Regulation and Function of the Caspase-1 in an Inflammatory Microenvironment.

The inflammasome is a complex of proteins that has a critical role in mounting an inflammatory response in reply to a harmful stimulus that compromises the homeostatic state of the tissue. The NLRP3 inflammasome, which is found in a wound-like environment, is comprised of three components: the NLRP3, the adaptor protein ASC and caspase-1. Interestingly, although ASC levels do not fluctuate, caspase-1 levels are elevated in both physiological and pathological conditions. Despite the observation that merely raising caspase-1 levels is sufficient to induce inflammation, the crucial question regarding the mechanism governing its expression is unexplored. We found that, in an inflammatory microenvironment, caspase-1 is regulated by NF-κB. Consistent with this association, the inhibition of caspase-1 activity parallels the effects on wound healing caused by the abrogation of NF-κB activation. Surprisingly, not only does inhibition of the NF-κB/caspase-1 axis disrupt the inflammatory phase of the wound-healing program, but it also impairs the stimulation of cutaneous epithelial stem cells of the proliferative phase. These data provide a mechanistic basis for the complex interplay between different phases of the wound-healing response in which the downstream signaling activity of immune cells can kindle the amplification of local stem cells to advance tissue repair

Tidal Effects on Circulation in and near the East China Sea

We incorporate tidal currents into a previously validated, three-dimensional, subtidal circulation model to assess tidal effects on the circulation in and around the East China Sea. Of particular interest is the tide-enhanced Changjiang plume dispersal and circulation in the southern East China Sea. The modeling results show that without tides, the Changjiang plume in summer presents itself as a stagnant, expansive pool in regions bordering the northern East China Sea and Yellow Sea, too far north and too accumulating relative to observations. The winter plume dispersal pushed by the north-northeast monsoon follows the China coastline southeastward as a coastal current that matches more closely with observations with or without tides. Incorporating the effect of tides brings the model closer to observation, especially in summer. During summer the Taiwan Warm Current shifts to lower latitudes, enhances upwelling off southeast China and induces a southward tidal residual coastal flow off southeast China. Tides also induce the observed seaward detachment of the summer plume. In winter, the prevailing north-northeast monsoon suppresses the Taiwan Warm Current to the minimum. However, if the winter monsoon is weakened for a few weeks, the Taiwan Warm Current reappears and these three mechanisms begin to operate as in summer. CTD surveys and satellite observations south of the Changjiang River estuary contribute to a better understanding of the tidal effects on regional ocean currents

Elderly Patients with Laryngeal and Hypopharyngeal Cancer Undergoing Total Pharyngolaryngectomy with a Radial Forearm, Free Flap-reconstructed Phonation Tube

SummaryBackgroundThe radial forearm, free-flap (RFFF)-reconstructed phonation tube was developed for functional restoration of voice after total pharyngolaryngectomy. We aimed to report the efficacy of RFFF phonation tube after pharyngolaryngectomy with radiotherapy (RT) or concurrent chemoradiation therapy (CCRT) with intensity-modulated radiotherapy (IMRT) for elderly.Materials and methodsTen patients with laryngeal and hypopharyngeal cancer underwent total pharyngolaryngectomy and one-stage reconstruction with an RFFF-accompanied phonation tube, followed by RT or CCRT. Voice restoration was achieved with the RFFF-reconstructed phonation tube. Functional outcomes of phonation and speech were evaluated and scored.ResultsPercentages of stage III and stage IV patients among all participants were 10% and 90%, respectively. The median follow-up time was 31 months (range, 4–67 months). Almost 9 out of 10 (90%) patients experienced phonation efficacy greater than 80%. The maximal phonation time per breath was 70% longer than 3 sec. The graded as mild of wet voice was 90%. Percentage of mild decreased loudness was 60% and that of low and high pitch was 80%. Of the 10 patients, 40% could count more than 10 and 70% could pronounce more than 1 to 5 words per breath. After RT or CCRT, of patients had moderately good to excellent speech intelligibility.ConclusionThe RFFF phonation tube that was used after pharyngolaryngectomy with RT or CCRT with IMRT provided acceptable complications and functional restoration of voice for elderly patients

Efficacy of Mammographic Evaluation of Breast Cancer in Women Less Than 40 Years of Age: Experience from a Single Medical Center in Taiwan

Background/PurposeMammography is the standard imaging modality for breast cancer diagnosis. However, the value of mammographic diagnosis in breast cancer patients aged less than 40 years old has not been well assessed. The goal of our study was to determine the diagnostic efficacy of mammography for the detection of breast cancer in women under 40 years of age in a single medical center in Taiwan.MethodsOf 1766 women diagnosed with breast cancer in one medical center between 1999 and 2005, 227 (12.9%) who were younger than 40 years of age were enrolled, and 105 of these 227 patients had pre-biopsy mammograms available for analysis. The sensitivities for mammography at first (prospective) and second (retrospective) readings and for corresponding ultrasound were calculated. The distribution of different breast composition between the mammographic true-positive (TP) and false-negative (FN) lesions at the first and second readings was analyzed.ResultsOf the 105 patients, 104 presented with a palpable mass and the other one was asymptomatic. There were 109 pathologically proven breast cancers from the 105 patients; 92 of 109 cancerous lesions were detected at the first mammographic reading (sensitivity 84.4%), and the most common mammographic sign was microcalcifications (40.2%). The second reading detected seven additional cancers (99 of 109 lesions; sensitivity 90.8%). There was no significant difference between mammographic TP and FN lesions for the different breast composition on first and second readings. Ninety patients also had ultrasound available for correlation with 94 cancers diagnosed from them. The diagnostic sensitivity of ultrasound was 94.7% (89 of 94 lesions).ConclusionMammography has an acceptable sensitivity for the detection of breast cancer in women aged less than 40 years, regardless of different breast composition. Breast ultrasound can offer a higher sensitivity for such a population

M-SpeechCLIP: Leveraging Large-Scale, Pre-Trained Models for Multilingual Speech to Image Retrieval

This work investigates the use of large-scale, pre-trained models (CLIP and HuBERT) for multilingual speech-image retrieval. For non-English speech-image retrieval, we outperform the current state-of-the-art performance by a wide margin when training separate models for each language, and show that a single model which processes speech in all three languages still achieves retrieval scores comparable with the prior state-of-the-art. We identify key differences in model behavior and performance between English and non-English settings, presumably attributable to the English-only pre-training of CLIP and HuBERT. Finally, we show that our models can be used for mono- and cross-lingual speech-text retrieval and cross-lingual speech-speech retrieval, despite never having seen any parallel speech-text or speech-speech data during training.Comment: Submitted to ICASSP 202

Panax notoginseng Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

Panax notoginseng (PN) is a traditional Chinese herb experimentally proven to have anti-inflammatory effects, and it is used clinically for the treatment of atherosclerosis, cerebral infarction, and cerebral ischemia. This study aimed to determine the anti-inflammatory effects of PN against bleomycin-induced pulmonary fibrosis in mice. First, in an in vitro study, culture media containing lipopolysaccharide (LPS) was used to stimulate macrophage cells (RAW 264.7 cell line). TNF-α and IL-6 levels were then determined before and after treatment with PN extract. In an animal model (C57BL/6 mice), a single dose of PN (0.5 mg/kg) was administered orally on Day 2 or Day 7 postbleomycin treatment. The results showed that TNF-α and IL-6 levels increased in the culture media of LPS-stimulated macrophage cells, and this effect was significantly inhibited in a concentration-dependent manner by PN extract. Histopathologic examination revealed that PN administered on Day 7 postbleomycin treatment significantly decreased inflammatory cell infiltrates, fibrosis scores, and TNF-α, TGF-β, IL-1β, and IL-6 levels in bronchoalveolar lavage fluid when compared with PN given on Day 2 postbleomycin treatment. These results suggest that PN administered in the early fibrotic stage can attenuate pulmonary fibrosis in an animal model of idiopathic pulmonary fibrosis

The influence of serotonin transporter polymorphisms on cortical activity: A resting EEG study

<p>Abstract</p> <p>Background</p> <p>The serotonin transporter gene (<it>5-HTT</it>) is a key regulator of serotonergic neurotransmission and has been linked to various psychiatric disorders. Among the genetic variants, polymorphisms in the <it>5-HTT </it>gene-linked polymorphic region (<it>5-HTTLPR</it>) and variable-number-of-tandem-repeat in the second intron (<it>5-HTTVNTR</it>) have functional consequences. However, their genetic impact on cortical oscillation remains unclear. This study examined the modulatory effects of <it>5-HTTLPR </it>(L-allele carriers vs. non-carriers) and <it>5-HTTVNTR </it>(10-repeat allele carriers vs. non-carriers) polymorphism on regional neural activity in a young female population.</p> <p>Methods</p> <p>Blood samples and resting state eyes-closed electroencephalography (EEG) signals were collected from 195 healthy women and stratified into 2 sets of comparisons of 2 groups each: L-allele carriers (<it>N </it>= 91) vs. non-carriers for <it>5-HTTLPR </it>and 10-repeat allele carriers (<it>N </it>= 25) vs. non-carriers for <it>5-HTTVNTR</it>. The mean power of 18 electrodes across theta, alpha, beta, gamma, gamma1, and gamma2 frequencies was analyzed. Between-group statistics were performed by an independent t-test, and global trends of regional power were quantified by non-parametric analyses.</p> <p>Results</p> <p>Among <it>5-HTTVNTR </it>genotypes, 10-repeat allele carriers showed significantly low regional power at gamma frequencies across the brain. We noticed a consistent global trend that carriers with low transcription efficiency of 5-HTT possessed low regional powers, regardless of frequency bands. The non-parametric analyses confirmed this observation, with <it>P </it>values of 3.071 × 10^-8and 1.459 × 10^-12for <it>5-HTTLPR </it>and <it>5-HTTVNTR</it>, respectively.</p> <p>Conclusions and Limitations</p> <p>Our analyses showed that genotypes with low 5-HTT activity are associated with less local neural synchronization during relaxation. The implication with respect to genetic vulnerability of 5-HTT across a broad range of psychiatric disorders is discussed. Given the low frequency of 10-repeat allele of <it>5-HTTVNTR </it>in our research sample, the possibility of false positive findings should also be considered.</p

Clinical Impacts of Delayed Diagnosis of Hirschsprung’s Disease in Newborn Infants

BackgroundAsian infants are at a higher risk of having Hirschsprung’s disease (HD). Although HD is surgically correctable, serious and even lethal complications such as Hirschsprung’s-associated enterocolitis (HAEC) can still occur. The aim of this study was to investigate the risk factors of HAEC, and the clinical impacts of delayed diagnosis of HD in newborn infants.Patients and methodsBy review of medical charts in a medical center in Taiwan, 51 cases of neonates with HD between 2002 and 2009 were collected. Patients were divided into two groups based on the time of initial diagnosis: Group I, diagnosis made within 1 week after birth, and Group II after 1 week. Clinical features including demographic distribution, presenting features of HD, short-term and long-term complications related to HD were compared between the two groups of patients.ResultsThere were 25 patients in Group I and 19 in Group II. Group II patients had more severe clinical signs and symptoms of HAEC than Group I patients. The incidence of preoperative HAEC was 12% in Group I and 63% in Group II (adjusted odds ratio = 12.81, confidence interval = 2.60–62.97). Patients with preoperative HAEC were more likely to develop adhesive bowel obstruction after operation (33% vs. 3%, p = 0.013) and failure to thrive (33% vs. 3%, p = 0.013). Also, patients with long-segment or total colonic aganglionosis were at risk of developing both postoperative HAEC (85% vs. 29%, p = 0.001) and failure to thrive (39% vs. 3%, p = 0.002).ConclusionIn our study, we found that delayed diagnosis of HD beyond 1 week after birth significantly increases the risk of serious complications in neonatal patients. Patients with long-segment or total colonic aganglionosis have higher risk of postoperative HAEC and failure to thrive. Patients with preoperative HAEC are more likely to have adhesive bowel obstruction and failure to thrive

A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study

BACKGROUND: Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified. METHODS: We conducted a genome-wide association study (Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study. We report on 2 cancer traits – prostate cancer and breast cancer – in up to 1335 participants from 330 families (54% women, mean entry age 33 years). Multivariable-adjusted residuals, computed using Cox proportional hazards models, were tested for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate ≥80%, minor allele frequency ≥10%, Hardy-Weinberg test p ≥ 0.001) using generalized estimating equations (GEE) models and family based association tests (FBAT). RESULTS: There were 58 women with breast cancer and 59 men with prostate cancer. No SNP associations attained genome-wide significance. The top SNP associations in GEE models for each trait were as follows: breast cancer, rs2075555, p = 8.0 × 10-8 in COL1A1; and prostate cancer, rs9311171, p = 1.75 × 10-6 in CTDSPL. In analysis of selected candidate cancer susceptibility genes, two MSR1 SNPs (rs9325782, GEE p = 0.008 and rs2410373, FBAT p = 0.021) were associated with prostate cancer and three ERBB4 SNPs (rs905883 GEE p = 0.0002, rs7564590 GEE p = 0.003, rs7558615 GEE p = 0.0078) were associated with breast cancer. The previously reported risk SNP for prostate cancer, rs1447295, was not included on the 100K chip. Results of cancer phenotype-genotype associations for all autosomal SNPs are web posted at. CONCLUSION: Although no association attained genome-wide significance, several interesting associations emerged for breast and prostate cancer. These findings can serve as a resource for replication in other populations to identify novel biologic pathways contributing to cancer susceptibility.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1