bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNF-α receptor 1 knockdown in the subfornical organ ameliorates sympathetic excitation and cardiac hemodynamics in heart failure rats
Authors: Yu Yang , Wei Shun-Guang , Weiss Robert M. , Felder Robert B. 
Published: July 2017

In systolic heart failure (HF), circulating proinflammatory cytokines upregulate inflammation and renin-angiotensin system (RAS) activity in cardiovascular regions of the brain, contributing to sympathetic excitation and cardiac dysfunction. Important among these is the subfornical organ (SFO), a forebrain circumventricular organ that lacks an effective blood-brain barrier and senses circulating humors. We hypothesized that the tumor necrosis factor-α (TNF-α) receptor 1 (TNFR1) in the SFO contributes to sympathetic excitation and cardiac dysfunction in HF rats. Rats received SFO microinjections of a TNFR1 shRNA or a scrambled shRNA lentiviral vector carrying green fluorescent protein, or vehicle. One week later, some rats were euthanized to confirm the accuracy of the SFO microinjections and the transfection potential of the lentiviral vector. Other rats underwent coronary artery ligation (CL) to induce HF or a sham operation. Four weeks after CL, vehicle- and scrambled shRNA-treated HF rats had significant increases in TNFR1 mRNA and protein, NF-κB activity, and mRNA for inflammatory mediators, RAS components and c-Fos protein in the SFO and downstream in the hypothalamic paraventricular nucleus, along with increased plasma norepinephrine levels and impaired cardiac function, compared with vehicle-treated sham-operated rats. In HF rats treated with TNFR1 shRNA, TNFR1 was reduced in the SFO but not paraventricular nucleus, and the central and peripheral manifestations of HF were ameliorated. In sham-operated rats treated with TNFR1 shRNA, TNFR1 expression was also reduced in the SFO but there were no other effects. These results suggest a key role for TNFR1 in the SFO in the pathophysiology of systolic HF. NEW & NOTEWORTHY Activation of TNF-α receptor 1 in the subfornical organ (SFO) contributes to sympathetic excitation in heart failure rats by increasing inflammation and renin-angiotensin system activity in the SFO and downstream in the hypothalamic paraventricular nucleus. Cytokine receptors in the SFO may be a target for central intervention in cardiovascular conditions characterized by peripheral inflammation.
Is normobaric hypoxia an effective treatment for sustaining previously acquired altitude acclimatization?
Authors: Beidleman Beth A. , Fulco Charles S. , Cadarette Bruce S. , Cymerman Allen , Buller Mark J. , Salgado Roy M. , Posch Alexander M. , Staab Janet E. , Sils Ingrid V. , Yurkevicius Beau R. , Luippold Adam J. , Welles Alexander P. , Muza Stephen R. 
Published: July 2017

This study examined whether normobaric hypoxia (NH) treatment is more efficacious for sustaining high-altitude (HA) acclimatization-induced improvements in ventilatory and hematologic responses, acute mountain sickness (AMS), and cognitive function during reintroduction to altitude (RA) than no treatment at all. Seventeen sea-level (SL) residents (age = 23 ± 6 yr; means ± SE) completed in the following order: 1) 4 days of SL testing; 2) 12 days of HA acclimatization at 4,300 m; 3) 12 days at SL post-HA acclimatization (Post) where each received either NH ( n = 9, [Formula: see text] = 0.122) or Sham ( n = 8; [Formula: see text] = 0.207) treatment; and 4) 24-h reintroduction to 4,300-m altitude (RA) in a hypobaric chamber (460 Torr). End-tidal carbon dioxide pressure ([Formula: see text]), hematocrit (Hct), and AMS cerebral factor score were assessed at SL, on HA2 and HA11, and after 20 h of RA. Cognitive function was assessed using the SynWin multitask performance test at SL, on HA1 and HA11, and after 4 h of RA. There was no difference between NH and Sham treatment, so data were combined. [Formula: see text] (mmHg) decreased from SL (37.2 ± 0.5) to HA2 (32.2 ± 0.6), decreased further by HA11 (27.1 ± 0.4), and then increased from HA11 during RA (29.3 ± 0.6). Hct (%) increased from SL (42.3 ± 1.1) to HA2 (45.9 ± 1.0), increased again from HA2 to HA11 (48.5 ± 0.8), and then decreased from HA11 during RA (46.4 ± 1.2). AMS prevalence (%) increased from SL (0 ± 0) to HA2 (76 ± 11) and then decreased at HA11 (0 ± 0) and remained depressed during RA (17 ± 10). SynWin scores decreased from SL (1,615 ± 62) to HA1 (1,306 ± 94), improved from HA1 to HA11 (1,770 ± 82), and remained increased during RA (1,707 ± 75). These results demonstrate that HA acclimatization-induced improvements in ventilatory and hematologic responses, AMS, and cognitive function are partially retained during RA after 12 days at SL whether or not NH treatment is utilized.NEW & NOTEWORTHY This study demonstrates that normobaric hypoxia treatment over a 12-day period at sea level was not more effective for sustaining high-altitude (HA) acclimatization during reintroduction to HA than no treatment at all. The noteworthy aspect is that athletes, mountaineers, and military personnel do not have to go to extraordinary means to retain HA acclimatization to an easily accessible and relevant altitude if reexposure occurs within a 2-wk time period.
Local Delivery of OncoVEXmGM-CSF Generates Systemic Antitumor Immune Responses Enhanced by Cytotoxic T-Lymphocyte–Associated Protein Blockade
Authors: Moesta Achim K. , Cooke Keegan , Piasecki Julia , Mitchell Petia , Rottman James B. , Fitzgerald Karen , Zhan Jinghui , Yang Becky , Le Tiep , Belmontes Brian , Ikotun Oluwatayo F. , Merriam Kim , Glaus Charles , Ganley Kenneth , Cordover David H. , Boden Andrea M. , Ponce Rafael , Beers Courtney , Beltran Pedro J. 
Published: July 2017

Abstract
Purpose: Talimogene laherparepvec, a new oncolytic immunotherapy, has been recently approved for the treatment of melanoma. Using a murine version of the virus, we characterized local and systemic antitumor immune responses driving efficacy in murine syngeneic models.
Experimental Design: The activity of talimogene laherparepvec was characterized against melanoma cell lines using an in vitro viability assay. Efficacy of OncoVEXmGM-CSF (talimogene laherparepvec with the mouse granulocyte-macrophage colony-stimulating factor transgene) alone or in combination with checkpoint blockade was characterized in A20 and CT-26 contralateral murine tumor models. CD8+ depletion, adoptive T-cell transfers, and Enzyme-Linked ImmunoSpot assays were used to study the mechanism of action (MOA) of systemic immune responses.
Results: Treatment with OncoVEXmGM-CSF cured all injected A20 tumors and half of contralateral tumors. Viral presence was limited to injected tumors and was not responsible for systemic efficacy. A significant increase in T cells (CD3+/CD8+) was observed in injected and contralateral tumors at 168 hours. Ex vivo analyses showed these cytotoxic T lymphocytes were tumor-specific. Increased neutrophils, monocytes, and chemokines were observed in injected tumors only. Importantly, depletion of CD8+ T cells abolished all systemic efficacy and significantly decreased local efficacy. In addition, immune cell transfer from OncoVEXmGM-CSF-cured mice significantly protected from tumor challenge. Finally, combination of OncoVEXmGM-CSF and checkpoint blockade resulted in increased tumor-specific CD8+ anti-AH1 T cells and systemic efficacy.
Conclusions: The data support a dual MOA for OncoVEXmGM-CSF that involves direct oncolysis of injected tumors and activation of a CD8+-dependent systemic response that clears injected and contralateral tumors when combined with checkpoint inhibition. Clin Cancer Res; 23(20); 6190–202. ©2017 AACR.
СУЧАСНІ АСПЕКТИ ДІАГНОСТИКИ ГАСТРОЕЗОФАГЕАЛЬНОЇ РЕФЛЮКСНОЇ ХВОРОБИ
Authors: Boiko T. V. 
Published: July 2017

Резюме: Гастроезофагеальна рефлюксна хвороба (ГЕРХ) надзвичайно поширене захворювання зумовлене порушенням моторно-евакуаторної функції органів гастроезофагеальної зони, яке характеризується спонтанним закидом шлункового або дуоденального вмісту в стравохід, що призводить до ураження його дистального відділу з розвитком у ньому запальних та ерозивно-виразкових уражень. Серед дорослого населення поширеність ГЕРХ становить до 40%.Мета роботи − проаналізувати сучасні погляди науковців і основні методи діагностики ГЕРХ.В діагностиці ГЕРХ потрібно орієнтуватися на рекомендації Монреальського консенсуса, згідно якого захворювання може бути діагностовано при наявності як мінімум одного із трьох критеріїв: а) характерних симптомів захворювання; в) інструментального підтвердження наявності патологічного гастроезофагеального рефлюксу в осіб з симптомами ГЕРХ; с) змін слизової оболонки стравоходу, гістологічного дослідження біоптату.Згідно V Маастрихтcького консенсусу рекомендовано проводити ерадикацію H-pylori незалежно від наявності чи відсутності симптомів ГЕРХ при наявності прямих показів.Діагноз ГЕРХ встановлюється на підставі клінічних критеріїв, якщо пацієнта турбує печія більше ніж двічі на тиждень впродовж трьох місяців і довше. Для діагностики ГЕРХ запропоновані тест з ІПП, альгінатний тести. Показом до проведення езофагогастродуоденоскопії (ЕГДС) у пацієнтів з ГЕРХ є наявність тривожних симптомів (дисфагія, нудота, кровотеча, зменшення маси тіла), неефективність пробного лікування (негативні альгінатний або омепразоловий тести), тривалий перебіг захворювання, вік більше 50 років. ЕГДС виконують для виявлення або виключення значних пошкоджень в окремих випадках. При типових симптомах ГЕРХ проводити ЕГДС не потрібно. При проведенні ЕГДС беруть біоптат стравоходу при ускладненнях ГЕРХ, новоутвореннях, для діагностики еозинофільного езофагіту. Для кількісного визначення впливу кислоти на стравохід та оцінки асоціації між печією та епізодами рефлюксу використовують рН-метрію в стравоході або імпеданс-метрію протягом 24 год. Стравохідний імпеданс рН застосовують у пацієнтів зі стійкими симптомами рефлюксу, які погано відповіли на стандартну терапію для оцінки як кислотної, так і некислотної рефлюксної хвороби. Для виявлення мінімальних уражень слизової оболонки стравоходу у хворих на ГЕРХ застосовують хромоскопію, ендоскопію з високою роздільністю та збільшенням, вузьку спектральну ендоскопію.Таким чином, основним методом діагностики гастроезофагеальної рефлюксної хвороби є езофагогастродуоденоскопія. Сучасні ендоскопічні технології дають можливість діагностувати ГЕРХ на ранній стадії.
Ендоскопічна папілосфінктеротомія у хворих на цироз печінки з наявністю холестазу
Authors: Dzygal A. F. 
Published: July 2017

Мета дослідження: аналіз способів хірургічних втручань у хворих із провідними симптомами цирозу печінки, (ЦП), ускладненим холедохолітіазом, для вибору індивідуальної тактики їх лікування.Матеріали і методи. З числа 1117 обстежених хворих з підозрою на ЦП, жовчнокам’яну хворобу, гострий холецистит та механічну жовтяницю відібрали 52 пацієнти з клінічними проявами біліарного блоку внаслідок холедохолітіазу. 42 хворим з їх числа виконували ендоскопічну папілосфінктеротомію (ЕПСТ) з літекстракцією, ЕПСТ з механічною літотрипсією, стентування та балонну дилатацію, а також назобіліарне дренування.Результати досліджень та їх обговорення. Сформульовано показання та протипоказання до виконання ендоскопічної операції у хворих на ЦП, ускладнений холедохолітіазом. Наведені окремі деталі виконання різних типів ЕПСТ – типової або канюляційної, атипової або неканюляційної та змішаної. Виконання ЕПСТ супроводжувалося літекстракцією у 33 хворих. ЕПСТ виявилася успішною у 35 з 37 хворих. Ускладнення після, які виявлені під час операції або розвинулися впродовж 24 год після неї, спостерігали в 6 із 37 хворих.Висновки. Ефективність ЕПСТ у хворих на ЦП при холедохолітіазі та розвитку механічної обструкції жовчовивідних шляхів сягає 94,6 %, що дозволяє рекомендувати її як операцію вибору при лікуванні хворих із непрохідністю загальної жовчної протоки, що виникла внаслідок холедохолітіазу, а також вважати дане хірургічне втручання ефективним методом лікування вказаного контингенту хворих із високим ступенем операційного ризику.
Effects of Transcranial Direct Current Stimulation on Neural Networks in Young and Older Adults
Authors: Martin Andrew K. , Meinzer Marcus , Lindenberg Robert , Sieg Mira M. , Nachtigall Laura , Flöel Agnes 
Published: July 2017

Abstract
Transcranial direct current stimulation (tDCS) may be a viable tool to improve motor and cognitive function in advanced age. However, although a number of studies have demonstrated improved cognitive performance in older adults, other studies have failed to show restorative effects. The neural effects of beneficial stimulation response in both age groups is lacking. In the current study, tDCS was administered during simultaneous fMRI in 42 healthy young and older participants. Semantic word generation and motor speech baseline tasks were used to investigate behavioral and neural effects of uni- and bihemispheric motor cortex tDCS in a three-way, crossover, sham tDCS controlled design. Independent components analysis assessed differences in task-related activity between the two age groups and tDCS effects at the network level. We also explored whether laterality of language network organization was effected by tDCS. Behaviorally, both active tDCS conditions significantly improved semantic word retrieval performance in young and older adults and were comparable between groups and stimulation conditions. Network-level tDCS effects were identified in the ventral and dorsal anterior cingulate networks in the combined sample during semantic fluency and motor speech tasks. In addition, a shift toward enhanced left laterality was identified in the older adults for both active stimulation conditions. Thus, tDCS results in common network-level modulations and behavioral improvements for both age groups, with an additional effect of increasing left laterality in older adults.
Using Event-related Potentials to Inform the Neurocognitive Processes Underlying Knowledge Extension through Memory Integration
Authors: Varga Nicole L. , Bauer Patricia J. 
Published: July 2017

Abstract
To build a general knowledge base, it is imperative that individuals acquire, integrate, and further extend knowledge across experiences. For instance, in one episode an individual may learn that George Washington was the first president. In a separate episode they may then learn that Washington was the commander of the Continental Army. Integration of the information in memory may then support self-derivation of the new knowledge that the leader of the Continental Army was also the first president. Despite a considerable amount of fMRI research aimed at further elucidating the neuroanatomical regions supporting this ability, a consensus has yet to be reached with regards to the precise neurocognitive processes involved. In the present research, we capitalized on the high temporal resolution of event-related potentials (ERPs) to inform the time course of processes elicited during successful integration and further extension of new factual knowledge. Adults read novel, related stem facts and were tested for self-derivation of novel integration facts while ERPs were recorded. Consistent with current theoretical models, memory integration was first triggered by novelty detection within 400 msec of experience of a second, related stem fact. Two additional temporally staged encoding processes were then observed interpreted to reflect (1) explicit meaning comprehension and (2) representation of the integrated relation in memory. During the test for self-derivation, a single ERP was elicited, which presumably reflected retrieval and/or recombination of previously integrated knowledge. Together, the present research provides important insight into the time course of neurocognitive processing associated with the formation of a knowledge base.
The Impossibility of Liberal Secularism: Religious (In)tolerance, Spirituality, and Not-Religion
Authors: Crosson J. Brent 
Published: July 2017

AbstractThis article re-thinks the problem of religious (in)tolerance by analyzing the 2015 deportation of three “Hindu priests” from a Caribbean nation for the practice of obeah. Defined popularly as “witchcraft” or “African tradition,” obeah was first criminalized as the alleged inspiration for the largest slave uprising of the eighteenth century British Caribbean. I argue that the recent deportations in a nation that constitutionally enshrines freedom of conscience foregrounds some of the foundational limits of liberal secularism. I trace a genealogy of liberalism to critique the secular ideal of the “freedom from difference.” I suggest that attempts to invoke “spirituality” as a more inclusive idiom for denigrated forms of “not-religion” such as obeah extend rather than eliminate these limits of liberal secularism. I close by drawing some parallels with anti-Muslim nationalism in theu.s.and suggest some ways of thinking about a trinary formation of religion, not-religion, and secular power in modern nation-states.
Practical Considerations for Computing Dimensional Spectra from Gridded Data
Authors: Durran Dale , Weyn Jonathan A. , Menchaca Maximo Q. 
Published: July 2017

AbstractSpectra are often computed from gridded data to determine the horizontal-scale dependence of quantities such as kinetic energy, vertical velocity, or perturbation potential temperature. This paper discusses several important considerations for the practical computation of such spectra. To ensure that the sum of the spectral energy densities in wavenumber space matches the sum of the energies in the physical domain (the discrete Parseval relation), the constant coefficient multiplying the spectral energy density must properly account for the way the discrete Fourier transform pair is normalized. The normalization factor appropriate of many older FORTRAN-based fast Fourier transforms (FFTs) differs from that in Matlab and Python’s numpy.fft, and as a consequence, the correct scaling factor for the kinetic energy (KE) spectral density differs between one-dimensional FFTs computed using these two approaches by a factor equal to the square of the number of physical grid points. A common algorithm used to compute two-dimensional spectra as a function of the total-wavenumber magnitude sums the contributions from all pairs of x- and y-component wavenumbers whose vector magnitude lies with a series of bins. This approach introduces systematic short-wavelength noise, which can be largely eliminated though a simple multiplicative correction. One- and two-dimensional spectra will differ by a constant if computed for flows in which the KE spectral density decreases as a function of the wavenumber to some negative power. This constant is evaluated and the extension of theoretical results to numerically computed FFTs is examined.
The Determination and Significance of Low Blood Carboxyhaemoglobin Levels
Authors: Bowden C. H. , Woodhall W. R. 
Published: July 2017

The method described by Whitehead and Worthington (1961) for the determination of carboxyhaemoglobin has been examined and minor modifications are suggested. The sensitivity and specificity of the method has been confirmed at low COHb saturations. Forty-two non-smokers and 58 smokers were examined at various times of day using this technique. The mean COHb values obtained in the morning prior to smoking were 0.7 per cent. for non-smokers and 1.5 per cent for smokers; the difference in means was highly significant. In the afteroon, smokers gave a mean value of 2.7 per cent. It is calculated that a saturation of 8 per cent. COHb will be achieved “normally” by a smoker only in exceptional circumstances. The significance of the results in relation to the reconstruction of fatal transportation accidents is briefly discussed.
Report of the Traffic Safety Division of the Arizona Highway Department
Authors: Camps F. E. 
Published: July 2017

To those of us who read, it must be a constant source of frustration that we have no access to information which may be of use to us. For this reason those who have not the opportunity—in an enormous mass of information—to read this immaculate periodic report of the Traffic Safety Division of the Arizona Highway Department must be an eye-opener. It might even impress our Minister of Transport when she is considering decisions. For this reason Medicine, Science and the Law reproduces the periodic report with due permission, but without any humility. Pages 1–9, June 1966 issue of Arizona Safety Sad-istics. Perhaps we might be humble to see such a realistic approach. On this occasion Medicine, Science and the Law will be willing to receive comments for publication in its next number.
The Application of a Micro-Elution Technique Using Anti-Human Globulin for the Detection of the S, S, K, Fya, Fyb and JKa Antigens in Stains
Authors: Lincoln Patrick J. , Dodd Barbara E. 
Published: July 2017

A micro-elution technique using anti-globulin is described which increases the number of blood group antigens detectable in bloodstains. When compared with the older inhibition technique it is shown to be not only markedly more sensitive but to require far less stained material for each individual test. Yet another advantage is that the antigens detectable by this method are those which appear to withstand well the passage of time by remaining active in stains for many months. This is in contrast to the majority of red cell enzymes which, while being readily detectable, do not usually give readable results beyond about 8 weeks.
Contaminating Antibodies May Produce Unexpected Reactions in Counter-Current Immunoelectrophoresis
Authors: Boettcher B. 
Published: July 2017

ABSTRACT: The possibility of contaminating antibodies in an antiserum causing reactions in countercurrent immunoelectrophoresis at low antigen concentrations, though not at higher concentrations, was raised, and also argued against, in a recent, widely-publicized legal case. This study has demonstrated that, in this technique, precipitin bands can be produced in tests involving low concentrations of antibodies only where there are also low concentrations of antigen, not where there are higher concentrations of antigen. These results indicate that, under appropriate circumstances, in counter-current Immunoelectrophoresis, a low concentration of contaminating antibodies in an antiserum could produce a precipitin band with a low concentration of an unsuspected antigen. This possibility points up the necessity of establishing the identities of the reacting antigens and antibodies in such tests, using a different procedure, such as the double radial immunodiffusion (Ouchterlony) technique. It is suggested that the value of counter-current immunoelectrophoresis in forensic testing should be given consideration.
Mortality following Release from Prison
Authors: Harding-Pink Deborah 
Published: July 2017

We have studied deaths occurring after release from prison in the Canton of Geneva during the period 1982–86. The mortality rate during the first year after release was about 5 deaths/1000 person years, a rate over four times the age-adjusted rate in the general population. The majority of deaths were due to overdose by opiate drugs among young, frequently imprisoned drug abusers, and occurred within the first few weeks after release. Likely risk factors include loss of tolerance to opiates while in prison, and psychological and social stresses following release.
Suicidal Strangulation by Ligature: Three Case Reports
Authors: Claydon S. M. 
Published: July 2017

Self-strangulation by ligature is distinctly uncommon. It is distinct from self-suspension in cases of hanging, the latter being a far more common form of suicide. Self-strangulation must be separated from homicidal strangulation and from accidental sexual asphyxia. The ligature in suicidal strangulation may be knotted or tightened like a tourniquet. As the ligature is tightened the face and neck may become congested due to slow venous compression. Laryngeal fractures are rare and injuries are mild and often confined to the single ligature mark around the neck. The three cases discussed here were initially treated by the police as suspicious. Detailed examination of the scene and of the deceased person, along with investigation of the circumstances leading to the death, produced clear verdicts of suicide in all three cases.