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[PMID]: 26041110
[Au] Autor:Lloyd A; Hodder S; Havenith G
[Ad] Address:Environmental Ergonomics Research Centre, Loughborough University, Loughborough, United Kingdom.
[Ti] Title:The interaction between peripheral and central fatigue at different muscle temperatures during sustained isometric contractions.
[So] Source:Am J Physiol Regul Integr Comp Physiol;309(4):R410-20, 2015 Aug 15.
[Is] ISSN:1522-1490
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Changes in central fatigue have been linked to active and passive changes in core temperature, as well as integration of sensory feedback from thermoreceptors in the skin. However, the effects of muscle temperature (Tm), and thereby metaboreceptor and local afferent nerve temperature, on central fatigue (measured using voluntary activation percentage) during sustained, high muscle fatigue exercise remain unexamined. In this study, we investigated Tm across the range of cold to hot, and its effect on voluntary activation percentage during sustained isometric contractions of the knee extensors. The results suggest that contrary to brief contractions, during a sustained fatiguing contraction Tm significantly (P < 0.001) influences force output (-0.7%/°C increase) and central fatigue (-0.5%/°C increase), showing a negative relationship across the Tm continuum in moderately trained individuals. The negative relationship between voluntary activation percentage and Tm indicates muscle temperature may influence central fatigue during sustained and high muscle fatigue exercise. On the basis of on an integrative analysis between the present data and previous literature, the impact of core and muscle temperature on voluntary muscle activation is estimated to show a ratio of 5.5 to 1, respectively. Accordingly, Tm could assume a secondary or tertiary role in the reduction of voluntary muscle activation when body temperature leaves a thermoneutral range.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1152/ajpregu.00061.2015

  2 / 620546 MEDLINE  
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[PMID]: 26138464
[Au] Autor:Rosekrans SL; Baan B; Muncan V; van den Brink GR
[Ad] Address:Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands....
[Ti] Title:Esophageal development and epithelial homeostasis.
[So] Source:Am J Physiol Gastrointest Liver Physiol;309(4):G216-28, 2015 Aug 15.
[Is] ISSN:1522-1547
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The esophagus is a relatively simple organ that evolved to transport food and liquids through the thoracic cavity. It is the only part of the gastrointestinal tract that lacks any metabolic, digestive, or absorptive function. The mucosa of the adult esophagus is covered by a multilayered squamous epithelium with a remarkable similarity to the epithelium of the skin despite the fact that these tissues originate from two different germ layers. Here we review the developmental pathways involved in the establishment of the esophagus and the way these pathways regulate gut-airway separation. We summarize current knowledge of the mechanisms that maintain homeostasis in esophageal epithelial renewal in the adult and the molecular mechanism of the development of Barrett's metaplasia, the precursor lesion to esophageal adenocarcinoma. Finally, we examine the ongoing debate on the hierarchy of esophageal epithelial precursor cells and on the presence or absence of a specific esophageal stem cell population. Together the recent insights into esophageal development and homeostasis suggest that the pathways that establish the esophagus during development also play a role in the maintenance of the adult epithelium. We are beginning to understand how reflux of gastric content and the resulting chronic inflammation can transform the squamous esophageal epithelium to columnar intestinal type metaplasia in Barrett's esophagus.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1508
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1152/ajpgi.00088.2015

  3 / 620546 MEDLINE  
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[PMID]: 26012728
[Au] Autor:Paller CJ; Rudek MA; Zhou XC; Wagner WD; Hudson TS; Anders N; Hammers HJ; Dowling D; King S; Antonarakis ES; Drake CG; Eisenberger MA; Denmeade SR; Rosner GL; Carducci MA
[Ad] Address:Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland....
[Ti] Title:A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination.
[So] Source:Prostate;75(14):1518-25, 2015 Oct.
[Is] ISSN:1097-0045
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: New therapies are being explored as therapeutic options for men with biochemically recurrent prostate cancer (BRPC) who wish to defer androgen deprivation therapy. MPX is pulverized muscadine grape (Vitis rotundifolia) skin that contains ellagic acid, quercetin, and resveratrol and demonstrates preclinical activity against prostate cancer cells in vitro. METHODS: In the phase I portion of this phase I/II study, non-metastatic BRPC patients were assigned to increasing doses of MPX (Muscadine Naturals. Inc., Clemmons, NC) in cohorts of two patients, with six patients at the highest dose, using a modified continual reassessment method. Initial dose selection was based on preclinical data showing the equivalent of 500 to 4,000 mg of MPX to be safe in mouse models. The primary endpoint was the recommended phase II dosing regimen. RESULTS: The cohort (n = 14, 71% Caucasian, 29% black) had a median follow-up of 19.2 (6.2-29.7) months, median age of 61 years, and median Gleason score of 7. Four patients had possibly related gastrointestinal symptoms, including grade 1 flatulence, grade 1 soft stools, and grade 1 eructation. No other related adverse events were reported and one patient reported improvement of chronic constipation. Six of 14 patients came off study for disease progression (five metastatic, one rising PSA) after exposure for a median of 15 months. One patient came off for myasthenia gravis that was unrelated to treatment. Seven patients remain on study. The lack of dose-limiting toxicities led to the selection of 4,000 mg/d as the highest dose for further study. Median within-patient PSADT increased by 5.3 months (non-significant, P = 0.17). No patients experienced a maintained decline in serum PSA from baseline. CONCLUSION: These data suggest that 4,000 mg of MPX is safe, and exploratory review of a lengthening in PSADT of a median of 5.3 months supports further exploration of MPX. Both low-dose (500 mg) and high-dose (4,000 mg) MPX are being further investigated in a randomized, multicenter, placebo-controlled, dose-evaluating phase II trial. Prostate 75:1518-1525, 2015. © 2015 Wiley Periodicals, Inc.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150815
[Lr] Last revision date:150815
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/pros.23024

  4 / 620546 MEDLINE  
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[PMID]: 26164446
[Au] Autor:Mattingly JK; Greene NT; Jenkins HA; Tollin DJ; Easter JR; Cass SP
[Ad] Address:*Departments of Otolaryngology and †Physiology and Biophysics, University of Colorado School of Medicine, Aurora; and ‡Cochlear Boulder LLC, Boulder, Colorado, U.S.A.
[Ti] Title:Effects of Skin Thickness on Cochlear Input Signal Using Transcutaneous Bone Conduction Implants.
[So] Source:Otol Neurotol;36(8):1403-11, 2015 Sep.
[Is] ISSN:1537-4505
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:HYPOTHESIS: Intracochlear sound pressures (PIC) and velocity measurements of the stapes, round window, and promontory (VStap/RW/Prom) will show frequency-dependent attenuation using magnet-based transcutaneous bone conduction implants (TCBCIs) in comparison with direct-connect skin-penetrating implants (DCBCIs). BACKGROUND: TCBCIs have recently been introduced as alternatives to DCBCIs. Clinical studies have demonstrated elevated high-frequency thresholds for TCBCIs as compared with DCBCIs; however, little data exist examining the direct effect of skin thickness on the cochlear input signal using TCBCIs. METHODS: Using seven cadaveric heads, PIC was measured in the scala vestibuli and tympani with fiber-optic pressure sensors concurrently with VStap/RW/Prom via laser Doppler vibrometry. Ipsilateral titanium implant fixtures were placed and connected to either a DCBCI or a TCBCI. Soft tissue flaps with varying thicknesses (no flap and 3, 6, and 9 mm) were placed successively between the magnetic plate and sound processor magnet. A bone conduction transducer coupled to custom software provided pure-tone stimuli between 120 and 10,240 Hz. RESULTS: Stimulation via the DCBCI produced the largest response magnitudes. The TCBCI showed similar PSV/ST and VStap/RW/Prom with no intervening flap and a frequency-dependent nonlinear reduction of magnitude with increasing flap thickness. Phase shows a comparable dependence on transmission delay as the acoustic baseline, and the slope steepens at higher frequencies as flap thickness increases, suggesting a longer group delay. CONCLUSION: Proper soft tissue management is critical to optimize the cochlear input signal. The skin thickness-related effects on cochlear response magnitudes should be taken into account when selecting patients for a TCBCI.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150815
[Lr] Last revision date:150815
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1097/MAO.0000000000000814

  5 / 620546 MEDLINE  
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[PMID]: 26269744
[Au] Autor:Hoogenboom M; van Amerongen MJ; Eikelenboom DC; Wassink M; den Brok MH; Hulsbergen-van de Kaa C; Dumont E; Adema GJ; Heerschap A; Fütterer JJ
[Ad] Address:Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6500 HB Nijmegen, The Netherlands....
[Ti] Title:Development of a high-field MR-guided HIFU setup for thermal and mechanical ablation methods in small animals.
[So] Source:J Ther Ultrasound;3:14, 2015.
[Is] ISSN:2050-5736
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Thermal and mechanical high intensity focused ultrasound (HIFU) ablation techniques are in development for non-invasive treatment of cancer. However, knowledge of in vivo histopathologic and immunologic reactions after HIFU ablation is still limited. This study aims to create a setup for evaluation of different HIFU ablation methods in mouse tumors using high-field magnetic resonance (MR) guidance. An optimized MR-guided-HIFU setup could be used to increase knowledge of the different pathologic and immunologic reactions to different HIFU ablation methods. METHODS: Three different HIFU treatment strategies were applied in mouse melanomas (B16): a thermal (continuous wave), a mechanical (5 ms pulsed wave), and an intermediate setting (20 ms pulsed wave) for HIFU ablation, all under MR guidance using a 7 tesla animal MR system. Histopathologic evaluation was performed 3 days after treatment. RESULTS: The focus of the ultrasound transducer could accurately be positioned within the tumor under MR image guidance, without substantial damage to the surrounding tissue and skin. All mice retained complete use of the treated leg after treatment. Temperatures of >60, <50, and <44 °C were reached during thermal, intermediate, and mechanical HIFU ablation, respectively. Thermal-treated tumors showed large regions of coagulative necrosis. Tumors of both the mechanical and intermediate groups showed fractionated tissue with islands of necrosis and some pseudocysts with hemorrhage. CONCLUSION: A stable small animal MR-guided HIFU setup was designed and evaluated for follow-up MR imaging and histopathologic responses of the treated tumors. This will facilitate further studies with a larger number of mice for detailed evaluation of the pathologic and immunologic response to different HIFU strategies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150815
[Lr] Last revision date:150815
[Da] Date of entry for processing:150813
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1186/s40349-015-0035-6

  6 / 620546 MEDLINE  
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[PMID]: 25905589
[Au] Autor:Li Y; Lei D; Swindell WR; Xia W; Weng S; Fu J; Worthen CA; Okubo T; Johnston A; Gudjonsson JE; Voorhees JJ; Fisher GJ
[Ad] Address:Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA....
[Ti] Title:Age-Associated Increase in Skin Fibroblast-Derived Prostaglandin E2 Contributes to Reduced Collagen Levels in Elderly Human Skin.
[So] Source:J Invest Dermatol;135(9):2181-8, 2015 Sep.
[Is] ISSN:1523-1747
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Production of type I collagen declines during aging, leading to skin thinning and impaired function. Prostaglandin E2 (PGE2) is a pleiotropic lipid mediator that is synthesized from arachidonic acid by the sequential actions of cyclooxygenases (COX) and PGE synthases (PTGES). PGE2 inhibits collagen production by fibroblasts in vitro. We report that PTGES1 and COX2 progressively increase with aging in sun-protected human skin. PTGES1 and COX2 mRNA were increased 3.4-fold and 2.7-fold, respectively, in the dermis of elderly (>80 years) versus young (21-30 years) individuals. Fibroblasts were the major cell source of both enzymes. PGE2 levels were increased 70% in elderly skin. Fibroblasts in aged skin display reduced spreading due to collagen fibril fragmentation. To investigate the relationship between spreading and PGE2 synthesis, fibroblasts were cultured on micropost arrays or hydrogels of varying mechanical compliance. Reduced spreading/mechanical force resulted in increased expression of both PTGES1 and COX2 and elevated levels of PGE2. Inhibition of PGE2 synthesis by diclofenac enhanced collagen production in skin organ cultures. These data suggest that reduced spreading/mechanical force of fibroblasts in aged skin elevates PGE2 production, contributing to reduced collagen production. Inhibition of PGE2 production may be therapeutically beneficial for combating age-associated collagen deficit in human skin.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150815
[Lr] Last revision date:150815
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/jid.2015.157

  7 / 620546 MEDLINE  
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[PMID]: 25860385
[Au] Autor:Bai X; Lei M; Shi J; Yu Y; Qiu W; Lai X; Liu Y; Yang T; Yang L; Widelitz RB; Chuong CM; Lian X
[Ad] Address:Department of Cell Biology, Third Military Medical University, Chongqing, People's Republic of China....
[Ti] Title:Roles of GasderminA3 in Catagen-Telogen Transition During Hair Cycling.
[So] Source:J Invest Dermatol;135(9):2162-72, 2015 Sep.
[Is] ISSN:1523-1747
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Hair follicles undergo cyclic behavior through regression (catagen), rest (telogen), and regeneration (anagen) during postnatal life. The hair cycle transition is strictly regulated by the autonomous and extrinsic molecular environment. However, whether there is a switch controlling catagen-telogen transition remains largely unknown. Here we show that hair follicles cycle from catagen to the next anagen without transitioning through a morphologically typical telogen after Gsdma3 mutation. This leaves an ESLS (epithelial strand-like structure) during the time period corresponding to telogen phase in WT mice. Molecularly, Wnt10b is upregulated in Gsdma3 mutant mice. Restoration of Gsdma3 expression in AE (alopecia and excoriation) mouse skin rescues hair follicle telogen entry and significantly decreases the Wnt10b-mediated Wnt/ß-catenin signaling pathway. Overexpression of Wnt10b inhibits telogen entry by increasing epithelial strand cell proliferation. Subsequently, hair follicles with a Gsdma3 mutation enter the second anagen simultaneously as WT mice. Hair follicles cannot enter the second anagen with ectopic WT Gsdma3 overexpression. A luciferase reporter assay proves that Gsdma3 directly suppresses Wnt signaling. Our findings suggest that Gsdma3 has an important role in catagen-telogen transition by balancing the Wnt signaling pathway and that morphologically typical telogen is not essential for the initiation of a new hair cycle.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150815
[Lr] Last revision date:150815
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/jid.2015.147

  8 / 620546 MEDLINE  
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[PMID]: 25848980
[Au] Autor:Monteleon CL; McNeal A; Duperret EK; Oh SJ; Schapira E; Ridky TW
[Ad] Address:Department of Dermatology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA....
[Ti] Title:IQGAP1 and IQGAP3 Serve Individually Essential Roles in Normal Epidermal Homeostasis and Tumor Progression.
[So] Source:J Invest Dermatol;135(9):2258-65, 2015 Sep.
[Is] ISSN:1523-1747
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:IQ motif-containing GTPase-activating protein (IQGAP) scaffolding proteins regulate many essential cellular processes including growth factor receptor signaling, cytoskeletal rearrangement, adhesion, and proliferation and are highly expressed in many cancers. Using genetically engineered human skin tissue in vivo, we demonstrate that diminished, sub-physiologic expression of IQGAP1 or IQGAP3 is sufficient to maintain normal epidermal homeostasis, whereas significantly higher levels are required to support tumorigenesis. To target this tumor-specific IQGAP requirement in vivo, we engineered epidermal keratinocytes to express individual IQGAP protein domains designed to compete with endogenous IQGAPs for effector protein binding. Expression of the IQGAP1-IQ motif decoy domain in epidermal tissue in vivo inhibits oncogenic Ras-driven mitogen-activated protein kinase signaling and antagonizes tumorigenesis, without disrupting normal epidermal proliferation or differentiation. These findings define essential non-redundant roles for IQGAP1 and IQGAP3 in the epidermis and demonstrate the potential of IQGAP antagonism for cancer therapy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150815
[Lr] Last revision date:150815
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/jid.2015.140

  9 / 620546 MEDLINE  
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[PMID]: 26269720
[Au] Autor:Hashmi F; Nester C; Wright C; Newton V; Lam S
[Ad] Address:School of Health Sciences, Centre for Health Sciences Research, University of Salford, Manchester, UK....
[Ti] Title:Characterising the biophysical properties of normal and hyperkeratotic foot skin.
[So] Source:J Foot Ankle Res;8:35, 2015.
[Is] ISSN:1757-1146
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Plantar foot skin exhibits unique biophysical properties that are distinct from skin on other areas of the body. This paper characterises, using non-invasive methods, the biophysical properties of foot skin in healthy and pathological states including xerosis, heel fissures, calluses and corns. METHODS: Ninety three people participated. Skin hydration, elasticity, collagen and elastin fibre organisation and surface texture was measured from plantar calluses, corns, fissured heel skin and xerotic heel skin. Previously published criteria were applied to classify the severity of each skin lesion and differences in the biophysical properties compared between each classification. RESULTS: Calluses, corns, xerotic heel skin and heel fissures had significantly lower levels of hydration; less elasticity and greater surface texture than unaffected skin sites (p < 0.01). Some evidence was found for a positive correlation between hydration and elasticity data (r ≤ 0.65) at hyperkeratotic sites. Significant differences in skin properties (with the exception of texture) were noted between different classifications of skin lesion. CONCLUSIONS: This study provides benchmark data for healthy and different severities of pathological foot skin. These data have applications ranging from monitoring the quality of foot skin, to measuring the efficacy of therapeutic interventions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150815
[Lr] Last revision date:150815
[Da] Date of entry for processing:150813
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1186/s13047-015-0092-7

  10 / 620546 MEDLINE  
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[PMID]: 26269703
[Au] Autor:Suchonwanit P; Chaiyabutr C; Vachiramon V
[Ad] Address:Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
[Ti] Title:Primary Cutaneous Chrysosporium Infection following Ear Piercing: A Case Report.
[So] Source:Case Rep Dermatol;7(2):136-40, 2015 May-Aug.
[Is] ISSN:1662-6567
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:Chrysosporium is a large genus of saprophytic fungi that is commonly found in the soil. Infection caused by this organism is rare in humans and typically occurs in immunocompromised patients. Primary cutaneous Chrysosporium infection is relatively rare and has been reported in a heart transplant patient. The prognosis is usually favorable, but very poor in the setting of persistent profound immunosuppression. We herein report a case of primary cutaneous Chrysosporium infection following ear piercing in an immunocompetent patient. It is important for clinicians to consider this condition in patients with slow-onset skin and soft tissue infection following cutaneous injury, even in an immunocompetent setting.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150815
[Lr] Last revision date:150815
[Da] Date of entry for processing:150813
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1159/000436989


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