Dietary Fiber Confers Protection against Flu by Shaping Ly6c- Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism.

Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two complementary mechanisms. High-fiber diet (HFD)-fed mice exhibited altered bone marrow hematopoiesis, characterized by enhanced generation of Ly6c- patrolling monocytes, which led to increased numbers of alternatively activated macrophages with a limited capacity to produce the chemokine CXCL1 in the airways. Blunted CXCL1 production reduced neutrophil recruitment to the airways, thus limiting tissue immunopathology during infection. In parallel, diet-derived SCFAs boosted CD8+ T cell effector function by enhancing cellular metabolism. Hence, dietary fermentable fiber and SCFAs set an immune equilibrium, balancing innate and adaptive immunity so as to promote the resolution of influenza infection while preventing immune-associated pathology.

Clinically relevant mouse models of Charcot-Marie-Tooth type 2S.

Charcot-Marie-Tooth disease is an inherited peripheral neuropathy that is clinically and genetically heterogenous. Mutations in IGHMBP2, a ubiquitously expressed DNA/RNA helicase, have been shown to cause the infantile motor neuron disease spinal muscular atrophy with respiratory distress type 1 (SMARD1), and, more recently, juvenile-onset Charcot-Marie-Tooth disease type 2S (CMT2S). Using CRISPR-cas9 mutagenesis, we developed the first mouse models of CMT2S [p.Glu365del (E365del) and p.Tyr918Cys (Y918C)]. E365del is the first CMT2S mouse model to be discovered and Y918C is the first human CMT2S allele knock-in model. Phenotypic characterization of the homozygous models found progressive peripheral motor and sensory axonal degeneration. Neuromuscular and locomotor assays indicate that both E365del and Y918C mice have motor deficits, while neurobehavioral characterization of sensory function found that E365del mutants have mechanical allodynia. Analysis of femoral motor and sensory nerves identified axonal degeneration, which does not impact nerve conduction velocities in E365del mice, but it does so in the Y918C model. Based on these results, the E365del mutant mouse, and the human allele knock-in, Y918C, represent mouse models with the hallmark phenotypes of CMT2S, which will be critical for understanding the pathogenic mechanisms of IGHMBP2. These mice will complement existing Ighmbp2 alleles modeling SMARD1 to help understand the complex phenotypic and genotypic heterogeneity that is observed in patients with IGHMBP2 variants.

Direct visualization of polaron formation in the thermoelectric SnSe.

SnSe is a layered material that currently holds the record for bulk thermoelectric efficiency. The primary determinant of this high efficiency is thought to be the anomalously low thermal conductivity resulting from strong anharmonic coupling within the phonon system. Here we show that the nature of the carrier system in SnSe is also determined by strong coupling to phonons by directly visualizing polaron formation in the material. We employ ultrafast electron diffraction and diffuse scattering to track the response of phonons in both momentum and time to the photodoping of free carriers across the bandgap, observing the bimodal and anisotropic lattice distortions that drive carrier localization. Relatively large (18.7 Å), quasi-one-dimensional (1D) polarons are formed on the 300-fs timescale with smaller (4.2 Å) 3D polarons taking an order of magnitude longer (4 ps) to form. This difference appears to be a consequence of the profoundly anisotropic electron-phonon coupling in SnSe, with strong Fröhlich coupling only to zone-center polar optical phonons. These results demonstrate a high density of polarons in SnSe at optimal doping levels. Strong electron-phonon coupling is critical to the thermoelectric performance of this benchmark material and, potentially, high performance thermoelectrics more generally.

Functioning and neurocognition in very early and early-life onset bipolar disorders: the moderating role of bipolar disorder type.

Defining homogeneous subgroups of bipolar disorder (BD) is a major goal in personalized psychiatry and research. According to the neurodevelopmental theory, age at onset may be a key variable. As potential trait markers of neurodevelopment, cognitive and functional impairment should be greater in the early form of the disease, particularly type 1 BD (BD I). The age at onset was assessed in a multicenter, observational sample of 4190 outpatients with BD. We used a battery of neuropsychological tests to assess six domains of cognition. Functioning was measured using the Functioning Assessment Short Test (FAST). We studied the potential moderation of the type of BD on the associations between the age at onset and cognitive and functioning in a subsample of 2072 euthymic participants, controlling for potential clinical and socio-demographic covariates. Multivariable analyses showed cognition to not be impaired in individuals with early (21-30 years) and very early-life (before 14 years) onset of BD. Functioning was equivalent between individuals with early and midlife-onset of BD II and NOS but better for individuals with early onset of BD I. In contrast, functioning was not worse in individuals with very early-onset BD I but worse in those with very early-onset BD II and NOS. Early-life onset BDs were not characterized by poorer cognition and functioning. Our results do not support the neurodevelopmental view that a worse cognitive prognosis characterizes early-life onset BD. This study suggests that functional remediation may be prioritized for individuals with midlife-onset BD I and very early life onset BD 2 and NOS.

Direct View of Phonon Dynamics in Atomically Thin MoS2.

Transition-metal dichalcogenide monolayers and heterostructures are highly tunable material systems that provide excellent models for physical phenomena at the two-dimensional (2D) limit. While most studies to date have focused on electrons and electron-hole pairs, phonons also play essential roles. Here, we apply ultrafast electron diffraction and diffuse scattering to directly quantify, with time and momentum resolution, electron-phonon coupling (EPC) in monolayer molybdenum disulfide and phonon transport from the monolayer to a silicon nitride substrate. Optically generated hot carriers result in a profoundly anisotropic distribution of phonons in the monolayer within ∼5 ps. A quantitative comparison with ab initio ultrafast dynamics simulations reveals the essential role of dielectric screening in weakening EPC. Thermal transport from the monolayer to the substrate occurs with the phonon system far from equilibrium. While screening in 2D is known to strongly affect equilibrium properties, our findings extend this understanding to the dynamic regime.

Closed reduction and fluoroscopic-guided percutaneous pinning of femoral capital physeal or neck fractures: Thirteen fractures in 11 dogs.

OBJECTIVES: To report the short-term clinical outcome and complications in dogs that underwent surgical repair of femoral capital physeal or neck fractures via fluoroscopic-guided percutaneous pinning (FGPP). STUDY DESIGN: Retrospective case series. ANIMALS: Client owned dogs (n = 11) with femoral capital physeal or neck fractures (n = 13). METHODS: Records (July 2018-July 2021) of dogs that underwent surgery for femoral capital physeal or neck fracture repair with FGPP from two hospitals were reviewed. Data collected included signalment, age, weight, preoperative lameness severity, fracture factors (etiology, Salter-Harris classification, time from injury to surgery, radiographic displacement), surgical factors (surgery time, number/size of implants, reduction quality) and outcome (follow-up examination findings, radiographic findings, complications). RESULTS: Most fractures (11/13) occurred secondary to trauma. The median time from injury to surgery was 5.5 days. There was mild radiographic displacement preoperatively in 10/13 fractures. Satisfactory fracture healing and limb function was achieved in 10/13 femurs. Complications occurred in 5/11 cases and included intra-articular implants, implant failure/nonunion, implant migration (2), and malunion. Of these five complications, two resolved with implant removal, and a salvage procedure was recommended in the remaining cases. Of the three cases requiring salvage procedures, two originally presented with radiographic evidence of fracture chronicity. CONCLUSIONS: FGPP can be used to successfully treat femoral head and neck fractures with appropriate case selection and precise surgical technique.

The impact of orthostatic intolerance on early ambulation following abdominal surgery in an enhanced recovery programme.

BACKGROUND: The prevalence of orthostatic intolerance on the day of surgery is more than 50% after abdominal surgery. The impact of orthostatic intolerance on ambulation on the day of surgery has been little studied. We investigated orthostatic intolerance and walking ability after colorectal and bariatric surgery in an enhanced recovery programme. METHODS: Eighty-two patients (colorectal: n = 46, bariatric n = 36) were included and analysed in this prospective study. Walk tests for 2 min (2-MWT) and 6 min (6-MWT) were performed before and 24 h after surgery, and 3 h after surgery for 2-MWT. Orthostatic intolerance characterised by presyncopal symptoms when rising was recorded at the same time points. Multivariate binary logistic regressions modelling the probability of orthostatic intolerance and walking inability were performed taking into account potential risk factors. RESULTS: Prevalence of orthostatic intolerance and walking inability was, respectively, 65% and 18% 3-hour after surgery. The day after surgery, patients' performance had greatly improved: approximately 20% of the patients experienced orthostatic intolerance, whilst only 5% of the patients were unable to walk. Adjusted binary logistic regressions demonstrated that age (p = .37), sex (p = .39), BMI (p = .74), duration of anaesthesia (p = .71) and type of surgery (p = .71) did not significantly influence walking ability. CONCLUSION: Our study confirms that orthostatic intolerance was frequent (~ 60%) 3-hour after abdominal surgery but prevented a 2-MWT only in ~20% of patients. No risk factors for orthostatic intolerance and walking inability were evidenced.

How optical excitation controls the structure and properties of vanadium dioxide.

We combine ultrafast electron diffraction and time-resolved terahertz spectroscopy measurements to link structure and electronic transport properties during the photoinduced insulator-metal transitions in vanadium dioxide. We determine the structure of the metastable monoclinic metal phase, which exhibits antiferroelectric charge order arising from a thermally activated, orbital-selective phase transition in the electron system. The relative contribution of the photoinduced monoclinic and rutile metals to the time-dependent and pump-fluence-dependent multiphase character of the film is established, as is the respective impact of these two distinct phase transitions on the observed changes in terahertz conductivity. Our results represent an important example of how light can control the properties of strongly correlated materials and demonstrate that multimodal experiments are essential when seeking a detailed connection between ultrafast changes in optical-electronic properties and lattice structure.

Microbiome-induced antigen-presenting cell recruitment coordinates skin and lung allergic inflammation.

BACKGROUND: Allergic skin inflammation often presents in early childhood; however, little is known about the events leading to its initiation and whether it is transient or long-term in nature. OBJECTIVE: We sought to determine the immunologic rules that govern skin inflammation in early life. METHODS: Neonatal and adult mice were epicutaneously sensitized with allergen followed by airway allergen challenge. Epicutaneous application of labeled allergen allowed for determination of antigen uptake and processing by antigen-presenting cells. RNAseq and microbiome analysis was performed on skin from neonatal and adult specific pathogen-free and germ-free mice. RESULTS: A mixed TH2/TH17 inflammatory response in the skin and the lungs of adult mice was observed following sensitization and challenge. Comparatively, neonatal mice did not develop overt skin inflammation, but exhibited systemic release of IL-17a and a TH2-dominated lung response. Mechanical skin barrier disruption was not sufficient to drive allergic skin inflammation, although it did promote systemic immune priming. Skin of neonatal mice and adult germ-free mice was seeded with low numbers of antigen-presenting cells and impaired chemokine and alarmin production. Enhanced chemokine and alarmin production, and seeding of the skin with antigen-presenting cells capable of instructing recruited cells to elicit their effector function, was, at least in part, dependent on formation of the microbiome, and consequently contributed to the development of overt skin disease. CONCLUSIONS: These data shed light on the principles that underlie allergic inflammation in different tissues and highlight a window of opportunity that might exist for early-life prevention of allergic diseases.

Swiss Recommendations for the Follow-Up and Treatment of Pulmonary Long COVID.

INTRODUCTION: Emerging evidence suggests that long-term pulmonary symptoms and functional impairment occurs in a proportion of individuals following SARS-CoV-2 infection. Although the proportion of affected patients remains to be determined, physicians are increasingly being confronted with patients reporting respiratory symptoms and impairment beyond the acute phase of COVID-19. In face of limited evidence, the Swiss Society for Pulmonology established a working group to address this area of unmet need and formulated diagnostic and treatment recommendations for the care of patients with pulmonary long COVID (LC). METHOD: The Swiss COVID Lung Study group and Swiss Society for Pulmonology (SSP) formulated 13 questions addressing the diagnosis and treatment of pulmonary LC. A survey within the SSP special interest groups involved in care of LC patients was conducted in Switzerland. A CORE process/Delphi-like process was used to formulate recommendations. Forty experienced pulmonologists replied to the first survey and 22 completed the second follow-up survey. Agreement of ≥70% consensus led to formulation of a recommendation. RESULTS: The participants in the survey reached consensus and formulated a strong recommendation for regarding the following points. Patients hospitalized for COVID-19 should have a pulmonary assessment including pulmonary function tests. Symptomatic subjects affected by COVID-19, including those with mild disease, should benefit from a pulmonary follow-up. Persistent respiratory symptoms after COVID-19 should be investigated by a pulmonary follow-up including plethysmography, diffusion capacity measurement, and blood gases analysis. Individuals having suffered from COVID-19 and who present with persistent respiratory symptoms should be offered a rehabilitation. Additional questions were given moderateor weak recommendations for. The panel did not reach sufficient consensus for pharmacological therapy (e.g., therapy specifically targeting lung fibrosis) to formulate recommendations for LC drug treatment. CONCLUSION: The formulated recommendations should serve as an interim guidance to facilitate diagnosis and treatment of patients with pulmonary LC. As new evidence emerges, these recommendations may need to be adapted.

Immunotherapy-Induced Airway Disease: A New Pattern of Lung Toxicity of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

Rumen function in goats, an example of adaptive capacity.

The aim of this Research Reflection is to describe the basic rumen function of goats and its modification in response to environmental factors, as well as to discuss similarities and differences when compared to other ruminants. In so doing we shall reveal the adaptive capacity of goats to harsh environments. The basic rumen function in goats is similar to other species of ruminants, as stressed by the opportunity to apply the updates of feeding systems for ruminants to goats. The rumen epithelium acts as a protective barrier between the rumen and the host, but it can be damaged by toxic compounds or acidosis. The rumen also plays an important role in water balance, both for dehydration and rehydration. Recent studies show that the microbiota exhibits a high fractional stability due to functional redundancy and resilience, but this needs more investigation. The microbial community structure differs between goats and cows, which explains the difference in sensitivity to milk fat depression following intake of high lipid diets. Goats also differ from other ruminants by their enhanced ability to feed-sort, but as with cows they can suffer from acidosis. Nevertheless, goats can be considered to be very resistant to environmental factors such as water stress, salt stress or heat stress, and this is especially so in some endogenous breeds. They also are able to detoxify tannins, polyphenols and other secondary metabolites. Some new trials involving feeding behaviour, microbiota and omics or approaches by meta-analyses or modelling will improve our knowledge of rumen function in goats.

Total hip replacement in dogs with contralateral pelvic limb amputation: A retrospective evaluation of 13 cases.

OBJECTIVE: To report the clinical characteristics, surgical management, and medium-term outcomes of total hip replacement (THR) performed in dogs with previous contralateral pelvic limb amputation. ANIMALS: Thirteen client-owned dogs. STUDY DESIGN: Multi-institutional retrospective clinical study. METHODS: Data recorded from medical records included signalment, indication for amputation and THR, and surgical complications. Implant positioning and complications were assessed on radiographs. Clinical outcomes were evaluated during follow-up examinations by one of the authors and through a mobility- and lifestyle-based questionnaire completed by owners. RESULTS: All 13 dogs had satisfactory clinical results at follow-up a median of 3 months (range, 2-36) after THR. No postoperative luxation was recorded. Four dogs had minor complications that did not require additional treatment. The only major complication was one failure of osseointegration of a cementless acetabular cup, and it was successfully revised. CONCLUSION: Total hip replacement resulted in satisfactory clinical results and acceptable morbidity in this population. CLINICAL SIGNIFICANCE: Total hip replacement should be considered in dogs with severe coxofemoral joint disease and contralateral pelvic limb amputation.

Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung.

BACKGROUND: Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. OBJECTIVE: This study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation. METHODS: Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture. RESULTS: We identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition. CONCLUSIONS: Host-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome.

Minimally invasive percutaneous medial plate rod osteosynthesis for treatment of bicondylar humeral fractures in dogs: Surgical technique and case report.

OBJECTIVE: To describe a minimally invasive surgical technique for the treatment of comminuted humeral bicondylar (also known as T-Y) fractures in dogs and report outcome in 3 cases. STUDY DESIGN: Surgical technique description and case report. ANIMALS: Three consecutive dogs with traumatic comminuted humeral T-Y fractures. METHODS: Dogs that presented with a traumatic humeral T-Y fracture were prospectively included. The condylar component of the fractures was reduced first by using a combination of percutaneous forceps and K-wires. A transcondylar screw was applied, and epicondylar pins were preplaced medially and laterally. The metaphyseal component of the fracture was then reduced and stabilized with the pins. Finally, a bone plate was applied percutaneously along the medial humeral surface. Intraoperative fluoroscopy was used throughout surgery in all cases. Postoperative alignment in the frontal and sagittal planes was compared to the contralateral limbs. Time to clinical union, clinical outcome, and complications were recorded. RESULTS: Three dogs were included. Body weight ranged from 5.9 to 40 kg. Incomplete ossification of the humeral condyle was identified as the primary pathology leading to the fracture in 2 cases. All cases experienced uncomplicated healing with good to excellent functional recovery. CONCLUSION: The reported technique was associated with good outcomes without complications in 3 cases. CLINICAL SIGNIFICANCE: This study provides evidence that minimally invasive plate osteosynthesis represents an alternative to open reduction and internal fixation in the treatment of comminuted humeral T-Y fractures.

Minimally invasive percutaneous medial plate-rod osteosynthesis for treatment of humeral shaft fractures in dog and cats: Surgical technique and prospective evaluation.

OBJECTIVE: To describe and prospectively report outcomes associated with a novel minimally invasive percutaneous osteosynthesis (MIPO) technique for the treatment of humeral fractures in dogs and cats. STUDY DESIGN: Prospective clinical case series. ANIMALS: Eleven dogs and 4 cats with traumatic nonarticular humeral fractures. METHODS: Dogs and cats that presented with traumatic humeral fractures were enrolled in the study. After closed reduction, the fracture was stabilized by using a plate-rod combination applied via remote medial incisions. Postoperative alignment in the frontal and sagittal planes was statistically compared with the contralateral limbs. Time to clinical union and complications were also recorded. RESULTS: Eleven dogs and 4 cats were included in this study. Body weight ranged from 4.5 to 33.6 kg in dogs and from 2.2 to 3.6 kg in cats. A veterinary cuttable plate (6/11 dogs and 3/4 cats) or locking compression plate was used in a plate-rod configuration (11/11 dogs and 2/4 cats) or alone (2/4 cats). Rod-to-medullary-cavity ratio was 30%. Plate-span ratio was 5.8 (range, 2-13.5). No significant differences were found in frontal or sagittal plane alignment. Healing time in cases that completed on-time follow-up (12/15) was 36 ± 14 days (range, 20-69). No major complications were recorded. CONCLUSION: The reported technique was associated with good outcomes in a large variety of fracture configurations and animal sizes, with no complications. CLINICAL SIGNIFICANCE: This report provides evidence that MIPO is a compelling alternative to open reduction and internal fixation in the treatment of various humeral fractures.

[Lower limb postoperative analgesia evolution : Time for sensitive blocks]. / Evolution de l'analgésie après chirurgie du membre inférieur. La place des blocs sensitifs.

For about twenty years, peripheral nervous blocks have become the gold standard in postoperative analgesia for knee and foot surgery. The development of echography adapted to anesthesia gave anesthesiologists the opportunity to perform distal, mostly sensitive nerve blocks. Proximal nervous blocks associated analgesia used to be better than general (intravenous or oral) analgesia. Most of all it was associated with fewer side effects (nauseas, vomiting, drowsiness…). They reached an analgesia level comparable to central nerve blocks (epidural) with also fewer side effects (hypotension, bradycardia, lateralization...). A main problem with those blocks was that they involved motor blockade, impeding fast revalidation and walking restart. Distal nerve blocks, without motor blockade, offer as efficient analgesia as produced by proximal nerve blocks, without impeding motricity. Using those new techniques, it is now possible, with optimal analgesia, to allow almost immediate walking after a total knee replacement, and to perform most surgical foot operations in a one-day procedure.

Depuis une vingtaine d'années, les blocs nerveux périphériques sont devenus les techniques de choix pour l'analgésie de la chirurgie osseuse du genou et du pied. L'avènement de l'échographie adaptée à l'anesthésie permet désormais la réalisation de blocs nerveux distaux essentiellement sensitifs. Les blocs périphériques proximaux offraient une antalgie supérieure par rapport à l'antalgie intraveineuse ou per os traditionnelle, avec moins d'effets secondaires généraux (nausées, vomissements, somnolence…). Ils procuraient une antalgie semblable aux blocs centraux (épidurale en particulier), avec beaucoup moins d'effets secondaires (hypotension, bradycardie, latéralisation). Le défaut principal de ces blocs est qu'ils s'accompagnaient de blocs moteurs, constituant un obstacle à la rééducation rapide et à la reprise de la marche. La réalisation de blocs distaux, dépourvus d'effet moteur permet d'obtenir une antalgie aussi efficace que les celle des blocs proximaux, mais sans entraver la motricité. Grâce au développement de ces techniques, il est désormais possible, avec une antalgie optimale, de permettre la reprise quasi immédiate de la marche après mise en place d'une prothèse de genou, et de pratiquer la majorité de la chirurgie du pied en hôpital de jour.

B Cell-Specific Expression of Ataxia-Telangiectasia Mutated Protein Kinase Promotes Chronic Gammaherpesvirus Infection.

Manipulation of host cellular pathways is a strategy employed by gammaherpesviruses, including mouse gammaherpesvirus 68 (MHV68), in order to negotiate a chronic infection. Ataxia-telangiectasia mutated (ATM) plays a unique yet incompletely understood role in gammaherpesvirus infection, as it has both proviral and antiviral effects. Chronic gammaherpesvirus infection is poorly controlled in a host with global ATM insufficiency, whether the host is a mouse or a human. In contrast, ATM facilitates replication, reactivation, and latency establishment of several gammaherpesviruses in vitro, suggesting that ATM is proviral in the context of infected cell cultures. The proviral role of ATM is also evident in vivo, as myeloid-specific ATM expression facilitates MHV68 reactivation during the establishment of viral latency. In order to better understand the complex relationship between host ATM and gammaherpesvirus infection, we depleted ATM specifically in B cells, a cell type critical for chronic gammaherpesvirus infection. B cell-specific ATM deficiency attenuated the establishment of viral latency due to compromised differentiation of ATM-deficient B cells. Further, we found that during long-term infection, peritoneal B-1b, but not related B-1a, B cells display the highest frequency of gammaherpesvirus infection. While ATM expression did not affect gammaherpesvirus tropism for B-1 B cells, B cell-specific ATM expression was necessary to support viral reactivation from peritoneal cells during long-term infection. Thus, our study reveals a role of ATM as a host factor that promotes chronic gammaherpesvirus infection of B cells.IMPORTANCE Gammaherpesviruses infect a majority of the human population and are associated with cancer, including B cell lymphomas. ATM is a unique host kinase that has both proviral and antiviral roles in the context of gammaherpesvirus infection. Further, there is insufficient understanding of the interplay of these roles in vivo during chronic infection. In this study, we show that ATM expression by splenic B cells is required for efficient establishment of gammaherpesvirus latency. We also show that ATM expression by peritoneal B cells is required to facilitate viral reactivation during long-term infection. Thus, our study defines a proviral role of B cell-specific ATM expression during chronic gammaherpesvirus infection.

GLI 2012 equations define few spirometric anomalies in the general population: the PneumoLaus study.

BACKGROUND: Reduced lung function predicts increased mortality, but its prevalence may vary depending on definition considered, use of bronchodilation and applied reference values. We aimed to assess lung function abnormalities in Lausanne, Switzerland, and their association with clinical history. METHODS: In a general population sample, spirometry was performed and bronchodilation applied if the ratio forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) or the FVC was below the lower limit of normal (LLN) according to Global Lung Function Initiative 2012 references. Results for FEV1/FVC according to the LLN were compared to the 0.7 fixed ratio. Respiratory risk factors, symptoms and self-reported respiratory diagnoses were recorded through a questionnaire. RESULTS: Out of the 3342 included subjects, 3.8% had chronic obstruction and 2.5% reversible obstruction when using the LLN; possible lung restriction alone was present in 1.8%, and associated with chronic obstruction in 0.4%. Ever smokers had a higher prevalence of abnormal spirometry, chronic obstruction and reversible obstruction; there was no difference with regard to possible restriction. Overall, chronic airway obstruction was found in 8.9% of current smokers, 4.6% of former smokers and 1.5% of never smokers. Only one third of participants with chronic obstruction were aware of a respiratory disease. CONCLUSION: Prevalence of abnormal lung function in the population of Lausanne is low. This may be due to a low rate of ever-smokers, the application of a full bronchodilation dose, but also to inherent characteristics of this population.

Diagnosis and Management of Asthma - The Swiss Guidelines.

The Global Initiative for Asthma (GINA) is a network of individuals, organizations, and public health officials that was established to disseminate information about the care of patients with asthma and to improve asthma care. The GINA ("Global Strategy for Asthma Management and Prevention") report has been updated annually since 2002. Due to new knowledge and therapeutic development in the field, the Swiss Respiratory Society felt the need to provide a new document that is based on both the available literature and the recommendations of the 2016 GINA report. Key new features of the 2016 GINA report include a "new" definition of asthma, underscoring its heterogeneous nature, and the core elements of variable symptoms and variable expiratory airflow limitation; the importance of confirming the diagnosis of asthma in order to minimize both under- and overtreatment; practical tools for the assessment of symptom control and risk factors for adverse outcomes; a comprehensive approach to asthma management that acknowledges the foundational role of inhaled corticosteroid therapy, but also provides a framework for individualizing patient care; an emphasis on maximizing the benefit of available medications by addressing common problems such as incorrect inhaler technique and poor adherence; a continuum of care for worsening asthma, starting with early self-management and progressing to primary care or acute care management; and diagnosis of the asthma/chronic obstructive pulmonary disease overlap syndrome. This document is meant to advice the key stakeholders on the diagnosis and management of asthma and highlights the need to individualize the care of each and every asthmatic patient.