Type 2 diabetes (T2D) is strongly linked to obesity and an adipose tissue unresponsive to insulin. The insulin resistance is due to defective insulin signaling, but details remain largely unknown. We examined insulin signaling in adipocytes from T2D patients, and contrary to findings in animal studies, we observed attenuation of insulin activation of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). As a consequence, mTORC1 downstream effects were also affected in T2D: feedback signaling by insulin to signal-mediator insulin receptor substrate-1 (IRS1) was attenuated, mitochondria were impaired and autophagy was strongly upregulated. There was concomitant autophagic destruction of mitochondria and lipofuscin particles, and a dependence on autophagy for ATP production. Conversely, mitochondrial dysfunction attenuated insulin activation of mTORC1, enhanced autophagy and attenuated feedback to IRS1. The overactive autophagy was associated with large numbers of cytosolic lipid droplets, a subset with colocalization of perlipin and the autophagy protein LC3/atg8, which can contribute to excessive fatty acid release. Patients with diagnoses of T2D and overweight were consecutively recruited from elective surgery, whereas controls did not have T2D. Results were validated in a cohort of patients without diabetes who exhibited a wide range of insulin sensitivities. Because mitochondrial dysfunction, inflammation, endoplasmic-reticulum stress and hypoxia all inactivate mTORC1, our results may suggest a unifying mechanism for the pathogenesis of insulin resistance in T2D, although the underlying causes might differ. the dephosphorylation by phosphotyrosine protein phosphatases (13).TOR coordinates control of cell growth and metabolism in accordance with nutrient availability in unicellular organisms. During evolution of multicellular organisms this control was seized by insulin and other growth factors. However, the ancient ability of TOR to sense nutrient levels in cells independently of insulin is retained in multicellular organisms, including man, giving TOR a key role in cellular control of metabolism and cell growth, as well as tolerance to starvation through control of autophagy. In mammalian cells mTOR, in complex with the protein raptor (mTORC1), is activated by insulin and the insulin receptor substrate-1 (IRS1) via either or both of the two signaling branches of insulin that lead to activation of protein kinase B/Akt or the Map-kinase ERK1/2, respectively. By responding to amino acid and energy levels in the cell, mTORC1 thus integrates insulin signaling with nutrient availability to control cellular processes such as cell growth, protein synthesis, mitochondrial function and autophagy ( Figure 1A), reviewed in (14). In several studies, in particular on animals after high-fat feeding regimens, insulin resistance has been coupled with hyperactive mTORC1 (reviewed in [6]). However, because mTORC1 mediates the positive feedback signal to phosphorylation of IRS1 at serine 307, we wanted to further...

Objective. To describe a general population of women with regard to factors associated with urinary and fecal incontinence and genital prolapse symptoms. Methods. A questionnaire about medical background, urinary and fecal incontinence and genital prolapse symptoms was mailed to 1000 40-year-old and 1000 60-year-old Swedish women. Associations were described by odds ratios (ORs) with 95% confidence intervals (CIs). Results. Sixty-seven percent answered the questionnaire. Multivariate analysis showed urinary incontinence to be associated with anal sphincter rupture [OR 4.4 (95% CI 1.0-18.8)], pelvic heaviness [3.8 (2.1-7.0)], body mass index (BMI) !30 kg/m 2 [3.7 (2.0-6.7)], multiparity [1.8 (1.0-3.4)], varicose veins surgery [1.9 (1.2-3.2)] and age [1.9 (1.2-3.2)]. Univariate analyses revealed statistically significant associations between urinary incontinence and incontinence for flatus [4.8 (3.0-7.8)], for liquid stool [5.0 (2.9-8.6)] and for solid stool [5.9 (2.4-14.2)]. Chronic bronchitis [5.7 (1.7-18.9)] was strongly associated with urinary incontinence but was only reported by the older age group. Prolapse symptoms were strongly associated with both urinary and fecal incontinence. Prolapse symptoms as opposed to urinary and fecal incontinence seemed to be associated more with injuries at delivery than with chronic pelvic floor strain. Conclusions. Women with urinary incontinence are also likely to suffer from fecal incontinence and prolapse and vice versa. Other associated factors for pelvic floor dysfunction were overweight, and especially obesity, chronic bronchitis, vaginal delivery and multiparity, age, heredity and diseases suggestive of collagen disorders. A multidisciplinary management of women with pelvic floor symptoms is suggested and possible prevention is discussed.Pelvic floor insufficiency is a general public health problem with great impact on quality of life and health economy (1). Possible preventive measures are of particular interest for individual women as well as for the community. Some risk factors for the development of urinary and fecal incontinence as well as genital prolapse have been established. However, most studies in this field deal with either urinary or fecal incontinence or Abbreviations: aAT: alpha-1-antitrypsin; BMI: body mass index; CI: confidence interval; OR: odds ratio; PFME: pelvic floor muscle exercises.

Objectives: To evaluate the associations between maternal age and obstetric and neonatal outcomes in primiparous women with emphasis on teenagers and older women.Design: A population-based cohort study. Setting: The Swedish Medical Birth Register. Participants: Primiparous women with singleton births from 1992 through 2010 (N=798 674) were divided into seven age groups: <17 years, 17-19 years and an additional five 5-year classes. The reference group consisted of the women aged 25-29 years.

Insulin controls cell metabolism via metabolic signal transduction pathways and cell proliferation via mitogenic signal pathways. Metabolic signalling occurs through receptor-activated phosphorylation of insulin receptor substrate (IRS) proteins that subsequently activate phosphatidylinositide 3-kinase (PI3-kinase) to generate second messengers that produce increased phosphorylation and activation of protein kinase B ⁄ Akt (PKB). PKB appears to be central to downstream control of both glucose uptake and glycogen synthesis by insulin [1,2]. Although adipocytes are terminally differentiated cells that do not divide further, insulin has the potential for genomic control via a mitogenic signalling pathway. This may also be mediated by IRS; insulin activation of the G-protein Ras leads to phosphorylation and activation of mitogenactivated protein (MAP) kinases -extracellular signal-related kinase (ERK) 1 and 2 [3], and p38 [4,5] Insulin resistance is a cardinal feature of type 2 diabetes and also a consequence of trauma such as surgery. Directly after surgery and cell isolation, adipocytes were insulin resistant, but this was reversed after overnight incubation in 10% CO 2 at 37°C 2 . Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)1 was insulin sensitive, but protein kinase B (PKB) and downstream metabolic effects exhibited insulin resistance that was reversed by overnight incubation. MAP-kinases ERK1 ⁄ 2 and p38 were strongly phosphorylated after surgery, but was dephosphorylated during reversal of insulin resistance. Phosphorylation of MAP-kinase was not caused by collagenase treatment during cell isolation and was present also in tissue pieces that were not subjected to cell isolation procedures. The insulin resistance directly after surgery and cell isolation was different from insulin resistance of type 2 diabetes; adipocytes from patients with type 2 diabetes remained insulin resistant after overnight incubation. IRS1, PKB, and downstream metabolic effects, but not insulinstimulated tyrosine phosphorylation of insulin receptor, exhibited insulin resistance. These findings suggest a new approach in the study of surgeryinduced insulin resistance and indicate that human adipocytes should recover after surgical procedures for analysis of insulin signalling. Moreover, we pinpoint the signalling dysregulation in type 2 diabetes to be the insulin-stimulated phosphorylation of IRS1 in human adipocytes.Abbreviations ERK, extracellular signal-related kinase; GLUT4, insulin-sensitive glucose transporter-4; IRS, insulin receptor substrate; MAP, mitogenactivated protein; PKB, protein kinase B; PI3-kinase, phosphatidylinositide 3-kinase.

A single dose of tranexamic acid given immediately before surgery reduces blood loss and transfusion rates significantly in advanced ovarian cancer surgery. Tranexamic acid may be recommended as standard prophylactic treatment in advanced ovarian cancer surgery.

Objective To determine whether the duration of hospital stay after abdominal hysterectomy in a fast-track setting differed between women operated under general anaesthesia or in spinal anaesthesia with intrathecal morphine.Design An open randomised controlled multicentre study.Setting Five hospitals in the south-east of Sweden.Population One hundred and eighty women scheduled for benign hysterectomy were randomised: 162 completed the study, 82 were allocated to spinal anaesthesia and 80 were allocated to general anaesthesia.Methods Fast-track model comprising no use of sedatives for premedication, pre-emptive anti-emetic therapy, intravenous fluid restriction, analgesics based on non-opioids, early enteral nutrition and mobilisation, and standard criteria for discharge. Spinal anaesthesia with 20 mg hyperbaric bupivacaine and 0.2 mg morphine. General anaesthesia with propofol, fentanyl and rocuronium, and with continuous propofol and ventilation with oxygen-in-air for maintenance of anaesthesia.Main outcome measures Hospital stay, consumption of analgesics, vomiting, pruritus and bowel function recovery.Results Median hospitalisation did not differ significantly between women who had hysterectomy with spinal or general anaesthesia (46 and 50 hours, respectively). Spinal anaesthesia was associated with a significantly lower use of opioids and a faster recovery of bowel function, although vomiting and pruritus were more prevalent.Conclusions In a fast-track model the duration of hospitalisation after abdominal hysterectomy was <50 hours, independent of the mode of anaesthesia. Spinal anaesthesia reduced the need for postoperative morphine compared with general anaesthesia. In order to improve patient recovery after gynaecological surgery further studies based on fast-track programmes are needed.

Aims and objectives To identify and describe the experience of healthcare encounters among women with endometriosis. Background Endometriosis is a “hidden” chronic gynaecological disease appearing in every 10th woman of fertile age. Different manifestations of pain are the main symptoms, often leading to impaired physical and mental health, and lower quality of life. Previous research on healthcare experiences among women with endometriosis has focused on diagnostic delay and experiences of encountering general practitioners. Design A qualitative, interpretive, phenomenological approach was used. Methods We interviewed nine women aged 23–55, with a laparoscopy‐confirmed diagnosis of endometriosis. The interviews were recorded and transcribed verbatim. The data were analysed following the steps of the interpretive phenomenological approach. Results Two themes were identified in the interview transcripts: being treated with ignorance and being acknowledged. The essence: “the double‐edged experience of healthcare encounters” emerged from the themes. The women's experience was double‐edged as it involved contradictory feelings: the encounters were experienced as both destructive or constructive. On the one hand, the destructive side was characterised by ignorance, exposure and disbelief. On the other hand, the constructive side made the women feel acknowledged and confirmed, boosting their self‐esteem. Conclusions The new and important aspects of the findings are that the experience of healthcare encounters is for the first time expressed as double‐edged: both destructive and constructive. The experience was of specific importance as it affected the women's perceptions of themselves and of their bodies. Relevance to clinical practice The information about the constructive side of the experience is of clinical valuable for all healthcare professionals (nurses, midwives and doctors) encountering these women, as it provides a new level of understanding of the experiences. The findings demonstrate both psychological and practical aspects that can help professionals to improve the encounters.

The purpose of this retrospective study was to evaluate the importance of different preoperative estimates and postoperative complications on the outcome of the Burch colposuspension with respect to urinary continence. During the period 1980-1988 243 women were operated upon with the Burch colposuspension for stress incontinence or mixed incontinence. The patient records have been analysed with respect to preoperative assessments and postoperative complications. 236 patients were alive at the follow-up, median 6 years after operation, and 232 (98%) answered a postal questionnaire about their present urinary symptoms. According to the postal questionnaire the overall cure-rate was 63 per cent, another 27 per cent were improved. Prognostic factors for an unsuccessful outcome of the operation were previous urinary incontinence surgery, postoperative febrile morbidity, and immediate voiding difficulties (stranguria and difficulties emptying the urinary bladder). At the follow-up the voiding difficulties were still significantly more often seen in patients not cured from incontinence than among women cured by the colposuspension. Among the patients with recurrent incontinence we also found a significantly higher rate of lower urinary tract infections ( > 3 UTI per year). The continence rate was found to be almost constant between the second and tenth year postoperatively. No significant differences in preoperatively measured maximal urethral closure pressure and functional urethral length were found between cured and not cured patients. Although not significant, the cure-rate showed a tendency to decrease with age at the operation, both in the short-term result as well as the long-term result.