bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment outcomes in a cohort of patients with mucosal‐predominant pemphigus vulgaris
Authors: Ojaimi S. , O'Connor K. , Lin M. W. , Schifter M. , Fulcher D. A.
Published: December 2014

Background

Pemphigus vulgaris (PV) is a rare autoimmune blistering condition. Treatment typically combines corticosteroids with another immunosuppressive agent, such as azathioprine, mycophenolate mofetil (MMF) or rituximab.

Aim

This study aims to compare these second agents for their clinical efficacy and steroid‐sparing effect.

Methods

This was a single‐centre, retrospective observational cohort study of 21 patients with oral PV over a 6‐year period, 18 of whom were newly diagnosed. Of the latter, the first 13 were initially given azathioprine, progressing to MMF and then rituximab on treatment failure, while the next five patients started directly on MMF.

Results

Of the 13 newly diagnosed patients, 2/13 were intolerant of azathioprine, and only 1/11 was controlled, with a median time to treatment failure (MTTF) of 254 days. MMF was given to 17 patients, either de novo (5) or after azathioprine (12), and was significantly more effective, controlling activity in 4/17 patients, and for a significantly longer time (MTTF 395 days, P = 0.019). All 13 patients failing MMF received rituximab, seven required a second dose, and three, a third dose. All patients responded, with 11/13 able to cease steroids. Control was maintained for a similar time to MMF (MTTF 364 days, P = NS). Rituximab also had the best steroid‐sparing effect followed by MMF, then azathioprine. Side‐effects were common with azathioprine, while the other two agents were well tolerated.

Conclusion

Rituximab was the most effective of the three immunosuppressives for PV, although repeat dosing was frequently required. These observations have significant implications for the choice of drugs for this condition.
National social protection policies in West Africa: A comparative analysis
Authors: Pino Ariel , Confalonieri Anna Maria Badini
Published: December 2014

The West African States recognize the importance of social protection and its dual social and economic function; a perspective that coincides fully with the topic of this special issue on Dynamic Social Security. Between 2007 and 2013 theses States developed national social protection policies, strategies or action plans and are now engaged in their implementation. This article reviews these national social protection policies (or strategies) in ten countries in the sub‐region (Benin, Burkina Faso, Côte d'Ivoire, Ghana, Mali, Mauritania, Nigeria, Niger, Senegal and Togo) and presents their contents, revealing a similarity of approach in the development of policies. Specifically, after having carried out a diagnostic study of social protection in their respective countries, the States followed seven distinct stages: defining a national vision, defining precisely what is meant by social protection, laying down the principles on which policies were to be based and finally setting out the general objectives, key areas and mechanisms for implementing and financing their national social protection policies. Following these stages, this comparative study seeks to outline the main trends and key elements of the national social protection policies and bring out best practices to provide a basic structure and general guidelines for developing a national social protection policy, implementing a social protection floor and promoting access to higher levels of protection.
Bias in the Determination of Zr, Y and Rare Earth Element Concentrations in Selected Silicate Rocks by ICP‐MS when Using Some Routine Acid Dissolution Procedures: Evidence from the GeoPT Proficiency Testing Programme
Authors: Potts Philip J. , Webb Peter C. , Thompson Michael
Published: December 2014

The analytical results for the modified river sediment, SdAR‐1 circulated in Round 31 of the GeoPT proficiency testing programme, revealed unexpected discrepancies for Zr, Y and most higher atomic number rare earth elements, in determinations made by ICP‐MS using acid attack digestion methods. This investigation compares these ICP‐MS results with those obtained for SdAR‐1 by three other methods: (a) ICP‐MS using fusion/sintering for sample digestion, (b) XRF analysis and (c) INAA. The distribution of results for the elements Rb, Sr, Ce, Y, Yb and Zr is examined and compared with those of the test material for Round 25 of GeoPT, Paraná basalt, HTB‐1. A substantial proportion (though not all) of Y, Yb and Zr determinations in SdAR‐1 by ICP‐MS/acid attack was variably low (sometimes very low) compared with other methods. A detailed evaluation of the procedures used to determine these results indicated that successful determinations by ICP‐MS/acid attack could be made if digestions were made at 180 °C for 48 hr using at least 2 ml HF per 100 mg of sample. We suggest that the more benign conditions (used by many laboratories) resulted in incomplete digestion of resistant minerals, such as zircon.
Perceptions, experiences and needs of patients with idiopathic pulmonary fibrosis
Authors: Duck Annette , Spencer Lisa G. , Bailey Simon , Leonard Colm , Ormes Jennifer , Caress Ann‐Louise
Published: December 2014

Aims

To understand the perceptions, needs and experiences of patients with Idiopathic Pulmonary Fibrosis.

Background

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease, with a mean life expectancy similar to some forms of cancer of 2–4 years from diagnosis. Unlike the cancer literature, which is rich with studies exploring the needs of their disease group, few publications exist on patient needs with this severe fibrotic lung disease.

Design

A Qualitative study which took place between 2007–2012.

Methods

Seventeen patients with a multidisciplinary team confirmed diagnosis of Idiopathic Pulmonary Fibrosis, with moderate to advanced disease severity and six of their informal carers were interviewed. An interview topic guide was developed by the researchers and service user group. The interviews were audio‐recorded, semi‐structured and took place at a regional respiratory and lung transplant centre in North West England. Interviews were transcribed verbatim and data analysed using Framework Analysis.

Findings

Three main themes were identified: ‘Struggling to get a diagnosis’; ‘Loss of the life I previously had’; and ‘Living with Idiopathic Pulmonary Fibrosis’. Patients reported struggling to get a diagnosis and coping with a life‐limiting, rapidly progressive illness with no good treatment and few support structures.

Conclusions

There is an urgent need for a better understanding of the difficulties faced by people with Idiopathic Pulmonary Fibrosis and their carers. This can be used to develop better supportive care in the United Kingdom and ultimately improve the quality of life of these patients.
Five‐Year Outcomes of Catheter Ablation in Patients with Atrial Fibrillation and Left Ventricular Systolic Dysfunction
Authors: BUNCH T. JARED , MAY HEIDI T. , BAIR TAMI L. , JACOBS VICTORIA , CRANDALL BRIAN G. , CUTLER MICHAEL , WEISS J. PETER , MALLENDER CHARLES , OSBORN JEFFREY S. , ANDERSON JEFFREY L. , DAY JOHN D.
Published: December 2014

Catheter Ablation and Long‐Term Outcomes

Background

Catheter ablation of atrial fibrillation (AF) is an established therapy for symptomatic patients. The long‐term efficacy and impact of catheter ablation among patients with severe systolic heart failure (SHF) requires additional study to understand if outcomes achieved at 1 year are maintained and mechanisms of AF recurrence.

Methods

Three groups with SHF and 5 years of follow‐up were matched 1:4:4 by age (±5 years) and sex: AF ablation patients receiving their first ablation (n = 267), AF patients that did not receive an ablation (n = 1,068), and SHF patient without AF (n = 1,068). SHF was based upon clinical diagnosis and an ejection fraction (EF) ≤35%. Patients were followed for 5‐year primary outcomes of AF recurrence, heart failure, stroke, death, and cardiac function.

Results

At 5 years, 60.7% of patients had clinical recurrence of AF. Diabetes and a prior heart attack were significant predictors of long‐term risk of AF recurrence. Long‐term mortality rates were 27%, 55%, 50%, in the AF ablation, AF, and no AF groups, respectively (P < 0.0001), with the lower rates attributed to lower cardiovascular mortality. At 5 years, there was no difference in EF, yet HF hospitalizations were lower following AF ablation compared to patients with AF and no ablation. Stroke rates at 5 years trended to be lower in the AF ablation group, but the difference was not statistically significant.

Conclusion

Recurrence rates of AF in patients with SHF after ablation are common at 5 years with an anticipated ongoing increase. Long‐term AF‐related comorbidities tended to be less in the AF ablation group.
ASPP2 enhances Oxaliplatin (L‐OHP)‐induced colorectal cancer cell apoptosis in a p53‐independent manner by inhibiting cell autophagy
Authors: Shi Ying , Han Yue , Xie Fang , Wang Anna , Feng Xiaokun , Li Ning , Guo Hongliang , Chen Dexi
Published: December 2014

Inactivation of p53‐mediated cell death pathways is a central component of cancer progression. ASPP2 (apoptosis stimulated protein of p53‐2) is a p53 binding protein that specially stimulates pro‐apoptosis function of p53. Down‐regulation of ASPP2 is observed in many human cancers and is associated with poor prognosis and metastasis. In this study, ASPP2 was found to enhance L‐OHP‐induced apoptosis in HCT116 p53−/− cells in a p53‐independent manner. Such apoptosis‐promoting effect of ASPP2 was achieved by inhibiting autophagy. Further experiments with ASPP2 RNA interference and autophagy inhibitor (3‐methyladenine, 3‐MA) confirmed that ASPP2 enhanced HCT116 p53−/− cell apoptosis via inhibiting the autophagy. The association of cell death and autophagy was also found in ASPP2+/− mice, where colon tissue with reduced ASPP2 expression displayed more autophagy and less cell death. Finally, colorectal tumours and their adjacent normal tissues from 20 colorectal cancer patients were used to examine ASPP2 expression, p53 expression and p53 mutation, to understand their relationships with the patients' outcome. Three site mutations were found in p53 transcripts from 16 of 20 patients. ASPP2 mRNA expressions were higher, and autophagy level was lower in the adjacent normal tissues, compared with the tumour tissues, which was independent of both p53 mutation and expression level. Taken together, ASPP2 increased tumour sensitivity to chemotherapy via inhibiting autophagy in a p53‐independent manner, which was associated with the tumour formation, suggesting that both p53 inactivation and ASPP2 expression level were involved in the sensitivity of colorectal cancer to chemotherapy.
Practical Problems with Medication Use that Older People Experience: A Qualitative Study
Authors: Notenboom Kim , Beers Erna , van Riet‐Nales Diana A. , Egberts Toine C. G. , Leufkens Hubert G. M. , Jansen Paul A. F. , Bouvy Marcel L.
Published: December 2014

Objectives

To identify the practical problems that older people experience with the daily use of their medicines and their management strategies to address these problems and to determine the potential clinical relevance thereof.

Design

Qualitative study with semistructured face‐to‐face interviews.

Setting

A community pharmacy and a geriatric outpatient ward.

Participants

Community‐dwelling people aged 70 and older (N = 59).

Measurements

Participants were interviewed at home. Two researchers coded the reported problems and management strategies independently according to a coding scheme. An expert panel classified the potential clinical relevance of every identified practical problem and associated management strategy using a 3‐point scale.

Results

Two hundred eleven practical problems and 184 management strategies were identified. Ninety‐five percent of the participants experienced one or more practical problems with the use of their medicines: problems reading and understanding the instructions for use, handling the outer packaging, handling the immediate packaging, completing preparation before use, and taking the medicine. For 10 participants, at least one of their problems, in combination with the applied management strategy, had potential clinical consequences and 11 cases (5% of the problems) had the potential to cause moderate or severe clinical deterioration.

Conclusion

Older people experience a number of practical problems using their medicines, and their strategies to manage these problems are sometimes suboptimal. These problems can lead to incorrect medication use with clinically relevant consequences. The findings pose a challenge for healthcare professionals, drug developers, and regulators to diminish these problems.
A systematic review of behavioural interventions to increase maternal calcium intake
Authors: Jung Mary E. , Stork Matthew J. , Stapleton Jessica , Bourne Jessica E. , Martin Ginis Kathleen A.
Published: December 2014

Pregnancy and lactation are a time when adequate calcium consumption is essential for the development of the fetus and to ensure the health of the mother. Over 50% of Canadian women of childbearing and rearing age fail to meet the recommended daily intake of calcium. Identification of effective behavioural intervention strategies for increasing calcium intake is needed within this specific population. This paper brings together all published behavioural interventions designed to increase calcium consumption in pregnant, lactating or post‐partum mothers in a systematic review. Relevant studies were obtained through searches of MEDLINE, EMBASE, PsycINFO, CINAHL and the Cochrane Library with no date restrictions. Studies were evaluated using previously published criteria for evaluating calcium behaviour change interventions. This systematic literature review identified five behavioural calcium interventions conducted within this population. Three interventions aimed to improve overall dietary behaviours, the fourth aimed to promote breastfeeding (including increasing calcium consumption) and the fifth aimed to increase daily servings of yoghurt. Only one of the five interventions yielded large effect sizes, with a mean change of 954 mg of calcium per day post‐intervention. The number of behavioural change techniques did not appear to be related to intervention efficacy. Only one study used a theoretical framework to guide the intervention. This review highlights the lack of research examining behaviour change interventions aimed at increasing calcium consumption in pregnant, lactating and post‐partum women and provides practical suggestions for researchers wishing to intervene with this population in the future.
The mosquitoAnopheles(Cellia)oreiossp. n., formerly species 6 of theAustralasianAnopheles farauticomplex, and a critical review of its biology and relation to disease
Authors: BANGS M. J. , TAAI K. , HOWARD T. M. , COOK S. , HARBACH R. E.
Published: December 2014

Species 6 of theAustralasianAnopheles farautisibling species complex (Diptera:Culicidae) is described and formally namedAnopheles oreiosBangs &Harbach, sp. n. Adult, pupal and fourth‐instar larval specimens collected in theBaliemValley,PapuaProvince,Indonesia, are characterized and compared with those ofAnopheles farauti,Anopheles hinesorum,Anopheles irenicusandAnopheles torresiensis(formerly informally denoted as species 1, 2, 7 and 3, respectively). The variable wings of adult females, the male genitalia, the pupa and the fourth‐instar larva ofAn. oreiosare illustrated andDNAsequence data are included for regions coding for sections of the mitochondrialCOIandCOIIgenes. The biology ofAn. oreiosand its relation to malaria transmission are discussed in detail and contrasted with the biology and disease relations of some members of theAn. farautiandAnopheles punctulatussibling species complexes.
Head and neck cancer: from research to therapy and cure
Authors: Varelas Xaralabos , Kukuruzinska Maria A.
Published: December 2014

Cumulative findings from many research groups have identified new signaling mechanisms associated with head and neck cancers. We summarize these findings, including discussion of aberrant NOTCH, PI3K, STAT3, immune recognition, oxidative pathway, and regulation of cell cycle and cell death. The genomic landscape of head and neck cancers has been shown to differ depending on human papillomavirus (HPV) status. We discuss studies examining the integration of HPV into genomic regions, as well as the epigenetic alterations that occur in response to HPV infection, and how these may help reveal new biomarker and treatment predictors. The characterization of premalignant lesions is also highlighted, as is evidence indicating that the surgical removal of these lesions is associated with better clinical outcomes. Current surgical methods are also discussed, including several less aggressive approaches such as minimal invasive robotic surgery. While much remains to be done in the fight against head and neck cancer, continued integration of basic research with new treatment options will likely lead to more effective therapeutic strategies directed against this disease.
Orchestrating care: nursing practice with hospitalised older adults
Authors: Dahlke Sherry Ann , Phinney Alison , Hall Wendy Ann , Rodney Patricia , Baumbusch Jennifer
Published: December 2014

Background

The increased incidence of health challenges with aging means that nurses are increasingly caring for older adults, often in hospital settings. Research about the complexity of nursing practice with this population remains limited.

Objective

To seek an explanation of nursing practice with hospitalised older adults.

Methods

Design. A grounded theory study guided by symbolic interactionism was used to explore nursing practice with hospitalised older adults from a nursing perspective. Glaserian grounded theory methods were used to develop a mid‐range theory after analysis of 375 hours of participant observation, 35 interviews with 24 participants and review of selected documents.

Results

The theory of orchestrating care was developed to explain how nurses are continuously trying to manage their work environments by understanding the status of the patients, their unit, mobilising the assistance of others and stretching available resources to resolve their problem of providing their older patients with what they perceived as ‘good care’ while sustaining themselves as ‘good’ nurses. They described their practice environments as hard and under‐resourced. Orchestrating care is comprised of two subprocesses: building synergy and minimising strain. These two processes both facilitated and constrained each other and nurses’ abilities to orchestrate care.

Conclusions

Although system issues presented serious constraints to nursing practice, the ways in which nurses were making meaning of their work environment both aided them in managing their challenges and constrained their agency.

Implications for practice

Nurses need to be encouraged to share their important perspective about older adult care. Administrators have a role to play in giving nurses voice in workplace committees and in forums. Further research is needed to better understand how multidisciplinary teams influence care of hospitalized older adults.
Refractive indices used by the Haag‐Streit Lenstar to calculate axial biometric dimensions
Authors: Suheimat Marwan , Verkicharla Pavan K. , Mallen Edward A. H. , Rozema Jos J. , Atchison David A.
Published: December 2014

Purpose

To estimate refractive indices used by the Lenstar biometer to translate measured optical path lengths into geometrical path lengths within the eye.

Methods

Axial lengths of model eyes were determined using the IOLMaster and Lenstar biometers; comparing those lengths gave an overall eye refractive index estimate for the Lenstar. Using the Lenstar Graphical User Interface, we noticed that boundaries between media could be manipulated and opposite changes in optical path lengths on either side of the boundary could be introduced. Those ratios were combined with the overall eye refractive index to estimate separate refractive indices. Furthermore, Haag‐Streit provided us with a template to obtain ‘air thicknesses’ to compare with geometrical distances.

Results

The axial length estimates obtained using the IOLMaster and the Lenstar agreed to within 0.01 mm. Estimates of group refractive indices used in the Lenstar were 1.340, 1.341, 1.415, and 1.354 for cornea, aqueous, lens, and overall eye, respectively. Those refractive indices did not match those of schematic eyes, but were close in the cases of aqueous and lens. Linear equations relating air thicknesses to geometrical thicknesses were consistent with our findings.

Conclusion

The Lenstar uses different refractive indices for different ocular media. Some of the refractive indices, such as that for the cornea, are not physiological; therefore, it is likely that the calibrations in the instrument correspond to instrument‐specific corrections and are not the real optical path lengths.
MicroRNA156 as a promising tool for alfalfa improvement
Authors: Aung Banyar , Gruber Margaret Y. , Amyot Lisa , Omari Khaled , Bertrand Annick , Hannoufa Abdelali
Published: December 2014

A precursor of miR156 (MsmiR156d) was cloned and overexpressed in alfalfa (Medicago sativa L.) as a means to enhance alfalfa biomass yield. Of the five predicted SPL genes encoded by the alfalfa genome, three (SPL6, SPL12 and SPL13) contain miR156 cleavage sites and their expression was down‐regulated in transgenic alfalfa plants overexpressing miR156. These transgenic plants had reduced internode length and stem thickness, enhanced shoot branching, increased trichome density, a delay in flowering time and elevated biomass production. Minor effects on sugar, starch, lignin and cellulose contents were also observed. Moreover, transgenic alfalfa plants had increased root length, while nodulation was maintained. The multitude of traits affected by miR156 may be due to the network of genes regulated by the three target SPLs. Our results show that the miR156/SPL system has strong potential as a tool to substantially improve quality and yield traits in alfalfa.
Determinants of crop diversity in the regions of Bangladesh (1990–2008)
Authors: Rahman Sanzidur , Kazal Mohammad Mizanul Haque
Published: December 2014

The paper measures the level of crop diversity and identifies factors influencing diversification using a panel data of 17 regions of Bangladesh covering a 19 year period (1990–2008). Results revealed the trends that agricultural areas allocated to high‐yielding variety rice, spices and vegetables has increased, while areas cultivating traditional rice, minor cereals, oilseeds, pulses, jute and sugarcane has declined at variable rates across regions with significant differences. The level of crop diversity is also significantly different across regions and has decreased in 2008 from its 1990 level in most regions except Faridpur, Khulna and Sylhet. Among the determinants, an increase in the relative prices of vegetables and urea fertilizer, extension expenditure, labour stock per farm, average farm size, irrigation and a reduction in livestock per farm significantly increase crop diversity. Price policies to improve vegetable prices and investment in irrigation infrastructure and extension services are suggested to promote crop diversity in Bangladesh.
The effect of lactate on intracellular pH and force recovery of fatigued sartorius muscles of the frog, Rana pipiens.
Authors: Renaud J M
Published: December 2014

1. The effects of pHo (extracellular pH) and lactic acid on pHi (intracellular pH) and tetanic force were examined in frog sartorius muscle. Ion‐selective microelectrodes were used to measure pHi. Tetanic force was elicited by field stimulation. Experiments were performed in HEPES‐buffered solution equilibrated with 100% O2. 2. Mean pHi values (+/‐ S.E.M.) of unfatigued frog sartorius muscles were 7.14 +/‐ 0.02 and 7.05 +/‐ 0.09 at pHo 7.2 and 6.4, respectively. 3. A stimulation at a rate of one 100 ms tetanic contraction per second for 3 min reduced pHi to 6.21 +/‐ 0.09 and 6.20 +/‐ 0.04 at pHo 7.2 and 6.4, respectively. Meanwhile at pHo 7.2, the tetanic force (defined as the maximum force developed during a tetanus) decreased by 82.9 +/‐ 2.6%, the maximum rate of relaxation decreased by 92.9 +/‐ 0.9%, and the rate constant of the relaxation decreased by 88.5 +/‐ 1.6%. At pHo 6.4, the decrease in tetanic force, maximum rate of relaxation and rate constant were 90.6 +/‐ 1.8%, 93.8 +/‐ 0.5 and 87.5 +/‐ 2.7%, respectively. 4. The maximum rates of recovery of pHi following fatigue were 0.068 +/‐ 0.05 and 0.025 +/‐ 0.05 pH units min‐1 at pHo 7.2 and 6.4, respectively. Recovery of normal tetanic force and relaxation rate was also slower at acidic pHo than at neutral pHo. 5. In the presence of 40 mmol l‐1 L‐lactic acid at pHo 7.2, the maximum rate of pHi recovery following fatigue was only 0.027 +/‐ 0.03 pH units min‐1 at pHo 7.2. The presence of lactic acid also reduced the recovery of the relaxation phase, but not the recovery of tetanic force. 6. It is suggested that pHi recovery is not a limiting factor for tetanic force recovery and that the extracellular H+ inhibits tetanic force recovery by acting at a site located on the outer surface of the sarcolemma. The recovery of the relaxation phase is believed to be pHi dependent.
Heterogeneous distribution of fast and slow potassium channels in myelinated rat nerve fibres.
Authors: Röper J , Schwarz J R
Published: December 2014

1. Potassium currents were measured in voltage‐clamped single myelinated rat nerve fibres before and after paranodal demyelination with 0.2% pronase or 0.2% lysolecithin added to the external solution. Sodium currents were blocked by 300 nM‐tetrodotoxin. For the purpose of comparison, intact frog nerve fibres were also investigated. 2. Our results suggest the existence of at least two distinct types of K+ channels in the intact node of Ranvier, one with slow and another with fast gating kinetics, in the ratio 4:1. 3. In the rat nodal membrane, slow K+ channels have voltage‐dependent time constants of K+ deactivation with tau n = 68 ms at E = ‐105 mV and tau n = 26 ms at E = ‐150 mV at 20 degrees C. The activation curve of the slow K+ conductance is sigmoid with an inflexion point at ‐60 mV. This means that about 35% of the slow K+ channels are in the open state at the resting potential of ‐77 mV. Slow K+ channels could be blocked by 10 mM‐tetraethylammonium chloride, but were insensitive to 4‐aminopyridine. 4. After paranodal demyelination the ratio of fast to slow K+ channels increased from 17 to 83%. As in the frog (Dubois, 1981 alpha), the population of fast K+ channels in the rat may consist of two different subgroups, both of which can be blocked by 4‐aminopyridine. 5. Demyelination was accompanied by an increase in the capacity current which was used to estimate the exposed membrane area. The density of slow and fast K+ channels was calculated from the quotient of the steady‐state K+ conductance to membrane area. The density of the slow K+ channels is maximal in the nodal membrane and decreases to 1/31 in the internode. By contrast, the distribution of the fast K+ channels differs, their density being maximal in the paranode and decreasing to one‐sixth in the node and internode.
Actions of caffeine on fast‐ and slow‐twitch muscles of the rat.
Authors: Fryer M W , Neering I R
Published: December 2014

1. The effects of caffeine (0.2‐20 mmol l‐1) have been examined on calcium transients (measured with aequorin) and isometric force in intact bundles of fibres from soleus (slow‐twitch) and extensor digitorum longus (EDL; fast‐twitch) muscles of the rat. 2. At 25 degrees C, threshold caffeine concentration for an observable increase in resting [Ca2+]i was 0.2 and 1.0 mmol l‐1 for soleus and EDL muscles respectively. Increases in resting force were first detectable at about 0.5 mmol l‐1 caffeine for soleus muscles and 5.0 mmol l‐1 caffeine for EDL muscles and occurred in the range 0.2‐0.4 mumol l‐1 [Ca2+]i for soleus and 0.7‐0.9 mumol l‐1 for EDL. 3. Caffeine potentiated the twitch responses of soleus and EDL in a dose‐related manner. The soleus was more sensitive in this respect, with 50% potentiation occurring at 1 mmol l‐1 caffeine compared with 3.5 mmol l‐1 for the EDL. Concentrations of caffeine below 2 mmol l‐1 potentiated Ca2+ transients associated with twitches in both soleus and EDL muscles with no apparent change in the decay rate constant. 4. High concentrations of caffeine (greater than 2 mmol l‐1) further potentiated peak Ca2+ in the EDL but depressed it in the soleus. The rate of decay of the Ca2+ transient in high caffeine was significantly prolonged in the soleus but remained unaffected in the EDL. 5. The phosphodiesterase inhibitor, 3‐isobutyl‐1‐methylxanthine (IBMX) had little effect on force or [Ca2+]i at concentrations known to significantly increase intracellular cyclic AMP levels. 6. The Ca2+ transient during fused tetani was characterized by an initial peak, a decline to a plateau level and sometimes a gradual rise towards the end of the stimulus train. Peak [Ca2+]i during normal tetani ranged between 1.1 and 2.4 mumol l‐1 in the soleus and 1.9 and 4.0 mumol l‐1 in the EDL. 7. Caffeine potentiated both force and [Ca2+]i during tetanus. Since the increase of the Ca2+ transient was significantly greater than potentiation of force, it is likely that saturation of myofilaments occurs. The primary effect of caffeine on the Ca2+ transient was an elevation of the plateau phase. 8. Caffeine concentrations below 5 mmol l‐1 potentiate twitch and tetanic force in both fast‐ and slow‐twitch mammalian skeletal muscles primarily by increasing both the basal and stimulus‐evoked release of Ca2+ from the sarcoplasmic reticulum.
Acute carotid baroreflex resetting in conscious dogs.
Authors: Tan W , Zucker I H
Published: December 2014

1. Acute baroreflex resetting in the control of arterial pressure was studied in six chronically instrumented, conscious dogs. Following aortic baroreceptor denervation, the carotid sinuses were surgically prepared for reversible vascular isolation. 2. During the experiments both carotid sinuses were temporarily isolated from the systemic circulation and conditioned with a pulsatile pressure. The carotid sinus conditioning pressure (CPCSP) was at a level of 100, 140 or 60 mmHg for 20 min each. Carotid sinus pressure (CSP) versus mean arterial pressure (MAP) baroreflex curves were constructed after each conditioning period. 3. The baroreflex curves were shifted downward and to the left at low CPCSP and upward and to the right at high CPCSP. 4. We used four parameters to quantify baroreflex resetting. These were: (1) the set point pressure (PSP), (2) the threshold pressure (PTh), (3) BP50 or mid‐point pressure and (4) the CSP at maximum gain (PGmax). At high CPCSP, these four parameters were increased by 18.5 +/‐ 4.0, 23.4 +/‐ 4.3, 21.7 +/‐ 5.0 and 22.0 +/‐ 5.1 mmHg, respectively (P less than 0.05). 5. Resetting was not complete in these studies. The extent of resetting was approximately 50% for upward and 35% for downward baroreflex conditioning. 6. Analysis of the present experimental data indicates that when the cardiovascular system is exposed to a short‐term hyper‐ or hypotension, the baroreflex is capable of correcting the baseline arterial pressure while preserving its ability to buffer transient disturbances as a result of partial resetting.
Membrane conductance oscillations induced by serum in quiescent human skin fibroblasts.
Authors: Pallotta T , Peres A
Published: December 2014

1. Application of fetal calf serum to quiescent human fibroblasts, kept under whole‐cell voltage clamp at positive potentials, induced a series of transient rises in membrane conductance. 2. The first transient increase in conductance developed with very short time lag (2‐10 s) after serum addition, while the period between successive transients was 30‐90 s, being remarkably constant in each particular cell. 3. Raising the Ca2(+)‐buffering capacity of the intracellular solution with 1 mM‐EGTA suppressed the appearance of the sustained oscillations. 4. The conductance increase was strongly voltage dependent: voltage ramps applied before, during and after the transients revealed the activation of an outwardly rectifying conductance with variable reversal potentials (between +14 and ‐55 mV). 5. No significant shifts of the reversal potential were observed when the extracellular K+ concentration was increased to 126 mM. Substitution of K+ with Cs+ as intracellular cation eliminated the outward current in response to serum. 6. External application of the Ca2+ ionophore A23187 elicited currents which were very similar in voltage dependence and time course to those triggered by serum. 7. The serum‐induced response persisted unaffected by the absence of external Ca2+. The response was also seen in the presence of 1 mM‐Cd2+ in the external solution. 8. Serum addition caused a rapid morphological rearrangement of the cells. 9. It is concluded that serum triggers a mobilization of Ca2+ from intracellular stores which in turn activates cationic channels.
The monosynaptic excitatory connections of single trigeminal interneurones to the V motor nucleus of the rat.
Authors: Appenteng K , Conyers L , Moore J A
Published: December 2014

1. We have used the extracellular spike‐triggered averaging method to identify a population of trigeminal interneurones that make monosynaptic connections within the V motor nucleus. The experiments were performed on rats anaesthetized with pentobarbitone (60 mg/kg I.V.; supplementary doses given as necessary to maintain a deep level of anaesthesia). 2. A tungsten microelectrode (tip exposure of some 200 microns) was inserted into the masseter motoneurone pool to allow recording of extracellular activity. A glass electrode filled with DL‐homocysteic acid was used to make simultaneous extracellular recordings of the firing of single neurones in the region immediately caudal to the motor nucleus. 3. Fifty‐eight out of 166 interneurones tested gave unitary extracellular fields in the motor nucleus. The responses consisted of a terminal spike (presynaptic spike) followed by a negative field of duration approximately 3 ms and amplitude 0.4‐10.8 microV. The mean latency between the positive peak of the terminal spike and the onset of the field (synaptic delay) was 0.43 ms (S.D. = 0.10 ms), and the mean latency from the onset of the interneurone spike to the positive peak of the presynaptic spike was 0.35 ms (S.D. = 0.22 ms). Thus the interneurones project directly to the motor nucleus where they then make monosynaptic connections. 4. The negative extracellular fields were taken to reflect an excitatory synaptic input onto neurones within the motor nucleus. The fields were of maximum amplitude at the point of maximum masseter motoneurone antidromic field, suggesting that the connection may be onto elevator motoneurones. 5. The location of the interneurone appeared to the main factor governing the likelihood of obtaining a field. Interneurones located more than 400 microns from the caudal border of the motor nucleus rarely produced fields whereas most of those located within this distance gave fields. This pattern of distribution is strikingly similar to that of trigeminal interneurones labelled by the transneuronal transport of wheatgerm agglutinin‐horseradish peroxidase after an intramuscular injection of the tracer into the masseter muscle. We suggest that this provides electrophysiological support for the suggestion that the tracer does indeed label interneurones by means of retrograde transsynaptic transport.
Human photopic vision with only short wavelength cones: post‐receptoral properties.
Authors: Hess R F , Mullen K T , Zrenner E
Published: December 2014

1. Spatial and temporal contrast sensitivities were investigated in two subjects whose photopic vision has been previously shown to be subserved by only short wavelength cones. 2. Spatial contrast sensitivity was uniformly reduced compared with that of the normal trichromatic observer. Peak contrast sensitivity reached 40 which is a factor of 2‐3 better than previous estimates and extrapolated acuity was around 15 cycles deg‐1. Central, non‐aliased grating acuity was between 6‐9 cycles deg‐1. This declined with eccentricity such that at 20 deg it was around 1 cycle deg‐1. 3. The variation in contrast sensitivity across the visual field was measured for a range of different spatial frequencies. It was found to be of the same form as that for the normal trichromat but reduced in overall sensitivity. 4. Temporal contrast sensitivity was measured for two different spatial frequencies and found to exhibit the spatio‐temporal covariation which is typical of normal trichromatic vision. Temporal acuity exhibited a strong dependence on illuminance and reached asymptotic values of around 40‐45 Hz. While this is more than a factor of two above most previous estimates for the short wavelength receptors of normal vision it agrees with some more recent estimates obtained using a different technique. Temporal resolution was found to be evenly distributed across the visual field. 5. Similarities were found between the post‐receptoral properties of these achromats and the properties of the isolated blue mechanism of normal vision and also the properties of normal luminance contrast processing in general. The present results provide an upper bound on the contribution of the short wavelength mechanism to normal vision and also provide a suitable model of its possible contribution to the processing of luminance contrast in the normal visual system.
A calcium‐ and voltage‐dependent chloride current in developing chick skeletal muscle.
Authors: Hume R I , Thomas S A
Published: December 2014

1. Depolarization of embryonic chick myotubes from negative potentials elicits a rapid spike followed by a long‐duration after‐potential. The ionic basis of the long‐duration after‐potential was examined by making intracellular recordings from cultured myotubes, and by making whole‐cell patch‐clamp recordings from myoblasts and myoballs. 2. The peak potential of the long‐duration after‐potential varied with the chloride gradient, suggesting that a conductance increase to chloride is involved in generating the after‐potential. However, a calcium current was also implicated, since lowering the extracellular calcium or replacing extracellular calcium with cobalt abolished the after‐potential. 3. When extracellular calcium was replaced with strontium or barium, short‐duration spikes similar to calcium spikes were observed, but only strontium was able to support activation of long‐duration after‐potentials. Intracellular injection of calcium or strontium into myotubes bathed in calcium‐free extracellular solutions restored the ability of depolarization to evoke an after‐potential. Intracellular injection of magnesium, barium, nickel or cobalt did not restore this ability. These experiments strongly suggested that the long‐duration after‐potential was due to a calcium‐ and voltage‐activated chloride current. 4. Whole‐cell voltage‐clamp recordings from myoballs and myoblasts showed that a large chloride conductance could be activated by depolarization when the internal free calcium concentration was buffered at levels greater than 10(‐7) M. At 2.5 x 10(‐7) M‐calcium, the voltage dependence of activation was steepest in the range of ‐30 to ‐20 mV and the activation kinetics varied with the membrane potential. The time to half‐maximal activation ranged from 0.1 s at positive potentials to greater than 1 s at more negative potentials. The time constant for deactivation was approximately 1 s at ‐50 mV. No inactivation was observed. 5. The selectivity of the chloride current was measured by substituting other anions for chloride. The following permeability series was found: I‐ greater than NO3‐ greater than Br‐ greater than Cl‐ greater than acetate greater than F‐ greater than SO4‐ = glucuronate. Thus anion permeability decreased as the hydration radius increased. 6. Measurements of the resting potential of developing myoblasts and myotubes under ‘physiological’ conditions (37 degrees C, bicarbonate buffer) suggest that the after‐potential acts to depolarize these cells 10‐20 mV above their resting potential (approximately ‐60 mV) for several seconds. 7. We discuss the possibility that the long‐duration after‐potential may be involved in triggering myoblast fusion and in the generation of bursts of spontaneous contractions in developing myotubes.
Comparison of sodium‐calcium exchanger and transient inward currents in single cells from rabbit ventricle.
Authors: Giles W , Shimoni Y
Published: December 2014

1. Whole‐cell voltage‐clamp measurements have been made in rabbit ventricular myocytes under conditions in which both Na(+)‐Ca2+ exchanger currents (IEX, slow tails) and transient inward currents (ITI or TI) can be recorded. A number of experimental manoeuvres have been used in an attempt to separate or dissociate these two currents. 2. As expected, partial inhibition of the Na(+)‐K+ pump by application of 0.54 mM [K+] Tyrode solution or 10(‐5) M‐strophanthidin induced TI currents which were recorded in the presence of IEX slow tails. 3. Complete inhibition of the Na(+)‐K+ pump with zero [K+] Tyrode solution resulted in larger and more frequent TIs but smaller IEX tails. 4. A somewhat similar dissociation between ITI and IEX was observed when NaCl was reduced to 37.5 mM by using LiCl to replace NaCl. This inhibited the Na(+)‐Ca2+ exchanger current, but induced ITI. 5. Transient inward currents and IEX tails could also be separated by selected patterns of stimulation (voltage‐clamp depolarizations): following the second pulse of a pair of stimuli, IEX was significantly reduced whereas the TIs increased in size and frequency. 6. Additional experimental tests involving changes in external divalent ions could also separate these two currents. Increasing [Ca2+]o 3‐fold increased the TIs without changing IEX. Shortly after [Ca2+]o was replaced with either [Ba2+]o or [Sr2+]o the TIs were blocked but IEX was unchanged. Application of MnCl2 (1 mM) and elevation of [K+]o inhibited IEX but did not significantly change the TI currents. 7. Application of caffeine (5‐10 mM) or ryanodine (2 x 10(‐6) M) blocked the TI currents at times when the IEX tails were not changed. 8. In combination these results suggest that even though both IEX and ITI are triggered (activated) by increases in [Ca2+]i, these two currents are distinct. IEX is generated by electrogenic Na(+)‐Ca2+ exchange, while the TI currents may be due to Ca2(+)‐activated cation‐selective channels in the sarcolemma.
Task‐dependent changes in cutaneous reflexes recorded from various muscles controlling finger movement in man.
Authors: Evans A L , Harrison L M , Stephens J A
Published: December 2014

1. Cutaneous reflex responses have been recorded from muscles involved in the control of finger movement following electrical stimulation of the digital nerves of the fingers in man. 2. Recordings have been made while subjects performed various manual tasks. 3. Reflexes recorded while subjects performed a relatively isolated finger movement consisted of an initial short‐latency increase in muscle electrical activity, followed by a decrease, followed by a prominent longer‐latency increase. The long‐latency excitatory component was smaller or absent during those grips used in the present study. 4. The short‐latency excitatory (E1) and inhibitory (I1) components of the cutaneomuscular reflex response are mediated via spinal pathways. The second longer‐latency excitatory component (E2) is of supraspinal origin, requiring the integrity of the dorsal columns, sensorimotor cortex and corticospinal tract (Jenner & Stephens, 1982). The results of the present study suggest that one or more of these supraspinal pathways is more active when a finger is used in a relatively isolated manner than when the same finger participates in any of the gripping manoeuvres used in the present experiments.
Influence of the endothelium and alpha‐adrenoreceptor antagonists on responses to noradrenaline in the rabbit basilar artery.
Authors: Garland C J
Published: December 2014

1. Noradrenaline (10(‐6)‐10(‐2) M) produced slow, concentration‐dependent depolarization of smooth muscle cells in the rabbit basilar artery, which preceded the onset of contraction by around 8 s (n = 18). 2. With concentrations greater than 10(‐4) M, noradrenaline produced action potentials and fast rhythmic depolarizations superimposed on the slow depolarization. Each fast event was followed by a clear increase in the rate of smooth muscle contraction. The selective alpha 1‐adrenoreceptor agonist phenylephrine produced very similar membrane and contractile responses. 3. Action potentials were not produced in artery segments where the endothelium had been removed. In these segments, the amplitude of both contraction and slow depolarization to noradrenaline was similar to that observed in segments with an intact endothelium, but the tension increased more slowly; 84 s compared to the 52 s required to produce 50% of total contraction when the endothelium was functional. 4. The selective alpha 1‐antagonist prazosin (10(‐6) M) either abolished or significantly reduced both the slow depolarization (with concentrations less than 10(‐3) M‐noradrenaline) and smooth muscle contraction to noradrenaline. When prazosin was present, action potentials with 10(‐3) M‐noradrenaline were only produced in 50% of the cells studied. 5. Irreversible blockade of alpha‐adrenoreceptors with benextramine (10(‐5) M for 20 min) abolished action potentials and both the depolarization and contraction produced with all but the highest concentrations of noradrenaline. With 10(‐3) M‐noradrenaline, depolarization was produced but it was significantly reduced and usually not associated with smooth muscle contraction. 6. The results show that smooth muscle depolarization, contraction and possibly endothelium‐dependent action potentials are produced by alpha‐adrenoreceptor stimulation. They also show that noradrenaline‐induced action potentials produce smooth muscle contraction, and that slow depolarization is an important, but not absolute requirement for contraction. The fact that action potentials were produced in response to high concentrations of noradrenaline in the presence of prazosin, but not after benextramine, suggests that these concentrations of noradrenaline can surmount competitive antagonism with prazosin.