Sudden sensorineural hearing loss: what can we learn from examining Reddit posts?

BACKGROUND: Many patients with sudden sensorineural hearing loss may seek hearing health information and social support online, although little is known about the online information seeking behaviour. OBJECTIVE: The present study aimed to examine the discussions around sudden sensorineural hearing loss in Reddit posts. METHOD: A total of 526 Reddit posts about sudden sensorineural hearing loss were extracted and analysed using qualitative and quantitative methods. RESULTS: The content analysis identified eight main categories. Most of the posts were on topics of: sharing personal experiences (34 per cent), describing symptoms (31 per cent), discussing treatment options (36 per cent) and discussing possible causes (19 per cent) of sudden sensorineural hearing loss. The sudden sensorineural hearing loss Reddit posts varied significantly in terms of linguistic variables when compared to baseline Reddit posts. Reddit posts by individuals with sudden sensorineural hearing loss had significantly higher engagement, higher authenticity and made more references to their body when compared to other users. CONCLUSION: The study results provide insights that can be helpful for professionals during clinical interactions.

Establishment of transplantation tolerance via minimal conditioning in aged recipients.

Mixed hematopoietic chimerism is a powerful means of generating donor-specific tolerance, allowing long-term graft acceptance without lifelong dependence on immunosuppressive drugs. To avoid the need for whole body irradiation and associated side effects, we utilized a radiation-free minimal conditioning regime to induce long-term tolerance across major histocompatibility barriers. We found that low-dose busulfan, in combination with host T cell depletion and short-term sirolimus-based immunosuppression, facilitated efficient donor engraftment. Tolerance was achieved when mice were transplanted with whole or T cell-depleted bone marrow, or purified progenitor cells. Tolerance induction was associated with an expansion in regulatory T cells and was not abrogated in the absence of a thymus, suggesting a dominant or compensatory peripheral mode of tolerance. Importantly, we were able to generate durable chimerism and tolerance to donor skin grafts in both young and aged mice, despite age-related thymic atrophy and immune senescence. Clinically, this is especially relevant as the majority of transplant recipients are older patients whose immune recovery might be dangerously slow and would benefit from radiation-free minimal conditioning regimes that allow efficient donor engraftment without fully ablating the recipient immune system.

Using three-dimensional imaging to assess treatment outcomes in orthodontics: a progress report from the University of the Pacific.

Past research in integrated three-dimensional (3D) craniofacial mapping at the Craniofacial Research Instrumentation Laboratory (CRIL) of the University of the Pacific is summarized in narrative form. The advantages and limitations of recent commercial developments in the application of cone beam geometry volumetric X-ray scanners in dentistry and surface digital mapping of study casts are discussed. The rationale for methods currently in development at CRIL for merging longitudinal information from existing 3D study casts and two-dimensional lateral X-ray cephalograms in studies of orthodontic treatment outcome is presented.

Analysis of thymic stromal cell populations using flow cytometry.

The complexity of the lymphostromal interplay that is essential to alphabetaT-cell development is reflected by the heterogeneity of both lymphocytes and thymic stromal cells. While panels of monoclonal antibodies have described many of the cellular components of these microenvironments, the means to quantify stromal cell subsets using flow cytometry remains poorly defined. This study refines and compares various stromal cell isolation procedures and determines the effects of various digestion enzymes on important surface molecules. Three- and four-color flow cytometry is used to correlate established and novel stromal cell markers to define thymic fibroblasts, epithelium and a unique subset of thymic endothelium that express MHC class II. This work provides a basis for the purification of thymic stromal cells for further phenotypic, functional and genetic analysis.

Synergistic effects of alpha-toxin and perfringolysin O in Clostridium perfringens-mediated gas gangrene.

To examine the synergistic effects of alpha-toxin and perfringolysin O in clostridial myonecrosis, homologous recombination was used to construct an alpha-toxin deficient derivative of a perfringolysin O mutant of Clostridium perfringens. The subsequent strain was complemented with separate plasmids that carried the alpha-toxin structural gene (plc), the perfringolysin O gene (pfoA), or both toxin genes, and the resultant isogenic strains were examined in a mouse myonecrosis model. Synergistic effects were clearly observed in these experiments. Infection with the control strain, which did not produce either toxin, resulted in very minimal gross pathological changes, whereas the isogenic strain that was reconstituted for both toxins produced a pathology that was clearly more severe than when alpha-toxin alone was reconstituted. These changes were most apparent in the rapid spread of the disease, the gross pathology of the footpad and in the rate at which the mice had to be euthanatized for ethical reasons. Elimination of both alpha-toxin and perfringolysin O production removed most of the histopathological features typical of clostridial myonecrosis. These effects were restored when the mutant was complemented with the alpha-toxin structural gene, but reconstituting only perfringolysin O activity produced vastly different results, with regions of coagulative necrosis, apparently enhanced by vascular disruption, being observed. Reconstitution of both alpha-toxin and perfringolysin O activity produced histopathology most similar to that observed with the alpha-toxin reconstituted strain. The spreading of myonecrosis was very rapid in these tissues, and coagulative necrosis appeared to be restricted to the lumen of the blood vessels. The results of these virulence experiments clearly support the hypothesis that alpha-toxin and perfringolysin O have a synergistic effect in the pathology of gas gangrene.

Thymic stromal cells and positive selection.

The intrathymic differentiation events leading to the development and export of mature T cells tolerant to self yet capable of responding to foreign peptide antigen in the context of self-MHC are clearly both dynamic and complex. The changing phenotype of the developing thymocyte as it migrates through and interacts with the heterogeneous thymic microenvironment and the intracellular signalling events associated with such interactions are being extensively studied, yet many aspects remain poorly defined, such as the precise relationship between stromal cells and thymic selection. Positive and negative selection are crucial events in the development of T cells, leading to a diverse yet non-autoreactive immune system. A breakdown in either of these processes could lead to either a reduced T cell repertoire or the escape into the periphery of autoreactive T cells - both clearly having deleterious consequences for the health of the individual. This review aims to summarise the current status of research in thymic positive selection with emphasis on the role of different cell types and peptides.

Neutral proteases in crevicular fluid as an indicator for periodontal treatment intervention.

PURPOSE: To longitudinally determine if early therapeutic intervention, based on a positive neutral protease activity (NPA) assay score could effectively arrest the progress of periodontal disease destruction. MATERIALS AND METHODS: 63 periodontal sites which had previously undergone probing attachment loss were identified from among 31 previously treated adult periodontitis patients who were monitored during periodontal maintenance for an average of 3 yrs. Clinical levels of gingival inflammation and attachment levels and NPA assay data were collected at the beginning of each maintenance visit. When a site tested negative with the assay, routine Supportive Periodontal Therapy (SPT) was followed during the same appointment, while sites exhibiting a positive NPA score received more aggressive periodontal treatment. RESULTS: During the study period, 51 of 63 sites displayed at least one positive NPA score. Our protocol of administering periodontal treatment rendered at the visit showing a positive NPA score revealed that only 1 of the 51 sites lost > or = 1 mm attachment during the study period. The remaining 50 positive assay sites showed an overall gain of > or = 1 mm of probing attachment over the course of the study. 12 of 63 sites consistently tested negative for neutral protease enzyme activity and remained stable, although 9 of these sites exhibited bleeding on probing (BOP) at least once during this study. Initial group mean probing attachment measurements were 5.6 mm for NPA negative and 5.7 mm for NPA positive sites.

Stress-free T-cell development: glucocorticoids are not obligatory.

A role for glucocorticoids in thymopoiesis has been suggested by studies using glucocorticoid receptor (GR) anti-sense transgenic mice, glucocorticoid synthesis inhibitors and GR antagonists. Unfortunately, no consensus has been reached on exactly how glucocorticoids influence T-cell development. The most recent approach, using GR knockout (GR(-/-)) mice, indicates that GR signaling is, in fact, dispensable in this entire process.

Intrathymic T cell development and selection proceeds normally in the absence of glucocorticoid receptor signaling.

Glucocorticoids are believed to play a role in T cell development and selection, although their precise function is controversial. Glucocorticoid receptor (GR)-deficient mice were used to directly investigate this problem. GR-deficient thymocytes were resistant to dexamethasone-mediated apoptosis, confirming the absence of glucocorticoid responsiveness. An absence of GR signaling had no impact on thymocyte development either in vivo or in vitro. T cell differentiation, including positive selection, was normal as assessed by normal development of CD4+CD8+, alphabetaTCR+CD4+, and alphabetaTCR+CD8+ thymocytes. Negative selection, mediated by the superantigen staphylococcal enterotoxin B (SEB), or anti-CD3/CD28, was also normal in the absence of GR signaling. In contrast to earlier reports, these data demonstrate that GR signaling is not essential for intrathymic T cell development or selection.

Construction and virulence testing of a collagenase mutant of Clostridium perfringens.

Clostridium perfringens produces several extracellular toxins and enzymes, including an extracellular collagenase or kappa toxin that is encoded by the colA gene. To determine if the ability to produce collagenase was a significant virulence factor in cases of gas gangrene or clostridial myonecrosis that are caused by C. perfringens, a chromosomal colA mutant was constructed by homologous recombination and subsequently virulence tested in the mouse myonecrosis model. The results clearly indicate that loss of the ability to produce collagenase does not alter the ability of the mutant to establish a virulent infection. By contrast, infection with a mutant unable to produce alpha-toxin led to a marked decrease in virulence. These results indicate that collagenase is not a major determinant of virulence in C. perfringens -mediated clostridial myonecrosis.

Abnormal thymic expression of epithelial cell adhesion molecule (EP-CAM) in New Zealand Black (NZB) mice.

New Zealand Black (NZB) mice have been well documented to have a variety of thymic epithelial cell microenvironmental abnormalities, including disruption of corticoepithelial cell networks and medullary cell clusters. These abnormalities of the thymic stromal network are particularly important because similar observations have been noted in other models of murine lupus. Thymic epithelial cells, a key component of the microenvironment, play an important role in selection of the mature T cell receptor repertoire. Recently, a homotypic calcium-independent human and murine epithelial cell adhesion molecule, Ep-CAM, has been described which is located at the thymocyto-cortical cell junction. The function of Ep-CAM is still unclear but its unique location within the thymus suggests that it is critical in the process of providing maturation signals. Consequently, we examined the thymic expression of Ep-CAM in a series of autoimmune prone mice by thymic distribution of Ep-CAM in NZB, NZW, NZB/W, BXSB-Yaa, MRL- lpr/lpr, C3H- gld/gld and the control strains BALB/c, C57BL6, C3H and MRL(+/+), by immunohistology and flow cytometry. Interestingly, NZB mice are similar to control mice from day 4 to 2 weeks of age, having a very low expression of Ep-CAM at the thymocyto-cortical junction. In control strains, there is a marked increased in expression of Ep-CAM beginning at 5 weeks of age. In contrast, NZB mice fail to show significant expression of Ep-CAM even well into adulthood. This abnormality of NZB mice was also noted in NZB/W F1 and BXSB mice, but not MRL- lpr/lpr or C3H- gld/gld mice. Given the potential importance of Ep-CAM in thymic selection, this study provides important evidence that a defective stromal microenvironment is likely to be of etiological significance in the susceptibility of NZB to autoimmune disease.

Apoptosis and the thymic microenvironment in murine lupus.

The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with monoclonal antibodies specific for the thymic microenvironment. We took advantage of these findings, as well as our large panel of monoclonal antibodies which recognize thymic stroma, to study the induction of apoptosis in the thymus of murine lupus and including changes of epithelial architecture. We studied NZB, MRL/lpr, BXSB/Yaa, C3H/gld mice and BALB/c and C57BL/6 as control mice. Apoptosis was studied both at basal levels and following induction with either dexamethasone or lipopolysaccharide (LPS). The apoptotic cells were primarily found in the thymic cortex, and the frequency of apoptosis in murine lupus was less than 20% of controls. Moreover, all strains of murine lupus had severe abnormalities of the cortical network. These changes were not accentuated by dexamethasone treatment in cultured thymocytes. However, the thymus in murine lupus was less susceptible to LPS-induced apoptosis than control mice. Finally we note that the number of thymic nurse cells (TNC) was lowest in NZB mice. Our findings demonstrate significant abnormalities in the induction of apoptosis and the formation of TNC-like epithelial cells in SLE mice, and suggest that the abnormalities of the thymic microenvironment have an important role in the pathogenesis of murine lupus.

Use of genetically manipulated strains of Clostridium perfringens reveals that both alpha-toxin and theta-toxin are required for vascular leukostasis to occur in experimental gas gangrene.

A hallmark of gas gangrene (clostridial myonecrosis) pathology is a paucity of leukocytes infiltrating the necrotic tissue. The cause of this paucity most likely relates to the observation of leukocyte aggregates at the border of the area of tissue necrosis, often within the microvasculature itself. Infecting mice with genetically manipulated strains of Clostridium perfringens type A (deficient in either alpha-toxin or theta-toxin production) resulted in significantly reduced leukocyte aggregation when alpha-toxin was absent and complete abrogation of leukocyte aggregation when theta-toxin was absent. Thus, both alpha-toxin and theta-toxin are necessary for the characteristic vascular leukostasis observed in clostridial myonecrosis.

A central role for thymic emigrants in peripheral T cell homeostasis.

After initial seeding by thymic emigrants, homeostatic regulation of the T cell pool has been thought to occur entirely within the periphery. Here we report that the degree of thymic emigration directly affects the number and the CD4/CD8 ratio of peripheral T cells. We demonstrate that the increase in T cell pool size caused by the engraftment of 2, 6, or 9 thymic lobes correlates almost exactly with the number of emigrants exported from those grafts in the previous 3 weeks, regardless of how long the graft has been in place. The extent of the increase supports the concept of a 3-week period after thymic export in which emigrant T cells are exempt from peripheral T cell homeostasis. This apparent exclusion of recent thymic emigrants from the niche-based regulation of peripheral T cell numbers ensures repertoire turnover throughout adult life and provides the basis of a direct and previously unrecognized role for the thymus in the regulation of peripheral T cell homeostasis.

Fluoroscopy-guided retrieval of a sheared endotracheal stylet sheath from the tracheobronchial tree in a premature infant.

Endotracheal intubation of premature infants with respiratory distress is a commonly performed procedure in the neonatal intensive care unit. We report a rare complication of this procedure, shearing of the plastic sheath that is bonded to and surrounds the stylet used to assist intubation and lodging of the sheared stylet in the tracheobronchial tree of a small premature infant. We suggest a method for removing the plastic foreign body using fluoroscopy and an Amplatz gooseneck snare directed through the existing endotracheal tube, a technique not previously reported.

Thymic shared antigen-2: a novel cell surface marker associated with T cell differentiation and activation.

Thymic shared Ag-2 (TSA-2) is a 28-kDa, glycophosphatidylinitosol-linked cell surface molecule expressed on various T cell and thymic stromal cell subsets. It is expressed on most CD3-CD4-CD8-, CD4+CD8+, and CD3highCD4-CD8+ thymocytes but is down-regulated on approximately 40% of CD3highCD4+CD8- thymocytes. Expression on peripheral TCR-alphabeta+ T cells is similar to that of CD3+ thymocytes, although a transient down-regulation occurs with cell activation. Consistent with the recent hypothesis that emigration from the thymus is an active process, recent thymic emigrants are primarily TSA-2-/low. TSA-2 expression reveals heterogeneity among subpopulations of CD3highCD4+CD8- thymocytes and TCR-gamma delta+ T cell previously regarded as homogenous. The functional importance of TSA-2 was illustrated by the severe block in T cell differentiation caused by adding purified anti-TSA-2 mAb to reconstituted fetal thymic organ culture. While each CD25/CD44-defined triple-negative subset was present, differentiation beyond the TN stage was essentially absent, and cell numbers of all subsets were significantly below those of control cultures. Cross-linking TSA-2 on thymocytes caused a significant Ca2+ influx but no increase in apoptosis, unless anti-TSA-2 was used in conjunction with suboptimal anti-CD3 mAb. Similar treatment of mature TSA-2+ T cells had no effect on cell survival or proliferation. This study reveals TSA-2 to be a functionally important molecule in T cell development and a novel indicator of heterogeneity among a variety of developing and mature T cell populations.