Unknowing immunity status make migrants vaccine catch-up difficult. The interest of using a rapid tetanus immunotest as the Tétanos Quick Stick® (TQS®) to assess immunity status against tetanus has ...been evaluated in emergency rooms and it is now commonly used. The study aim was to evaluate TQS® as a tool for migrants’ vaccine catch-up.
From December 2018 to February 2019, a prospective study was performed and included consecutively migrants who attented to the primary medicine outconsultation of a health care centre in Paris. Migrants above 18, without any records of tetanus immunization were included and a TQS® was performed during a medical consultation. Adapted vaccine catch-up was then proposed. Immunity against tetanus among migrants, factors associated with positive TQS® and costs savings were evaluated.
TQS® test was positive for 32% of the 310 included patients. In the univariable analysis, factors associated to the presence of a positive TQS® test were a female gender (OR = 1.69 CI95% 1.02–2.80) and an urban living in the country of origin (OR = 1.79 CI95% 1.07–3.02). In the multivariable analysis, these factors were not significantly associated to a positive TQS®. Anamnesis was not correlated to the immunity status: only 26% of the migrants who reported vaccinations in childhood, adolescence and adulthood had a positive TQS® test. The use of TQS® test allowed savings of 6,522 US$ as compared to the immediate catch-up strategy for the 310 patients.
The TQS® test is an acceptable, simple, rapid and cost saving test that could find a place in the migrants’ vaccine catch-up.
Nuclear Dbf2-related (NDR) kinases are a subgroup of evolutionarily conserved AGC protein kinases that regulate various aspects of cell growth and morphogenesis. There are 4 NDR protein kinases in ...mammals, LATS1, LATS2 and STTK8/NDR1, STK38L/NDR2 protein kinases. LATS1 and 2 are core components of the well-studied Hippo pathway, which play a critical role in the regulation of cell proliferation, differentiation, and cell migration via YAP/TAZ transcription factor. The Hippo pathways play an important role in nervous tissue development and homeostasis, especially with regard to the central nervous system (CNS) and the ocular system. The ocular system is a very complex system generated by the interaction in a very tightly coordinated manner of numerous and diverse developing tissues, such as, but not limited to choroidal and retinal blood vessels, the retinal pigmented epithelium and the retina, a highly polarized neuronal tissue. The retina development and maintenance require precise and coordinated regulation of cell proliferation, cell death, migration, morphogenesis, synaptic connectivity, and balanced homeostasis. This review highlights the emerging roles of NDR1 and NDR2 kinases in the regulation of retinal/neuronal function and homeostasis via a noncanonical branch of the Hippo pathway. We highlight a potential role of NDR1 and NDR2 kinases in regulating neuronal inflammation and as potential therapeutic targets for the treatment of neuronal diseases.
•Hippo kinases are fundamental for neuronal cell death and cell proliferation.•Ndr deletion leads to concurrent apoptosis and proliferation of retinal neurons.•Ndr kinases regulates vesicle trafficking and polarity in neuronal tissues.•Ndr2 deletion increases mitochondrial oxidative stress genes.•Ndr kinases could be important players of the neuroimmunity.
The TAF6δ pathway of apoptosis can dictate life versus death decisions independently of the status of p53 tumor suppressor. TAF6δ is an inducible pro-apoptotic subunit of the general RNA polymerase ...II (Pol II) transcription factor TFIID. Alternative splice site choice of TAF6δ has been shown to be a pivotal event in triggering death via the TAF6δ pathway, yet nothing is currently known about the mechanisms that promote TAF6δ splicing. Furthermore the transcriptome impact of the gain of function of TAF6δ versus the loss of function of the major TAF6α splice form remains undefined. Here we employ comparative microarray analysis to show that TAF6δ drives a transcriptome profile distinct from that resulting from depletion of TAF6α. To define the cis-acting RNA elements responsible for TAF6δ alternative splicing we performed a mutational analysis of a TAF6 minigene system. The data point to several new RNA elements that can modulate TAF6δ and also reveal a role for RNA secondary structure in the selection of TAF6δ.
The thymine DNA glycosylase （TDG） is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair （BER） of G：T and G：U DNA mismatches arising from the ...deamination of 5-methyl cytosine （5-MeC） and cytosine,respectively.Recent studies have pointed at a role of TDG during the active demethylation of 5-MeC within CpG islands.TDG interacts with the histone acetylase CREB-binding protein （CBP） to activate CBP-dependent transcription.In addition,TDG also interacts with the retinoic acid receptor α （RARα）,resulting in the activation of RARα target genes.Here we provide evidence for the existence of a functional ternary complex containing TDG,CBP and activated RARα.Using global transcriptome profiling,we uncover a coupling of de novo methylation-sensitive and RA-dependent transcription,which coincides with a significant subset of CBP target genes.The introduction of a point mutation in TDG,which neither affects overall protein structure nor BER activity,leads to a significant loss in ternary complex stability,resulting in the deregulation of RA targets involved in cellular networks associated with DNA replication,recombination and repair.We thus demonstrate for the first time a direct coupling of TDG＇s epigenomic and transcription regulatory function through ternary complexes with CBP and RARα.
Sexual health is an integral part of overall health and should be discussed with all people who seek help. The Vaccination and Prevention working group of the French Infectious Diseases Society ...(SPILF) and the Migrant Commission of the French AIDS Society (SFLS) developed recommendations to address this issue with migrants presenting vulnerability factors. After defining sexual health and target migrants, practical recommendations were issued. Sexual health can be discussed simply with migrants or people with an immigrant background. Some migrants are exposed to sexual vulnerability due to their migration route, social isolation, administrative and housing insecurity, gender inequalities, and discrimination. Situations of sexual vulnerability, sexual violence, and female genital mutilation should be systematically identified and followed by appropriate care that respects the migrant's needs. Extended screening for HIV and sexually transmitted infections (STI) should be systematically offered as part of a "migrant health checkup" and completed, if necessary, with information on preventing tools for HIV, STIs, unwanted pregnancies, and sexual violence. In this population, it is important to check if vaccinations are up to date. Sexology and addiction counselling is sometimes useful. The specific needs of LGBTQIA+ people with an immigrant background should be taken into account.
Aims/Purpose: Diabetic retinopathy is characterized by a chronic low‐grade retinal neuroinflammation triggered by diabetes and mediated, at least in part, by microglial cells. We previously showed ...that sitagliptin, an oral drug for type 2 diabetes, developed to inhibit dipeptidyl peptidase 4 (DPP4) and increase insulin release, can prevent retinal neuroinflammation in diabetic rat models and the LPS‐induced morphological changes of microglial cells in retinal organotypic cultures. However, the mechanisms underlying these effects are not clarified. We hypothesize that sitagliptin is able to directly inhibit microglia reactivity via Dpp4.
Methods: BV‐2 microglia cell line was exposed to a non‐toxic dose of lipopolysaccharide (LPS, 0.1 μg/mL) in the presence or absence of 200 μM sitagliptin. The expression of Dpp4, iNOS, IL‐1 beta and TNF were assessed by Western Blot and/or RT‐qPCR. The BV‐2 phagocytic efficiency was assessed using fluorescent microbeads. The metabolic activity and proliferation of BV‐2 cells were assessed by resazurin assay and Edu staining, respectively. Dpp4 deletion in BV‐2 cells was generated using Crispr‐cas9 method.
Results: Sitagliptin inhibited the LPS‐induced increase in protein levels of iNOS, IL‐1 beta and TNF to 39.9 ± 6.3%, 47.2 ± 8.1% and 34.0 ± 7.2%, respectively, comparing to LPS. Sitagliptin reduced the LPS‐induced increase in phagocytic efficiency by approximately 40%. Sitagliptin did not affect the metabolism and proliferation of BV‐2. BV‐2 cells express Dpp4. Dpp4 deletion does not affect the LPS‐induced phagocytosis but abrogated the effect of sitagliptin on the reduction of BV‐2 phagocytic efficiency (approx. 320% as in LPS).
Conclusions: Sitagliptin exerts direct anti‐inflammatory effects on microglia, mediated by DPP4. These results suggest that sitagliptin can potentially be used in retinal pathologies characterized by microglia‐mediated neuroinflammation.
Support.
FCT‐Portugal: PEst UID/NEU/04539/2013, UIDB/04539/2020 and UIDP/04539/2020 and PTDC/NEU‐OSD/1113/2012. COMPETE‐FEDER.
Kinases play crucial roles in the pathophysiology of retinal degenerative diseases. These diseases, such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinitis pigmentosa, ...are characterized by progressive degeneration of retinal cells, including photoreceptors, ganglion cells, vascular cells, and retinal pigment epithelium, among others. The involvement of kinases in cell survival and apoptosis, immune responses and inflammation regulation, mitochondrial functions and mitophagy, autophagy, and proteostasis is crucial for maintaining cellular homeostasis and responding to various stressors. This review highlights the importance of studying kinases to better understand their functions and, regulation permitting, enable the identification of novel molecular players or potential drug targets and, consequently, the development of more effective and precise treatments to slow or halt the progression of retinal degenerative diseases.
In adaptive immunity, Th17 lymphocytes produce the IL-17 and IL-22 cytokines that stimulate mucosal antimicrobial defenses and tissue repair. In this study, we observed that the TLR5 agonist ...flagellin induced swift and transient transcription of genes encoding IL-17 and IL-22 in lymphoid, gut, and lung tissues. This innate response also temporarily enhanced the expression of genes associated with the antimicrobial Th17 signature. The source of the Th17-related cytokines was identified as novel populations of CD3(neg)CD127(+) immune cells among which CD4-expressing cells resembling lymphoid tissue inducer cells. We also demonstrated that dendritic cells are essential for expression of Th17-related cytokines and so for stimulation of innate cells. These data define that TLR-induced activation of CD3(neg)CD127(+) cells and production of Th17-related cytokines may be crucial for the early defenses against pathogen invasion of host tissues.
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