Cytogenetics in the management of mature B-cell non-Hodgkin lymphomas: Guidelines from the Groupe Francophone de Cytogénétique Hematologique (GFCH).

Non-Hodgkin lymphomas (NHL) consist of a wide range of clinically, phenotypically and genetically distinct neoplasms. The accurate diagnosis of mature B-cell non-Hodgkin lymphoma relies on a multidisciplinary approach that integrates morphological, phenotypical and genetic characteristics together with clinical features. Cytogenetic analyses remain an essential part of the diagnostic workup for mature B-cell lymphomas. Karyotyping is particularly useful to identify hallmark translocations, typical cytogenetic signatures as well as complex karyotypes, all bringing valuable diagnostic and/or prognostic information. Besides the well-known recurrent chromosomal abnormalities such as, for example, t(14;18)(q32;q21)/IGH::BCL2 in follicular lymphoma, recent evidences support a prognostic significance of complex karyotype in mantle cell lymphoma and Waldenström macroglobulinemia. Fluorescence In Situ Hybridization is also a key analysis playing a central role in disease identification, especially in genetically-defined entities, but also in predicting transformation risk or prognostication. This can be exemplified by the pivotal role of MYC, BCL2 and/or BCL6 rearrangements in the diagnostic of aggressive or large B-cell lymphomas. This work relies on the World Health Organization and the International Consensus Classification of hematolymphoid tumors together with the recent cytogenetic advances. Here, we review the various chromosomal abnormalities that delineate well-established mature B-cell non-Hodgkin lymphoma entities as well as newly recognized genetic subtypes and provide cytogenetic guidelines for the diagnostic management of mature B-cell lymphomas.

The Tout-Monde of disaster studies.

This essay expands the postcolonial agenda for future disaster studies that we suggested in the conclusion of the book The Invention of Disaster. It provides some refined perspectives on how to capture the diversity and complexity of the world that we draw from the philosophy of Martinican poet and novelist Edouard Glissant. Glissant's philosophy of creolisation and relation offers critical pathways towards pluralistic approaches to understanding what we call disaster in a world that is marked by hybridity and relationships rather than essentialism and nativism. A Tout-Monde, in Glissant's terms, that is the combined additions of different and hybrid interpretations of disaster. Contribution: Exploring the Tout-Monde of disaster studies will constitute a radical and forward-looking postcolonial agenda; radical in the sense that it will challenge many of our scholarly assumptions, popular discourses as well as common-sense policies and practices.

Discontinuation of tyrosine kinase inhibitor in chronic myeloid leukemia: a retrospective cohort in east occitania.

Tyrosine kinase inhibitor (TKI) discontinuation in chronic phase chronic myeloid leukemia (CML) patients has been examined in a real-life setting in the east occitania region of France. We have collected sex, age, prognostic scores, pre-TKI treatment, TKI length and response, relapse data from patients who had stopped TKI in prolonged complete molecular remission (CMR), and analyzed relapse risk factors. Sixty consecutive patients were included from january 2010 to december 2016. Sixteen received pre-TKI treatment. Fifty-three received a first-generation TKI, and seven had a second-generation TKI in first-line therapy. The median TKI time to achieve CMR was 20.5 months [5-137]. The median TKI length before discontinuation treatment was 73 months [12-158]. Twenty-two patients (37%) relapsed with a median time to relapse of 6 months [3-27]. An intermediate or high Sokal score was the only relapse risk factor (HR = 3.32, p < 0.05) associated with relapse after TKI discontinuation. TKI discontinuation was possible without relapse for half of the patients in chronic phase CML. In a real-life cohort, a high-risk Sokal score at diagnosis appears to be an adverse prognosis feature for TKI discontinuation.

Chromoanagenesis, the mechanisms of a genomic chaos.

Designated under the name of chromoanagenesis, the phenomena of chromothripsis, chromanasynthesis and chromoplexy constitute new types of complex rearrangements, including many genomic alterations localized on a few chromosomal regions, and whose discovery over the last decade has changed our perception about the formation of chromosomal abnormalities and their etiology. Although exhibiting specific features, these new catastrophic mechanisms generally occur within a single cell cycle and their emergence is closely linked to genomic instability. Various non-exclusive exogenous or cellular mechanisms capable of generating chromoanagenesis have been evoked. However, recent experimental data shed light on 2 major processes, which following a defect in the mitotic segregation of chromosomes, can generate a cascade of cellular events leading to chromoanagenesis. These mechanisms are the formation of micronuclei integrating isolated chromosomal material, and the occurrence of chromatin bridges around chromosomal material resulting from telomeric fusions. In both cases, the cellular and molecular mechanisms of fragmentation, repair and transmission of damaged chromosomal material are consistent with the features of chromoanagenesis-related complex chromosomal rearrangements. In this review, we introduce each type of chromoanagenesis, and describe the experimental models that have allowed to validate the existence of chromoanagenesis events and to better understand their cellular mechanisms of formation and transmission, as well as their impact on the stability and the plasticity of the genome.

Murine AML12 hepatocytes allow Salmonella Typhimurium T3SS1-independent invasion and intracellular fate.

Numerous studies have demonstrated the key role of the Salmonella Pathogenicity Island 1-encoded type III secretion system (T3SS1) apparatus as well as its associated effectors in the invasion and intracellular fate of Salmonella in the host cell. Several T3SS1 effectors work together to control cytoskeleton networks and induce massive membrane ruffles, allowing pathogen internalization. Salmonella resides in a vacuole whose maturation requires that the activity of T3SS1 subverts early stages of cell signaling. Recently, we identified five cell lines in which Salmonella Typhimurium enters without using its three known invasion factors: T3SS1, Rck and PagN. The present study investigated the intracellular fate of Salmonella Typhimurium in one of these models, the murine hepatocyte cell line AML12. We demonstrated that both wild-type Salmonella and T3SS1-invalidated Salmonella followed a common pathway leading to the formation of a Salmonella containing vacuole (SCV) without classical recruitment of Rho-GTPases. Maturation of the SCV continued through an acidified phase that led to Salmonella multiplication as well as the formation of a tubular network resembling Salmonella induced filaments (SIF). The fact that in the murine AML12 hepatocyte, the T3SS1 mutant induced an intracellular fate resembling to the wild-type strain highlights the fact that Salmonella Typhimurium invasion and intracellular survival can be completely independent of T3SS1.

Sex differences in condition dependence of natal dispersal in a large herbivore: dispersal propensity and distance are decoupled.

Evolution should favour plasticity in dispersal decisions in response to spatial heterogeneity in social and environmental contexts. Sex differences in individual optimization of dispersal decisions are poorly documented in mammals, because species where both sexes commonly disperse are rare. To elucidate the sex-specific drivers governing dispersal, we investigated sex differences in condition dependence in the propensity and distance of natal dispersal in one such species, the roe deer, using fine-scale monitoring of 146 GPS-collared juveniles in an intensively monitored population in southwest France. Dispersal propensity increased with body mass in males such that 36% of light individuals dispersed, whereas 62% of heavy individuals did so, but there was no evidence for condition dependence in dispersal propensity among females. By contrast, dispersal distance increased with body mass at a similar rate in both sexes such that heavy dispersers travelled around twice as far as light dispersers. Sex differences in the strength of condition-dependent dispersal may result from different selection pressures acting on the behaviour of males and females. We suggest that females disperse prior to habitat saturation being reached, likely in relation to the risk of inbreeding. By contrast, natal dispersal in males is likely governed by competitive exclusion through male-male competition for breeding opportunities in this strongly territorial mammal. Our study is, to our knowledge, a first demonstration that condition dependence in dispersal propensity and dispersal distance may be decoupled, indicating contrasting selection pressures drive the behavioural decisions of whether or not to leave the natal range, and where to settle.

Academic publishing in disaster risk reduction: past, present, and future.

Nowadays there are approximately 80 Anglophone journals that deal primarily with disaster risk reduction (DRR) and allied fields. This large array signals a sustained, if uneven, growth in DRR scholarship but also competition between the offerings of different publishers and institutions. The purpose of this article is first to summarise the development of academic publishing on DRR from its early beginnings to the present day. The paper then evaluates the current state of publishing in this field and discusses possible future trends. Next, it identifies some possible opportunities, challenges, expectations, and commitments for journal editors both within DRR and academia more broadly, including those that refer to changes in the use of terminology, the relentless increase in the number of papers submitted, the expansion and dangers of predatory journals, different peer review models, open access versus paywalls, citations and bibliography metrics, academic social networks, and copyright and distribution issues.

Case series of carbapenemase-producing Enterobacteriaceae osteomyelitis: Feel it in your bones.

OBJECTIVES: Limited data have been reported regarding osteomyelitis due to carbapenemase-producing Enterobacteriaceae (CPE), including co-infections with extended-spectrum ß-lactamase (ESBL)-producing micro-organisms. METHODS: We conducted a retrospective study in a reference centre for bone and joint infections from 2011 to 2019 among patients infected with CPE. RESULTS: Nine patients (mean age 46.8 ± 16.6 years), including three with infected implants, were identified. Infections were mostly polymicrobial (n = 8/9), including Staphylococcus aureus (n = 6/9). CPE were mainly OXA-48-type, associated with ESBL-producing Enterobacteriaceae (n = 8/9), of which 5/9 isolates were Klebsiella pneumoniae. Control of the infection was achieved in seven cases. CONCLUSIONS: CPE osteomyelitides are essentially polymicrobial and fluoroquinolone-resistant infections, highlighting the need for efficient surgery with implant removal.

[The wrapping induced membrane technique for treating recalcitrant non unions]. / La technique de la membrane induite « engainante ¼ pour le traitement des pseudarthroses rebelles sans perte de substance osseuse et le renforcement des reconstructions osseuses segmentaires fragiles. Rapport préliminaire.

The induced membrane technique is now well accepted for reconstruction of segmental bone defect. On the other hand, some cases of aseptic non-union are unsuccessfully treated by several surgical attempts for obtaining bone healing. The two stages wrapping induced membrane technique was developed initially for treating atrophic and recalcitrant aseptic non union without bone loss. At the first stage, the site of non-union was firmly fixed and tiles of cement were placed close to the bone on two or three aspects of the bone. At the second stage, after removing the spacers, the induced cavities were filled with cancellous bone autograft. In the two reported cases bone healing was acquired in 4 months. One case was a recalcitrant atrophic non-union of the humeral shaft, the other case concerned the enhancement of an insufficient segmental reconstruction of the femur. The follow up were respectively 3 years and 2 years without complication. The membrane induced by the cement tiles prevents the bone graft resorption and improves the osteogenicity through its biological properties.

[Clinical presentation and performance of urine dipstick for diagnosis of urinary infection in geriatric population]. / Présentation clinique et performance de la bandelette urinaire pour le diagnostic d'infection urinaire en population gériatrique.

BACKGROUND: Urinary tract infections (UTI) are the second cause of community-acquired bacterial infections in the elderly. Distinguishing symptomatic UTI from asymptomatic bacteriuria is problematic, as older adults are less likely to present with localized urinary symptoms. We evaluated characteristics of patients presenting UTI among elderly with sepsis. Moreover, we aimed to evaluate the sensibility and specificity of urine dipstick tests in the diagnosis of UTI in geriatric population. PATIENTS AND METHOD: We led a prospective, monocentric, observational study between April 2017 and January 2018. We included patients hospitalized in geriatric wards, who were prescribed urine culture for UTI symptoms or/and infection without primary sites for which a urine culture was prescribed. Dipstick urinalyses were performed for all patients. Clinical and biological characteristics of all patients were compared according to the final diagnosis of UTI. Moreover, results of dipstick tests were evaluated for the diagnosis of UTI in this population. RESULTS: Among 165 patients, 67 (40.6 %) had a UTI and 98 (59.4 %) had another diagnosis. These two groups were comparable for age and daily-living activities. In the UTI group, the proportion of women was higher than in the other group (P<0.05), and mean MMSE score was lower (P<0.05). Positive urine dipstick test for leukocytes and/or nitrites had high sensitivity (92 %), but low specificity (50 %). Negative predictive value of this test was high (91 %). CONCLUSION: For suspicion of UTI among elderly, few criteria are specific. Negative dipstick tests can suggest an absence of UTI due to its high negative predictive value.

Urinary tract infections in patients with neurogenic bladder.

Urinary tract infections (UTIs) in patients with neurogenic bladder are a major public health issue due to their high incidence and major consequences. Despite their frequency and potential severity, their physiopathology and management are poorly known. We provide a narrative literature review on the epidemiology, physiopathology, diagnostic criteria, microbiology, antimicrobial management, and prevention. UTIs among patients with neurogenic bladder are associated with high morbidity and healthcare utilization. Risk factors for UTI among this population are: indwelling catheter, urinary stasis, high bladder pressure, and bladder stones. Their diagnosis is a major challenge as clinical signs are often non-specific and rare. A urinary sample should be analyzed in appropriate conditions before any antibiotic prescription. According to most guidelines, a bacterial threshold≥103CFU/ml associated with symptoms is acceptable to define UTI in patients with neurogenic bladder. The management of acute symptomatic UTI is not evidence-based. A management with a single agent and a short antibiotic treatment of 10 days or less seems effective. Antibiotic selection should be based on the patient's resistance patterns. Asymptomatic bacteriuria should not be treated to avoid the emergence of bacterial resistance. Regarding preventive measures, use of clean intermittent catheterization, intravesical botulinum toxin injection, and prevention using antibiotic cycling are effective. Bacterial interference is promising but randomized controlled trials are needed. Large ongoing cohorts and randomized controlled trials should soon provide more evidence-based data.

Does body growth impair immune function in a large herbivore?

According to the principle of allocation, trade-offs are inevitable when resources allocated to one biological function are no longer available for other functions. Growth, and to a lesser extent, immunity are energetically costly functions that may compete with allocation to reproductive success and survival. However, whether high allocation to growth impairs immune system development during the growing period or immune system performance during adulthood is currently unknown in wild mammals. Using three roe deer (Capreolus capreolus) populations experiencing contrasting environmental conditions, we tested for potential costs of growth on immune phenotype over both the short-term (during growth), and the long-term (during adulthood) over the course of an individuals' life. We investigated potential costs on a set of 12 immune traits that reflect both innate and adaptive responses, and compared them between sexes and populations. Although fast growth tended to be associated with low levels of some humoral traits (globulins) during the growing period and some cellular immune traits (i.e. eosinophil and neutrophil counts) during adulthood, evidence for a trade-off between growth and other immune components was limited. Unexpectedly, no detectable growth costs on immunity were found in females from the population experiencing the least favourable environment. We discuss our findings in the light of the complex interplay between resource allocation strategies among reproduction, maintenance and immunity, in relation to local environmental conditions experienced by roe deer.

Disaster studies inside out.

Disaster studies is faced with a fascinating anomaly: frequently it claims to be critical and innovative, as suggested by the so-called vulnerability paradigm that emerged more than 40 years ago, yet often it is perpetuating some of the core and problematic tenets of the hazard paradigm that we were asked to challenge initially. This paper interrogates why such an anomaly persists. In so doing, it employs Antonio Gramsci's concept of hegemony to unpack why disaster studies is still dominated by Western epistemologies and scholars that perpetuate an orientalist view of disasters. Ultimately, it suggests a research agenda for the 40 years to come, which builds on the importance of local researchers analysing local disasters using local epistemologies, especially in the non-Western world. Such subaltern disaster studies are to be fuelled by increasing consciousness of the need to resist the hegemony of Western scholarship and to relocate disaster studies within the realm of its original political agenda.

[The fascio-cutaneous fibular island flap]. / Le lambeau fasciocutané fibulaire en ilôt.

The perforators of the fibular artery provide a well vascularised supra fascial network which allows to raise a proximally or a distally based island fascio cutaneous flap with an adipo-fascial pedicle. We present a short series of five cases of this flap for coverage of soft tissue defects involving the region of the knee, the distal third of the leg and the lateral aspect of the heel. All flaps healed entirely without venous congestion. The advantages of the fascio cutaneous fibular island flap are the supine operative position, the preservation of the sural nerve and the lesser saphenous vein and a pivot point which can be located at the middle third of the leg. According to our experience, the fascio cutaneous fibular island flap is especially indicated for repairing defects of the distal leg.

Human kallikrein-related peptidase 12 stimulates endothelial cell migration by remodeling the fibronectin matrix.

Kallikrein-related peptidase 12 (KLK12) is a kallikrein family peptidase involved in angiogenesis - a complex biological process in which the sprouting, migration and stabilization of endothelial cells requires extracellular matrix remodeling. To characterize the molecular mechanisms associated with KLK12's proangiogenic activity, we evaluated its ability to hydrolyze various matrix proteins. Our results show that KLK12 efficiently cleaved the human extracellular matrix proteins fibronectin and tenascin, both of which are involved in the regulation of endothelial cell adhesion and migration. For fibronectin, the major proteolytic product generated by KLK12 was a 29 kDa fragment containing the amino-terminal domain and the first five type I fibronectin-domains, which are essential for regulating fibronectin assembly. We also demonstrated that KLK12-mediated fibronectin proteolysis antagonizes fibronectin polymerization and fibronectin fibril formation by endothelial cells, leading to an increase in cell migration. Furthermore, a polyclonal antibody raised against KLK12's proteolytic cleavage site on fibronectin prevented the KLK12-dependent inhibition of fibronectin polymerization and the KLK12-mediated pro-migratory effect on endothelial cells. Taken as a whole, our results indicate that KLK12's proangiogenic effect is mediated through several molecular mechanisms.

Between-population differences in the genetic and maternal components of body mass in roe deer.

BACKGROUND: Understanding the genetic and environmental mechanisms governing variation in morphology or phenology in wild populations is currently an important challenge. While there is a general consensus that selection is stronger under stressful conditions, it remains unclear whether the evolutionary potential of traits should increase or decrease with increasingly stressful conditions. Here, we investigate how contrasting environmental conditions during growth may affect the maternal and genetic components of body mass in roe deer, the most abundant and widespread wild ungulate in Western Europe. Body mass is a key life history trait that strongly influences both survival and reproductive performance in large herbivores. We used pedigrees and animal models to determine the variance components of juvenile and adult winter body mass in two populations experiencing contrasting early-life conditions. RESULTS: Our analyses showed that roe deer at Chizé, where habitat was poor and unpredictable, exhibited very low genetic variance in juvenile body mass. Instead, variance in mass was mainly driven by among-cohort differences in early-life conditions and maternal environment. In contrast, roe deer at Bogesund, where resource availability during the critical period of fawn rearing was higher, displayed a substantial level of genetic variance in body mass. We discuss the potential role of past demography and viability selection on fawn body mass on the erosion of genetic variance in the poor habitat. CONCLUSIONS: Our study highlights the importance of accounting for both spatial (i.e. between-population variation) and temporal (i.e. cohort variation) heterogeneity in environmental conditions, especially in early life, to understand the potential for adaptive responses of wild populations to selection.

Immunosenescence patterns differ between populations but not between sexes in a long-lived mammal.

In animals, physiological mechanisms underlying reproductive and actuarial senescence remain poorly understood. Immunosenescence, the decline in the ability to display an efficient immune response with increasing age, is likely to influence both reproductive and actuarial senescence through increased risk of disease. Evidence for such a link has been reported from laboratory animal models but has been poorly investigated in the wild, where variation in resource acquisitions usually drives life-history trade-offs. We investigated immunosenescence patterns over 7 years in both sexes of two contrasting roe deer populations (Capreolus capreolus). We first measured twelve immune markers to obtain a thorough identification of innate and adaptive components of immunity and assessed, from the same individuals, the age-dependent variation observed in parasitic infections. Although the level of innate traits was maintained at old age, the functional innate immune traits declined with increasing age in one of two populations. In both populations, the production of inflammatory markers increased with advancing age. Finally, the adaptive response declined in late adulthood. The increasing parasite burden with age we reported suggests the effective existence of immunosenescence. Age-specific patterns differed between populations but not between sexes, which indicate that habitat quality could shape age-dependent immune phenotype in the wild.

Evolutionary allometry reveals a shift in selection pressure on male horn size.

How selection pressures acting within species interact with developmental constraints to shape macro-evolutionary patterns of species divergence is still poorly understood. In particular, whether or not sexual selection affects evolutionary allometry, the increase in trait size with body size across species, of secondary sexual characters, remains largely unknown. In this context, bovid horn size is an especially relevant trait to study because horns are present in both sexes, but the intensity of sexual selection acting on them is expected to vary both among species and between sexes. Using a unique data set of sex-specific horn size and body mass including 91 species of bovids, we compared the evolutionary allometry between horn size and body mass between sexes while accounting for both the intensity of sexual selection and phylogenetic relationship among species. We found a nonlinear evolutionary allometry where the allometric slope decreased with increasing species body mass. This pattern, much more pronounced in males than in females, suggests either that horn size is limited by some constraints in the largest bovids or is no longer the direct target of sexual selection in very large species.

Experimental separation steps influence the protein content of corona around mesoporous silica nanoparticles.

In order to direct nanocarriers to their targets efficiently, we have to understand the interactions occurring at the nano-bio interface between nanocarriers and human proteins, which forms the layer called the corona. However, experiments aiming to identify and quantify the proteins in the corona, especially critical steps in the separation of nanoparticles from biological media may affect the corona composition. Here, we used nano-LC MS/MS to compare the protein corona contents obtained after using two different separation methods. We showed that applying centrifugation versus magnetization to isolate nanoparticles surrounded by a corona resulted in protein loss and a reshuffling of their respective abundances.