tbuckley/cabot-search huggingface dataset:
Abstract 14859: Mras Knockout Leads To Obesity And Affects In Atherosclerosis
Authors: Jennifer Freyer, Maren Behrensen, Jimmy F Berbee, Jaap J Zwaginga, Zouhair Aherrahrou, Heribert Schunkert, Jeanette Erdmann
Journal: Circulation (2011)

Background: In our recent genome-wide association study the MRas gene on human chromosome 3q22 displayed significant association with coronary disease (p=7,44x10-13). M-Ras is a member of the Ras s...
Abstract 1522: Local Ca Releases And Spontaneous Beating Rate Of Rabbit Sinoatrial Node Cells Are Controlled By Interaction Of Basal Phosphodiesterase 3 And 4 Activity
Authors: Tatiana M Vinogradova, Alexey E Lyashkov, Harold Spurgeon, Edward G Lakatta
Journal: Circulation (2008)

A high basal phosphodiesterase (PDE) activity in sinoatrial node cells (SANC) regulates cAMP and modulates cAMP-mediated PKA-dependent phosphorylation of Ca 2+ cycling proteins that determines the characteristics of local subsarcolemmal Ca 2+ releases (LCR). LCRs occur during the terminal diastolic depolarization and activate the inward Na + -Ca 2+ exchange current, thus, regulating the SANC basal spontaneous beating rate. Though both PDE3 and PDE4 are present in rabbit SANC, a role of PDE4 or its interaction with PDE3 is not clear. To determine to what extent PDE4 controls LCRs and the SANC spontaneous beating rate, we used perforated patch to record spontaneous action potentials (APs) in conjunction with confocal linescan images or whole-cell patch clamp to measure L-type Ca 2+ current (I Ca,L ) at 35 o C. A specific PDE3 inhibitor, cilostamide (Cil, 0.3 μmol/L), increased the spontaneous beating rate by 28% (from 154 ± 21 to 191 ± 17 beat/min); in contrast a specific PDE4 inhibitor, rolipram (Rol, 2 μmol/L), had no effect on the firing rate. The substantial role of PDE4 in the control of basal spontaneous SANC firing was unmasked when PDE3 and PDE4 were simultaneously inhibited: the combination of Rol and Cil produced ~57% acceleration of the beating rate (from129 ± 10 to 200 ± 10 beat/min) equivalent to that produced by the broad-spectrum PDE inhibitor, IBMX (100μM), i.e. ~55% (from 145 ± 8 to 221 ± 6 beat/min). The combination of Cil and Rol increased LCR amplitude, size and decreased the LCR period similar to IBMX. Both IBMX and the combination of Cil and Rol produced a substantial increase in I Ca,L ~135% (from 10 ± 2 to 22 ± 3 pA/pF) and ~125% (from 6 ± 1 to 13 ± 3 pA/pF) respectively. The efficiency of PDE3 inhibition alone on spontaneous beating rate might be ascribed to its lower K m for cAMP, than that of PDE4. When PDE3 is suppressed level of cAMP is sufficiently elevated to activate PDE4. Therefore, in the presence of PDE3 inhibition, PDE4 inhibition contributes to the increase in the spontaneous beating rate. Thus, an interaction of basal PDE3 and PDE4 activities in SANC modulates cAMP level and I Ca,L which controls Ca 2+ influx, cell Ca 2+ load, determining LCR characteristics. When both PDE3 and PDE4 are inhibited the maximum spontaneous beating rate of SANC is achieved.
Abstract 3742: Elevated Brain Natriuretic Peptide and C-reactive Protein Interactively Increased Cardiovascular and All-cause Mortality Risk in Hemodialysis Patients
Authors: Kyuichi Furuhashi, Hideki Ishii, Hiroshi Takahashi, Toru Aoyama, Takanobu Toriyama, Yoshitaka Kumada, Miho Tanaka, Tetsuji Morishita, Tetsuya Amano, Ryuichiro Murakami, Hideo Izawa, Tatsuaki Matsubara, Toyoaki Murohara
Journal: Circulation (2007)

Background: It has been established that elevated brain natriuretic peptide (BNP) and C-reactive protein (CRP) levels are increasingly associated with cardiovascular (CV) morbidity. We examined the prognostic usefulness of combining BNP and CRP for predicting CV mortality in hemodialysis (HD) patients. Methods: Plasma BNP and serum CRP were measured consecutively in 500 HD patients. These patients were divided into 4 groups according to plasma BNP levels; Quartile 1 (Q1): &lt; 45 ng/L, Q2: 145–266 ng/L, Q3: 267– 628 ng/L, and Q4: &gt;628 ng/L, and serum CRP levels; Q1: &lt;0.09 mg/dl, Q2: 0.09 – 0.27 mg/dl, Q3: 0.27–1.17mg/dl and Q4: &gt;1.17mg/dl, respectively. All patients were followed up for 8 years. Results: On Cox proportional hazards analysis, hazard ratio (HR) of elevated BNP levels was 3.93 (95%CI 2.06 –7.52 for Q4 vs Q1) for CV mortality and 3.51 (95%CI 2.18 –5.64 for Q4 vs Q1) for all-cause mortality, respectively (both p&lt;0.0001). Similarly, HR of elevated CRP levels was 6.00 (95%CI 2.89 –12.45) for CV mortality and 8.19 (95%CI 4.53–14.77) for all-cause mortality, respectively (both p&lt;0.0001). In the setting of combination of BNP and CRP, the risk of CV mortality was 23.6-fold in the highest quartile on both BNP and CRP compared with the lowest quartile on both BNP and CRP. Similarly, the risk of mortality was 45.3-fold (Figure ). These variables were significant after adjustment for other CV risk factors. Conclusions: Elevated BNP and CRP interactively increased CV and all-cause mortality risk in HD patients. The combination of BNP and CRP is useful for risk stratification in HD patients because the combination of these variables is more closely related to outcome than either variable alone.
Resolving Some, But Not All Informed Consent Issues in DCDD—the Swiss Experiences
Authors: Markus Christen, Sohaila Bastami, Martina Gloor, Tanja Krones
Journal: The American Journal of Bioethics (2015)

We fully agree with Overby and colleagues (2015) that donation after circulatory determination of death (DCDD) poses special problems that need to be addressed in the consent procedure (Bastami, Kr...
Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010
Authors: M Unemo, D Golparian, A Hestner
Journal: Eurosurveillance (2011)

This report describes one case of verified treatment failure of pharyngeal gonorrhoea using ceftriaxone in Sweden. Previous reports described verified treatment failure of urogenital gonorrhoea using the internationally recommended first-line drug cefixime, but not with ceftriaxone, the last remaining option for empirical treatment of gonorrhoea. Enhanced awareness of clinical failures, pharmacodynamic considerations, follow-up and test of cure, adherence to appropriate case management and treatment guidelines as well as verification/falsification of presumed clinical treatment failures should be emphasised worldwide.
MicroRNA‐9 Promotion of Interleukin‐6 Expression by Inhibiting Monocyte Chemoattractant Protein–Induced Protein 1 Expression in Interleukin‐1β–Stimulated Human Chondrocytes
Authors: Mohammad S. Makki, Abdul Haseeb, Tariq M. Haqqi
Journal: Arthritis & Rheumatology (2015)

Objective Enhanced expression of interleukin‐6 (IL‐6) plays an important role in the pathogenesis of osteoarthritis (OA). Monocyte chemoattractant protein–induced protein 1 (MCPIP‐1) is a novel posttranscriptional regulator of IL‐6 expression and is targeted by microRNA‐9 (miR‐9). We investigated the expression of MCPIP‐1 in OA cartilage and explored whether targeting of MCPIP‐1 by miR‐9 contributes to enhanced IL‐6 expression in OA. Methods Gene and protein expression in IL‐1β–stimulated human OA chondrocytes/cartilage was determined by TaqMan assay and immunoblotting, respectively. Messenger RNA (mRNA) for MCPIP‐1 and IL‐6 expression at the single‐cell level was analyzed using RNAscope. MCPIP‐1 protein interaction with IL‐6 mRNA was investigated using RNA immunoprecipitation. Transient transfections were used for the small interfering RNA (siRNA)–mediated knockdown and overexpression of MCPIP‐1, its RNase‐defective mutant miR‐9, or antagomir. The role of signaling pathways was evaluated using small‐molecule inhibitors. Binding of miR‐9 with the “seed sequence” in the 3′‐untranslated region of MCPIP‐1 mRNA was investigated using a luciferase reporter assay. Results MCPIP‐1 mRNA expression was low, but expression of miR‐9 and IL‐6 was high, in damaged OA cartilage. In IL‐1β–stimulated OA chondrocytes, the expression of miR‐9 and MCPIP‐1 was mutually exclusive, and increased expression of miR‐9 correlated with reduced MCPIP‐1 expression and enhanced IL‐6 expression. MCPIP‐1 protein directly binds with IL‐6 mRNA, and overexpression of wild‐type MCPIP‐1 destabilized the IL‐6 mRNA. MCPIP‐1 expression was altered by overexpression or inhibition of miR‐9. Transfection with miR‐9 mimics inhibited the reporter activity, and mutation of the “seed sequence” abolished the repression of reporter activity. Conclusion These findings implicate miR‐9–mediated suppression of MCPIP‐1 in the pathogenesis of OA via up‐regulation of IL‐6 expression in IL‐1β–stimulated human OA chondrocytes.
Inflammatory markers in serum and lavage fluid in young adult's patients with postinfectious bronchiolitis obliterans
Authors: Ludmila Fiodorovna Kovaleva, Elena Arcadievna Surkova, Maria Anatolievna Petrova
Journal: European Respiratory Journal (2013)

The aim of the present study was to determine the myeloperoxidase (MPO), neutrophil elastase(NE) and α1 proteinase inhibitor (α1–Pi) in serum and bronchoalveolar lavage fluid (BALF) in patients with postinfectious chronic bronchiolitis. We studied 28 patients (age range was from 18 to 32 years with a mean age of 19,7 ± 1,13 years) in exacerbation and minimal activity period.  It was obtained a significant increase in/of MPO level in serum and BALF in patients with exacerbation of the disease (787,8 ± 73,6 ng / ml and 79 - 110 ng / ml, respectively). MPO levels in the sputum (brush-biopsy) and in BALF of patients with minimal activity was: 242,1 ± 17,8 ng / ml and 15-18 ng / ml, respectively. Similar changes were observed for NE activity. Exacerbation significantly increased NE activity in serum (an exacerbation of 515 ± 63,4 nM / ml min, with minimal activity indicators NE were 271 ± 26,5 nM / ml min) and in BALF (sharpening and minimal activity - p   These data reflect the local inflammatory processes and may serve as informative material to use to assess the severity of chronic bronchiolitis.
Elder Abuse
Authors: Carolyn J. Hildreth, Alison E. Burke, Richard M. Glass
Journal: JAMA (2009)

lder abuse, also referred to as elder mistreatment, is any abuse or neglect of a person aged 60 or older by a caregiver or another person in a relationship involving an expectation of trust that threatens his or her health or safety.It is difficult to determine the prevalence of elder abuse because many times cases are not reported.A 2003 National Research Council report estimated that there are between 1 million and 2 million cases of elder abuse and neglect in the United States every year.Family members, adult children, or spouses are implicated in 90% of the cases of elder abuse.Those affected are usually elderly people who are cognitively or physically frail, depressed, lonely, or lacking social support.The August 5, 2009, issue of JAMA is a theme issue on violence and human rights that includes an article reporting that both elder abuse and self-neglect in a community-dwelling population are associated with an increased risk of death.
Effect of percutaneous transluminal coronary angioplasty on deep breathing heart rate variability
Authors: Milena Pelosi Rizk Sperling, Daniela Bassi Dutra, Daniel Eduardo Cunha Leme, Rodrigo Jorge Lobo, Vivian Maria Arakelian, Flavia Rossi Caruso, Audrey Borghi-Silva
Journal: European Respiratory Journal (2012)

BACKGROUND: Coronary angioplasty (PTCA) is a common treatment method in patients with coronary heart disease, but its effects on deep-breathing heart rate variability (HRV) has not been well established.

OBJECTIVE: The aim of the study was to analyse deep breathing heart rate variability, which reflect the sympathovagal control of heart rate in patients before, after 1 and 30 days of elective PTCA.

METHODS: The study consisted of 10 consecutive patients (7 men, 3 women) with age of 62.4±11.6 years, single-vessel coronary artery disease (CAD) who underwent elective coronary angioplasty with stent implant. Heart-rate variability (HRV) was obtained at rest (spontaneous breathing) and during respiratory sinus arrhythmia maneuver (RSA-M) by cardiofrequencimeter (Polar S810i) before, after 1 and 30 days of PTCA. RSA-M consisted of deep-breathing in 6 respiratory cycles per minute. HRV analyses were obtained by the time, frequency-domain (high frequency- HF; and low frequency-LF) and non-linear methods (triangular R-R intervals-RR-tri and Approximate Entropy -ApEn).

RESULTS: The PTCA did not induce changes during deep-breathing when compared to spontaneous breathing in the time domain indices (P>0.05). However, before of PTCA higher values of BF/AF ratio were observed (P<0.05). Interestingly, deep-breathing increased RR-tri only before and after 1 day of PTCA (P<0.05) and ApEn decreased only after 1 month (P<0.05).

CONCLUSION: Patients with CAD presented sympathetic activation before PTCA, which produced altered responses during deep-breathing after the procedure.
The relation of body mass index to astma severity, control level of disease and quality of life
Authors: Engin Aynaci, Baris Anil, Pinar Yildiz
Journal: European Respiratory Journal (2011)

Objectives:  Epidemiologic studies have suggested a relationship between body mass index (BMI) and asthma. The effects of obesity on asthma control as well as asthma related quality of life are not well known. We investigated the effect of BMI on asthma control level (ACQ), severity of the disease, lung function, symptoms and asthma related quality of life (AQLQ).   Methods:  In a cross-sectional study, 204 patients (162 female, 42 male; mean age 36±13 years) were enrolled with mild and moderate asthma according to Global Initiative for Asthma (GINA) guidelines. Patients were stratified by BMI of ≥30 kg/m 2  (obese), 25-29.9 kg/m 2  (overweight), ≤24.9 kg/m 2  (normal and underweight). Outcomes included the recent control of asthma (ACQ), Asthma Quality of Life Questionnaire (AQLQ), forced expiratory volume in 1 second (FEV1) and daily symptom scores.   Results:  Fourty nine of the patients (24%) were considered as an obese and 119 (58.3%) were overweight and obese. No relationship has been observed between sex and obesity (p>0.05). BMI was strongly correlated with age (r=0.533, p=0.01). There was no association between BMI and outcomes as asthma control, asthma related symptom score, FEV1, quality of life.   Conclusions:  Our findings suggested that obesity is not associted with worse asthma outcomes in our population. Weight loss may not improve asthma control and quality of life in this population.
Hydrogen gas alters the production of reactive oxygen species in alveolar epithelial cells in vitro
Authors: Kenichi Kokubo, Takashi Inoue, Kazuko Yamashita, Toshihiro Shinbo, Minoru Hirose, Hirosuke Kobayashi
Journal: European Respiratory Journal (2012)

[Aim] The pulmonary toxicity of high concentration of oxygen during mechanical ventilation relates to reactive oxygen species (ROS). Hydrogen gas (H 2 ) has potential as eliminating highly reactive ROS. We therefore expected that H 2  could reduce the adverse effects of the oxygen exposure. The aim of the present study was to determine the protective effects of H 2  against various oxidative stresses on epithelial cells  in vitro .  [Methods] Human alveolar epithelial cells (A549) were incubated with antimycin A which enhances the generation of superoxide anions (O 2  - ) in mitochondria, with menadione which exogenously generates O 2  -  and H 2 O 2  in the cells, or with Cu +  (converted from Cu 2+  by ascorbic acid) which exogenously generates hydroxyl radical by the Fenton reaction with added Cu +  and endogenous H 2 O 2 . The viability of the cells as well as the levels of O 2  -  and highly reactive ROS in the cells was evaluated with or without 2% H 2 .  [Results] The viability of the cells incubated with menadione or Cu +  decreased or did not change in the presence of H 2 , respectively, while that with antimycin A significantly increased in the presence of H 2  (n=12,  P  2  -  induced by antimycin A significantly decreased with the addition of H 2  (n=11,  P  ,  while highly reactive ROS induced by menadione significantly increased in the cells incubated with H 2  (n=5,  P   [Conclusions] H 2  protects alveolar epithelial cells against injury induced by antimycin A probably due to the decrease in the production of O 2  -  in mitochondria, while H 2  cannot act protective against ROS induced by menadione or the Fenton reaction, meaning that H 2  cannot overcome the effects of exogenously provided ROS.
Immunotherapy concepts under investigation
Authors: T. M. Kündig
Journal: Allergy (2011)

To cite this article: Kündig TM. Immunotherapy concepts under investigation. Allergy 2011; 66 (Suppl. 95): 60–62. Abstract Allergen‐specific immunotherapy (SIT) is effective, but used by only 5% of allergy patients, partly because it requires several years. Intralymphatic immunotherapy (ILIT) administers allergen directly into a subcutaneous lymph node and requires only three injections and a lower allergen dose than subcutaneous administration. ILIT was further improved using a recombinant allergen with enhanced uptake and decreased degradation by antigen‐presenting cells. Another interesting route is transcutaneous/epicutaneous immunotherapy (TCIT, EPIT), which administers allergen by a skin patch. Clinical trials show that TCIT, EPIT is safe and comparably effective to conventional immunotherapy. Implementation of these new methods would increase the spectrum of SIT options, allowing greater individual choice of SIT.
Nonlinear dynamics of heart rate variability in patients with chronic obstructive pulmonary disease and changes after 4-week rehabilitation
Authors: Ina Zivanovic, Eva Zupanic, Mitja Lainscak, Viktor Avbelj, Jurij Matija Kalisnik
Journal: European Respiratory Journal (2014)

Introduction. Nonlinear dynamics (NLD) study fractal geometry and complex dynamics of heart rate variability (HRV) and reflect autonomic nervous system function. There is lack of methodology consensus thus NLD HRV in COPD remains largely unknown.

Aims. The aim of our study was to assess (1) NLD HRV in patients with COPD in comparison to healthy individuals and (2) changes after 4-week comprehensive inpatient rehabilitation (CIR).

Methods. 20-minute electrocardiograms were used to compare NLD HRV (1) between 31 patients with COPD and 45 healthy individuals and (2) between 16 patients with COPD receiving CIR and 13 age- and sex-matched controls with COPD without rehabilitation. We studied detrended fluctuation analysis (DFA) with short-term (≤11 beats, α1) and long-term (>11 beats, α2) correlation properties of RR intervals; low, high and average fractal dimension (FD) and sample entropy (SampEn). During CIR, St. George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT) and incremental shuttle walking test (ISWT) were performed.

Results. Compared to healthy individuals, patients with COPD had significantly lower α1 (p = 0.038). During CIR α2 increased significantly (p = 0.043) and high FD decreased significantly (p = 0.018) in the rehabilitation group. NLD HRV did not change in the control group. Change in 6MWT had negative correlation with change in α2 (r = -0.540, p = 0.031) and positive correlation with change in high FD (r = 0.517, p = 0.040).

Conclusions. α1, an important NLD predictor of arrhythmias, is decreased in COPD. Restitution of cardiac complexity after rehabilitation is related to clinical improvement.
Misleading meta-analysis
Authors: M R Law, N J Wald
Journal: BMJ (1995)

One incorrect meta-analysis does not invalidate them all

EDITOR,--Guilt by association is dangerous practice in medicine as in law, yet James Le Fanu seeks to discredit the results of all meta-analyses1 because of the incorrect result of one: small trials of intravenous magnesium in acute myocardial infarction suggested an effect not confirmed by a large trial.2 The misleading suggestion was probably due to publication bias.2 Meta-analyses are not immune to error and must be evaluated as critically as individual studies.

Le Fanu considers that …
Proteomics: State of the Art and Its Relevance for Gene Therapy
Authors: Sergiu Scobioala, Rainer Klocke, Günter Michel, Sigrid Nikol
Journal: Cardiovascular Research (2006)

The molecular mechanisms underlying most diseases, including those of the cardiovascular system, are widely unknown. Basically, pathological changes in the organism arise from protein alterations. Proteomics comprises a set of tools allowing the identification of protein alterations, i.e. changes of protein abundance and posttranslational modifications, associated with diseases. The linkage of information about such protein changes with functional alterations as revealed by physiological studies constitutes functional proteomics that enables the disclosure of disease mechanisms.
Abstract 5428: Transcutaneous Bionic Baroreflex System Is Widely Applicable For Preventing Severe Orthostatic Hypotension In Patients With Cervical Cord Injury
Authors: Masayoshi Yoshida, Akiko Chishaki, Yoshinori Murayama, Satoshi Kimura, Makoto Ando, Toshirou Saito, Touru Shiino, Keiichiro Shiba, Koji Todaka, Kenji Sunagawa
Journal: Circulation (2008)

Background: We proposed an artificial baroreflex system (bionic baroreflex system: BBS) capable of feedback control of arterial pressure (AP) (Circulation 1999, 2002, 2004). Using BBS, in 2007, we reported a case where we prevented severe orthostatic hypotension in “a patient” with cervical cord injury. It remained unknown, however, if the bionic mechanism is widely applicable for other patients with cervical cord injury in preventing orthostatic hypotension.

Methods and Results: In 8 patients with cervical cord injury who have been suffering from severe orthostatic hypotension, we scanned the body surface and successfully identified the region in every patient capable of increasing AP in response to electrical stimulation. We then stimulated the region with current-modulated electrical pulse-train at 10 Hz with a duty cycle of 0.25, identified the transfer function from the stimulation to AP, and parameterized the respective transfer function (gain = 1.95±0.62 mmHg/mA, time-constant = 75.3±13.1 sec, lag = 0.39±0.37 sec). Using those parameters, we developed a feedback regulator of BBS to control AP. Orthostatic stress decreased mean AP by 30.7±2.9 mmHg. Activation of BBS restored AP to a preset-target value (73.6±6.4 mmHg) by 50% at 34.6±12.1 sec, and by 90% at 60.0±18.3 sec. The regulated AP remains at the target level at least for 10 minutes (Figure[⇓][1]).

Conclusion: The transcutaneous BBS is noninvasive and widely applicable for stabilizing AP in patients with cervical cord injury with serious orthostatic hypotension. The oriental wisdom, i.e., making the use of a skin region as a window to modulate the autonomic system, revitalizes patients with central baroreflex failure.



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