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Blood cell counts often fail to report on immune processes occurring in remote tissues. Here, we use immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying human immune cell dynamics. We characterized cfDNA released from specific immune cell types in healthy individuals (N = 242), cross sectionally and longitudinally. Immune cfDNA levels had no individual steady state as opposed to blood cell counts, suggesting that cfDNA concentration reflects adjustment of cell survival to maintain homeostatic cell numbers. We also observed selective elevation of immune-derived cfDNA upon perturbations of immune homeostasis. Following influenza vaccination (N = 92), B-cell-derived cfDNA levels increased prior to elevated B-cell counts and predicted efficacy of antibody production. Patients with eosinophilic esophagitis (N = 21) and B-cell lymphoma (N = 27) showed selective elevation of eosinophil and B-cell cfDNA, respectively, which were undetectable by cell counts in blood. Immune-derived cfDNA provides a novel biomarker for monitoring immune responses to physiological and pathological processes that are not accessible using conventional methods.

In addition to well-known attention deficiencies, attention deficit hyperactivity disorder (ADHD) is accompanied by deficiencies in social cognition. Both intentional and spontaneous interpersonal synchrony have been found to be an essential part of successful human interaction. Here, we used a novel paradigm to assess intentional and spontaneous interpersonal synchrony in adults with and without ADHD. Our data indicate that intentional interpersonal synchrony is reduced in ADHD, whereas spontaneous interpersonal synchrony remains intact. These results suggest that a dysfunctional pattern of interpersonal synchrony may account for interpersonal difficulties in ADHD.

The purpose of the present long-term retrospective study was to assess the changing preference of one- vs. two-stage implant placement in partially edentulous individuals. The clinical outcome measures were one- vs. two-stage implant placement, implant survival, and gingival index. The radiological outcome measure was crestal bone loss. Other recorded information included gender, age, implant characteristics (brand, type, length, diameter) and implant location (maxilla/mandible). A total of 393 implants in 111 patients were included. The results revealed that there were no significant demographic differences between the one- and two-stage implant placement groups. There was a preference for one-stage surgery when wide diameter implants were used and when the number of implants per patient was ≤3. The mandible was the major implant site in the one-stage surgery group. Crestal bone loss and gingival index were similar for the two groups in both the short and long term. It can be concluded that lack of any long-term differences in implant survival, crestal bone loss and gingival health around implants after one- or two-stage implant placement promoted a significant change over 18 years, increasing to 50% the prevalence of one-stage surgery.

Group G Streptococcus (GGS) can cause severe infections, including bacteremia. These organisms often express a surface protein homologous to the Streptococcus pyogenes M protein. We retrospectively studied the characteristics of patients from the Hadassah Medical Center with GGS bacteremia from 1989 to 2000. Ninety-four cases of GGS bacteremia were identified in 84 patients. The median age was 62 years, 54% were males, and 92% had underlying diseases (35% had a malignancy, and 35% had diabetes mellitus). The most frequent source for bacteremia was cellulitis (61%). emm typing of 56 available isolates disclosed 13 different types, including 2 novel types. Six patients had recurrent bacteremia with two to four bacteremic episodes, five had chronic lymphatic disorders, and two had emm type stG840.0 in every episode. Recurrent bacteremia has not been described for invasive group A Streptococcus. We describe an entity of recurrent GGS bacteremia, which is associated with lymphatic disorders and possibly with emm stG840.0.

Given the broad implementation of immune checkpoint inhibitors (ICI) for cancer therapy, we encounter a variety of immune-related adverse events (irAE) including immune-related blood eosinophilia. Eosinophilia demonstrated a potential positive predictive marker for a beneficial clinical response to ICI. However, there are reports of eosinophil-induced adverse events (Eo-irAE) with organ dysfunction requiring initiation of oral glucocorticoid therapy and discontinuation of ICI.We aim to assess the efficacy and safety of interleukin (IL) 5-axis inhibition in Eo-irAE secondary to ICI therapy.We present three cases of Eo-irAE referred to our allergy and clinical immunology unit at Hadassah Hebrew University Medical Center following therapy with pembrolizumab and nivolumab, monoclonal antibodies that target the programmed cell death 1 (PD-1) receptor, for two cases of melanoma and one metastatic non-small cell lung carcinoma. Following informed consent and committee approval, two patients were treated with 1–3 doses of mepolizumab, 100 mg, monoclonal IgG1 kappa anti-IL-5 antibody, and one patient received up-to-date 9 doses of benralizumab, 30 mg, monoclonal IgG1 kappa antibody directed against the alpha chain of the interleukin-5 receptor, both administered subcutaneously. Patients were carefully followed and treatment response was assessed by physical examinations and laboratory tests.Hypereosinophilia at the level of 2300–8000 K/UL was observed 8–12 months following therapy accompanied by symptoms of dyspnea, arthralgia, myalgia, fasciitis, ‘morphea’-like lesions, fatigue, abdominal discomfort, pruritus, and chest pain. ICI discontinuation did not improve symptoms, two patients were resistant to glucocorticoids and therefore biological treatment was initiated to inhibit the IL5 axis. Patients demonstrated rapid clinical response and a decrease in peripheral blood eosinophil levels with long-term symptoms remission. There were no signals of negative impacts, such as tumor progression following IL5 axis inhibition.Eosinophilia secondary to ICI therapy can lead to organ dysfunction. Discontinuation of ICI might not be effective and symptoms may be refractory to steroid therapy hence targeted inhibition of the IL5 axis should be considered.

Introduction: Acute bronchiolitis epidemics are known to destabilize healthcare structures and stand as a major public health issue. Our tertiary care regional university hospital designed an organizational infrastructure paediatric plan (OIPP) to adapt to bronchiolitis epidemics. This study aimed to assess the impact of the OIPP on the length of stay and quality of care of children hospitalized for bronchiolitis. Methods: This epidemiological study analyzed data from 2 epidemic seasons before and after the OIPP implementation. The OIPP used a standardized algorithm of patient orientation and a 4-level stratification of care. Results: A total of 1636 children were included in the study, with 718 children before and 918 children after the OIPP implementation. The length of stay significantly decreased after the OIPP implementation, from 5.1 ± 6.8 days to 3.9 ± 3 days (P

Anti-CK7 and anti-CK20 immunohistochemistry is sometimes used to establish a diagnosis of primary lung cancer. We performed a retrospective study on the value of anti-CK7 and anti-CK20 immunohistochemistry in 359 biopsies of patients with suspected lung carcinoma in order to assess the usefulness of these antibodies in the evaluation of lung tumors in biopsies. Our results showed TTF-1 positivity in 73.3% of patients. EGFR mutations and ALK rearrangements were significantly different between TTF-1 positive and TTF-1 negative tumors (p < 0.001 and p = 0.023, respectively). Our results show a significant difference (p < 0.001) between TTF-1 positive and TTF-1 negative carcinomas with a median survival of 21.97 months (CI95% = 17.48–30.9 months) and 6.52 months (CI95% = 3.34–10.3 months), respectively. In the group of TTF-1 negative patients, anti-CK7 and CK20 immunohistochemistry was performed in 70 patients and showed CK7+/CK20- staining in 61 patients (87.1%), CK7-/CK20- in 4 patients (5.7%), CK7+/CK20+ in 3 patients (4.3%), and CK7-/CK20- in 2 patients (2.8%). No specific or molecular pattern was found in these groups of CK7/CK20 combinations. In total, this work brings arguments concerning the uselessness of anti-CK7/CK20 immunohistochemistry in the case of suspicion of primary lung cancer in biopsies.

Bronchial dysplasia is the pre-neoplastic lesion recognized for invasive squamous cell carcinoma. The mechanisms leading to invasive squamous cell carcinoma for this lesion are not fully known. Programmed Death-Ligand 1 (PD-L1) expression by the bronchial dysplasia neoplastic epithelium might suggest a response to immunotherapy. The objective of this work is to further characterize PD-L1 and CD8 expression in bronchial dysplasia and bronchial metaplasia compared to normal bronchial epithelium. Immunohistochemical analysis of PD-L1 and CD8 staining were characterized in bronchial dysplasia of 24 patients and correlated with clinical data. We also compared PD-L1 expression in dysplasia samples to 30 normal epithelium and 20 samples with squamous bronchial metaplasia. PD-L1 was never expressed in normal epithelium and in metaplastic epithelium whereas 37.5% of patients with bronchial dysplasia were stained by PD-L1 (p < 0.001). PD-L1 expression was not related to the degree of dysplasia or a medical history of invasive squamous cell carcinoma, while CD8 expression and its localization were related to medical history of squamous cell carcinoma (p = 0.044). Our results show that PD-L1 is expressed in roughly one third of patients with bronchial dysplasia and is not expressed in normal and metaplastic epithelium. This suggests that PD-L1 is expressed in preneoplastic lesions of squamous cell carcinoma.

Dentro del contexto de la denominada Sociedad del Conocimiento, resulta vital conocer en profundidad cómo interactúan los usuarios en las redes sociales y muy en concreto con la interfaz de Twitter. Hasta la fecha, se han realizado infinidad de investigaciones sobre la relevancia comercial, reputacional, de alcance o de penetración de este microblog. Casi todas ellas, han puesto de manifiesto la importancia de tener presencia personal o empresarial en esta red social. No obstante, con este informe realizado por Redbility, Influenzia, y la Universidad Europea de Madrid, se pretende reconocer cómo los usuarios emplean esta herramienta desde sus diferentes dispositivos y descubrir cuál es la manera más eficiente de participar en esta red social.

The paper looks into liquid flow simulation in the annular tube around the heated rod. The numerical simulation serves primarily the purpose of describing the temperature field in the annular tube that represents a simplified model of a nuclear reactor fuel rod. The fuel rod model uses several configurations of spacers which affect the flow of coolant - water - in the annular flow channel. For selected variants of spacers, temperature fields have been mutually compared in respect to various mass flow characteristics of the coolant.