bluuebunny/crossref_metadata_2025 huggingface dataset:
A brief perspective on insulin production
Authors: Steiner D. F. , Park S.‐Y. , Støy J. , Philipson L. H. , Bell G. I.
Published: October 2009

The preeminent role of the beta cell is to manufacture, store and release insulin. The mature insulin molecule is composed of two polypeptide chains designated as A and B that are joined by two pairs of disulfide bonds with an additional intramolecular disulfide bond in the A chain. However, the two chains of the insulin molecule are not synthesized as separate polypeptide chains but rather are generated by specific proteolytic processing of a larger precursor, proinsulin. This discovery in 1967 and the concept of prohormones changed our view of the biosynthesis of hormones and neuropeptides. It allowed studies of the regulation of insulin biosynthesis that highlighted the key role of glucose. In addition, the C‐peptide, the polypeptide that joins the A and B chains in proinsulin and is stored with insulin in the secretory granules and secreted in equimolar amounts, allowed studies of pancreatic β cell function in vivo including in patients with diabetes. Subsequent studies have identified the specific proteases, prohormone convertases 1/3 and 2 and carboxypeptidase E, that are involved in the conversion of proinsulin to proinsulin intermediates and then to insulin. Disorders of (pro)insulin biosynthesis continue to illuminate important aspects of this pathway, revealing important connections to diabetes pathogenesis. Recent studies of patients with insulin gene mutations that cause permanent neonatal diabetes have identified key residues affecting the folding and structural organization of the preproinsulin molecule and its subsequent processing. These findings have renewed interest in the key role of endoplasmic reticulum function in insulin biosynthesis and the maintainance of normal beta cell health.
Roles of cAMP signalling in insulin granule exocytosis
Authors: Seino S. , Takahashi H. , Fujimoto W. , Shibasaki T.
Published: October 2009

Insulin secretion is regulated by a series of complex events generated by various intracellular signals including Ca2+, ATP, cAMP and phospholipid‐derived signals. Glucose‐stimulated insulin secretion is the principal mode of insulin secretion, and the mechanism potentiating the secretion is critical for physiological responses. Among the various intracellular signals involved, cAMP is particularly important for amplifying insulin secretion. Recently, glucagon‐like peptide‐1 (GLP‐1) analogues and dipeptidyl peptidase‐IV (DPP‐IV) inhibitors have been developed as new antidiabetic drugs. These drugs all act through cAMP signalling in pancreatic β‐cells. Until recently, cAMP was generally thought to potentiate insulin secretion through protein kinase A (PKA) phosphorylation of proteins associated with the secretory process. However, it is now known that in addition to PKA, cAMP has other targets such as Epac (also referred to as cAMP‐GEF). The variety of the effects mediated by cAMP signalling may be linked to cAMP compartmentation in the pancreatic β‐cells.
Shortcomings of current models of glucose‐induced insulin secretion
Authors: Henquin J. C. , Nenquin M. , Ravier M. A. , Szollosi A.
Published: October 2009

Glucose‐induced insulin secretion by pancreatic β‐cells is generally schematized by a ‘consensus model’ that involves the following sequence of events: acceleration of glucose metabolism, closure of ATP‐sensitive potassium channels (KATP channels) in the plasma membrane, depolarization, influx of Ca2+ through voltage‐dependent calcium channels and a rise in cytosolic‐free Ca2+ concentration that induces exocytosis of insulin‐containing granules. This model adequately depicts the essential triggering pathway but is incomplete. In this article, we first make a case for a model of dual regulation in which a metabolic amplifying pathway is also activated by glucose and augments the secretory response to the triggering Ca2+ signal under physiological conditions. We next discuss experimental evidence, largely but not exclusively obtained from β‐cells lacking KATP channels, which indicates that these channels are not the only possible transducers of glucose effects on the triggering Ca2+signal. We finally address the identity of the widely neglected background inward current (Cl− efflux vs. Na+ or Ca2+ influx through voltage‐independent channels) that is necessary to cause β‐cell depolarization when glucose closes KATP channels. More attention should be paid to the possibility that some components of this background current are influenced by glucose metabolism and have their place in a model of glucose‐induced insulin secretion.
Lipid receptors and islet function: therapeutic implications?
Authors: Kebede M. A. , Alquier T. , Latour M. G. , Poitout V.
Published: October 2009

G‐protein coupled receptors (GPCRs) are targets of approximately 30% of currently marketed drugs. Over the last few years, a number of GPCRs expressed in pancreatic β‐cells and activated by lipids have been discovered. GPR40 was shown to be activated by medium‐ to long‐chain fatty acids (FAs). It has since been shown that GPR40 contributes to FA amplification of glucose‐induced insulin secretion. Although some controversy still exists as to whether GPR40 agonists or antagonists should be designed as novel type 2 diabetes drugs, data obtained in our laboratory and others strongly suggest that GPR40 agonism might represent a valuable therapeutic approach. GPR119 is expressed in pancreatic β‐cells and enteroendocrine L‐cells, and augments circulating insulin levels both through its direct insulinotropic action on β‐cells and through FA stimulation of glucagon‐like peptide 1 (GLP‐1) secretion. GPR120 is expressed in L‐cells and was also shown to mediate FA‐stimulated GLP‐1 release. Finally, GPR41 and GPR43 are receptors for short‐chain FAs and may indirectly regulate β‐cell function via adipokine secretion. Although the discovery of these various lipid receptors opens new and exciting avenues of research for drug development, a number of questions regarding their mechanisms of action and physiological roles remain to be answered.
Genetic basis of β‐cell dysfunction in man
Authors: Groop L. , Lyssenko V.
Published: October 2009

Although the genetic causes of monogenic disorders have been successfully identified in the past, the success in dissecting the genetics of complex polygenic diseases has until now been limited. With the introduction of whole genome wide association studies (WGAS) in 2007, the picture has been dramatically changed. Today we know of about 20 genetic variants increasing the risk of type 2 diabetes (T2D). Most of them seem to influence the capacity of β‐cells to increase insulin secretion to meet the demands imposed by an increase in body weight and insulin resistance. This probably represents only the tip of the iceberg, and over the next few years refined tools will provide a more complete picture of the genetic complexity of T2D. This will not only include the current dissection of common variants increasing the susceptibility of the disease but also rare variants with stronger effects, copy number variations and epigenetic effects like DNA methylation and histone acetylation. For the first time, we can anticipate with some confidence that the genetics of a complex disease like T2D really can be dissected.
Reverse breeding: a novel breeding approach based on engineered meiosis
Authors: Dirks Rob , Van Dun Kees , De Snoo C. Bastiaan , Van Den Berg Mark , Lelivelt Cilia L. C. , Voermans William , Woudenberg Leo , De Wit Jack P. C. , Reinink Kees , Schut Johan W. , Van Der Zeeuw Eveline , Vogelaar Aat , Freymark Gerald , Gutteling Evert W. , Keppel Marina N. , Van Drongelen Paul , Kieny Matthieu , Ellul Philippe , Touraev Alisher , Ma Hong , De Jong Hans , Wijnker Erik
Published: October 2009

Reverse breeding (RB) is a novel plant breeding technique designed to directly produce parental lines for any heterozygous plant, one of the most sought after goals in plant breeding. RB generates perfectly complementing homozygous parental lines through engineered meiosis. The method is based on reducing genetic recombination in the selected heterozygote by eliminating meiotic crossing over. Male or female spores obtained from such plants contain combinations of non‐recombinant parental chromosomes which can be cultured in vitro to generate homozygous doubled haploid plants (DHs). From these DHs, complementary parents can be selected and used to reconstitute the heterozygote in perpetuity. Since the fixation of unknown heterozygous genotypes is impossible in traditional plant breeding, RB could fundamentally change future plant breeding. In this review, we discuss various other applications of RB, including breeding per chromosome.
Patterns of Informal Help and Caregiving in Sweden: A Thirteen‐Year Perspective
Authors: Jegermalm Magnus , Jeppsson Grassman Eva
Published: October 2009

This article analyses informal help and caregiving in Sweden with a focus on the scope and trends of change over time. The discussion is based on the results of three national surveys and of one survey conducted in the county of Stockholm. The results indicated that informal help and caregiving was common throughout the period under study. In the 1990s, the figures were fairly stable, while from the late 1990s to 2005 there seems to have been a dramatic increase in the prevalence of such support. Two interpretative perspectives are used to discuss this pattern. One locates its point of departure in recent welfare state changes and in the substitution argument, according to which cuts in welfare services put more pressure on people to provide informal help and care. The second perspective relates to the present debate on civil society and to its possible role in contemporary society. According to the civil society perspective, an increase in the prevalence of informal help and caregiving might be interpreted as an expression of growing civic involvement ‘in its own right’, without a straightforward and simple relationship to changes in the welfare state. It is argued in the article that the two frames of interpretation should not be viewed as mutually exclusive, but rather that they represent two partly complementary approaches to the understanding of the complex dynamics of unpaid work in contemporary Swedish society.
Social Policy: Now and Then
Authors: Wilding Paul
Published: October 2009

This article explores the way aspects of our approach to social policy in the UK have changed over the last 40 years – one academic lifetime and also, coincidentally, the lifetime of this journal – and the significance of six particular changes. More social problems have come to be seen as having a supra‐national dimension: the scale and ramifications of problems are much better appreciated; the accepted territory of social policy has greatly widened; the state has lost people's confidence; we have come to see organizational and management issues as much more important; and the health of the economy has come to be regarded as a greater priority than the development of systems of social welfare.
EMPLOYER SIZE, WAGES AND UNOBSERVED SKILLS: EVIDENCE FROM MOONLIGHTERS IN THE UK*
Authors: MURAVYEV ALEXANDER
Published: October 2009

In this paper we examine the labour quality explanation of the employer size–wage gap: larger firms pay higher wages because they employ more skilled workers. Most previous studies control for unobserved skills of workers by applying the fixed‐effects estimator to longitudinal data, thus assuming time‐invariant unobserved individual heterogeneity. We release this assumption by using a sample of moonlighters; hence, identification is achieved by differencing across two jobs held simultaneously rather than sequentially. Using the UK Quarterly Labour Force Survey, we find that controlling for unobserved skills in the sample of moonlighters does not reduce the estimate of the wage gap.
STRUCTURE REGULATION, PRICE STRUCTURE, CROSS‐SUBSIDIZATION AND MARGINAL COST OF PUBLIC FUNDS*
Authors: CHANG MING CHUNG , PENG HSIAO‐PING
Published: October 2009

In this paper we study the social desirability of the structure regulation which transforms a single multi‐product monopoly into an oligopoly where the industry produces differentiated complementary goods. In particular, we pay special attention to the cross‐subsidization which will be eliminated by the structure regulation. It is established that if horizontal externalities between the goods are not too strong, then the monopoly has a socially optimal price structure. In contrast, the oligopoly always distorts the price structure. We also demonstrate that the monopoly will cross‐subsidize a product if and only if this product has a relatively low absolute advantage.
ORIGINAL ARTICLE: Referrals to a learning disability social work team 1996 to 2005
Authors: Morrison Aine , Bickerstaff David , Taylor Brian J
Published: October 2009

Accessible summary

 This research is about people with learning disabilities who were referred to the North Belfast social work team.

 There were 252 referrals between 1995 and 2005 but only 127 cases were closed.

 Over a third of the people being referred had behaviour problems.

 There were more people with autism referred in the second half of the 10 years.

 A fifth of the people who were referred only found out they had a learning disability when they were aged 16 or over.

 People with learning disabilities often have health problems but these were often not mentioned when people were referred.

 This research matters to people with learning disabilities because it is important to know what problems people have and what help they need.

In order to understand better the needs of clients and to inform the delivery of services, referrals to the North Belfast Learning Disability Social Work Team between 1 January 1996 and 31 December 2005 were studied. The documentary analysis of all 252 referrals during the 10‐year period included referral books, social work files and the electronic client‐based system Soscare. There were increases in referrals with recorded autism and in those aged 18–25, and high levels of recorded behavioural difficulties. There were low levels of recorded visual impairment, hearing impairment and mental health problems. Twenty‐one per cent of referrals were likely to have been diagnosed with a learning disability at age 16 or over. Child referrals showed a broad spectrum of identified need whereas adult referrals were predominantly identified as needing daytime occupation. There was an increase in the team caseload from 364 to 489 over the period caused by the number of referrals exceeding the number of closures every year except 1997. We recommend a greater focus on health status in social work assessments, a review of case management practice and greater inclusion of ‘newly diagnosed’ adolescents and adults in service planning.
Differential gene expression of bgp and mgp in trabecular and compact bone of Atlantic salmon (Salmo salar L.) vertebrae
Authors: Krossøy Christel , Ørnsrud Robin , Wargelius Anna
Published: October 2009

The tissue‐specific gene expression of the vitamin K‐dependent proteins bone γ‐carboxyglutamate‐protein (BGP) and matrix γ‐carboxyglutamate‐protein (MGP) in Atlantic salmon (Salmo salar L.) was investigated. In previous studies, BGP, the most abundant non‐collagenous protein of bone, was almost exclusively associated with bone, whereas the non‐structural protein MGP has a more widespread tissue distribution. In‐situ hybridization of juvenile Atlantic salmon (∼40 g, fresh water) vertebrae demonstrated expression of bgp and mgp mRNA in osteoblasts lining the trabecular bone, whereas no staining was observed in the compact bone. By separating the trabecular and compact bone of both juvenile (∼40 g, fresh water) and adult (∼1000 g, sea water) Atlantic salmon, we observed that the two vertebral bone compartments displayed different levels of bgp, whereas no such differences were seen for mgp. Measurements of the mineral content and Ca/P molar ratio in adult salmon revealed no significant differences between trabecular and compact bone. In conclusion, the osteoblasts covering the salmon vertebrae have unique gene expression patterns and levels of bgp and mgp. Further, the study confirms the presence of mRNA from the vitamin K‐dependent proteins BGP and MGP in the vertebrae, fin and gills of Atlantic salmon.
Correspondence between physiological and self‐report measures of emotion dysregulation: A longitudinal investigation of youth with and without psychopathology
Authors: Vasilev Christina A. , Crowell Sheila E. , Beauchaine Theodore P. , Mead Hilary K. , Gatzke‐Kopp Lisa M.
Published: October 2009

Background:  Several theoretical perspectives suggest that emotion dysregulation is a predisposing risk factor for many psychiatric disorders. Yet despite a rapidly evolving literature, difficulties with emotion regulation (ER) are often measured inconsistently across studies, with little regard to whether different approaches capture the same construct. In this study, we evaluate the correspondence between two widely used measures of emotion dysregulation that cut across self‐report and physiological levels of analysis. Our objectives were to (1) evaluate whether youth self‐reports of ER difficulties correspond with physiological measures of emotion dysregulation collected at baseline and during sad emotion induction, and (2) validate the Difficulties in Emotion Regulation Scale (DERS) in a youth sample.

Method:  We measured emotion dysregulation among a sample of youth with depression, conduct problems, comorbid depression/conduct problems, or no psychiatric condition. Youth were assessed initially at ages 8–12 (Year 1) and followed up at Years 2 and 3. Respiratory sinus arrhythmia (RSA), a widely used physiological index of emotion regulation, was measured across all three years during sad emotion induction. At Year 3, the DERS was also administered.

Results:  Multilevel modeling analyses indicated that slopes in RSA collected across the three assessments were associated with later self‐reported ER abilities at the transition into adolescence. These findings were replicated across contexts (baseline and emotional challenge), suggesting that adolescents whose physiological responding to emotional challenge improves also experience fewer difficulties with emotion regulation as they mature.
Upper limb activity measures for 5‐ to 16‐year‐old children with congenital hemiplegia: a systematic review
Authors: GILMORE ROSE , SAKZEWSKI LEANNE , BOYD ROSLYN
Published: October 2009

Aim  This systematic review aimed to compare the validity, reliability, evaluative validity, and clinical utility of upper limb activity measures for children aged 5 to 16 years with congenital hemiplegia.

Method  Electronic databases were searched to identify assessments that measure upper limb activity available for use and for which published validity and reliability data for the population are obtainable. Assessment items were coded according to the International Classification of Functioning, Disability and Health (ICF) categories to determine if at least 35% of the assessment items fell within the activity component of the ICF. Assessments that met these criteria were included in the review.

Results  Thirty‐eight measures were identified, and five met the inclusion criteria. The best measure of unimanual capacity was the Melbourne Assessment of Unilateral Upper Limb Function (MUUL); however, the Shriners Hospital Upper Extremity Evaluation (SHUEE) and the Quality of Upper Extremity Skills Test (QUEST) could also be considered, depending on the type of information required. The performance‐based measure of bimanual upper limb activity in children with hemiplegia with the best psychometric properties was the Assisting Hand Assessment (AHA). The ABILHAND‐Kids is a parent‐report, performance‐based questionnaire with excellent clinical utility and psychometric properties.

Interpretation  Clinicians may choose to use more than one of these measures to detect changes in unimanual or bimanual upper limb activity.
Assessment and correction of skinfold thickness equations in estimating body fat in children with cerebral palsy
Authors: GURKA MATTHEW J , KUPERMINC MICHELLE N , BUSBY MARJORIE G , BENNIS JACEY A , GROSSBERG RICHARD I , HOULIHAN CHRISTINE M , STEVENSON RICHARD D , HENDERSON RICHARD C
Published: October 2009

Aim To assess the accuracy of skinfold equations in estimating percentage body fat in children with cerebral palsy (CP), compared with assessment of body fat from dual energy X‐ray absorptiometry (DXA).

Method Data were collected from 71 participants (30 females, 41 males) with CP (Gross Motor Function Classification System [GMFCS] levels I–V) between the ages of 8 and 18 years. Estimated percentage body fat was computed using established (Slaughter) equations based on the triceps and subscapular skinfolds. A linear model was fitted to assess the use of a simple correction to these equations for children with CP.

Results Slaughter’s equations consistently underestimated percentage body fat (mean difference compared with DXA percentage body fat −9.6/100 [SD 6.2]; 95% confidence interval [CI] −11.0 to −8.1). New equations were developed in which a correction factor was added to the existing equations based on sex, race, GMFCS level, size, and pubertal status. These corrected equations for children with CP agree better with DXA (mean difference 0.2/100 [SD=4.8]; 95% CI −1.0 to 1.3) than existing equations.

Interpretation A simple correction factor to commonly used equations substantially improves the ability to estimate percentage body fat from two skinfold measures in children with CP.
Development and validation of item sets to improve efficiency of administration of the 66‐item Gross Motor Function Measure in children with cerebral palsy
Authors: RUSSELL DIANNE J , AVERY LISA M , WALTER STEPHEN D , HANNA STEVEN E , BARTLETT DOREEN J , ROSENBAUM PETER L , PALISANO ROBERT J , GORTER JAN WILLEM
Published: October 2009

Aim To develop an algorithmic approach to identify item sets of the 66‐item version of the Gross Motor Function Measure (GMFM‐66) to be administered to individual children, and to examine the validity of the algorithm for obtaining a GMFM‐66 score.

Method An algorithmic approach was used to identify item sets of the GMFM‐66 (GMFM‐66‐IS) using data from 95 males and 79 females with cerebral palsy (CP; mean age 14y 7mo, SD 1y 8mo, range 12y 7mo to 17y 8mo). The GMFM‐66‐IS scores were then validated using combined data from three Dutch studies involving 134 males and 92 females with CP (mean age 7y, SD 4y 6mo, range 1y 4mo to 13y 8mo), representing all levels of the Gross Motor Function Classification System.

Results The final algorithm contains three decision items from the GMFM‐66 that determine which one of four item sets to administer. The GMFM‐66‐IS has excellent agreement with the full GMFM‐66 both at a single assessment (intraclass correlation coefficient [ICC]=0.994, 95% confidence intervals [CI] 0.993–0.996) and across repeat assessments (ICC=0.92, 95% CI 0.89–0.95).

Interpretation The GMFM‐66‐IS is a promising alternative to the full GMFM‐66. Users should be consistent in their choice of measure (GMFM‐66 or GMFM‐66‐IS) on repeat testing and clearly identify which method was used.
Bilateral iliococcygeal fixation for vaginal vault prolapse and enterocele repair using a new suturing device—the digital needle driver
Authors: Krissi Haim , Stanton Stuart L.
Published: October 2009

The objective of our study was to evaluate the surgical feasibility, efficacy and safety of the digital needle driver (DND 202), a modified, flexible surgical device, during iliococcygeal fixation (ICF) for vaginal vault prolapse and enterocele repair. A prospective longitudinal study was carried out among 21 consecutive patients who underwent bilateral iliococcygeal fixation at St George's Hospital, London. All patients filled a comprehensive questionnaire for pre‐ and post‐operative prolapse, urinary, bowel and sexual symptoms and underwent pre‐ and post‐operative site‐specific vaginal examination, following the standardized International Continence Society scoring for prolapse, pre‐operative urodynamic studies and analysis of the surgical results. The outcome measures were the feasibility of the procedure, the time needed, intra‐ and post‐operative complications, short‐term post‐operative prolapse‐associated symptoms and pelvic organ prolapse quantification. The mean age of the patients was 65 [5] years and the mean body mass index (kg/m2) was 23 [2.7]. In addition to ICF, 8 patients underwent vaginal hysterectomy, 18 had posterior repairs, 7 had anterior repairs and 6 had TVT. The mean time for ICF was 20 [11] minutes, the mean blood loss per surgical procedure was 264 [225] mL and the mean hospitalization time was 4.6 [1.2] days. Postoperatively, one patient had mesh erosion. At short‐term post‐operative evaluation none of the patient had prolapse symptoms. There was a statistically significant improvement in all stages of the apical and posterior walls prolapse (p < 0.001). The mean total vaginal length was significantly shorter postoperatively (7.8 [1.0] cm vs 6.6 [1.4] cm, p < 0.001). Thus, we can conclude that the use of DND device may facilitate the vaginal approach for vaginal vault prolapse and enterocele repair.
A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs
Authors: Jack Stuart A. , Cooper Kevin G. , Seymour Janelle , Graham Wendy , Fitzmaurice Ann , Perez Juan
Published: October 2009

Objective  To compare outpatient microwave endometrial ablation (MEA) in the postmenstrual phase to standard MEA treatment after drug preparation in a day case theatre environment.

Design  A randomised controlled trial.

Setting  A large United Kingdom teaching hospital.

Population  Two hundred and ten women complaining of excessive menstrual loss.

Methods  Two hundred and ten women with excessive menstrual loss were randomised. Ninety‐seven women were treated as outpatients in the immediate post‐menstrual phase and 100 were treated in an operating theatre after hormonal preparation. All procedures were commenced under local anaesthesia with or without conscious sedation. Analysis was by modified intention to treat.

Main outcome measures  Primary outcome measures were satisfaction with treatment (measured at one year) and acceptability of treatment (measured at two weeks). Secondary outcome measures were menstrual outcome and financial cost.

Results  Significantly more women found treatment post‐menses acceptable; 86 (89.5%) versus 76 (76.0%) [difference in proportions 13.6%, 95% CI (3.0%, 23.9%)]. Similar numbers in each arm were totally or generally satisfied with the treatment, 86 (92.5%) versus 84 (88.4%) [difference in proportions 4.1%, 95% CI (−4.7%, 12.9%)] while amenorrhoea rates at one year were comparable, 52 (55.9%) versus 60 (61.9%). [difference in proportions −5.9%, 95% CI (−19.8%, 7.6%)]. The mean health service costs were £124 (95% CI £86–194) lower for the patients in the post‐menses group.

Conclusion  MEA performed under local anaesthesia (with or without conscious sedation) in the post‐menstrual phase achieves high levels of satisfaction is very acceptable to patients and results in significantly reduced health service costs. Importantly menstrual outcomes are not affected by omission of drug preparation. There is now good evidence to support the use of MEA, without drug endometrial preparation, in the outpatient setting.
Thermal ablation performed in a primary care setting: the South Warwickshire Experience
Authors: Oláh Karl S. , Alliston Joanne , Jones Julia , Stewart Gavin , Mavrommatis Ruth
Published: October 2009

Objective  To assess the feasibility of performing outpatient thermal ablation in a primary care setting.

Design  Prospective study.

Setting  A small peripheral hospital in the UK used by local general practitioners and visiting hospital practitioners for its outpatient facilities.

Population  The area of South Warwickshire serves a population of 270,000.

Methods  Two general practitioners were trained to perform outpatient thermal ablation using the Thermachoice thermal ablation system (Thermachoice II). The unit functioned autonomously with support from a local gynaecologist and radiologist, accepting referrals from hospital consultants and general practitioners.

Main outcome measures  Severity of menstrual loss, premenstrual symptoms, dysmenorrhoea and quality of life assessed by visual analogue scales before treatment and at one month, two months, one year and two years.

Results  Eighty‐seven women were treated. No major complications were encountered from the procedure. Reduction of menstrual loss or cure was reported by over 94% of women. Premenstrual syndrome (PMS) and symptoms of dysmenorrhoea were also improved by treatment. The majority of women were satisfied with the operation at one month (96%), two months (93%), one year (92%) and two years (94%).

Conclusions  Thermal ablation is a simple procedure well suited to an outpatient setting. There are few complications as a result of the use of the thermal ablation catheters, and this study has shown that the procedure can be undertaken in a primary care setting with excellent results.
A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation
Authors: Hamoda Haitham , Ashok Premila W. , Flett Gillian M.M. , Templeton Allan
Published: October 2009

Objective  To assess women's acceptability, the efficacy and side effects of sublingual versus vaginal administration of misoprostol in combination with mifepristone for medical abortion up to 13 weeks of gestation.

Design  Randomised controlled trial.

Setting  Aberdeen Royal Infirmary.

Population  Women undergoing medical abortion under the terms of the 1967 Abortion Act.

Methods  Mifepristone (200 mg) was given orally followed 36–48 hours later by misoprostol administration (sublingual: 600 μg; vaginal: 800 μg). A second dose of misoprostol 400 μg was given 3 hours later (sublingually or vaginally). Women between 9 and 13 weeks of gestation received a further (third) dose of misoprostol 400 μg (sublingually or vaginally), 3 hours later if abortion had not occurred.

Main outcome measures  Women's acceptability, efficacy of the regimen and side effects experienced.

Results  A total of 340 women were recruited (171 sublingual and 169 vaginal). A total of 70% of women in the sublingual group expressed satisfaction with the route of misoprostol administration; 18% answered ‘Don't know’ while 12% were dissatisfied, compared with 68%, 28% and 4%, respectively, in the vaginal group (P= 0.02). There was no significant difference in the need for surgical evacuation for women in the sublingual (3/158, 1.9%) and vaginal groups (4/156, 2.6%) (P= 0.70). Women receiving misoprostol sublingually were more likely to experience diarrhoea (P < 0.01), shivering (P < 0.01) and unpleasant mouth taste (P < 0.01).

Conclusions  Sublingual administration of misoprostol is an effective alternative to vaginal administration for medical abortion up to 13 weeks of gestation. The prevalence of prostaglandin‐related side effects, however, was higher with this route of administration.
Peritoneal fluid concentrations of interleukin‐17 correlate with the severity of endometriosis and infertility of this disorder
Authors: Zhang Xinmei , Xu Hong , Lin Jun , Qian Yuli , Deng Lin
Published: October 2009

This prospective study aimed to determine whether patients with endometriosis are having different level of interlukin‐17 (IL‐17) in peritoneal fluid when compared with patients without endometriosis. The patients with minimal/mild endometriosis had a significantly higher level of IL‐17 in peritoneal fluid compared with those with moderate/severe endometriosis or without endometriosis. The concentration of IL‐17 in peritoneal fluid was significantly higher when endometriosis and infertility coexist. However, the concentration of IL‐17 in peritoneal fluid did not correlate with the phase of the menstrual cycle in the patients with or without endometriosis. Our study suggested that IL‐17 might play an important role in the pathogenesis of early endometriosis and endometriosis‐associated infertility.
Are mediolateral episiotomies actually mediolateral?
Authors: Andrews Vasanth , Thakar Ranee , Sultan Abdul H. , Jones Peter W.
Published: October 2009

This study investigated potential differences in the cutting of mediolateral episiotomy between doctors and midwives. Depth, length, distance from midline and shortest distance from the midpoint of the anal canal to the episiotomy were measured in a sample of primigravid women. The angle subtended from the sagittal or parasagittal plane was calculated. Two hundred and forty‐one women participated of whom 98 (41%) had a mediolateral episiotomy. Doctors performed episiotomies that were significantly deeper, longer and more obtuse than those by midwives. No midwife and only 13 (22%) doctors performed truly mediolateral episiotomies. It appears that the majority of episiotomies are not truly mediolateral but closer to the midline. More focused training in mediolateral episiotomy technique is required.
Long term review of laparoscopic sacrocolpopexy
Authors: Higgs P.J. , Chua H.‐L. , Smith A.R.B.
Published: October 2009

Objective  Assessment of long term outcome following laparoscopic sacrocolpopexy.

Design  Retrospective follow up study using standardised examination with pelvic organ prolapse quantification system (POP‐Q) and questionnaires.

Setting  A tertiary urogynaecology unit in the North West of England.

Population  One hundred and forty consecutive cases who had a laparoscopic sacrocolpopexy at St Mary's Hospital, Manchester, between 1993 and 1999.

Methods  Women completed questionnaires and were examined in gynaecology clinic or sent postal questionnaires if unable to attend the clinic.

Main outcome measures  Adequacy of vault support and recurrent vaginal prolapse assessed by POP‐Q score. Assessment of prolapse, urinary and bowel symptoms and sexual function using questionnaires.

Results  One hundred and three women were contacted after a median of 66 months. Sixty‐six women were examined and a further 37 women filled in questionnaires only. Recurrent vault prolapse occurred in 4 of the 66 women who were examined. Prolapse had recurred or persisted in 21 of 66 women, with equal numbers of anterior and posterior vaginal wall prolapse. Overall, 81/102 (79%) said that their symptoms of prolapse were ‘cured’ or ‘improved’; 39/103 (38%) still had symptoms of prolapse. For every two women who were cured of their urinary or bowel symptoms, one woman developed worse symptoms.

Conclusions  Among the 66 women available for examination laparoscopic sacrocolpopexy provided good long term support of the vault in 92%. Forty‐two percent of these women had recurrent vaginal wall prolapse. Despite this, 79% of women felt that their symptoms of prolapse were cured or improved following surgery.
Factors influencing repeat caesarean section: qualitative exploratory study of obstetricians' and midwives' accounts
Authors: Kamal Pallavi , Dixon‐Woods Mary , Kurinczuk Jennifer J. , Oppenheimer Christina , Squire Patricia , Waugh Jason
Published: October 2009

Objective  To explore the views of health professionals on the factors influencing repeat caesarean section.

Design  Qualitative study involving semi‐structured interviews with professionals who care for women in pregnancy and labour.

Setting  Acute hospital trust with two maternity units and community midwifery service, Leicestershire, UK.

Sample  Twenty‐five midwives and doctors.

Methods  Interviews with professionals were undertaken using a prompt guide. All interviews were audiotaped and transcribed verbatim. Analysis was based on the constant comparative method, assisted by QSR N5 software.

Main outcome measures  Identification of factors influencing professional decision making about repeat caesarean section.

Results  Decision making in relation to repeat caesarean is a complex process involving several parties. Professionals identify the relevance of evidence for decision making for repeat caesarean. However, professionals feel that following strict protocols is of limited value because of the perceived substandard quality of evidence in this area, other external pressures and the contingent, unique and often unanticipated features of each case. Professionals also perceive that the organisation of care plays an important role in rates of repeat caesarean.

Conclusions  Decision making for repeat caesarean is a social practice where standardised protocols may have limited value. Attention needs to be given to the multiple parties involved in the decision‐making process. Reflective practice, opinion leadership and role modelling may offer ways forward but will require evaluation.
Risk scoring system for prediction of obstetric anal sphincter injury
Authors: Williams Abimbola , Tincello Douglas G. , White Sarah , Adams Elisabeth J. , Alfirevic Zarko , Richmond David H.
Published: October 2009

Objective  The objective was to begin the process of developing an antenatal risk scoring system, as a first step towards examining whether elective Caesarean section for women at high risk of injury could be an effective and acceptable intervention.

Design  Retrospective study.

Setting  Tertiary maternity unit in the UK.

Population  One hundred and twenty‐three women who sustained an obstetric anal sphincter injury (OASI) and 123 controls without OASI.

Methods  Case notes of women with a third or fourth degree tear between 1997 and 1999 were examined for risk factors. Controls matched for age and week of delivery were identified from the maternity record database and case records reviewed for the presence of risk factors. Unweighted and weighted risk scores were produced using odds ratios, and compared between cases and controls. Receiver operating characteristics (ROC) curve analysis of the risk scores was performed to discriminate between cases and controls and to calculate the sensitivity and specificity of each scoring system.

Main outcome measures  Odds ratio (OR) and 95% confidence interval (CI) for each risk factor. Sensitivity and specificity from ROC curves for weighted and unweighted risk score.

Results  Among the cases there were more nulliparous women (OR 1.77; CI 1.05–2.99) and a trend towards more women with an episiotomy (OR 1.57; CI 0.99–2.47). Among women with sphincter injury, trends towards more epidurals (OR 1.64; CI 0.97–2.75), and more babies weighing more than 4000 g among (OR 1.45; CI 0.85–2.49) were noted. The median unweighted risk score was 2 for cases and 2 for controls (P= 0.05), while the weighted risk score was 2.1 and 1.37 (P= 0.03), respectively. The ROC curves approximated to a straight line demonstrating very poor discrimination between cases and controls.

Conclusion  The predictive test performed poorly, suggesting that the risk factors identified do not exert a large enough effect in a cohort of this size.
Faecal incontinence and mode of first and subsequent delivery: a six‐year longitudinal study
Authors: MacArthur Christine , Glazener Charis , Lancashire Robert , Herbison Peter , Wilson Don , Grant Adrian
Published: October 2009

Objective  To investigate the prevalence of persistent and long term postpartum faecal incontinence and associations with mode of first and subsequent deliveries.

Design  Longitudinal study.

Setting  Maternity units in Aberdeen, Birmingham and Dunedin.

Population  Four thousand two hundred and fourteen women who returned postal questionnaires three months and six years postpartum.

Methods  Symptom data were obtained from both questionnaires and obstetric data from case‐notes for the index birth and the second questionnaire for subsequent births. Logistic regression investigated the independent effects of mode of first delivery and delivery history.

Main outcome measures  Incontinence to bowel motions three months and six years after index birth. For delivery history, the outcome was incontinence only at six years.

Results  The prevalence of persistent faecal incontinence was 3.6%. Almost 90% of these women reported no symptoms before their first birth. The forceps delivery of a first baby was independently predictive of persistent symptoms (OR 2.06, 95% CI 1.40–3.04). A caesarean section first birth was not significantly associated with persistent symptoms (OR 1.07, 95% CI 0.64–1.81). Delivering exclusively by caesarean section also showed no association with subsequent symptoms (OR 1.04, 95% CI 0.72–1.50) but ever having forceps was significantly predictive (OR 1.48, 95% CI 1.18–1.87). Other factors independently associated with persistent faecal incontinence were older maternal age, increasing number of births and Asian ethnic group. Birthweight and long second stage were not significantly associated.

Conclusions  The risk of persistent faecal incontinence is significantly higher after a first delivery by forceps. We found no evidence of a lower risk of subsequent faecal incontinence for exclusive caesarean section deliveries.
Functional effects of somatostatin receptor 1 activation on synaptic transmission in the mouse hippocampus
Authors: Cammalleri Maurizio , Martini Davide , Timperio Anna Maria , Bagnoli Paola
Published: October 2009

Somatostatin‐14 (SRIF) co‐localizes with GABA in the hippocampus and regulates neuronal excitability. A role of SRIF in the control of hippocampal activity has been proposed, although the exact contribution of each SRIF receptor (sst1–sst5) in mediating SRIF action requires some clarification. We used hippocampal slices of wild‐type and sst1 knockout (KO) mice and selective pharmacological tools to provide conclusive evidence for a role of sst1 in mediating SRIF inhibition of synaptic transmission. With single‐ and double‐label immunohistochemistry, we determined the distribution of sst1 in hippocampal slices and we quantified sst1 colocalization with SRIF. With electrophysiology, we found that sst1 activation with CH‐275 inhibited both the NMDA‐ and the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐mediated responses. Results from sst1 KO slices confirmed the specificity of CH‐275 effects; sst1 activation did not affect the inhibitory transmission which was in contrast increased by sst4 activation with L‐803,087 in both wild‐type and sst1 KO slices. The AMPA‐mediated responses were increased by L‐803,087. Functional interaction between sst1 and sst4 is suggested by the finding that their combined activation prevented the CH‐275‐induced inhibition of AMPA transmission. The involvement of pre‐synaptic mechanisms in mediating inhibitory effects of sst1 on excitatory transmission was demonstrated by the finding that CH‐275 (i) increased the paired‐pulse facilitation ratio, (ii) did not influence the AMPA depolarization in the presence of tetrodotoxin, and (iii) inhibited glutamate release induced by epileptiform treatment. We conclude that SRIF control of excitatory transmission through an action at sst1 may represent an important contribution to the regulation of hippocampal activity.
Comparison of nuclear and capacitance‐based soil water measuring techniques in salt‐affected soils
Authors: Al‐Ain F. , Attar J. , Hussein F. , Heng L. K.
Published: October 2009

A field calibration experiment was carried out on salt‐affected clayey soil in Syria, to compare the sensitivity to soil electrical conductivity (ECe), and bulk density (ρb) of two instruments for estimating soil moisture: the neutron probe (NP) and the Diviner 2000 capacitance probe (CP). The results showed that the values of the correlation coefficient of the calibration were decreased when the ECe and ρb values increased; this decrease was more pronounced for the Diviner 2000, indicating that it was more sensitive to ρb and ECe than the NP. When only scaled frequency was used in the fitted equation, the Diviner 2000 in wet soil underestimated soil water content significantly at all depths, but especially in the top layer, by up to 0.09 cm3/cm3 compared with gravimetric determinations. However, in dry soil, the Diviner 2000 overestimated the volumetric water content by up to 0.05 cm3/cm3 in the top 15 cm, and by 0.03 cm3/cm3 at 30‐45 cm depth. The performance of the neutron probe was better overall; using a factory calibration curve no significant differences were observed between NP estimates and the gravimetric values. Including both ρb and ECe in the calibration equations improved the fits, although the regression coefficient (R2) for the Diviner 2000 remained low.
Co‐ordinated autophagy with resveratrol and γ‐tocotrienol confers synergetic cardioprotection
Authors: Lekli Istvan , Ray Diptarka , Mukherjee Subhendu , Gurusamy Narasimman , Ahsan Md. Kaimul , Juhasz Bela , Bak Istvan , Tosaki Arpad , Gherghiceanu Mihaela , Popescu Lawrence M. , Das Dipak K.
Published: October 2009

This study compared two dietary phytochemicals, grape‐derived resveratrol and palm oil‐derived γ‐tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague‐Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ‐tocotrienol + I/R, resveratrol +γ‐tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ‐tocotrienol experiments the rats were gavaged with γ‐tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ‐tocotrienol experiments, the rats were gavaged with γ‐tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ‐tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ‐toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ‐tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt‐Bcl‐2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3‐II as well as mTOR signalling, which were inhibited by either 3‐methyl adenine (3‐MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.