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Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis
Get PDFAmong the intrathecal inflammatory niches where compartmentalized inflammation persists and plays a pivotal role in progressive multiple sclerosis (MS), choroid plexus (CP) has recently received renewed attention. To better characterize the neuropathological/molecular correlates of CP in progressive MS and its potential link with other brain inflammatory compartments, such as perivascular spaces and leptomeninges, the levels, composition and phenotype of CP immune infiltration in lateral ventricles of the hippocampus were examined in 40 post-mortem pathologically confirmed MS and 10 healthy donors, using immunochemistry/immunofluorescence and in-situ sequencing. Significant inflammation was detected in the CP of 21 out of the 40 MS cases (52%). The degree of CP inflammation was found correlated with: number of CP macrophages (R: 0.878, p = 1.012 x 10-13) and high frequency of innate immune cells expressing the markers MHC-class II, CD163, CD209, CD11c, TREM2 and TSPO; perivascular inflammation (R: 0.509, p = 7.921 x 10-4), and less with meningeal inflammation (R: 0.365, p = 0.021); number of active lesions (R: 0.51, p: 3.524 x 10-5). However, it did not significantly correlate with any clinical/demographic characteristics of the examined population. In-situ sequencing analysis of gene expression in the CP of 3 representative MS cases and 3 controls revealed regulation of inflammatory pathways mainly related to 'type 2 immune response', 'defense to infections', 'antigen processing/presentation'. Analysis of 78 inflammatory molecules in paired post-mortem CSF, the levels of fibrinogen (R: 0.640, p = 8.752 x 10-6), PDGF-bb (R: 0.470, p = 0.002), CXCL13 (R: 0.428, p = 0.006) and IL15 (R: 0.327, p = 0.040) were correlated with extent of CP inflammation. Elevated fibrinogen and complement deposition were found in CP and in underlying subependymal periventricular areas, according to "surface-in" gradient associated with concomitant prominent microglia activation. CP inflammation, predominantly characterized by innate immunity, represents another key determinant of intrathecal, compartmentalised inflammation persisting in progressive MS, which may be possibly activated by fibrinogen and influence periventricular pathology, even without substantial association with clinical features
Radiologic Findings after Transpromontorial Approach: Clinical and Pathophysiological Considerations
No full textObjectives: Transpromontorial approaches require obliteration of the surgical cavity and the eustachian tube, along with cul-de-sac external auditory canal closure, without obliteration of the mastoid air cells. This study aims to evaluate the clinical and radiological implications of tympanic cavity obliteration when the mastoid air cell system is preserved. Study design: Retrospective observational study. Setting: Tertiary referral center. Patients: Thirty-one adult patients with unilateral vestibular schwannoma. Intervention: Patients underwent resection of a vestibular schwannoma through either an exclusive endoscopic transcanal transpromontorial approach (endoTTA) or an expanded transcanal transpromontorial approach (expTTA). Main outcome measure: Postoperative radiologic mastoid and surgical cavity content and clinical outcomes. Results: Thirty-one patients met the inclusion criteria. The mean radiological follow-up was 54 months. Regarding mastoid content, air was present in 13 patients (42%) and trapped fluid in 18 patients (58%). Surgical cavity content revealed air in 14 patients (45%), trapped fluid in 8 patients (26%), total fat obliteration in 5 patients (16%), and partial fat obliteration in 4 patients (13%). No cases of mucocele, cholesterol granuloma, or iatrogenic cholesteatoma were observed. Three main radiological patterns were identified by combining mastoid and surgical cavity findings. EndoTTA was found to be significantly associated with postoperative radiological air content in the mastoid cavity (p value = 0.013), while no association was found between the type of radiological pattern and the development of complications or symptoms at the last follow-up. Conclusions: EndoTTA and expTTA are safe and effective procedures, with no increased risk of meningitis or CSF leak, even in cases where obliteration tissue is reabsorbed
The Effects of a 24-Week Combined Circuit Training and Mobility Program on the Physical Fitness and Body Composition of an Adult Academic Community
Get PDFWorkplace physical activity programs (WPAPs) are increasingly being recognized for improving employee health, though the results remain inconsistent. Universities provide favorable settings for WPAPs. This study examined the effects of a 24-week circuit training and mobility program on the physical fitness (PF) and body composition of university employees. Thirty-eight university employees (9 males and 29 females; 51.5 ± 12.6 years) followed a 24-week training program consisting of two circuit training sessions and one mobility session per week. PF (including cardiorespiratory fitness (CRF), grip strength, shoulder mobility, core endurance, lower limb strength, and balance) body composition, anthropometric variables, and physical activity (PA) levels were assessed at baseline (T0), 12 weeks (T1), and 24 weeks (T2). CRF, strength, mobility, and core endurance significantly improved. A body composition analysis indicated a decrease in fat mass and an increase in lean mass at T2. Minor changes were observed in anthropometric variables. Furthermore, PA levels increased throughout the intervention. The 24-week WPAP improved the PF and body composition of university employees
Automate the process of formalin-fixed paraffin-embedded blocks storage in the pathology laboratory: A proof of concept study
No full text: Pathology laboratories are currently facing remarkable issues in the management of their archives due to the ongoing increase in the production of formalin-fixed paraffin-embedded (FFPE) blocks, which is often coupled with inadequate spatial and environmental storing conditions. The manual process of storage and retrieving further increases the likelihood of human-based mistakes, wastes professionals' working time, and, ultimately, widens reports signing turn-around times. In the present work, we outline the strategies underlying the development of an automated archive at the pathology services of the University of Modena. The proposed project relies on the controlled interaction of a mechanic robotic arm with racks and shelves in a fully traced manner, driven by the integration with the local laboratory information system (LIS). This automated archive aims to significantly improve the time-saving of laboratory professionals and standardize the storage of FFPE samples both before and after the pathology diagnosis is rendered. The system's modularity suits the needs and spaces of the different institutions, opening novel strategies in archiving thanks to its connection with the LIS and integration with artificial intelligence algorithms
The neuropsychological profile of SSADH deficiency, a neurotransmitter disorder of GABA metabolism
No full textBackground and objectives: Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder resulting in hyper-physiologic concentrations of the neurotransmitter γ-aminobutyrate (GABA). This study aims to provide the most comprehensive description, to date, of the neuropsychological profile of individuals with SSADHD and assess whether neuroimaging, neurophysiologic, and biochemical indices of cortical inhibition correlate with those of standardized behavioral tests. Methods: Participants enrolled in the SSADHD Natural History Study underwent medical and neurological examinations, magnetic resonance imaging (MRI) and spectroscopy (MRS), biochemical tests of GABA and its related metabolites, transcranial magnetic stimulation (TMS), and gene expression quantification, as well as complete neuropsychological assessment including standardized measures for cognition, adaptive skills, motor function, receptive and expressive language, autism spectrum disorder, and behavior problems. Results: The neuropsychological profile of the study's 65 enrollees [54 % females, median (interquartile range) age 9.6 (5.4-14.7)] consisted almost universally of intellectual disability, delays in adaptive skills, and deficits in expressive more than receptive language. Autism Spectrum Disorder was noted in ∼50 %, and behavioral problems in ∼70 %, predominated by obsessive-compulsive behaviors and attention problems but also including affective problems, anxiety, and, rarely, aggression and possible psychosis. Correlation analyses showed that increased internalizing, externalizing, and overall psychiatric morbidity significantly correlated with increasing age (R = 0.391, p = 0.033), as well as age-independent indices representing decreased cortical inhibition such as lower MRS-derived GABA (R = -0.530, p = 0.029) and TMS-derived resting motor threshold (R = -0.418, p = 0.053). Discussion: The natural history study of SSADHD indicates that intellectual disability, delayed adaptive skills, and expressive>receptive language deficits are nearly universal, with behavior problems in the vast majority. Increased psychiatric morbidity in SSADHD with age-independent decreased cortical inhibition may serve as the basis for establishing disorder-specific biomarkers for behavioral and psychiatric outcomes in SSADHD and other non-syndromic psychiatric disorders
Positive Lymph Nodes Independently Affect Long-Term Survival After Pancreaticoduodenectomy for Non-Ampullary Duodenal Adenocarcinoma: A Single-Center, Retrospective Analysis
No full textBackground/Objectives: The main treatment for non-ampullary duodenal adenocarcinoma (NDA) is pancreatoduodenectomy (PD) with lymphadenectomy (LN). Several studies have proposed a minimum number of examined lymph nodes (MNELN) to ensure proper staging. This study investigated the impact of nodal parameters-including the pattern of nodal spread-on oncologic outcomes following PD for NDA. Furthermore, we sought to determine the MNELN to ensure reliable detection of nodal involvement. Methods: This was a single-center, retrospective study. Consecutive patients who underwent PD from 2000 to 2019 with a final diagnosis of NDA were retrieved from a prospectively maintained database. The probability of detecting at least one metastatic LN in a node-positive patient was assessed using a model based on the binomial probability law. Results: A total of 70 patients met the inclusion criteria. The median number of ELNs was 35 (22-43, IQR). Thirty-six patients (51%) had at least one PLN. A node-positive disease was associated with adverse pathologic features, including high tumor grade and perineural and peripancreatic fat invasion. This translated into a greater recurrence rate (p < 0.001). The MNELN yielding a 95% probability of detecting at least one metastatic node in a node-positive patient was 25. After a median follow-up of 73 months, the median recurrence-free survival (RFS) was 33 months (95% CI 13-97), and the overall survival (OS) was 41 months (95% CI 17-96). The LN ratio, tumor grade, and metastases at stations 8 and 12 were independently associated with OS (p < 0.05). Conclusions: Nodal metastases are common among patients with NDA and have a considerable impact on long-term survival. Stations 8 and 12 were associated with OS. Therefore, an adequate lymphadenectomy, possibly including stations 8 and 12, is recommended in patients with NDA.
Background/Objectives: The main treatment for non-ampullary duodenal adenocarcinoma (NDA) is pancreatoduodenectomy (PD) with lymphadenectomy (LN). Several studies have proposed a minimum number of examined lymph nodes (MNELN) to ensure proper staging. This study investigated the impact of nodal parameters—including the pattern of nodal spread—on oncologic outcomes following PD for NDA. Furthermore, we sought to determine the MNELN to ensure reliable detection of nodal involvement. Methods: This was a single-center, retrospective study. Consecutive patients who underwent PD from 2000 to 2019 with a final diagnosis of NDA were retrieved from a prospectively maintained database. The probability of detecting at least one metastatic LN in a node-positive patient was assessed using a model based on the binomial probability law. Results: A total of 70 patients met the inclusion criteria. The median number of ELNs was 35 (22–43, IQR). Thirty-six patients (51%) had at least one PLN. A node-positive disease was associated with adverse pathologic features, including high tumor grade and perineural and peripancreatic fat invasion. This translated into a greater recurrence rate (p < 0.001). The MNELN yielding a 95% probability of detecting at least one metastatic node in a node-positive patient was 25. After a median follow-up of 73 months, the median recurrence-free survival (RFS) was 33 months (95% CI 13–97), and the overall survival (OS) was 41 months (95% CI 17–96). The LN ratio, tumor grade, and metastases at stations 8 and 12 were independently associated with OS (p < 0.05). Conclusions: Nodal metastases are common among patients with NDA and have a considerable impact on long-term survival. Stations 8 and 12 were associated with OS. Therefore, an adequate lymphadenectomy, possibly including stations 8 and 12, is recommended in patients with NDA
Force control and EMG-based adaptive assistance for enhanced human-exoskeleton interaction
No full textThe increasing diffusion of exoskeletons in industrial, domestic, and medical environments highlights their potential to reduce work-related musculoskeletal disorders, support rehabilitation, and improve the mobility of people with disabilities.
Unfortunately, control technologies capable of ensuring a reliable physical human-exoskeleton interaction and providing optimal assistance based on the load lifted by the user are still missing. This thesis investigates advanced control strategies that address key limitations of existing approaches by acting at both the low-level and high-level layers of exoskeleton control architectures.
The first part of the thesis focuses on low-level force control. First, a force control benchmarking framework is developed to highlight well-known critical challenges in force control and to evaluate force control algorithms by taking into account diverse interacting environments. Next, a high-performance friction compensation solution for benchmarking applications is proposed to guarantee non-biased benchmarking results. Since the latter solution cannot be exploited outside the benchmarking scenario and given the importance of accurate friction compensation for reliable human-exoskeleton interaction, this thesis proposes a novel force control architecture that includes a model-reference friction observer. Since passivity is a fundamental requirement for interaction control, the conditions under which the proposed observer preserves passivity at the environment, control, and friction ports were investigated. This implies that the proposed architecture can perform passive friction compensation for any friction dynamics and can be combined with any passive force controller while guaranteeing a stable interaction with any passive environment. Experimental validation shows that the proposed approach outperforms existing friction compensation solutions in force control applications.
The second part of the thesis focuses on high-level Electromyography (EMG)-based control strategies for Adaptive Gravity Compensation (AGC). To introduce the reader, a brief overview of Myoelectric Control Strategies (MCSs) is presented, showing that MCSs found in the literature are generally composed of three distinct functional modules: a decoder to extract the movement intention from EMG signals, a controller to accomplish the desired motion through a command given to the actuators, and a shaper to connect them. Subsequently, two EMG-based AGC approaches are proposed. Differently from existing AGC solutions, the proposed approaches (1) do not require knowledge of the anthropomorphic properties of the human arm and (2) recognize the importance of accounting for the human-exoskeleton dynamics within the adaptation law to improve payload estimation performance in dynamic conditions. The feasibility of the proposed approaches is experimentally validated on a 1-degree-of-freedom upper-limb exoskeleton
A Refined Score, Namely Thoracic Ultrasound Score, to Predict the Need for Surfactant in Preterm Neonates: A Prospective, Multicenter, Observational Study
No full textIntroduction: Lung ultrasound score (LUS) is used to predict the need for surfactant in preterm neonates. Its performance is lower in neonates with a gestational age (GA) ≥ 34 weeks. We developed a score, thoracic ultrasound score (TUS), to overcome the shortcomings of LUS. Objectives: To assess the feasibility and diagnostic accuracy of TUS to evaluate oxygenation and predict the need for surfactant administration, compared to LUS. Materials and methods: This was a prospective, multicenter, observational study. Preterm neonates in noninvasive ventilation with GA between 24 + 0 and 36 + 6 weeks were assessed for eligibility. Lung ultrasound were performed within 3 h of life, and TUS and LUS were calculated. Results: Fifty-eight neonates who received surfactant were compared with 112 neonates who did not receive surfactant: GA 30.2 ± 3.1 weeks versus 32.6 ± 2.3 weeks, (p < 0.001), and birth weight 1466 ± 674 g versus 1725 ± 519 g, (p = 0.006), respectively. TUS and LUS showed a similar association with S/F ratio (r = -0.670 and r = 0.615) and OSI (r = 0.524 and r = 0.423), all p < 0.001. In neonates with GA < 34 weeks, the AUC (95% CI) was similar: 0.956 (0.923-0.989) versus 0.952 (0.921-0.984). In neonates with GA ≥ 34 weeks, the AUC (95% CI) of TUS was superior to LUS: 0.971 (0.914-1.000) versus 0.797 (0.639-0.980), p = 0.02. Conclusion: Compared to LUS, TUS showed a similar association with the oxygenation status and a superior ability to predict the need for surfactant in neonates with GA ≥ 34 weeks. The latter was similar in neonates with GA < 34 weeks
The experience of an innovative interdisciplinary model of primary care delivery in changing organizational dynamics: a grounded theory study
No full textIntroduction: Changing dynamics are pushing institutions to focus on care delivery innovation. To address the shortage of general practitioners (GPs), an Italian health district recently introduced a new primary care model called Primary Health Point (PHP) to provide primary integrated care to its population. Aim: To investigate the healthcare professionals' (HCPs) experience regarding the introduction of the PHP and to describe its process of care delivery. Methods: Qualitative study design with a grounded theory approach and convenience sampling. Interviews were conducted using a semi structured guide to explore the experience of HCPs working at the PHP. The development of open coding was followed by the creation of categories. The analysis was conducted utilizing NVivo software. Results: Twelve HCPs working at the PHP were interviewed and highlighted the model structure. The themes were the context and the antecedents that identified the most common health complaints and the patients with more needs and reflected on the traditional GP model; the process, which highlighted the complexity of interdisciplinary teamwork and the role of the Family and Community Nurse (FCN) in the new model; the outcome identified the factors mediating satisfaction with the care delivered by the PHP. Conclusions: The PHP has been considered a possible alternative to the GP model by its end users. It addresses disease pathway coordination, referrals, and medication management, focusing on chronic and older adult populations. It features interdisciplinary workflows with rotating physicians and consistent family nurse support. Proactive monitoring and a focus on disease education benefit fragile patients
Short-term acute outcomes by clinical and socioeconomic characteristics in adults with SARS-CoV-2: a population-based cohort study focused on the first two years of the COVID-19 pandemic
No full textBackground: The COVID-19 pandemic disproportionately affected vulnerable populations in terms of comorbidity and socioeconomic disadvantage, both between and within countries. This retrospective population-based cohort study is part of the Horizon 2020 ORCHESTRA project, was conducted in the Emilia-Romagna (E-R) Region, and aimed to investigate the risk of hospitalization, disease severity and all-cause mortality during the 30 days following SARS-CoV-2 infection. Methods: All adult positive cases notified in E-R from 2020 to 2022 were included. Poisson regression with robust standard error was used to estimate risk ratios for the three outcomes, stratified by sex, pandemic period and adjusted for age, citizenship, deprivation index, risk of hospitalization and death score (RHDS), and vaccination status. Data sources were regional healthcare databases. Supplementary analyses considered citizenship in relation to duration of residency in E-R or aggregated in areas of origin. Results: During the first two years of the pandemic 859,653 E-R residents tested positive for SARS-CoV-2 (47.8% males); 9.6% of them were citizens from high migratory pressure countries (HMPCs). The risk of severe outcomes increased steeply with age, especially in males. RHDS predicted worse outcomes in both sexes while vaccination showed a strong protective effect against all outcomes of acute infection (i.e., recent vaccination was 85% more protective against in-hospital severe disease in both sexes). Immigrants from HPMCs, especially females, showed a higher risk of hospitalization and in-hospital severe disease, in particular those who arrived within 5 years ago from the infection (RR for hospitalization = 1.92, 95%CI = 1.76-2.00 for males, and RR = 2.40, 95%CI = 2.23-2.59 for females), whereas the risk of all-cause mortality was lower compared to residents from low migratory pressure countries (LMPCs) that showed a RR for females of 0.73 (95%CI = 0.59-0.90). Conclusions: The results provided an overall view of course of acute COVID-19 outcomes in E-R and allowed the risk associated with clinical, demographic, and social characteristics to be measured. The findings suggest that, although national and regional public health policies have helped to mitigate the impact of the pandemic in the general population, inequalities in outcomes among persons with comorbidities and social disadvantages remain. Improvements in the appropriateness, effectiveness and equity of public health strategies are needed