tbuckley/cabot-search huggingface dataset:
Circadian variation of sudden cardiac death reflects age-related variability in ventricular fibrillation.
Authors: H RArntz, S NWillich, MOeff, TBrüggemann, RStern, AHeinzmann, BMatenaer, RSchröder
Journal: Circulation (1993)

BACKGROUNDPrevious studies report a morning peak in the occurrence of out-of-hospital sudden cardiac death but lack detailed information on underlying arrhythmias. We used the documentation system of the semiautomated defibrillators used by emergency medical technicians to investigate the circadian pattern of defined arrhythmias and the influence of demographic patient characteristics on this pattern.METHODS AND RESULTSFrom December 1988 to December 1990, 703 consecutive patients (63% men; age, 67 +/- 17 years) with sudden cardiac death were registered in the Klinikum Steglitz area of the Berlin emergency care system. Determination of time of day of the event was based on the arrival time of the rescue squad. A marked circadian variation (P < .0001) in the occurrence of sudden cardiac death was observed with a primary morning peak (6 AM to noon) and a secondary afternoon peak (3 to 7 PM). The subgroup of 294 patients with ventricular fibrillation as initially documented arrhythmia showed a similar circadi...
The gut microbiota metabolite capsiate promotes Gpx4 expression by activating <i>TRPV1</i> to inhibit intestinal ischemia reperfusion-induced ferroptosis
Authors: Fan Deng, Bing-Cheng Zhao, Xiao Yang, Ze-Bin Lin, Qi-Shun Sun, Yi-Fan Wang, Zheng-Zheng Yan, Wei-Feng Liu, Cai Li, Jing-Juan Hu, Ke-Xuan Liu
Journal: Gut Microbes (2021)

Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes of gut microbiota and metabolites in intestinal I/R and the role of gut microbiota metabolites on ferroptosis-induced intestinal I/R injury. This study aimed to establish a mouse intestinal I/R model and ileum organoid hypoxia/reoxygenation (H/R) model to explore the changes of the gut microbiota and metabolites during intestinal I/R and protective ability of capsiate (CAT) against ferroptosis-dependent intestinal I/R injury. Intestinal I/R induced disturbance of gut microbiota and significant changes in metabolites. We found that CAT is a metabolite of the gut microbiota and that CAT levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with intestinal I/R injury. Furthermore, CAT reduced ferroptosis-dependent intestinal I/R injury in vivo and in vitro. However, the protective effects of CAT against ferroptosis-dependent intestinal I/R injury were abolished by RSL3, an inhibitor of glutathione peroxidase 4 (Gpx4), which is a negative regulator of ferroptosis. We also found that the ability of CAT to promote Gpx4 expression and inhibit ferroptosis-dependent intestinal I/R injury was abrogated by JNJ-17203212, an antagonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). This study suggests that the gut microbiota metabolite CAT enhances Gpx4 expression and inhibits ferroptosis by activating TRPV1 in intestinal I/R injury, providing a potential avenue for the management of intestinal I/R injury.
Excimer laser-induced simultaneous ablation and spectral identification of normal and atherosclerotic arterial tissue layers.
Authors: GLaufer, GWollenek, KHohla, RHorvat, K HHenke, MBuchelt, GWutzl, EWolner
Journal: Circulation (1988)

A krypton-fluorine excimer laser at a 248-nm wavelength was used to irradiate normal and severely atherosclerotic segments of human postmortem femoral arteries. Single pulses and multiple pulses required for penetration or perforation of the arterial wall were applied with 16 nsec pulse width and 5 J/cm2/pulse energy fluence. The total fluorescence of irradiated and ablated tissue was analyzed in real-time mode by means of spectroscopy. Each laser pulse produced one spectrum that was characteristic of the composition of the tissue layer, which was ablated. Fluorescence spectroscopy indicated a broad-continuum emission between 300 and 700 nm with peak fluorescence of equal intensity at wavelengths of 370 and 460 nm (ratio, 1.004 +/- 0.087) for normal media layers. Atheromas without calcification (lipid, fibrous, and mixed) were found with spectral maxima at the same wavelengths but with significantly reduced intensity at 460 nm (ratio, 1.765 +/- 0.263; p less than 0.001). In contrast to this broad-continuu...
Fetal Surgery for Myelomeningocele
Authors: Alan H Jobe
Journal: New England Journal of Medicine (2002)

The most common nonlethal malformation in the spectrum of neural-tube defects is myelomeningocele. This defect, caused by failure of the neural tube to close completely at about four weeks of gestation, occurs in approximately 1 in 2000 births. The extent and severity of the neurologic deficits (which include motor dysfunction in the legs and lack of bladder and bowel control) depend on the location of the lesion along the neuroaxis; the cord below the lesion is dysplastic. Myelomeningocele is often associated with the type II Chiari hindbrain malformation, a downward displacement of the cerebellar vermis into the cervical spinal canal, . . .
In vivo effect of methylene blue on endothelium-dependent and endothelium-independent dilations of brain microvessels in mice.
Authors: MWatanabe, W IRosenblum, G HNelson
Journal: Circulation Research (1988)

Arterioles on the surface of the mouse brain were observed by in vivo TV microscopy. Four dilators were topically applied to relax the vessels in vivo. Two of the dilators were acetylcholine and bradykinin, whose action in this vascular bed is dependent upon production of endothelium-dependent relaxing factors. The other two dilators were sodium nitroprusside and 8-bromo-cGMP, whose action is not endothelium dependent. The dilations by acetylcholine, bradykinin, and nitroprusside were significantly depressed by 10(-4) M methylene blue applied topically for 7 minutes prior to application of the dilators. The inhibitory effect was reversible, was greatest against acetylcholine, and was least against nitroprusside. These data parallel reports of methylene blue's action against these dilators when applied to large blood vessels in vitro. Our data appear to be the first microvascular data and the first in vivo data showing this effect. The data thus suggest that the mechanisms underlying dilation of cerebral a...
Echocardiographic assessment of the level of cardiac compensation in valvular heart disease.
Authors: ARosenblatt, RClark, JBurgess, KCohn
Journal: Circulation (1976)

The level of cardiac compensation in valvular disease was studied by relating echocardiographic and cardiac catheterization measurements. Three groups -- compensated, intermediately compensated, and decompensated -- were defined according to the left ventricular angiographic pattern and cardiac output. The echocardiographic ejection indices, percent left ventricular minor diameter shortening, ejection fraction, and fiber shortening rate were significantly higher than  in compensated mitral regurgitation, lower then  in compensated aortic stenosis, and within  limits in compensated aortic insufficiency. In the decomposed state these indices were depressed. Intermediate compensation was best recognized by combining several echocardiographic variables into an echocardiographic score based on multivariate discriminant function analysis. Thus, the compensated volume overload states (aortic and mitral regurgitation) and pressure overload state (aortic stenosis) have separate sets of normal e...
Inward sodium current at resting potentials in single cardiac myocytes induced by the ischemic metabolite lysophosphatidylcholine.
Authors: A IUndrovinas, I AFleidervish, J CMakielski
Journal: Circulation Research (1992)

To investigate possible ionic current mechanisms underlying ischemic arrhythmias, we studied single Na+ channel currents in rat and rabbit cardiac myocytes treated with the ischemic metabolite lysophosphatidylcholine (LPC) using the cell-attached and excised inside-out patch-clamp technique at 22 degrees C. LPC has been reported previously to reduce open probability and to induce sustained open channel activity at depolarized potentials. We now report two new observations for Na+ currents in LPC-treated patches: 1) The activation-voltage relation of the peak of the ensemble currents is shifted in the negative (hyperpolarizing) direction by approximately 20 mV compared with control currents. This effect was observed in all patches for depolarizations from a holding potential of -150 mV to different test potentials. 2) In some LPC-treated patches, Na+ channels exhibited sustained bursting activity at potentials as negative as -150 mV, giving a nondecaying inward current. This bursting activity was accompani...
Dissociation of end systole from end ejection in patients with long-term mitral regurgitation.
Authors: M EBrickner, M RStarling
Journal: Circulation (1990)

To determine whether left ventricular (LV) end systole and end ejection uncouple in patients with long-term mitral regurgitation, 59 patients (22 control patients with atypical chest pain, 21 patients with aortic regurgitation, and 16 patients with mitral regurgitation) were studied with micromanometer LV catheters and radionuclide angiograms. End systole was defined as the time of occurrence (Tmax) of the maximum time-varying elastance (Emax), and end ejection was defined as the time of occurrence of minimum ventricular volume (minV) and zero systolic flow as approximated by the aortic dicrotic notch (Aodi). The temporal relation between end systole and end ejection in the control patients was Tmax (331 +/- 42 [SD] msec), minV (336 +/- 36 msec), and then, zero systolic flow (355 +/- 23 msec). This temporal relation was maintained in the patients with aortic regurgitation. In contrast, in the patients with mitral regurgitation, the temporal relation was Tmax (266 +/- 49 msec), zero systolic flow (310 +/- ...
Increasing breast milk betaine modulates <i>Akkermansia</i> abundance in mammalian neonates and improves long-term metabolic health
Authors: Silvia Ribo, David Sánchez-Infantes, Laura Martinez-Guino, Izaskun García-Mantrana, Marta Ramon-Krauel, Mireia Tondo, Erland Arning, Miquel Nofrarías, Óscar Osorio-Conles, Antonio Fernández-Pérez, Pedro González-Torres, Judith Cebrià, Aleix Gavaldà-Navarro, Empar Chenoll, Elvira Isganaitis, Francesc Villarroya, Mario Vallejo, Joaquim Segalés, Josep C. Jiménez-Chillarón, Teodoro Bottiglieri, Ellen W. Demerath, David A. Fields, María Carmen Collado, Carles Lerin
Journal: Science Translational Medicine (2021)

Maternal betaine supplementation during lactation increases breast milk betaine content with beneficial metabolic effects on mouse offspring.
High mean platelet volume after myocardial infarction
Authors: T M E Davis
Journal: BMJ (1985)

retrospective study and a graph of symphysisfundus height was not used.Dr Neilson and colleagues admit that mothers who may have been referred before 34 weeks with suspected intrauterine growth retardation were not included in their study and report that of six babies with intrauterine growth retardation who died three died before 34 weeks.Gentz et al have pointed out that in a Swedish study nearly half the stillbirths occurred before admission and 80O, of these fetuses died before the onset of labour.Yet use of the symphysis-fundus graph in their hands can detect intrauterine growth retardation as early as 28 weeks (16 000 deliveries).No serious student of intrauterine growth retardation can afford to neglect reading Westin's account of his work.Symphysis-fundus graphs are simple to use and indicate in a much more specific way in each patient when to refer for an ultrasound check.This is much better than an expensive, time consuming routine test which may be done too late.
No reflow and extent of infarction during maximal vasodilation in the porcine heart.
Authors: W BJohnson, S AMalone, G APantely, C GAnselone, J DBristow
Journal: Circulation (1988)

To explore the relation between myocardial and vascular injury in the generation of the no-reflow phenomenon, the pressure-flow relation during maximal vasodilation after coronary artery reperfusion was studied in the open-chest porcine model. During both endogenous and maximal vasodilation with intracoronary adenosine, pressure-flow (P/Q) plots were constructed before and after 20-minute (n = 9) or 40-minute (n = 17) circumflex artery occlusions. Decreases in circumflex vascular bed conductance were represented by downward shifts in P/Q plot regression lines. No significant change occurred in P/Q line slope or pressure at zero flow 30 minutes after release of the 20-minute occlusion, and no infarction was found. After release of the 40-minute occlusion, a small but insignificant decrease in P/Q line slope occurred during endogenous vasodilation. However, during maximal vasodilation, a significant (p less than 0.01) decrease in P/Q line slope was present during reperfusion compared with preocclusion corre...
Novel therapies emerging in oncology to target the TGF-β pathway
Authors: Byung-Gyu Kim, Ehsan Malek, Sung Hee Choi, James J. Ignatz-Hoover, James J. Driscoll
Journal: Journal of Hematology & Oncology (2021)

Abstract The TGF-β signaling pathway governs key cellular processes under physiologic conditions and is deregulated in many pathologies, including cancer. TGF-β is a multifunctional cytokine that acts in a cell- and context-dependent manner as a tumor promoter or tumor suppressor. As a tumor promoter, the TGF-β pathway enhances cell proliferation, migratory invasion, metastatic spread within the tumor microenvironment and suppresses immunosurveillance. Collectively, the pleiotropic nature of TGF-β signaling contributes to drug resistance, tumor escape and undermines clinical response to therapy. Based upon a wealth of preclinical studies, the TGF-β pathway has been pharmacologically targeted using small molecule inhibitors, TGF-β-directed chimeric monoclonal antibodies, ligand traps, antisense oligonucleotides and vaccines that have been now evaluated in clinical trials. Here, we have assessed the safety and efficacy of TGF-β pathway antagonists from multiple drug classes that have been evaluated in completed and ongoing trials. We highlight Vactosertib, a highly potent small molecule TGF-β type 1 receptor kinase inhibitor that is well-tolerated with an acceptable safety profile that has shown efficacy against multiple types of cancer. The TGF-β ligand traps Bintrafusp alfa (a bifunctional conjugate that binds TGF-β and PD-L1), AVID200 (a computationally designed trap of TGF-β receptor ectodomains fused to an Fc domain) and Luspatercept (a recombinant fusion that links the activin receptor IIb to IgG) offer new ways to fight difficult-to-treat cancers. While TGF-β pathway antagonists are rapidly emerging as highly promising, safe and effective anticancer agents, significant challenges remain. Minimizing the unintentional inhibition of tumor-suppressing activity and inflammatory effects with the desired restraint on tumor-promoting activities has impeded the clinical development of TGF-β pathway antagonists. A better understanding of the mechanistic details of the TGF-β pathway should lead to more effective TGF-β antagonists and uncover biomarkers that better stratify patient selection, improve patient responses and further the clinical development of TGF-β antagonists.
Abstract 15592: Anatomical Change and Stenosis of the Pulmonary Vein After Cryoballoon Ablation for Atrial Fibrillation
Authors: Hiroshi Miyama, Terumasa Yamashita, Taishi Fujisawa, Kazuaki Nakajima, Yoshinori Katsumata, Takahiko Nishiyama, Takehiro Kimura, Yoshiyasu Aizawa, Keiichi Fukuda, Seiji Takatsuki
Journal: Circulation (2018)

Introduction: Cryoballoon ablation (CBA) for atrial fibrillation (AF) became quite common, however, little is known about consequence of anatomy of the pulmonary vein (PV) ostium and the prevalence...
Serotypic evolution of measles virus is constrained by multiple co-dominant B cell epitopes on its surface glycoproteins
Authors: Miguel Ángel Muñoz-Alía, Rebecca A. Nace, Lianwen Zhang, Stephen J. Russell
Journal: Cell Reports Medicine (2021)

After centuries of pestilence and decades of global vaccination, measles virus (MeV) genotypes capable of evading vaccine-induced immunity have not emerged. Here, by systematically building mutations into the hemagglutinin (H) glycoprotein of an attenuated measles virus strain and assaying for serum neutralization, we show that virus evolution is severely constrained by the existence of numerous co-dominant H glycoprotein antigenic sites, some critical for binding to the pathogenicity receptors SLAMF1 and nectin-4. We further demonstrate the existence in serum of protective neutralizing antibodies targeting co-dominant fusion (F) glycoprotein epitopes. Lack of a substantial reduction in serum neutralization of mutant measles viruses that retain even one of the co-dominant antigenic sites makes evolution of pathogenic measles viruses capable of escaping serum neutralization in vaccinated individuals extremely unlikely.
Hypertrophic cardiomyopathy mutation is expressed in messenger RNA of skeletal as well as cardiac muscle.
Authors: Q TYu, JIfegwu, A JMarian, AMares, RHill, M BPerryman, L LBachinski, RRoberts, A JMarlan
Journal: Circulation (1993)

BACKGROUNDThe beta-myosin heavy chain (beta-MHC) gene has been identified as a major locus for familial hypertrophic cardiomyopathy (FHCM). We recently showed that one of the common mutations associated with FHCM is expressed in the cardiac muscle messenger RNA (mRNA) of an affected individual. Since beta-MHC is a major sarcomeric protein of cardiac and skeletal muscle, studies were performed to determine whether the mutation is also expressed in skeletal muscle.METHODS AND RESULTSBiopsies were obtained of skeletal muscle (biceps brachii) from a proband with FHCM known to have the missense mutation in exon 13 of the beta-MHC gene. RNA was extracted from skeletal muscle and lymphocytes by the RNAzol method. First-strand complementary DNA was synthesized by reverse transcription using an antisense primer to exon 16. Polymerase chain reaction (PCR) was performed using primers to exons 12 and 14 to amplify the segment encompassing exon 13. The PCR products were digested with Ddel restriction endonuclease. Und...
Sexual dimorphism in vasopressin and cardiovascular response to hemorrhage in the rat.
Authors: J TCrofton, LShare
Journal: Circulation Research (1990)

There is evidence for sex-related differences in the cardiovascular actions of vasopressin. Furthermore, receptors for the gonadal steroid hormones are located in centers in the brain involved in the control of vasopressin release and in cardiovascular regulation. We have, therefore, examined the effects of hemorrhage on mean arterial blood pressure, the plasma vasopressin concentration, and plasma renin concentration in conscious male and female rats. In preliminary experiments, no differences were found in blood and plasma volumes with respect to either sex or phase of the estrous cycle. In separate experiments, rats were subjected to two hemorrhages of 10% of blood volume, separated by an interval of 15 minutes. There were no substantial gender- or cycle-related differences in the ability of hemorrhaged rats to maintain mean arterial blood pressure or increase plasma renin concentration. The increase in plasma vasopressin concentration was greater in proestrous females than in males after the first hem...
Response to Open Peer Commentaries: Distinguishing the “Gift” from “Donation” as a Path toward Reciprocity and Relational Ethics
Authors: Sandra Soo-Jin Lee
Journal: The American Journal of Bioethics (2021)

This article refers to:Obligations of the “Gift”: Reciprocity and Responsibility in Precision MedicineA Value-Oriented Framework for Precision MedicineGift, Reciprocity and Learning Health SystemsAporia of the Gift: Precision Medicine’s Obligations Without ExpectationsPrecision Medicine, Data, and the Anthropology of Social StatusResponsible Research with Human Tissues: The Need for Reciprocity Toward Both Collectives and IndividualsWe Have “Gifted” Enough: Indigenous Genomic Data Sovereignty in Precision MedicineExperiences at a Federally Qualified Health Center Support Expanded Conception of the Gifts of Precision MedicineThe Gift in Precision Medicine: Unwrapping the Significance of Reciprocity and GenerosityFostering Relationships in Pediatric Oncology Research: A Relational Ethics Approach to Clinically Integrated ResearchThe Underdeveloped “Gift”: Ethics in Implementing Precision Medicine ResearchReciprocity’s Baggage
Demographic History, Adaptation, and NRAP Convergent Evolution at Amino Acid Residue 100 in the World Northernmost Cattle from Siberia
Authors: Laura Buggiotti, Andrey A Yurchenko, Nikolay S Yudin, Christy J Vander Jagt, Nadezhda V Vorobieva, Mariya A Kusliy, Sergei K Vasiliev, Andrey N Rodionov, Oksana I Boronetskaya, Natalia A Zinovieva, Alexander S Graphodatsky, Hans D Daetwyler, Denis M Larkin
Journal: Molecular Biology and Evolution (2021)

Abstract Native cattle breeds represent an important cultural heritage. They are a reservoir of genetic variation useful for properly responding to agriculture needs in the light of ongoing climate changes. Evolutionary processes that occur in response to extreme environmental conditions could also be better understood using adapted local populations. Herein, different evolutionary histories of the world northernmost native cattle breeds from Russia were investigated. They highlighted Kholmogory as a typical taurine cattle, whereas Yakut cattle separated from European taurines approximately 5,000 years ago and contain numerous ancestral and some novel genetic variants allowing their adaptation to harsh conditions of living above the Polar Circle. Scans for selection signatures pointed to several common gene pathways related to adaptation to harsh climates in both breeds. But genes affected by selection from these pathways were mostly different. A Yakut cattle breed-specific missense mutation in a highly conserved NRAP gene represents a unique example of a young amino acid residue convergent change shared with at least 16 species of hibernating/cold-adapted mammals from six distinct phylogenetic orders. This suggests a convergent evolution event along the mammalian phylogenetic tree and fast fixation in a single isolated cattle population exposed to a harsh climate.
Carpal Tunnel Syndrome
Authors: A. A. van der Bracht
Journal: BMJ (1958)

<h3>Background</h3> In Finnish elementary schools injuries happen mostly in physical education (PE) classes, recesses and on the way to school. Most injuries are mild, but treatment can be time consuming and expensive. Especially knee, low back and head injuries may cause long-term pain and disabilities. A remarkable part of these injuries can be prevented by enhancing pupils9 motor skills and awareness of injury risks by improving quality and contents of PE and health education classes, and taking care of safety equipment and environment. <h3>Methods</h3> The Sports and Exercise Safety in Finland programme (LiVE) and its second nationwide implementation project TEKO (2010−), is delivering research findings and producing educational material to the internet to promote physical activity and safety of sports and leisure time (http://www.tervekoululainen.fi). The main target group for TEKO is secondary school teachers and pupils. <h3>Results</h3> In TEKO project the safety promotion is focused on 10 segments; physical activity, sports skills, maturation, nutrition, rest and sleep, environment and equipment, health care, atmosphere and rules, injuries and support network. Teachers can use free of charge information packages and practical toolkits per segment to enhance the sports and leisure time safety. <h3>Contribution to the Field</h3> The implementation set up developed in TEKO project has received a positive feedback. Experiences indicate that this kind of set up might be a spreadable and affordable way to do safety promotion in schools.