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The fusion of non-Abelian anyons is a fundamental operation in measurement-only topological quantum computation 1 . In one-dimensional topological superconductors (1DTSs) 2-4 , fusion amounts to a determination of the shared fermion parity of Majorana zero modes (MZMs). Here we introduce a device architecture 5 that is compatible with future tests of fusion rules. We implement a single-shot interferometric measurement of fermion parity 6-11 in indium arsenide-aluminium heterostructures with a gate-defined superconducting nanowire 12-14 . The interferometer is formed by tunnel-coupling the proximitized nanowire to quantum dots. The nanowire causes a state-dependent shift of the quantum capacitance of these quantum dots of up to 1 fF. Our quantum-capacitance measurements show flux h/2e-periodic bimodality with a signal-to-noise ratio (SNR) of 1 in 3.6 μs at optimal flux values. From the time traces of the quantum-capacitance measurements, we extract a dwell time in the two associated states that is longer than 1 ms at in-plane magnetic fields of approximately 2 T. We discuss the interpretation of our measurements in terms of both topologically trivial and non-trivial origins. The large capacitance shift and long poisoning time enable a parity measurement with an assignment error probability of 1%., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Telemonitoring may offer promising opportunities in health care. In obstetric health care, there is a need to expand and improve digitalization. Nevertheless, there is limited knowledge based on healthcare professionals' perspectives regarding the use of telemedicine and remote cardiotocography during pregnancy, as well as its implementation., Aim: To explore the perspectives of health-care professionals who manage telemonitoring of complicated pregnancies., Design and Setting: A qualitative interview study undertaken in a hospital with a tertiary obstetric unit in Northen Denmark., Methods: Based on a purposive sample strategy, 11 semi-structured interviews of health-care professionals involved in the management of telemonitoring in women with complicated pregnancies were conducted and analyzed using a reflexive thematic analytical approach., Findings: The findings are assembled into two main themes. The experience of relevance to own practice: included the embedded potentials in telemonitoring providing women-centred care, but also challenges related to the implementation of a new technology. Experience of challenges and potential in day-to-day operation: included frustrations regarding the technological devices and software, working experiences increasing confidence in telemonitoring, and perspectives on the required interdependence across departments., Conclusion: This study adds important knowledge to support awareness and reflection on how challenges impact the successful implementation of telemonitoring in obstetric and midwifery care. This includes knowledge of important processes and resources to ensure ongoing implementation and evaluation. Implementation strategies and collaborations to support a multiple-level system change, such as an interdisciplinary team, seem crucial to minimize challenges, build shared visions, and engage staff., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: The use of telemonitoring in healthcare is generally increasing. Women with complicated pregnancies are using telemonitoring as an alternative to conventional management, encompassing hospitalization or frequent outpatient clinic visits. However, there is sparse evidence on how pregnant women experience monitoring of their unborn babies at home. Women might feel uncomfortable with this responsibility, and moreover they might miss face-to-face contact with healthcare personnel., Study Design: The study setting was a Danish hospital with a tertiary obstetric unit attending approximately 3400 births annually. A qualitative study design with interview as method included 11 pregnant women with type 1 diabetes or Gestational Diabetes Mellitus. This design was used to investigate how pregnant women with complicated pregnancies experienced telemonitoring of the fetus. Reflexive thematic analysis was used to analyze the pregnant women's experiences of telemonitoring., Results: Women with type 1 diabetes or Gestational Diabetes Mellitus found the advantages of telemonitoring to outweigh the disadvantages. They experienced telemonitoring as time-saving and that telemonitoring decreased the level of stress. Moreover, telemonitoring supports positive collaboration with healthcare professionals. The women also experienced a lack of coordination of consultations between different departments at the hospital and challenges with timing, feedback, and technical issues. Moreover, the women requested an opportunity to discuss family formation and emotions., Conclusions: Pregnant women with type 1 diabetes or Gestational Diabetes Mellitus benefit from the use of telemonitoring. To further improve the implementation and use of telemonitoring clinical implications, consider how timing and coordination of care, technical equipment, and feedback mechanisms could be improved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Proinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells., Methods: A luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity. The gain- or loss-of-function of two key NMD components, UPF3B and UPF2, is used to reveal the effect of cytokines on cell viability and function. RNA-sequencing and siRNA-mediated silencing are deployed using standard techniques., Results: Cyt attenuate NMD activity in insulin-producing cell lines and primary human ß cells. These effects are found to involve ER stress and are associated with the downregulation of UPF3B. Increases or decreases in NMD activity achieved by UPF3B overexpression (OE) or UPF2 silencing raise or lower Cyt-induced cell death, respectively, in EndoC-ßH3 cells and are associated with decreased or increased insulin content, respectively. No effects of these manipulations are observed on glucose-stimulated insulin secretion. Transcriptomic analysis reveals that Cyt increases alternative splicing (AS)-induced exon skipping in the transcript isoforms, and this is potentiated by UPF2 silencing. Gene enrichment analysis identifies transcripts regulated by UPF2 silencing whose proteins are localized and/or functional in the extracellular matrix (ECM), including the serine protease inhibitor SERPINA1/α-1-antitrypsin, whose silencing sensitizes ß-cells to Cyt cytotoxicity. Cytokines suppress NMD activity via UPR signaling, potentially serving as a protective response against Cyt-induced NMD component expression., Conclusion: Our findings highlight the central importance of RNA turnover in ß cell responses to inflammatory stress., Competing Interests: Author GR is a consultant for, and has received grant funding from, Sun Pharmaceuticals Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ghiasi, Marchetti, Piemonti, Nielsen, Porse, Mandrup-Poulsen and Rutter.)

Rationale, Aims and Objectives: Women with previous gestational diabetes mellitus (GDM) are more than eight times more likely to develop type 2 diabetes (T2DM) compared to women without GDM. Annual follow-up T2DM-screening is recommended, but participation rates decrease rapidly after the first year. In the North Denmark Region, an electronic reminder has been tested with the aim of improving follow-up care for women with prior GDM. The aim of this study was to explore women's perspectives on receiving an electronic reminder, and the role of reminders in both women's decision-making and informed choice regarding participation in follow-up screening., Methods: A qualitative process evaluation informed by a critical realistic perspective. Data consisted of 20 semi-structured interviews with women previously diagnosed with GDM who had received the reminder. Interviews were analyzed using reflexive thematic analysis., Results: The reminder affected women's decision-making and informed choices through a range of mechanisms. Its personalized design prompted feelings of co-responsibility and care from the healthcare system, supported continuity in women's care pathways, and helped women bridge the gap between healthcare sectors. Women's perception of diabetes risk and the importance of follow-up influenced their decision-making. Participation in follow-up screening was influenced by several contextual factors, as women's everyday life impeded their prioritizing follow-up screening. Women who experienced being met by their general practitioner (GP) with acknowledgement rather than stigmatization and received supportive information tailored to their life situation were more motivated to participate in future follow-up screenings., Conclusion: The reminder indicated both concern and co-responsibility for women's follow-up care after GDM and was well received by the women. It supported participation in follow-up screening through an emphasis on shared decision-making and informed choice. Women's interaction with their GP played a significant role., (© 2022 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Background: Major depressive disorder (MDD) is closely associated with sexual dysfunction, which may worsen during treatment with selective serotonin reuptake inhibitors (SSRIs) due to the side effects of pharmacologic treatment., Aim: To examine the association between sexual function and severity of MDD in drug-naïve patients as compared with healthy controls and how treatment with SSRIs affects sexual function over time in individuals with MDD. Interaction with gender and treatment response was examined., Methods: In 92 patients with MDD, we measured MDD severity with 6- and 17-item versions of the Hamilton Depression Rating Scale (HDRS6 and HDRS17) and the level of sexual function with the Changes in Sexual Functioning Questionnaire at baseline and 4, 8, and 12 weeks after initiating treatment with escitalopram. Baseline sexual function was compared with the sexual function of 73 healthy controls. Linear regression models were used to assess differences in sexual function between healthy controls and patients and change in sexual function from baseline to week 12. Linear mixed models were used to assess differences in change in sexual function between treatment response groups., Outcomes: Outcomes included total scores on the HDRS6, HDRS17, and Changes in Sexual Functioning Questionnaire and changes in total scores from baseline to week 12., Results: Unmedicated patients with MDD reported impaired sexual function as compared with healthy controls. Level of sexual function was not associated with severity of MDD at baseline. Patients' sexual function improved significantly during treatment, which was coupled with amelioration of depressive symptoms. Treatment response groups (remitters, intermediate responders, nonresponders) did not predict change in sexual function. Gender had no effect on sexual dysfunction symptoms during treatment., Clinical Implications: Major depression is a risk factor for sexual problems, and improvement in sexual function was coupled with amelioration of depressive symptoms., Strengths and Limitations: Among its strengths, this was a naturalistic study reflecting real-world settings in clinical practice. It additionally included a baseline measurement of sexual function and MDD severity on drug-naïve patients prior to the initiation of treatment. Finally, the follow-up of 12 weeks extends beyond the acute phase of treatment in which previous research has observed a peak in sexual side effects. In terms of limitations, there was no placebo arm; thus, the study cannot attribute the effects on sexual function to treatment with antidepressants per se. Also, the patients were young, which may have served as a protective factor against sexual side effects., Conclusion: Sexual dysfunction was strongly associated with MDD and improved in parallel with overall symptoms of depression across a standard 12-week treatment with SSRI antidepressants., Clinical Trial Registration: NCT02869035 (https://clinicaltrials.gov/ct2/show/NCT02869035)., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To determine the effectiveness of despatching an electronic reminder of participation in screening for gestational diabetes. The reminder was sent to the women 1-8 years after delivery., Methods: A registry-based, randomized controlled trial in the North Denmark Region among women with gestational diabetes. Randomization was made, which included seven groups stratified by the child's birth year (2012-2018). The intervention group received standard care supplemented by an electronic reminder through a secure nationwide email system (n = 731), while the control group received only standard care (n = 732). The primary outcome was based on blood testing for diabetes (OGTT, HbA1c or fasting P-glucose)., Results: A total of 471 (32.1%) women participated in screening. The primary outcome was experienced by 257 women (35.1%) in the intervention group and 214 women (29.2%) in the control group. The effect of the reminder seemed to increase with recipient's age, non-western origin, urban dwelling, and multiparity. Of those who participated in follow-up screening, 56 (3.8%) were diagnosed with type 2 diabetes., Conclusion: Electronic reminders, based on the principles of informed choice and patient-centred care, to women have been shown to support life-long participation in follow-up screening. Attempts to further stimulation of coverage could however be considered., Trail Registration: ISRCTN registry (22/04/2022, ISRCTN23558707)., (© 2023. The Author(s).)

Background: Women whose pregnancies are complicated by gestational diabetes mellitus (GDM) are approximately eight times more likely to develop type 2 diabetes mellitus (T2DM). Although regular participation in follow-up screening increases the chance of early detection of diabetes, participation rates are often suboptimal. A better understanding of general practice as a key contextual setting for screening could help inform the development and adoption of, for example, electronic reminder interventions to support women's participation., Aim: To explore the perspectives of GPs and relevant staff members engaged in early detection of diabetes after gestational diabetes in order to identify barriers to and facilitators of follow-up screening., Design & Setting: A qualitative interview study undertaken in general practices in the North Denmark Region., Method: Based on a purposive sample strategy, 18 semi-structured interviews of 12 GPs and six staff members, who were either nurses or midwives, were analysed using a reflexive thematic analytical approach., Results: The following three main themes were formulated: (1) challenges of addressing women's risk; (2) prioritisation of early detection of diabetes; and (3) system influence on clinical procedures., Conclusion: Follow-up screening was facilitated by knowledge of guidelines. Professional collaboration and adaptation support were found to lead to successful implementation of guidelines in general practice. Supporting GPs and their staff's reflection and discussion of ways to engage in communication and decisionmaking processes with women is, however, important; it was found to create an important barrier to follow-up screening. Overall, the findings can help inform the future development of interventions to increase uptake., (Copyright © 2022, The Authors.)

In rats, the time of birth is characterized by a transient rise in beta cell replication, as well as beta cell neogenesis and the functional maturation of the endocrine pancreas. However, the knowledge of the gene expression during this period of beta cell expansion is incomplete. The aim was to characterize the perinatal rat pancreas transcriptome and to identify regulatory pathways differentially regulated at the whole organ level in the offspring of mothers fed a regular control diet (CO) and of mothers fed a low-protein diet (LP). We performed mRNA expression profiling via the microarray analysis of total rat pancreas samples at embryonic day (E) 20 and postnatal days (P) 0 and 2. In the CO group, pancreas metabolic pathways related to sterol and lipid metabolism were highly enriched, whereas the LP diet induced changes in transcripts involved in RNA transcription and gene regulation, as well as cell migration and apoptosis. Moreover, a number of individual transcripts were markedly upregulated at P0 in the CO pancreas: growth arrest specific 6 ( Gas6 ), legumain ( Lgmn ), Ets variant gene 5 ( Etv5 ), alpha-fetoprotein ( Afp ), dual-specificity phosphatase 6 ( Dusp6 ), and angiopoietin-like 4 ( Angptl4 ). The LP diet induced the downregulation of a large number of transcripts, including neurogenin 3 ( Neurog3 ), Etv5 , Gas6 , Dusp6 , signaling transducer and activator of transcription 3 ( Stat3 ), growth hormone receptor ( Ghr ), prolactin receptor ( Prlr ), and Gas6 receptor (AXL receptor tyrosine kinase; Axl ), whereas upregulated transcripts were related to inflammatory responses and cell motility. We identified differentially regulated genes and transcriptional networks in the perinatal pancreas. These data revealed marked adaptations of exocrine and endocrine in the pancreas to the low-protein diet, and the data can contribute to identifying novel regulators of beta cell mass expansion and functional maturation and may provide a valuable tool in the generation of fully functional beta cells from stem cells to be used in replacement therapy.

Background: Previous studies of association between exposure to poly- and perfluoroalkyl substances (PFAS) and gestational hypertension (GH) and preeclampsia (PE) have shown conflicting results, but most dichotomized outcome and did not study continuous blood pressure (BP) changes., Objectives: To study the association between PFAS exposure in early pregnancy and maternal BP trajectories in pregnancy, gestational hypertension and preeclampsia., Methods: 1436 women were enrolled in the Odense Child Cohort in early pregnancy and had a serum sample drawn, from which perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were measured using LC-MS/MS. Repeated BP measurements through pregnancy and information on PE were obtained from hospital files. Adjusted linear mixed models were used to investigate association between PFAS exposure and BP trajectory. Associations between PFAS and PE and GH were assessed by Cox proportional hazards model., Results: All women had measurable concentrations of PFAS. In all of many comparisons higher PFAS exposure (apart from PFHxS) was associated with higher systolic (SBP) and diastolic (DBP) blood pressures, although not all were significant, which is unlikely to be due to chance. After adjustment, each doubling in PFOS or PFOA exposure was associated with 0.47 mmHg (95% CI: -0.13; 1.08) and 0.36 mmHg (-0.19; 0.92) higher SBP; and 0.58 mmHg (0.13; 1.04) and 0.37 mmHg (-0.05; 0.79) higher DBP. No clear associations between PFAS exposure and PE or GH were found., Discussion: The magnitude of the association between PFAS exposure and BP might appear small, statistically non-significant and the possible clinical importance low. However, at a population level this may slightly shift the distribution of BP towards an increased incidence of GH. If BP increases in pregnancy, it may have long-term impact on health not only of the pregnant woman but also of her offspring., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Women with previous gestational diabetes have an increased risk of developing type 2 diabetes later in life. Recommendations therefore urge these women to participate in follow-up screening, 4-12 weeks postpartum and every 1-3 years thereafter. We sought to theorize how reminder interventions to support early detection of diabetes work, for whom, and in what circumstances., Methods: We used a method informed by realist review and synthesis. A systematic, iterative search in six electronic databases (PubMed, MEDLINE Ovid, The Cochrane Library, CINAHL, EMBASE) had a primary focus on experimental intervention studies and included additional information in relation to identified intervention studies. Analysis inductively identified context-mechanism-outcome configurations present in the evidence., Results: We located 16 articles eligible for inclusion. A cross-case comparison identified seven grouped context-mechanism-outcome configurations leading to intervention mechanisms relating to changes in women's reasoning and behavior. Configurations were thematically ordered in relation to Systems Resources, Women's Circumstances, and Continuity of Care. These were mapped onto a socio-ecological model and discussed according to identified middle-range theories., Conclusion: Our findings adds to the body of evidence, that reminders have the potential to be effective in increasing participation in the recommended follow-up screening. Our study may assist researchers and policy and decision makers to analyze and judge if reminders are feasible and/or likely to succeed in their specific context. Further research into the perspective of socially disadvantaged and overweight women is needed to avoid unintended consequences such as social inequality in service use and stigmatization in future programs.

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease characterized by pruritus and abnormal liver function tests and it has been associated with intrauterine fetal distress and stillbirth. We compared two guidelines of the management of ICP: one mandating induction at 38 weeks of gestation (Rigshospitalet and Hvidovre Hospital before 2012) and another separating ICP into mild and severe forms, and only women with severe ICP were recommended for induction at 38 weeks (Hvidovre Hospital after 2012)., Material and Methods: We performed a historical cohort study at two Copenhagen Hospitals from 2004 to 2015. We included 62 937 women with singleton deliveries at Rigshospitalet and 71 015 at Hvidovre Hospital, of whom 971 women (1.5%) and 998 women (1.4%) were diagnosed with ICP at Rigshospitalet and Hvidovre Hospital, respectively. Data were retrieved from a local medical database. For the analysis of induction and comparison of obstetrical outcomes we only included pregnancies with an ICP diagnosis and excluded women with other medical conditions that could mandate induction. Main outcome measures were induction and cesarean section rates, asphyxia and stillbirth., Results: We found no changes in the rate of spontaneous labor, cesarean section and induction over the years at Rigshospitalet (P = .17) and Hvidovre Hospital (P = .38). For women with intended vaginal delivery we found no change in the final mode of delivery over the years at Rigshospitalet (P = .28) and Hvidovre Hospital (P = .57)., Conclusions: The two approaches to the management of mild ICP regarding the timing of induction are comparable. Women with mild ICP and their clinicians should be encouraged to engage in shared decision-making when discussing timing of induction., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Objective: Binge-eating disorder (BED) is characterized by recurrent episodes of binge eating, accompanied by a lack of control and feelings of shame. Online intervention is a promising, accessible treatment approach for BED. In the current study, we compared completers with noncompleters in a 10-session guided internet-based treatment program (iBED) based on cognitive behavioral therapy., Methods: Adults (N = 75) with mild to moderate BED participated in iBED with weekly written support from psychologists. Participants were compared on the Eating Disorder Examination Questionnaire (EDE-Q), diagnostic criteria for BED (BED-Q), major depression inventory (MDI), quality of life (EQ-5D-5L), body mass index (BMI) and sociodemographic variables., Results: Minor differences were observed between completers and noncompleters on depression. No differences were found in BED-symptoms, BMI, and sociodemographic variables. Participants who completed treatment showed large reductions in eating disorder pathology., Discussion: More research is needed to determine risk factors for attrition or treatment outcome in internet-based interventions for BED. It is suggested that iBED is an efficient intervention for BED. However, more studies of internet-interventions are needed., (© 2020 Wiley Periodicals LLC.)

Neonatal mortality remains a significant health problem in low-income settings. Low-cost essential newborn care (ENC) interventions with proven efficacy and cost-effectiveness exist but have not reached high coverage (≥90%). Little is known about the strategies used to implement these interventions or how they relate to improved coverage. We conducted a systematic review of implementation strategies and implementation outcomes for ENC in low- and low middle-income countries capturing evidence from five medical and global health databases from 1990 to 2018. We included studies of implementation of delayed cord clamping, immediate drying, skin-to-skin contact (SSC) and/or early initiation of breastfeeding implemented in the first hour (facility-based studies) or the 1st day (community-based studies) of life. Implementation strategies and outcomes were categorized according to published frameworks: Expert Recommendations for Implementing Change and Outcomes for Implementation Research. The relationship between implementation strategies and outcomes was evaluated using standardized mean differences and correlation coefficients. Forty-three papers met inclusion criteria. Interventions included community-based care/health promotion and facility-based support and health care provider training. Included studies used 3-31 implementation strategies, though the consistency with which strategies were applied was variable. Conduct educational meetings was the most frequently used strategy. Included studies reported 1-4 implementation outcomes with coverage reported most frequently. Heterogeneity was high and no statistically significant association was found between the number of implementation strategies used and coverage of ENC. This review highlights several challenges in learning from implementation of ENC in low- and low middle-income countries, particularly poor description of interventions and implementation outcomes. We recommend use of UK Medical Research Council guidelines (2015) for process evaluations and checklists for reporting implementation studies. Improved reporting of implementation research in this setting is necessary to learn how to improve service delivery and outcomes and thereby reduce neonatal mortality., (© The Author(s) 2020. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Introduction: The aim of this study was to compare blood pressure and prevalence of pregnancy-induced hypertension in women with polycystic ovary syndrome and the reference group throughout pregnancy., Material and Methods: This retrospective study was part of the prospective study Odense Child Cohort. Pregnant women were recruited from January 2010 to December 2012. Blood pressure was measured in 200 women with polycystic ovary syndrome and in 2197 in the reference group. Main outcome measures were blood pressure and pregnancy-induced hypertension. Pregnancy-induced hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg occurring after gestational week 20 at two separate visits. Mann-Whitney U test and Chi-square test were used to test differences between women with polycystic ovary syndrome and the reference group. Associations between polycystic ovary syndrome status (PCOS; the reference group) and blood pressure were tested using random mixed-effect linear regression analyses with subjects as random effect to comply with repeated blood pressure measurements., Results: Median blood pressure was comparable in women with polycystic ovary syndrome and the reference group throughout pregnancy: systolic blood pressure 116 (111-123) vs 119 (112-124) (P = .06), diastolic blood pressure 72 (69-77) vs 73 (69-78) (P = .23) and mean arterial pressure 87 (83-93) vs 88 (84-92) (P = .13). In first trimester where systolic blood pressure was lower in polycystic ovary syndrome, median systolic blood pressure was 116 (111-123) vs 119 (112-124) mmHg (P = .04). The prevalence of pregnancy-induced hypertension was similar in polycystic ovary syndrome and the reference group: 17/200 (8.5%) vs 178/1997 (8.9%) (P = .84). Regression analyses showed no significant associations between polycystic ovary syndrome and blood pressure., Conclusions: Blood pressure and prevalence of pregnancy-induced hypertension were comparable in pregnant women with polycystic ovary syndrome and the reference group., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF [placental growth factor] and sFlt-1 [soluble fms-like tyrosine kinase-1]) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associations: Girls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM: 1.81±0.59 and 2.11±0.59 mm Hg, respectively, all P <0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM: 1.11±0.45 and 1.03±0.45, respectively, all P <0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted β coefficients (95% CI) for predicting systolic blood pressure (SBP): -3.18 (-4.66 to -1.70) mm Hg, for predicting diastolic blood pressure (DBP): -2.48 (-3.57 to -1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.

Pregnancy is known to be associated with an increased demand for insulin that is normally compensated by an increased beta cell mass and insulin secretion. Recent studies have suggested enhanced beta cell function during pregnancy in women with type 1 diabetes (T1D). To explore the possible mechanisms behind enhanced beta cell function during pregnancy in women with T1D we investigated the impact of circulating factors in serum from nine women from each group of pregnant women with and without T1D, after pregnancy and non-diabetic non-pregnant women on rat islet cell proliferation and apoptosis, and on T-lymphocyte activation. In addition, circulating levels of pancreatic hormones and selected cytokines and adipokines were measured. Rat islet cell proliferation was higher in serum from pregnant women with T1D (p < 0.05) compared to T1D women after pregnancy. Apoptosis in INS-1E cell was lower (p < 0.05) in serum from pregnant women with T1D compared to T1D women after pregnancy. T-lymphocyte cell (Jurkat) proliferation was reduced by serum from pregnant women without T1D only (p < 0.05). Higher C-peptide levels and lower levels of ghrelin, IL-6, MCP-1, IL-8 and adipsin were observed in pregnant women with T1D compared to T1D women after pregnancy. In conclusion, the improved beta cell function in women with T1D during pregnancy may be due to lower levels of proinflammatory cytokines and/or higher levels of pregnancy-associated growth factors., (© 2020 The Authors.)

Albuminuria in the pathological range is a significant predictor of preeclampsia. In healthy persons, high normal urinary albumin predicts a later incidence of hypertension and is associated with salt sensitivity of blood pressure. We hypothesized that in pregnancy urinary albumin in the normal range associates with blood pressure through activation of distal Na + reabsorption and renal salt retention by plasma factors cofiltered with albumin. We analyzed 24-h urine collections and plasma samples from gestational week 29 of 560 pregnant women from the Odense Child Cohort, a Danish population-based cohort. Plasma and urinary aldosterone were measured by ELISA. Plasma and urinary Na + , K + , Cl - , and creatinine were also determined. Predictive values of urinary albumin were assessed by linear mixed, multiple, and Cox regression analyses. Primary outcomes were blood pressure and renal electrolyte handling. Twenty-four-hour urinary albumin excretion at gestational week 29 associated with gestational blood pressure trajectory, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urinary albumin as follows: 5.71 (1.60 to 9.81) mmHg for systolic blood pressure and 4.39 (1.41 to 7.38) mmHg for diastolic blood pressure. Urinary albumin was inversely associated with fractional excretion rates of Na + , K + , and Cl - , with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urine albumin as follows: -0.25 (-0.35 to -0.14), -5.06 (-6.81 to -3.30), and -0.28 (-0.41 to -0.15), respectively. In conclusion, at gestational week 29 , urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders.

Aim: During pregnancy, the maternal β-cell mass is increased in order to adapt to the physiological changes in insulin demand. Lactogenic hormones stimulate rodent β-cell attachment and proliferation in vitro. The aim of this study was to identify adhesion molecules involved in expansion of the β-cell mass during pregnancy in the rat., Methods: Quantitative RT-PCR was used to evaluate the expression of several integrins and laminins in isolated neonatal rat islets in response to growth hormone (GH) and prolactin (PRL) treatment. Double-immunofluorescence staining of rat pancreas was used to localize the expression of integrin α6β1. β-cell proliferation was evaluated by incorporation of bromodeoxyuridine (BrdU). The role of STAT5 phosphorylation was tested by addition of STAT5 mutants., Results: We found that the mRNA level of integrin-α6A, was upregulated 2.5-fold by PRL or GH. During pregnancy, a biphasic 3.4-4.5-fold increase of integrin-α6A and B mRNA levels was detected. A disintegrin peptide (DP) reduced the hormone-stimulated mitotic activity in neonatal rat β-cells from 2.9 ± 0.4-fold to 1.3 ± 0.3-fold. The hormone-induced expression of α6β1 integrin was shown to be mediated via STAT5 as a dominant negative (DN) mutant prevented and a constitutive active (CA) mutant augmented the hGH-stimulated expression. The DP was found to inhibit hGH-induced transactivation of the PRL receptor promoter 1A and reduce the hGH-induced phosphorylation of STAT5., Conclusion: These results show that integrin-α6 in β-cells is upregulated by lactogenic hormones and is required but not sufficient for the expansion of the β-cell mass in pregnancy in the rat, which may have implications for the understanding and treatment of gestational diabetes mellitus., (© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Background: The physical place and environment has a profound influence on experiences, health and wellbeing of birthing women. An alternatively designed delivery room, inspired by the principles of healing architecture and Snoezelen, was established in a Danish regional hospital. These principles provided knowledge of how building and interior design affects the senses, including users' pain experience and stress levels. The aim of the study was to explore women's experience of the environment and its ability to support the concept of patient-centeredness in the care of birthing women., Methods: Applying a hermeneutical-phenomenological methodology, fourteen semi-structured interviews with low-risk women giving birth in an alternative delivery room at an obstetric unit in Denmark were undertaken 3-7 weeks after birth., Results: Overall, women's experiences of given birth in the alternative delivery room were positive. Our analysis suggests that the environment was well adapted to the women's needs, as it offered a stress- and anxiety-reducing transition to the hospital setting, at the same time as it helped them obtain physical comfort. The environment also signaled respect for the family's needs as it supported physical and emotional interaction between the woman and her partner and helped relieve her concern for the partner's well-being. The psychosocial support provided by the midwives appeared inseparable from the alternative delivery room, as both affected, amplified, and occasionally restricted the women's experience of the physical environment., Conclusion: Our findings support the use of principles of healing architecture and Snoezelen in birth environments and add to the evidence on how the physical design of hospital environments influence on both social and physical aspects of the well-being of patients. The environment appeared to encompass several dimensions of the concept of patient-centered care.

Background: Social Anxiety Disorder (SAD) is characterized by an intense fear of negative judgement by others. Cognitive Behavioral Therapy (CBT) is recommended for treatment, but a substantial part of individuals with SAD either do not seek treatment or drop-out. CBT with Virtual Reality (VR)-based exposure has several advantages compared to traditional exposure methods, mainly due to increased control of situational elements. The aim of the current study is to develop a CBT program containing VR-based exposure. The intervention is targeted to adult patients suffering from SAD and treatment effect will be assessed by changes in SAD symptoms., Methods: This article describes the study protocol of a Randomized Controlled Trial with three arms: 1) CBT with VR exposure based on 360° videos 2) CBT with in vivo exposure and 3) VR relaxation therapy. There will be 30 participants in each arm with a crossover at the end of the treatment period during which the participants in the third group will be randomly re-allocated to one of the two former groups. The treatment program consists of 10 weekly individual sessions with a psychologist, and a six month follow-up consisting of a questionnaire. The primary outcome measure is reduction in SAD symptoms which will be assessed with the Social Interaction Anxiety Scale (SIAS)., Discussion: There are currently no published studies on CBT with VR exposure based on 360° videos for SAD treatment. Furthermore, the current study will be the first Danish SAD treatment program that includes VR technology., Trial Registration: clinicaltrials.gov (NCT03973541) June 3rd 2019.

We present autofluorescence of six zooplankton species, including salmon lice (Lepeophtheirus salmonis), for the purpose of classification in marine environments. Using a 410 nm excitation wavelength, we find that all measured zooplankton species exhibit broad cyan fluorescence centered around 510-520 nm. Furthermore, salmon lice show an absence of red fluorescence from undigested chlorophyll, which is measured from the gut of the herbivorous zooplankton species. We show the capability to distinguish noneating species, including salmon lice, from algae-eating species using a dual-band analysis of the fluorescence spectra. This shows the potential of autofluorescence as an important signature in real-time monitoring and classification of salmon lice.

This RCT investigated the effect on children of integrating physical activity (PA) into math lessons. The primary outcome was math achievement and the secondary outcomes were executive functions, fitness and body mass index. Twelve Danish schools were randomized to either an intervention group or a control group. A total of 505 children with mean age 7.2 ± 0.3 years were enrolled in the study. Change in math achievement was measured by a 45-minute standardized math test, change in executive function by a modified Eriksen flanker task, aerobic fitness by the Andersen intermittent shuttle-run test, and body mass index by standard procedures. PA during the math lessons and total PA (including time spent outside school) were assessed using accelerometry (ActiGraph, GT3X and GT3X+). Children in the intervention group improved their math score by 1.2 (95% CI 0.3; 2.1) more than the control group (p = 0.011) and had a tendency towards a higher change in physical activity level during math lessons of 120,4 counts/min (95% CI -9.0;249.8.2, p = 0.067). However, the intervention did not affect executive functions, fitness or body mass index. Participation in a 9-month PA intervention (from 2012-2013) improved math achievement among elementary school children. If replicated, these findings would suggest that implementation of physical activity in school settings could lead to higher academic achievement., Competing Interests: The authors have declared that no competing interests exist.

The DNA damage-activated protein kinase Chk1 is known to undergo auto-phosphorylation, however the sites and functional significance of this modification remain poorly understood. We have identified two novel Chk1 auto-phosphorylation sites, threonines 378 and 382 (T378/382), located in a highly conserved motif within the C-terminal Kinase Associated 1 (KA1) domain. T378/382 occur within optimal consensus Chk1 phosphorylation motifs and substitution with phospho-mimetic aspartic acid residues results in a constitutively active mutant Chk1 kinase (Chk1-DD) that arrests cell cycle progression in G2 phase of the cell cycle in the absence of DNA damage. Remarkably, the mutant Chk1-DD protein is also subject to very rapid proteasomal degradation, with a half-life approximately one tenth that of wild-type Chk1. Consistent with this, T378/T382 auto-phosphorylation also accelerates the proteasomal degradation of constitutively active Chk1 KA1 domain structural mutants. T378/382 auto-phosphorylation and accelerated degradation of wild-type Chk1 occurs at low levels during unperturbed growth, but surprisingly, is not augmented in response to genotoxic stress. Taken together, these observations demonstrate that Chk1 T378/T382 auto-phosphorylation within the KA1 domain is linked to kinase activation and rapid proteasomal degradation, and suggest a non-canonical mechanism of regulation.

The effect of free cysteine (in different concentrations) on the thermal aggregation of calcium-saturated (Ca-sat) and -depleted (Ca-dep) α-lactalbumin (α-LA) was investigated at 25, 50, and 70 °C. The temperatures chosen were below the denaturation temperature ( T d ) of Ca-dep and Ca-sat α-LA (25 °C), above the T d of Ca-dep α-LA and below that of Ca-sat α-LA (50 °C), and above the T d of Ca-sat α-LA (70 °C). Size-exclusion chromatography coupled to multiangle light scattering showed that no aggregation or only minor aggregation was obtained at the investigated temperatures for both Ca-dep and Ca-sat α-LA even at extended holding times. Aggregates of Ca-sat α-LA were larger than those developed for Ca-dep α-LA. The addition of cysteine, a low-molecular-mass free thiol, resulted in increased aggregation of both Ca-sat and Ca-dep α-LA. Comparisons of SDS-PAGE run under reducing and nonreducing conditions showed that the formed cross-links were primarily disulfide bonds, but Western blots also showed small contributions from dityrosine cross-link formation. The aggregation kinetics related to monomer loss during heat treatment were determined by RP-UPLC and showed that the addition of cysteine increased the rate of aggregation. The activation energies for Ca-dep α-LA with 0.35 and 0.7 mM cysteine were found to be 59 ± 1 and 46 ± 4 kJ/mol, respectively, which showed that less energy was needed for the enhanced thermal aggregation of α-LA when the cysteine concentration was increased. This study showed that it was possible to control the aggregation size of α-LA by manipulating the incubation temperature and the cysteine concentration.

We propose that when consumers encounter really new products (RNPs), defined as products that allow consumers to do something they have never been able to do before and whose benefits are often ambiguous at first, they spontaneously generate mental simulations in an attempt to assess the value of these products. When these self-generated simulations are in the form of sufficiently engrossing and vivid narratives, they can evoke transportation, a phenomenological experience of being "lost" in a story. We also assert that consumers with extensive experience in a related product category are most likely to produce vivid and absorbing simulations that lead to narrative transportation. When consumers are transported within their simulations, it ultimately enhances their overall evaluations of the RNP. Thus, we find that those with more product category knowledge evaluate RNPs more favorably than those with less knowledge, due to the extent to which they are transported by their thoughts. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E. Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3. These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.

abYsis is a web-based antibody research system that includes an integrated database of antibody sequence and structure data. The system can be interrogated in numerous ways-from simple text and sequence searches to sophisticated queries that apply 3D structural constraints. The publicly available version includes pre-analyzed sequence data from the European Molecular Biology Laboratory European Nucleotide Archive (EMBL-ENA) and Kabat as well as structure data from the Protein Data Bank. A researcher's own sequences can also be analyzed through the web interface. A defining characteristic of abYsis is that the sequences are automatically numbered with a series of popular schemes such as Kabat and Chothia and then annotated with key information such as complementarity-determining regions and potential post-translational modifications. A unique aspect of abYsis is a set of residue frequency tables for each position in an antibody, allowing "unusual residues" (those rarely seen at a particular position) to be highlighted and decisions to be made on which mutations may be acceptable. This is especially useful when comparing antibodies from different species. abYsis is useful for any researcher specializing in antibody engineering, especially those developing antibodies as drugs. abYsis is available at www.abysis.org., (Copyright © 2016. Published by Elsevier Ltd.)

The aim of the study was to investigate the role of diabetic intrauterine environment on circulating insulin, glucagon, and somatostatin levels in pregnant rats, fetuses, and offspring. Diabetes was induced in female Wistar rats by streptozotocin at birth or as adult and the animals were assigned into: control (C); mildly diabetic (MD); and severely diabetic (SD). The rats were mated and distributed into 2 subgroups: euthanasia at day 21 of pregnancy and at day 10 postpartum. Both MD and SD dams showed impaired oral glucose tolerance. SD dams had lower body weight and insulin levels compared to C and MD dams. SD fetuses presented hyperglycemia and reduction of insulin and glucagon levels compared to C and MD fetuses. SD newborns had diminished total pancreatic insulin and plasma somatostatin compared to the other groups. MD dams and fetuses had lower glucagon and somatostatin levels compared to C dams. MD offspring had maintained lower somatostatin levels to neonatal period. Diabetes causes alterations in circulating levels of pancreatic hormones in the mother and offspring., (© Georg Thieme Verlag KG Stuttgart · New York.)

Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades, but the mechanisms involved are still not clarified. In this review the information obtained in previous studies is recapitulated together with some of the current attempts to resolve the controversy in the field: identification of the putative progenitor cells, identification of the factors involved in the expansion of the beta cell mass in human pregnancy, and the relative roles of endocrine factors and nutrients.

We apply a three-fold covariance imaging method to analyse previously acquired data [C. S. Slater et al., Phys. Rev. A 89, 011401(R) (2014)] on the femtosecond laser-induced Coulomb explosion of spatially pre-aligned 3,5-dibromo-3',5'-difluoro-4'-cyanobiphenyl molecules. The data were acquired using the "Pixel Imaging Mass Spectrometry" camera. We show how three-fold covariance imaging of ionic photofragment recoil trajectories can be used to provide new information about the parent ion's molecular structure prior to its Coulomb explosion. In particular, we show how the analysis may be used to obtain information about molecular conformation and provide an alternative route for enantiomer determination.

Background: Integration of physical activity (PA) into the classroom may be an effective way of promoting the learning and academic achievement of children at elementary school. This paper describes the research design and methodology of an intervention study examining the effect of classroom-based PA on mathematical achievement, creativity, executive function, body mass index and aerobic fitness., Methods: The study was designed as a school-based cluster-randomized controlled trial targeting schoolchildren in 1st grade, and was carried out between August 2012 and June 2013. Eligible schools in two municipalities in the Region of Southern Denmark were invited to participate in the study. After stratification by municipality, twelve schools were randomized to either an intervention group or a control group, comprising a total of 505 children with mean age 7.2 ± 0.3 years. The intervention was a 9-month classroom-based PA program that involved integration of PA into the math lessons delivered by the schools' math teachers. The primary study outcome was change in math achievement, measured by a 45-minute standardized math test. Secondary outcomes were change in executive function (using a modified Eriksen flanker task and the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire filled out by the parents), creativity (using the Torrance Tests of Creative Thinking, TTCT), aerobic fitness (by the Andersen intermittent shuttle-run test) and body mass index. PA during math lessons and total PA (including time spent outside school) were assessed using accelerometry. Math teachers used Short Message Service (SMS)-tracking to report on compliance with the PA intervention and on their motivation for implementing PA in math lessons. Parents used SMS-tracking to register their children's PA behavior in leisure time., Discussion: The results of this randomized controlled trial are expected to provide schools and policy-makers with significant new insights into the potential of classroom-based PA to improve cognition and academic achievement in children., Trial Registration: Clinicaltrials.gov: NCT02488460 (06/29/2015).

The design, fabrication and performance of a novel and highly sensitive micro-reactor device for performing in situ grazing-incidence X-ray scattering experiments of model catalyst systems is presented. The design of the reaction chamber, etched in silicon on insulator (SIO), permits grazing-incidence small-angle X-ray scattering (GISAXS) in transmission through 10 µm-thick entrance and exit windows by using micro-focused beams. An additional thinning of the Pyrex glass reactor lid allows simultaneous acquisition of the grazing-incidence wide-angle X-ray scattering (GIWAXS). In situ experiments at synchrotron facilities are performed utilizing the micro-reactor and a designed transportable gas feed and analysis system. The feasibility of simultaneous in situ GISAXS/GIWAXS experiments in the novel micro-reactor flow cell was confirmed with CO oxidation over mass-selected Ru nanoparticles.

Diabetes is characterized by insulin insufficiency due to a relative paucity of functional β-cell mass. Thus, strategies for increasing β-cell mass in situ are sought-after for therapeutic purposes. Pregnancy is a physiological state capable of inducing robust β-cell mass expansion, however, the mechanisms driving this expansion are not fully understood. Thus, the aim of this study was to characterize pregnancy-induced changes in the islet proteome at the peak of β-cell proliferation in mice. Islets from pregnant and nonpregnant littermates were compared via 2 proteomic strategies. In vivo pulsed stable isotope labeling of amino acids in cell culture was used to monitor de novo protein synthesis during the first 14.5 days of pregnancy. In parallel, protein abundance was determined using ex vivo dimethyl labelling at gestational day 14.5. Comparison of the 2 datasets revealed 170 islet proteins to be up regulated as a response to pregnancy. These included several proteins, not previously associated with pregnancy-induced islet expansion, such as CLIC1, STMN1, MCM6, PPIB, NEDD4, and HLTF. Confirming the validity of our approach, we also identified proteins encoded by genes known to be associated with pregnancy-induced islet expansion, such as CHGB, IGFBP5, MATN2, EHHADH, IVD, and BMP1. Bioinformatic analyses demonstrated enrichment and activation of the biological functions: "protein synthesis" and "proliferation," and predicted the transcription factors HNF4α, MYC, MYCN, E2F1, NFE2L2, and HNF1α as upstream regulators of the observed expressional changes. As the first characterization of the islet-proteome during pregnancy, this study provides novel insight into the mechanisms involved in promoting pregnancy-induced β-cell mass expansion and function.

Background: Due to the increased risk of type 2 diabetes, follow-up screening after birth is recommended to women with previous gestational diabetes. Low participation in such screening has been shown to delay detection of diabetes with potentially serious consequences for the women's future health. The women's experiences of treatment and care during their pregnancies may affect participation., Aim: This study aimed at understanding the women's experiences with treatment and care during pregnancy and to understand how these experiences influence participation in follow-up screening., Methods: A qualitative study was undertaken drawing on a phenomenological methodology. Seven women treated for gestational diabetes at a university hospital in the North Denmark Region participated in interviews., Findings: The women experienced lack of continuity in care between hospital departments and health sectors. We identified the following causes for low participation in follow-up screening: poor coordination, little elaboration of information, a lack of clear coordination of responsibility for follow-up screening among health care professionals and absence of focus and inclusion of their individual needs and preferences., Conclusion: The women wished to be reminded of screening to increase their sense of safety. The women's experiences seem to reflect a lack of patient-centeredness during the pregnancy, which may be remedied by increasing the focus on the women's need for improved continuity in treatment and care. Participation in follow-up screening after gestational diabetes may be increased by sending reminders to the women. Raised awareness of the women's individual needs and preferences for treatment and care offers potential for improvement., (Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Patients following meniscectomy are at increased risk of developing knee osteoarthritis in the tibiofemoral compartment and at the patellofemoral joint. As osteoarthritis is widely considered a mechanical disease, it is important to understand the potential effect of arthroscopic partial meniscectomy (APM) on knee joint mechanics. The purpose of this study was to evaluate changes in knee joint biomechanics during a forward lunge in patients with a suspected degenerative meniscal tear from before to three months after APM., Methods: Twenty-two patients (35-55 years old) with a suspected degenerative medial meniscal tear participated in this study. Three dimensional knee biomechanics were assessed on the injured and contralateral leg before and three months after APM. The visual analogue scale was used to assess knee pain and the Knee Injury Osteoarthritis Outcome Score was used to assess sport/recreation function and knee-related confidence before and after APM., Results: The external peak knee flexion moment reduced in the APM leg compared to the contralateral leg (mean difference (95% CI)) -1.08 (-1.80 to -0.35) (Nm/(BW × HT)%), p = 0.004. Peak knee flexion angle also reduced in the APM leg compared to the contralateral leg -3.94 (-6.27 to -1.60) degrees, p = 0.001. There was no change in knee pain between the APM leg and contralateral leg (p=0.118). Self-reported sport/recreation function improved (p = 0.004)., Conclusions: Although patients self-reported less difficulty during strenuous tasks following APM, patients used less knee flexion, a strategy that may limit excessive patellar loads during forward lunge in the recently operated leg., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The global epidemic of diabetes is a serious threat against health and healthcare expenses. Although genetics is important it does not explain the dramatic increase in incidence, which must involve environmental factors. Two decades ago the concept of the thrifty phenotype was introduced, stating that the intrauterine environment during pregnancy has an impact on the gene expression that may persist until adulthood and cause metabolic diseases like obesity and type 2 diabetes. As the pancreatic beta cells are crucial in the regulation of metabolism this article will describe the influence of normal pregnancy on the beta cells in both the mother and the fetus and how various conditions like diabetes, obesity, overnutrition and undernutrition during and after pregnancy may influence the ability of the offspring to adapt to changes in insulin demand later in life. The influence of environmental factors including nutrients and gut microbiota on appetite regulation, mitochondrial activity and the immune system that may affect beta cell growth and function directly and indirectly is discussed. The possible role of epigenetic changes in the transgenerational transmission of the adverse programming may be the most threatening aspect with regard to the global diabetes epidemics. Finally, some suggestions for intervention are presented., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors., Samples: Serum samples from nonpregnant and pregnant women., Methods: The effect of serum from pregnant women on the proliferation of rat beta cells was studied using [3H]thymidine incorporation and 5-ethynyl-2'-deoxyuridine proliferation assays. In addition, serum from pregnant and nonpregnant women was fractionated by gel filtration and high performance liquid chromatography. The fractionated serum was screened for mitogenic activity in INS-1E cells. Proteins and peptides in mitogenic active serum fractions were identified by amino acid sequencing and mass spectrometry., Main Outcome Measures: Presence of circulating beta cell proliferating factors., Results: Late gestational pregnancy serum significantly increased proliferation of rat beta cells compared with early pregnancy and nonpregnancy. The mitogenic active serum fractions contained proteins and peptides derived from kininogen-1, fibrinogen-α, α1-antitrypsin, apolipoprotein-A1, placental lactogen, angiotensinogen and serum albumin., Conclusion: Pregnancy serum is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Several studies have shown increased beta cell mass during pregnancy in both rodents and humans. Proliferation of existing beta cells seems to be the predominant mechanism in rodents, whereas the mechanism in humans is unclear. We hypothesized that neogenesis contributes to the increased beta cell mass in pregnancy and that circulating factors are involved., Samples: Pancreatic tissue from mice and rat and serum from pregnant women., Method: Morphometric analysis of pancreas of pregnant and nonpregnant mice was carried out by immunocytochemical staining for the neogenic marker neurogenin-3. Messenger RNA levels of neurogenin-3 and the transcription factor musculoaponeurotic fibrosarcoma oncogene family protein B in fetal rat pancreas cells, cultured with serum from pregnant women, were measured by quantitative polymerase chain reaction., Main Outcome Measures: The number of neurogenin-3-positive cells present in pregnant mice was increased compared with nonpregnant mice. Neurogenin-3 and musculoaponeurotic fibrosarcoma oncogene family protein B mRNA was detected in fetal rat pancreas exposed to serum from pregnant women., Results: In pregnant mice we found a 3.6-fold increase in beta cell volume at day 18 compared with nonpregnant mice and a 3.5-fold increase in neurogenin-3 volume at day 14, mainly located in the acinar compartment where it was eightfold higher than in nonpregnant mice. In fetal rat pancreatic cells exposed to serum from pregnant women we found a marked increase in both neurogenin-3 and musculoaponeurotic fibrosarcoma oncogene family protein B mRNA levels in fibroblast-like cells., Conclusion: These results suggest that neogenesis contributes to the increased beta cell mass in pregnancy and that circulating factors are involved in beta cell formation in both the maternal and fetal pancreas during pregnancy., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

There is currently limited understanding of the role played by haemodynamic forces on the processes governing vascular development. One of many obstacles to be overcome is being able to measure those forces, at the required resolution level, on vessels only a few micrometres thick. In this paper, we present an in silico method for the computation of the haemodynamic forces experienced by murine retinal vasculature (a widely used vascular development animal model) beyond what is measurable experimentally. Our results show that it is possible to reconstruct high-resolution three-dimensional geometrical models directly from samples of retinal vasculature and that the lattice-Boltzmann algorithm can be used to obtain accurate estimates of the haemodynamics in these domains. We generate flow models from samples obtained at postnatal days (P) 5 and 6. Our simulations show important differences between the flow patterns recovered in both cases, including observations of regression occurring in areas where wall shear stress (WSS) gradients exist. We propose two possible mechanisms to account for the observed increase in velocity and WSS between P5 and P6: (i) the measured reduction in typical vessel diameter between both time points and (ii) the reduction in network density triggered by the pruning process. The methodology developed herein is applicable to other biomedical domains where microvasculature can be imaged but experimental flow measurements are unavailable or difficult to obtain.

The torsional motion of a molecule composed of two substituted benzene rings, linked by a single bond, is coherently controlled by a pair of strong (3×10^{13}  W cm^{-2}), nonresonant (800 nm) 200-fs-long laser pulses-both linearly polarized perpendicular to the single-bond axis. If the second pulse is sent at the time when the two benzene rings rotate toward (away from) each other the amplitude of the torsion is strongly enhanced (reduced). The torsional motion persists for more than 150 ps corresponding to approximately 120 torsional oscillations. Our calculations show that the key to control is the strong transient modification of the natural torsional potential by the laser-induced dynamic Stark effect.

Background: Women whose pregnancy was complicated by gestational diabetes have a 7-fold higher risk of developing diabetes, primarily type 2. Early detection can prevent or delay the onset of late complications, for which follow-up screening is important. This study investigated the extent of participation in follow-up screening and the possible consequences of nonattendance in the Region of North Jutland, Denmark., Method: In Danish national registers covering the years 1994-2011 we identified 2171 birthing women whose pregnancy was complicated by first-time gestational diabetes. Control visits to general practitioners and biochemical departments after giving birth were charted. Following national guidelines we defined four intervals for assessment of participation in follow-up screening. Diagnosis of diabetes or treatment with glucose-lowering agents after giving birth were also identified. Participation in follow-up screening and risk of diabetes was calculated. Time to obtaining diagnosis of diabetes or initiating treatment was analysed by Cox regression models. All models were adjusted for age, ethnicity and income., Results: High attendance was found during the first control interval, after which attendance decreased with time after giving birth for both controls at general practitioners and biochemical departments. All differences in proportions were statistically significant. Women attending controls at general practitioners had a significantly higher risk of diabetes diagnosis and treatment after gestational diabetes than women not attending. The results for women attending testing at biochemical departments also showed an increased risk of initiation of treatment. Women attending at least one general practitioners control had a significantly higher risk of early diabetes diagnosis or treatment. Time to initiation of treatment was significantly higher for testing at biochemical departments. Women with high incomes had a significantly lower risk of diabetes diagnosis or initiation of treatment compared to low-income women., Conclusion: Participation in follow-up screening after gestational diabetes is low in the North Denmark Region. Follow-up screening ensures early detection of diabetes and initiation of treatment. Our results emphasize the importance of development of interventions to improve early detection and prevention of diabetes after gestational diabetes.

Low-temperature fuel cells are limited by the oxygen reduction reaction, and their widespread implementation in automotive vehicles is hindered by the cost of platinum, currently the best-known catalyst for reducing oxygen in terms of both activity and stability. One solution is to decrease the amount of platinum required, for example by alloying, but without detrimentally affecting its properties. The alloy PtxY is known to be active and stable, but its synthesis in nanoparticulate form has proved challenging, which limits its further study. Herein we demonstrate the synthesis, characterization and catalyst testing of model PtxY nanoparticles prepared through the gas-aggregation technique. The catalysts reported here are highly active, with a mass activity of up to 3.05 A mgPt(-1) at 0.9 V versus a reversible hydrogen electrode. Using a variety of characterization techniques, we show that the enhanced activity of PtxY over elemental platinum results exclusively from a compressive strain exerted on the platinum surface atoms by the alloy core.

Over 40 susceptibility loci have been identified for type 1 diabetes (T1D). Little is known about how these variants modify disease risk and progression. Here, we combined in vitro and in vivo experiments with clinical studies to determine how genetic variation of the candidate gene cathepsin H (CTSH) affects disease mechanisms and progression in T1D. The T allele of rs3825932 was associated with lower CTSH expression in human lymphoblastoid cell lines and pancreatic tissue. Proinflammatory cytokines decreased the expression of CTSH in human islets and primary rat β-cells, and overexpression of CTSH protected insulin-secreting cells against cytokine-induced apoptosis. Mechanistic studies indicated that CTSH exerts its antiapoptotic effects through decreased JNK and p38 signaling and reduced expression of the proapoptotic factors Bim, DP5, and c-Myc. CTSH overexpression also up-regulated Ins2 expression and increased insulin secretion. Additionally, islets from Ctsh(-/-) mice contained less insulin than islets from WT mice. Importantly, the TT genotype was associated with higher daily insulin dose and faster disease progression in newly diagnosed T1D patients, indicating agreement between the experimental and clinical data. In line with these observations, healthy human subjects carrying the T allele have lower β-cell function, which was evaluated by glucose tolerance testing. The data provide strong evidence that CTSH is an important regulator of β-cell function during progression of T1D and reinforce the concept that candidate genes for T1D may affect disease progression by modulating survival and function of pancreatic β-cells, the target cells of the autoimmune assault.