Risk of prevalence of latent tuberculosis infection in health care workers-an idiographic meta-analysis from a Chinese perspective.

BACKGROUND: China is one of the countries sharing the major burden of tuberculosis (TB) in the world. Health care workers (HCWs) are subject to a high risk of occupational latent tuberculosis infection (LTBI)-an asymptomatic state of TB disease. However, the heterogenic composition of healthcare professionals in terms of nature of their work leads to the inconsistency in predicting the prevalence of LTBI amongst them. Furthermore, the global statistics do not account for the analysis conducted within the Chinese population. Our study reflects a systemic and epidemiological meta-analysis to investigate the risk of contracting LTBI by the HCWs of China. METHODS: A systematic review of the literature was performed to identify studies reporting LTBI prevalence or incidence among HCWs and a control groups in China. Risk of infection, as well as subgroup analysis was calculated by pooled effect estimates. Review Manager 5.0 was used to perform the meta-analyses. RESULTS: Twenty studies containing 9,654 HCWs met the inclusion criteria. The average prevalence of LTBI among HCWs was 51.5%, ranging from 27.9-88.8%. HCWs had a higher risk of prevalence of LTBI than the control groups [odds ratio (OR), 1.78, 95% confidence interval (CI), 1.46-2.16]. In the subgroup analysis, the prevalence of LTBI in HCWs with respect to the control groups was observed to be highest in Eastern China (OR, 2.05; 95% CI, 1.35-3.11). Furthermore, the pooled OR for LTBI was 1.90 and 1.65 separately from the results of the tuberculin skin test (TST) and the interferon-gamma release assay. Lastly, upon comparing the HCWs with the control groups from the community and the nosocomial source, it was observed that the pooled OR favored for the prevalence of LTBI, which was primarily community-sourced (3.12 and 1.54). HCWs had an increased risk of prevalence of LTBI than the control groups, both in general hospitals and TB specific hospitals (pooled OR 2.4 and 1.57). CONCLUSIONS: Risk of LTBI infection among HCWs is relatively high in China, especially in the eastern region, predisposed by the cumulative exposure to Mycobacterium tuberculosis from the community and the general hospitals. Overall, our data reflects an alarming risk posed to our HCWs, and calls for immediate reforms at the policy levels, so as to implement effective screening and treatment of affected HCWs in China.

Matrix metalloprotease-mediated cleavage of neural glial-related cell adhesion molecules activates quiescent olfactory stem cells via EGFR.

Quiescent stem cells have been found in multiple adult organs, and activation of these stem cells is critical to the restoration of damaged tissues in response to injury or stress. Existing evidence suggests that extrinsic cues from the extracellular matrix or supporting cells of various stem cell niches may interact with intrinsic components to initiate stem cell differentiation, but the molecular and cellular mechanisms regulating their activation are not fully understood. In the present study, we find that olfactory horizontal basal cells (HBCs) are stimulated by neural glial-related cell adhesion molecules (NrCAMs). NrCAM activation requires matrix metalloproteases (MMPs) and epidermal growth factor receptors (EGFRs). Inhibiting MMP activity or EGFR activation not only blocks HBC proliferation in the cultured olfactory organoids, but also severely suppresses HBC proliferation in the olfactory epithelium following methimazole-induced injury, resulting in a delay of olfactory mucosa reconstitution and functional recovery of the injured mice. Both NrCAMs and EGFR are expressed by the HBCs and their expression increases upon injury. Our data indicate that MMP-mediated cleavage of NrCAMs serves as an autocrine or paracrine signal that activates EGFRs on HBCs to trigger HBC proliferation and differentiation to reconstruct the entire olfactory epithelium following injury.

Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells.

The parasitic helminth Trichinella spiralis, which poses a serious health risk to animals and humans, can be found worldwide. Recent findings indicate that a rare type of gut epithelial cell, tuft cells, can detect the helminth, triggering type 2 immune responses. However, the underlying molecular mechanisms remain to be fully understood. Here we show that both excretory-secretory products (E-S) and extract of T. spiralis can stimulate the release of the cytokine interleukin 25 (IL-25) from the mouse small intestinal villi and evoke calcium responses from tuft cells in the intestinal organoids, which can be blocked by a bitter-taste receptor inhibitor, allyl isothiocyanate. Heterologously expressed mouse Tas2r bitter-taste receptors, the expression of which is augmented during tuft-cell hyperplasia, can respond to the E-S and extract as well as to the bitter compound salicin whereas salicin in turn can induce IL-25 release from tuft cells. Furthermore, abolishment of the G-protein γ13 subunit, application of the inhibitors for G-protein αo/i, Gßγ subunits, and phospholipase Cß2 dramatically reduces the IL-25 release. Finally, tuft cells are found to utilize the inositol triphosphate receptor type 2 (Ip3r2) to regulate cytosolic calcium and thus Trpm5 activity, while potentiation of Trpm5 by a sweet-tasting compound, stevioside, enhances tuft cell IL-25 release and hyperplasia in vivo. Taken together, T. spiralis infection activates a signaling pathway in intestinal tuft cells similar to that of taste-bud cells, but with some key differences, to initiate type 2 immunity.

Mammalian Taste Bud Cells Utilize Extragemmal 5-Hydroxy-L-Tryptophan to Biosynthesize the Neurotransmitter Serotonin.

Serotonin or 5-hydroxytryptamine (5-HT) is an important neurotransmitter that is found in mammalian taste buds and can regulate the output of intragemmal signaling networks onto afferent nerve fibers. However, it is unclear how 5-HT is produced, synthesized locally inside taste buds or absorbed from outside sources. In this study, we attempt to address this question by delineating the process of possible 5-HT biosynthesis within taste buds. First, we verified that the rate-limiting enzyme tryptophan hydroxylase (TPH2) responsible for converting L-tryptophan into the intermediate 5-hydroxy-L-tryptophan (5-HTP) is expressed in a subset of type II taste bud cells (TBCs) whereas the enzyme aromatic L-aromatic amino acid decarboxylase (AADC) capable of converting 5-HTP into 5-HT is found in type III TBCs. And abolishment of TPH2 did not affect the production of intragemmal 5-HT or alter TBCs; the mutant mice did not show any changes in behavioral responses to all five primary taste qualities: sweet, umami, bitter, salty, and sour. Then we identified that 5-HTP as well as AADC are abundant in type III TBCs; and application of an AADC inhibitor significantly blocked the production of 5-HT in taste buds. In contrast, administration of an inhibitor on serotonin-reuptake transporters had minimal impact on the 5-HT amount in taste buds, indicating that exogenous 5-HT is not a major source for the intragemmal transmitter. Taken together, our data indicate that intragemmal serotonin is not biosynthesized de novo from tryptophan; instead, it is produced by AADC-mediated conversion of 5-HTP absorbed from the plasma and/or nerve fibers into 5-HT. Thus, our results suggest that the overall bodily 5-HTP level in the plasma and nervous system can regulate taste buds' physiological function, and provide an important molecular mechanism connecting these peripheral taste organs with the circulatory and nervous systems.