Soft skin-interfaced mechano-acoustic sensors for real-time monitoring and patient feedback on respiratory and swallowing biomechanics.

Swallowing is a complex neuromuscular activity regulated by the autonomic nervous system. Millions of adults suffer from dysphagia (impaired or difficulty swallowing), including patients with neurological disorders, head and neck cancer, gastrointestinal diseases, and respiratory disorders. Therapeutic treatments for dysphagia include interventions by speech-language pathologists designed to improve the physiology of the swallowing mechanism by training patients to initiate swallows with sufficient frequency and during the expiratory phase of the breathing cycle. These therapeutic treatments require bulky, expensive equipment to synchronously record swallows and respirations, confined to use in clinical settings. This paper introduces a wireless, wearable technology that enables continuous, mechanoacoustic tracking of respiratory activities and swallows through movements and vibratory processes monitored at the skin surface. Validation studies in healthy adults (n = 67) and patients with dysphagia (n = 4) establish measurement equivalency to existing clinical standard equipment. Additional studies using a differential mode of operation reveal similar performance even during routine daily activities and vigorous exercise. A graphical user interface with real-time data analytics and a separate, optional wireless module support both visual and haptic forms of feedback to facilitate the treatment of patients with dysphagia.

Efficacy of high-flow nasal oxygenation compared with tracheal intubation for oxygenation during laryngeal microsurgery: a randomised non-inferiority study.

BACKGROUND: Oxygenation via a high-flow nasal cannula (HFNC) can be an alternative to tracheal intubation during short apnoeic procedures. This randomised, non-inferiority study assessed the efficacy of HFNC compared with tracheal intubation in laryngeal microsurgery. METHODS: Patients (≥20 yr old) undergoing laryngeal microsurgery under general anaesthesia and neuromuscular blockade were randomised to either the HFNC or tracheal intubation groups. The primary endpoint was lowest pulse oxygen saturation (SpO2) during the first 30 min of surgery. Secondary endpoints included incidence of desaturation (SpO2 <95%), hypercarbia (transcutaneous carbon dioxide [CO2] ≥8.7 kPa), and rescue intervention. RESULTS: Amongst 130 patients randomised, 118 were included in the analysis. The lowest SpO2 was 100 (98-100)% in the HFNC group (n=56) and 100 (100-100)% in the tracheal intubation group (n=62), with a mean difference of -1.4% (95% confidence interval: -2.4% and -0.3%), failing to confirm non-inferiority with a non-inferiority margin of 2%. The peak transcutaneous CO2 and end-tidal CO2 at the end of surgery were higher in the HFNC group compared with the tracheal intubation group. Incidences of desaturation, hypercarbia, and rescue intervention were more frequent in patients receiving HFNC compared with tracheal intubation. CONCLUSIONS: HFNC oxygenation was not non-inferior to tracheal intubation for maintaining oxygen saturation during laryngeal microsurgery. Considering more frequent desaturation, hypercarbia, and requirement for rescue intervention compared with tracheal intubation, HFNC should be used with cautious monitoring even for short duration airway surgery. CLINICAL TRIAL REGISTRATION: NCT03629353.

Protracted course of disseminated adenovirus disease with necrotizing granulomas in the liver.

A 52- year-old male with chronic lymphocytic leukemia was hospitalized with disseminated adenovirus disease. More than a month following recovery, hepatic necrotizing granulomas secondary to adenovirus were found. This case illustrates the protracted course that adenovirus disease may take and emphasizes an unusual presentation with hepatic necrotizing granulomas.

Mutations in RELT cause autosomal recessive amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a collection of isolated (non-syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic conditions. We characterized three consanguineous AI families with generalized irregular hypoplastic enamel with rapid attrition that perfectly segregated with homozygous defects in a novel gene: RELT that is a member of the tumor necrosis factor receptor superfamily (TNFRSF). RNAscope in situ hybridization of wild-type mouse molars and incisors showed specific Relt mRNA expression by secretory stage ameloblasts and by odontoblasts. Relt-/- mice generated by CRISPR/Cas9 exhibited incisor and molar enamel malformations. Relt-/- enamel had a rough surface and underwent rapid attrition. Normally unmineralized spaces in the deep enamel near the dentino-enamel junction (DEJ) were as highly mineralized as the adjacent enamel, which likely altered the mechanical properties of the DEJ. Phylogenetic analyses showed the existence of selective pressure on RELT gene outside of tooth development, indicating that the human condition may be syndromic, which possibly explains the history of small stature and severe childhood infections in two of the probands. Knowing a TNFRSF member is critical during the secretory stage of enamel formation advances our understanding of amelogenesis and improves our ability to diagnose human conditions featuring enamel malformations.

The velocity curve of the clotting waveform of rotational thromboelastometry predicts bleeding after cardiac surgery but conventional rotational thromboelastometric parameters do not.

BACKGROUND: Early detection of a risk of postoperative bleeding is essential in cardiac surgery patients. The aim of the present study was to evaluate the utility of the first derivative curve (the V-curve) of the clotting waveform of rotational thromboelastometry (ROTEM) in terms of predicting bleeding after cardiac surgery. METHODS: We retrospectively analysed 534 cardiac surgery patients. We used the chest tube output during the stay in the intensive care unit to divide patients into a higher blood loss group (HBL group; the fourth quartile) and a lower blood loss group (LBL group; the lower quartiles). We performed multivariable logistic regression using the V-curve parameters and potential confounders including conventional ROTEM parameters. RESULTS: In the multivariable model, the adjusted odds ratios for HBL of patients with a lower maximum clotting velocity (MaxVel ≤9 mm*100 s-1) as revealed by extrinsically activated ROTEM (EXTEM), and the area under the velocity curve (AUC ≤988 mm*100) of the fibrin-based extrinsically activated ROTEM (FIBTEM), both measured at skin closure in the end of surgery, were 1.78 (95% CI 1.03 to 3.07) and 2.14 (95% CI 1.20 to 3.82), respectively. However, conventional ROTEM parameters were not included in the final model. Additionally, lower EXTEM MaxVel and FIBTEM AUC values were associated with the need for a higher transfusion volume, longer postoperative intensive care unit and hospital stays, and more frequent re-exploration to control bleeding. CONCLUSIONS: The ROTEM V-curve parameters can predict postoperative bleeding and clinical outcomes after cardiac surgery.

The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study).

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

Molecular screening for Rickettsia, Anaplasmataceae and Coxiella burnetii in Rhipicephalus sanguineus ticks from Malaysia.

A total of 44 Rhipicephalus sanguineus ticks collected from 23 dogs from Malaysia were screened for Rickettsia, Anaplasmataceae and Coxiella burnetii. Coxiella burnetii was detected in 59% (26/44) of ticks however Rickettsia and Anaplasmataceae were not detected in any of the ticks. In order to genotype the strains of C. burnetii, multispacer sequence typing (MST) was carried out using three different spacers. One of the spacers; Cox2 successfully amplified a fragment for which the full length sequence of 397 bp was obtained. The sequenced product revealed only a single nucleotide difference with the Cox2.3 type sequence.

Could colorimetric method replace the individual minimal erythemal dose (MED) measurements in determining the initial dose of narrow-band UVB treatment for psoriasis patients with skin phototype III-V?

BACKGROUND: Assessment of minimal erythemal dose (MED) for individual patients has been used to guide the narrowband Ultraviolet B (NB-UVB) phototherapy, which sometimes causes discomfort and additional time. The L* value (the lightness of color in Commission Internationlale de l'Eclairge L*a*b* color scale) measured by colorimeter was shown to be useful for predicting sensitivity to NB-UVB irradiation. OBJECTIVE: To compare the efficacy and safety of NB-UVB phototherapy between 50% of MED and colorimetric L* value starting dose regimens for skin phototype III-V Korean patients with psoriasis. METHOD: Twenty seven patients determined starting doses based on colorimetric L* value, and 27 patients based on 50% of MED. Since correlation analysis showed that L* value had the most significant association with MED compared with skin phototypes, a*, and b* values, we designated starting doses of L* value regimen as follows: 300 mJ/cm(2) (L* >66), 400 mJ/cm(2) (62 < L* ≤ 66), and 500 mJ/cm(2) (L* ≤ 62). RESULTS: There was no significant difference between two groups in clinical efficacy including response rate, mean number of sessions, duration of treatment, maximum dose and cumulative dose until achieving the state of near clearance. The proportion of adverse effects was not also significantly different. CONCLUSIONS: NB-UVB starting dose determination based on colorimetric L* value was comparable with conventional MED based regimen in efficacy and safety for skin phototype III-V patients. Since it provides much convenience and ease for both patients and physicians, colorimetric L* value could partly substitute the MED checking methods in NB-UVB phototherapy.

Bacillus-derived poly-γ-glutamic acid reciprocally regulates the differentiation of T helper 17 and regulatory T cells and attenuates experimental autoimmune encephalomyelitis.

Forkhead box protein 3 (FoxP3(+)) regulatory T (T(reg)) cells and interleukin (IL)-17-producing T helper 17 (Th17) cells have opposing effects on autoimmunity, as the former are crucial for maintaining self-tolerance while the latter play a key role in precipitating inflammatory autoimmune diseases. Here we report that Bacillus-derived poly-γ-glutamic acid (γ-PGA) signals naive CD4(+) T cells to promote the selective differentiation of T(reg) cells and to suppress the differentiation of Th17 cells. The γ-PGA inducibility of FoxP3 expression was due partially to transforming growth factor (TGF)-ß induction through a Toll-like receptor (TLR)-4/myeloid differentiating factor 88 (MyD88)-dependent pathway. However, this pathway was dispensable for γ-PGA suppression of Th17 differentiation. γ-PGA inhibited IL-6-driven induction of Th17-specific factors including signal transducer and activator of transcription-3 (STAT-3) and retinoic acid-related orphan receptor γt (RORγt) while up-regulating the STAT-3 inhibitor suppressor of cytokine signalling 3 (SOCS3). Importantly, in vivo administration of γ-PGA attenuated the symptoms of experimental autoimmune encephalomyelitis and at the same time reduced Th17 cell infiltrates in the central nervous system. Thus, we have identified the microbe-associated molecular pattern, γ-PGA, as a novel regulator of autoimmune responses, capable of promoting the differentiation of anti-inflammatory T(reg) cells and suppressing the differentiation of proinflammatory Th17 cells. These findings draw attention to the potential of γ-PGA for treating Th17 cell-mediated autoimmune diseases.

Comprehensive histologic analysis of interstitial lipolysis with the 1444 nm wavelength during a 3-month follow-up.

A number of near-infrared wavelengths have been proposed and studied for laser lipolysis, but the histologic evaluation of tissue response to laser lipolysis during long-term follow-up has been lacking. A 1444 nm Nd:YAG laser with better absorption in both fat and water has recently attracted attention. The present study was designed to investigate the comprehensive histopathology of 1444 nm Nd:YAG laser-assisted lipolysis at different energy levels during a 3-month follow-up. Laser lipolysis was performed on porcine fat tissue in vivo using a 1444 nm Nd:YAG laser (AccuSculpt®, Lutronic Corporation, Ilsan, Republic of Korea) and the total energies delivered interstitially to 10x10 cm² areas were 750 J, 1500 J, 2250 J, 3000 J, 3750 J, 4500 J, and 5250 J. Biopsy samples were taken and histologically analyzed immediately after biopsy and at 1, 2, 4, and 12 weeks postoperatively. With a fluence setting above 3000J/100 cm², inflammation was severe and remained by the 3-month follow-up, resulting in severe scarring of the fat tissue. Below this energy level, mild lobular inflammation in the early phase biopsy had resolved with no scarring by the 3-month follow-up. No histologic changes in the epidermis or dermal connective tissue were present. This study suggested that controlling the energy level is important for clinical applications of laser lipolysis with no significant complications.

Branched oligomerization of cell-permeable peptides markedly enhances the transduction efficiency of adenovirus into mesenchymal stem cells.

Cell-permeable peptides (CPPs) promote the transduction of nonpermissive cells by recombinant adenovirus (rAd) to improve the therapeutic efficacy of rAd. In this study, branched oligomerization of CPPs significantly enhanced the transduction of human mesenchymal stem cells (MSCs) by rAd in a CPP type-independent manner. In particular, tetrameric CPPs increased transduction efficiency at 3000-5000-fold lower concentrations than did monomeric CPPs. Although branched oligomerization of CPPs also increases cytotoxicity, optimal concentrations of tetrameric CPPs required for maximum transduction are at least 300-1000-fold lower than those causing 50% cytotoxicity. Furthermore, although only approximately 60% of MSCs were maximally transduced at 500 muM of monomeric CPPs, >95% of MSCs were transduced with 0.1 muM of tetrameric CPPs. Tetrameric CPPs also significantly increased the formation and net surface charge of CPP/rAd complexes, as well as the binding of rAd to cell membranes at a greater degree than did monomeric CPPs, followed by rapid internalization into MSCs. In a critical-size calvarial defect model, the inclusion of tetrameric CPPs in ex vivo transduction of rAd expressing bone morphogenetic protein 2 into MSCs promoted highly mineralized bone formation. In addition, MSCs that were transduced with rAd expressing brain-derived neurotrophic factor in the presence of tetrameric CPPs improved functional recovery in a spinal cord injury model. These results demonstrated the potential for tetrameric CPPs to provide an innovative tool for MSC-based gene therapy and for in vitro gene delivery to MSCs.

Acupuncture-mediated inhibition of inflammation facilitates significant functional recovery after spinal cord injury.

Here, we first demonstrated the neuroprotective effect of acupuncture after SCI. Acupuncture applied at two specific acupoints, Shuigou (GV26) and Yanglingquan (GB34) significantly alleviated apoptotic cell death of neurons and oligodendrocytes, thereby leading to improved functional recovery after SCI. Acupuncture also inhibited caspase-3 activation and reduced the size of lesion cavity and extent of loss of axons. We also found that the activation of both p38 mitogen-activated protein kinase and resident microglia after injury are significantly attenuated by acupuncture. In addition, acupuncture significantly reduced the expression or activation of pro-nerve growth factor, proinflammatory factors such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, nitric oxide synthase, cycloxygenase-2, and matrix metalloprotease-9 after SCI. Thus, our results suggest that the neuroprotection by acupuncture may be partly mediated via inhibition of inflammation and microglial activation after SCI and acupuncture can be used as a potential therapeutic tool for treating acute spinal injury in human.

CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells.

Cancer stem cells (CSCs) have been identified in solid tumors and cancer cell lines. In this study, we isolated a series of cancer cell clones, which were heterogeneous in growth rate, cell cycle distribution and expression profile of genes and proteins, from ovarian tumor specimens of a patient and identified a sub-population enriched for ovarian CSCs defined by CD24 phenotype. Experiments in vitro demonstrated CD24(+) sub-population possessed stem cell-like characteristics of remaining quiescence and more chemoresistant compared with CD24(-) fraction, as well as a specific capacity for self-renewal and differentiation. In addition, injection of 5 x 10(3) CD24(+) cells was able to form tumor xenografts in nude mice, whereas equal number of CD24(-) cells remained nontumorigenic. We also found that CD24(+) cells expressed higher mRNA levels of some 'stemness' genes, including Nestin, beta-catenin, Bmi-1, Oct4, Oct3/4, Notch1 and Notch4 which were involved in modulating many functions of stem cells, and lower E-cadherin mRNA level than CD24(-) cells. Altogether, these observations suggest human ovarian tumor cells are organized as a hierarchy and CD24 demarcates an ovarian cancer-initiating cell population. These findings will have important clinical applications for developing effective therapeutic strategies to treat ovarian cancer.

The effects of daily irradiation with polychromatic visible polarized light on human lymphocyte populations.

OBJECTIVE: The goal of this randomized, placebo controlled, double-blind study was to investigate the effects of transcutaneous irradiation with polychromatic visible polarized light (540-780 nm; 68% polarization; power density 3.0 E-10 W/cm(2)) on a subset population of human lymphocytes using flow cytometry. BACKGROUND DATA: The biomodulation and therapeutic effects of visible light of different wavelengths are well known, but the immunological effects of polychromatic visible polarized light have not been investigated sufficiently. METHODS: Before and after 28 consecutive days of irradiation, blood samples were collected from the subjects and the population count of the lymphocyte subset was measured. RESULTS: The absolute count of total lymphocytes, CD3(+) lymphocytes, and CD3(+)CD4(+) lymphocytes increased by 7% (p = 0.023), 9% (p = 0.058), and 13% (p = 0.021), respectively. Yet the absolute count of WBCs, CD3(+)CD8(+), CD19(+), and CD16(+)56(+) lymphocytes did not change significantly. CONCLUSION: The application of polychromatic visible polarized light with the aforementioned features increases the CD3(+)CD4(+) lymphocyte population. It is suggested that this regimen may be useful for the promotion of natural defenses in cell-mediated immunity.

Enhanced delivery efficiency of recombinant adenovirus into tumor and mesenchymal stem cells by a novel PTD.

Protein transduction domains (PTDs) are small peptides that facilitate the transduction of large molecules such as polyproteins, DNA and viruses into a eukaryotic cell. Here, we demonstrated that a novel PTD (HP4) derived from herring protamine appeared to enter C6Bu1 rat glioma cell lines more rapidly than other known PTDs such as Tat, Antp and Hph-1. Moreover, HP4 significantly enhanced in vitro transduction of recombinant adenoviruses (rAds) into various cancer cell lines, mesenchymal stem cells (MSCs) and dendritic cells, which are relatively resistant to rAd infection. Enhancement of rAd delivery into C6Bu1 and MSCs by HP4 is 20 and 7 times higher than that by Tat, respectively. The increase in the expression of rAd encoding IL-12N220L by HP4 is proportional to its antitumor effect in the ex vivo transduced mouse colon cancer model. Thus, these results suggest that HP4 could be utilized to improve the transduction efficiency of rAd, resulting in enhanced efficacy of rAd-mediated gene therapy, especially for ex vivo-transduced cell therapy.

Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects.

A novel cytokine interleukin (IL)-23 bears a structural and functional resemblance to IL-12. A recombinant adenovirus expressing IL-23N220L (recombinant replication-defective adenovirus (rAd)/IL-23N220L) that selectively secrets IL-23 was constructed and compared with rAd/IL-12N220L in terms of immunological and antitumor effects. In a prophylactic setting, vaccination with rAd/ovalbumin (OVA) and rAd/IL-23N220L enhanced OVA-specific CD8(+) T-cell responses that were closely associated with complete protection against the subsequent challenge of OVA-expressing E.G7 thymoma. However, in a therapeutic setting, the intratumoral injection of rAd/IL-23N220L showed only marginal antitumor activity against several established tumors such as E.G7, CT26 and B16F10. Interestingly, whereas IL-23 still induced tumor-specific CD8(+) T-cell responses, it could not activate natural killer (NK) cells in vitro and in vivo. In addition, the adoptive transfer of activated NK cells partially restored the therapeutic antitumor effect of IL-23, indicating that NK cells are one of the crucial factors responsible for the regression of established tumors. Taken together, we demonstrated that adenovirus-mediated gene transfer of IL-23 induces a potent prophylactic, but not a therapeutic, antitumor effect.

Ectopic Cushing's syndrome due to concurrent corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) secreted by malignant gastrinoma.

Ectopic Cushing's syndrome due to various malignancies is not uncommon. However, a few cases of ectopic Cushing's syndrome caused by corticotropin-releasing hormone (CRH), or CRH with adrenocorticotropic hormone (ACTH) have been reported. A 28-year-old woman presented with acute upper gastrointestinal bleeding caused by an active ulcer, located atypically in the 2nd portion of duodenum. Further work-up revealed high gastrin levels and abdominal computed tomography (CT) scans showed a large pancreatic head mass with multiple liver metastases. The serum cortisol and ACTH levels were checked due to hypokalemia with metabolic alkalosis and recent amenorrhea. Cortisol and ACTH were both highly elevated with pituitary hyperplasia and elevated CRH. The existence of ectopic ACTH and CRH in the liver biopsy was also demonstrated immunohistochemically. Since an operation was not feasible, chemotherapy was conducted using paclitaxel and etoposide. These two drugs were chosen according to the IN VITRO chemotherapy response assay to maximize the treatment. This report demonstrates concurrent ACTH- and CRH-related ectopic Cushing's syndrome caused by malignant gastrinoma with multiple liver metastases that was treated with marginal success using a multidisciplinary medical approach.

Factors affecting long-term clinical outcomes of endoscopic mucosal resection of early gastric cancer.

BACKGROUND/AIMS: Endoscopic mucosal resection (EMR) has been widely accepted as a treatment option for early gastric cancer (EGC) in selected cases. The purposes of this study were to evaluate the long-term outcomes and the factors affecting the clinical outcomes, of EMR performed in EGC. METHODOLOGY: Between April 1996 and March 2005, 147 patients have undergone EMR to treat EGC at Yonsei University Medical Center, Seoul, Korea. We assessed the clinical outcomes of the EMR for EGC in a long-term follow-up period. We also reviewed the medical records of the patients including demographic data, endoscopic characteristics of the lesion and histopathologic findings. RESULTS: The histopathologic evaluations after the EMR treatment showed that overall complete resection rate was 84.6% (126/149) while complete resec tion rate of 93.5% was achieved in mucosal cancers (115/123). The success of complete resection was significantly affected by endoscopic gross type (depressed lesion), the degree of differentiation, and the depth of invasion, independently. There were only 5 cases of local recurrence during the follow-up periods, and the recurred or incompletely resected lesions were successfully treated by salvage operation or endoscopic retreatment. There was no disease-related or treatment-related mortality during the follow-up period. CONCLUSIONS: EMR is a good and safe curative treatment option with feasible clinical outcomes in patients with EGC. It must be emphasized that a proper selection of candidates is mandatory to improve the clinical outcome of EMR in EGC.

NF-kappa B activation pathway is essential for the chemokine expression in intestinal epithelial cells stimulated with Clostridium difficile toxin A.

Intestinal epithelial cells are known to upregulate the expression of several chemokines in response to stimulation with bacterial toxin. However, the cellular mechanisms of Clostridium difficile toxin A-induced mucosal inflammation have not yet been fully elucidated. In this study, we investigated whether nuclear factor-kappa B (NF-kappaB) could regulate chemokine expression in intestinal epithelial cells. Toxin A increased the levels of NF-kappaB complexes containing p65/p50 heterodimers and p65/p65 homodimers. Concurrently, toxin A decreased the levels of IkappaBalpha. Toxin A stimulation also increased the signals of phosphorylated IkappaB kinase (IKK)alpha/beta and NF-kappaB-inducing kinase (NIK). In the toxin A-stimulated HT-29 cells, the suppression of IKK or NIK inhibited the upregulation of downstream target genes of NF-kappaB such as IL-8 and monocyte-chemotactic protein (MCP)-1 and similarly, inhibition of NF-kappaB also downregulated the expression of IL-8, growth-related oncogene-alpha, and MCP-1. These results suggest that NF-kappaB signalling events may be involved in the inflammatory responses to toxin A produced by toxigenic C. difficile.