CCR4+ CD8+ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis.

Psoriasis is a chronic inflammatory skin disease with an autoimmune component and associated with joint inflammation in up to 30% of cases. To investigate autoreactive T cells, we developed an imiquimod-induced psoriasis-like inflammation model in K5-mOVA.tg C57BL/6 mice expressing ovalbumin (OVA) on the keratinocyte membrane, adoptively transferred with OT-I OVA-specific CD8+ T cells. We evaluated the expansion of OT-I CD8+ T cells and their localization in skin, blood, and spleen. scRNA-seq and TCR sequencing data from patients with psoriatic arthritis were also analyzed. In the imiquimod-treated K5-mOVA.tg mouse model, OT-I T cells were markedly expanded in the skin and blood at early time points. OT-I T cells in the skin showed mainly CXCR3+ effector memory phenotype, whereas in peripheral blood there was an expansion of CCR4+ CXCR3+ OT-I cells. At a later time point, expanded OVA-specific T-cell population was found in the spleen. In patients with psoriatic arthritis, scRNA-seq and TCR sequencing data showed clonal expansion of CCR4+ TCM cells in the circulation and further expansion in the synovial fluid. Importantly, there was a clonotype overlap between CCR4+ TCM in the peripheral blood and CD8+ T-cell effectors in the synovial fluid. This mechanism could play a role in the generation and spreading of autoreactive T cells to the synovioentheseal tissues in psoriasis patients at risk of developing psoriatic arthritis.

From volume to value: a watershed moment for the clinical laboratory.

The clinical laboratory is often evaluated for the volume of testing. However, it is undeniable that laboratory tests affect clinical decision-making and are included in many clinical guidelines, meaning their contribution to determining clinical outcomes. Therefore, the clinical laboratory professional has the task of enhancing laboratory tests by optimizing the request and reporting phase and addressing patient outcomes. This opinion paper, presenting practical examples of managing value-based health care in the clinical laboratory context, underlines the need to shift towards value-based management to optimize outcome-based health care.

Blood over-testing: impact, ethical issues and mitigating actions.

Plenty of studies demonstrate that hospital-acquired anemia (HAA) can increase transfusion rates, mortality, morbidity and cause unnecessary patient burden, including additional length of hospital stay, sleep disruption and venipuncture harms resulting from blood samples unlikely to change clinical management. Beyond patient costs, community costs should also be considered, such as laboratory time and resources waste, environmental impact, increasing pressure on labs and fewer tests available on time for patients who can benefit from them most. Blood over-testing does not support the principles of non-maleficence, justice and respect for patient autonomy, at the expense dubious beneficence. Reducing the number and frequency of orders is possible, to a certain extent, by adopting nudge strategies and raising awareness among prescribing doctors. However, reducing the orders may appear unsafe to doctors and patients. Therefore, reducing blood volume from each order is a better alternative, which is worth implementing through technological, purchasing and organizational arrangements, possibly combined according to need (smaller tubes, adequate analytic platforms, blind dilution, blood conservative devices, aggregating tests and laboratory units).

Rising adoption of artificial intelligence in scientific publishing: evaluating the role, risks, and ethical implications in paper drafting and review process.

BACKGROUND: In the rapid evolving landscape of artificial intelligence (AI), scientific publishing is experiencing significant transformations. AI tools, while offering unparalleled efficiencies in paper drafting and peer review, also introduce notable ethical concerns. CONTENT: This study delineates AI's dual role in scientific publishing: as a co-creator in the writing and review of scientific papers and as an ethical challenge. We first explore the potential of AI as an enhancer of efficiency, efficacy, and quality in creating scientific papers. A critical assessment follows, evaluating the risks vs. rewards for researchers, especially those early in their careers, emphasizing the need to maintain a balance between AI's capabilities and fostering independent reasoning and creativity. Subsequently, we delve into the ethical dilemmas of AI's involvement, particularly concerning originality, plagiarism, and preserving the genuine essence of scientific discourse. The evolving dynamics further highlight an overlooked aspect: the inadequate recognition of human reviewers in the academic community. With the increasing volume of scientific literature, tangible metrics and incentives for reviewers are proposed as essential to ensure a balanced academic environment. SUMMARY: AI's incorporation in scientific publishing is promising yet comes with significant ethical and operational challenges. The role of human reviewers is accentuated, ensuring authenticity in an AI-influenced environment. OUTLOOK: As the scientific community treads the path of AI integration, a balanced symbiosis between AI's efficiency and human discernment is pivotal. Emphasizing human expertise, while exploit artificial intelligence responsibly, will determine the trajectory of an ethically sound and efficient AI-augmented future in scientific publishing.

Point-of-care testing, near-patient testing and patient self-testing: warning points.

Point-of-care testing (POCT), near-patient testing (NPT) and patient self-tests (PST) are diagnostic examinations performed at the time and place of patient care. While POCT and NPT are performed and analyzed by medical professionals, PST are based on samples and parameters directly collected and analyzed by lay users. These tests are spreading both in high income countries and in low to middle income countries as they are expected to improve healthcare efficiency and equity, by saving resources, releasing pressure from hospitals and reducing logistical barriers. However, accurate multidisciplinary assessment is mandatory to ensure that what they promise is real. We reviewed some important ethical aspects, international standards and regulations. The current risks associated with alternative ways of testing are explained by the principles of respect for patient autonomy and non-maleficence. Further evidence from multidisciplinary assessment is needed to evaluate pros and cons in light of the principles of beneficence and justice. Although POCT or NPT need common regulation and accurate provider training to ensure safe and appropriate interpretation of results, PST needs even more attention as they are subject to direct patient use. Randomized controlled trails including patient education should be conducted in order to provide reliable evidence on clinical outcomes, patient acceptance and cost-effectiveness. Mandatory regulation is needed to avoid harm and EU regulation should help different countries maintain a safe use of devices in a global population of producers and users.

Point-of-care testing: state-of-the art and perspectives.

Point-of-care testing (POCT) is becoming an increasingly popular way to perform laboratory tests closer to the patient. This option has several recognized advantages, such as accessibility, portability, speed, convenience, ease of use, ever-growing test panels, lower cumulative healthcare costs when used within appropriate clinical pathways, better patient empowerment and engagement, and reduction of certain pre-analytical errors, especially those related to specimen transportation. On the other hand, POCT also poses some limitations and risks, namely the risk of lower accuracy and reliability compared to traditional laboratory tests, quality control and connectivity issues, high dependence on operators (with varying levels of expertise or training), challenges related to patient data management, higher costs per individual test, regulatory and compliance issues such as the need for appropriate validation prior to clinical use (especially for rapid diagnostic tests; RDTs), as well as additional preanalytical sources of error that may remain undetected in this type of testing, which is usually based on whole blood samples (i.e., presence of interfering substances, clotting, hemolysis, etc.). There is no doubt that POCT is a breakthrough innovation in laboratory medicine, but the discussion on its appropriate use requires further debate and initiatives. This collective opinion paper, composed of abstracts of the lectures presented at the two-day expert meeting "Point-Of-Care-Testing: State of the Art and Perspective" (Venice, April 4-5, 2024), aims to provide a thoughtful overview of the state-of-the-art in POCT, its current applications, advantages and potential limitations, as well as some interesting reflections on the future perspectives of this particular field of laboratory medicine.

Effectiveness of Telemedicine for Musculoskeletal Disorders: Umbrella Review.

BACKGROUND: Several systematic reviews (SRs) assessing the use of telemedicine for musculoskeletal conditions have been published in recent years. However, the landscape of evidence on multiple clinical outcomes remains unclear. OBJECTIVE: We aimed to summarize the available evidence from SRs on telemedicine for musculoskeletal disorders. METHODS: We conducted an umbrella review of SRs with and without meta-analysis by searching PubMed and EMBASE up to July 25, 2022, for SRs of randomized controlled trials assessing telemedicine. We collected any kind of patient-reported outcome measures (PROMs), patient-reported experience measures (PREMs), and objective measures, including direct and indirect costs. We assessed the methodological quality with the AMSTAR 2 tool (A Measurement Tool to Assess systematic Reviews 2). Findings were reported qualitatively. RESULTS: Overall, 35 SRs published between 2015 and 2022 were included. Most reviews (n=24, 69%) were rated as critically low quality by AMSTAR 2. The majority of reviews assessed "telerehabilitation" (n=29) in patients with osteoarthritis (n=13) using PROMs (n=142 outcomes mapped with n=60 meta-analyses). A substantive body of evidence from meta-analyses found telemedicine to be beneficial or equal in terms of PROMs compared to conventional care (n=57 meta-analyses). Meta-analyses showed no differences between groups in PREMs (n=4), while objectives measures (ie, "physical function") were mainly in favor of telemedicine or showed no difference (9/13). All SRs showed notably lower costs for telemedicine compared to in-person visits. CONCLUSIONS: Telemedicine can provide more accessible health care with noninferior results for various clinical outcomes in comparison with conventional care. The assessment of telemedicine is largely represented by PROMs, with some gaps for PREMs, objective measures, and costs. TRIAL REGISTRATION: PROSPERO CRD42022347366; https://osf.io/pxedm/.

Second opinion machine learning for fast-track pathway assignment in hip and knee replacement surgery: the use of patient-reported outcome measures.

BACKGROUND: The frequency of hip and knee arthroplasty surgeries has been rising steadily in recent decades. This trend is attributed to an aging population, leading to increased demands on healthcare systems. Fast Track (FT) surgical protocols, perioperative procedures designed to expedite patient recovery and early mobilization, have demonstrated efficacy in reducing hospital stays, convalescence periods, and associated costs. However, the criteria for selecting patients for FT procedures have not fully capitalized on the available patient data, including patient-reported outcome measures (PROMs). METHODS: Our study focused on developing machine learning (ML) models to support decision making in assigning patients to FT procedures, utilizing data from patients' self-reported health status. These models are specifically designed to predict the potential health status improvement in patients initially selected for FT. Our approach focused on techniques inspired by the concept of controllable AI. This includes eXplainable AI (XAI), which aims to make the model's recommendations comprehensible to clinicians, and cautious prediction, a method used to alert clinicians about potential control losses, thereby enhancing the models' trustworthiness and reliability. RESULTS: Our models were trained and tested using a dataset comprising 899 records from individual patients admitted to the FT program at IRCCS Ospedale Galeazzi-Sant'Ambrogio. After training and selecting hyper-parameters, the models were assessed using a separate internal test set. The interpretable models demonstrated performance on par or even better than the most effective 'black-box' model (Random Forest). These models achieved sensitivity, specificity, and positive predictive value (PPV) exceeding 70%, with an area under the curve (AUC) greater than 80%. The cautious prediction models exhibited enhanced performance while maintaining satisfactory coverage (over 50%). Further, when externally validated on a separate cohort from the same hospital-comprising patients from a subsequent time period-the models showed no pragmatically notable decline in performance. CONCLUSIONS: Our results demonstrate the effectiveness of utilizing PROMs as basis to develop ML models for planning assignments to FT procedures. Notably, the application of controllable AI techniques, particularly those based on XAI and cautious prediction, emerges as a promising approach. These techniques provide reliable and interpretable support, essential for informed decision-making in clinical processes.

Men and women undergoing total hip arthroplasty have different clinical presentations before surgery and different outcomes at 1-year follow-up.

PURPOSE: The purpose of this study was to investigate the influence of sex on patients undergoing total hip arthroplasty (THA) for hip osteoarthritis (HOA), aiming to assess the clinical and functional outcomes using patient-reported outcome measures (PROMs). METHODS: A retrospective analysis of patients undergoing THA at Ospedale Galeazzi-Sant'Ambrogio between 2016 and 2022 was conducted. Inclusion criteria encompassed Kellgren-Lawrence grade III or IV HOA, with preoperative and 12-month postoperative PROMs. Enroled patients have been selected from a larger cohort without matching design for confounders. The analyses were performed using R software v4.0.3 (R Core Team) and data distributions were assessed using the Shapiro-Wilk normality test. RESULTS: One hundred ninety patients (72 male and 118 female) who had both preoperative and postoperative PROMs have been analysed from our institutional prosthesis registry (Datareg). Baseline and 12-month post-THA PROMs showed significant improvements overall. VAS score dropped notably from baseline to 3 months postsurgery (7.1 ± 2.1 vs. 0.9 ± 1.7). Functional and mental PROMs, including Harris Hip Score-functional (HHS-F), Harris Hip Score-total (HHS-t), SF-12PS and SF-12MS, exhibited substantial improvements post-THA. Stratifying by sex, males had lower baseline VAS, higher HHS-F, SF-12MS and hip disability and osteoarthritis outcome score-physical function short form (HOOS-PS). At 12 months, males displayed significantly better VAS, HHS-F, SF-12PS and HOOS-PS scores. Complication rates were minimal (1.5%), with stable rates across genders, mostly involving dislocation and periprosthetic fractures. Implant survival at 12 months reached an impressive 99%. CONCLUSION: THA remains an effective treatment for severe HOA. However, females presented with worse baseline conditions and showed relatively less improvement at 1-year postsurgery compared to males. This difference could be attributed to physiological and psychosocial factors associated with sex, including hormonal changes, muscle mass decline and perception of pain. Longer follow-ups and prospective studies are necessary to validate these findings and facilitate personalised approaches in HOA treatment, emphasising the need for careful consideration of sex-related variables in clinical decision-making for THA patients. LEVEL OF EVIDENCE: Level III.

Health technology assessment in musculoskeletal radiology: the case study of EOSedge™.

OBJECTIVES: Health technology assessment (HTA) is a systematic process used to evaluate the properties and effects of healthcare technologies within their intended use context. This paper describes the adoption of HTA process to assess the adoption of the EOSedge™ system in clinical practice. METHODS: The EOSedge™ system is a digital radiography system that delivers whole-body, high-quality 2D/3D biplanar images covering the complete set of musculoskeletal and orthopedic exams. Full HTA model was chosen using the EUnetHTA Core Model® version 3.0. The HTA Core Model organizes the information into nine domains. Information was researched and obtained by consulting the manufacturers' user manuals, scientific literature, and institutional sites for regulatory aspects. RESULTS: All nine domains of the EUnetHTA Core Model® helped conduct the HTA of the EOSedge, including (1) description and technical characteristics of the technology; (2) health problem and current clinical practice; (3) safety; (4) clinical effectiveness; (5) organizational aspects; (6) economic evaluation; (7) impact on the patient; (8) ethical aspects; and (9) legal aspects. CONCLUSIONS: EOS technologies may be a viable alternative to conventional radiographs. EOSedge has the same intended use and similar indications for use, technological characteristics, and operation principles as the EOS System and provides significant dose reduction factors for whole spine imaging compared to the EOS System without compromising image quality. Regarding the impact of EOS imaging on patient outcomes, most studies aim to establish technical ability without evaluating their ability to improve patient outcomes; thus, more studies on this aspect are warranted.

When action prediction grows old: An fMRI study.

Predicting the unfolding of others' actions (action prediction) is crucial for successfully navigating the social world and interacting efficiently. Age-related changes in this domain have remained largely unexplored, especially for predictions regarding simple gestures and independent of contextual information or motor expertise. Here, we evaluated whether healthy aging impacts the neurophysiological processes recruited to anticipate, from the observation of implied-motion postures, the correct conclusion of simple grasping and pointing actions. A color-discrimination task served as a control condition to assess the specificity of the age-related effects. Older adults showed reduced efficiency in performance that was yet not specific to the action prediction task. Nevertheless, fMRI results revealed task-specific age-related differences: while both groups showed stronger recruitment of the lateral occipito-temporal cortex bilaterally during the action prediction than the control task, the younger participants additionally showed a higher bilateral engagement of parietal regions. Importantly, in both groups, the recruitment of visuo-motor processes in the right posterior parietal cortex was a predictor of good performance. These results support the hypothesis of decreased involvement of sensorimotor processes in cognitive tasks when processing action- and body-related stimuli in healthy aging. These results have implications for social interaction, which requires the fast reading of others' gestures.

Remote decentralized clinical trials: a new opportunity for laboratory medicine.

The traditional venue of clinical trials has been hospitals or specialized research units, usually requiring participants to come on-site. Although their contribution to biomedical progress is beyond dispute, they are characterised by two crucial logistical and ultimately scientifical limitations: poor retention and poor generalizability of results, as patients often have problems in concluding the investigation on-site. Remote Decentralised Clinical Trials (RDCTs) take advantage of digital technologies to design trial activities closer to the home of participants, with the aims of minimizing travel to health facilities and the risk of infections, improving the quality of life of participants and caregivers, reducing work absenteeism, including broader cohorts of patients and possibly reducing costs. RDCTs represent a minority of current global research, but the Covid-19 pandemic brought them to the fore. The authors of this paper promote the spread of RDCTs, building on early recommendations from international institutions, and provide some examples of their use and potential benefits in laboratory medicine.

The total testing process harmonization: the case study of SARS-CoV-2 serological tests.

The total testing process harmonization is central to laboratory medicine, leading to the laboratory test's effectiveness. In this opinion paper the five phases of the TTP are analyzed, describing, and summarizing the critical issues that emerged in each phase of the TTP with the SARS-CoV-2 serological tests that have affected their effectiveness. Testing and screening the population was essential for defining seropositivity and, thus, driving public health policies in the management of the COVID-19 pandemic. However, the many differences in terminology, the unit of measurement, reference ranges and parameters for interpreting results make analytical results difficult to compare, leading to the general confusion that affects or completely precludes the comparability of data. Starting from these considerations related to SARS-CoV-2 serological tests, through interdisciplinary work, the authors have highlighted the most critical points and formulated proposals to make total testing process harmonization effective, positively impacting the diagnostic effectiveness of laboratory tests.

Review on adherence of the literature to official recommendations on albuminuria harmonization and standardization.

Albuminuria standardization is a key issue to produce reliable and equivalent results between laboratories. We investigated whether official recommendations on albuminuria harmonization are followed in the literature. The PubMed database was searched from June 1 to September 26, 2021. The search terms included urine albumin, urine albumin-to-creatinine ratio (uACR), and albuminuria. A total of 159 articles were considered eligible; 50.9 % reported the type of urine collection. Specifically, 58.1 % collected a random spot urine specimen, 21 % collected a first morning void, and 6.2 % collected a 24-h specimen. Overall, 15 % of articles reported data on sample shipping, storage, and centrifugation and 13.3 % mentioned the preanalytical phase without any data on albuminuria. The method for albuminuria was properly described in 31.4 % of articles; of these, 54.9 % used immunological methods, and 8.9 % contained errors or missing data. Most articles (76.7 %) expressed test results as albuminuria-to-creatininuria ratio. Different decision levels were utilized in 130 articles; of these, 36 % used a decision level of ≤30 mg/g creatininuria and 23.7 % used three decision levels (≤30, 30-300, and ≥300 mg/g). The failure to follow guidelines on albuminuria harmonization was mainly found in the preanalytical phase. The poor awareness of the importance of preanalytical steps on test result may be a possible explanation.

How shared goals shape action monitoring.

Cooperation triggers expectations on our partners' contributions to achieve a common goal. A partner, however, may sometimes violate such expectations, driving us to perform immediate adjustments. What neurophysiological mechanisms support these adaptations? We tested the hypothesis of an interaction-specific brain system that can decode a partner's error and promote adaptive responses when cooperating toward a shared goal. During functional magnetic resonance imaging, the participants played short melodies with a virtual partner by performing one note each in turn-taking. A colored cue indicated which melody they had to execute at each trial, thus generating expectations on what notes the partner would play. The participants also performed the task in a perceptually matched Non-Interactive context. The results showed that task interactivity modulates the brain responses to a partner's error in dorsal fronto-temporoparietal and medial cingulo-opercular networks. Multivariate pattern analysis revealed that these neural activations reflect deep decoding of the partner's mistake. Within these networks, the automatic tendency to correct the partner's errors, as indexed by specific reaction times adaptations, depended on the activity of a right-lateralized fronto-opercular system that may enable mutual support during real-life cooperation. Future studies may unveil the role of this putative "interaction monitoring" brain system in social dysfunctions and their motor foundations.

Proximal hip fractures in 71,920 elderly patients: incidence, epidemiology, mortality and costs from a retrospective observational study.

BACKGROUND: The risk of proximal femoral fractures increases with aging, causing significant morbidity, disability, mortality and socioeconomic pressure. The aims of the present work are (1) to investigate the epidemiology and incidence of these fractures among the elderly in the Region of Lombardy; (2) to identify the factors influencing survival; (3) to identify the factors influencing hospitalization and post-operative costs. METHODS: The Region of Lombardy provided anonymized datasets on hospitalized patients with a femoral neck fracture between 2011 and 2016, and anonymized datasets on extra-hospital treatments to track the patient history between 2008 and 2019. Statistical evaluations included descriptive statistics, survival analysis, Cox regression and multiple linear models. RESULTS: 71,920 older adults suffered a femoral fracture in Lombardy between 2011 and 2016. 76.3% of patients were females and the median age was 84. The raw incidence of fractures was stable from year 2011 to year 2016, while the age-adjusted incidence diminished. Pertrochanteric fractures were more spread than transcervical fractures. In patients treated with surgery, receiving treatment within 48 h reduced the hazard of death within the next 24 months. Combined surgical procedures led to increased hazard in comparison with arthroplasty alone, while no differences were observed between different arthroplasties and reduction or fixation. In patients treated conservatively, age and male gender were associated with higher hazard of death. All patients considered, the type of surgery was the main factor determining primary hospitalization costs. A higher number of surgeries performed by the index hospital in the previous year was associated with financial savings. The early intervention significantly correlated with minor costs. CONCLUSIONS: The number of proximal femoral fractures is increasing even if the age-adjusted incidence is decreasing. This is possibly due to prevention policies focused on the oldest cohort of the population. Two policies proved to be significantly beneficial in clinical and financial terms: the centralization of patients in high-volume hospitals and a time limit of 48 h from fracture to surgery. TRIAL REGISTRATION: Non applicable.

How do patients sleep after orthopaedic surgery? Changes in objective sleep parameters and pain in hospitalized patients undergoing hip and knee arthroplasty.

PURPOSE: The aim of this observational cohort study was to assess actigraphy-based sleep characteristics and pain scores in patients undergoing knee or hip joint replacement and hospitalized for ten days after surgery. METHODS: N=20 subjects (mean age: 64.0±10.39 years old) wore the Actiwatch 2 actigraph (Philips Respironics, USA) to record sleep parameters for 11 consecutive days. Subjective scores of pain, by a visual analog scale (VAS), were constantly monitored and the following evaluation time points were considered for the analysis: pre-surgery (PRE), the first (POST1), the fourth (POST4), and the tenth day (POST10) after surgery. RESULTS: Sleep quantity and timing parameters did not differ from PRE to POST10, during the hospitalization whereas sleep efficiency and immobility time significantly decreased at POST1 compared to PRE by 10.8% (p=0.003; ES: 0.9, moderate) and 9.4% (p=0.005; ES: 0.86, moderate) respectively, and sleep latency increased by 18.7 min (+320%) at POST1 compared to PRE (p=0.046; ES: 0.70, moderate). Overall, all sleep quality parameters showed a trend of constant improvement from POST1 to POST10. VAS scores were higher in the first day post-surgery (4.58 ± 2.46; p=0.0011 and ES: 1.40, large) compared to POST10 (1.68 ± 1.58). During the time, mean VAS showed significant negative correlations with mean sleep efficiency (r = -0.71; p=0.021). CONCLUSION: Sleep quantity and timing parameters were stable during the entire hospitalization whereas sleep quality parameters significantly worsened the first night after surgery compared to the pre-surgery night. High scores of pain were associated with lower overall sleep quality.

Osteoporosis and Covid-19: Detected similarities in bone lacunar-level alterations via combined AI and advanced synchrotron testing.

While advanced imaging strategies have improved the diagnosis of bone-related pathologies, early signs of bone alterations remain difficult to detect. The Covid-19 pandemic has brought attention to the need for a better understanding of bone micro-scale toughening and weakening phenomena. This study used an artificial intelligence-based tool to automatically investigate and validate four clinical hypotheses by examining osteocyte lacunae on a large scale with synchrotron image-guided failure assessment. The findings indicate that trabecular bone features exhibit intrinsic variability related to external loading, micro-scale bone characteristics affect fracture initiation and propagation, osteoporosis signs can be detected at the micro-scale through changes in osteocyte lacunar features, and Covid-19 worsens micro-scale porosities in a statistically significant manner similar to the osteoporotic condition. Incorporating these findings with existing clinical and diagnostic tools could prevent micro-scale damages from progressing into critical fractures.

Soy diet induces intestinal inflammation in adult Zebrafish: Role of OTX and P53 family.

Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the colon and small intestine, including Crohn's disease and ulcerative colitis. Since Danio rerio is a promising animal model to study gut function, we developed a soy-dependent model of intestinal inflammation in adult zebrafish. The soya bean meal diet was given for 4 weeks and induced an inflammatory process, as demonstrated by morphological changes together with an increased percentage of neutrophils infiltrating the intestinal wall, which developed between the second and fourth week of treatment. Pro-inflammatory genes such as interleukin-1beta, interleukin-8 and tumour necrosis factor alpha were upregulated in the second week and anti-inflammatory genes such as transforming growth factor beta and interleukin-10. Interestingly, an additional expression peak was found for interleukin-8 at the fourth week. Neuronal genes, OTX1 and OTX2, were significantly upregulated in the first two  weeks, compatible with the development of the changes in the gut wall. As for the genes of the p53 family such as p53, DNp63 and p73, a statistically significant increase was observed after two weeks of treatment compared with controls. Interestingly, DNp63 and p73 were shown an additional peak after four weeks. Our data demonstrate that soya bean meal diet negatively influences intestinal morphology and immunological function in adult zebrafish showing the features of acute inflammation. Data observed at the fourth week of treatment may suggest initiation of chronic inflammation. Adult zebrafish may represent a promising model to better understand the mechanisms of food-dependent intestinal inflammation.

Artificial intelligence in laboratory medicine: fundamental ethical issues and normative key-points.

The contribution of laboratory medicine in delivering value-based care depends on active cooperation and trust between pathologist and clinician. The effectiveness of medicine more in general depends in turn on active cooperation and trust between clinician and patient. From the second half of the 20th century, the art of medicine is challenged by the spread of artificial intelligence (AI) technologies, recently showing comparable performances to flesh-and-bone doctors in some diagnostic specialties. Being the principle source of data in medicine, the laboratory is a natural ground where AI technologies can disclose the best of their potential. In order to maximize the expected outcomes and minimize risks, it is crucial to define ethical requirements for data collection and interpretation by-design, clarify whether they are enhanced or challenged by specific uses of AI technologies, and preserve these data under rigorous but feasible norms. From 2018 onwards, the European Commission (EC) is making efforts to lay the foundations of sustainable AI development among European countries and partners, both from a cultural and a normative perspective. Alongside with the work of the EC, the United Kingdom provided worthy-considering complementary advice in order to put science and technology at the service of patients and doctors. In this paper we discuss the main ethical challenges associated with the use of AI technologies in pathology and laboratory medicine, and summarize the most pertaining key-points from the guidelines and frameworks before-mentioned.