Visualizing a Cold Stress-Specific Pulse Wave in Traditional Pulse Diagnosis ('Tight Pulse') Correlated with Vascular Changes in the Radial Artery Induced by a Cold Pressor Trial.

Radial pulse diagnosis is the most common method to examine the human health state in Traditional East Asian Medicine (TEAM). A cold stress-related suboptimal health state (subhealth) is often undetectable during routine medical examinations, however, it can be detected through the palpation of specific pulse waves, particularly a 'tight pulse', in TEAM. Therefore, this study examined a correlation between 'tight pulse' and vascular changes in the radial artery (RA) induced by a cold pressor trial (CPT). Twenty healthy subjects underwent sequentially control trial and CPT with room-temperature and ice-cold water, respectively, on the right forearm. The radial pulse and vascular changes were then examined on the left arm. The radial pulse scores for frequencies of 'tight pulse' with strong arterial tension increased after the CPT compared with the control trial. The pulse scores were reversely correlated with the RA thickness and volumes in ultrasonography, but not with changes in the systolic/diastolic blood pressure. The RA thickness-based vascular surface and three-dimensional images visualized a 'tight pulse' showing the vasoconstriction and bumpy-/rope-shaped vascular changes in the radial pulse diagnostic region after the CPT. These findings provide valuable insights into the potential integration of clinical radial pulse diagnosis with ultrasonography for cold-related subhealth.

Efficacy of combination therapy with pentosan polysulfate sodium and adipose tissue-derived stem cells for the management of interstitial cystitis in a rat model.

We evaluated the synergistic effects of pentosan polysulfate sodium (PPS) and mesenchymal stem cells (MSCs) in an interstitial cystitis (IC) rat model. After generation of the IC rat model, the rats were divided into 4 groups according to the treatment they received: phosphate-buffered saline injection into bladder submucosa, daily oral PPS feeding, MSC injection into bladder submucosa, or MSC injection into bladder submucosa with daily oral PPS feeding. After treatment, conscious cystometry and pain scale measurement were performed and their bladders were obtained for histological and proinflammatory-related gene expression analysis. On cystometric analysis, all treatment groups showed significantly increased intercontraction intervals and lower pain scores compared to those of the control group. Histological analysis revealed regenerated urothelium, less fibrosis, and decreased mast cell infiltration in all treatment groups compared to the control group. Significantly lower expression of TNF-α, IFN-γ, MCP, IL-6, TLR2, and TLR11 was observed in the PPS with MSC group compared to the other groups. Combination therapy with PPS and MSCs showed histological and functional effects in an IC rat model, including synergistic effects leading to increased intercontraction interval and decreased inflammatory reactions.

The bracteatus pineapple genome and domestication of clonally propagated crops.

Domestication of clonally propagated crops such as pineapple from South America was hypothesized to be a 'one-step operation'. We sequenced the genome of Ananas comosus var. bracteatus CB5 and assembled 513 Mb into 25 chromosomes with 29,412 genes. Comparison of the genomes of CB5, F153 and MD2 elucidated the genomic basis of fiber production, color formation, sugar accumulation and fruit maturation. We also resequenced 89 Ananas genomes. Cultivars 'Smooth Cayenne' and 'Queen' exhibited ancient and recent admixture, while 'Singapore Spanish' supported a one-step operation of domestication. We identified 25 selective sweeps, including a strong sweep containing a pair of tandemly duplicated bromelain inhibitors. Four candidate genes for self-incompatibility were linked in F153, but were not functional in self-compatible CB5. Our findings support the coexistence of sexual recombination and a one-step operation in the domestication of clonally propagated crops. This work guides the exploration of sexual and asexual domestication trajectories in other clonally propagated crops.

Outcomes and Predictive Factors of Electroacoustic Stimulation Rehabilitation in Children With Limited Low-Frequency Hearing.

OBJECTIVE: To evaluate the clinical feasibility and auditory benefits of hearing rehabilitation using electroacoustic stimulation (EAS) after cochlear implantation (CI) and to identify the predictive factors for successful EAS rehabilitation in children with limited low-frequency hearing. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Seventeen children (21 ears) under the age of 15 years with residual low-frequency hearing who underwent CI using hearing preservation techniques. INTERVENTION: Patients underwent CI using hearing preservation techniques, and the postoperative audiograms were obtained to evaluate the hearing preservation rate. EAS rehabilitation was applied in patients with successful low-frequency hearing preservation. OUTCOME MEASURES: Improvements in speech perception in both quiet and noise conditions were compared between the EAS mode and the CI-only mode. The predictive factors for successful EAS rehabilitation in children were analyzed. RESULTS: Functional low-frequency residual hearing less than or equal to 85 dB at 250 and 500 Hz was achieved postoperatively in six of 21 ears, and successful EAS rehabilitation was possible in nine of 21 ears. Better speech perception scores were observed in quiet conditions using the EAS mode compared with the CI-only mode, although the difference did not reach statistical significance. Significantly, better scores were observed in noise conditions with the EAS mode compared with the CI-only mode. Postoperative low-frequency pure-tone average was the only significant predictive factor of successful EAS rehabilitation. CONCLUSION: CI surgery using hearing preservation techniques with EAS rehabilitation should be performed in children, even in patients with limited residual hearing, to improve auditory outcomes.

Single-Chain Atomic Crystals as Extracellular Matrix-Mimicking Material with Exceptional Biocompatibility and Bioactivity.

In this study, Mo3Se3- single-chain atomic crystals (SCACs) with atomically small chain diameters of ∼0.6 nm, large surface areas, and mechanical flexibility were synthesized and investigated as an extracellular matrix (ECM)-mimicking scaffold material for tissue engineering applications. The proliferation of L-929 and MC3T3-E1 cell lines increased up to 268.4 ± 24.4% and 396.2 ± 8.1%, respectively, after 48 h of culturing with Mo3Se3- SCACs. More importantly, this extremely high proliferation was observed when the cells were treated with 200 µg mL-1 of Mo3Se3- SCACs, which is above the cytotoxic concentration of most nanomaterials reported earlier. An ECM-mimicking scaffold film prepared by coating Mo3Se3- SCACs on a glass substrate enabled the cells to adhere to the surface in a highly stretched manner at the initial stage of cell adhesion. Most cells cultured on the ECM-mimicking scaffold film remained alive; in contrast, a substantial number of cells cultured on glass substrates without the Mo3Se3- SCAC coating did not survive. This work not only proves the exceptional biocompatible and bioactive characteristics of the Mo3Se3- SCACs but also suggests that, as an ECM-mimicking scaffold material, Mo3Se3- SCACs can overcome several critical limitations of most other nanomaterials.

A stepwise approach to conduit puncture for electrophysiological procedures in patients with Fontan circulation.

Aims: In patients with Fontan circulation, the conduit may be punctured for electrophysiological procedures. We evaluated the feasibility and safety of a stepwise approach to conduit puncture in adults who have undergone Fontan operation. Methods and results: We included 13 consecutive patients with lateral tunnel or extracardiac conduit Fontan circulation [median age (interquartile range), 24.0 (16.0-25.0) years; seven men] who had undergone electrophysiological procedures. We performed a stepwise approach to conduit puncture: 1st, Brockenbrough needle; 2nd, Brockenbrough needle with snare; 3rd, extra-steep Brockenbrough needle with/without snare; 4th radiofrequency transseptal needle with/without snare; 5th, wiring through the puncture; 6th, conduit dilation with angioplasty balloon; 7th, non-compliant or cutting balloon; and 8th, Inoue dilator. In 12 patients, conduit puncture was successful. In two, one, and two patients with a lateral tunnel made of the pericardium or right atrial wall, conduit puncture was performed by steps 1st, 2nd, and 4th, respectively. In one, three, two, and one patient with the Goretex lateral tunnel or extracardiac conduit, conduit puncture was performed by steps 1st, 6th, 7th, and 8th, respectively. Puncture time was significantly longer in patients with Goretex conduits than with pericardial conduits [62.0 (50.0-120.0) and 11.5 (10.0-14.8) min, respectively; P < 0.001]. A snare was necessary in patients with angles ≤ 35° between the conduit wall and vertical line. Conclusion: A stepwise conduit puncture approach is feasible and safe in patients with lateral tunnel and extracardiac conduit Fontan circulation. Goretex conduit puncture was more difficult than pericardial conduit puncture.

Comparative evaluation of the white matter fiber integrity in patients with prelingual and postlingual deafness.

The aim of this study was to perform a comparative investigation of white matter integrity in patients with prelingual and postlingual deafness; we carried out a tract-based statistical analysis of diffusion tensor anisotropy in eight and ten adults with prelingual and postlingual deafness, respectively. Patients with deafness showed significant decreases in diffusion anisotropy at the right internal capsule, the right thalamus, and the splenium of the corpus callosum as well as within the bilateral superior temporal gyrus (including Heschl gyrus) and right temporal white matter. Furthermore, relative to patients with postlingual deafness, those with prelingual deafness showed lower anisotropy in the right superior temporal gyrus, bilateral temporal white matter, and the genu and anterior body of the corpus callosum. We believe that, in patients with deafness, reception of early auditory stimuli before language acquisition might be more critical to white matter maturation and brain reorganization than the nature of auditory stimuli itself or the duration of disuse. These findings provide the theoretical background for early auditory rehabilitation.

Hearing Preservation During Cochlear Implantation and Electroacoustic Stimulation in Patients With SLC26A4 Mutations.

BACKGROUND AND OBJECTIVES: Patients with SCL26A4 mutations presenting with Mondini deformity and enlarged vestibular aqueduct (EVA) tend to have comparable residual hearing. Although cochlear implantation (CI) produces good results in this group, deterioration of residual hearing can be an adverse event after surgery due to accompanying cochlear malformation and perilymph leakage during cochleostomy. The purpose of this study was to investigate if CI in patients with SCL26A4 mutations via the round window (RW) approach could achieve preservation of residual hearing, and to evaluate their speech reception with electroacoustic stimulation (EAS). SUBJECTS AND METHODS: This is a retrospective chart review of eight patients with bilateral EVA, who were bi-allelic patients with SCL26A4 mutations. CI was performed in all patients by a single surgeon using the RW approach. Audiological results were compared before and after implantation. RESULTS: Additional hearing loss after CI was less than 10 dBHL in five out of eight patients. Average hearing deterioration after CI was 8.75 dB (range, 0-26). Six out of eight patients used EAS mode after CI. The acoustic stimulation frequency ranged from 271 to 438 Hz. Patients showed better speech recognition in quiet and in noise using EAS mode compared with electrical stimulation alone. CONCLUSIONS: Preservation of residual hearing could be achieved after CI in patients with the SLC26A4 mutation via the RW approach. For successful preservation of residual hearing, application of newly-developed soft electrode and meticulous surgical is necessary. Our study showed that patients with the SLC26A4 mutation can be good candidates for EAS surgery.

A Novel and Facile Route to Synthesize Atomic-Layered MoS2 Film for Large-Area Electronics.

High-quality and large-area molybdenum disulfide (MoS2 ) thin film is highly desirable for applications in large-area electronics. However, there remains a challenge in attaining MoS2 film of reasonable crystallinity due to the absence of appropriate choice and control of precursors, as well as choice of suitable growth substrates. Herein, a novel and facile route is reported for synthesizing few-layered MoS2 film with new precursors via chemical vapor deposition. Prior to growth, an aqueous solution of sodium molybdate as the molybdenum precursor is spun onto the growth substrate and dimethyl disulfide as the liquid sulfur precursor is supplied with a bubbling system during growth. To supplement the limiting effect of Mo (sodium molybdate), a supplementary Mo is supplied by dissolving molybdenum hexacarbonyl (Mo(CO)6 ) in the liquid sulfur precursor delivered by the bubbler. By precisely controlling the amounts of precursors and hydrogen flow, full coverage of MoS2 film is readily achievable in 20 min. Large-area MoS2 field effect transistors (FETs) fabricated with a conventional photolithography have a carrier mobility as high as 18.9 cm2 V-1 s-1 , which is the highest reported for bottom-gated MoS2 -FETs fabricated via photolithography with an on/off ratio of ≈105 at room temperature.

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo.

Vestibular schwannoma (VS) is an intracranial tumor that causes significant morbidity, including hearing loss, tinnitus, dizziness, and possibly even death from brainstem compression. However, FDA-approved pharmacologic treatments for VS do not exist. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli, with potent chemoprotective effects in several cell types. Our objective was to determine whether SFN is effective against VS in vitro and in vivo. Human primary VS cells, HEI-193 schwannoma cells, and SC4 Nf2-/- Schwann cells were used to investigate the inhibitory effects of SFN in vitro. Cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and cell viability and metabolic activity was calculated by MTT assay. Apoptosis was measured by flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and Western blot for cleaved caspases. A mouse model with a murine schwannoma allograft was also used to examine the antitumor activity of SFN. SFN exhibited significant antiproliferative activity in schwannoma cells in vitro, via the inhibition of HDAC activity and the activation of ERK. SFN treatment induced apoptosis and cell cycle arrest at the G2/M phase. SFN also significantly inhibited schwannoma growth in vivo. Our preclinical studies motivate a future prospective clinical study of SFN for the treatment of VS.

Extracranial vertebral artery rupture likely secondary to "cupping therapy" superimposed on spontaneous dissection.

The extracranial vertebral artery (VA) is vulnerable to dissection and the V3 segment is the most common location for dissection. Dissection accounts for about 2% of all ischemic strokes and can occur after trauma or chiropractic neck maneuvers. We report an extremely rare case of spontaneous extracranial VA dissection presenting with posterior neck hematoma aggravated after cupping therapy, a treatment in traditional Oriental medicine. We treated the patient successfully by endovascular treatment without any complication.

The effect of subthreshold continuous electrical stimulation on the facial function of patients with Bell's palsy.

CONCLUSION: The drug regimen plus electrical stimulation was more effective in treating Bell's palsy than the conventional drug treatment alone. The effectiveness of such a sub-threshold, continuous, low frequency electrical stimulation suggests a new therapeutic approach to accelerate nerve regeneration and improve functional recovery after injury. OBJECTIVES: The purpose of this study was to determine whether sub-threshold, continuous electrical stimulation at 20 Hz facilitates functional recovery of patients with Bell's palsy. MATERIALS AND METHODS: The authors performed a prospective randomized study that included 60 patients with mild-to-moderate grade Bell's palsy (HB grade ≤4, SB grade ≥40), to evaluate the effect of developed electrical stimulation on the resolution of symptoms. Thirty patients were treated with prednisolone or/and acyclovir plus electrical stimulation within 7 days of the onset of symptoms. The other 30 patients were treated with only prednisolone or/and acyclovir as a control group. RESULTS: The overall rate of patient recovery among those treated with prednisolone or/and acyclovir plus electrical stimulation (96%) was significantly better (p < 0.05) than the rate among those treated with only prednisolone or/and acyclovir (88%).

A novel siderophore system is essential for the growth of Pseudomonas aeruginosa in airway mucus.

Pseudomonas aeruginosa establishes airway infections in Cystic Fibrosis patients. Here, we investigate the molecular interactions between P. aeruginosa and airway mucus secretions (AMS) derived from the primary cultures of normal human tracheal epithelial (NHTE) cells. PAO1, a prototype strain of P. aeruginosa, was capable of proliferating during incubation with AMS, while all other tested bacterial species perished. A PAO1 mutant lacking PA4834 gene became susceptible to AMS treatment. The ΔPA4834 mutant was grown in AMS supplemented with 100 µM ferric iron, suggesting that the PA4834 gene product is involved in iron metabolism. Consistently, intracellular iron content was decreased in the mutant, but not in PAO1 after the AMS treatment. Importantly, a PAO1 mutant unable to produce both pyoverdine and pyochelin remained viable, suggesting that these two major siderophore molecules are dispensable for maintaining viability during incubation with AMS. The ΔPA4834 mutant was regrown in AMS amended with 100 µM nicotianamine, a phytosiderophore whose production is predicted to be mediated by the PA4836 gene. Infectivity of the ΔPA4834 mutant was also significantly compromised in vivo. Together, our results identify a genetic element encoding a novel iron acquisition system that plays a previously undiscovered role in P. aeruginosa airway infection.

Fermented green tea extract alleviates obesity and related complications and alters gut microbiota composition in diet-induced obese mice.

Obesity is caused by an imbalance between caloric intake and energy expenditure and accumulation of excess lipids in adipose tissues. Recent studies have demonstrated that green tea and its processed products (e.g., oolong and black tea) are introduced to exert beneficial effects on lipid metabolism. Here, we propose that fermented green tea (FGT) extract, as a novel processed green tea, exhibits antiobesity effects. FGT reduced body weight gain and fat mass without modifying food intake. mRNA expression levels of lipogenic and inflammatory genes were downregulated in white adipose tissue of FGT-administered mice. FGT treatment alleviated glucose intolerance and fatty liver symptoms, common complications of obesity. Notably, FGT restored the changes in gut microbiota composition (e.g., the Firmicutes/Bacteroidetes and Bacteroides/Prevotella ratios), which is reported to be closely related with the development of obesity and insulin resistance, induced by high-fat diets. Collectively, FGT improves obesity and its associated symptoms and modulates composition of gut microbiota; thus, it could be used as a novel dietary component to control obesity and related symptoms.

Increased risk of respiratory illness associated with kerosene fuel use among women and children in urban Bangalore, India.

BACKGROUND: Kerosene is a widely used cooking and lighting fuel in developing countries. The potential respiratory health effects of cooking with kerosene relative to cooking with cleaner fuels such as liquefied petroleum gas (LPG) have not been well characterised. METHODS: We sampled 600 households from six urban neighbourhoods in Bangalore, India. Each household's primary cook, usually the woman of the house, was interviewed to collect information on current domestic fuel use and whether there was any presence of respiratory symptoms or illness in her or in the children in the household. Our analysis was limited to 547 adult females (ages 18-85) and 845 children (ages 0-17) in households exclusively cooking with either kerosene or LPG. We investigated the associations between kerosene use and the likelihood of having respiratory symptoms or illness using multivariate logistic regression models. RESULTS: Among adult women, cooking with kerosene was associated with cough (OR=1.88; 95% CI 1.19 to 2.99), bronchitis (OR=1.54; 95% CI 1.00 to 2.37), phlegm (OR=1.51; 95% CI 0.98 to 2.33) and chest illness (OR=1.61; 95% CI 1.02 to 2.53), relative to cooking with LPG in the multivariate models. Among children, living in a household cooking with kerosene was associated with bronchitis (OR=1.91; 95% CI 1.17 to 3.13), phlegm (OR=2.020; 95% CI 1.29 to 3.74) and chest illness (OR=1.70; 95% CI 0.99 to 2.90) after adjusting for other covariates. We also found associations between kerosene use and wheezing, difficulty breathing and asthma in adults and cough and wheezing in children, though these associations were not statistically significant. CONCLUSIONS: Women and children in households cooking with kerosene were more likely to have respiratory symptoms and illnesses compared with those in households cooking with LPG. Transitioning from kerosene to LPG for cooking may improve respiratory health among adult women and children in this population.

Intraindividual comparison of psychophysical parameters between perimodiolar and lateral-type electrode arrays in patients with bilateral cochlear implants.

OBJECTIVE: Perimodiolar electrode arrays were developed to improve stimulation of specific neuronal populations and to decrease power consumption; however, they can damage the cochlear structure. We examined and compared psychophysical parameters of perimodiolar and lateral-type electrode arrays in patients who received a different type of bilateral cochlear implant (CI) in each ear. STUDY DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Eight child patients (three males, five females) received a different CI in each ear (perimodiolar array and lateral array). They received the CIs sequentially (n = 7) or simultaneously (n = 1). INTERVENTIONS: Diagnostic, therapeutic, and rehabilitative. MAIN OUTCOME MEASURES: Electrically evoked compound action potential, threshold level, comfort level, and dynamic range (DR) of the basal, mid, and apical electrodes were compared. We also surveyed battery consumption for each device. RESULTS: Electrically evoked compound action potential threshold, threshold level, and comfort level were lower for the perimodiolar-type electrode array than for the lateral-type electrode array in most patients. However, the DR for the perimodiolar array was narrower than for the lateral array. For most patients, there was little difference in battery life. CONCLUSION: Although the level of electrical energy required for auditory stimulation seems to be lower for the perimodiolar electrode array than for the laterally placed array, the DR was wider and the amount of battery consumption was similar. The electrode array should be chosen by considering various patient factors, such as residual hearing.

A drug-repositioning screening identifies pentetic acid as a potential therapeutic agent for suppressing the elastase-mediated virulence of Pseudomonas aeruginosa.

Pseudomonas aeruginosa, a Gram-negative bacterium of clinical significance, produces elastase as a predominant exoprotease. Here, we screened a library of chemical compounds currently used for human medication and identified diethylene triamine penta-acetic acid (DTPA, pentetic acid) as an agent that suppresses the production of elastase. Elastase activity found in the prototype P. aeruginosa strain PAO1 was significantly decreased when grown with a concentration as low as 20 µM DTPA. Supplementation with Zn(2+) or Mn(2+) ions restored the suppressive effect of DTPA, suggesting that the DTPA-mediated decrease in elastase activity is associated with ion-chelating activity. In DTPA-treated PAO1 cells, transcription of the elastase-encoding lasB gene and levels of the Pseudomonas quinolone signal (PQS), a molecule that mediates P. aeruginosa quorum sensing (QS), were significantly downregulated, reflecting the potential involvement of the PQS QS system in DTPA-mediated elastase suppression. Biofilm formation was also decreased by DTPA treatment. When A549 alveolar type II-like adenocarcinoma cells were infected with PAO1 cells in the presence of DTPA, A549 cell viability was substantially increased. Furthermore, the intranasal delivery of DTPA to PAO1-infected mice alleviated the pathogenic effects of PAO1 cells in the animals. Together, our results revealed a novel function for a known molecule that may help treat P. aeruginosa airway infection.

Dietary vitamin intake correlates with hearing thresholds in the older population: the Korean National Health and Nutrition Examination Survey.

BACKGROUND: Previous animal studies have shown that vitamins may prevent age-related hearing loss. However, no concrete conclusions have been reached about the association between vitamin intake and presbycusis in humans. OBJECTIVE: We investigated the association between dietary vitamin intake and hearing thresholds in adults between 50 and 80 y of age by using data from a large population-based survey. DESIGN: We used data from the 2011 Korea National Health and Nutrition Examination Survey. A pure-tone audiogram and physical examination of the ear were performed, and vitamin intake was calculated by using the 24-h recall method. Data from 1910 participants were analyzed through univariate and multivariate linear regression analyses. RESULTS: After adjustment for age, sex, smoking, and exposure to occupational and explosive noise, intake of vitamin C correlated with better hearing at midfrequency (2000 and 3000 Hz) (coefficient: -0.012; 95% CI: -0.022, -0.002). Dietary supplement use was positively associated with better hearing at all frequencies. The univariate analysis indicated that dietary intakes of retinol, riboflavin, niacin, and vitamin C were positively correlated with better hearing at most frequencies. In contrast, serum concentrations of vitamin D were associated with worse hearing at mid and high (4000 and 6000 Hz) frequencies. CONCLUSIONS: Dietary intake of vitamin C was associated with better hearing in the older population. Because less than one-half of elderly participants in this study consumed a sufficient amount of vitamins, and vitamin intake decreased with age, we should consider proper diet counseling to prevent hearing decline.