bluuebunny/crossref_metadata_2025 huggingface dataset:
Garlic oil polysulfides: H2S- and O2-independent prooxidants in buffer and antioxidants in cells
Authors: DeLeon Eric R. , Gao Yan , Huang Evelyn , Olson Kenneth R.
Published: April 2016

The health benefits of garlic and other organosulfur-containing foods are well recognized and have been attributed to both prooxidant and antioxidant activities. The effects of garlic are surprisingly similar to those of hydrogen sulfide (H2S), which is also known to be released from garlic under certain conditions. However, recent evidence suggests that polysulfides, not H2S, may be the actual mediator of physiological signaling. In this study, we monitored formation of H2S and polysulfides from garlic oil in buffer and in human embryonic kidney (HEK) 293 cells with fluorescent dyes, 7-azido-4-methylcoumarin and SSP4, respectively and redox activity with two redox indicators redox-sensitive green fluorescent protein (roGFP) and DCF. Our results show that H2S release from garlic oil in buffer requires other low-molecular-weight thiols, such as cysteine (Cys) or glutathione (GSH), whereas polysulfides are readily detected in garlic oil alone. Administration of garlic oil to cells rapidly increases intracellular polysulfide but has minimal effects on H2S unless Cys or GSH are also present in the extracellular medium. We also observed that garlic oil and diallyltrisulfide (DATS) potently oxidized roGFP in buffer but did not affect DCF. This appears to be a direct polysulfide-mediated oxidation that does not require a reactive oxygen species intermediate. Conversely, when applied to cells, garlic oil became a significant intracellular reductant independent of extracellular Cys or GSH. This suggests that intracellular metabolism and further processing of the sulfur moieties are necessary to confer antioxidant properties to garlic oil in vivo.
Prior exercise training blunts short-term high-fat diet-induced weight gain
Authors: Snook Laelie A. , MacPherson Rebecca E. K. , Monaco Cynthia M. F. , Frendo-Cumbo Scott , Castellani Laura , Peppler Willem T. , Anderson Zachary G. , Buzelle Samyra L. , LeBlanc Paul J. , Holloway Graham P. , Wright David C.
Published: April 2016

High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (−30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet.
Mechanisms of animal diapause: recent developments from nematodes, crustaceans, insects, and fish
Authors: Hand Steven C. , Denlinger David L. , Podrabsky Jason E. , Roy Richard
Published: April 2016

Life cycle delays are beneficial for opportunistic species encountering suboptimal environments. Many animals display a programmed arrest of development (diapause) at some stage(s) of their development, and the diapause state may or may not be associated with some degree of metabolic depression. In this review, we will evaluate current advancements in our understanding of the mechanisms responsible for the remarkable phenotype, as well as environmental cues that signal entry and termination of the state. The developmental stage at which diapause occurs dictates and constrains the mechanisms governing diapause. Considerable progress has been made in clarifying proximal mechanisms of metabolic arrest and the signaling pathways like insulin/Foxo that control gene expression patterns. Overlapping themes are also seen in mechanisms that control cell cycle arrest. Evidence is emerging for epigenetic contributions to diapause regulation via small RNAs in nematodes, crustaceans, insects, and fish. Knockdown of circadian clock genes in selected insect species supports the importance of clock genes in the photoperiodic response that cues diapause. A large suite of chaperone-like proteins, expressed during diapause, protects biological structures during long periods of energy-limited stasis. More information is needed to paint a complete picture of how environmental cues are coupled to the signal transduction that initiates the complex diapause phenotype, as well as molecular explanations for how the state is terminated. Excellent examples of molecular memory in post-dauer animals have been documented in Caenorhabditis elegans. It is clear that a single suite of mechanisms does not regulate diapause across all species and developmental stages.
Peripheral venous distension elicits a blood pressure raising reflex in young and middle-aged adults
Authors: Matthews Evan L. , Brian Michael S. , Coyle Dana E. , Edwards David G. , Stocker Sean D. , Wenner Megan M. , Farquhar William B.
Published: April 2016

Distension of peripheral veins in humans elicits a pressor and sympathoexcitatory response that is mediated through group III/IV skeletal muscle afferents. There is some evidence that autonomic reflexes mediated by these sensory fibers are blunted with increasing age, yet to date the venous distension reflex has only been studied in young adults. Therefore, we tested the hypothesis that the venous distension reflex would be attenuated in middle-aged compared with young adults. Nineteen young (14 men/5 women, 25 ± 1 yr) and 13 middle-aged (9 men/4 women, 50 ± 2 yr) healthy normotensive participants underwent venous distension via saline infusion through a retrograde intravenous catheter in an antecubital vein during limb occlusion. Beat-by-beat blood pressure, muscle sympathetic nerve activity (MSNA), and model flow-derived cardiac output (Q), and total peripheral resistance (TPR) were recorded throughout the trial. Mean arterial pressure (MAP) increased during the venous distension in both young (baseline 83 ± 2, peak 94 ± 3 mmHg; P < 0.05) and middle-aged adults (baseline 88 ± 2, peak 103 ± 3 mmHg; P < 0.05). MSNA also increased in both groups [young: baseline 886 ± 143, peak 1,961 ± 242 arbitrary units (AU)/min; middle-aged: baseline 1,164 ± 225, peak 2,515 ± 404 AU/min; both P < 0.05]. TPR ( P < 0.001), but not Q ( P = 0.76), increased during the trial. However, the observed increases in blood pressure, MSNA, and TPR were similar between young and middle-aged adults. Additionally, no correlation was found between age and the response to venous distension (all P > 0.05). These findings suggest that peripheral venous distension elicits a pressor and sympathetic response in middle-aged adults similar to the response observed in young adults.
Cutaneous vascular and sweating responses to intradermal administration of prostaglandin E1 and E2 in young and older adults: a role for nitric oxide?
Authors: Fujii Naoto , Singh Maya Sarah , Halili Lyra , Boulay Pierre , Sigal Ronald J. , Kenny Glen P.
Published: April 2016

Cyclooxygenase (COX) contributes to cutaneous vasodilation and sweating responses; however, the mechanisms underpinning these responses remain unknown. We hypothesized that prostaglandin E1 (PGE1) and E2 (PGE2) (COX-derived vasodilator products) directly mediate cutaneous vasodilation and sweating through nitric oxide synthase (NOS)-dependent mechanisms in young adults. Furthermore, we hypothesized that this response is diminished in older adults, since aging attenuates COX-dependent cutaneous vasodilation and sweating. In 9 young (22 ± 5 yr) and 10 older (61 ± 6 yr) adults, cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites receiving incremental doses (0.05, 0.5, 5, 50, 500 μM each for 25 min) of PGE1 or PGE2 with and without coadministration of 10 mM Nω-nitro-l-arginine, a nonspecific NOS inhibitor. Nω-nitro-l-arginine attenuated PGE1-mediated increases in CVC at all concentrations in young adults, whereas it reduced PGE2-mediated increases in CVC at lower concentrations (0.05–0.5 μM) in older adults (all P < 0.05). However, the magnitude of the PGE1- and PGE2-mediated increases in CVC did not differ between groups (all P > 0.05). Neither PGE1 nor PGE2 increased sweat rate at any of the administered concentrations for either the young or older adults (all P > 0.05). We show that although cutaneous vascular responsiveness to PGE1 and PGE2 is similar between young and older adults, the cutaneous vasodilator response is partially mediated through NOS albeit via low-to-high concentrations of PGE1 in young adults and low concentrations of PGE2 in older adults, respectively. We also show that in both young and older adults, PGE1 and PGE2 do not increase sweat rate under normothermic conditions.
Beta modulation reflects name retrieval in the human anterior temporal lobe: an intracranial recording study
Authors: Abel Taylor J. , Rhone Ariane E. , Nourski Kirill V. , Ando Timothy K. , Oya Hiroyuki , Kovach Christopher K. , Kawasaki Hiroto , Howard Matthew A. , Tranel Daniel
Published: April 2016

Naming people, places, and things is a fundamental human ability that is often impaired in patients with language-dominant anterior temporal lobe (ATL) dysfunction or ATL resection as part of epilepsy treatment. Convergent lines of evidence point to the importance of the ATL in name retrieval. The physiologic mechanisms that mediate name retrieval in the ATL, however, are not well understood. The purpose of this study was to characterize the electrophysiologic responses of the human ATL during overt cued naming of famous people and objects. Eight neurosurgical patients with suspected temporal lobe epilepsy who underwent implantation of intracranial electrodes for seizure focus localization were the subjects of this study. Specialized coverage of the ATL was achieved in each subject. The subjects named pictures of U.S. presidents and images of common hand-held tools. Event-related band power was measured for each ATL recording site. Both the left and right ATL demonstrated robust and focal increases in beta-band (14–30 Hz) power during person and tool naming. The onset of this response typically occurred at 400 ms but sometimes as early as 200 ms. Visual naming of famous people and tools is associated with robust and localized modulation of the beta band in both the left and right ATL. Measurement of visual naming responses may provide the groundwork for future mapping modalities to localize eloquent cortex in the ATL.
Dissociating vestibular and somatosensory contributions to spatial orientation
Authors: Alberts Bart B. G. T. , Selen Luc P. J. , Bertolini Giovanni , Straumann Dominik , Medendorp W. Pieter , Tarnutzer Alexander A.
Published: April 2016

Inferring object orientation in the surroundings heavily depends on our internal sense of direction of gravity. Previous research showed that this sense is based on the integration of multiple information sources, including visual, vestibular (otolithic), and somatosensory signals. The individual noise characteristics and contributions of these sensors can be studied using spatial orientation tasks, such as the subjective visual vertical (SVV) task. A recent study reported that patients with complete bilateral vestibular loss perform similar as healthy controls on these tasks, from which it was conjectured that the noise levels of both otoliths and body somatosensors are roll-tilt dependent. Here, we tested this hypothesis in 10 healthy human subjects by roll tilting the head relative to the body to dissociate tilt-angle dependencies of otolith and somatosensory noise. Using a psychometric approach, we measured the perceived orientation, and its variability, of a briefly flashed line relative to the gravitational vertical (SVV). Measurements were taken at multiple body-in-space orientations (−90 to 90°, steps of 30°) and head-on-body roll tilts (30° left ear down, aligned, 30° right ear down). Results showed that verticality perception is processed in a head-in-space reference frame, with a systematic SVV error that increased with larger head-in-space orientations. Variability patterns indicated a larger contribution of the otolith organs around upright and a more substantial contribution of the body somatosensors at larger body-in-space roll tilts. Simulations show that these findings are consistent with a statistical model that involves tilt-dependent noise levels of both otolith and somatosensory signals, confirming dynamic shifts in the weights of sensory inputs with tilt angle.
Regionally distinct cutaneous afferent populations contribute to reflex modulation evoked by stimulation of the tibial nerve during walking
Authors: Nakajima Tsuyoshi , Suzuki Shinya , Futatsubashi Genki , Ohtsuska Hiroyuki , Mezzarane Rinaldo A. , Barss Trevor S. , Klarner Taryn , Zehr E. Paul , Komiyama Tomoyoshi
Published: April 2016

During walking, cutaneous reflexes in ankle flexor muscle [tibialis anterior (TA)] evoked by tibial nerve (TIB) stimulation are predominantly facilitatory at early swing phase but reverse to suppression at late swing phase. Although the TIB innervates a large portion of the skin of the foot sole, the extent to which specific foot-sole regions contribute to the reflex reversals during walking remains unclear. Therefore, we investigated regional cutaneous contributions from discrete portions of the foot sole on reflex reversal in TA following TIB stimulation during walking. Summation effects on reflex amplitudes, when applying combined stimulation from foot-sole regions with TIB, were examined. Middle latency responses (MLRs; 70–120 ms) after TIB stimulation were strongly facilitated during the late stance to mid-swing phases and reversed to suppression just before heel (HL) strike. Both forefoot-medial (f-M) and forefoot-lateral stimulation in the foot sole induced facilitation during stance-to-swing transition phases, but HL stimulation evoked suppression during the late stance to the end of swing phases. At the stance-to-swing transition, a summation of MLR amplitude occurred only for combined f-M&TIB stimulation. However, the same was not true for the combined HL&TIB stimulation. At the swing-to-stance transition, there was a suppressive reflex summation only for HL&TIB stimulation. In contrast, this summation was not observed for the f-M&TIB stimulation. Our results suggest that reflex reversals evoked by TIB stimulation arise from distinct reflex pathways to TA produced by separate afferent populations innervating specific regions of the foot sole.
A sodium afterdepolarization in rat superior colliculus neurons and its contribution to population activity
Authors: Ghitani Nima , Bayguinov Peter O. , Basso Michele A. , Jackson Meyer B.
Published: April 2016

The mammalian superior colliculus (SC) is a midbrain structure that integrates multimodal sensory inputs and computes commands to initiate rapid eye movements. SC neurons burst with the sudden onset of a visual stimulus, followed by persistent activity that may underlie shifts of attention and decision making. Experiments in vitro suggest that circuit reverberations play a role in the burst activity in the SC, but the origin of persistent activity is unclear. In the present study we characterized an afterdepolarization (ADP) that follows action potentials in slices of rat SC. Population responses seen with voltage-sensitive dye imaging consisted of rapid spikes followed immediately by a second distinct depolarization of lower amplitude and longer duration. Patch-clamp recordings showed qualitatively similar behavior: in nearly all neurons throughout the SC, rapid spikes were followed by an ADP. Ionic and pharmacological manipulations along with experiments with current and voltage steps indicated that the ADP of SC neurons arises from Na+ current that either persists or resurges following Na+ channel inactivation at the end of an action potential. Comparisons of pharmacological properties and frequency dependence revealed a clear parallel between patch-clamp recordings and voltage imaging experiments, indicating a common underlying membrane mechanism for the ADP in both single neurons and populations. The ADP can initiate repetitive spiking at intervals consistent with the frequency of persistent activity in the SC. These results indicate that SC neurons have intrinsic membrane properties that can contribute to electrical activity that underlies shifts of attention and decision making.
Influence of Gelatin-Thrombin Matrix Tissue Sealant on Bacterial Colony Formation and Risk of Pelvic Infection
Authors: Jarrett Michael J. , Vázquez-Torres Andres , Frank Daniel N. , McCollister Bruce D. , Henthorn Patrick K. , Ir Diana , Sheeder Jeanelle , Guy Michael S. , Anwar Hiba Q. , Behbakht Kian
Published: April 2016

Objective. Gelatin-thrombin matrix (GTM) tissue sealant use was previously identified as an independent predictor of pelvic infection following hysterectomies. We aim to elucidate contributing factors by assessing influence of GTM on bacterial colony formation and characterizing bacteria present at the vaginal cuff.Methods.Escherichia coliwas incubated in phosphate-buffered saline (PBS) and pelvic washings with and without GTM to assess influence on colony formation. Pelvic washings of the vaginal cuff were collected from hysterectomies occurring from June through October 2015.In vitrotechniques, 16S rRNA gene qPCR, and 16S amplicon sequencing were performed with washings to characterize bacteria at the vaginal cuff.Results. Mean bacterial colony formation in PBS was greater forE. coliincubated in the presence of GTM (1.48 × 107 CFU/mL) versus without (9.95 × 105 CFU/mL) following 20-hour incubation (p=0.001). Out of 61 pelvic washings samples, 3 were culture positive (≥5000 CFU/mL) withEnterococcus faecalis.Conclusion.In vitroexperiments support a facilitating role of GTM on colony formation ofE. coliin PBS. However, given the negative results of surgical site washings following adequate disinfection, the role of GTM in promoting posthysterectomy pelvic infections may be limited. Analysis of pelvic washings revealed presence ofE. faecalis, but results were inconclusive. Further studies are recommended.
Correlation ofA2bARandKLF4/KLF15with Obesity-Dyslipidemia Induced Inflammation in Uygur Population
Authors: Wang Cuizhe , Ha Xiaodan , Li Wei , Xu Peng , Gu Yajuan , Wang Tingting , Wang Yan , Xie Jianxin , Zhang Jun
Published: April 2016

In this paper, the researchers collected visceral adipose tissue from the Uygur population, which were divided into two groups: the normal control group (NC,n=50, 18.0 kg/m2≤ BMI ≤ 23.9 kg/m2) and the obese group (OB,n=45, BMI ≥ 28 kg/m2), and then use real-time PCR to detect the mRNA expression level of key genes involved in inflammation signaling pathway. The findings suggest that, in obese status, the lower expression level ofA2bAR,KLF4, andKLF15of visceral adipose tissue may correlate with obese-dyslipidemia induced inflammation in Uygur population.
Additional Analgesia for Central Venous Catheter Insertion: A Placebo Controlled Randomized Trial of Dexmedetomidine and Fentanyl
Authors: Samantaray Aloka , Hanumantha Rao Mangu , Sahu Chitta Ranjan
Published: April 2016

We aimed to show that a single preprocedural dose of either dexmedetomidine or fentanyl reduces procedural pain and discomfort and provides clinically acceptable sedation. In this prospective, double-blind study, sixty patients scheduled for elective surgery and requiring planned central venous catheter insertion were randomized to receive dexmedetomidine (1 μg/kg), fentanyl (1 μg/kg), or 0.9% normal saline intravenously over ten minutes followed by local anesthetic field infiltration before attempting central venous catheterization. The primary outcome measures are assessment and analysis of pain, discomfort, and sedation level before, during, and after the central venous catheter insertion at five time points. The median (IQR) pain score is worst for normal saline group at local anaesthetic injection [6 (4–6.7)] which was significantly attenuated by addition of fentanyl [3 (2–4)] and dexmedetomidine [4 (3–5)] in the immediate postprocedural period (P=0.001). However, the procedure related discomfort was significantly lower in dexmedetomidine group compared to fentanyl group in the first 10 min of procedure after local anaesthetic Injection (P=0.001). Fentanyl is more analgesically efficient for central venous catheter insertion along with local anaesthetic injection. However, dexmedetomidine has the potential to be superior to fentanyl and placebo in terms of providing comfort to the patients during the procedure.
Correlation between Serum Osteopontin and miR-181a Levels in Allergic Rhinitis Children
Authors: Liu Wenlong , Zeng Qingxiang , Luo Renzhong
Published: April 2016

Background. Osteopontin (OPN) has been proved to be associated with allergic airway inflammation. However, the roles of OPN and its regulation in childhood allergic rhinitis (AR) are poorly understood.Objective. This study aims to evaluate the expression of OPN and miR-181a in children with AR and their association with Th1/Th2 immune response.Methods. Children who suffered from AR were included along with control subjects. Serum was collected to examine the level of OPN and Th1/Th2 cytokines by enzyme-linked immunosorbent assay (ELISA) and the level of miR-181a by quantitative polymerase chain reaction (qPCR).Results. Children with AR had significantly higher serum levels of OPN and lower serum levels of miR-181a than healthy controls. Furthermore, serum levels of OPN were positively correlated with Th2 cytokine and negatively correlated with Th1 cytokine. On the contrary, miR-181a level had a negative correlation with IL-4/IL-5 and positive correlation with IFN-γ/IL-12. More importantly, there was also significant negative correlation between OPN and miR-181a.Conclusion. The OPN protein and miR-181a levels may serve as predictors of disease severity in childhood AR and appear to be promising targets for modulating AR.
The Ribonucleic Complex HuR-MALAT1 Represses CD133 Expression and Suppresses Epithelial–Mesenchymal Transition in Breast Cancer
Authors: Latorre Elisa , Carelli Stephana , Raimondi Ivan , D'Agostino Vito , Castiglioni Ilaria , Zucal Chiara , Moro Giacomina , Luciani Andrea , Ghilardi Giorgio , Monti Eleonora , Inga Alberto , Di Giulio Anna Maria , Gorio Alfredo , Provenzani Alessandro
Published: April 2016

Epithelial-to-mesenchymal transition (EMT) is a core process underlying cell movement during embryonic development and morphogenesis. Cancer cells hijack this developmental program to execute a multi-step cascade, leading to tumorigenesis and metastasis. CD133 (PROM1), a marker of cancer stem cells, has been shown to facilitate EMT in various cancers, but the regulatory networks controlling CD133 gene expression and function in cancer remain incompletely delineated. In this study, we show that a ribonucleoprotein complex including the long noncoding RNA MALAT1 and the RNA-binding protein HuR (ELAVL1) binds the CD133 promoter region to regulate its expression. In luminal nonmetastatic MCF-7 breast cancer cells, HuR silencing was sufficient to upregulate N-cadherin (CDH2) and CD133 along with a migratory and mesenchymal-like phenotype. Furthermore, we found that in the basal-like metastatic cell line MDA-MB-231 and primary triple-negative breast cancer tumor cells, the repressor complex was absent from the CD133-regulatory region, but was present in the MCF-7 and primary ER+ tumor cells. The absence of the complex from basal-like cells was attributed to diminished expression of MALAT1, which, when overexpressed, dampened CD133 levels. In conclusion, our findings suggest that the failure of a repressive complex to form or stabilize in breast cancer promotes CD133 upregulation and an EMT-like program, providing new mechanistic insights underlying the control of prometastatic processes. Cancer Res; 76(9); 2626–36. ©2016 AACR.
Nationwide 2.5-Year School-Based Public Health Intervention Program Designed to Reduce the Incidence of Caries in Children of Grenada
Authors: Wolff Mark S. , Hill Rachel , Wilson-Genderson Maureen , Hirsch Stuart , Dasanayake Ananda P.
Published: April 2016

This paper describes an innovative public health intervention, called ‘Smile Grenada', targeting the oral health of children in Grenada utilizing the resources of a US dental school, several oral health care companies, local governmental and public health authorities, and Grenadian school personnel. Methods: Preintervention visual/tactile caries examinations were collected from 1,092 schoolchildren (mean age 9.9 years, standard deviation, SD = 3.7) in 2010. The intervention included: (1) classroom-based toothbrushing with fluoridated toothpaste, (2) fluoride varnish applied by trained dental students, teachers and local providers 3 times a year and (3) glass ionomer sealants placed on first permanent molars in children aged 6-8 years. Postintervention data were collected in May, 2013 (n = 2,301, mean age 9.8 years, SD = 3.7). Decayed and demineralized surfaces were examined for the whole sample and decay/demineralization and sealant retention on 6-year molars were examined separately (ages 6-8 in 2013 cohort). Results: The number of decayed/demineralized surfaces declined across all age groups. The average number of decayed surfaces dropped from 9 at baseline to just over 6 (F1, 3,393 = 69.8, p < 0.0001) and the average number of demineralized surfaces dropped from 6 to less than 2 (1.8 surfaces; F1, 3,393 = 819.0, p < 0.0001). For children aged 6-8 years, there were statistically significantly fewer decayed surfaces (t1, 2,086 = 12.40, p < 0.0001; mean baseline 0.93, SD = 1.75; mean follow-up 0.23, SD = 0.83) and demineralized surfaces (t1, 2,086 = 19.7, p < 0.0001; mean baseline 2.11, SD = 2.74; mean follow-up 0.50, SD = 0.97) on 6-year molars. The Smile Grenada program successfully demonstrated a locally sustainable model for improving oral health in children in a developing country.
Network Consumption and Storage Needs when Working in a Full-Time Routine Digital Environment in a Large Nonacademic Training Hospital
Authors: Nap Marius
Published: April 2016

Objective: Digital pathology is indisputably connected with high demands on data traffic and storage. As a consequence, control of the logistic process and insight into the management of both traffic and storage is essential. Method: We monitored data traffic from scanners to server and server to workstation and registered storage needs for diagnostic images and additional projects. Results: The results showed that data traffic inside the hospital network (1 Gbps) never exceeded 80 Mbps for scanner-to-server activity, and activity from the server to the workstation took at most 5 Mbps. Data storage per image increased from 300 MB to an average of 600 MB as a result of camera and software updates, and, due to the increased scanning speed, the scanning time was reduced with almost 8 h/day. Introduction of a storage policy of only 12 months for diagnostic images and rescanning if needed resulted in a manageable storage window of 45 TB for the period of 1 year. Conclusion: Using simple registration tools allowed the transition of digital pathology into a concise package that allows planning and control. Incorporating retrieval of such information from scanning and storage devices will reduce the fear of losing control by the management when introducing digital pathology in daily routine.
International Telepathology: Promises and Pitfalls
Authors: Farahani Navid , Riben Michael , Evans Andrew J. , Pantanowitz Liron
Published: April 2016

Innovative technologies for digital imaging and telecommunications are changing the way we deliver health care. Telepathology collaborations are one example of how delivering remote pathology services to patients can benefit from leveraging this change. Over the years, several academic and commercial teleconsultation networks have been established. Herein, we review the landscape of these international telepathology efforts and highlight key supportive factors and potential barriers to successful cross-border collaborations. Important features of successful international telepathology programs include efficient workflows, dedicated information technology staff, continuous maintenance, financial incentives, ensuring that all involved stakeholders are satisfied, and value-added clinical benefit to patient care. Factors that plague such telepathology operations include legal/regulatory issues, sustainability, and cultural and environmental issues. Pathologists, vendors and laboratory accreditation agencies will need to embrace and capitalize on this new paradigm of international telepathology accordingly.
Die gegenwärtige Landschaft der endokrinen Therapie für prämenopausale Frauen mit Brustkrebs
Authors: Rossi Lorenzo , Pagani Olivia
Published: April 2016

Die optimale endokrine Therapie bei prämenopausalen Frauen mit Brustkrebs in frühen wie in fortgeschrittenen Stadien ist nach wie vor ein wichtiges und umstrittenes Thema. Seit über 30 Jahren ist Tamoxifen der Goldstandard im adjuvanten Setting. Neue Behandlungsoptionen wie z.B. die ovarielle Suppression zusätzlich zur oralen endokrinen Therapie (entweder mit Tamoxifen oder mit Aromataseinhibitoren) können bei sorgfältig ausgewählten Patientinnen den Behandlungserfolg gegenüber Tamoxifen allein verbessern. Auch die Frage der Behandlungsdauer ist noch einmal überdacht worden, und eine verlängerte Therapie etabliert sich derzeit als neuer Standard insbesondere bei Hochrisikopatientinnen. Die endokrine Therapie bei fortgeschrittener Erkrankung stellt weiterhin eine Herausforderung und eine Priorität für die Forschung dar. Neue Wirkstoffe und Kombinationstherapien, mit denen sich die endokrine Resistenz überwinden lässt, sind in greifbarer Nähe; ihre Rolle bei prämenopausalen Frauen muss noch besser untersucht werden. Nebenwirkungen und die Lebensqualität (einschließlich des Aspekts der Familienplanung) spielen eine wichtige Rolle für die Therapieplanung und die Adhärenz der Patientin; dieses Thema ist vor Therapiebeginn grundsätzlich zu besprechen. Dieser Artikel befasst sich mit der Frage, welcher Platz den verschiedenen neuen Behandlungsoptionen innerhalb des gegenwärtigen Instrumentariums der endokrinen Therapien speziell bei prämenopausalen Frauen zukommt; dabei besteht das übergeordnete Ziel darin, die Therapieplanung bestmöglich auf die individuelle Risiko/Nutzen-Beurteilung abzustimmen.
Comparison of Ambulatory Blood Pressure Patterns in Patients With Intradialytic Hypertension and Hemodialysis Controls
Authors: Hompesch Catherine , Ma Tsung-wei , Neyra Javier A. , Ripley Lindsay , Xiao Guanghua , Inrig Jula , Toto Robert , Van Buren Peter N.
Published: April 2016

Background/Aims: Intradialytic hypertension (IH) patients have higher mortality risk than other hemodialysis patients and have been shown to have higher ambulatory blood pressure (BP). We hypothesized that interdialytic BP patterns would differ in IH patients and hypertensive hemodialysis controls. Methods: We consecutively screened hemodialysis patients at our university-affiliated units. Based on pre and post-HD BP measurements during the prior 2 week period, we identified IH patients and demographically matched hemodialysis controls. We measured ambulatory interdialytic BP, flow-mediated vasodilation, and intradialytic endothelin-1 (ET-1). Using linear mixed-models, we compared BP slopes during the following intervals: 1-24 hours post-dialysis, 25-44 hours post-dialysis, and 1-44 hours post-dialysis. Results: There were 25 case subjects with IH and 24 controls. Systolic BP during hours 1-44, 1-24, and 25-44 were 143.1 (16.5), 138.0 (21.2), and 150.8 (22.3) mmHg in controls. For IH subjects, they were 155.4 (14.2), 152.7 (22.8), and 156.5 (20.8) mmHg (p=0.008, 0.02, 0.4). In controls, the slopes were +0.6, +0.6, and +0.4 mmHg/hr. In IH subjects, they were +0.1, -0.3, and +0.3 mmHg/hr. The IH 1-24 hour slope differed from the IH 25-44 hour slope (p=0.001) and the control 1-24 hour slope (p=0.002). The change in ET-1 from pre to post dialysis was 0.5 (1.5) pg/mL in controls and 1.0 (2.3) pg/mL in IH patients (p=0.4). In a univariate model, there was an association with screening BP and BP slope (p=0.002 for controls and p=0.1 for IH patients). Conclusions: Interdialytic BP patterns differ in IH patients and hemodialysis controls. The elevated post dialysis blood pressure persists for many hours in IH patients contributing to the overall increased BP burden.
New Trends of Emerging Technologies in Digital Pathology
Authors: Bueno Gloria , Fernández-Carrobles M. Milagro , Deniz Oscar , García-Rojo Marcial
Published: April 2016

The future paradigm of pathology will be digital. Instead of conventional microscopy, a pathologist will perform a diagnosis through interacting with images on computer screens and performing quantitative analysis. The fourth generation of virtual slide telepathology systems, so-called virtual microscopy and whole-slide imaging (WSI), has allowed for the storage and fast dissemination of image data in pathology and other biomedical areas. These novel digital imaging modalities encompass high-resolution scanning of tissue slides and derived technologies, including automatic digitization and computational processing of whole microscopic slides. Moreover, automated image analysis with WSI can extract specific diagnostic features of diseases and quantify individual components of these features to support diagnoses and provide informative clinical measures of disease. Therefore, the challenge is to apply information technology and image analysis methods to exploit the new and emerging digital pathology technologies effectively in order to process and model all the data and information contained in WSI. The final objective is to support the complex workflow from specimen receipt to anatomic pathology report transmission, that is, to improve diagnosis both in terms of pathologists' efficiency and with new information. This article reviews the main concerns about and novel methods of digital pathology discussed at the latest workshop in the field carried out within the European project AIDPATH (Academia and Industry Collaboration for Digital Pathology).
Eosinophilic Esophagitis, Eosinophilic Gastroenteritis, and Eosinophilic Colitis: Common Mechanisms and Differences between East and West
Authors: Ishihara Shunji , Kinoshita Yoshikazu , Schoepfer Alain
Published: April 2016

Background: Eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EoC) have been diagnosed with an increasing frequency over the last decades. All these diseases share pathogenic similarities with respect to triggering by food antigens in the majority of patients once secondary causes of tissue eosinophilia have been excluded. While diagnostic criteria for EoE have been published, the exact criteria for EGE and EoC still need to be defined. This review highlights similarities and differences between affected patients when comparing the Western with the Eastern world. Summary: The incidence and prevalence of EoE are on the rise in countries from the Western and Eastern world. Very limited epidemiologic data exist regarding EGE and EoC. Characteristics of patients with eosinophilic gastrointestinal disorders regarding gender distribution, age at diagnosis, and associated comorbidities are similar when comparing Eastern with Western countries. Similar modalities are applied to diagnose EoE, EGE, and EoC when comparing Eastern with Western countries. Additionally, comparable therapeutic measures are applied to treat eosinophilic gastrointestinal diseases in Eastern and Western countries. While EoE treatment recommendations are based on increasingly solid evidence, recommendations for the treatment of EGE and EoC are based on low evidence. Key Messages: Eosinophilic gastrointestinal diseases are diagnosed and treated using similar approaches in Eastern and Western countries. Further efforts should be undertaken to help clarify the underlying pathogenic mechanisms and to establish evidence-based diagnostic and therapeutic protocols.
Regulation of Memory T Cells by Interleukin-23
Authors: Li Yanchun , Wang Hongbo , Lu Honghua , Hua Shucheng
Published: April 2016

Interleukin-23 (IL-23), a member of the IL-12 family of cytokines, is a heterodimeric cytokine. It is composed of subunits p40 (shared with IL-12) and p19 (an IL-12 p35-related subunit) and is secreted by several types of immune cells, such as natural killer cells and dendritic cells. The IL-23 receptor is composed of the subunit IL-12Rβ1 and the IL-23-specific subunit IL-23R. The binding of IL-23 to its specific cell surface receptor regulates a number of functions, including proliferation and differentiation of cells and secretion of cell factors. Memory T cells are a subset of T cells that secrete numerous important cell factors, and they function in the immune response to infection and diseases like cancer, autoimmune disease and bronchial asthma. IL-23R is expressed on the surface of memory T cells, which suggests that it can specifically regulate memory T cell function. IL-23 has been widely used as a clinical indicator in immune-related diseases and shows potential for use in disease treatment. Here we review the current progress in the study of the role of IL-23 in the regulation of memory T cells.
Cardiovascular events occur independently of high on-aspirin platelet reactivity and residual COX-1 activity in stable cardiovascular patients
Authors: Nagatsuka Kazuyuki , Miyata Shigeki , Kada Akiko , Kawamura Atsushi , Nakagawara Jyoji , Furui Eisuke , Takiuchi Shin , Taomoto Katsushi , Kario Kazuomi , Uchiyama Shinichiro , Saito Kozue , Nagao Takehiko , Kitagawa Kazuo , Hosomi Naohisa , Tanaka Keiji , Kaikita Koichi , Katayama Yasuo , Abumiya Takeo , Nakane Hiroshi , Wada Hideo , Hattori Akira , Kimura Kazumi , Isshiki Takaaki , Nishikawa Masakatsu , Yamawaki Takemori , Yonemoto Naohiro , Okada Hiromi , Ogawa Hisao , Minematsu Kazuo , Miyata Toshiyuki
Published: April 2016

Several studies have indicated that approximately 25% of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B2 or urinary 11-dehydro TXB2. Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8%). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients.

Supplementary Material to this article is available at www.thrombosis-online.com.
Availability of Clinical Trial Data From Industry‐Sponsored Cardiovascular Trials
Authors: Murugiah Karthik , Ritchie Jessica D. , Desai Nihar R. , Ross Joseph S. , Krumholz Harlan M.
Published: April 2016

Background

Industry‐sponsored clinical trials produce high‐quality data sets that can be used by researchers to generate new knowledge. We assessed the availability of individual participant‐level data (IPD) from large cardiovascular trials conducted by major pharmaceutical companies and compiled a list of available trials.

Methods and Results

We identified all randomized cardiovascular interventional trials registered on ClinicalTrials.gov with >5000 enrollment, sponsored by 1 of the top 20 pharmaceutical companies by 2014 global sales. Availability of IPD for each trial was ascertained by searching each company's website/data‐sharing portal. If availability could not be determined, each company was contacted electronically. Of 60 included trials, IPD are available for 15 trials (25%) consisting of 204 452 patients. IPD are unavailable for 15 trials (25%). Reasons for unavailability were: cosponsor did not agree to make IPD available (4 trials) and trials were not conducted within a specific time (5 trials); for the remaining 6 trials, no specific reason was provided. For 30 trials (50%), availability of IPD could not be definitively determined either because of no response or requirements for a full proposal (23 trials).

Conclusions

IPD from 1 in 4 large cardiovascular trials conducted by major pharmaceutical companies are confirmed available to researchers for secondary research, a valuable opportunity to enhance science. However, IPD from 1 in 4 trials are not available, and data availability could not be definitively determined for half of our sample. For several of these trials, companies require a full proposal to determine availability, making use of the IPD by researchers less certain.
A Biblical Investigation of Matriarchal Structures in Ancient Semitic Life
Authors: de Alminana Margaret English
Published: April 2016

This article demonstrates that a gender-stratified template for the leadership of family and government believed to be modeled after ancient Semitic patriarchal structures according to a pattern found in Old Testament biblical texts is erroneous. It shall demonstrate that strong elements of matriarchalism existed alongside of patriarchalism and that Old Testament texts offer no accurate template for gender-based governance.
All the Saints of God: Expanding a Plural Pneumatology through the Communion of the Saints
Authors: Gathje Jon B.
Published: April 2016

This article argues, in the spirit of Veli-Matti Kärkkäinen’s goal of loosening the spirits into a plural pneumatology, that one population of spirits regularly encountered in the world are the spirits of the dead. Through reflection upon the theological statements made across centuries about the communion of saints and the saints themselves, honest consideration of the experiences, practices, and worship lives of the living faithful, and a consideration of how the saints are present to the living through memory and hope, it will be shown that the connection between the living and the dead is alive, present, and spirit-filled.
Hijab in a Changing Tajik Society
Authors: Nozimova Shahnoza
Published: April 2016

This article investigates Islamic veiling (hijab), an issue that has occupied center stage in the public debate in Tajikistan. State officials and institutions view it as alien (begona), while proponents argue it is a religious obligation (farz) to be fulfilled by every pious woman, especially outside of her domestic settings. I detail the limitations and functionalities that hijab offers for women in contemporary Tajikistan. In particular, as women experience increased pressure to seek employment outside of the home, there appears to be a need to construct new, socially acceptable, mechanisms to manifest conformity to patriarchy and to protect female purity (iffat) and honor (nomus): hijab and (pious) Islamic identity can potentially offer both. This study is based upon analysis of the existing literature on veiling in diverse contexts and the author’s field research in Tajikistan.
Observations of Large Wind Shear above the Marine Boundary Layer near Point Buchon, California
Authors: Rahn David A. , Parish Thomas R. , Leon David
Published: April 2016

Particularly strong winds along the coast of Southern California on 24 May 2012 were measured by the Wyoming King Air research aircraft during the Precision Atmospheric Marine Boundary Layer Experiment (PreAMBLE). The fast flow is bounded laterally by the coastal topography and vertically by a pronounced temperature inversion separating the cool, moist air in the marine boundary layer (MBL) from the warm, dry air aloft. Many studies have investigated the response of this two-layer flow to changes in the coastline by invoking hydraulic theory, which explains the essential characteristics including changes in MBL depth and the attendant wind. Processes occurring just above the MBL are important to the low-level thermodynamic and kinematic structure. Observations on this day demonstrate how the large shear above the MBL can impact the lower atmosphere. A typical two-layer system was observed north of Point Buchon, which was supercritical. Around Point Buchon, the depth of the MBL decreased and wind increased, characteristic of an expansion fan. As a result, the Richardson number becomes reduced and favors shear instability that breaks down into turbulence. Observations indicate that a secondary well-mixed layer develops above the MBL that is bounded by narrow layers of high stability separating the secondary layer from the MBL below and the free troposphere above. It is hypothesized that the secondary layer develops as a result of Kelvin–Helmholtz instability, although more targeted observations are needed to confirm or reject that hypothesis.
A Geometric Interpretation of Eddy Reynolds Stresses in Barotropic Ocean Jets
Authors: Tamarin Talia , Maddison James R. , Heifetz Eyal , Marshall David P.
Published: April 2016

Barotropic eddy fluxes are analyzed through a geometric decomposition of the eddy stress tensor. Specifically, the geometry of the eddy variance ellipse, a two-dimensional visualization of the stress tensor describing the mean eddy shape and tilt, is used to elucidate eddy propagation and eddy feedback on the mean flow. Linear shear and jet profiles are analyzed and theoretical results are compared against fully nonlinear simulations. For flows with zero planetary vorticity gradient, analytic solutions for the eddy ellipse tilt and anisotropy are obtained that provide a direct relationship between the eddy tilt and the phase difference of a normal-mode solution. This allows a straightforward interpretation of the eddy–mean flow interaction in terms of classical stability theory: the initially unstable jet gives rise to eddies that are tilted “against the shear” and extract energy from the mean flow; once the jet stabilizes, eddies become tilted “with the shear” and return their energy to the mean flow. For a nonzero planetary vorticity gradient, ray-tracing theory is used to predict ellipse geometry and its impact on eddy propagation within a jet. An analytic solution for the eddy tilt is found for a Rossby wave on a constant background shear. The ray-tracing results broadly agree with the eddy tilt diagnosed from a fully nonlinear simulation.