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Objectives: Patients with borderline personality disorder (pw-BPD) have decreased levels of cognitive empathy, which may be subtended by mirror-like mechanisms in the somatosensory cortices, i.e., the Tactile Mirror System (TaMS). Here, we aimed to shed light on the TaMS and empathic deficits in pw-BPD focusing on connectivity, using transcranial magnetic stimulation and electroencephalography (TMS-EEG)., Methods: After study preregistration, we collected self-report measures of empathic abilities, behavioral performance in a visuo-tactile spatial congruency task investigating TaMS activity, and TMS-evoked potentials (TEPs) from 20 pw-BPD and 20 healthy controls. TMS was delivered over the right primary somatosensory cortex (S1) during touch observation and real touch delivery., Results: Pw-BPD reported significantly lower levels of cognitive empathy than controls and made significantly more errors in reporting the side of real touches during touch observation. Moreover, pw-BPD presented an altered connectivity pattern from S1-TEPs during touch perception and touch observation, in the last case without differences between human- and object-directed touches., Conclusions: The results do not support a specific impairment of TaMS in pw-BPD, but reveal significant behavioral and connectivity alterations within the somatosensory network during touch processing., Significance: The present findings temper the proposed role of the TaMS in BPD, while still highlighting the involvement of somatosensory network alterations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Federation of Clinical Neurophysiology. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest.

The aim of this study was to retrospectively evaluate the direct costs of OSCC treatment and postsurgical surveillance in a tertiary hospital in northeast Italy. Sixty-three consecutive patients surgically treated for primitive OSCC at S. Orsola Hospital in Bologna (Italy) between January 2018 and January 2020 were analyzed. Billing records of the Emilia Romagna healthcare system and institutional costs were used to derive specific costs for the following clinical categories: operating theatre costs, intensive and ordinary hospitalization, radiotherapy, chemotherapy, postsurgical complications, visits, and examinations during the follow-up period. The study population comprised 17 OSCC patients classified at stage I, 14 at stage II, eight at stage III, and 24 at stage IV. The estimated mean total direct cost for OSCC treatment and postsurgical surveillance was €26 338.48 per patient (stage I: €10 733, stage II: €19 642.9, stage III: €30 361.4, stage IV: €39 957.2). An advanced diagnosis (stages III and IV), complex surgical procedure, and loco-regional recurrences resulted in variables that were significantly associated with a higher cost of OSCC treatment and postsurgical surveillance. Redirection of funds used for OSCC treatment to screening measures may be an effective strategy to improve overall health outcomes and optimize national health resources., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The transition from acute (e.g., psychiatric hospitalization) to outpatient care is associated with increased risk for rehospitalization, treatment disengagement, and suicide among people with serious mental illness (SMI). Mobile interventions (i.e., mHealth) have the potential to increase monitoring and improve coping post-acute care for this population. This protocol paper describes a Hybrid Type 1 effectiveness-implementation study, in which a randomized controlled trial will be conducted to determine the effectiveness of a multi-component mHealth intervention (tFOCUS) for improving outcomes for adults with SMI transitioning from acute to outpatient care., Methods: Adults meeting criteria for schizophrenia-spectrum or major mood disorders (n = 180) will be recruited from a psychiatric hospital and randomized to treatment-as-usual (TAU) plus standard discharge planning and aftercare (CHECK-IN) or TAU plus tFOCUS. tFOCUS is a 12-week intervention, consisting of: (a) a patient-facing mHealth smartphone app with daily self-assessment prompts and targeted coping strategies; (b) a clinician-facing web dashboard; and, (c) mHealth aftercare advisors, who will conduct brief post-hospital clinical calls with patients (e.g., safety concerns, treatment engagement) and encourage app use. Follow-ups will be conducted at 6-, 12-, and 24-weeks post-discharge to assess primary and secondary outcomes, as well as target mechanisms. We also will assess barriers and facilitators to future implementation of tFOCUS via qualitative interviews of stakeholders and input from a Community Advisory Board throughout the project., Conclusions: Information gathered during this project, in combination with successful study outcomes, will inform a potential tFOCUS intervention scale-up across a range of psychiatric hospitals and healthcare systems., Clinicaltrials: govregistration: NCT05703412., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A well-corroborated numerical methodology ensuring reproducibility in the modeling of pharmaceutical aerosols deposition in the respiratory system via CFD-DEM simulations within the RANS framework is currently missing. Often, inadequately clarified assumptions and approximations and the lack of evidences on their quantitative impact on the simulated deposition phenomenology, make a direct comparison among the different theoretical studies and the limited number of experiments a very challenging task. Here, with the ultimate goal of providing a critical analysis of some crucial computational aspects of aerosols deposition, we address the issues of velocity fluctuations propagation in the upper intra-thoracic airways and of the persistence of secondary flows using the SimInhale reference benchmark. We complement the investigation by describing how methodologies used to drive the flow through a truncated lung model may affect numerical results and how small discrepancies are observed in velocity profiles when comparing simulations based on different meshing strategies., Competing Interests: Declaration of competing interest A.B. and C.C. are Chiesi Farmaceutici employees. R.R. is a consultant/contractor currently engaged by Chiesi Farmaceutici., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In pediatric anterior cruciate ligament reconstruction, many factors should be considered: (1) risk of growth disturbance; (2) high risk of re-tear; (3) determination of the skeletal age, which is sometimes challenging; and (4) no single technique indicated for all patients. The choice of the technique mostly depends on the patients' age and growth potential. Whereas prepubescent patients can be safely treated with physeal sparing techniques (i.e., the Kocher-Micheli technique or its modifications), in postpubescent patients physeal respecting or adult-type reconstructions are generally indicated. In pubescent patients, both all-inside all-epiphyseal and partial transphyseal techniques can be safely performed, but these are not without shortcomings. With the goal of overcoming some of the drawbacks of the existing techniques, the authors describe this technical note. The technique entails an over-the-top femoral position of a 6-strand hamstring graft and an all-epiphyseal tibial tunnel. The femoral physis is completely preserved, and only a 4.5 mm transphyseal tunnel is drilled in the tibia with an all-epiphyseal tibial half socket. With this technique, the graft diameter is adequate, there is no need for fluoroscopy, no risk of graft/tunnel mismatch, and a modified Arnold-Coker lateral tenodesis can be associated via the same lateral incision., (© 2024 The Authors.)

We generated iPSC line using skin fibroblasts obtained from a female patient affected by Joubert syndrome, caused by two compound heterozygous variants (c.143G > A; p.Gly48Glu and c.1784 T > G; p.Leu595Ter) in CPLANE1. We used Sendai-virus-based technique for reprogramming and then we applied karyotype analysis, to exclude possible acquired big rearrangements. We verified the presence of the same STR profile as fibroblasts, the stem cell state (by immunofluorescence and qPCR) and, finally, the pluripotency state (by in vitro trilineage differentiation)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Immunohistochemical analysis of podoplanin expression as a pre-operative molecular marker for perineural invasion (PNI) may represent an attractive strategy for surgical management of oral squamous cell cancer (OSCC). We evaluated the relationship between podoplanin expression and PNI in pre-operative incisional biopsies of OSCC., Study Design: After performing pathological staging and histologic and immunohistochemical evaluation of 83 surgical specimens, we performed multivariable logistic regression analysis to examine the relationship between PNI and independent variables. To evaluate the utility of podoplanin immunopositivity for discrimination of PNI status pre-operatively, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value. We performed receiver operating characteristic curve analysis to evaluate the diagnostic accuracy of podoplanin immunopositivity for predicting PNI alone and in combination with age, T stage, N stage, and index site., Results: We observed podoplanin expression in 42 (50.6%) of all the 83 pre-operative incisional biopsies and 29 of the pre-operative biopsies of the 31 (93.5%) postoperative specimens with PNI. The rate of podoplanin expression was significantly higher in patients with pT3 to pT4 stage and pN+ stage disease. Podoplanin positivity in the pre-operative biopsy showed high sensitivity in predicting PNI in the surgical specimen., Conclusion: Podoplanin expression appears to be an independent pre-operative variable significantly related to PNI and a possibly valuable prognostic marker for therapeutical planning and surgical treatment of OSCC., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Octreotide and lanreotide are the two somatostatin analogs (SSA) currently available in clinical practice. They have been approved first to control the clinical syndrome (mainly carcinoid syndrome) associated with functioning neuroendocrine tumors (NET) and later for tumor growth control in advanced low/intermediate grade NET. Although evidence regarding their role, especially as antiproliferative therapy, has been increasing over the years some clinical indications remain controversial. Solicited by AIOM (Italian Association of Medical Oncology) a group of clinicians from various specialties, including medical oncology, endocrinology, and gastroenterology, deeply involved in NET for their clinical and research activity, addressed eight open questions, critically reviewing evidence and guidelines and sharing clinical take-home messages. The questions regarded the use of long-acting octreotide and lanreotide in the following settings: functioning and non-functioning NET refractory to label dose, first-line metastatic pulmonary NET, combination with other therapy with an antiproliferative intent, maintenance in NET responding to other therapies, adjuvant treatment, Ki-67-related cut-off, somatostatin receptor imaging, safety, and feasibility. The level of evidence is not absolute for the majority of these clinical contexts, so it is recommended to distinguish routine versus sporadic utilization in very selected cases. Mention of such specific issues by the main European guidelines (ENETS, European Neuroendocrine Tumor Society, and ESMO, European Society for Medical Oncology) was explored and their position reported. However, different clinical decisions on single patients could be made if the case is carefully discussed within a NET-dedicated multidisciplinary team., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Emotional regulation (ER) is a core variable involved in the onset and maintenance of mental health disorders; therefore, interventions targeting ER in adolescence represent a promising preventive action. The current systematic review provides a synthesis of the evidence on school-based interventions on ER in adolescent students., Methods: Six electronic databases (Medline, Psychology Database, Embase, Scopus, Psychinfo, and Web of Science) were searched. The methodological quality of the included studies was assessed by the Methodological Index for Nonrandomized Studies., Results: A total of 36 studies were identified. The interventions were based on different theoretic frameworks and focused on different components of ER. There were universal interventions that addressed the entire class, as well as interventions for a selected population of at-risk students. Only one-third of the studies were based on manualized programs. Small to moderate effect sizes were found for mental health and ER skills. Only a few studies assessed risky behaviors, and these studies showed a reduction with moderate to large effect size. Studies conducted on high-risk populations showed medium-high effect sizes on ER skills. In contrast, studies conducted on unselected samples of students showed greater variability in the outcome estimates. Acceptability analysis and attendance rates suggested that the interventions were well received by students. The lack of follow-up assessments and the absence of sample-size calculation were the most frequent methodological weaknesses., Conclusions: The content of the present review could be useful for professionals involved in the planning of school psychological services. Overall, the findings of the current review support the applicability and beneficial effect of school-based intervention for adolescents. Moreover, the results clearly point out the utility of a multitiered model to structure coordinated and integrated preventive interventions and to optimize resources., (© 2022 The Authors. Journal of Adolescence published by Wiley Periodicals LLC on behalf of Foundation for Professionals in Services to Adolescents.)

Context: Inflammation is proposed to influence tumor response in radiotherapy (RT). Clinical studies to investigate the relationship between inflammatory markers and RT response is warranted to understand the variable RT efficacy in patients with painful bone metastases., Objectives: To evaluate the association between inflammatory markers and analgesic response to RT in patients with painful bone metastases., Methods: Adult patients from 7 European study sites undergoing RT for painful bone metastases were included in this prospective and longitudinal analysis. The association between RT response and 17 inflammatory markers at baseline, as well as the association between RT response and the changes observed in inflammatory markers between baseline and three and eight weeks after RT, was analyzed with univariate regression analyses. Baseline analyses were adjusted for potential clinical predictors of RT response., Results: None of the inflammatory markers were significantly associated with an upcoming RT response in the analysis of 448 patients with complete baseline data. In patients available for follow-up, the three-week change in TNF (P 0.017), IL-8 (P 0.028), IP-10 (P 0.032), eotaxin (P 0.043), G-CSF (P 0.033) and MCP-1 (P 0.002) were positively associated with RT response, while the three-week change in CRP (P 0.006) was negatively associated., Conclusion: Results from this study show an association between RT response and change in pro-inflammatory mediators and indicate that inflammation may be important to achieve an analgesic RT response in patients with painful bone metastases. None of the investigated inflammatory markers were found to be pre-treatment predictors of RT response., Competing Interests: Disclosures This research received no specific funding/grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The perinatal period and early infancy are considered critical periods for lung development. During this period, adversities such as environmental exposures, allergic sensitization, and asthma are believed to impact lung health in adulthood. Therefore, we hypothesized that concomitant exposure to allergic sensitization and urban-derived fine particulate matter (PM 2.5 ) in the early postnatal period of mice would cause more profound alterations in lung alveolarization and growth and differently modulate lung inflammation and gene expression than either insult alone in adult life. BALB/c mice were sensitized with ovalbumin (OVA) and exposed to PM 2.5 from the fifth day of life. Then, we assessed lung responsiveness, inflammation in BALF, lung tissue, and alveolarization by stereology. In addition, we performed a transcriptomic analysis of lung tissue on the 40th day of life. Our results showed that young adult mice submitted to allergic sensitization and exposure to ambient PM 2.5 since early life presented decreased lung growth with impaired alveolarization, a mixed neutrophilic-eosinophilic pattern of lung inflammation, increased airway responsiveness, and increased expression of genes linked to neutrophil recruitment when compared to animals that were OVA-sensitized or PM 2.5 exposed only. Both, early life allergic sensitization and PM 2.5 exposure, induced inflammation and impaired lung growth, but concomitant exposure was associated with worsened inflammation parameters and caused alveolar enlargement. Our experimental data provide pathological support for the hypothesis that allergic or environmental insults in early life have permanent adverse consequences for lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice. Together with our data, current evidence points to the urgent need for healthier environments with fewer childhood disadvantage factors during the critical windows of lung development and growth., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Tibial tubercle osteotomy (TTO) is indicated to treat patellofemoral (PF) malalignment and chondral disease refractory to conservative treatment. However, there are no systematic reviews describing TTO outcomes in chondral damages without instability., Aim: The aims of this study were to (1) assess the quality of the published studies, (2) identify indication for TTO to treat PFP with chondral disease without instability, (3) evaluate the most common TTO techniques, (4) evaluate the clinical outcomes, and (5) evaluate TTO's complication and failure rates., Evidence Review: In December 2020, a literature search was performed applying the following criteria: (1) peer-reviewed Level 1-4 studies; (2) English language; (3) human subjects with clinical and/or radiological outcomes; (4) TTO alone or associated with minor cartilage procedure (only drilling, no instability); (5) minimum follow-up 12 months, minimum 10 patients; and (6) no more than 20% of drop-out rate. Data from studies were collected and described with weighted averages and standard deviations., Findings: A total of 18 Level 4 studies were included. The average Coleman Methodology Score was 61.5 points (range 48-81). A total of 851 patients (892 knees) were included, with 64.8% of female patients. The weighted average follow-up was 49.1 months (range 12-128.5). Indication for TTOs was poorly described. The main technique used was anteromedialisation (60.4%). In 27.7% of the cases, TTO was associated with lateral release. Different scoring systems were used to evaluate outcomes, with significant improvements. The average rate of good/excellent results was 78.7% (range 57%-100%). Fifteen studies described the complication rate (9.9%), whereas only four reported the failure rate (6.2%)., Conclusion and Relevance: TTOs performed to treat PF malalignment associated with chondral disease without instability provided good clinical outcomes, with acceptable complication/failure rates. However, high-level studies are necessary because of studies' heterogeneity regarding patellofemoral malalignment and chondral disease treatment., Study Design and Level of Evidence: Systematic review., Level of the Study: Level IV, systematic review of Level IV studies., Competing Interests: Competing interests R.R. is a teaching consultant for Arthrex®, Zimmer Biomet®, Depuy Mitek®, Medacta®, Lima Corporate® and Smith and Nephew®. D.E.B. is a paid teaching consultant for Arthrex and Zimmer Biomet. He received editorial royalties for Elsevier and Springer, and he is in the editorial board “The Knee” journal, Elsevier. The other authors certify that they have no commercial associations that might pose a conflict of interest in connection with the submitted article. Conflict of interest is described in the appropriate uploaded document., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Alkaptonuria (AKU) is an ultra-rare genetic disease caused by a deficient activity of the enzyme homogentisate 1,2-dioxygenase (HGD) leading to the accumulation of homogentisic acid (HGA) on connective tissues. Even though AKU is a multi-systemic disease, osteoarticular cartilage is the most affected system and the most damaged tissue by the disease. In chondrocytes, HGA causes oxidative stress dysfunctions, which induce a series of not fully characterized cellular responses. In this study, we used a human chondrocytic cell line as an AKU model to evaluate, for the first time, the effect of HGA on autophagy, the main homeostasis system in articular cartilage. Cells responded timely to HGA treatment with an increase in autophagy as a mechanism of protection. In a chronic state, HGA-induced oxidative stress decreased autophagy, and chondrocytes, unable to restore balance, activated the chondroptosis pathway. This decrease in autophagy also correlated with the accumulation of ochronotic pigment, a hallmark of AKU. Our data suggest new perspectives for understanding AKU and a mechanistic model that rationalizes the damaging role of HGA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nucleophosmin (NPM1) mutations in acute myeloid leukemia (AML) affect exon 12, but also sporadically affect exons 9 and 11, causing changes at the protein C-terminal end (tryptophan loss, nuclear export signal [NES] motif creation) that lead to aberrant cytoplasmic NPM1 (NPM1c+), detectable by immunohistochemistry. Combining immunohistochemistry and molecular analyses in 929 patients with AML, we found non-exon 12 NPM1 mutations in 5 (1.3%) of 387 NPM1c+ cases. Besides mutations in exons 9 (n = 1) and 11 (n = 1), novel exon 5 mutations were discovered (n = 3). Another exon 5 mutation was identified in an additional 141 patients with AML selected for wild-type NPM1 exon 12. Three NPM1 rearrangements (NPM1/RPP30, NPM1/SETBP1, NPM1/CCDC28A) were detected and characterized among 13 979 AML samples screened by cytogenetic/fluorescence in situ hybridization and RNA sequencing. Functional studies demonstrated that in AML cases, new NPM1 proteins harbored an efficient extra NES, either newly created or already present in the fusion partner, ensuring its cytoplasmic accumulation. Our findings support NPM1 cytoplasmic relocation as critical for leukemogenesis and reinforce the role of immunohistochemistry in predicting AML-associated NPM1 genetic lesions. This study highlights the need to develop new assays for molecular diagnosis and monitoring of NPM1-mutated AML., (© 2021 by The American Society of Hematology.)

Background: Radiotherapy (RT) reduces pain in about 60% of patients with painful bone metastases, leaving many patients without clinical benefit. This study assesses predictors for RT effectiveness in patients with painful bone metastases., Materials and Methods: We included adult patients receiving RT for painful bone metastases in a multicenter, multinational longitudinal observational study. Pain response within 8 weeks was defined as ≥2-point decrease on a 0-10 pain score scale, without increase in analgesics; or a decrease in analgesics of ≥25% without increase in pain score. Potential predictors were related to patient demographics, RT administration, pain characteristics, tumor characteristics, depression and inflammation (C-reactive protein [CRP]). Multivariate logistic regression analysis with multiple imputation of missing data were applied to identify predictors of RT response., Results: Of 513 eligible patients, 460 patients (90 %) were included in the regression model. 224 patients (44%, 95% confidence interval (CI) 39%-48%) responded to RT. Better Karnofsky performance status (Odds ratio (OR) 1.39, CI 1.15-1.68), breast cancer (OR 2.54, CI 1.12-5.73), prostate cancer (OR 2.83, CI 1.27-6.33) and soft tissue expansion (OR 2.00, CI 1.23-3.25) predicted RT response. Corticosteroids were a negative predictor (OR 0.57, CI 0.37-0.88). Single and multiple fraction RT had similar response. The discriminative ability of the model was moderate; C-statistic 0.69., Conclusion: This study supports previous findings that better performance status and type of cancer diagnosis predicts analgesic RT response, and new data showing that soft tissue expansion predicts RT response and that corticosteroids is a negative predictor for RT response in patients with painful bone metastases., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The addition of electrically conductive materials may enhance anaerobic digestion (AD) efficiency by promoting direct interspecies electron transfer (DIET) between electroactive microorganisms, but an equivalent enhancement can also be achieved using non-conductive materials. Four high surface area brush materials were added to AD reactors: non-conductive horsehair (HB) and polyester (PB), and conductive carbon fiber (CB) and stainless steel (SB) brushes. Reactors with the polyester material showed lower methane production (68 ± 5 mL/g COD fed ) than the other non-conductive material (horsehair) and the conductive (graphite or stainless steel) materials (83 ± 3 mL/g COD fed ) (p < 0.05). This difference was due in part to the higher biomass concentrations using horsehair or carbon (135 ± 43 mg) than polyester or stainless steel or materials (26 ± 1 mg). A microbial community analysis indicated that the relative abundance of electroactive microorganisms was not directly related to enhanced AD performance. These results show that non-conductive materials such as horsehair can produce the same AD enhancement as conductive materials (carbon or stainless steel). However, if the material, such as polyester, does not have good biomass retention, it will not enhance methane production. Thus, electrical conductivity alone was not responsible for enhancing AD performance. Polyester, which has been frequently used as a non-conductive control material in DIET studies, should not be used for this purpose due to its poor biocompatibility as shown by low biomass retention in AD tests., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: In this observational, retrospective, multicenter study, we aimed to assess the safety of the combination of local metastasis-directed radiotherapy (RT) and immunotherapy (IT) in a cohort of advanced non-small-cell lung cancer (aNSCLC) patients., Material and Methods: We collected clinical data of aNSCLC patients who received concomitant RT and anti-PD-1/PD-L1 inhibitors in seven Italian centers from September 2015 to June 2019. Concomitant RT was defined as delivered ≤4 weeks before or after the first or last administration of immunotherapy, or within two consecutive cycles of ICI. All adverse events apparently related to RT and/or IT were graded according to the Common Terminology Criteria for Adverse Events, version 4.0, and reported in terms of incidence and severity as immune related or RT related, or combined., Results: We analyzed the clinical charts of 187 patients. Median follow-up time was 23 months, and median overall survival was 16.5 months (range, 3-162). Thirteen patients developed pure RT-related side effects, and 43 patients (23.9%) developed immune-related side effects. No additive toxic effects were observed. A case of grade 5 pulmonary toxicity was recorded as a possible consequence of a combined effect., Conclusion: This analysis suggests that the combination of concomitant RT and anti-PD-1/PD-L1 agents is safe, and the two toxicity profiles are independent., (Published by Elsevier Inc.)

Protein Thiolation Index (PTI) has been recently proposed as a new biomarker of oxidative stress. It is calculated by measuring both free thiols and S-thiolated proteins in plasma with the assumption that this redox ratio is altered by a pro-oxidant stimulus. Here the original protocol was modified and adapted to the use of microvolumes of blood collected by finger prick and down to 3 μl blood was shown to be the lowest volume suitable for this kind of analysis. The new procedure was used to evaluate both the circadian rhythm and the annual fluctuations of PTI in healthy humans., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) infection can cause alterations in the coagulation mechanism conditioning thrombotic phenomena such as acute limb ischemia (ALI) as the only manifestation of the infection. The aim of the study was to describe clinical and surgical characteristics of a group of patients infected with severe acute respiratory syndrome coronavirus 2 who presented ALI in the context of the COVID-19 pandemic at Lima, Peru., Methods: A multicenter, observational, and retrospective study was performed in six general hospitals, from March to July 2020. The variables considered were the pathological history and associated habits, laboratory tests, the severity of COVID-19 infection and ALI, the anatomic location of the lesion, treatment, evolution, and discharge conditions., Results: Thirty patients with ALI infected with COVID-19 were evaluated. Their mean age was 60 ± 15 years, the condition being more frequent in men (76.6%). The main comorbidities were arterial hypertension (33.3%), obesity (33.3%), and diabetes mellitus 2 (26.6%). There were 23.3% asymptomatic patients, and their only manifestation was ALI. Rutherford IIA and IIB stage included 93.2% of patients. The most frequent location of the thrombosis was the lower limbs (73.3% vs. 26.6%). Thrombectomy was performed in 76.6% of the patients, and amputation (primary and secondary) was performed in 30% of the patients. The mortality rate was 23.3%, all of it because of acute respiratory distress syndrome., Conclusions: ALI is a vascular pathology associated with embolic and thrombotic processes. COVID-19 infection can cause severe alterations in coagulation mechanisms, leading some patients to present severe acute arterial complications such as thrombosis, as the only associated manifestation. We report a younger cohort than those described in other studies and with a high frequency of amputations despite adequate surgical treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population., Aim: This study aimed to analyze the occurrence of second primary malignancies., Methods: A retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included., Results: Between 2000 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5- and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms., Conclusion: In NEN patients the prevalence of second primary malignancies was not negligible, suggesting a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy., Competing Interests: Declaration of Competing Interest The Authors have no conflicts of interest to declare., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Treatment of Borderline Personality Disorder (BPD) in Italy has a relatively recent history. In the last few years, based on the increasing number of BPD patients admitted in Italian Mental Health Services (MHS), several regions have introduced treatment for BPD among their clinical priorities. A general 'call for action' has been launched within the psychiatric community. The aim of the current review is to describe the state of the art of research and clinical programs for personality disorders in young people. The Italian clinical context will be described with a focus on the transition discontinuity of care between adult and child/adolescent services. Prevention and early intervention programs available in Italy will be reviewed and a new agenda will be discussed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

H,K-ATPase and Na,K-ATPase show the highest degree of sequence similarity among all other members of the P-type ATPases family. To explore their common features in terms of ligand binding, we evaluated conformational transitions due to the binding of Na + , K + and Pi in the H,K-ATPase, and compared the results with those obtained for the Na,K-ATPase. This work shows that eosin fluorescence time courses provide a reasonably precise method to study the kinetics of the E1-E2 conformational changes in the H,K-ATPase. We found that, although Na + shifts the equilibrium toward the E1 conformation and seems to compete with H + in ATPase activity assays, it was neither possible to isolate a Na + -occluded state, nor to reveal an influx of Na + related to H,K-ATPase activity. The high rate of the E2K → E1 transition found for the H,K-ATPase, which is not compatible with the presence of a K + -occluded form, agrees with the negligible level of occluded Rb + (used as a K + congener) found in the absence of added ligands. The use of vanadate and fluorinated metals to induce E2P-like states increased the level of occluded Rb + and suggests that-during dephosphorylation-the probability of K + to remain occluded increases from the E2P-ground to the E2P-product state. From kinetic experiments we found an unexpected increase in the values of k obs for E2P formation with [Pi]; consequently, to obey the Albers-Post model, the binding of Pi to the E2 state cannot be a rapid-equilibrium reaction., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although the tambaqui (Colossoma macropomum) is the most cultivated native fish species in Brazil, estimated breeding values for growth traits are rarely used for selection of superior individuals in commercial fingerling production. This study aimed to estimate the (co)variance components of growth traits. Body weight, length and width of 2500 tambaqui were determined at tagging and at 6 and 12 months after tagging in a commercial breeding programme in Brazil. Heritability estimates were low for traits measured at tagging (0.10 to 0.19) and moderate to high for traits measured at 6 and 12 months (0.23 to 0.81). Common full-sib effects were high at tagging (>73%), low at 6 months and negligible at 12 months. Positive genetic correlations were found among growth traits at 12 months (0.84 to 0.99) and between growth traits at 6 and 12 months (0.80 to 0.92). These results show that animal selection can be performed at 6 months after tagging. Expected genetic gains for growth traits ranged from 8% to 31%. A simulation of the sex ratio was performed, as individuals did not reach sexual maturity during the experimental period. Because of the sexual dimorphism, more accurate heritability estimates were obtained when considering the female proportion to be 90% in the high-weight group. The findings indicate that it is possible to obtain considerable genetic gains in growth by selecting for growth traits. The development of a tool to determine the sex of animals at early stages can improve the response to selection in tambaqui.

Growth performances, carcass characteristics and meat quality parameters from growing rabbit fed with two levels of dietary brown seaweed (Laminaria spp) and plant polyphenols were investigated. One hundred and forty-four New Zealand White rabbits were allotted into three dietary treatments containing 0 (C), 0.3% (T1), and 0.6% (T2) of brown seaweed and plant polyphenols mixture for 42 days. Growth performances and carcass weight were improved in T1 group. Vitamin A and E content in Longissimus thoracis and lumborum (LTL) and Semimembranosus (SM) muscle were enhanced in the treated groups. In the SM muscle, the oxidative stability was improved in rabbit fed with both dosages of dietary supplement, and the cholesterol content tended to be lower in T1 than in T2 and C groups. The LTL and SM muscle sensory characteristics were improved. In conclusion, dietary integration with a low dosage of brown seaweed and plant polyphenols is a valid strategy for enhance growth performance and produce healthier rabbit meat., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Elastomers have been extensively exploited to study cell physiology in fields such as mechanobiology, however, their intrinsic high hydrophobicity renders their surfaces incompatible for prolonged cell adhesion and proliferation. Electrospun fiber networks on the other side provide a promising environment for enhanced cell adhesion and growth due to their architecture closely mimicking the structure of the extracellular matrix present within tissues of the human body. Here, we explored the stable integration of electrospun fibers onto the surfaces of elastomeric materials to promote cytocompatibility of these composites. Elastomers based on room temperature vulcanizing silicone (RTV), polydimethylsiloxane (PDMS) as well as functionalized PDMS-based materials were chosen as wafer substrates for attachment of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDFhfp) fibers, a well-known antithrombotic polymer. Electrospinning the fibers onto uncured interfaces acted as bonding agents on the wafers, enabling penetration and formation of a stable bond between the fibers surfaces and the elastomers after curing the interface. Dimensional analysis revealed a relationship between peeling force, intrusion depth and the elastic modulus of the wafers. A design parameter Π α was extrapolated to be used as a predictive tool of the peeling force when intrusion depth of PVDFhfp fibers and elastic modulus of the wafers are known. Cultivating fibroblasts on these hybrid membranes showed cell attachment and growth over 7 days regardless of the composition of the substrate, confirming high cytocompatibility for all composite materials. The presented approach opens avenues to establish nanofiber morphologies as a novel, stable surface texturing tool for tissue engineering, cell biology, medical devices and textiles., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In Africa, the HIV prevalence in rural areas has begun to reach levels estimated within urban settings, where women are also more at risk for both malaria and intestinal parasitic infections. The objective of this review is to assess whether concomitant infections with malaria and/or helminthic diseases have an impact on cervical disease progression in women on HAART. This scoping review was conducted in August 2018. To conduct this scoping review, we searched the relevant studies in electronic databases such as PUBMED, Global Health, EMBASE, CINAHL and SCOPUS published in the year between 1960 and 2018 using the following search terms HAART AND malaria OR Helminth and Female OR women. Eight studies qualified for this review. The literature underscores the need for women on HAART with multiple co-infections to use adjuncts to retain immune recovery and undetectable HIV viral load, to reduce risk of cervical disease progression. A trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection was observed in one study. Given the public health impact of synergistic interactions between malaria and helminthic infections in HIV/HPV co-infected women on HAART, it is urgent that these interactions are elucidated.

Distal femoral osteotomy (DFO) is a valid option for the treatment of young and active patients with lateral compartment osteoarthritis/overload and valgus malalignment. DFOs can be performed with a closing wedge or opening wedge technique. Lateral opening wedge DFO is usually preferred for smaller corrections, whereas medial closing wedge for larger corrections and in patients with high risk of nonunion. This article describes the relevant aspects regarding lateral opening wedge DFO, including patient selection, preoperative planning, surgical technique, results, and complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

High tibial osteotomy (HTO) may be performed in association with anterior cruciate ligament (ACL) reconstruction/revision in patients with medial osteoarthritis, varus malalignment, and anterior instability. Furthermore, it may be performed in patients with varus alignment and increased posterior tibial slope (exceeding 12°), because it is related to an increased risk for ACL failure. There are different techniques to perform HTO, and consequently, a concomitant HTO and ACL reconstruction/revision. This article describes the indication, surgical techniques, and outcomes of concomitant HTO and ACL reconstruction/revision., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate the development and growth of the digestive system organs, from the 11th day of incubation until the 14 d post-hatch in European and Japanese quail. On days 11, 13 and 15 of incubation at hatch and at 4, 7, 10 and 14 d post-hatch, embryos or chicks of European and Japanese quail were analyzed. After 15 d of incubation, samples from stomach and small intestine were analyzed by microscopy. European quail had significantly heavier body weight at 15 d of incubation and after 4 d post-hatch. The digestive system weight progressively increased with age and was similar between European and Japanese quail at 11, 13, and 15 d of incubation and 10 d post-hatch, while relative weight of digestive system was similar between quail type with great values at 4 d post-hatch. For relative weight of the small intestine + pancreas, the weight of the proventriculus and of the gastric ventricle increased significant by among ages analyzed in both types of quail. At hatch, proventriculus had functional secretory cells and mucosa of gastric ventricle had a thin coilin membrane. In small intestine segments, at 15 d of incubation the height of the villi was similar among duodenum, jejunum, and ileum (80 μm). Villi had elongated shape towards the intestinal lumen, covered by enterocytes and dispersed goblet cells with PAS+ and AB+ contend in all segments. The number of goblet cell/villi increased in segments until 7 to 10 d post-hatch. Duodenum increases the villi up to 14 d, while the jejunum and ileum up to 10 and 4 d, respectively. Based on our data in digestive system growth, a shorter period of post-hatch fast and specific diets to quail during first days of growth is recommended to both quail types. It is concluded that the development and growth of different organs of the digestive system up to 14 d of age was similar between European and Japanese quail., (© 2018 Poultry Science Association Inc.)

Among the protozoa of the genus Sarcocystis (Apicomplexa; Sarcocystidae), Sarcocystis bertrami (syn. Sarcocystis fayeri) is an obligate intracellular parasite of donkeys and horses with worldwide distribution. Here, we report the detection of S. bertrami in naturally infected donkeys from southern Italy and describe their structure by light microscopy (LM) and transmission electron microscopy (TEM). Protozoal cysts were detected both morphologically and molecularly in skeletal muscles of 28.57% (40/140) donkeys. Mature cysts of S. bertrami were found in skeletal muscle measuring 31-102 μm long and 19-83 μm wide with radially striated thick cyst wall. The high prevalence of infected donkeys suggests that dogs, the definitive hosts of S. bertrami, are contaminating environment with environmentally resistant sporocysts. Considering the increased consumption of raw donkey meat results also suggest a potential risk for human health., (Copyright © 2019 Elsevier B.V. All rights reserved.)

HIV infection is characterized by a state of chronic activation of the immune system, which is not completely reversed by antiretroviral treatment (ART). The aim of this study was to assess myeloid and lymphoid activation markers during HIV infection, before and one year after ART initiation, in AIDS and non-AIDS presenters. Treatment naïve HIV positive patients were enrolled in this study. Myeloid dendritic cell (mDC), plasmacytoid dendritic cell (pDC), slanDC, monocyte and T-lymphocyte cell counts and activation status, were assessed by flow cytometry in peripheral blood samples. Soluble (s)CD14 and sCD163 were assessed in plasma samples using ELISA assays. Statistical analyses were performed using GraphPad Prism and Minitab Express. Thirty-four ART naïve HIV-1 infected subjects were enrolled in this study (22 non-AIDS and 12 AIDS presenters). Seventeen healthy donors (HD) were included as control group. Although circulating mDC levels resulted unchanged, HLA-DR expression was decreased on mDCs of HIV positive subjects compared to HD (p < 0,0001). AIDS presenters showed the lowest level of expression of HLA-DR on mDCs. Circulating levels of pDCs were decreased in HIV patients compared to HD (p < 0,001), without any changes in HLA-DR expression. SlanDC cell counts were extremely reduced in AIDS presenters, compared to non-AIDS presenters and HD (p < 0,01 and p < 0,0001, respectively) and showed higher HLA-DR expression in HIV patients compared to HD (p < 0,01). Intermediate monocyte (IM) cell counts were increased in AIDS and non-AIDS presenters compared to HD (p < 0,001 and p < 0,001 respectively). Furthermore, IM expansion was directly correlated to HIV viral load (p = 0,036) and independent from CD4 cell counts and activation levels. Plasma concentrations of sCD14 and sCD163 resulted increased in HIV infected subjects compared to HD (p < 0,0001 and p < 0,001), with the highest levels observed in AIDS presenters. After 1 year, ART was able to increase pDC and decrease IM absolute cell counts and modify HLA-DR expression on mDCs and slanDCs, approaching the levels observed in HD. ART reduced also CD4 and CD8 activation levels. In conclusion, in untreated HIV infected subjects circulating dendritic cells resulted altered either in numbers or in HLA-DR expression, especially in AIDS presenters. IM absolute counts were equally increased in AIDS and non-AIDS presenters. ART was able to reduce myeloid and lymphoid inflammation in both advanced and non-advanced HIV patients, confirming the role of ART in hampering disease progression and immune activation associated non-AIDS events., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

A few studies reported functional abnormalities at rest in borderline personality disorder (BPD), but their relationship with clinical aspect is unclear. We aimed to assess functional connectivity (FC) in BPD patients and its association with BPD clinical features. Twenty-one BPD patients and 14 healthy controls (HC) underwent a multidimensional assessment and resting-state fMRI. Independent component analysis was performed to identify three resting-state networks: default mode network (DMN), salience network (SN), and executive control network (ECN). FC differences between BPD and HC were assessed with voxel-wise two-sample t-tests. Additionally, we investigated the mean FC within each network and the relationship between connectivity measures and BPD clinical features. Patients showed significant lower mean FC in the DMN and SN, while, at the local level, a cluster of lower functional connectivity emerged in the posterior cingulate cortex of the DMN. The DMN connectivity was positively correlated with the anger-state intensity and expression, while the SN connectivity was positively correlated with metacognitive abilities and a negative correlation emerged with the interpersonal aggression. The dysfunctional connectivity within these networks might explain clinical features of BPD patients., (Copyright © 2018. Published by Elsevier B.V.)

Piglets can often suffer impaired antioxidant status and poor immune response during post-weaning, especially when chronic inflammation takes place, leading to lower growth rates than expected. Oral administration of dietary antioxidant compounds during this period could be a feasible way to balance oxidation processes and increase health and growth performance. The aim of the trial was to study the effects of an antioxidant feed supplement (melon pulp concentrate) that contains high concentration of the antioxidant superoxide dismutase (SOD) on inflammation, antioxidant status and growth performance of lipopolysaccharide (LPS) challenged weaned piglets. In total, 48 weaned piglets were individually allocated to four experimental groups in a 2×2 factorial design for 29 days. Two different dietary treatments were adopted: (a) control (CTR), fed a basal diet, (b) treatment (MPC), fed the basal diet plus 30 g/ton of melon pulp concentrate. On days 19, 21, 23 and 25 half of the animals within CTR and MPC groups were subjected to a challenge with intramuscular injections of an increasing dosage of LPS from Escherichia coli (serotype 0.55:B5) (+) or were injected with an equal amount of PBS solution (-). Blood samples were collected at the beginning of the trial and under the challenge period for interleukin 1β, interleukin 6, tumour necrosis factor α, haptoglobin, plasma SOD activity, total antioxidant capacity, reactive oxygen species, red blood cells and plasma resistance to haemolysis, and 8-oxo-7, 8-dihydro-2'-deoxyguanosine. Growth performance was evaluated weekly. A positive effect of melon pulp concentrate was evidenced on total antioxidant capacity, half-haemolysis time of red blood cells, average daily gain (ADG) and feed intake, while LPS challenge increased pro-inflammatory cytokines and haptoglobin serum concentrations, with a reduced feed intake and gain : feed (G : F). The obtained results show that oral SOD supplementation with melon pulp concentrate ameliorates the total antioxidant capacity and the half-haemolysis time in red blood cell of post-weaning piglets, with positive results on growing performance.

Background: The clinical response after comprehensive symptom management is difficult to determine in terms of a clinically important difference. Moreover, therapies should try to reach the threshold perceived by the individual patient for the determination of a favorable response to a treatment., Measures: The Edmonton Symptom Assessment Score (ESAS) was measured at admission (T0), and seven days after starting palliative care (T7). Patient Global Impression and Goal Response after one week of palliative care and its relation with the Personalized Dyspnea Goal were measured at T7., Intervention: Patients admitted to palliative care units underwent a comprehensive symptom assessment by a specialist palliative care team. At T0, patients were asked about their Personalized Dyspnea Intensity Goal on ESAS. One week later (T7), after a comprehensive palliative care treatment, Personalized Dyspnea Intensity Goals were measured again. Patients were considered to have achieved a Patient Dyspnea Goal Response if dyspnea intensity (measured at T7) was equal or less than their expected Personalized Dyspnea Intensity Goal. At the same interval (T7), Patient Global Impression (improvement or deterioration) was measured., Outcomes: 279 patients were analyzed in this study. The mean Personalized Dyspnea Intensity Goal at T0 and T7 were 0.97 (SD 1.3), and 0.71 (SD 2.1), respectively. 263 patients (94.2%) indicated a Personalized Dyspnea Intensity Goal of ≤3 as a target at T0. Patients perceived a bit better, a better improvement, and a much better improvement with a mean decrease in dyspnea intensity of -2.1, -3.5, and -4.3 points on the dyspnea intensity scale, respectively. In 60 patients (21.5%), dyspnea intensity did not change, and in 4.7%, dyspnea intensity worsened. Patients perceived a Minimal Clinically Important Difference (little worse) with a mean increase in dyspnea intensity of 0.10, and they perceived a worse with a mean increase of 1.7 points. Higher dyspnea intensity at T0 and lower dyspnea intensity at T7 were independently related to Patient Global Impression. At T7, 93 (33.3%) patients achieved their Personalized Goal Response, based on Personalized Dyspnea Intensity. Patient Dyspnea Goal Response was associated with Memorial Delirium Assessment Scale score and Personalized Dyspnea Intensity Goal at T0, and inversely associated with dyspnea intensity at T0 and T7, and lower Karnofsky level. For Patient Dyspnea Goal Response, no significant differences among categories of dyspnea intensity were found (P>0.05)., Conclusion: Patient Dyspnea Goal Response and Patient Global Impression seem to be relevant for evaluating the effects of a comprehensive management of symptoms, including dyspnea, assisting decision making process. Some factors may be implicated in determining the individual target and clinical response. A personalized symptom goal may translate in terms of therapeutic intervention, according to the achievement of the patients' expectations. High values of dyspnea intensity, a lower Karnofsky level, as well as high level of Dyspnea Intensity Goal (that is less patients' expectations) favor the achievement of the target., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

A multiclass screening method to detect fifty-three forbidden substances by liquid-chromatography coupled to hybrid high-resolution mass spectrometry (LC-Q-Orbitrap) was developed and validated in bovine bile and urine. Eight classes of compounds were included in the method's scope (β-agonists, corticosteroids, nitroimidazoles, progestins, resorcylic acid lactones (RALs), sedatives, steroids and stilbenes) plus chloramphenicol and dapsone. After hydrolysis, the sample was divided in two aliquots, which followed two parallel purification steps. The reunified extracts were injected and two chromatographic runs performed in positive and negative ionization mode, respectively. The validation data (60 different samples per matrix) proved that the method was fit for purpose with detection capabilities lower than 1 μg L -1 in both matrices. The combined application of accurate mass acquisition and two-stage mass spectrometry (parallel reaction monitoring) was crucial to achieve suitable selectivity, which is the most critical parameter mainly for urines. Finally, the long-standing problem of the high rate of false positive results for RALs, due to the natural ingestion of mycotoxin, zearalenone, was taken on including all their labelled standards. That allowed a very satisfactory management of this screening test., (Copyright © 2018 Elsevier B.V. All rights reserved.)