Low NETosis Induced in Anaplasma phagocytophilumInfected Cells

Anaplasma phagocytophilum are obligatory intracellular bacteria that preferentially replicate inside leukocytes by utilizing biological compounds and processes of these primary host defensive cells. In this study, bioinformatics analysis was conducted to further characterize A. phagocytophilum–host interactions using the neutrophil-like model of human Caucasian promyelocytic leukemia HL60 cells. We detected a hierarchy of molecules involved in A. phagocytophilum-HL60 interactions with overrepresentation in infected human cells of proteins involved in the reactive oxygen species (ROS) pathway and cell surface monocyte markers. As A. phagocytophilum phagocytosis by neutrophils is inhibited, the results suggested a possible explanation for our bioinformatics data: radical oxygen compounds could induce the killing of bacteria activating NETosis, a unique form of defense mechanism resulting in cell death that is characterized by the release of decondensed chromatin and granular contents to the extracellular space, forming neutrophil extracellular traps (NETs) to eliminate invading microorganisms. Thus, we confirmed the existence of a low NETosis induced in A. phagocytophilum-infected cells by immunofluorescence (IF) experiments. These results provide new insights into the complex mechanisms that govern immune response during A. phagocytophilum host interactions.Anaplasma phagocytophilum son bacterias intracelulares obligatorias que se replican preferentemente dentro de los leucocitos mediante la utilización de compuestos biológicos y procesos de estas células defensivas primarias del huésped. En este estudio, se realizó un análisis bioinformático para caracterizar aún más las interacciones entre A. phagocytophilum y el huésped utilizando el modelo similar a los neutrófilos de células HL60 de leucemia promielocítica caucásica humana. Detectamos una jerarquía de moléculas involucradas en las interacciones A. phagocytophilum -HL60 con una sobrerrepresentación en células humanas infectadas de proteínas involucradas en la vía de especies reactivas de oxígeno (ROS) y marcadores de monocitos de superficie celular. Como A. phagocytophilumse inhibe la fagocitosis de los neutrófilos, los resultados sugirieron una posible explicación para nuestros datos bioinformáticos: los compuestos radicales de oxígeno podrían inducir la muerte de bacterias activando NETosis, una forma única de mecanismo de defensa que resulta en la muerte celular que se caracteriza por la liberación de cromatina descondensada y granular. contenido al espacio extracelular, formando trampas extracelulares de neutrófilos (NET) para eliminar los microorganismos invasores. Por lo tanto, confirmamos la existencia de una NETosis baja inducida en células infectadas por A. phagocytophilum mediante experimentos de inmunofluorescencia (IF). Estos resultados proporcionan nuevos conocimientos sobre los complejos mecanismos que gobiernan la respuesta inmunitaria durante las interacciones del huésped con A. phagocytophilum

Insights into healthcare professionals’ perceptions and attitudes toward nanotechnological device application: What is the current situation in glioblastoma research?

Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the application of nanotechnologies, especially for malignant brain tumors with a low-survival rate such as glioblastoma (GBM). As to improving patients’ quality of life and life expectancy, innovative treatments are worth being explored. Indeed, it is important to explore clinicians’ intention to use experimental technologies in clinical practice. In the present study, we conducted an exploratory review of the literature about healthcare workers’ knowledge and personal opinions toward nanomedicine. Our search (i) gives evidence for disagreement between self-reported and factual knowledge about nanomedicine and (ii) suggests the internet and television as main sources of information about current trends in nanomedicine applications, over scientific journals and formal education. Current models of risk assessment suggest time-saving cognitive and affective shortcuts, i.e., heuristics support both laypeople and experts in the decision-making process under uncertainty, whereas they might be a source of error. Whether the knowledge is poor, heuristics are more likely to occur and thus clinicians’ opinions and perspectives toward new technologies might be biased

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

La risoluzione del mutuo fondiario e i suoi effetti restitutori (nota a Cass. S.U. 12639/2008)

a) L’orientamento delle Sezioni Unite Le S.U. smentiscono il consolidato e piu` risalente indirizzo giurisprudenziale che sosteneva la prosecuzione del rapporto di mutuo anche dopo la dichiarazione della banca di avvalersi della condizione risolutiva di cui all’art. 15, d.p.r. n. 7/1976 e affermano invece la natura di clausola risolutiva espressa della disposizione in esame, l’esercizio della quale risolve il rapporto di mutuo. b) Il superamento delle precedenti interpretazioni La Corte supera cosı` l’equivoco terminologico nel quale a suo parere e` incorsa la giurisprudenza precedente, confondendo i concetti di decadenza dal beneficio del termine, condizione risolutiva e clausola risolutiva espressa. c) L’oggetto della restituzione La sentenza procede quindi alla materiale quantificazione della somma oggetto di restituzione da parte del mutuatario affrontando il problema della base di calcolo da adottare, sia per le rate scadute, sia per quelle ancora da scadere. d) Le rate e gli interessi dovuti Per le semestralita` gia` scadute, infatti, il soggetto mutuante avra` diritto all’importo globale, comprensivo quindi di capitale e interessi corrispettivi, come previsti dal piano di ammortamento. Invece per le rate a scadere dovra` essere restituita solo la quota di capitale e non anche gli interessi (corrispettivi) conglobati. Sull’intera somma cosı` determinata (rate scadute piu` rate a scadere) si applicheranno gli interessi di mora al tasso convenzionale ai sensi dell’art. 1224, 1º co., ult. parte, c.c

Parkinson Patients' needs during {COVID}-19 pandemic in a red zone: a Framework Analysis of Open-Ended Survey Questions

Background and purpose During the first phase of the COVID-19 pandemic, a lockdown was imposed in Italy. The aim of this study was to investigate the perceptions, feelings and unmet needs of Parkinson's disease (PD) patients who experienced the 2-month lockdown in a "red zone" in the northern part of Italy during the COVID-19 outbreak.Methods The study had a descriptive design that used a cross-sectional online survey which included open-ended questions to elicit responses on the participant's feelings concerning their risk of contracting coronavirus, how their physical activity had changed, and their personal needs, dictated by their condition, which were not met in this pandemic period as compared to previous periods. Demographic data were analysed using descriptive frequencies, while the open-ended questions were analysed using thematic framework analysis.Results The study included 103 participants (63 men/40 women [61.17 vs. 38.83%]). Framework analysis led to the identification of four main themes: (i) fearing the risk of contracting coronavirus; (ii) reduction of physical activity; (iii) perception of the risk of not being able to access outpatient clinics or support services; and (iv) negative experiences of the important reduction in socialization. The perceptions of unmet needs appeared to be greater than the actual experience, particularly for the reduction in physical activity and the interruption of contacts with the neurologist and other specialists.Conclusions This study highlights how perceptions and actual experience shape the meaning of living with PD during the pandemic. Worth noting is the divergence between perceptions and real impact in some aspects of the COVID-19 outbreak

Negotiating the Beginning of Care: A Grounded Theory Study of Health Services for Amyotrophic Lateral Sclerosis

A range of professional figures are needed to preserve the quality of life of people with amyotrophic lateral sclerosis. This study aimed to explore the beginning of the care process as negotiated by people with amyotrophic lateral sclerosis, their caregivers, and healthcare professionals. We designed the study according to the constructivist Grounded Theory method, collecting data through open-ended, semi-structured interviews, employing theoretical sampling and constant comparison, and performing conceptual coding as data analysis. By naming the core category “off-beat interfacing”, we were able to show how the demands of the professionals concerned did not correspond to the ability of people with ALS and their proxies to process information, deal with requests, and be at ease in making decisions at the beginning of the shared care pathway. Three categories were generated: (i) navigating different paths, (ii) offering and experiencing a standard, non-personalized pathway, and (iii) anticipating decisions. The network of services must be organized according to guidelines, but must also contemplate a patient-family-centered approach that permits more personalized assistance

Co-Occurrence of Multiple Sclerosis and Amyotrophic Lateral Sclerosis in an FUS-Mutated Patient: A Case Report

A concomitant presentation of relapsing remitting multiple sclerosis (RRMS) and amyotrophic lateral sclerosis (ALS) is quite rare. However, a review of the literature showed an increased co-occurrence of both diseases, including in genetically determined cases. We report the case of a 49-year-old woman with a history of RRMS who developed a progressive subacute loss of strength in her left arm. The patient’s father died from ALS, and her paternal uncle had Parkinson’s disease. Brain and cervical MRIs were performed, and new demyelinating lesions were excluded. Electromyography (EMG) of the upper limbs showed fibrillations and fasciculations in distal muscles of both arms. In the following months, the patient presented a progressive loss of strength in the proximal and distal muscles of the right arm and hyperreflexia in the lower limbs. EMG and central motor conduction were consistent with ALS. A genetic test was carried out, revealing a mutation in the FUS gene (exon 15; c. 1562 G>A). To our knowledge, the co-occurrence of MS and ALS in patients with FUS mutation is extremely rare. We hypothesize a common pathway for both diseases based on the possibility of a shared oligodendroglial dysfunction due to FUS mutation