Legume roots develop two types of lateral organs, lateral roots and nodules. Nodules develop as a result of a symbiotic interaction with rhizobia and provide a niche for the bacteria to fix ...atmospheric nitrogen for the plant. The Arabidopsis NAC1 transcription factor is involved in lateral root formation, and is regulated post-transcriptionally by miRNA164 and by SINAT5-dependent ubiquitination. We analyzed in Medicago truncatula the role of the closest NAC1 homolog in lateral root formation and in nodulation. MtNAC1 shows a different expression pattern in response to auxin than its Arabidopsis homolog and no changes in lateral root number or nodulation were observed in plants affected in MtNAC1 expression. In addition, no interaction was found with SINA E3 ligases, suggesting that post-translational regulation of MtNAC1 does not occur in M. truncatula. Similar to what was found in Arabidopsis, a conserved miR164 target site was retrieved in MtNAC1, which reduced protein accumulation of a GFP-miR164 sensor. Furthermore, miR164 and MtNAC1 show an overlapping expression pattern in symbiotic nodules, and over-expression of this miRNA led to a reduction in nodule number. This work suggests that regulatory pathways controlling a conserved transcription factor are complex and divergent between M. truncatula and Arabidopsis.
Malgré l’ouverture aux femmes dans le milieu policier au Québec, on constate une stagnation de leur présence. Une recherche a été entreprise auprès de services de polices municipaux au Québec pour ...mieux comprendre le parcours des policières dans leur contexte organisationnel, répertorier les résistances au changement et mettre en évidence des pistes pour favoriser la progression et la rétention des policières. Sur la base des théories féministes et de la théorie institutionnelle ainsi que d’une démarche méthodologique qualitative inspirée de la théorie ancrée et de la connaissance située, les résultats obtenus montrent que la faible progression des policières s’explique par la primauté des changements individuels exigés de leur part en accentuant les différences hommes/femmes et en laissant présager un déficit de compétences. On note également une perte de crédibilité associée à la maternité et la quasi-absence de changements sur le plan organisationnel.
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The new WHO 2016 classification of lymphoid neoplasms requires the identification of Activated B-cell like (ABC) and Germinal center B-cell like (GCB) Diffuse large B-cell lymphomas (DLBCL) NOS as ...oncogenetic pathways and probably sensitivity to specific therapies differ between these two subtypes. Whereas RNA based signatures from FFPE DLBCL seem promising in reproducibility, still 15% to 20% of DLBCL NOS are of the Unclassified subtype and there is variability between gene expression profiling (GEP) and RNA signatures considering this unclassified subtype. Therefore, the immunohistochemical tool, used during the diagnostic process of the lymphoma, might be useful to maintain and develop in addition to the molecular tools. Hans and coworkers previously developed an immunohistochemical algorithm with 86% concordance with GEP among patients treated with Rituximab with antracyclin based regimens. However, some antibodies such as BCL6 are difficult to evaluate and might hamper reproducibility of scoring. We propose an alternative to the Hans algorithm using 4 easy to use antibodies while keeping the classification process fairly simple.
Methods
One thousand eight hundred forty-three patients with previously untreated de novo CD20+ DLBCL were enrolled in the GELA (Groupe d'Etudes des Lymphomes de l'Adulte)/LYSA (Lymphoma Study Association) LNH01-5B and LNH03-B clinical trials. A Tissue microarray of 854 tumors were built and immunostaining with CD10, MUM1, FOXP1 (Barrans' threshold, 0 vs Variable/Strong), BCL6, IGM, MYC, BCL2 was performed. 761 cases of DLBCL NOS had immunostains data available. For 150 of these patients, frozen tissue was available and GEP has been analyzed using GeneChip Human Genome HGU133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA). A new immunohistochemical algorithm was then developped and validated in concordance with GEP using a training set and a validation set (100 cases for training, 50 cases for validation). The first step was to choose the best and most parsimonious machine learning algorithm capable of predicting DLBCL subtypes. Then, logical rules were created based on the predicted probabilities of class membership using a probability threshold that optimize concordance between machine learning and logical rules predictions. xgBoost algorithm (boosted trees models) with 4 covariables was chosen, using a cut-off of 0.39 for predicted class membership probabilities.
Results
A new algorithm (Table 1) using CD10, MUM1, FOXP1 and IGM was then derived with an accuracy of 93% (IC95 0.80 ; 0.98) on the validation set, compared to GEP classification. This algorithm has four arms taking into account the GCB marker CD10 and independently one of the three ABC (MUM1, FOXP1, IGM) markers to classify as GCB, ABC or non classified. Hans algorithm had an accuracy of 0.88 (IC95 0.75 ; 0.96) on this same dataset. On the training and validation set combined, our algorithm re-classified correctly 7 GCB subtypes compared to the Hans algorithm.
Survival analysis on the remaining cases (611 patients) found an ABC vs GC hazard ratio (HR) of 2.0 (IC95 1.47 ; 2.73) for progression free survival (PFS) and 1.95 (IC95 1.36-2.80) for overall survival (OS), using ABC vs GCB classification of our new algorithm. In our series, Hans' algorithm found an ABC vs GCB HR of 1,74 IC95 1,27-2,39 for PFS and 1,87 IC95 1,29-2,71 for OS.
Conclusion
Our new algorithm shows excellent performance compared to the Gold Standard GEP classification, using only 4 immunostains, and allows for more accurate risk stratification both for PFS and OS than Hans'algorithm. Therefore, it can be used as a useful tool in addition to molecular signatures.
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Bruneau:Innate Pharma: Research Funding. Delarue:Gilead: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Haioun:PFIZER: Consultancy, Honoraria; GILEAD: Consultancy, Honoraria; JANSSEN: Consultancy, Honoraria; Sandoz: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Casasnovas:BMS: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding. Morschhauser:Roche: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Gilead: Consultancy; Servier: Consultancy. Emile:Merck Serono: Honoraria. Tilly:Gilead: Honoraria; Immunogen: Honoraria; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria. Salles:Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Servier: Consultancy, Honoraria; BMS: Consultancy; morphosys: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding. Jardin:Roche: Honoraria; celgen: Honoraria; Janssen: Honoraria. Molina:Merck Serono: Honoraria; Novartis: Honoraria; Takeda: Other: travel support to the ASH meeting.
Abstract Background Salvage therapy for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL) is based on polychemotherapy, followed by high-dose therapy and autologous stem cell ...transplantation in eligible patients (HDT/ASCT). R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone. Patients and Methods We substituted cisplatin with oxaliplatin to avoid nephrotoxicity and retrospectively analyzed a large series of 91 patients with refractory/relapsed B-cell NHL to evaluate toxicities, response rates (RRs), and survival. Median age at R-DHAX (rituximab/dexamethasone/cytarabine/oxaliplatin) treatment was 60 years (range, 28-82 years). Renal insufficiency was present in 18 patients. The most frequent histologic subtypes were diffuse large B-cell lymphoma (n = 42) and follicular lymphoma (n = 30). Seventeen patients (19%) were naive to rituximab at time of R-DHAX. Results Grade III/IV toxicities were mainly hematologic, including anemia (n = 9), neutropenia (n = 44), and thrombocytopenia (n = 47). Grade I/II neurologic toxicities, sensitive or motor, were observed, and these were mainly transient except for 3 cases of motor neuropathy associated with previous exposure to vincristine. Neither renal toxicities nor degradation of previous renal insufficiency were observed. The overall RR was 75%, with a complete RR of 57%, with no statistical difference between patients previously treated with rituximab versus without rituximab. At a median follow-up of 23 months, 2-year probability rates of overall survival and progression-free survival were 75% and 43%, respectively, with a significant difference between patients treated with HDT/ASCT and patients not eligible for HDT/ASCT. Conclusion R-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.
Background
We assessed feasibility and safety of laparoscopic sigmoidectomy for complicated fistulizing diverticular disease in a tertiary care colorectal center.
Methods
A single-center ...retrospective study of patients undergoing sigmoidectomy for fistulizing diverticular disease between 2011 and 2021 was realized. Primary outcomes were rates of conversion to open surgery and severe postoperative morbidity at 30 days. Secondary outcomes included rates of postoperative bladder leaks on cystogram.
Results
Among the 104 patients, 32.7% had previous laparotomy. Laparoscopy was the initial approach in 103 (99.0%), with 6 (5.8%) conversions to laparotomy. Clavien-Dindo grade ≥ III complication rate at 30 days was 10.6%, including two (1.9%) anastomotic leaks. The median postoperative length of stay was 4.0 days. Seven (6.7%) patients underwent reoperation, six (5.8%) were readmitted, and one (0.9%) died within 30 days. Twelve (11.5%) ileostomies were created initially, and two (1.9%) were created following anastomotic leaks. At last follow-up, 101 (97.1%) patients were stoma-free. Urgent surgeries had a higher rate of severe postoperative complications. Among colovesical fistula patients (
n
= 73), postoperative cystograms were performed in 56.2%, identifying two out of the three bladder leaks detected on closed suction drains. No differences in postoperative outcomes occurred between groups with and without postoperative cystograms, including Foley catheter removal within seven days (73.2% vs. 90.6%,
p
= 0.08).
Conclusions
Laparoscopic surgery for complicated fistulizing diverticulitis showed low rates of severe complications, conversions to open surgery and permanent stomas in high-volume colorectal center.
For the elderly to get the care and services they need, they may need to make the difficult decision about staying in their home or moving to another home. Many other people may be involved in their ...care too (friends, family and healthcare providers), and can support them in making the decision. We asked informal caregivers of elderly people to help us develop a decision guide to support them and their loved ones in making this decision. This guide will be used by health providers in home care who are trained to help people make decisions. The guide is in French and English. To design and test this decision guide we involved elderly people, their caregivers and health administrators. We first asked them what they needed for making the decision, and then designed a first version of the guide. Then we asked them to look at it and give feedback, which was used to make the final version. We then used scientific criteria to check its content and the language used. The final decision guide was acceptable to the caregivers, their elderly loved ones, and the health administrators. The guide is currently being evaluated in a large research project with home care teams in the province of Quebec.
As they grow older, many elderly people are faced with the difficult and preference-sensitive decision about staying in their home or moving to a residence better adapted to their evolving care needs. We aimed to develop an English and French decision aid (DA) for elderly people facing this decision, and to involve end-users in all phases of the development process.
A three-cycle design with involvement of end-users in Quebec. End-users were elderly people (
= 4) caregivers of the elderly (
= 5), health administrators involved in home-care service delivery or policy (
= 6) and an interprofessional research team (
= 19).
: Decisional needs assessment and development of the first prototype based on existing tools and input from end-users; overview of reviews examining the impact of location of care on elderly people's health outcomes.
: Usability testing with end-users, adaptation of prototype.
: Refinement of the prototype with a linguist, graphic designer and end-users. The final prototype underwent readability testing and an International Patient Decision Aids (IPDAS) criteria compatibility assessment to verify minimal requirements for decision aids and was tested for usability by the elderly.
We used the Ottawa Personal Decision Guide to design a first prototype. As the overview of reviews did not find definitive evidence regarding optimal locations of care for elderly people, we were not able to add evidence-based advantages and disadvantages to the guide.
Overall, the caregivers and health administrators who evaluated the prototype (
= 10) were positive. In response to their suggestions, we deleted some elements (overview of pros, cons, and consequences of the options) that were necessary to qualify the tool as a DA and renamed it a "decision guide".
We developed French and English versions of the guide, readable at a primary school level. The elderly judged the guide as acceptable.
We developed a decision guide to support elderly people and their caregivers in decision making about location of care. This paper is one of few to report on a fully collaborative approach to decision guide development that involves end-users at every stage (caregivers and health administrators early on, the frail elderly in the final stages). The guide is currently being evaluated in a cluster randomized trial.
NCT02244359.
Objectives Since 2002, the French Institute for Public Health Surveillance (InVS) has developed an epidemiological surveillance program for work-related musculoskeletal disorders (MSDs) in order to ...set up health indicators according to gender, age, occupational categories and economic sectors. Methods As indicators of health impact, the incidence of carpal tunnel syndrome (CTS), the prevalence of the main upper limb MSDs, the fractions of incident CTS cases and the number of surgical CTS cases attributable to work were estimated. As indicators of exposure, scores of exposure to biomechanical, psychosocial and organisational risk factors were constructed using a random sample of 3710 workers from the Pays-de-la-Loire region. Results Incidence rates of CTS and prevalence rates of clinically-diagnosed MSDs were estimated (data published). Other health impact indicators show that fractions of incident CTS cases attributable to work ranged from 16% to 33% in females clerks, from 8% to 16% in females blue-collar workers, and from 30% to 56% in male blue-collar workers. The estimated number of surgical CTS cases attributable to work among female workers aged 20–59 ranged from 22% to 51% of all surgical cases of this age group in France. Occupational exposure indicators show for instance that 20% (95% CI 18 to 22) of females and 17% (15 to 19) of males were exposed to a highly repetitive job (>4 h/day), to at least one extreme posture and to a forceful exertion (>2 h/day). Conclusions These indicators will be regularly produced to make the results of this surveillance program more helpful for prioritising preventive strategies.
Summary
Most cases of human immunodeficiency virus (HIV)‐associated non‐Hodgkin Lymphoma (NHL) are of B‐cell origin; T‐cell NHLs are rarely reported. Within a single centre prospective cohort of 370 ...HIV‐NHL, 17 (5%) were of T‐cell origin (82% male; median age, 39 years). Median CD4+ cell count was 0·194 × 109/l and 41% had undetectable plasma HIV‐RNA at lymphoma diagnosis. All patients received combination antiretroviral therapy during chemotherapy. All histological samples were centrally reviewed. The distribution of the histological subtypes differed from the general population with absence of angioimmunoblastic subtype. Lymphoma was disseminated in 14 patients, and seven patients had performance status >2. All patients received full‐dose chemotherapy: eight standard and nine intensive regimens. Two patients who received intensive chemotherapy died during therapy. The complete remission rate was 53%; 62·5% with standard therapy and 44% with intensive therapy. After a median follow‐up of 7·2 years, the median overall survival was 9·4 months. Most deaths (85%) occurred within the first year following diagnosis, as a consequence of lymphoma progression in 10/13 cases. In this rare but severe complication of HIV infection the use of intensive chemotherapy does not appear to be beneficial for response, with increased toxicity.
Scleromyxedema is a generalized skin disease mostly associated with monoclonal gammopathy. In its chronic course, it can lead to systemic disorders related to mucin deposits in organs. We describe ...here specific lymph node involvement, hitherto not reported in scleromyxedema. A 68-year-old man with a 1-year history of micropapular eruption and skin sclerosis involving the neck, trunk, hands, and face was diagnosed with scleromyxedema associated with IgG kappa monoclonal gammopathy. Enlarged mediastinal lymph nodes found on thoracic X-ray and computed tomography scan were hypermetabolic on positron emission tomography. Lymph node biopsy showed partial nodal infiltration by numerous fibroblasts surrounded by mucin and collagen deposits, the same being observed on the skin biopsy. Lymph node and skin lesions both improved after intravenous immunoglobulin and corticosteroid treatment. Lymph node involvement in scleromyxedema should be considered in the etiological diagnosis of hypermetabolic, enlarged lymph nodes, especially if monoclonal gammopathy is associated.
Psychological health among students was an important issue even before the Covid-19 crisis. University students are exposed to high levels of psychological stress. Among the dimensions studied with ...student psychological well-being, perfectionism is increasingly explored in the literature. While perfectionism can be adaptive, it can also be a source of vulnerability to stress when expectations and aspirations exceed the student’s resources. Furthermore, the literature has repeatedly shown the role of social support in good psychological health. The present study investigates the mediating and moderating effects of social support on the relationship between perfectionism (self-oriented and socially prescribed) and internalizing symptoms (anxiety and depression) in university students. Longitudinal data were collected at three measurement times among 60 undergraduate students from the University of Montreal. First, correlational analyses showed that socially prescribed perfectionism was related to anxiety symptoms at Time 1 and Time 3, as well as to depressive symptoms at Time 1. Second, perceived social support was negatively associated with anxiety and depressive symptoms. Linear regression analyses did not show that self-oriented perfectionism and socially prescribed perfectionism are associated with increased anxiety and depressive symptoms over time. Third, mediation analyses fail to show that social support mediates the relationship between perfectionism and students’ internalized symptoms. Finally, moderation analyses fail to confirm the role of social support as a moderator of the relationship between perfectionism and symptoms of anxiety and depression. (PsycInfo Database Record (c) 2023 APA, all rights reserved) (Source: journal abstract)
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