tbuckley/cabot-search huggingface dataset:
Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey
Authors: None Gupta, None Konnikov, None Macdonald, None Rich, None Rodger, None Edmonds, None Mcmanus, None Summerbell
Journal: British Journal of Dermatology (1998)

The number of individuals diagnosed with diabetes mellitus is increasing. The diabetic may present with complications involving all systems of the body. While onychomycosis is often observed in diabetics, there have been no large studies on the prevalence of the condition in this patient group. We examined the prevalence of onychomycosis in diabetics attending diabetes and dermatology clinics in London, Ontario, Canada and Boston, MA, U.S.A. Diabetic subjects seen in dermatology offices were for unrelated dermatoses; those referred specifically for the management of onychomycosis were excluded from the sample. A total of 550 diabetic subjects was evaluated (283 males and 267 females), age 56.1 ± 0.7 years (mean ± SEM). Patients with type I diabetes constituted 34% of the sample. The racial origin was: 531 Caucasians, 17 Asians, one African-American and one American-Indian. Abnormal-appearing nails and mycological evidence of onychomycosis (mostly due to dermatophytes) were present in 253 (46%) and 144 (26%), respectively, of 550 subjects. The development of onychomycosis was significantly correlated with age (P < 0.0001) and male gender (P < 0.0001). Males were 2.99 times more likely to have onychomycosis compared with females (95% confidence interval, CI 1.94–4 61). After controlling for age and sex, the risk odds ratio for diabetic subjects to have toenail onychomycosis was 2.77 times compared with normal individuals (95% CI 2.15–3.57). After controlling for age and sex, a stepwise logistic regression demonstrated that significant predictors for onychomycosis included a family history of onychomycosis (P = 0.0001), concurrent intake of immunosuppressive therapy (P = 0.035) and peripheral vascular disease (P = 0.023). Toenail onychomycosis was present in 26% of the sample and is projected to affect approximately one-third of subjects with diabetes. Predisposing factors include increasing age, male gender, family history of onychomycosis, concurrent intake of immunosuppressive agents and peripheral vascular disease.
Abstract 9960: Does the Airway Management Device for Out-of-Hospital Cardiac Arrest Have No Effect to Patient’s Outcome?
Authors: Hiroshi Takyu, Hideharu Tanaka, Takashi Nakagawa
Journal: Circulation (2014)

Introduction:  Supraglottic airway devices (SADs) and endotracheal tube (ET) are widely used for out-of-hospital cardiac arrest (OHCA) patients. However, it remains unclear whether SADs or ET are used on patients with worse conditions or not.   Hypothesis:  The aim of this study was to assess the incidence of shockable rhythm in those on whom a bag valve mask (BVM), SADs and ET is used at the first contact of emergency medical services (EMS).   Methods:  A total of 925288 OHCA patients from January 1, 2005 through December 31, 2012 in Japan’s nationwide registry were stidied. All OHCA data was collected according to the Utstein-style guidelines. We included adult patient (age from 15 to 89 years) with presumed cardiac origin, for whom the collapse was witnessed. We excluded epinephrine administration, non-cardiac origin, patients who regained return of spontaneous circulation before EMS arrival, and patients for whom the time exceeded a 99 percentile of EMS response time which is defined by EMS call-contact interval. The primary end point was shockable rhythm defined by initial ECG.  Cox’s proportional hazards regression model was used to test the significance of shockable rhythm adjusting for age, gender, airway management and EMS response time. Patient’s age was stratified into 4 groups as 15-49, 50-69, 70-79, 80-89 years of age. ANOVA was used to test the difference of EMS response time among airway management.   Results:  A total of 80960 patients met the inclusion criteria, 42768 patients (53%) in the BVM group, 34062 patients (42%) in the SADs group and 4130 patients (5%) in the ET group. Adjusted hazard ratio compared to the BVM group was; 0.82 (95% CI 0.79-0.84) for the SADs group and 0.72 (95% CI 0.67-0.78) for the ET group. EMS mean response times +/- SEM were BVM:498.1 +/- 1.00 seconds, SADs: 511.1 +/- 1.12 seconds and ET:525.5 +/- 3.22 seconds (p   Conclusions:  In conclusion, SADs and ET are used when the incidence of shockable rhythm is lower and EMS response time is longer. Therefore, SADs or ET is used when the condition of patients is worse than BVM. We have to consider the patients’ medical status for analyzing the effectiveness of airway management devices.
Dietary omega-3 polyunsaturated fatty acids prevent impaired social behaviour and prefrontal dopamine metabolism in food allergic mice
Authors: C.G.M. De Theije, L.W.J. Van Den Elsen, L.E.M. Willemsen, V. Milosevic, S. Lopes Da Silva, B. Olivier, J. Garssen, S.M. Korte, A.D. Kraneveld
Journal: Allergy (2014)

Background: It is suggested that allergic immune activation, combined with a genetic predisposition, may contribute to the expression of aberrant social behaviour relevant to autism. We have previously shown that a food allergic response reduced social behaviour in mice, which was associated with altered dopaminergic activity in brain regions relevant for social and emotional behaviour. Dietary fatty acid composition has been shown to affect both the immune system and neurological processes and may therefore contribute to the prevention of food allergy-induced abnormalities in social behaviour. Method: The aim of this study was to assess whether dietary supplementation with fish oil rich in long chain omega-3 polyunsaturated fatty acids (n-3 LCPUFA) prevents food allergy-induced abnormalities in social behaviour and associated deficits of the dopaminergic system in the prefrontal cortex of whey-sensitised mice. Results: The n-3 LCPUFA-enriched fish oil diet decreased the acute allergic skin response and was able to prevent the disturbance in social behaviour of whey-sensitised mice. N-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation in the brain and restored levels of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA) in the prefrontal cortex of allergic mice. Moreover, reduced levels of 5-HIAA, metabolite of serotonin, in intestines of allergic mice was also restored by the n-3 LCPUFA-enriched diet. Conclusion: In addition to its effects on the allergic skin response, n-3 LCPUFA restored allergy-induced deficits in social behaviour and in prefrontal dopamine and metabolite levels. Therefore, n-3 LCPUFA may exert its beneficial effect on behaviour via modulation of the dopaminergic system in the prefrontal cortex and may therefore be an interesting target in the use of dietary interventions for immune-mediated psychiatric disorders such as ASD.
A memorable patient: Long term follow up
Authors: R. Doherty
Journal: BMJ (1999)

In 1968,although an obstetrician by training, I was appointed as general surgeon to a mobile surgical team embarked in the aircraft carrier Eagle to provide cover for the naval task group covering the withdrawal from Aden.

This eccentric appointment arose from a temporary shortage of available surgical specialists and was a cause of some amusement on board and some concern on my part. I was not reassured to hear that, in the second world war, the United States marine corps had recruited several obstetricians who were unwanted by the other services and found them to have the best battlefield mortality figures, since they were well used to working fast in a welter of blood. A further complication was …
Depression–Heart Disease Link Probed
Authors: Mike Mitka
Journal: JAMA (2005)

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Fetal bile salt metabolism
Authors: B. T. Jackson, R. A. Smallwood, G. J. Piasecki, A. S. Brown, H. F. J. Rauschecker, R. Lester
Journal: Journal of Clinical Investigation (1971)

Cholate metabolism was studied in fetal dogs 1 wk before term and was compared with cholate metabolism in adult dogs. Tracer amounts of sodium cholate-(14)C were administered to the fetus in utero by intravenous infusion over 6 hr. Fetal plasma disappearance, biliary excretion, tissue distribution, and placental transfer of cholate were measured over 10 hr. Infused cholate-(14)C was cleared rapidly from fetal plasma principally by the fetal liver and to a minor extent by placental transfer to the mother. The taurine conjugate was formed in the fetal liver and was excreted into the proximal small intestine via the biliary tree. Indirect evidence for the functioning enterohepatic circulation of bile salt in the fetus was obtained. Comparison with the results of similar experiments in adult dogs showed that the fetal liver was almost as efficient as the adult liver in the uptake, conjugation, and excretion of tracer amounts of cholate-(14)C. The maximal rate of excretion of radiolabel attained by the fetus was somewhat slower than in the adult (82.8 +/-1.4% and 96.1 +/-4.0% [mean +/-SE] of the infusion rate, respectively), and the proportion of the total dose excreted by the fetal liver during 10 hr was smaller (81.4 +/-1.3% vs. 96.6 +/-4.4%). This difference could be only partly accounted for by placental transfer (2.8 +/-0.6% of the fetal dose). Labeled cholate and taurocholate were excreted by the fetus at similar rates, which suggests that, under the conditions of study, conjugation had little influence on the rate of transfer of cholate across the liver cell. It is concluded that the fetal dog, 1 wk before birth, has a remarkably mature and efficient mechanism for the uptake and excretion of cholate.
309. Controlling Embryogenesis Using Engineered Zinc Fingers in Drosophila
Authors: Andrew C. Jamieson, Thomas J. Cradick, Bo Guan, Hong Xiao, Pamela M. Carroll
Journal: Molecular Therapy (2004)

Using zinc finger protein transcription factors (ZFP TFs) to control gene expression has many possible applications in gene therapy, including their use in the differentiation of tissues and, potentially, in the context of an entire embryo. Towards this goal, we have used zinc finger protein transcription factors (ZFP TFs11) to achieve the specific regulation of the Drosophila fushi tarazu gene during insect embryogenesis. ZFP TFs fused to either the VP16 activation domain or to the MBD-like D protein (a repression domain specific to the Drosophila embryo22) were expressed in the embryos of transgenic flies under the control of a heat-shock inducible promoter. Expression of the engineered ZFP activator or repressor resulted in reciprocal effects on the ftz phenotype, including alterations in the stripe pattern of the developing embryo corresponding to pair-rule morphological defects and changes in Engrailed (En) staining in alternate stripes. These results demonstrate that ZFP TFs can be used in the context of a developing animal to achieve specific regulation of a particular gene, and hold promise for future gene therapy applications.
Abstract 17710: Phrenic Nerve Injury Despite High-Output Pacing in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation
Authors: Brett Izzo, Miki Yokokawa, Krit Jongnarangsin, Hamid Ghanbari, Rakesh Latchamsetty, Thomas Crawford, Eric Good, Frank Bogun, Frank Pelosi, Hakan Oral, Fred Morady, Aman Chugh
Journal: Circulation (2014)

Introduction: High-output pacing has been advocated as a strategy to avoid injury to the phrenic nerve (PN) during antral pulmonary vein (PV) isolation. We assessed the hypothesis that pacing does not prevent PN injury in patients undergoing radiofrequency (RF) ablation of atrial fibrillation (AF). Methods: The medical records of 198 consecutive patients (age=63±12 years, 129 men, ejection fraction=57±10%, LA=44±6mm, paroxysmal=49%) undergoing their first ablation procedure for AF were reviewed. All patients underwent antral PV isolation using a 3D mapping system (CARTO XP or CARTO 3) and a 3.5 mm irrigated-tip ablation catheter (maximum power, 25 W). Prior to RF energy delivery, high-output pacing (20 mA @ 10 ms, maximum output) was performed to asses for PN capture. Sites that afforded PN capture were avoided and RF energy was delivered at adjacent sites without PN capture. The 3-D maps were reviewed to identify the prevalence and sites of PN capture. Results: High-output pacing along the anterior right antrum resulted in PN capture in 35 patients (18%). The most common site with a positive response was the crux between the upper and lower PVs (60%), followed by the right superior PV (43%), and the right inferior PV (20%). Of the patients with PN capture, 49% had only one site of capture, 20% with two sites, and 31% had 3 or more sites. All PVs were isolated at the end of the procedure. Two patients (1%) developed PN injury (symptom onset on the day after the procedure), which was confirmed on radiography. In neither case was there evidence of PN capture during the procedure. Symptoms resolved in both patients within 3 months, with normalization of radiographic findings. Conclusions: High-output pacing along the anterior right PV antrum yields PN capture in roughly one-fifth of the patients undergoing PV isolation. Despite a negative response to pacing and alteration of the lesion set, PN injury may occur. The reason for this discordance is unknown, but may include the possibility that the capture threshold of the PN exceeds the maximum output of the stimulator, or that RF energy may injure the pericardiophrenic artery, which accompanies the PN. Avoiding high-power or long-duration lesions and high contact force in this region may minimize the risk of PN injury.
Abstract 17427: Arachidonic Acid-Derived 14,15-Epoxyeicosatrienoic Acid Exerts Antihypertrophic Effects via Inhibition of Calcineurin Activation
Authors: Venkatesh Rajapurohitam, Xiaohong T Gan, Xilan Tang, Cathy Huang, Kasem Nithipatikom, Garrett J Gross, Morris Karmazyn
Journal: Circulation (2014)

Introduction: Epoxyeicosatrienoic acids (EETs) are epoxides derived from arachidonic acid catalyzed by an epoxygenase system. Although EETs have been shown to protect against ischemia little is known regarding their effects on the hypertrophic program. In this study we determined the direct effect of 14,15-EET on phenylephrine (PE)-induced hypertrophy in neonatal rat ventricular myocytes (NRVMs) as well as its effect on the postinfarction response in rats subjected to 4 weeks of sustained coronary artery ligation (CAL).

Methods and Results: Treatment of NRVMs with 10 μM PE for 24 increased the cell surface area by 1.3 fold and ANP gene expression measured by real-time PCR by 1.8 fold (P<0.05 for both). These responses was associated with increased production of 14,15 EET by approximately 1.6 fold (P<0.05) determined by liquid chromatography-mass spectrometry. The hypertrophic response to PE was associated with significantly increased intracellular Na+ (1.75 fold) and Ca2+ (1.3 fold) levels which were prevented by 100 nM 14,15-EET. In addition, PE induced an increase in MCIP1 expression, an index of calcineurin activation by 2-fold (P<0.05) which was completely prevented by 14,15 EET. Post-CAL administration of 14,15-EET (3μg/kg bw/day) via osmotic minipump significantly improved left ventricular function as determined by echocardiography (ejection fraction: CAL+saline 57.48±2.18% vs CAL+EET 72.75±2.19%, fractional shortening: CAL+saline 34.03±2.07% vs CAL+EET 44.55±1.00%, E/A ratio: CAL+saline 2.21±0.17 vs CAL+EET 1.63±0.13). These effects were associated with significantly reduced left ventricular internal dimensions during diastole and systole (CAL + saline LVIDd 8.59±0.14 mm and LVIDs 5.15 ± 0.26 mm vs CAL+14,15-EET LVIDd 7.89 ± 0.1 mm and LVIDs 4.01 ± 0.24 mm). These effects were associated with significantly reduced indices of hypertrophy as well as abrogation in the 10-fold increase in MCIP1 expression.

Conclusion: Our results demonstrate that 14,15-EET induces a marked antihypertrophic and antiremodelling effect likely by preventing calcineurin activation. Exogenous administration, enhancing its endogenous synthesis or preventing 14,15-EET degradation may represent effective heart failure treatment strategies.
Abstract 1606: A Novel Cardiac-Specific Isoform of the Cell Cycle-Related Kinase Provides Cardioprotection during Myocardial Ischemia
Authors: Hongyu Qiu, Bin Tian, You-Tang Shen, Dorothy E Vatner, Stephen F Vatner, Christophe Depre
Journal: Circulation (2008)

Since heart failure (HF) is characterized by the decreased activity of pro-survival signaling pathways, we reasoned that examining genomic changes in a clinically relevant model of HF would uncover novel genes involved in protecting the heart that were downregulated in HF. Accordingly, we examined a genomic profile by DNA microarray in a primate model of myocardial infarction (MI) followed by three weeks pacing to develop HF, and compared to sham animals (n=5/group). In this array, the transcript of the gene encoding the cell cycle-related kinase (CCRK), for which no function is known in adult heart, was down-regulated by 50% in HF versus sham (P&lt;0.05), which was confirmed by quantitative PCR. Upon sequencing, the cardiac CCRK (cCCRK) showed a conservation of the N-terminal kinase domain, but differed in its C-terminal half from the “generic” CCRK cloned in other tissues, due to alternative splicing. Although the “generic” CCRK phosphorylated its substrate, the cyclin-dependent kinase 2, and doubled the number of myocytes in the S phase of the cell cycle, these effects were not observed with cCCRK (P&lt;0.05 between groups). Rather, overexpression of cCCRK in cardiac myocytes induced a 36% increase in protein/DNA ratio and a 50% decrease in apoptosis upon chelerythrine treatment (both, P&lt;0.05 vs. LacZ). A tetracycline (Tet)-dependent transgenic (TG) mouse model with cardiac-specific overexpression of cCCRK was generated, which showed a 3-fold increase in cCCRK abundance compared to wild type (WT) mice (P&lt;0.01 vs. WT) upon Tet removal. Both WT and TG mice (n=3/group) underwent 45 min no-flow ischemia of the left anterior descending artery and 24h reperfusion, followed by measurement of the area-at-risk (AAR) and infarct size (IS). The AAR/left ventricular mass was similar in WT and TG. However, IS/AAR was reduced (P&lt;0.01) by more than 50% in TG (29±3%) compared with WT (61±5%). Therefore, a variant of CCRK is expressed in the heart, which is down-regulated in HF, which promotes cell growth and survival, when overexpressed in vitro , and which provides major protection against myocardial ischemia when overexpressed in vivo . Thus, CCRK is a novel mechanism for cardioprotection in ischemia, and may be a new approach to HF treatment. This research has received full or partial funding support from the American Heart Association, AHA National Center.
591. Comparison of Plant-TK/AZT Versus HSV-TK/Ganciclovir Enzyme/Prodrug Systems in a Human Glioma Cell Line
Authors: Mette Willer, Peter Kristoffersen, Zoran Gojkovic
Journal: Molecular Therapy (2004)

Nucleoside analogs were among the first chemotherapeutic agents to be used for the medical treatment of malignant and viral diseases. Although these compounds are used as first line therapy for many cancer types, several disadvantages still remain. Therefore alternative strategies like gene therapy are being developed to improve their therapeutic properties. There are many barriers to overcome in developing clinically useful suicide therapy systems. Effective tumor destruction depends on the chemistry of the prodrugs, the interaction between enzyme and prodrug, and the choice of the gene therapy vector. The perfect prodrug should be rapidly activated, so issues like prodrug half-life, degradation or clearance mechanisms will not be limiting factors. On the other hand, highly efficient enzymes should prove beneficial since gene expression and gene transfer are usually not high in vivo. Because current delivery methods cannot transfer the gene to all tumor cells, the strong bystander effect, where activated prodrug can kill neighboring tumor cells that are not expressing the suicide gene, is also needed.
NKp46<sup>+</sup> cells express granulysin in multiple cutaneous adverse drug reactions
Authors: C. Schlapbach, A. Zawodniak, N. Irla, J. Adam, R. E. Hunger, D. Yerly, W. J. Pichler, N. Yawalkar
Journal: Allergy (2011)

To cite this article: Schlapbach C, Zawodniak A, Irla N, Adam J, Hunger RE, Yerly D, Pichler WJ, Yawalkar N. NKp46 + cells express granulysin in multiple cutaneous adverse drug reactions. Allergy 2011; 66 : 1469–1476. Abstract Background: The spectrum of cutaneous adverse drug reactions (cADRs) ranges from benign presentations to severe life‐threatening forms such as toxic epidermal necrolysis (TEN). In TEN, granulysin has been shown to be the key cytotoxic molecule. Still, little is known about the expression of granulysin in other cADRs. As an important source of granulysin, natural killer (NK) cells are of major interest in cADRs. Recently, NKp46 has been identified as the most selective NK‐cell marker. However, the role of NKp46 + cells in cADRs and their contribution to granulysin expression remain to be elucidated. Methods: Immunohistochemical and immunofluorescence staining of tissue sections from multiple cADRs were quantitatively and qualitatively evaluated. Further, in vivo and in vitro drug‐stimulation tests were performed. Results: Granulysin is expressed at different levels in multiple cADRs both by NKp46 + cells and by CD8 + T cells. Even in mild forms of cADRs, granulysin can be induced in vivo and in vitro in a drug‐specific manner. NKp46 + cells were found to infiltrate the dermal/epidermal junction particularly in TEN. Conclusion: The impressive clinical differences of cADRs may not be uniquely explained by the expression of granulysin. Additional factors such as drug‐specific activation and recruitment of NKp46 + cells to the epidermis may play a role in determining the severity of cADRs. Therefore, unraveling the effects of drugs on NK‐cell activation and trafficking may help to better understand the cytotoxic mechanisms behind cADRs.