Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify ...patterns of gene expression in patients with primary Sjögren's syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs.
Digital phenotyping consists of moment-by-moment quantification of behavioral data from individual people, typically collected passively from smartphones and other sensors. Within the evolving ...context of precision health, digital phenotyping can advance the use of mobile health -based self-management tools and interventions by enabling more accurate prediction for prevention and treatment, facilitating supportive strategies, and informing the development of features to motivate self-management behaviors within real-world conditions. This represents an advancement in self-management science: with digital phenotyping, nurse scientists have opportunities to tailor interventions with increased precision. In this paper, we discuss the emergence of digital phenotyping, the historical background of ecological momentary assessment, and the current state of the science of digital phenotyping, with implications for research design, computational requirements, and ethical considerations in self-management science, as well as limitations.
•Digital phenotyping can inform precision self-management initiatives.•Digital phenotyping can explain response variances to interventions.•Ethical, computation, and design issues confine digital phenotyping research.
In older persons with heart failure (HF), an inability to self-manage their disease condition can result in poor health outcomes and quality of life. With the rise in smartphone use and digital game ...playing among older adults, digital tools such as sensor-controlled digital games (SCDGs) can offer accessible health-promoting tools that are enjoyable and easy to use. However, designing SCDGs that are compelling and aligned with their life values and self-management needs can be challenging. This article describes a qualitative study with older adults with HF who were recruited from a cardiac rehabilitation laboratory in central Texas to identify their perceptions and expectations regarding a SCDG for HF self-management.
A low-fidelity prototype that demonstrated the features of a SCDG was used to obtain the participants' perceptions about the value of SCDGs for HF self-management with respect to content, customization, flexibility, and usability through qualitative interviews.
We interviewed 15 patients with HF (53% women; age range, 53-90 years; 60% white). The concept of SCDGs for HF self-management was highly acceptable (80%). Participants provided suggestions for game characters, progress in the game, and game notifications and incentives. Perceived benefits included helping users track their behaviors and establish routines, become informed on strategies to manage HF, and empower themselves to take charge of their health.
The study's findings will guide personalization of SCDG development to motivate patient engagement in HF self-management behaviors.
Few studies report on therapy to improve language comprehension in children with specific language impairment (SLI). We address this gap by measuring the effect of a systematic intervention to ...improve inferential comprehension using dialogic reading tasks in conjunction with pre-determined questions and cues. Sixteen children with a diagnosis of SLI aged 4-6 participated in 10 weekly treatment sessions carried out by their regular therapists. Baseline and maintenance periods were also tabulated. Two experimental measures and a standardized test revealed that children's total scores and the quality of their responses post-treatment were better than those obtained pre-treatment. However, perhaps due to the use of non-equivalent probes, this change could not be interpreted solely as a significant effect of intervention. These results nevertheless suggest that a systematically designed intervention focusing on the comprehension of specific types of questions requiring inferencing and using a carefully scaffolded cueing strategy can be beneficial.
Objectives: (1) To analyze the preferential pathways of sound transmission and sound waves travelling properties in the skull and (2) to identify the location(s) on the skull where bone conduction to ...the cochlea is optimal. Study design: Basic research Methods: Nine cadaveric heads were placed in an anechoic chamber and equipped with six Bone Anchored Hearing Aids (BAHA™) implants (Cochlear™, Sydney, NSW, Australia) and fifteen accelerometers. A laser velocimeter was used to measure cochlear response by placing a reflector on the round window. Different frequency sweeps were applied to each implant, and measurements were recorded simultaneously by the laser velocimeter and accelerometers. Results: Low-frequency sound waves mostly travel the frontal transmission pathways, and there is no clear predominant pattern for the high frequencies. The mean inter-aural time lag is 0.1 ms. Optimal sound transmission to the cochlea occurs between 1000 and 2500 Hz with a contralateral 5 to 10 dB attenuation. The implant location does not influence mean transmission to the cochlea. Conclusion: There is a pattern of transmission for low frequencies through a frontal pathway but none for high frequencies. We were also able to demonstrate that the localization of the BAHA™ implant on the skull had no significant impact on the sound transmission, either ipsi or contralaterally.
We previously compared by microarray analysis gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) tissues. Among the set of genes identified as a molecular signature of RA, clusterin ...(clu) was one of the most differentially expressed. In the present study we sought to assess the expression and the role of CLU (mRNA and protein) in the affected joints and in cultured fibroblast-like synoviocytes (FLS) and to determine its functional role. Quantitative RT-PCR, Northern blot, in situ hybridization, immunohistochemistry, and Western blot were used to specify and quantify the expression of CLU in ex vivo synovial tissue. In synovial tissue, the protein was predominantly expressed by synoviocytes and it was detected in synovial fluids. Both full-length and spliced isoform CLU mRNA levels of expression were lower in RA tissues compared with OA and healthy synovium. In synovium and in cultured FLS, the overexpression of CLU concerned all protein isoforms in OA whereas in RA, the intracellular forms of the protein were barely detectable. Transgenic overexpression of CLU in RA FLS promoted apoptosis within 24 h. We observed that CLU knockdown with small interfering RNA promoted IL-6 and IL-8 production. CLU interacted with phosphorylated IkappaBalpha. Differential expression of CLU by OA and RA FLS appeared to be an intrinsic property of the cells. Expression of intracellular isoforms of CLU is differentially regulated between OA and RA. We propose that in RA joints, high levels of extracellular CLU and low expression of intracellular CLU may enhance NF-kappaB activation and survival of the synoviocytes.
To compare the effectiveness of the Endolymphatic duct blockage (EDB) and intratympanic methylprednisolone(ITMP) injection to control refractory Ménière's disease(MD) symptoms and evaluate their ...impact on hearing level.
Retrospective study in a tertiary care center.
36 received ITMP injection and 52 EDB. Mean outcome measures at 24 months included vertigo control, tinnitus, aural fullness and hearing level: pure-tone average (PTA), bone conduction average(BCA) and speech discrimination score(SDS).
At 24 months postoperatively, 90.4% of the EDB group had complete control of vertigo and 43.4% of the ITMP group (p = 0.001). There was no significant difference in tinnitus or aural fullness control (p = 0.34 and p 0.21 respectively). In each group, the drop in tinnitus and aural fullness frequency at 24 months were significant for EDB (p = 0.03; p < 0.001 respectively) and for ITMP group in tinnitus (p = 0.03) but not aural fullness (p = 0.063). At 24 months, PTA, BCA and SDS were significantly worst in the ITMP group when compared to preoperative levels (p = 0.038, p = 0.027, p = 0.016). PTA in the EDB group was stable with no difference compared to ITMP group (p = 0.48). BCA and SDS in the EDB group were stable and better than the ITMP group (p = 0.032; p = 0.036). In each group, vestibular paresis was not significantly different before (p = 0.06) and after treatment (p = 0.68).
EDB is more effective than the ITMP for controlling the vertigo symptoms of Ménière's disease and in preserving hearing function. It is a novel surgical technique with promising results for a complete treatment of Ménière's disease. ITMP decreases the frequency and the severity of the symptoms but only control vertigo in 27.8% of cases.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destruction of cartilage and bone. The destructive lesions result from both immune responses and non-antigen-specific ...inflammatory processes. Little is known about the primary cause of RA. Although the primacy of T-cell-related events early in the disease remains debated, strong evidence indicates that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. We will discuss evolving concepts about T-cell involvement in RA and the roles for various T cell subsets in the development of joint abnormalities. The hypothesis that RA is a T-cell driven disease was put forward when studies of RA synovium showed numerous T cells carrying activation markers. These T cells were found to participate in the complex network of cell- and mediator-driven events leading to joint destruction. Conceivably, these T cells may be stimulated by an autoantigen (whether specific to the joints or ubiquitous), a highly conserved foreign protein cross-reacting with its human homolog, or a neo-antigen expressed as a result of posttranslational events. For many years, animal models have provided valuable evidence supporting a role for T cells in RA. We will review three murine models of arthritis caused by different mechanisms. In collagen-induced arthritis, the immune response to a joint antigen is mediated by pathogenic Th1 cells that elicit severe inflammatory synovitis. Spontaneous arthritis in K/BxN T-cell-receptor transgenic mice is related to an adaptive immune response against a ubiquitous protein whose end-stage effector mechanisms are heavily dependent on the innate immune system. In the SKG model of autoimmune inflammatory arthritis, a point mutation in the gene encoding a key signal-transduction molecule in T cells causes defective T cell selection in the thymus, which releases polyclonal autoreactive T cells. Studies in these and other animal models have established that a variety of T-cell subsets whose roles vary with cell location and disease stage can contribute to synovitis. Finally, in addition to direct autoimmune attack by effector T cells, arthritis may result from defective homeostatic control of immunity by regulatory T cells.
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