Macroautophagy in lymphatic endothelial cells inhibits T cell–mediated autoimmunity

Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. We investigated whether autophagy in LECs modulates T cell activation in experimental arthritis. Whereas genetic abrogation of autophagy in LECs does not alter immune homeostasis, it induces alterations of the regulatory T cell (T reg cell) population in LNs from arthritic mice, which might be linked to MHCII-mediated antigen presentation by LECs. Furthermore, inflammation-induced autophagy in LECs promotes the degradation of Sphingosine kinase 1 (SphK1), resulting in decreased S1P production. Consequently, in arthritic mice lacking autophagy in LECs, pathogenic Th17 cell migration toward LEC-derived S1P gradients and egress from LNs are enhanced, as well as infiltration of inflamed joints, resulting in exacerbated arthritis. Our results highlight the autophagy pathway as an important regulator of LEC immunomodulatory functions in inflammatory conditions.     

Tumor‐induced myeloid‐derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T‐cell activation events

Tumor growth coincides with an accumulation of myeloid‐derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic (MO) CD11b⁺CD115⁺Ly6G^?Ly6C^high MDSCs and granulocytic CD11b⁺CD115^?Ly6G⁺Ly6C^int polymorphonuclear (PMN)‐MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8⁺ T‐cell activation — including cytokine production, surface marker expression, survival, and cytotoxicity — is currently unclear. Here, employing an in vitro coculture system, we demonstrate that splenic MDSC subsets suppress antigen‐driven CD8⁺ T‐cell proliferation, but differ in their dependency on IFN‐γ, STAT‐1, IRF‐1, and NO to do so. Moreover, MO‐MDSC and PMN‐MDSCs diminish IL‐2 levels, but only MO‐MDSCs affect IL‐2Rα (CD25) expression and STAT‐5 signaling. Unexpectedly, however, both MDSC populations stimulate IFN‐γ production by CD8⁺ T cells on a per cell basis, illustrating that some T‐cell activation characteristics are actually stimulated by MDSCs. Conversely, MO‐MDSCs counteract the activation‐induced change in CD44, CD62L, CD162, and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8⁺ T‐cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL‐mediated apoptosis, and cytotoxicity. Hence, MDSCs intricately influence different CD8⁺ T‐cell activation events in vitro, whereby some parameters are suppressed while others are stimulated.     

Psychosocial Change in Members of Clubhouse Paris (France) Over an 18-Month Period: A Longitudinal Mixed Methods Study

Community Mental Health Journal - The community-based mental health organizations known as “Clubhouses” have existed since the 1940s in the United States, and the model has since spread...     

Sex and occupation are salient factors associated with lateral ankle sprain risk in military tactical athletes

ObjectivesTo assess the risk of lateral ankle sprain (LAS) in male and female tactical athletes across different military occupations in the US military.DesignRetrospective cohort.MethodsThe Defense Medical Epidemiology Database was queried for the number of individuals with ICD-9 diagnosis codes 845.00 (sprain of ankle, unspecified) and 845.02 (calcaneofibular ligament sprain) on their initial encounter from 2006 to 2015. Relative risk (RR) and chi-square statistics were calculated assessing sex and occupational category on LAS risk.Results272,970 enlisted males (27.9 per 1000 person-years), 56,732 enlisted females (34.5 per 1000 person-years), 24,534 male officers (12.6 per 1000 person-years), and 6020 female officers (16.4 per 1000 person-years) incurred a LAS. Enlisted females in all occupational groups were at significantly higher risk for LAS than their male counterparts (RR 1.09–1.68; p < 0.001), except for Engineers (p = 0.15). Female officers had consistently higher risk for LAS in all occupational groups (RR 1.10–1.42; p < 0.001) compared with male officers, except Ground/Naval Gunfire (p = 0.23). Contrasted with Infantry, enlisted tactical athletes in the Special Operations Forces, Mechanized/Armor, Aviation, Maintenance, and Maritime/Naval Specialties were at lower risk (RR 0.38?0.93; p < 0.001), Artillery, Engineers, and Logistics Specialties were at higher risk (RR 1.04–1.18; p < 0.001), and Administration, Intelligence, and Communications were no different (p = 0.69). Compared with Ground/Naval Gunfire officers, Aviation officers were at significantly lower risk (RR, 0.75; p < 0.001), and Engineers, Maintenance, Administration, Operations/Intelligence, and Logistics officers were at higher risk (RR, 1.08–1.20; p < 0.001).ConclusionsSex and military occupation were salient factors associated with LAS risk.     

Accuracy of non-guided versus ultrasound-guided injections in cervical muscles: a cadaver study

Journal of Neurology - The col-cap concept encouraged neurologists to inject a large group of muscles in the treatment of cervical dystonia. This includes deep muscles such as the obliquus capitis...     

Unusual concomitant rearrangements of Cyclin D1 and MYC genes in blastoid variant of mantle cell lymphoma: Case report and review of literature

We report herein a case of blastoid variant mantle cell lymphoma (MCL) with both aberrant phenotype and unusual genetics. Unexpectedly, lymphoma cells were CD5⁻ and CD10⁺. Standard karyotype and FISH techniques showed that tumor cells carried two distinct translocations which had not been reported together in a same tumor. The first translocation juxtaposed the immunoglobulin lambda light chain locus with CCND1 locus, leading to Cyclin D1 overexpression. The second translocation revealed MYC rearrangement with a non-immunoglobulin gene partner located on the short arm of chromosome 4. The interpretation of the case on tissue sections alone could have been challenging. Indeed, the lack of CD5 and expression of CD10 associated with MYC rearrangement detected on interphasic nuclei could support the diagnosis of diffuse large B-cell lymphoma or Burkitt lymphoma. This distinction is also especially important as these lymphoma subtypes require specific treatment.     

Successful use of azithromycin for Escherichia coli–associated renal allograft malakoplakia: a report of two cases

European Journal of Clinical Microbiology & Infectious Diseases - Malakoplakia is a chronic granulomatous disease associated with incomplete clearance of bacterial pathogens. A multimodal...     

How do people with knee pain from osteoarthritis respond to a brief video delivering empowering education about the condition and its management?

ObjectiveTo evaluate responses by people with knee osteoarthritis to a brief educational video about their condition that aimed to empower and motivate effective self-management. The video content addressed psychosocial contributors to pain and barriers to behaviour change.MethodsA mixed methods design, including a survey and semi-structured interviews, was used to collect data from 118 people (46–83 years, 78% female) with knee osteoarthritis.ResultsQuantitative data analysis showed the video was rated positively on 0–6 scales for enjoyability (mean 5.0), helpfulness (4.9), relevance (5.0) and believability (5.4). The majority would recommend the video (89%), learned new information (78%) and/or reported intentions to change behaviour (78%). A minority disliked aspects of the video (23%). The thematic analyses identified three main themes: Reactions to the video, including emotions; Learning from the video, including new knowledge and empowerment, but also unmet information needs or disagreement; and Intentions, including behaviour changes, cognitive changes and help seeking.ConclusionEducation about knee osteoarthritis with a focus on empowerment is well received by people with the condition, although some discordant views emerged.Practice implicationsThe educational video about knee osteoarthritis can be recommended to promote effective self-management and counteract potential drawbacks associated with biomedical-based education.