Analysis of the genetic basis of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.

PFAPA syndrome is the most common autoinflammatory syndrome in children from Western countries. In spite of its strong familial clustering, its genetic basis and inheritance pattern are still unknown. We performed a comprehensive genetic study on 68 individuals from 14 families. Linkage analysis suggested a susceptibility locus on chromosome 8, but direct molecular sequencing did not support this initial statistical finding. Exome sequencing revealed the absence of any gene that was mutated in all patients. Exhaustive screening of genes involved in other autoinflammatory syndromes or encoding components of the human inflammasome showed no DNA variants that could be linked to PFAPA molecular pathology. Among these, the previously-reported missense mutation V198M in the NLRP3 gene was clearly shown not to co-segregate with PFAPA. Our results on this relatively large cohort indicate that PFAPA syndrome is unlikely to be a monogenic condition. Moreover, none of the several genes known to be involved in inflammation or in autoinflammatory disorders seem to be relevant, alone, to its etiology, suggesting that PFAPA results from oligogenic or complex inheritance of variants in multiple disease genes and/or non-genetic factors

Antibiotic therapy, supportive treatment and management of immunomodulation-inflammation response in community acquired pneumonia: review of recommendations

Community-acquired pneumonia is a common and serious disease, with high rates of morbidity and mortality. Management and treatment of community-acquired pneumonia are described in three main documents: the 2007 American Thoracic Society guidelines, the 2011 European Respiratory Society guidelines, and the 2009 British Thoracic Society guidelines, updated by the NICE in 2015. Despite the validity of current guidelines in improving prognosis and management of patients with community-acquired pneumonia, not all recommendations have high levels of evidence and there are still some controversial issues. In particular, there are some areas of low evidence such as the efficacy of an antibiotic molecule or scheme in patients with same risk factors; duration of antibiotic treatment, supportive therapy for acute respiratory failure and immunomodulation molecules. This review will summarize the main recommendations with high level of evidence and discuss the recommendations with lower evidence, analyzing the studies published after the guidelines' release

An ordinary differential equation for velocity distribution and dip-phenomenon in open channel flows

An ordinary differential equation for velocity distribution in open channel flows is presented based on an analysis of the Reynolds-Averaged Navier-Stokes equations and a log-wake modified eddy viscosity distribution. This proposed equation allows to predict the velocity-dip-phenomenon, i.e. the maximum velocity below the free surface. Two different degrees of approximations are presented, a semi-analytical solution of the proposed ordinary differential equation, i.e. the full dip-modified-log-wake law and a simple dip-modified-log-wake law. Velocity profiles of the two laws and the numerical solution of the ordinary differential equation are compared with experimental data. This study shows that the dip correction is not efficient for a small Coles' parameter, accurate predictions require larger values. The simple dip-modified-log-wake law shows reasonable agreement and seems to be an interesting tool of intermediate accuracy. The full dip-modified-log-wake law, with a parameter for dip-correction obtained from an estimation of dip positions, provides accurate velocity profiles

Dépistage du cancer anal : doit-on faire de même que pour le cancer du col utérin ? [Screening for anal cancer : is it the same as for cervical cancer ?]

Anal dysplasia is usually caused by HPV infection and can lead to squamous anal cancer. The purpose of this article is to describe the classification of these precursor lesions but above all to identify the groups of patients at risk and to clarify the screening and follow-up that must be initiated

Análisis de protocolos de investigación

Fil: Vanoni, Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Carri, Julio Horacio. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Montrull, Hilda. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Análisis de protocolos de investigación. Experiencias de los Comités de Ética de Investigación en Latinoamérica.Ed. Programa de Ciencias Biomédicas y Bioética de la Facultad de Medicina de la Universidad Central de Chile, y Federación Latinoamericana de Instituciones de Bioética, Santiago de Chile 2014.Fil: Vanoni, Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Carri, Julio Horacio. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Montrull, Hilda. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Otras Ciencias de la Salu

Management of Acute Respiratory Failure Due to Community-Acquired Pneumonia: A Systematic Review

Community-acquired pneumonia (CAP) is a leading cause of mortality worldwide. CAP mortality is driven by the development of sepsis and acute respiratory failure (ARF). We performed a systematic review of the available English literature published in the period 1 January 1997 to 31 August 2017 and focused on ARF in CAP. The database searches identified 189 articles-of these, only 29 were retained for data extraction. Of these 29 articles, 12 addressed ARF in CAP without discussing its ventilatory management, while 17 evaluated the ventilatory management of ARF in CAP. In the studies assessing the ventilatory management, the specific treatments addressed were: high-flow nasal cannula (HFNC) (n = 1), continuous positive airway pressure (n = 2), non-invasive ventilation (n = 9), and invasive mechanical ventilation (n = 5). When analyzed, non-invasive ventilation (NIV) success rates ranged from 20% to 76% and they strongly predicted survival, while NIV failure led to an increased risk of adverse outcome. In conclusion, ARF in CAP patients may require both ventilatory and non-ventilatory management. Further research is needed to better evaluate the use of NIV and HFNC in those patients. Alongside the prompt administration of antimicrobials, the potential use of steroids and the implementation of severity scores should also be considered

PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions

Group 2 innate lymphoid cells (ILC2s) play a critical role in protection against helminths and in diverse inflammatory diseases by responding to soluble factors such as the alarmin IL-33, that is often overexpressed in cancer. Nonetheless, regulatory factors that dictate ILC2 functions remain poorly studied. Here, we show that peroxisome proliferator-activated receptor gamma (PPARγ) is selectively expressed in ILC2s in humans and in mice, acting as a central functional regulator. Pharmacologic inhibition or genetic deletion of PPARγ in ILC2s significantly impair IL-33-induced Type-2 cytokine production and mitochondrial fitness. Further, PPARγ blockade in ILC2s disrupts their pro-tumoral effect induced by IL-33-secreting cancer cells. Lastly, genetic ablation of PPARγ in ILC2s significantly suppresses tumor growth in vivo. Our findings highlight a crucial role for PPARγ in supporting the IL-33 dependent pro-tumorigenic role of ILC2s and suggest that PPARγ can be considered as a druggable pathway in ILC2s to inhibit their effector functions. Hence, PPARγ targeting might be exploited in cancer immunotherapy and in other ILC2-driven mediated disorders, such as asthma and allergy

Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells

Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epigenetic transcriptional reprogramming. By integrating metabolomics and transcriptomics in a triple-negative human breast cancer cell line, we show that genetic and pharmacological down-regulation of CtBP2 strongly reduces cell proliferation by modulating the redox balance, nucleotide synthesis, ROS generation, and scavenging. Our data highlight the critical role of NADH in controlling the oncogene-dependent crosstalk between metabolism and the epigenetically mediated transcriptional program that sustains energetic and anabolic demands in cancer cells

Endobronchial Ultrasound Transbronchial Needle Aspiration In Thoracic Diseases: Much More Than Mediastinal Staging

Background and Objective. EBUS-TBNA has revolutionized the diagnostic approach to thoracic diseases from a surgical to minimally invasive procedure. In non small-cell lung cancer (NCSLC) patients, EBUS-TBNA is able to dictate the consecutive therapy both for early and advanced stages, providing pathological diagnosis, mediastinal staging, and even adequate specimens for molecular analysis. This study reports on the ability of EBUS-TBNA to make different diagnoses and dictates the consecutive therapy in a large cohort of patients presenting different thoracic diseases. Methods. All procedures performed from January 2012 to September 2016 were reviewed. Five groups of patients were created according to the main indications for the procedure. Group 1: lung cancer staging; Group 2: pathological diagnosis in advanced stage lung cancer; Group 3: lymphadenopathy in previous malignancies; Group 4: pulmonary lesions; Group 5: unknown origin lymphadenopathy. In each group, the diagnostic yield of the procedure was analysed. Non malignant diagnosis at EBUS-TBNA was confirmed by a surgical procedure or clinical and radiological follow-up. Results. 1891 patients were included in the analysis. Sensitivity, negative predictive value, and diagnostic accuracy in each group were 90.7%, 79.4%, and 93.1% in Group 1; 98.5%, 50%, and 98.5% in Group 2; 92.4%, 85.1%, and 94.7% in Group 3; 90.9%, 51.0%, and 91.7% in Group 4; and 25%, 83.3%, and 84.2% in Group 5. Overall sensitivity, negative predictive value, and accuracy were 91.7%, 78.5%, and 93.6%, respectively. Conclusions. EBUS-TBNA is the best approach for invasive mediastinal investigation, confirming its strategic role and high accuracy in thoracic oncology

The Swiss French version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Swiss French language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data, and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 98 JIA patients (3.1% systemic, 43.9% oligoarticular, 16.3% RF negative polyarthritis, 36.7% other categories), and 64 healthy children were enrolled in a paediatric rheumatology centre. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Swiss French version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research