401 research outputs found
Domain walls inside localised orientifolds
The equations of motion of toroidal orientifold compactifications with fluxes
are in one-to-one correspondence with gauged supergravity if the orientifold
(and D-brane) sources are smeared over the compact space. This smeared limit is
identical to the approximation that ignores warping. It is therefore relevant
to compare quantities obtained from the gauged supergravity with the true 10d
solution with localised sources. In this paper we find the correspondence
between BPS domain walls in gauged SUGRA and 10D SUGRA with localised sources.
Our model is the simplest orientifold with fluxes we are aware of: an O6/D6
compactification on T^3/Z_2 in massive IIA with H_3-flux. The BPS domain walls
correspond to a O6/D6/NS5/D8 bound state. Our analysis reveals that the domain
wall energy computed in gauged SUGRA is unaffected by the localisation of the
O6/D6 sources.Comment: 26 pages, 1 figur
Promoting students’ sexual and reproductive health in peer-led programmes at two South African universities: Emergent tensions and dilemmas
Sexual and reproductive health programmes with students in higher education in South Africa, are a neglected area of intervention. We report on piloting the peer-facilitated Auntie Stella intervention material at two South African universities. This participatory methodology encourages critical thinking by opening discussion on managing relationships, sexual decision-making, gender-based violence and risk-safety. The format involves various cards featuring a letter, a facilitated discussion, an answer-response and action points. Six focus groups of participants were facilitated by postgraduate students over four months. Using thematic analysis four tensions were identified in the student discussions: HIV awareness was in tension with relationship practices; awareness of risk was in tension with denial of vulnerability; awareness of individuals’ rights was in tension with claims on these rights; and HIV knowledge was in tension with HIV stigma. The Auntie Stella material has the potential to open up discursive spaces amongst students, and to develop agency in sexual decision-making
Insomnia and the incidence, recurrence and persistence of common mental disorders:Sex-differences in the general population
Insomnia is common throughout the population and thought to be a risk factor for mental disorders. We assessed the association of insomnia symptoms with incidence, recurrence and persistence of mood, anxiety and substance use disorders. In 4007 participants (55 % women, mean age 51.0 ± 12.3) of the population-based Netherlands Mental Health Survey and Incidence Study (NEMESIS), having insomnia symptoms increased the odds of developing, recurring and persisting mood disorders, mostly in men. Insomnia only associated with recurring anxiety disorders, particularly in women, and not with substance use disorders. Treating insomnia may aid recovery and prevention of mental disorders, particularly mood disorders.</p
Elucidation of in Vitro Chlorinated Tyrosine Adducts in Blood Plasma as Selective Biomarkers of Chlorine Exposure
[Image: see text] Chlorine is a widely available industrial chemical and involved in a substantial number of cases of poisoning. It has also been used as a chemical warfare agent in military conflicts. To enable forensic verification, the persistent biomarkers 3-chlorotyrosine and 3,5-dichlorotyrosine in biomedical samples could be detected. An important shortfall of these biomarkers, however, is the relatively high incidence of elevated levels of chlorinated tyrosine residues in individuals with inflammatory diseases who have not been exposed to chlorine. Therefore, more reliable biomarkers are necessary to distinguish between endogenous formation and exogeneous exposure. The present study aims to develop a novel diagnostic tool for identifying site-specific chlorinated peptides as a more unambiguous indicator of exogeneous chlorine exposure. Human blood plasma was exposed in vitro to various chlorine concentrations, and the plasma proteins were subsequently digested by pronase, trypsin, or pepsin. After sample preparation, the digests were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS) and liquid chromatography high-resolution tandem mass spectrometry (LC–HRMS/MS). In line with other studies, low levels of 3-chlorotyrosine and 3,5-dichlorotyrosine were found in blank plasma samples in this study. Therefore, 50 site-specific biomarkers were identified, which could be used as more unambiguous biomarkers for chlorine exposure. Chlorination of the peptides TY*ETTLEK, Y*KPGQTVK, Y*QQKPGQAPR, HY*EGSTVPEK, and Y*LY*EIAR could already be detected at moderate in vitro chlorine exposure levels. In addition, the latter two peptides were found to have dichlorinated fragments. Especially, Y*LY*EIAR, with a distinct chlorination pattern in the MS spectra, could potentially be used to differentiate exogeneous exposure from endogenous causes as other studies reported that this part of human serum albumin is nitrated rather than chlorinated under physiological conditions. In conclusion, trypsin digestion combined with high-resolution MS analysis of chlorinated peptides could constitute a valuable technique for the forensic verification of exposure to chlorine
Prediction and treatment of asthma in preschool children at risk: study design and baseline data of a prospective cohort study in general practice (ARCADE)
Background: Asthma is a difficult diagnosis to establish in preschool children. A few years ago, our group presented a prediction rule for young children at risk for asthma in general practice. Before this prediction rule can safely be used in practice, cross-validation is required. In addition, general practitioners face many therapeutic management decisions in children at risk for asthma. The objectives of the study are: (1) identification of predictors for asthma in preschool children at risk for asthma with the aim of cross-validating an earlier derived prediction rule; (2) compare the effects of different treatment strategies in preschool children. Design: In this prospective cohort study one to five year old children at risk of developing asthma were selected from general practices. At risk was defined as 'visited the general practitioner with recurrent coughing (≥ 2 visits), wheezing (≥ 1) or shortness of breath (≥ 1) in the previous 12 months'. All children in this prospective cohort study will be followed until the age of six. For our prediction rule, demographic data, data with respect to clinical history and additional tests (specific immunoglobulin E (IgE), fractional exhaled nitric oxide (FENO), peak expiratory flow (PEF)) are collected. History of airway specific medication use, symptom severity and health-related quality of life (QoL) are collected to estimate the effect of different treatment intensities (as expressed in GINA levels) using recently developed statistical techniques. In total, 1,938 children at risk of asthma were selected from general practice and 771 children (40%) were enrolled. At the time of writing, follow-up for all 5-year olds and the majority of the 4-year olds is complete. The total and specific IgE measurements at baseline were carried out by 87% of the children. Response rates to the repeated questionnaires varied from 93% at baseline to 73% after 18 months follow-up; 89% and 87% performed PEF and FENO measurements, respectively. Discussion: In this study a prediction rule for asthma inyoung children, to be used in (general) practice, will be cross-validated. Our study will also provide more insight in the effect of treatment of asthma in preschool children
Screening for Postpartum Depression in Well-Baby Care Settings:A Systematic Review
Introduction Postpartum depression (PPD) is a mental health problem frequently experienced by mothers in the first year postpartum. Early detection and treatment can help to reduce its negative effect on the development of the newborn child. Well-baby care (WBC) is a promising screening setting for early detection of PPD. This systematic review investigates the evidence of the effectiveness of screening for PPD in WBC settings regarding mother and child outcomes. Methods Three electronic databases were searched: SCOPUS, PsychINFO and CINAHL. Two reviewers independently performed the study selection. Data extraction was based on a predefined data extraction form. Results Six studies were included; a quality assessment rated two studies as strong and four as weak. Four studies measuring outcomes at process level showed improvement in detection, referral and/or treatment rates. Four studies, including the two strong ones, where screening and enhanced care were combined, showed improvements in the Edinburgh Postnatal Depression Scale scores of the mothers in the intervention groups. No improvements were reported on other outcomes at parent level or at child level. At child level, weight was the only outcome that was measured. Discussion This review provides limited yet positive evidence for the value of screening for PPD in a WBC setting. The outcomes are comparable with studies on screening for PPD in general. The evidence that we found is very promising but the small number of available studies shows a need for additional high-quality studies, to strengthen the evidence regarding the potential benefits of screening in a WBC setting.</p
Peer support to decrease diabetes-related distress in patients with type 2 diabetes mellitus:Design of a randomised controlled trial
BACKGROUND: Many type 2 diabetes mellitus patients face difficulties self-managing their illness, which can lead to high levels of diabetes-related distress. Diabetes distress may be decreased by peer support, as peers understand and have dealt with similar problems, and can help motivate each other. A recent systematic review concluded that evidence of benefits of peer support in patients with type 2 diabetes mellitus is too inconsistent due to weak theoretical foundation of the interventions. This study describes the design of a trial evaluating the effectiveness of a group-based, peer support programme with a strong theoretical foundation on diabetes-related distress in type 2 diabetes patients. METHODS: This is a parallel group randomised controlled trial of a six session group-based peer support intervention, delivered by peer leaders and group psychotherapists, compared with one educational meeting on diabetes. At least 152 patients with a type 2 diabetes duration of three years or more and between 50 and 70Â years of age, recruited via their general practitioner, will be randomised to receive the peer support intervention or one educational meeting. The intervention is developed in line with three key stages of research development of the Medical Research Council framework. The primary outcome measure for this study is diabetes-related distress. Secondary outcomes include self-management behaviour, well-being and health-related quality of life. Perceived social support is a process measure. Outcomes will be measured one month before, and 6, and 12Â months after the intervention by means of self-reported questionnaires. Analysis will be on an intention-to-treat basis. DISCUSSION: This article contains a description of the design of a study that will investigate the effect of a group-based, peer support intervention on diabetes-related distress in type 2 diabetes patients. The intervention was developed in recognition of the limited evidence, and the importance of a theoretical foundation and its implementation. Findings will contribute to knowledge in the field of peer support and patient-important outcomes in type 2 diabetes patients. TRIAL REGISTRATION: Dutch Trial Registry: NTR347
Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer’s disease pathology
Background Alzheimer’s disease (AD) is the most common neurodegenerative disease. In addition to the occurrence of amyloid deposits and widespread tau pathology, AD is associated with a neuroinflammatory response characterized by the activation of microglia and astrocytes. Protein kinase 2 (CK2, former casein kinase II) is involved in a wide variety of cellular processes. Previous studies on CK2 in AD showed controversial results, and the involvement of CK2 in neuroinflammation in AD remains elusive. Methods In this study, we used immunohistochemical and immunofluorescent staining methods to investigate the localization of CK2 in the hippocampus and temporal cortex of patients with AD and non-demented controls. We compared protein levels with Western blotting analysis, and we investigated CK2 activity in human U373 astrocytoma cells and human primary adult astrocytes stimulated with IL-1β or TNF-α. Results We report increased levels of CK2 in the hippocampus and temporal cortex of AD patients compared to non-demented controls. Immunohistochemical analysis shows CK2 immunoreactivity in astrocytes in AD and control cases. In AD, the presence of CK2 immunoreactive astrocytes is increased. CK2 immunopositive astrocytes are associated with amyloid deposits, suggesting an involvement of CK2 in the neuroinflammatory response. In U373 cells and human primary astrocytes, the selective CK2 inhibitor CX-4945 shows a dose-dependent reduction of the IL-1β or TNF-α induced MCP-1 and IL-6 secretion. Conclusions This data suggests that CK2 in astrocytes is involved in the neuroinflammatory response in AD. The reduction in pro-inflammatory cytokine secretion by human astrocytes using the selective CK2 inhibitor CX-4945 indicates that CK2 could be a potential target to modulate neuroinflammation in AD
Organoid-based expansion of patient-derived primary alveolar type 2 cells for establishment of alveolus epithelial Lung-Chip cultures
Development of effective treatment strategies for lung tissue destruction as seen in emphysema would greatly benefit from representative human in vitro models of the alveolar compartment. Studying how cellular cross talk and/or (altered) biomechanical cues affect alveolar epithelial function could provide new insight for tissue repair strategies. Preclinical models of the alveolus ideally combine human primary patient-derived lung cells with advanced cell culture applications such as breathing-related stretch, to reliably represent the alveolar microenvironment. To test the feasibility of such a model, we isolated primary alveolar type 2 cells (AEC2s) from patient-derived lung tissues including those from patients with severe emphysema, using magnetic bead-based selection of cells expressing the AEC2 marker HTII-280. We obtained pure alveolar feeder-free organoid cultures using a minimally modified commercial medium. This was confirmed by known AEC2 markers as well as by detection of lamellar bodies using electron microscopy. Following (organoid-based) expansion, cells were seeded on both cell culture inserts and the Chip-S1 Organ-Chip that has a flexible polydimethylsiloxane (PDMS) membrane enabling the application of dynamic stretch. AEC2s cultured for 7 days on inserts or the chip maintained expression of HTII-280, prosurfactant protein C (SP-C), SP-A and SP-B, and zonula occludens-1 (ZO-1) also in the presence of stretch. AEC2s cultured on the chip showed lower expression levels of epithelial-mesenchymal transition-related vimentin expression compared with static cultures on inserts. The combination of a straightforward culture method of patient-derived AEC2s and their application in microfluidic chip cultures supports successful development of more representative human preclinical models of the (diseased) alveolar compartment.Microscopic imaging and technolog
Supra- and Infra-Renal Aortic Neck Diameter Increase after Endovascular Repair of a Ruptured Abdominal Aortic Aneurysm
Hypovolemia-induced hypotension may lead to an aortic diameter decrease in patients with a ruptured abdominal aortic aneurysm (rAAA). This study investigates the changes in supra- and infra-renal aortic neck diameters before and after endovascular aortic aneurysm repair (EVAR) for rAAA and the possible association with endograft apposition. A retrospective cohort study was conducted including 74 patients treated between 2010 and 2019 in two large European vascular centers. Outer-to-outer wall diameters were measured at +40, +10, 0, −10, and −20 mm relative to the lowest renal artery baseline on the last pre- and first post-EVAR computed tomography angiography (CTA) scan in a vascular workstation. Endograft apposition was determined on the first post-EVAR CTA scan. The post-operative diameter was significantly (p < 0.001) larger than the preoperative diameter at all aortic levels. The aortic diameter at +40 mm (supra-renal) and −10 mm (infra-renal) increased by 6.2 ± 7.3% and 12.6 ± 9.8%, respectively. The aortic diameter at +40 mm increased significantly more in patients with low preoperative systolic blood pressure (<90 mmHg; p = 0.005). A shorter apposition length was associated with a higher aortic diameter increase (R = −0.255; p = 0.032). Hypovolemic-induced hypotension results in a significant decrease in the aortic diameter in patients with an rAAA, which should be taken into account when oversizing the endograft
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