate (Cohen's K 0.524), with an agreement of 89.8%. All ELISPOT responders maintained their status and almost all non-responders became responders during follow-up (92.3%); the percentage of IgG seropositive subjects increased from 74.4% at the first month of follow-up to 97.4% after 1 year.

Conclusions: Despite a moderate concordance with serology, ELISPOT response predicted a lower incidence of CMV viremia in LTx patients; no effects were reported on pulmonary clinical manifestations nor on acute rejection. The ELISPOT response as well as serology changed during the follow-up, not only after first CMV contact.
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http://dx.doi.org/10.1177/1753466620981851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780175PMC
November 2021

SARS-CoV-2 Detection on Bronchoalveolar Lavage: An Italian Multicenter experience.

Respiration 2020 19;99(11):970-978. Epub 2020 Oct 19.

Cardiovascular and Thoracic Department, Respiratory Diseases Unit U, "AOU Città della Salute e della Scienza", Torino, Italy.

Background: Bronchoscopy with bronchoalveolar lavage (BAL) during the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic should be reserved to a limited number of clinical indications. The yield of BAL for the diagnosis of suspected or confirmed pulmonary SARS-CoV-2 infection is still unknown.

Objectives: We aimed to evaluate the diagnostic ratio of BAL in detecting SARS-CoV-2 pulmonary infection in patients undergoing bronchoscopy for different indications as well as describe the clinical, radiological, and endoscopic characteristics of patients with SARS-CoV-2 on BAL.

Method: We conducted a multicenter retrospective study including all patients who underwent bronchoscopy for the detection of SARS-CoV-2 on BAL. Clinical, computed tomography (CT), endoscopic, and microbiologic data were gathered from March 16th to May 27th, 2020.

Results: 131 patients were included. Bronchoscopy was performed for suspected SARS-CoV-2 infection (65.5%), alternative diagnosis (12.9%), suspected superinfections (19.8%), and lung atelectasis (1.5%). SARS-CoV-2 was isolated on BAL 43 times (32.8%) and the highest isolation rate was in patients with suspected SARS-CoV-2 infection (74.4%); 76% of positive patients had a double-negative nasopharyngeal swab. Peripheral, posterior and multilobar CT opacities were more frequent in SARS-CoV-2 patients, and the number of CT findings was higher in positive patients, particularly those with suspected SARS-CoV-2 infection. We recorded a progressive reduction of SARS-CoV-2 isolation during the observation period.

Conclusions: In our centers, the rate of detection of SARS-CoV-2 on BAL in patients with suspected infection was 37.2%. The agreement of BAL with nasopharyngeal swabs was high; CT alterations could predict the pretest probability of SARS-CoV-2 infection, but suspicion of viral infection should be always considered.
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http://dx.doi.org/10.1159/000511964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649696PMC
January 2021

Evaluation of Nonresponse Bias in a Case-Control Study of Pleural Mesothelioma.

Int J Environ Res Public Health 2020 08 24;17(17). Epub 2020 Aug 24.

Department of Translational Medicine, Unit of Medical Statistics and Cancer Epidemiology, University of Eastern Piedmont, CPO-Piedmont, 28100 Novara, Italy.

Nonparticipation limits the power of epidemiological studies, and can cause bias. In a case-control study on pleural malignant mesothelioma (MM), we found low participation in interviews (63%) among controls. Our goal was to characterize nonresponder controls and assess nonresponse bias in our study. We selected all nonresponder controls (204) and a random sample of responder controls (174). Data were obtained linking hospital admissions and town registrars, and concordance between sources was assessed. Nonresponse bias was evaluated using a logistic regression model applying the inverse probability weighting approach. The odds ratio (OR) for the status of the respondents was 0.61 (95% confidence interval (CI): 0.33-1.16) for controls aged 61-70, 0.37 (CI: 0.20-0.66) for those aged 71-80, and 0.40 (CI: 0.20-0.80) for those aged above 80 (reference group: ≤60 years). Controls with low education level had lower OR (0.47; CI: 0.26-0.84). After adjustment, the ORs for MM by categories of cumulative exposure to asbestos were similar to the unadjusted results, ranging from 4.6 (CI: 1.8-11.7) for cumulative exposures between 0.1 and 1 f/mL-y to 57.5 (CI: 20.2-163.9) above 10 f/mL-y. Responder controls were younger and had higher education level. Nevertheless, there was little evidence of bias from nonresponse in the risk estimates of MM.
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http://dx.doi.org/10.3390/ijerph17176146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504238PMC
August 2020

Evo-Devo: Tinkering with the Stem Cell Niche to Produce Thorns.

Curr Biol 2020 08;30(15):R873-R875

Department of Plant Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EA, UK. Electronic address:

A new study shows that the defensive thorns of Citrus plants are produced when a TCP transcription factor is expressed in axillary meristems and binds to the promoter of WUSCHEL, repressing the maintenance of cell proliferation.
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http://dx.doi.org/10.1016/j.cub.2020.06.019DOI Listing
August 2020

Resilience, trauma, and hopelessness: protective or triggering factor for the development of psychopathology among migrants?

BMC Psychiatry 2020 07 8;20(1):358. Epub 2020 Jul 8.

Department of Translational Medicine, Institute of Psychiatry, University of Western Piedmont, via Solaroli, 17, 28100, Novara, Italy.

Background: Recently, many studies have investigated the role of migration on mental health. Nonetheless, only few focused on the consequences of childhood trauma, hopelessness, and resilience on migrants' psychopathology, including psychiatric disorders and symptoms.

Method: 119 migrants were recruited between May 2017 and April 2018, among those applying for assessment to the Mental Health Operational Unit of the National Institute for Health, Migration and Poverty (NIHMP) in Rome, Italy. Assessment included the following: Zung Self-Rating Depression Scale (SDS), Zung Self-Rating Anxiety Scale (SAS), Connor-Davidson Resilience Scale (CD-RISC), Childhood Trauma Questionnaire (CTQ), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), Beck Hopelessness Scale (BHS), Beck's Suicide Intent Scale (SIS), Brief Aggression Questionnaire (BAQ), Deliberate Self-Harm Inventory (DSHI).

Results: 53.39% of migrants scored above the PCL-5 cut-off score (mean score was 39.45). SDS scores below the cutoff suggested the presence of depression in 42.37%, while According to SAS scores anxiety levels were low in 38.98% of migrants. During childhood, physical abuse and neglect were reported respectively by 56.78 and 69.49% of migrants.

Conclusion: We found that Post Traumatic Stress Disorders play the role of mediators for the relation between the childhood traumatic experiences and aggressiveness, anxious and depressive symptomatology, while hopelessness is a mediator between the childhood traumatic experiences and the development of depression in adulthood. Hopelessness seems to influence the strength of the relation between childhood traumatic experiences and the individual's current intensity of suicidal attitudes, plans, and behaviors. Further developments and future perspectives of the research project are to address key gaps in the field of resilience by means of a longitudinal evaluation study in migrants, including a native population control group, acceding to NIHMP.
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http://dx.doi.org/10.1186/s12888-020-02729-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346618PMC
July 2020

Safety margins for dermatofibrosarcoma protuberans: a comparison between wide local excision and Mohs Tubingen technique.

Eur J Dermatol 2020 Jun;30(3):289-293

Department of Health Science, University of Eastern Piedmont, Novara.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare, locally infiltrating, rarely metastasizing, soft tissue tumour. Due to its indistinct margins, local aggressive behaviour and high recurrence rate, the surgical approach is complex. Micrographic surgery and variants of this technique, e.g. Tubingen torte technique (TTT), should be considered as first-line treatment.

Objectives: To confirm that TTT is a safe and tissue-sparing technique, relative to theoretical wide local excision (WLE), for the same lesions, as recommended by the guidelines in the literature.

Materials And Methods: Seventeen patients with histologically confirmed DFSP, treated with TTT between September 2014 and February 2019, were retrospectively analysed. For each patient, the final TTT excision area was calculated and compared with the theoretical equivalent area based on WLE. The difference in area was calculated and presented as percentage difference of preserved healthy skin based on the two approaches.

Results: In our patients, the mean preoperative lesion size was 4.55 ± 5.34 cm. The mean final total excised area was 17.73 ± 11.75 cm for TTT and 53.65 ± 15.57 cm for WLE. The amount of preserved healthy tissue using the micrographic technique was significant; 69.15% (95% CI: 62.95-75.36) of healthy tissue was preserved using TTT. No recurrence or metastases were observed in any of the patients after a median follow-up period of 38.00 ± 21 months.

Conclusion: In our experience, TTT remains a safe, effective and tissue-sparing treatment for DFSP patients, especially when it is essential to spare tissue and in challenging locations.
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http://dx.doi.org/10.1684/ejd.2020.3771DOI Listing
June 2020

Deciphering the Ets-1/2-mediated transcriptional regulation of F8 gene identifies a minimal F8 promoter for hemophilia A gene therapy.

Haematologica 2021 06 1;106(6):1624-1635. Epub 2021 Jun 1.

Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.

A major challenge in the development of a gene therapy for hemophilia A (HA) is the selection of cell type- or tissue-specific promoters to ensure factor VIII (FVIII) expression without eliciting an immune response. As liver sinusoidal endothelial cells (LSECs) are the major FVIII source, understanding the transcriptional F8 regulation in these cells would help optimize the minimal F8 promoter (pF8) to efficiently drive FVIII expression. In silico analyses predicted several binding sites (BS) for the E26 transformation-specific (Ets) transcription factors Ets-1 and Ets-2 in the pF8. Reporter assays demonstrated a significant up-regulation of pF8 activity by Ets-1 or Ets-1/Est-2 combination, while Ets2 alone was ineffective. Moreover, Ets-1/Ets-2-DNA binding domain mutants (DBD) abolished promoter activation only when the Ets-1 DBD was removed, suggesting that pF8 up-regulation may occur through Ets-1/Ets-2 interaction with Ets-1 bound to DNA. pF8 carrying Ets-BS deletions unveiled two Ets-BS essential for pF8 activity and response to Ets overexpression. Lentivirus-mediated delivery of GFP or FVIII cassettes driven by the shortened promoters led to GFP expression mainly in endothelial cells in the liver and to long-term FVIII activity without inhibitor formation in HA mice. These data strongly support the potential application of these promoters in HA gene therapy.
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http://dx.doi.org/10.3324/haematol.2019.239202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168518PMC
June 2021

Comparative analysis of programmed death ligand 1 expression in paired cytologic and histologic specimens of non-small cell lung cancer.

Cancer Cytopathol 2020 08 28;128(8):580-588. Epub 2020 May 28.

Pathology Unit, University of Piemonte Orientale, Azienda Ospedaliero Universitaria Maggiore della Carità di Novara, Novara, Italy.

Background: In advanced non-small cell lung cancer (NSCLC), cytologic specimens from transbronchial needle aspiration (TBNA) or transthoracic needle aspiration are often the only cancer tissue material available for the analysis of programmed death ligand 1 (PD-L1) expression. This study was aimed at assessing the concordance of PD-L1 expression in histologic and cytologic samples and at evaluating interobserver agreement on specimens in this setting.

Methods: One hundred and thirty-eight specimens from 60 patients with NSCLC were analyzed. Histologic specimens were represented by endoscopic samples obtained with forceps (biopsies), whereas cytologic specimens were from TBNA and bronchial lavage (BL). PD-L1 expression was quantified with the immunohistochemistry (IHC)-based Ventana SP263 assay. For cytologic specimens, IHC was performed on cell block sections. Two independent pathologists who were blinded to the clinical data evaluated partial or complete membrane IHC staining. Concordance between 2 methods and between 2 pathologists was evaluated with normal and weighted Cohen's κ coefficients, overall agreement, and Bland-Altman plots.

Results: PD-L1 expression was quantified in 138 specimens from 60 patients. Concordance between cytologic and histologic approaches was moderate (κ = 0.56; weighted κ = 0.55). Also, concordance in the biopsy-TBNA and biopsy-BL subgroups was moderate (κ = 0.43 and κ = 0.47, respectively), whereas interobserver agreement was substantial (weighted κ = 0.72). A Bland-Altman plot showed an underestimation in PD-L1 values from cytologic samples in comparison with histologic ones.

Conclusions: The results demonstrate that in the absence of available histologic specimens, PD-L1 positivity in cytologic samples could be a reliable data for the oncologist to consider immune checkpoint inhibitor therapy. However, a comparison of cytologic and histologic samples has shown an underestimation of PD-L1 values in cytologic samples.
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http://dx.doi.org/10.1002/cncy.22292DOI Listing
August 2020

Vaginal birth after caesarean section: a multicentre study on prognostic factors and feasibility.

Arch Gynecol Obstet 2020 02 11;301(2):509-515. Epub 2020 Feb 11.

Department of Obstetrics and Gynecology, "Azienda Ospedaliera Universitaria Integrata", Verona, Italy.

Purpose: Vaginal birth after caesarean (VBAC) is an option to avoid major abdominal surgery and many consequences related to repeated caesarean delivery. In the last years, many efforts have been made to increase the number of patients attempting trial of labour after caesarean (TOLAC). The aim of our study was to identify the most important factors associated with the success of VBAC.

Methods: A retrospective study was conducted in two Italian referral centres. Subjects included were singleton and morphologically normal pregnancy with previous C-section. Subjects with an inter-pregnancy interval shorter than 18 months, a large for gestational age baby, a pregnancy complicated with gestational diabetes and a previous unclassified uterine scar were excluded. The characteristics of the subjects were compared and a logistic regression was performed to evaluate variables associated with successful VBAC.

Results: Of the 300 patients included, 224 (74.7%) achieved VBAC while 76 (25.3%) underwent C-section after failed TOLAC. The number of previous C-sections was not significantly associated with the success of TOLAC. Factors positively associated with achievement of VBAC were previous vaginal delivery (OR of 6.88 for one and 9.68 for more than one) and oxytocin implementation (OR 3.32). No maternal and neonatal adverse events occurred.

Conclusion: Our results show that attempting VBAC is a feasible option in referral centres after adequate evaluation of the potential factors affecting the probability of success. A careful record of obstetrical history and management of labour can provide clinicians useful information to counsel women before and during labour.
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http://dx.doi.org/10.1007/s00404-020-05454-0DOI Listing
February 2020

Estimation of Occupational Exposure to Asbestos in Italy by the Linkage of Mesothelioma Registry (ReNaM) and National Insurance Archives. Methodology and Results.

Int J Environ Res Public Health 2020 02 6;17(3). Epub 2020 Feb 6.

Unit of Medical Statistics and Cancer Epidemiology, Department of Translational Medicine, University of Eastern Piedmont, Novara, CPO-Piedmont, 28100 Novara, Italy.

The identification and monitoring of occupational cancer is an important aspect of occupational health protection. The Italian law on the protection of workers (D. Leg. 81/2008) includes different cancer monitoring systems for high and low etiologic fraction tumors. Record linkage between cancer registries and administrative data is a convenient procedure for occupational cancer monitoring. We aim to: (i) Create a list of industries with asbestos exposure and (ii) identify cancer cases who worked in these industries. The Italian National Mesothelioma Registry (ReNaM) includes information on occupational asbestos exposure of malignant mesothelioma (MM) cases. We developed using data from seven Italian regions a methodology for listing the industries with potential exposure to asbestos linking ReNaM to Italian National Social Security Institute (INPS) data. The methodology is iterative and adjusts for imprecision and inaccuracy in reporting firm names at interview. The list of asbestos exposing firms was applied to the list of cancer cases (all types associated or possibly associated with asbestos according to International Agency for Research on Cancer (IARC) monograph 100C) in two Italian regions for the indication of possible asbestos exposure. Eighteen percent of the cancer cases showed at least one work period in firms potentially exposing to asbestos, 48% of which in regions different from where the cases lived at diagnosis. The methodology offers support for the preliminary screening of asbestos exposing firms in the occupational history of cancer cases.
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http://dx.doi.org/10.3390/ijerph17031020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037801PMC
February 2020

TTG1 proteins regulate circadian activity as well as epidermal cell fate and pigmentation.

Nat Plants 2019 11 11;5(11):1145-1153. Epub 2019 Nov 11.

Department of Plant Sciences, University of Cambridge, Cambridge, UK.

The Arabidopsis genome contains three genes encoding proteins of the TRANSPARENT TESTA GLABRA 1 (TTG1) WD-repeat (WDR) subfamily. TTG1 is a known regulator of epidermal cell differentiation and pigment production, while LIGHT-REGULATED WD1 and LIGHT-REGULATED WD2 are known regulators of the circadian clock. Here, we discovered a new central role for TTG1 WDR proteins as regulators of the circadian system, as evidenced by the lack of detectable circadian rhythms in a triple lwd1 lwd2 ttg1 mutant. This shows that there has been subfunctionalization via protein changes within the angiosperms, with some TTG1 WDR proteins developing a stronger role in circadian clock regulation while losing the protein characteristics essential for pigment production and epidermal cell specification, and others weakening their ability to drive circadian clock regulation. Our work shows that even where proteins are very conserved, small changes can drive big functional differences.
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http://dx.doi.org/10.1038/s41477-019-0544-3DOI Listing
November 2019

Efficacy of new class I medical device for actinic keratoses: a randomized controlled prospective study.

J Dermatolog Treat 2021 Sep 7;32(6):625-630. Epub 2019 Nov 7.

Department of Health Science, Dermatologic Clinic, University of Eastern Piedmont, Novara, Italy.

Background: The presence of Actinic Keratoses (AKs) represent the most important warning sign of subclinical ultraviolet radiation. Currently, the regular use of sunscreens is considered essential for the prevention of the development of AKs.

Aim: We evaluated the effectiveness of a new class I Medical Device (MD) for the prevention and treatment of AKs vs traditional sunscreen alone (SPF 100+).

Methods: We conducted a randomized controlled prospective study in 90 Caucasian patients: 62 immunocompetent and 28 Organ Transplant Recipients (OTRs). We randomly assigned subjects to the MD group or sunscreen alone in a 1:1 assignment ratio. The patients have been reevaluated after three and six months.

Results: In immunocompetent patients treated with MD, at the end of the study the reduction of the mean number of AKs was 54.7 vs. 9.43% with photoprotector. In OTRs, the global reduction was of 36.7% after MD use compared to 14.3% with the sunscreen. The prevalence of NMSCs, in the patients treated with MD, was 11.11 and 17.18 with sunscreen; the incidence was 19.7 in patients treated with MD and 32.1 in those treated with sunscreen.

Conclusion: The MD has demonstrated good efficacy in the reduction of visible AKs, encouraging its use also in high-risk category, like OTRs.
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http://dx.doi.org/10.1080/09546634.2019.1687820DOI Listing
September 2021

The effects of two longpass filters on visual performance.

J Optom 2020 Apr - Jun;13(2):102-112. Epub 2019 Oct 18.

Department of Materials Science, University of Milano Bicocca, Milan, Italy; Research Centre in Optics and Optometry (COMiB), University of Milano Bicocca, Milan, Italy.

Purpose: This study compared visual performance and optical properties of three filters.

Method: Two groups of twenty adults were recruited: wearers of progressive addition lenses (PAL, 46-73 years) and wearers of single vision lenses (SVL, 26-55 years). Three spectacle filters (Hoya, Japan) were compared: clear control, Standard Drive (STD), and Professional Drive (PRO) lenses. Optical transmittance was measured by a Jasco V-650 spectrophotometer. Best corrected visual acuity (BCVA) was measured in photopic (BCVAphotopic) and mesopic (BCVAmesopic) conditions and under glare (BCVAglare). Photopic contrast sensitivity (CS) was also measured.

Results: The three longpass filters show cutoff at 426±2nm (STD/PRO) and 405±2nm (clear lens). BCVAglare improved with Drive filters compared to the clear one (p<0.05) from 0.03 to -0.02 (STD) and to -0.01 (PRO) for PAL and from -0.08 to -0.12 (STD and PRO) for SVL. For PAL, BCVAmesopic improved from 0.15 to 0.12 (STD, p<0.05) and 0.13 (PRO), while no substantial difference was observed for SVL. CS showed some improvements with Drive lenses at some angular frequencies between 6 and 18 cycles/deg, mainly for the PAL group. No BCVAphotopic differences were found. After testing all filters, each for two weeks, 79% (PAL) and 60% (SVL) of participants preferred Drive lenses.

Conclusions: Drive lenses are found to maintain or improve some visual functions compared to the clear lens. The improvement of mesopic visual acuity, visual acuity under glare, and contrast sensitivity is mainly attributed to the reduction of intraocular light scattering as a consequence of the total light attenuation in the spectral range below the cutoff.
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http://dx.doi.org/10.1016/j.optom.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182782PMC
May 2021

The cellular and genetic basis of structural colour in plants.

Curr Opin Plant Biol 2019 02 25;47:81-87. Epub 2018 Oct 25.

Department of Plant Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EA, UK. Electronic address:

While the pathways that produce plant pigments have been well studied for decades, the use by plants of nanoscale structures to produce colour effects has only recently begun to be studied. A variety of plants from across the plant kingdom have been shown to use different mechanism to generate structural colours in tissues as diverse as leaves, flowers and fruits. In this review we explore the cellular mechanisms by which these nanoscale structures are built and discuss the first insights that have been published into the genetic pathways underpinning these traits.
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http://dx.doi.org/10.1016/j.pbi.2018.10.002DOI Listing
February 2019

Master Regulatory Transcription Factors in Plant Development: A Blooming Perspective.

Methods Mol Biol 2018 ;1830:3-22

Department of Plant Sciences, University of Cambridge, Cambridge, UK.

Transcription factors that trigger major developmental decisions in plants and animals are termed "master regulators". Such master regulators are classically seen as acting on the top of a regulatory hierarchy that determines a complete developmental program, and they usually encode transcription factors. Here, we introduce master regulators of flowering time and flower development as examples to show how analysis of molecular interactions and gene-regulatory networks in plants has changed our view on the molecular mechanisms by which these factors control developmental processes. A picture has emerged that emphasizes a complex combinatorial interplay in determining cell-type transcriptional programs, and a high level of feedback control. The expression of master regulators themselves is usually regulated by multiple factors integrating environmental and endogenous spatiotemporal cues. Master regulatory transcription factors regulate gene expression by different mechanisms, including modifications in chromatin status in the bound regions. A poorly understood phenomenon is how developmental master regulators exert functions in different cell- and organ types. This is especially relevant for those factors that have important functions in several developmental processes.
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http://dx.doi.org/10.1007/978-1-4939-8657-6_1DOI Listing
April 2019

MAF2 Is Regulated by Temperature-Dependent Splicing and Represses Flowering at Low Temperatures in Parallel with FLM.

PLoS One 2015 8;10(5):e0126516. Epub 2015 May 8.

Centre for Plant Sciences, University of Leeds, Leeds, United Kingdom.

Plants enter their reproductive phase when the environmental conditions are favourable for the successful production of progeny. The transition from vegetative to reproductive phase is influenced by several environmental factors including ambient temperature. In the model plant Arabidopsis thaliana, SHORT VEGETATIVE PHASE (SVP) is critical for this pathway; svp mutants cannot modify their flowering time in response to ambient temperature. SVP encodes a MADS-box transcription factor that directly represses genes that promote flowering. SVP binds DNA in complexes with other MADS-box transcription factors, including FLOWERING LOCUS M (FLM), which acts with SVP to repress the floral transition at low temperatures. Small temperature changes post-transcriptionally regulate FLM through temperature-dependent alternative splicing (TD-AS). As ambient temperature increases, the predominant FLM splice isoform shifts to encode a protein incapable of exerting a repressive effect on flowering. Here we characterize a closely related MADS-box transcription factor, MADS AFFECTING FLOWERING2 (MAF2), which has independently evolved TD-AS. At low temperatures the most abundant MAF2 splice variant encodes a protein that interacts with SVP to repress flowering. At increased temperature the relative abundance of splice isoforms shifts in favour of an intron-retaining variant that introduces a premature termination codon. We show that this isoform encodes a protein that cannot interact with SVP or repress flowering. At lower temperatures MAF2 and SVP repress flowering in parallel with FLM and SVP, providing an additional input to sense ambient temperature for the control of flowering.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126516PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425511PMC
February 2016
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