Naresuan University Journal
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A novel Alzheimer disease locus located near the gene encoding tau protein.
No full textAPOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (
Evidence for unnatural-parity contributions to electron-impact ionization of laser-aligned atoms
No full textRecent measurements have examined the electron-impact ionization of excited-state laser-aligned Mg atoms. In this work we show that the ionization cross section arising from the geometry where the aligned atom is perpendicular to the scattering plane directly probes the unnatural parity contributions to the ionization amplitude. The contributions from natural parity partial waves cancel exactly in this geometry. Our calculations resolve the discrepancy between the nonzero measured cross sections in this plane and the zero cross section predicted by distorted-wave approaches. We demonstrate that this is a general feature of ionization from p-state targets by additional studies of ionization from excited Ca and Na atoms
The maternal environment programs postnatal weight gain and glucose tolerance of male offspring, but placental and fetal growth are determined by fetal genotype in the leprdb/+ model of gestational diabetes.
No full textMice heterozygous for a signaling-deficient leptin receptor (Leprdb/+ [db/+]) are widely used as a model of gestational diabetes that results in poor fetal outcomes. This study investigated the importance of fetal genotype (db/+) relative to abnormal maternal metabolism for placental function and therefore fetal growth and offspring health. Wild-type (WT) and db/+ females were mated to db/+ and WT males, respectively, generating litters of mixed genotype. Placentas and fetuses were weighed at embryonic day 18.5; offspring weight, hormone levels, glucose tolerance, and blood pressure were assessed at 3 and 6 months. Pregnant db/+, but not WT, dams had impaired glucose tolerance. The db/+ placentas and fetuses were heavier than WT, but the maternal environment had no effect; WT placentas/fetuses from db/+ mothers were no bigger than WT placentas/fetuses carried by WT mothers. Postnatal weight gain, glucose metabolism, and leptin levels were all influenced by offspring genotype. However, maternal environment affected aspects of offspring health because WT male offspring born to db/+ dams were heavier and had worse glucose tolerance than the sex-matched WT offspring of WT mothers. Blood pressure was not affected by maternal or offspring genotype. These data reveal that studies using the db/+ mouse to model outcomes of pregnancy complicated by gestational diabetes should be mindful of the genetically predisposed fetal/postnatal overgrowth. Although inappropriate for dissecting the effect of maternal hyperglycemia on the contribution of placental function to macrosomia, the db/+ mouse may prove useful for investigating mechanisms underlying programming of suboptimal postnatal weight gain and glucose metabolism by an adverse maternal metabolic environment
Trans-venous occlusion of incompetent pelvic veins for chronic pelvic pain in women: a systematic review
No full textChronic pelvic pain (CPP) affects 24% of women worldwide; the cause cannot be identified in 40% despite invasive investigations. Dilated, refluxing pelvic veins may be a cause of CPP and treatment by trans-venous occlusion is increasingly performed when gynaecological causes are excluded, but is it effective? A systematic review of the literature published between 1966 and July 2014 was conducted. Two authors independently reviewed potential studies according to a set of eligibility criteria, with a third assessor available as an arbiter. Thirteen studies including 866 women undergoing trans-venous occlusion of pelvic veins for CPP were identified (Level of evidence: one study grade 2b, 12 studies grade four). Statistical significant improvements in pelvic pain were reported in nine of the 13 studies. Technical success was reported in 865 of 866 (99.8%) with low complication rates: coil migration in 14 women (1.6%), abdominal pain in ten women (1.2%) and vein perforation in five (0.6%). In a study on varicose veins of the legs, recurrence was seen in 13% of 179 women 5- years following coil embolisation. Subjective improvements in pain were seen in all 13 studies after treatment by trans-venous occlusion. All 13 studies were of poor methodological quality. Complication rates were low and no fatalities occurred. Well-designed studies are essential to determine whether pelvic vein incompetence (PVI) is associated with CPP, and to explore whether trans-venous occlusion of PVI improves quality of life for these women
Mutations in SIPA1L3 cause eye defects through disruption of cell polarity and cytoskeleton organization.
No full textCorrect morphogenesis and differentiation are critical in development and maintenance of the lens, which is a classic model system for epithelial development and disease. Through germline genomic analyses in patients with lens and eye abnormalities, we discovered functional mutations in the Signal Induced Proliferation Associated 1 Like 3 (SIPA1L3) gene, which encodes a previously uncharacterized member of the Signal Induced Proliferation Associated 1 (SIPA1 or SPA1) family, with a role in Rap1 signalling. Patient 1, with a de novo balanced translocation, 46,XY,t(2;19)(q37.3;q13.1), had lens and ocular anterior segment abnormalities. Breakpoint mapping revealed transection of SIPA1L3 at 19q13.1 and reduced SIPA1L3 expression in patient lymphoblasts. SIPA1L3 downregulation in 3D cell culture revealed morphogenetic and cell polarity abnormalities. Decreased expression of Sipa1l3 in zebrafish and mouse caused severe lens and eye abnormalities. Sipa1l3(-/-) mice showed disrupted epithelial cell organization and polarity and, notably, abnormal epithelial to mesenchymal transition in the lens. Patient 2 with cataracts was heterozygous for a missense variant in SIPA1L3, c.442G>T, p.Asp148Tyr. Examination of the p.Asp148Tyr mutation in an epithelial cell line showed abnormal clustering of actin stress fibres and decreased formation of adherens junctions. Our findings show that abnormalities of SIPA1L3 in human, zebrafish and mouse contribute to lens and eye defects, and we identify a critical role for SIPA1L3 in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization
Allergen-induced airway responses.
No full textEnvironmental allergens are an important cause of asthma and can contribute to loss of asthma control and exacerbations. Allergen inhalation challenge has been a useful clinical model to examine the mechanisms of allergen-induced airway responses and inflammation. Allergen bronchoconstrictor responses are the early response, which reaches a maximum within 30 min and resolves by 1-3 h, and late responses, when bronchoconstriction recurs after 3-4 h and reaches a maximum over 6-12 h. Late responses are followed by an increase in airway hyperresponsiveness. These responses occur when IgE on mast cells is cross-linked by an allergen, causing degranulation and the release of histamine, neutral proteases and chemotactic factors, and the production of newly formed mediators, such as cysteinyl leukotrienes and prostaglandin D2. Allergen-induced airway inflammation consists of an increase in airway eosinophils, basophils and, less consistently, neutrophils. These responses are mediated by the trafficking and activation of myeloid dendritic cells into the airways, probably as a result of the release of epithelial cell-derived thymic stromal lymphopoietin, and the release of pro-inflammatory cytokines from type 2 helper T-cells. Allergen inhalation challenge has also been a widely used model to study potential new therapies for asthma and has an excellent negative predictive value for this purpose
ETHICAL ASPECTS OF CREATING HUMAN-NONHUMAN CHIMERAS CAPABLE OF HUMAN GAMETE PRODUCTION AND HUMAN PREGNANCY
No full textJoining UNISON: does the reform of a union organising strategy change how members perceive their recruitment?
No full textDrawing on survey evidence collected between 2001 and 2012, this article examines whether changes in the organising approach of UNISON were reflected in changes in the routes of entry of new members into the union. The article shows that shifts in UNISON policy were marginal to the pattern of entry into the union. The implications of these findings for the concept and implementation of organising are subsequently reviewed
Mindfulness-Based Cognitive Therapy for Psychosis: Measuring Psychological Change Using Repertory Grids.
No full textThere are an increasing, but limited, number of studies investigating the benefits of mindfulness interventions for people experiencing psychosis. To our knowledge, changes following mindfulness for psychosis have not yet been explored from a personal construct perspective. This study had two main aims: (i) to explore changes in the way a person construes their self, others and their experience of psychosis following a Mindfulness-Based Cognitive Therapy (MBCT) group; and (ii) to replicate the findings of other studies exploring the feasibility and potential benefits of MBCT for psychosis. Sixteen participants, with experience of psychosis, completed an 8-week MBCT group. Participants completed pre-group and post-group assessments including a repertory grid, in addition to a range of outcome measures. There was some evidence of changes in construing following MBCT, with changes in the way participants viewed their ideal self and recovered self, and an indication of increased self-understanding. Improvements were found in participants' self-reported ability to act with awareness and in recovery. This study demonstrates the feasibility and potential benefits of MBCT groups for people experiencing psychosis. Furthermore, it provides some evidence of changes in construal following MBCT that warrant further exploration. Large-scale controlled trials of MBCT for psychosis are needed, as well as studies investigating the mechanisms of change. Copyright © 2015 John Wiley & Sons, Ltd.KEY PRACTITIONER MESSAGE: MBCT may contribute to change in individuals' perceptions and increase self-understanding. The study highlights the importance of measuring change in recovery following MBCT. Findings support the need for person-centred approaches to assessment and monitoring of personal change following therapy. Similar studies using a control group are needed in order to identify whether the changes found are attributable to participation in an MBCT group. Copyright © 2015 John Wiley & Sons, Ltd
Illness beliefs and the sociocultural context of diabetes self-management in British South Asians: a mixed methods study.
No full textBACKGROUND: British South Asians have a higher incidence of diabetes and poorer health outcomes compared to the general UK population. Beliefs about diabetes are known to play an important role in self-management, yet little is known about the sociocultural context in shaping beliefs. This study aimed to explore the influence of sociocultural context on illness beliefs and diabetes self-management in British South Asians. METHODS: A mixed methods approach was used. 67 participants recruited using random and purposive sampling, completed a questionnaire measuring illness beliefs, fatalism, health outcomes and demographics; 37 participants completed a social network survey interview and semi-structured interviews. Results were analysed using SPSS and thematic analysis. RESULTS: Quantitative data found certain social network characteristics (emotional and illness work) were related to perceived concern, emotional distress and health outcomes (p <0.05). After multivariate analysis, emotional work remained a significant predictor of perceived concern and emotional distress related to diabetes (p <0.05). Analysis of the qualitative data suggest that fatalistic attitudes and beliefs influences self-management practices and alternative food 'therapies' are used which are often recommended by social networks. CONCLUSIONS: Diabetes-related illness beliefs and self-management appear to be shaped by the sociocultural context. Better understanding of the contextual determinants of behaviour could facilitate the development of culturally appropriate interventions to modify beliefs and support self-management in this population