bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lidocaine reduces the transition to slow inactivation in Nav1.7 voltage‐gated sodium channels
Authors: Sheets Patrick L , Jarecki Brian W , Cummins Theodore R 
Published: January 2011

BACKGROUND AND PURPOSEThe primary use of local anaesthetics is to prevent or relieve pain by reversibly preventing action potential propagation through the inhibition of voltage‐gated sodium channels. The tetrodotoxin‐sensitive voltage‐gated sodium channel subtype Nav1.7, abundantly expressed in pain‐sensing neurons, plays a crucial role in perception and transmission of painful stimuli and in inherited chronic pain syndromes. Understanding the interaction of lidocaine with Nav1.7 channels could provide valuable insight into the drug's action in alleviating pain in distinct patient populations. The aim of this study was to determine how lidocaine interacts with multiple inactivated conformations of Nav1.7 channels.EXPERIMENTAL APPROACHWe investigated the interactions of lidocaine with wild‐type Nav1.7 channels and a paroxysmal extreme pain disorder mutation (I1461T) that destabilizes fast inactivation. Whole cell patch clamp recordings were used to examine the activity of channels expressed in human embryonic kidney 293 cells.KEY RESULTSDepolarizing pulses that increased slow inactivation of Nav1.7 channels also reduced lidocaine inhibition. Lidocaine enhanced recovery of Nav1.7 channels from prolonged depolarizing pulses by decreasing slow inactivation. A paroxysmal extreme pain disorder mutation that destabilizes fast inactivation of Nav1.7 channels decreased lidocaine inhibition.CONCLUSIONS AND IMPLICATIONSLidocaine decreased the transition of Nav1.7 channels to the slow inactivated state. The fast inactivation gate (domain III–IV linker) is important for potentiating the interaction of lidocaine with the Nav1.7 channel.
Stable expression and functional characterization of a human nicotinic acetylcholine receptor with α6β2 properties: discovery of selective antagonists
Authors: Capelli Anna Maria , Castelletti Laura , Chen Yu Hua , Van der Keyl Harjeet , Pucci Luca , Oliosi Beatrice , Salvagno Cristian , Bertani Barbara , Gotti Cecilia , Powell Andrew , Mugnaini Manolo 
Published: January 2011

BACKGROUND AND PURPOSEDespite growing evidence that inhibition of α6β2‐containing (α6β2*) nicotinic acetylcholine receptors (nAChRs) may be beneficial for the therapy of tobacco addiction, the lack of good sources of α6β2*‐nAChRs has delayed the discovery of α6β2‐selective antagonists. Our aim was to generate a cell line stably expressing functional nAChRs with α6β2 properties, to enable pharmacological characterization and the identification of novel α6β2‐selective antagonists.EXPERIMENTAL APPROACHDifferent combinations of the α6, β2, β3, chimeric α6/3 and mutant β3V273Ssubunits were transfected in human embryonic kidney cells and tested for activity in a fluorescent imaging plate reader assay. The pharmacology of rat immune‐immobilized α6β2*‐nAChRs was determined with125I‐epibatidine binding.KEY RESULTSFunctional channels were detected after co‐transfection of α6/3, β2 and β3V273Ssubunits, while all other subunit combinations failed to produce agonist‐induced responses. Stably expressed α6/3β2β3V273S‐nAChR pharmacology was unique, and clearly distinct from α4β2‐, α3β4‐, α7‐ and α1β1δε‐nAChRs. Antagonist potencies in inhibiting α6/3β2β3V273S‐nAChRs was similar to their binding affinity for rat native α6β2*‐nAChRs. Agonist affinities for α6β2*‐nAChRs was higher than their potency in activating α6/3β2β3V273S‐nAChRs, but their relative activities were equivalent. Focussed set screening at α6/3β2β3V273S‐nAChRs, followed by cross‐screening with the other nAChRs, led to the identification of novel α6β2‐selective antagonists.CONCLUSIONS AND IMPLICATIONSWe generated a mammalian cell line stably expressing nAChRs, with pharmacological properties similar to native α6β2*‐nAChRs, and used it to identify novel non‐peptide, low molecular weight, α6β2‐selective antagonists. We also propose a pharmacophore model of α6β2 antagonists, which offers a starting point for the development of new smoking cessation agents.
β2‐adrenoceptor agonists: current and future direction
Authors: Cazzola Mario , Calzetta Luigino , Matera Maria Gabriella 
Published: January 2011

Despite the passionate debate over the use of β2‐adrenoceptor agonists in the treatment of airway disorders, these agents are still central in the symptomatic management of asthma and COPD. A variety of β2‐adrenoceptor agonists with long half‐lives, also called ultra long‐acting β2‐adrenoceptor agonists (ultra‐LABAs; indacaterol, olodaterol, vilanterol, carmoterol, LAS100977 and PF‐610355) are currently under development with the hopes of achieving once‐daily dosing. It is likely that the once‐daily dosing of a bronchodilator would be a significant convenience and probably a compliance‐enhancing advantage, leading to improved overall clinical outcomes. As combination therapy with an inhaled corticosteroid (ICS) and a LABA is important for treating patients suffering from asthma, and a combination with an inhaled long‐acting antimuscarinic agent (LAMA) is important for treating COPD patients whose conditions are not sufficiently controlled by monotherapy with a β2‐adrenoceptor agonist, some novel once‐daily combinations of LABAs and ICSs or LAMAs are under development.LINKED ARTICLESThis article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visithttp://dx.doi.org/10.1111/bph.2011.163.issue‐1
Use of cryopreserved autologous cells for extracorporeal photochemotherapy: clinical applications
Authors: Merlin Etienne , Jacomet Florence , D'Incan Michel , Halle Pascale , Berger Marc , Gandemer Virginie , Piguet Chirstophe , Souteyrand Pierre , Deméocq François , Kanold Justyna 
Published: January 2011

BACKGROUND: Using autologous cryopreserved mononuclear cells (MNCs) for extracorporeal photochemotherapy (ECP) offers several advantages, such as treating patients from geographically distant care centers or maintaining ECP schedule while dramatically reducing number of apheresis sessions. We previously reported that cryopreserved cells retain their immunomodulatory properties when exposed to UVA and psoralen. To date, there are no clinical data on the use of cryopreserved MNCs for ECP (“cryo‐ECP”).CASE REPORTS: Three patients were treated by cryo‐ECP for refractory dermatomyositis, juvenile localized scleroderma, and acute graft‐versus‐host disease. For the first two patients, cryo‐ECP aimed to reduce the number of apheresis sessions. Each cell product was split into three equal fractions: one was infused, and the other two were frozen for later infusion. The third patient was referred to our center from a hospital 700 km away. Fifteen apheresis procedures were performed during his stay: 12 were immediately treated and infused while three were cryopreserved. After discharge, the three cryopreserved bags were thawed, ECP‐treated, and then sent back to the patient.CONCLUSION: In all three patients, cryo‐ECP was safe and feasible. These cases illustrate promising clinical applications of the technique, opening perspectives for making ECP much more acceptable to patients while extending its indications.
International quotidian dialysis registry: Annual report 2010
Authors: LINDSAY Robert M. , SURI Rita S. , MOIST Louise M. , GARG Amit X. , CUERDEN Meaghan , LANGFORD Sarah , HAKIM Raymond , OFSTHUN Norma J. , MCDONALD Stephen P. , HAWLEY Carmel , CASKEY Ferqus J. , COUCHOUD Cecile , AWARAJI Christian , NESRALLAH Gihad E. 
Published: January 2011

AbstractThe International Quotidian Dialysis Registry (IQDR) is a global initiative designed to study practices and outcomes associated with the use of hemodialysis (HD) regimens of increased frequency and/or duration. The IQDR grew out of the initiative that lead to the randomized prospective studies of nocturnal HD and short hours daily dialysis vs. conventional thrice weekly HD that are conducted by the Frequent Hemodialysis Network sponsored by the National Institutes of Health. These 2 separate studies are drawing to a close and the first results are expected to be reported later this year. These studies use surrogate outcomes for their primary endpoints as they are not powered to look at outcomes of mortality and hospitalization. The IQDR attempts to aggregate long‐term follow‐up data from centers utilizing alternative HD regimens worldwide and will have adequate statistical power to examine those important outcomes. To date, the IQDR has enrolled patients from Canada, the United States, Australia, New Zealand, and France and has linked with commercial databases and national registries. This sixth annual report of the IQDR describes: (1) An update on the governance structure; (2) The recommendations made at the first general meetings of the IQDR Scientific Committee and Advisory Board; (3) The status of those recommendations; (4) A summary of current data sources and participating registries; (5) The status of recruitment to date; (6) The creation of a specific Canadian IQDR data set and; (7) The current research agenda.
The carbon footprints of home and in‐center maintenance hemodialysis in the United Kingdom
Authors: CONNOR Andrew , LILLYWHITE Robert , COOKE Matthew W. 
Published: January 2011

AbstractClimate change presents a global health threat. However, the provision of healthcare, including dialysis, is associated with greenhouse gas emissions. The aim of this study was to determine the carbon footprints of the differing modalities and treatment regimes used to deliver maintenance hemodialysis (HD), in order to inform carbon reduction strategies at the level of both individual treatments and HD programs. This was a component analysis study adhering to PAS2050. Emissions factors were applied to data that were collected for building energy use, travel and procurement. Thrice weekly in‐center HD has a carbon footprint of 3.8 ton CO2 Eq per patient per year. The majority of emissions arise within the medical equipment (37%), energy use (21%), and patient travel (20%) sectors. The carbon footprint of providing home HD varies with the regime. For standard machines: 4 times weekly (4 days, 4.5 hours), 4.3 ton CO2 Eq; 5 times weekly (5 days, 4 hours), 5.1 ton CO2 Eq; short daily (6 days, 2 hours), 5.2 ton CO2 Eq; nocturnal (3 nightly, 7 hours), 3.9 ton CO2 Eq; and nocturnal (6 nightly, 7 hours), 7.2 ton CO2 Eq. For NxStage equipment: short daily (5.5 days, 3 hours), 1.8 t CO2 Eq; 6 nightly nocturnal (2.1 ton CO2 Eq). The carbon footprint of HD is influenced more by the frequency of treatments than by their duration. The anticipated rise in the prevalence of home HD patients, dialyzing more frequently and for longer than in‐center patients, will increase the emissions associated with HD programs (despite reductions in patient travel emissions). Emerging technologies, such as NxStage, might offer a solution to this problem.
Early Indicators and Risk Factors for Ethical Issues in Clinical Practice
Authors: Pavlish Carol , Brown‐Saltzman Katherine , Hersh Mary , Shirk Marilyn , Nudelman Olga 
Published: January 2011

Abstract Purpose: Nurses in all clinical settings encounter ethical issues that frequently lead to moral distress. This critical incident study explored nurses’ descriptions of ethically difficult situations to identify risk factors and early indicators of ethical conflicts. Methods: Employing the critical incident technique, researchers developed a questionnaire that collected information on ethically difficult situations, their risk factors and early indicators, nurse actions, and situational outcomes. Two nurse researchers independently analyzed and categorized data using a constant comparison technique. Findings: Most of the ethically difficult situations pertained to end‐of‐life care for children and adults. Conflicts in interpersonal relationships were prevalent. Nurses were especially moved by patient and family suffering and concerned about patient vulnerability, harm‐benefit ratio, and patient autonomy. Researchers discovered risk factor categories for patients, families, healthcare providers, and health systems. Additionally, researchers found subcategories in six major categories of early indicators: signs of conflict, patient suffering, nurse distress, ethics violation, unrealistic expectations, and poor communication. Conclusions: Nurses are keenly aware of pertinent risk factors and early indicators of unfolding ethical conflicts. Many nurses reported feeling powerless in the face of ethical conflict. Research that develops interventions to strengthen nurses’ voices in ethically difficult situation is warranted. Clinical Relevance: Nurses are in a key position to identify patient situations with a high risk for ethical conflict. Initiating early ethics consultation and interventions can alter the course of pending conflicts and diminish the potential for patient and family suffering and nurses’ moral distress.
Intermittent Androgen Suppression in Prostate Cancer: Testosterone Levels and its Implication
Authors: Mearini Luigi , Zucchi Alessandro , Costantini Elisabetta , Bini Vittorio , Porena Massimo 
Published: January 2011

ABSTRACT

Introduction
Intermittent androgen suppression (IAS) in patients affected by prostate cancer seems to lessen the severity of the side effects that are associated with continuous androgen ablation.

Aim
This report monitors the effect of IAS on testosterone values, quality of life, and sexual function during phases of therapy.

Methods
A total of 100 patients entered a prospective study of IAS. Androgen blockade was prolonged until a serum prostate specific antigen (PSA) nadir was reached and then resumed for a PSA threshold of 10 ng/mL, in repeated cycles. During I phase, we assessed testosterone levels, well-being with quality-of-life score, and sexual function.

Main Outcome Measures
All patients were followed up every 3 months with PSA and total testosterone determinations, and with quality-of-life score using a 10-point questionnaire. Side effects were assessed using yes/no questions. Sexual function was assessed using yes/no questions and in the sexually active patients with International Index of Erectile Function-5 (IIEF).

Results
All patients completed I cycle of treatment (I ON plus I OFF phase). During the OFF phase, 46% of patients showed low testosterone levels, while the others recovered normal testosterone concentrations at a mean of 6.2 months after therapy. There is a negative correlation between baseline PSA values and length of OFF phase and testosterone recovery, and a negative correlation between length of OFF phase and testosterone value during OFF phase. Worsening in Quality of Life (QOL) was significant during active treatment with respect to baseline, but therapy withdrawal showed a positive impact with respect to treatment period. Improvement in quality of life correlated to testosterone recovery and time to testosterone recovery. Fifty-four percent of subjects had normal sexual intercourse at therapy withdrawal, with a correspondence to time to testosterone recovery.

Conclusions
Quality of life and sexual function seem to follow testosterone normalization. These results could have implications in the analysis of IAS.
Development and Validation of Chinese Version of Female Sexual Function Index in a Chinese Population—A Pilot Study
Authors: Sun Xiaoguang , Li Chunying , Jin Lina , Fan Yangjun , Wang Dongmei 
Published: January 2011

ABSTRACT

Introduction
Female sexual dysfunction (FSD) is a prevalent problem that has been continuously overlooked in mainland China. An assessment instrument for FSD is urgently needed.

Aim
To develop and validate the Chinese version of the Female Sexual Function Index (CVFSFI) to assess FSD in China.

Methods
A total of 328 women (20–65 years old) participated in this study. The CVFSFI was developed through the procedures of translation, back translation, revision by research team, and pilot study. After an interview for clinical diagnosis of FSD based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, all participants completed the CVFSFI for a validation study. Eighty-three women completed CVFSFI again 3–4 weeks after the first visit. Test–retest reliability was determined by Pearson product–moment correlations. Internal consistency reliability was estimated with Cronbach’s alpha coefficient. Construct validity was evaluated by principal component analysis using varimax rotation. Discriminant validity was assessed with between-groups analysis of variance.

Main Outcome Measures
Including the reliability and the validity of the CVFSFI and its domains.

Results
A total of 172 women (52.4%) met the DSM-IV-TR criteria for diagnosis of sexual dysfunction and were included in the FSD group, while 156 (47.6%) women without FSD were included in the control group. We showed that the overall test–retest reliability coefficients were high for total CVFSFI and each domain (r at least 0.69) and the internal consistency reliability of CVFSFI was within the acceptable range (Cronbach’s alpha values: from 0.69 to 0.94). Moreover, the principal component analysis with varimax rotation produced six-factor structure similar to the original FSFI. We found significant differences in both total and domain scores between FSD and control groups, demonstrating a good discriminant validity of CVFSFI.

Conclusion
The CVFSFI is a reliable and valid questionnaire, which can be used in the assessment of FSD among Chinese women.
Relationship between Premature Ejaculation and Depression in Korean Males
Authors: Son Hwancheol , Song Sang Hoon , Lee Jun-Young , Paick Jae-Seung 
Published: January 2011

Abstract

Introduction
The psychological impacts of premature ejaculation (PE), which include guilt, anxiety, and distress, have been well established in Western countries. However, in Asia, although a substantial number of epidemiological studies have surveyed the prevalence of PE, researchers have not thoroughly investigated the relationship between PE and depression, or have defined PE properly.

Aim
We studied the association between PE and depression and other psychological disturbances, in a Korean cohort by applying an appropriate definition for PE and validated outcome measures of depression.

Methods
A total of 956 males (≥20 years) were initially approached via an Internet survey company. Participants were asked to complete a questionnaire requesting detailed medical and sexual histories, which included questions from the Erectile Function Domain score in the International Index of Erectile Function (IIEF-EF) and the Beck Depression Inventory (BDI). The prevalence of PE was evaluated using two different definitions—self-assessed PE and presumed PE. Presumed PE was defined as a short ejaculation time (an estimated intravaginal ejaculatory latency time ≤5 minutes), an inability to control ejaculation, and the presence of distress resulting from PE.

Main Outcome Measures
Ejaculation-related questionnaire, the IIEF-EF, and BDI.

Results
A total of 334 men were evaluated. The prevalence of PE was 10.5% according to the Presumed PE definition, whereas by self-assessment, it was 25.4%. Self-assessed PE patients suffered from various psychological problems, such as depression, low self-esteem, bother, and low sexual satisfaction. Even after excluding erectile dysfunction (ED) subjects, a significant relationship was found between self-assessed PE and depression. Moreover, after further classification of the Self-assessed PE group, we found that subjects included in this group, but not in the Presumed PE group, suffered more from psychological burden than any other members of the cohort.

Conclusion
Korean men with subjective perceptions of PE are prone to various psychological problems, which include depression.
Three Phases of Corporal Tracing Elicited by Electrical Field Stimulation on Rabbit Corpus Cavernosum Smooth Muscle in Penile Perfusion Model
Authors: Zhao Chen , Cho Kyung Woo , Park Jong Kwan 
Published: January 2011

ABSTRACT

Introduction
Nitric oxide (NO) has been shown to mediate electrical field stimulation (EFS)-caused smooth muscle relaxation. It is known that the neural control of penile erection involves adrenergic, cholinergic, and non-adrenergic-non-cholinergic (NANC) neuro-effector systems; however, the effects of EFS on adrenergic and cholinergic nerves are not clear.

Aims
To elucidate EFS-induced signal transductions involved in adrenergic, cholinergic, and NANC neuro-effector systems by using an in vitro penile perfusion model.

Methods
EFS was performed on penile corpus cavernosum smooth muscle from male New Zealand White rabbits, which was pre-contracted with L-phenylephrine (10 µM). We investigated the penile tracing elicited by EFS on tissues pre-incubated with guanethidine (Guan, 50 µM), tetrodotoxin (TTX, 10 µM), Nω nitro-L-arginine-methyl ester (L-NAME, 1 mM), atropine (50 µM), or eserine (10 µM).

Main Outcome Measures
The time-to-peak of each phase, the percentage of relaxation, and the area under the curve (AUC).

Results
We discovered an extraordinary phenomenon: three distinct phases elicited by EFS. Phase I was abolished by L-NAME. Phase II was decreased by eserine and Guan, but increased by L-NAME. Phase III was abolished by atropine, but enhanced by eserine and Guan. TTX diminished all three phases. The time to reach the top of phase I was delayed by TTX. The time to attain the peak of phase II was shortened by L-NAME, but delayed by TTX and atropine. The time to reach the top of phase III was shortened by L-NAME, eserine, and Guan. AUC was significantly decreased by L-NAME and TTX.

Conclusions
EFS stimulated adrenergic, cholinergic, and NANC neuro-effector systems simultaneously. Phase I was related to the NO pathway. Phase II was multiply affected by self-recovery properties, and adrenergic and cholinergic nerves. Phase III was related to cholinergic nerves. The corporal tracing elicited by EFS was the balanced result of multiple factors.
Telomeres as age markers in vertebrate molecular ecology
Authors: DUNSHEA GLENN , DUFFIELD DEBORAH , GALES NICK , HINDELL MARK , WELLS RANDALL S. , JARMAN SIMON N. 
Published: January 2011

AbstractChronological age is a fundamental and yet elusive variable in studies of many wild animals. Telomeres are nucleoprotein structures on the ends of chromosomes that change size throughout the life of many animals and because of this property have been advocated as a means to estimate age. In this review, we assess the existing and potential application of using telomeres for age estimation. We argue that there are conceptual and statistical inconsistencies in previous studies and that the basis for telomere change over time is not well understood and affected by several intrinsic and extrinsic process unrelated to chronological time. Furthermore, these processes are likely to vary spatially and temporally for animal populations. We conclude that the current data suggest telomeres should not be used for age estimation. If telomere‐based age estimation is to be used, more work in understanding variability in key processes affecting telomere dynamics and rigorous substantiation via blind testing is needed.