Search

The general objective of this series of papers is to evaluate long duration limited area simulations with idealised tracers as a tool to assess tracer transport in chemistrytransport models (CTMs). In this first paper, we analyse the results of six simulations using different convection parameterizations. The simulations are using the Grell and Dévényi (2002) mass-flux framework for the convection parameterization with different closures (Grell=GR, Arakawa-Shubert=AS, Kain-Fritch=KF, Low omega=LO, Moisture convergence=MC) and an ensemble parameterization (EN) based on the other five closures. The simulations are run for one month during the SCOUT-O3 field campaign lead from Darwin (Australia) and have a 60km horizontal resolution and a fine vertical resolution in the upper troposphere/lower stratosphere. Meteorological results are compared with satellite products, radiosoundings and SCOUT-O3 aircraft campaign data. They show that the model is generally in good agreement with the measurements with less variability in the model. Except for the precipitation field the differences between the six simulations are small with respect to the differences with the meteorological observations. The comparison with TRMM rainrates shows that the six simulations have two different behaviours with the EN, AS and KF parameterizations (Group 1) providing better rain fields than LO, MC and GR (Group 2). The vertical distribution of tropospheric tracers is very different for the two groups showing significantly more transport into the TTL for Group 1 related to the larger average values of the upward velocities. Nevertheless the low values for the Group 1 fluxes at and above the cold point level indicate that the model does not simulate significant overshooting. For stratospheric tracers, the differences between the two groups of parameterizations are small indicating that the downward transport from the stratosphere is more related to the turbulent mixing parameterization than to the convection parameterization. [ABSTRACT FROM AUTHOR]

It has previously been suspected that patients who undergo extensive dental procedures after having had a total joint arthroplasty (TJA) within the preceding 2 years may be at risk for seeding their TJA with infection if prophylaxis antibiotic coverage is not implemented one hour prior to the dental procedure. A review of the literature was performed to determine whether there may be other infections which may be accountable for TJA infections within the first 2 years following a TJA. Patients with systemic diseases, those who undergo extensive dental procedures, those with bladder or skin infection were found to be at risk for development of a TJA if prophylactic antibiotic therapy was not implemented in a timely manner. [ABSTRACT FROM AUTHOR]

Objectives Methodology Results Conclusions Common Variable Immunodeficiency Disorders (CVID) and Large Granular Lymphocytes leukemia (LGLL) exhibit diverse clinical manifestations including infections, dysimmunity, and lymphoproliferation. Recent decades have seen the discovery of new genes in the lymphopoiesis pathway, such as JAK–STAT. This case series supplemented by a literature review aims to describe clinical and biological characteristics of patients with both CIVD and LGLL.Patients were included through a call for comments to French and Belgian centers and through a literature review via PubMed. Clinical characteristics were compared to two large French cohort involving CVID and LGLL patients.Twelve patients were included. In all cases, CVID precedes LLGL (median diagnosis delay for LLGL was 7 years). Most cases presented with splenomegaly and autoimmune cytopenia. Ten out of 12 patients underwent splenectomy during follow up.Patients with LGLL and CVID differ from patients without immune deficiency in term of clinical presentation and prognosis. We suggest CVID may act as a trigger of LGL lymphocytosis, due to endogenous and exogenous antigenic pressure leading to the selection of a dominant LGL clone and stimulation of the JAK–STAT pathway. The role of splenomegaly and splenectomy in LGLL onset warrant further investigation in future studies. [ABSTRACT FROM AUTHOR]

Background: The experimental evaluation of young children's socio-emotional abilities is limited by the lack of existing specific measures to assess this population and by the relative difficulty for researchers to adapt measures designed for the general population., Methods: This study examined six early social-emotional abilities in 86 typically developing children aged 1 to 3 years using an eye-tracking-based experimental paradigm that combined visual preference tasks adapted from pre-existing infant studies., Objectives: The aim of this study is to obtain developmental norms in six early social-emotional abilities in typical children aged 1 to 3 years that would be promising for an understanding of disorders of mental development. These developmental standards are essential to enable comparative assessments with children with atypical development, such as children with Profound Intellectual and Multiple Disabilities (PIMD)., Results: The participants had greater spontaneous visual preferences for biological (vs. non-biological) motion, socially salient (vs. non-social) stimuli, the eye (vs. mouth) area of emotional expressions, angry (vs. happy) faces, and objects of joint attention (vs. non-looked-at ones). Interestingly, although the prosocial (vs. antisocial) scene of the socio-moral task was preferred, both the helper and hinderer characters were equally gazed at. Finally, correlational analyses revealed that performance was neither related to participants' age nor to each other (dismissing the hypothesis of a common underpinning process)., Conclusion: Our revised experimental paradigm is possible in infants aged 1 to 3 years and thus provides additional scientific proof on the direct assessment of these six socio-emotional abilities in this population.

Rationale: On the occasion of the General stage meeting of Internal Medicine, the National College of Internal Medicine Teachers (CEMI) conducted a survey on teaching activity among all French university hospital (HU) internal medicine specialists., Method: The survey was carried out in September 2023 by sending an email to 101 hospital practitioners university professors (PU-PH) and 18 hospital practitioners assistant professors (MCU-PH) of internal medicine in subsection 53-01 of the National council of universities (CNU), as well as to the 11 HU internists working in immunology (subsection 47-01) or therapeutics (subsection 48-04)., Results: Seventy-three HUs (56.1%) responded to the survey, including 65 PU-PH, 7 MCU-PH and 1 university hospital practitioner (PHU). Internal medicine HUs participate in faculty teaching: 80% are responsible for teaching, 30% are responsible for the year or cycle or lead committees and 40% have had or have an elected mandate at the faculty or at university. Internal medicine HU are involved in the teaching of semiology during the first cycle of medical studies, but also in pharmaceutical sciences, dentistry, midwifery and in paramedical training. They are very invested in the implementation of the second cycle reform and 80% are involved in the preparation of Objective Structured Clinical Examinations (ECOS), mainly as examiners (90%). They also participate in teaching using simulation (60%), teaching advanced practice nurses (IPA) (25%), and writing CEMI books (75%). For ECOS, 90% participate as examiners, 60% participate in teaching using simulation, 25% are involved in teaching advanced practice nurses (IPA), 75% participated in the writing of CEMI works. Eight (12%) internal medicine HUs co-facilitate training with patients and 26 (38%) participate in master's courses at the Faculty of Sciences. Finally, 94% are affiliated with a research unit and 48% supervise university theses students., Conclusion: Internal medicine universities teachers have a strong educational commitment, particularly in semiology and in the reform of the second cycle of medical studies with ECOS and simulation., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Background: Understanding the transmission dynamics of Mycobacterium tuberculosis (Mtb) could benefit the design of tuberculosis (TB) prevention and control strategies for refugee populations. Whole Genome Sequencing (WGS) has not yet been used to document the Mtb transmission dynamics among refugees in Ethiopia. We applied WGS to accurately identify transmission clusters and Mtb lineages among TB cases in refugee camps in Ethiopia., Method and Design: We conducted a cross-sectional study of 610 refugees in refugee camps in Ethiopia presenting with symptoms of TB. WGS data of 67 isolates was analyzed using the Maximum Accessible Genome for Mtb Analysis (MAGMA) pipeline; iTol and FigTree were used to visualize phylogenetic trees, lineages, and the presence of transmission clusters., Results: Mtb culture-positive refugees originated from South Sudan (52/67, 77.6%), Somalia (9/67, 13.4%). Eritrea (4/67, 6%), and Sudan (2/67, 3%). The majority (52, 77.6%) of the isolates belonged to Mtb lineage (L) 3, and one L9 was identified from a Somalian refugee. The vast majority (82%) of the isolates were pan-susceptible Mtb, and none were multi-drug-resistant (MDR)-TB. Based on the 5-single nucleotide polymorphisms cutoff, we identified eight potential transmission clusters containing 23.9% of the isolates. Contact investigation confirmed epidemiological links with either family or social interaction within the refugee camps or with neighboring refugee camps., Conclusion: Four lineages (L1, L3, L4, and L9) were identified, with the majority of strains being L3, reflecting the Mtb L3 dominance in South Sudan, where the majority of refugees originated from. Recent transmission among refugees was relatively low (24%), likely due to the short study period. The improved understanding of the Mtb transmission dynamics using WGS in refugee camps could assist in designing effective TB control programs for refugees., Competing Interests: Declaration of Competing Interest We declare that there is no conflict of interest that might have influenced the performance and presentation of the work described in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The emergence of rituximab biosimilars offers the prospect of significant savings to the healthcare system. However, these drugs have never been evaluated for treating immune thrombocytopenia (ITP). This was an observational, matched study. We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from the historic ITP-ritux registry. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. Response status was defined according to international criteria. We included 107 patients; 55 receiving Rixathon™ and 52 Truxima™. Three months after the first infusion of rituximab biosimilars, the overall response rate was 47/74 (63.5%) versus 76/142 (53.5%) for the matched controls receiving the reference product ( p  = .13). The 3-month overall response rate was 76.5% for Rixathon™ versus 51.5% for the matched control group ( p  = .01) and 21/40 (52.5%) for Truxima™ versus 41/74 (55.4%) for the matched controls ( p  = .81). For non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. Rituximab biosimilars seemed safe and effective for ITP treatment.

Antioxidant actions of melatonin and its impact on testicular function and fertility have already been described. Considering that Sertoli cells contribute to provide structural support and nutrition to germ cells, we evaluated the effect of melatonin on oxidative state and lactate metabolism in the immature murine TM4 cell line and in immature hamster Sertoli cells. A prooxidant stimulus applied to rodent Sertoli cells expressing MT1/MT2 receptors, increased lipid peroxidation whereas decreased antioxidant enzymes (superoxide dismutase 1, catalase, peroxiredoxin 1) expression and catalase activity. These changes were prevented by melatonin. Furthermore, melatonin stimulated lactate dehydrogenase (LDH) expression/activity via melatonin receptors, and increased intracellular lactate production in rodent Sertoli cells. Interestingly, oral melatonin supplementation in infertile men positively regulated LDHA testicular mRNA expression. Overall, our work provides insights into the potential benefits of melatonin on Sertoli cells contributing to testicular development and the future establishment of a sustainable spermatogenesis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Peritubular myoid cells are emerging as key regulators of testicular function in adulthood. However, little is known about the role of testicular peritubular myoid cells (TPMCs) in the development of the male gonad. We found that, compared to testes of young adult hamsters, gonads of 21 day-old animals show increased melatonin concentration, seminiferous tubular wall thickening and a heterogeneous packaging of its collagen fibers thus raising the question whether melatonin may be involved in the regulation of TPMCs., Methods: We established primary cultures of TPMCs from immature hamsters (ihaTPMCs), which we found express melatonergic receptors., Results: Exogeneous melatonin decreased the levels of inflammatory markers (NLRP3 inflammasome, IL1β) but increased the expression of cyclooxygenase 2 (COX2, key enzyme mediating prostaglandin synthesis) and of the glial cell line-derived neurotrophic factor (GDNF) in ihaTPMCs. Melatonin also stimulated ihaTPMCs proliferation and the expression of extracellular matrix proteins such as collagen type I and IV. Furthermore, collagen gel contraction assays revealed an enhanced ability of ihaTPMCs to contract in the presence of melatonin., Conclusion: Melatonin regulates immune and inflammatory functions as well as contractile phenotype of the peritubular wall in the hamster testis., General Significance: If transferable to the in vivo situation, melatonin-dependent induction of ihaTPMCs to produce factors known to exert paracrine effects in other somatic cell populations of the gonad suggests that the influence of melatonin may go beyond the peritubular wall and indicates its contribution to testicular development and the establishment of a normal and sustainable spermatogenesis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Mast cells are key players in innate immunity and the T H 2 adaptive immune response. The latter counterbalances the T H 1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published., Objective: To study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting., Methods: Clinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti-SARS-CoV-2-specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies., Results: Overall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2-specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2-specific, IFN-γ-producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden)., Conclusions: Patients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ., (Copyright © 2022. Published by Elsevier Inc.)

Objective: IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer., Methods: We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study., Results: Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p < 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p < 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p < 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p < 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV., Conclusion: Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.

We have previously shown an inverse correlation between testicular melatonin concentration and inflammation/oxidative stress-related markers levels in infertile men showing unexplained azoospermia. Here, we evaluated the impact of melatonin oral supplementation (daily 3 mg dose used to treat sleep disorders) in the incidence of local inflammation, oxidative stress, and tubular wall fibrosis development in young and middle-aged infertile adult men. Compared with testes without histological alterations, gonads with morphological abnormalities showed lower melatonin concentration along with increased macrophage numbers, TBARS generation, and expression levels of inflammation-related markers and antioxidant enzymes, as well as tubular wall collagen fibers disorganization and thickening. Melatonin oral supplementation not only increased its own testicular levels but also decreased inflammation- and oxidative stress-related markers levels, and improved the tubular wall aspect. Overall, our work provides insights into the potential benefits of melatonin on the inflammatory and oxidative status in testes of patients suffering from unexplained infertility., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The ability of clinical algorithms to identify tuberculosis disease and the impact of empiric treatment on survival in people with a negative Xpert MTB/RIF (Xpert) result remains poorly documented., Methods: Hospitalized Xpert-negative patients (125 initiated on empiric tuberculosis treatment based on a clinical algorithm and 125 in whom tuberculosis treatment was not started) were enrolled. Sputum samples were evaluated for Mycobacterium tuberculosis by culture. All study participants were followed up for 6 months., Results: Xpert-negative inpatients in whom empiric tuberculosis treatment was initiated were more likely to have microbiological confirmed tuberculosis compared to those in whom empiric tuberculosis treatment was not started (24.8% vs 6.4%, p=0.0001). Six-month risk of death was 5.2%, but the risk was twice as high in people with bacteriological confirmation of TB (10.3% vs 4.3%, p=0.12). Cardinal symptoms of TB were associated with bacteriological confirmation and a decision to start empiric treatment. The positive predictive value of the clinical algorithm was 24.8% and empiric treatment did not affect 6-month risk of death (5.6% vs 4.8%, p=0.78)., Conclusions: Clinical algorithm identifies the majority of confirmed tuberculosis cases among Xpert-negative inpatients. Empiric treatment did not impact survival and resulted in substantial overtreatment. The more sensitive Xpert Ultra assay should be used to eliminate the need for empiric tuberculosis treatment., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Catecholaminergic neuronal elements (CNE) and macrophages (MACs) are increased in testes of patients with idiopathic infertility. Now, we describe an anatomical proximity between CNE and MACs, expression of specific α- and β-adrenergic receptors (ADRs) subtypes in MACs, and a positive correlation between the number of MACs and cyclooxygenase (COX2) expression - key enzyme in prostaglandin (PG) synthesis and an inflammatory marker - in testes of infertile men. To examine a potential effect of adrenergic input on COX2 expression, we used two additional experimental models: non-testicular human MACs (THP1 cell line) and non-human testicular MACs purified from adult Syrian hamsters. We found that epinephrine and norepinephrine up-regulate COX2 expression and PGD2 production through β1-and β2-ADRs. Our results demonstrate the existence of a yet unknown link between CNE and MACs in the human testis that could trigger inflammation and tissue homeostatic dysregulation associated with pathogenesis or maintenance of infertility states., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This review aims to increase understanding of health decision-making by children and adolescents with chronic illnesses and offer suggestions for improving shared decision-making with healthcare professionals., Methods: Using cross-disciplinary publication databases, we surveyed literature on children's and adolescents' health decision-making from psychology, health sciences, and neuroscience., Results: Several factors influencing health decision-making were identified. Considering neurobiological aspects, children lack functionality in the frontal lobe resulting in lesser cognitive control and higher risk-taking compared to adults. Additionally, adolescents' generally higher arousal of socioemotional systems demonstrates neurological underpinnings for reward-seeking behaviours. Psychological investigations of children's health decision-making indicate important age-dependent differences in risk-taking, locus of control, affect and cognitive biases. Furthermore, social influences, particularly from peers, have a large, often negative, effect on individual decision-making due to desire for peer acceptance., Conclusion: Acknowledging these factors is necessary for optimising the process of shared decision-making to support minors with chronic illnesses during healthcare consultations., Practice Implications: Doctors and other healthcare professionals may need to counteract some adolescents' risk-taking behaviours which are often spurred by peer pressure. This can be achieved by highlighting the patient's control over health outcomes, emphasising short-term benefits and long-term consequences of risky behaviours, and recommending peer support networks., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the present work, two new copper complexes 3a and 3b with a Cu 4 O 4 cubane core are reported. Both complexes are obtained by means of the in situ conversion of the imine functionality of Schiff's base ligands 1a [(E)-4-chloro-2-((thiazol-2-ylimino)methyl)phenol] and 1b [(E)-4-bromo-2-((thiazol-2-ylimino)methyl)phenol] into amino alcohols 2a (4-chloro-2-(hydroxy(thiazol-2-ylamino)methyl)phenol) and 2b (4-bromo-2-(hydroxy(thiazol-2-ylamino)methyl)phenol), respectively. The ligand transformation may be metal assisted and the generated ligands show an interesting mode of coordination in which the alkoxo-O atom binds in a μ 3 -manner connecting simultaneously three copper centers and forming a Cu 4 O 4 cubane core. The first analysis of single crystal X-ray diffraction studies reveals that both molecules possess a [4 + 2] cubane-type core, and low temperature magnetic measurements show antiferromagnetic behaviour, in agreement with DFT calculations. However, the best fit and DFT calculations point out three pairs of coupling constants, more coherent with a [2 + 2 + 2] situation, in accordance with the fine analysis of structural data. Finally, phenoxazinone synthase activity has been measured for both molecules, finding k cat = 86.3 h -1 for the chloride derivative copper(ii) complex in methanol, whereas the bromide derivative copper(ii) complex displays k cat = 3.4026 × 10 2 h -1 and 10.289 × 10 2 h -1 in methanol and DMSO, respectively.

Background: In thrombotic thrombocytopenic purpura (TTP), platelet (PLT) transfusion is contraindicated unless a life-threatening hemorrhage occurs. However, when PLT count is low (<20 × 10(9) /L), their benefit-risk balance before central venous catheter (CVC) insertion for plasma exchange (PE) has not specifically been addressed in guidelines., Case Reports: We report two cases in which PLTs were transfused before CVC insertion for PE, resulting in fatal myocardial infarction or neurologic complications., Discussion: To date, there is a paucity of high-quality, evidence-based information on prophylactic PLT transfusion for CVC placement in TTP. Several monocenter series report that CVC could be inserted safely without PLT transfusion by experienced teams under ultrasound guidance. Uncertainty makes most physicians uncomfortable with this decision and this is a common reason why PLT transfusion remains a "precautionary" albeit misguided position., Conclusion: We propose a practical algorithm to avoid unnecessary PLT transfusion before CVC insertion for rapid PE in the initial management of TTP patients. We recommend no prophylactic PLT transfusion but CVC insertion in a compressible vein under ultrasound guidance by an experienced team or quick PE started on two peripheral veins if possible. PLTs should only be transfused in case of severe bleeding in association with plasma infusion and CVC insertion for immediate PE., (© 2015 AABB.)

Introduction: Hypoxemia is a decrease in blood oxygen partial pressure. This work aims at presenting a practical conduct for patients with a lonely hypoxemia at rest or during exercise, defined by the absence of dyspnea at rest, obvious clinical or radiographic abnormality., State of the Art: Diagnostic tools available to the clinician are clinical examination, CT scan, echocardiography, hyperoxia test, trans cranial ultrasound and lung scintigraphy. This work proposes a practical diagnostic approach, with a main role of chest CT., Perspectives: Work is underway to determine more precisely the place of echocardiography for the diagnosis of intra or extra cardiac shunts., Conclusions: The finding of a lonely hypoxemia requires careful diagnostic approach to quickly rule out potentially serious causes and not to disregard the rare causes., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

A family of lanthanide complexes has been synthesized by the subcomponent self-assembly methodology. Molecular architectures, which were stable in solution and under ambient conditions, were designed by the in situ formation of ligands around lanthanide ion templates. Magnetic studies indicated that, despite the low C2 symmetry, 1 and 2 display single molecule magnet (SMM) behavior, with 1 exhibiting an effective energy barrier of the relaxation of the magnetization U(eff)/k(B) = 50 K and the pre-exponential factor τ(o) = 6.80 × 10(-7) s. Step-like features in the hysteresis loops indicate the presence of quantum tunneling of the magnetization (QTM).