The effects of an active breaks intervention on physical and cognitive performance: results from the I-MOVE study.

BACKGROUND: The present quasi-experimental study aimed to evaluate the effects of active breaks intervention (ABs) to promote physical and cognitive improvement in primary school. METHODS: The active breaks group (ABsG) performed 10 min of ABs three times per school day and the control group (CG) did normal lessons. The baseline and follow-up evaluation was conducted respectively in October 2019 and in May 2021. Cognitive performance was assessed using working memory test, physical performance was analyzed with ActiGraph accelerometers and physical fitness tests, quality of life was monitored using the Paediatric Quality of Life questionnaire (PedsQL) and classroom behavior was collected with an ad hoc questionnaire. RESULTS: We enrolled 153 children (age: 7.61 ± 1.41, 54.2% males). Working memory significantly increased in the ABsG (ΔWM: 1.30 ± 1.17) than in CG (ΔWM: 0.96 ± 1.20). The 6 min Cooper test increased in the ABsG (Δ: 1.77 ± 136.03) but not in CG (Δ: -156.42 ± 187.53), P < 0.05. The weekly physical activity levels increased in both groups; however, the sedentary behavior significantly increased both in ABsG and CG. Children reported improvements in their quality of school life including feeling better in class and in school when using ABs; moreover, children improved their time on task behaviors in ABsG. CONCLUSION: The present study has proven to be effective on children's physical and cognitive performance.

Longitudinal Gait Analysis of a Transfemoral Amputee Patient: Single-Case Report from Socket-Type to Osseointegrated Prosthesis.

The aim of the present case report was to provide a longitudinal functional assessment of a patient with transfemoral amputation from the preoperative status with socket-type prosthesis to one year after the osseointegration surgery. A 44 years-old male patient was scheduled for osseointegration surgery 17 years after transfemoral amputation. Gait analysis was performed through 15 wearable inertial sensors (MTw Awinda, Xsens) before surgery (patient wearing his standard socket-type prosthesis) and at 3-, 6-, and 12-month follow-ups after osseointegration. ANOVA in Statistical Parametric Mapping was used to assess the changes in amputee and sound limb hip and pelvis kinematics. The gait symmetry index progressively improved from the pre-op with socket-type (1.14) to the last follow-up (1.04). Step width after osseointegration surgery was half of the pre-op. Hip flexion-extension range significantly improved at follow-ups while frontal and transverse plane rotations decreased (p < 0.001). Pelvis anteversion, obliquity, and rotation also decreased over time (p < 0.001). Spatiotemporal and gait kinematics improved after osseointegration surgery. One year after surgery, symmetry indices were close to non-pathological gait and gait compensation was sensibly decreased. From a functional point of view, osseointegration surgery could be a valid solution in patients with transfemoral amputation facing issues with traditional socket-type prosthesis.

Spondylolisthesis in young patients: postoperative functional outcomes at 22-year mean follow-up.

INTRODUCTION: Previous short- and intermediate-term clinical and radiographic studies demonstrated good results in patients who underwent spine surgery for spondylolisthesis, long-term outcomes are lacking instead. Young patients are often involved in high-demanding and sport activities, therefore good/excellent functional outcomes are very important for their future quality of life. The aim of this study is to assess the long-term functional results in young patients surgically treated for developmental spondylolisthesis. MATERIALS AND METHODS: Retrospective evaluation of consecutive patients who underwent lumbar surgery for spondylolisthesis. Inclusion criteria were: spondylolisthesis from grade 1 to spondyloptosis, age at surgery < 25 years, follow-up > 15 years. The following outcomes were assessed: VAS back, VAS leg, Oswestry disability index (ODI) score, Short Form 12 (SF-12), rate of revision surgery, postoperative recovery and sport activity. RESULTS: 113 patients were enrolled. Mean age at surgery was 19.8 years and mean follow-up was 22.1 years (16-32). 16 patients (14.2%) needed revision surgery. Functional outcomes at last follow-up were: VAS back = 1.6, VAS leg = 1.4, ODI = 9.2%, SF-12 physical component summary = 50, SF-12 mental component summary = 48.7. Significant differences were assessed in terms of ODI (p = 0.047) and SF-12 PCS (p = 0.015) between group treated with instrumented and non-instrumented techniques. Among the patients who practiced a sport, 87% returned to sport postoperatively (55% at medium-high-intensity level). CONCLUSION: This study shows good long-term functional outcomes in patients surgically treated for developmental spondylolisthesis. After surgery, there is a low incidence of back pain, the residual disability is mild and almost half of patients recover the same level of sport activity. Instrumented surgical techniques developed over the years seem to be related to high revision rate, but this does not affect long-term functional results.

Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells.

BACKGROUND: Development of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new resistance-specific vulnerabilities, termed collateral sensitivities. Here we investigated anaplastic lymphoma kinase (ALK) inhibitor resistance in neuroblastoma, a childhood cancer frequently affected by activating ALK alterations. METHODS: Genome-wide forward genetic CRISPR-Cas9 based screens were performed to identify genes associated with ALK inhibitor resistance in neuroblastoma cell lines. Furthermore, the neuroblastoma cell line NBLW-R was rendered resistant by continuous exposure to ALK inhibitors. Genes identified to be associated with ALK inhibitor resistance were further investigated by generating suitable cell line models. In addition, tumor and liquid biopsy samples of four patients with ALK-mutated neuroblastomas before ALK inhibitor treatment and during tumor progression under treatment were genomically profiled. RESULTS: Both genome-wide CRISPR-Cas9-based screens and preclinical spontaneous ALKi resistance models identified NF1 loss and activating NRASQ61K mutations to confer resistance to chemically diverse ALKi. Moreover, human neuroblastomas recurrently developed de novo loss of NF1 and activating RAS mutations after ALKi treatment, leading to therapy resistance. Pathway-specific perturbations confirmed that NF1 loss and activating RAS mutations lead to RAS-MAPK signaling even in the presence of ALKi. Intriguingly, NF1 loss rendered neuroblastoma cells hypersensitive to MEK inhibition. CONCLUSIONS: Our results provide a clinically relevant mechanistic model of ALKi resistance in neuroblastoma and highlight new clinically actionable collateral sensitivities in resistant cells.

Bedside intra-aortic balloon pump insertion in cardiac intensive care unit: A single-center experience.

BACKGROUND: In contemporary Cardiac Intensive Care Unit (CICU), bedside intra-aortic balloon pump (IABP) insertion under echocardiographic guidance may be an attractive option for selected patients with cardiogenic shock (CS). Currently available data on this approach are limited. AIM: This study aimed to assess the feasibility and safety of bedside IABP insertion, as compared to fluoroscopic-guided insertion in the Catheterization Laboratory (CathLab), and to describe the clinical features of patients receiving bedside IABP insertion using a standardized technique in real-world CICU practice. METHODS: We prospectively evaluated all patients admitted the CICU who received transfemoral IABP between June 2020 and October 2021. The overall study cohort was divided according to implant strategy in bedside and CathLab groups. The primary outcome was correct radiographic IABP positioning at the first bedside chest X-ray obtained after insertion. Secondary outcomes included IABP-related complications. RESULTS: Among 115 patients, bedside IABP insertion was performed in 35 (30.4%) cases, mainly presenting with CS-related to acute decompensated heart failure (ADHF) (68.6 vs 33.8%; p < 0.001), with lower LVEF, higher proportion of right ventricular involvement and higher need of inotropes/vasopressors, compared to those receiving CathLab insertion. Bedside IABP insertion resulted feasible and safe, with similar rates of correct IABP positioning (82.9 vs. 82.5%; p = 0.963) and IABP-related major vascular complications (5.7 vs. 5.0%; p = 0.874), as compared to CathLab positioning. CONCLUSION: This study suggests the feasibility and safety of bedside IABP insertion, which could be of relevant interest in patients with ADHF-related CS who may not need coronary angiography or other urgent CathLab procedures.

On-Field Biomechanical Assessment of High and Low Dive in Competitive 16-Year-Old Goalkeepers through Wearable Sensors and Principal Component Analysis.

Diving saves are the main duty of football goalkeepers. Few biomechanical investigations of dive techniques have been conducted, none in a sport-specific environment. The present study investigated the characteristics of goalkeepers' dive in preferred (PS) and non-preferred (nPS) side through an innovative wearables-plus-principal-component analysis (PCA) approach. Nineteen competitive academy goalkeepers (16.5 ± 3.0 years) performed a series of high and low dives on their PS and nPS. Dives were performed in a regular football goal on the pitch. Full-body kinematics were collected through 17 wearable inertial sensors (MTw Awinda, Xsens). PCA was conducted to reduce data dimensionality (input matrix 310,878 datapoints). PCA scores were extracted for each kinematic variable and compared between PS and nPS if their explained variability was >5%. In high dive, participants exhibited greater hip internal rotation and less trunk lateral tilt (p < 0.047, ES > 0.39) in PS than nPS. In low dives, players exhibited greater ipsilateral hip abduction dominance and lower trunk rotation (p < 0.037, ES > 0.40) in PS than nPS. When diving on their nPS, goalkeepers adopted sub-optimal patterns with less trunk coordination and limited explosiveness. An ecological testing through wearables and PCA might help coaches to inspect relevant diving characteristics and improve training effectiveness.

Molecular Tools for the Yeast Papiliotrema terrestris LS28 and Identification of Yap1 as a Transcription Factor Involved in Biocontrol Activity.

Fungal attacks on stored fruit and vegetables are responsible for losses of products. There is an active research field to develop alternative strategies for postharvest disease management, and the use of biocontrol agents represents a promising approach. Understanding the molecular bases of the biocontrol activity of these agents is crucial to potentiate their effectiveness. The yeast Papiliotrema terrestris is a biocontrol agent against postharvest pathogens. Phenotypic studies suggest that it exerts its antagonistic activity through competition for nutrients and space, which relies on its resistance to oxidative and other cellular stresses. In this study, we developed tools for genetic manipulation in P. terrestris to perform targeted gene replacement and functional complementation of the transcription factors Yap1 and Rim101. In vitro phenotypic analyses revealed a conserved role of Yap1 and Rim101 in broad resistance to oxidative stress and alkaline pH sensing, respectively. In vivo analyses revealed that P. terrestris yap1Δ and rim101Δ mutants display decreased ability to colonize wounded fruit compared to that of the parental wild-type (WT) strain; the yap1Δ mutant also displays reduced biocontrol activity against the postharvest pathogens Penicillium expansum and Monilinia fructigena, indicating an important role for resistance to oxidative stress in timely wound colonization and biocontrol activity of P. terrestris In conclusion, the availability of molecular tools developed in the present study provides a foundation to elucidate the genetic mechanisms underlying biocontrol activity of P. terrestris, with the goal of enhancing this activity for the practical use of P. terrestris in pest management programs based on biological and integrated control.IMPORTANCE The use of fungicides represents the most effective and widely used strategy for controlling postharvest diseases. However, their extensive use has raised several concerns, such as the emergence of plant pathogens' resistance as well as the health risks associated with the persistence of chemical residues in fruit, in vegetables, and in the environment. These factors have brought attention to alternative methods for controlling postharvest diseases, such as the utilization of biocontrol agents. In the present study, we developed genetic resources to investigate at the molecular level the mechanisms involved in the biocontrol activity of Papiliotrema terrestris, a basidiomycete yeast that is an effective biocontrol agent against widespread fungal pathogens, including Penicillium expansum, the etiological agent of blue mold disease of pome fruits. A deeper understanding of how postharvest biocontrol agents operate is the basic requirement to promote the utilization of biological (and integrated) control for the reduction of chemical fungicides.

Comparison Between Diffusion-Weighted MRI and 123 I-mIBG Uptake in Primary High-Risk Neuroblastoma.

BACKGROUND: High-risk neuroblastoma (HR-NB) has a variable response to preoperative chemotherapy. It is not possible to differentiate viable vs. nonviable residual tumor before surgery. PURPOSE: To explore the association between apparent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI), 123 I-meta-iodobenzyl-guanidine (123 I-mIBG) uptake, and histology before and after chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Forty patients with HR-NB. FIELD STRENGTH/SEQUENCE: 1.5T axial DW-MRI (b = 0,1000 s/mm2 ) and T2 -weighted sequences. 123 I-mIBG scintigraphy planar imaging (all patients), with additional 123 I-mIBG single-photon emission computed tomography / computerized tomography (SPECT/CT) imaging (15 patients). ASSESSMENT: ADC maps and 123 I-mIBG SPECT/CT images were coregistered to the T2 -weighted images. 123 I-mIBG uptake was normalized with a tumor-to-liver count ratio (TLCR). Regions of interest (ROIs) for primary tumor volume and different intratumor subregions were drawn. The lower quartile ADC value (ADC25prc ) was used over the entire tumor volume and the overall level of 123 I-mIBG uptake was graded into avidity groups. STATISTICAL TESTS: Analysis of variance (ANOVA) and linear regression were used to compare ADC and MIBG values before and after treatment. Threshold values to classify tumors as viable/necrotic were obtained using ROC analysis of ADC and TLCR values. RESULTS: No significant difference in whole-tumor ADC25prc values were found between different 123 I-mIBG avidity groups pre- (P = 0.31) or postchemotherapy (P = 0.35). In the "intratumor" analysis, 5/15 patients (prechemotherapy) and 0/14 patients (postchemotherapy) showed a significant correlation between ADC and TLCR values (P < 0.05). Increased tumor shrinkage was associated with lower pretreatment tumor ADC25prc values (P < 0.001); no association was found with pretreatment 123 I-mIBG avidity (P = 0.17). Completely nonviable tumors had significantly lower postchemotherapy ADC25prc values than tumors with >10% viable tumor (P < 0.05). Both pre- and posttreatment TLCR values were significantly higher in patients with >50% viable tumor than those with 10-50% viable tumor (P < 0.05). DATA CONCLUSION: 123 I-mIBG avidity and ADC values are complementary noninvasive biomarkers of therapeutic response in HR-NB. LEVEL OF EVIDENCE: 4. TECHNICAL EFFICACY STAGE: 3.

Importance of Magnetic Resonance Imaging With Diffusion-weighted Imaging in Guiding Biopsy of Nodular Ganglioneuroblastoma: A Case Report.

BACKGROUND: Nodular ganglioneuroblastoma is a rare peripheral neuroblastic tumor of variable prognosis. Accurate diagnosis, staging, and risk categorization can be particularly challenging in patients with nodular ganglioneuroblastoma due to the inherent heterogeneity of these lesions. CASE PRESENTATION: We illustrate the use of diffusion-weighted magnetic resonance imaging to identify tumor nodules and guide tumor biopsy in an almost 5-year-old boy with a large abdominal tumor. CONCLUSIONS: Diffusion-weighted magnetic resonance imaging was successful in detecting and guiding biopsy of a poorly differentiated neuroblastoma nodule within the context of a well-differentiated ganglioneuroma, allowing the diagnosis and characterization of a ganglioneuroblastoma nodular, thus influencing the child's prognosis and treatment.

Causes of stiffness after total knee arthroplasty: a systematic review.

BACKGROUND: Knee stiffness after total knee arthroplasty (TKA) often leads to pain and discomfort, failing to meet patients' expectations on the surgical procedure. Despite the growing debate on the topic, a comprehensive literature analysis of stiffness causes has never been conducted. Thus, the purpose of the present study was to systematically review the literature regarding the main causes of stiffness after TKA. METHODS: Pubmed Central, Scopus, and EMBASE databases were systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for studies on stiffness and pain or discomfort after TKA through November 2020. Overall, 25 articles matched the selection criteria and were included in the study. Clinical relevance and strength of evidence of the included studies were graded using the risk of bias and the methodological index for non-randomized studies quality assessment tools. RESULTS: The main causes of pain and discomfort due to stiffness were surgery-related issues, i.e., component malpositioning and over-voluming, implant loosening, psychological distress, and obesity, which could be considered "modifiable" factors, and expression of profibrotic markers, high material hypersensitivity-related cytokines level, male gender, previous contralateral TKA, and high pre-operative pain, which could be considered "non-modifiable" factors. CONCLUSION: The use of alternative technologies such as surgical robots, anatomy-based devices, and more inert and less stiff component materials could help in reducing stiffness caused by both modifiable and even some non-modifiable factors. Furthermore, early diagnostic detection of stiffness onset could consistently support surgeons in patient-specific decision-making.

Preoperative computed tomography scanning for abdominal neuroblastomas is superior to magnetic resonance imaging for safe surgical planning.

BACKGROUND: Cross-sectional imaging is required to assess disease prior to surgery for neuroblastoma (NBL), and both magnetic resonance imaging (MRI) and computed tomography (CT) scan are considered acceptable. We had concerns that MRI was underestimating disease extent, so from early 2016 we have systematically used MRI and CT before all abdominal NBL resections. The aim of this retrospective study was to establish which imaging modality is more accurate in determining disease extent, particularly after chemotherapy. METHODS: Abdominal MRI and CT scans for all children with abdominal NBL referred for surgery from January 2016 to February 2018 were retrospectively reviewed to evaluate the extent of disease and the presence of imaging-defined risk factors (IDRFs). RESULTS: Thirty-one patients were eligible for consideration of surgery post disease reassessment with MRI/MIBG. Twenty-four of 31 children were included. CT was performed a median of 15 (range, 1-47) days after MRI. MRI underestimated IDRFs compared with CT in 13 of 24 patients (54%). Seventeen of 24 patients underwent surgery, and operative findings had 100% correlation with CT imaging. Notably, there were fundamental changes in management post CT in 6 of 24 patients (25%). CT did not underestimate disease compared with MRI in any patient. CONCLUSION: MRI underestimated the extent of the disease in half of our patients considered for NBL resection. This may be due in part to tumor fibrosis, calcification, and chemotherapy. Preoperative CT scan is the best imaging modality to identify all IDRFs after chemotherapy to ensure safe surgery.

Extensive Spinal Epidural Abscesses Resolved with Minimally Invasive Surgery: Two Case Reports and Review of the Recent Literature.

PURPOSE: An extensive spinal epidural abscess is a rare condition and causes significant morbidity and mortality. Few authors have described this uncommon entity, which requires early diagnosis and optimal treatment to avoid devastating complications. The purpose of this study was to evaluate a minimally invasive technique for treatment of an extensive spinal epidural abscess by describing two cases. Furthermore, we conducted a review of the recent literature on the management of this rare condition. METHODS: We report two cases of spinal abscesses extending to the whole epidural space, successfully treated by use of a minimally invasive technique consisting of multilevel laminotomy and catheter irrigation to decompress and drain the epidural space. RESULTS: This technique is able to decompress the spinal cord, isolate the pathogen and evacuate the abscess. No complications, late spine deformity or dura penetration were observed in our patients. CONCLUSION: Urgent surgical decompression, in combination with long-term antibiotic treatment, is generally considered the treatment of choice for an extensive spinal epidural abscess. A minimally invasive technique can be very useful as a surgical option.

Adult spinal deformity: effectiveness of interbody lordotic cages to restore disc angle and spino-pelvic parameters through completely mini-invasive trans-psoas and hybrid approach.

PURPOSE: The aim of the study is to assess and quantify the effectiveness of interbody lordotic cages applied by trans-psoas approach to improve radiographic parameters, showing the differences between completely mini-invasive and hybrid approach. METHODS: We collected data of 65 patients affected by degenerative lumbar deformity/diseases and underwent mini-invasive lateral interbody fusion followed by percutaneous (group A, completely mini-invasive) or open (group B, hybrid) posterior instrumentation. A subgroup underwent anterior column realignment (ACR). We assessed statistical differences in preoperative and postoperative (at least 6-month) coronal and sagittal parameters, and disc angle (DA) at each level of cage application. RESULTS: 107 lordotic cages were implanted. Group B had the most significant mean changes, especially in coronal Cobb angle, sagittal vertical axis, lumbar lordosis (LL), pelvic incidence-LL mismatch and DA. Concerning DA, at each level of lordotic cage application, in group A changed from -2.9° preop to -6.5° postop (p = 0.01); in group B, DA changed from -2.6° to -9.5° (p = 0.002) and from +1° to -13.2° in patients underwent ACR. CONCLUSIONS: Minimally invasive lateral lumbar interbody fusion is an effective technique in improving sagittal parameters. When combined with posterior open approach and/or application of ACR procedure greater corrections are possible.

Factors associated with recurrence and survival length following relapse in patients with neuroblastoma.

BACKGROUND: Despite therapeutic advances, survival following relapse for neuroblastoma patients remains poor. We investigated clinical and biological factors associated with length of progression-free and overall survival following relapse in UK neuroblastoma patients. METHODS: All cases of relapsed neuroblastoma, diagnosed during 1990-2010, were identified from four Paediatric Oncology principal treatment centres. Kaplan-Meier and Cox regression analyses were used to calculate post-relapse overall survival (PROS), post-relapse progression-free survival (PRPFS) between relapse and further progression, and to investigate influencing factors. RESULTS: One hundred eighty-nine cases were identified from case notes, 159 (84.0%) high risk and 17 (9.0%), unresectable, MYCN non-amplified (non-MNA) intermediate risk (IR). For high-risk patients diagnosed >2000, median PROS was 8.4 months (interquartile range (IQR)=3.0-17.4) and median PRPFS was 4.7 months (IQR=2.1-7.1). For IR, unresectable non-MNA patients, median PROS was 11.8 months (IQR 9.0-51.6) and 5-year PROS was 24% (95% CI 7-45%). MYCN amplified (MNA) disease and bone marrow metastases at diagnosis were independently associated with worse PROS for high-risk cases. Eighty percent of high-risk relapses occurred within 2 years of diagnosis compared with 50% of unresectable non-MNA IR disease. CONCLUSIONS: Patients with relapsed HR neuroblastomas should be treatment stratified according to MYCN status and PRPFS should be the primary endpoint in early phase clinical trials. The failure to salvage the majority of IR neuroblastoma is concerning, supporting investigation of intensification of upfront treatment regimens in this group to determine whether their use would diminish likelihood of relapse.

Toxicity and outcome of children and adolescents participating in phase I/II trials of novel anticancer drugs: the Royal Marsden experience.

Early phase trials are crucial in developing new therapies for poor prognosis childhood malignancies. Outcomes and toxicities of children treated on phase I/II trials at the Royal Marsden, one of the largest pediatric oncology early phase trial units in Europe, were examined to provide a baseline dataset and generate hypotheses. All patients recruited over a 10-year period to December 2011 were included. Variables including baseline characteristics, time on study, survival, toxicities, and admissions were collected. Seventy-two patients were recruited to 21 trials (5 phase I, 16 phase II; overall 12 involved molecularly targeted agents). Median age at consent was 12.4 years. Dose-limiting toxicities were rare in phase I trial participants (2 of 15 evaluable patients, 13%); the most common reason for leaving trials was disease progression (76%), rather than drug toxicity (1.7%). Median time on trial was 1.3 months (phase I patients) and 3.3 months (phase II). Early phase trials in children are safe and unexpected toxic side effects are infrequent. Patients and their families are willing to travel to access novel therapies, although the overall prognosis for these individuals is poor. Continued expansion of the portfolio is needed ultimately to improve the outcomes for those with resistant disease.

Pedicle subtraction osteotomy for the treatment of chin-on-chest deformity in a post-radiotherapy dropped head syndrome: a case report and review of literature.

PURPOSE: Chin-on-chest deformity is a rare and severe condition mostly related with ankylosing spondylitis, traumas and/or cervical spine surgery. We present a case of 69 years old woman with a rare form of chin-on-chest secondary to dropped head syndrome (DHS), developed after radiotherapy for Hodgkin disease. In addition, we reviewed the few publications about this specific condition; management and surgical treatment of DHS are discussed. METHODS: We performed a pedicle subtraction osteotomy (PSO) and stabilization through a posterior approach. Intraoperative monitoring using motor and somatosensory evoked potentials and wake-up test were carried out. RESULTS: At 19th month follow-up, the patient reported a significant improvement of cervical pain, dysphagia and respiratory difficulty and a complete restoration of the neurological impairment. The achieved correction was successful and the patient was very satisfied by the restoration of forward gaze. CONCLUSIONS: DHS is a very rare post-radiotherapy complication; there is lack of evidences in literature about its management. The only definitive treatment seems to be surgical intervention. PSO is a valid therapeutic option when fixed chin-on-chest deformity occurs; although it is a demanding technique and it presents high rate of complications, the actual neurological monitoring methods provide more intraoperative safety.

Transcriptomic investigation of the interaction between a biocontrol yeast, Papiliotrema terrestris strain PT22AV, and the postharvest fungal pathogen Penicillium expansum on apple.

Biocontrol strategies offer a promising alternative to control plant pathogens achieving food safety and security. In this study we apply a RNAseq analysis during interaction between the biocontrol agent (BCA) Papiliotrema terrestris, the pathogen Penicillium expansum, and the host Malus domestica. Analysis of the BCA finds overall 802 upregulated DEGs (differentially expressed genes) when grown in apple tissue, with the majority being involved in nutrients uptake and oxidative stress response. This suggests that these processes are crucial for the BCA to colonize the fruit wounds and outcompete the pathogen. As to P. expansum analysis, 1017 DEGs are upregulated when grown in apple tissue, with the most represented GO categories being transcription, oxidation reduction process, and transmembrane transport. Analysis of the host M. domestica finds a higher number of DEGs in response to the pathogen compared to the BCA, with overexpression of genes involved in host defense signaling pathways in the presence of both of them, and a prevalence of pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) only during interaction with P. expansum. This analysis contributes to advance the knowledge on the molecular mechanisms that underlie biocontrol activity and the tritrophic interaction of the BCA with the pathogen and the host.

In Vivo Total Ankle Arthroplasty Kinematic Evaluation: A Prospective Radiostereometric Analysis.

Ankle osteoarthritis (OA) represents a significant social burden and is one of the main causes of chronic disability in a rapidly growing part of the world's population. Total ankle arthroplasty (TAA) has become increasingly popular despite the poor results obtained with the first dedicated designs. The purpose of this paper was to evaluate the ankle kinematics, in vivo and under weight-bearing conditions, of a TAA through a dynamic model-based radiostereometric analysis (MB-RSA). The clinical evaluation was performed by administering the American Orthopaedic Foot and Ankle Society ankle-hindfoot score and Short Form-36 questionnaires. The kinematic evaluation was conducted through MB-RSA during the execution of an open kinetic chain and a closed kinetic chain motor task. Double radiographic images of the ankle joint were processed using dedicated software to obtain a 3D reconstruction of the ankle prosthetic components' motion. Eighteen patients (five females) completed the clinical and instrumental preoperative and postoperative evaluations (age 59.1 ± 10.3). All clinical scores showed a marked improvement (p < 0.005). During the closed kinetic chain motor tasks, the ankle showed a total range of motion (ROM) in dorsi-plantarflexion of 19.84°. The parameters in varus-valgus were recorded. Physiological motion can be achieved in TAA, characterized by a wide range of motion and coupling of movements on the three planes. The results of the present work may help to understand the real movement of a widespread TAA model and possibly to improve future designs and instrumentation.

Clinical burden and predictors of non-cardiovascular mortality and morbidity in advanced heart failure.

BACKGROUND: The changing demographic of heart failure (HF) increases the exposure to non-cardiovascular (non-CV) events. We investigated the distribution of non-CV mortality/morbidity and the characteristics associated with higher risk of non-CV events in patients with advanced HF. METHODS: Patients from the HELP-HF registry were stratified according to the number of 2018 HFA-ESC criteria for advanced HF. Endpoints were non-CV mortality and non-CV hospitalization. Competing risk analyses were performed assessing the association between HFA-ESC criteria and study outcomes and the additional predictors of non-CV endpoints. RESULTS: One thousand one hundred and forty-nine patients were included (median age 77 years-IQR 69-83). At 6, 12, 18 and 22 months, cumulative incidence of CV vs non-CV mortality was 13% vs 5%, 17% vs 8%, 20% vs 12%, 23% vs 12%, and of CV vs non-CV hospitalization was 26% vs 11%, 38% vs 17%, 45% vs 20%, 50% vs 21%. HFA-ESC criteria were associated with increasing adjusted risk of CV death, whereas no association was observed for CV hospitalization, non-CV death and non-CV hospitalization. Predictors of non-CV death were age, chronic obstructive pulmonary disease, dementia, preserved ejection fraction, >1 HF hospitalization and hemoglobin. CONCLUSIONS: Patients with advanced HF are exposed to high, even though not predominant, burden of non-CV outcomes. HFA-ESC criteria aid to stratify the risk of CV death, but are not associated with lower competing risk of non-CV outcomes. Alternative factors can be useful to define the patients with advanced HF at risk of non-CV events in order to better select patients for treatments specifically reducing CV risk.

Role of ejection fraction in patients at risk for advanced heart failure: insights from the HELP-HF registry.

AIMS: Patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) may all progress to advanced HF, but the impact of EF in the advanced setting is not well established. Our aim was to assess the prognostic impact of EF in patients with at least one 'I NEED HELP' marker for advanced HF. METHODS AND RESULTS: Patients with HF and at least one high-risk 'I NEED HELP' criterion from four centres were included in this analysis. Outcomes were assessed in patients with HFrEF (EF ≤ 40%), HFmrEF (EF 41-49%), and HFpEF (EF ≥ 50%) and with EF analysed as a continuous variable. The prognostic impact of medical therapy for HF in patients with EF < 50% and EF > 50% was also evaluated. All-cause death was the primary endpoint, and cardiovascular death was a secondary endpoint. Among 1149 patients enrolled [mean age 75.1 ± 11.5 years, 67.3% males, 67.6% hospitalized, median follow-up 260 days (inter-quartile range 105-390 days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1 year mortality was 28.3%, 26.2%, and 20.1, respectively (log-rank P = 0.036). As compared with HFrEF patients, HFpEF patients had a lower risk of all-cause death [adjusted hazard ratio (HRadj ) 0.67, 95% confidence interval (CI) 0.48-0.94, P = 0.022], whereas no difference was noted for HFmrEF patients. After multivariable adjustment, a lower risk of all-cause death (HRadj for 5% increase 0.94, 95% CI 0.89-0.99, P = 0.017) and cardiovascular death (HRadj for 5% increase 0.94, 95% CI 0.88-1.00, P = 0.049) was observed at higher EF values. Beta-blockers and renin-angiotensin system inhibitors or sacubitril/valsartan were associated with lower mortality in both EF < 50% and EF ≥ 50% groups. CONCLUSIONS: Among patients with HF and at least one 'I NEED HELP' marker for advanced HF, left ventricular EF is still of prognostic value.