The Face and Features of RNU4-2: A New, Common, Recognizable, Yet Hidden Neurodevelopmental Disorder.

Background: RNU4-2 is a newly identified, noncoding gene responsible for a significant proportion of individuals with neurodevelopmental disorders (NDDs). Diagnosis is hampered by the inability of commonly employed clinical testing methods, including exome sequencing and currently formulated multigene panels, to detect variants in the noncoding region. The relatively high prevalence of this condition, predicted to affect thousands of undiagnosed children with NDDs, makes it even more relevant to have better tools to facilitate diagnosis.

Cytokine-induced natural killer cell training is dependent on cellular metabolism and is defective in obesity.

Natural killer (NK) cells are a population of innate immune cells that can rapidly kill cancer cells and produce cytokines such as interferon-γ. A key feature of NK cells is their ability to respond without prior sensitization; however, it is now well established that NK cells can possess memory-like features. After activation with cytokines, NK cells demonstrate enhanced effector functions upon restimulation days or weeks later.

Is it time to use nucleic acid amplification tests for identification of persons with sexually transmitted infections?: evidence from seroprevalence and behavioral epidemiology risk surveys in men with chlamydia and gonorrhea.

Chlamydia and gonorrhea are common sexually transmitted infections (STIs) that can cause multiple problems, and can be easily treated, but frequently present without symptoms. Because of this, commonly used syndromic diagnosis misses a majority of infected persons. Previously, diagnostic tests were expensive and invasive, but newer nucleic-acid amplification tests (NAATs) are available that use urine to non-invasively test for these infections.

Targeting mitochondrial dysfunction in MAIT cells limits IL-17 production in obesity.

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Obesity Reduces mTORC1 Activity in Mucosal-Associated Invariant T Cells, Driving Defective Metabolic and Functional Responses.

Obesity underpins the development of numerous chronic diseases, such as type II diabetes mellitus. It is well established that obesity negatively alters immune cell frequencies and functions. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells, which we have previously reported are dysregulated in obesity, with altered circulating and adipose tissue frequencies and a reduction in their IFN-γ production, which is a critical effector function of MAIT cells in host defense.

Effectiveness of intervention with visual templates targeting tense and plural agreement in copula and auxiliary structures in school-aged children with complex needs: a pilot study.

This pilot study aims to evaluate the effectiveness of a school-based intervention using visual strategies for improving accurate use of auxiliary and copula marking in singular and plural, past and present tense by students with moderate learning disability and complex needs. Eleven students, aged 10-14 years, in a specialist school based in the UK, participated in the study. A within participants design was used which included testing at baseline, pre- and post-intervention to consider progress with intervention as compared with progress during a baseline period of similar length.

Measuring Aggregated and Specific Combat Exposures: Associations Between Combat Exposure Measures and Posttraumatic Stress Disorder, Depression, and Alcohol-Related Problems.

Research has shown combat exposure to be associated with negative mental health outcomes. Different combat exposure measures are not composed of the same combat experiences, and few combat exposure measures have been directly compared to another measure. Furthermore, research about the unique associations between specific combat experiences and mental health is lacking.

NK cells in childhood obesity are activated, metabolically stressed, and functionally deficient.

Childhood obesity is a major global concern, with over 50 million children now classified as obese. Obesity has been linked to the development of numerous chronic inflammatory diseases, including type 2 diabetes and multiple cancers. NK cells are a subset of innate effector cells, which play an important role in the regulation of adipose tissue and antitumor immunity.

Evaluation of a modified version of the Posttraumatic Growth Inventory-Short Form.

Background: Posttraumatic growth is the positive change resulting from traumatic experiences and is typically assessed with retrospective measures like the Posttraumatic Growth Inventory (PTGI). The PTGI was designed to include reference to a specific traumatic event, making it difficult to implement, without change, in prospective survey studies. Thus, a modified Posttraumatic Growth Inventory-Short Form (PTGI-SF) was included in a large prospective study of current and former U.

The signalling mechanisms of a novel mitochondrial complex I inhibitor prevent lipid accumulation and attenuate TNF-α-induced insulin resistance in vitro.

RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained.

Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity.

Mucosal-associated invariant T (MAIT) cells are innate MHC-unrestricted cells that regulate inflammatory responses through the rapid production of cytokines. In this article, we show that circulating MAIT cells are depleted in obese adults, and depletion is associated with diabetic status. Circulating MAIT cells more frequently produced IL-17 upon stimulation ex vivo, a cytokine implicated in insulin resistance.

Jagged-1 is required for the expansion of CD4+ CD25+ FoxP3+ regulatory T cells and tolerogenic dendritic cells by murine mesenchymal stromal cells.

Introduction: Mesenchymal stromal cells (MSC) have well defined immunomodulatory properties including the suppression of lymphocyte proliferation and inhibition of dendritic cell (DC) maturation involving both cell contact and soluble factors. These properties have made MSC attractive candidates for cellular therapy. However, the mechanism underlying these characteristics remains unclear.

Predictors of progression in high-grade appendiceal or colorectal peritoneal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Background: Long-term survival of patients with appendiceal or colorectal peritoneal carcinomatosis (PC) may be achieved by combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, such favorable outcomes are realized in a minority of patients. Given the morbidity of the CRS/HIPEC and the uncertain role of postresection systemic therapy, it is important that prognostic factors in high-grade PC be clearly defined.

(E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate-stimulated Vgamma9Vdelta2 T cells possess T helper type 1-promoting adjuvant activity for human monocyte-derived dendritic cells.

Vgamma9Vdelta2 T cells respond to pyrophosphate antigens and display potent antitumour activity in vitro. We have investigated the potential of the most potent phosphoantigen known to activate Vgamma9Vdelta2 T cells, (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate (HMB-PP), as an adjuvant for dendritic cell (DC)-based vaccines. A single stimulation of peripheral blood mononuclear cells with HMB-PP and IL-2 was sufficient to generate lines of effector memory Vgamma9Vdelta2 T cells that retained their cytolytic and cytokine secretion activities.