Publications by authors named "Magnus Sandberg"

31 Publications

Text message-based lifestyle intervention in primary care patients with hypertension: a randomized controlled pilot trial.

Scand J Prim Health Care 2020 Sep 20;38(3):300-307. Epub 2020 Jul 20.

Department of Clinical Sciences Malmö, Lund University, Sweden.

Objective: To evaluate the feasibility of a randomized controlled pilot study with lifestyle-promoting text messages as a treatment for hypertension in primary care.

Design: Randomized controlled pilot trial.

Setting: Three primary health care centers in southern Sweden.

Subjects: Sixty patients aged 40-80 years with hypertension were included.

Main Outcome Measures: Feasibility of the pilot study, i.e. recruitment rate, dropout rate and eligibility criteria. Secondary outcomes were change in blood pressure and other cardiovascular risk factors.

Methods: Thirty participants were randomized to the intervention group with four lifestyle-promoting text messages sent every week for six months. The control group received usual care. The baseline and follow-up visits for all 60 patients included measurements of blood pressure, anthropometrics, blood tests and a self-reported questionnaire.

Results: All feasibility criteria (recruitment rate (≥55%), dropout rate (≤15%) and eligibility (60 eligible patients during the four-month inclusion period) for the pilot study were fulfilled. This means that a larger study with a similar design may be conducted. After six months, there were no significant improvements in cardiovascular risk factors. However, we found favorable trends for all secondary outcomes in the intervention group as compared to the control group.

Conclusion: Lifestyle modification in patients with hypertension is important to reduce cardiovascular risk. However, primary healthcare has limited resources to work with modifying lifestyle habits. This is the first pilot study to test the feasibility of text message-based lifestyle intervention in patients with hypertension in Swedish primary healthcare. Whether significant improvement in cardiovascular risk factors may be achieved in a larger study population remains to be evaluated. Key points This pilot randomized controlled trial (RCT) is the first study to evaluate the feasibility of text message-based lifestyle advice to patients with hypertension in Swedish primary healthcare. •All feasibility criteria for the pilot study were fulfilled. This outcome means that a larger study with a similar design may be conducted. •The study was not powered to find significant changes in cardiovascular risk factors. Nevertheless, after six months we found favorable trends for all secondary outcomes in the intervention group compared to control. •If a future larger study can show significant results, this intervention could serve as a useful tool in everyday primary healthcare.
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http://dx.doi.org/10.1080/02813432.2020.1794392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470149PMC
September 2020

Using four different clinical tools as predictors for pain after total hip arthroplasty: a prospective cohort study.

BMC Anesthesiol 2020 03 3;20(1):57. Epub 2020 Mar 3.

Department of Anesthesiology, Zealand University Hospital, Lykkebækvej 1, 4600, Koege, Denmark.

Background: Treatment of postoperative pain remains a significant clinical problem, and prediction of patients with a risk of higher postoperative pain levels is an important focus. We aimed to identify patients undergoing total hip arthroplasty (THA) with risk of higher pain levels at 24 h postoperatively by using four simple and easily available clinical tools.

Methods: This prospective observational cohort study included 102 patients having THA at Zealand University Hospital in Denmark. The following predictive tools were investigated for identifying patients with higher postoperative pain levels at 24 h postoperatively, both at rest and during mobilization: preoperative pain by peripheral venous cannulation (PVC) (dichotomized according to numerical rating scale pain ≤ 2/> 2 (PVC-Low/PVC-High) (primary outcome); the post anesthesia care unit (PACU) nurses' expectations of patients pain levels; patients early pain levels at the PACU; and patients own forecast of postoperative pain levels. The Mann-Whitney U test was used to analyze comparisons between prediction groups. For the primary outcome we considered a p-value < 0.01 as statistically significant and for other outcomes a p-value of 0.05.

Results: We found no significant differences between the PVC groups for pain during mobilization at 24-h postoperatively: PVC-Low: 6 (4-8) (median, (IQR)) versus PVC-High: 7 (5-8) (median, (IQR)), p = 0.10; and for pain at rest: PVC-Low 2 (0-3) (median, (IQR)) versus PVC-High 3 (2-5) (median, (IQR)), p = 0.12. Other comparisons performed between predictive groups did not differ significantly.

Conclusions: In this prospective cohort study of 102 THA patients, we did not find that preoperative pain by PVC, when using a cut-off point of NRS ≤ 2, were able to predict postoperative pain at 24 h postoperatively. Neither did PACU nurses' prediction of pain, patients forecast of pain, nor did maximum pain levels at the PACU.

Trial Registration: Retrospectively registered 20th February 2018 at ClinicalTrials.gov (NCT03439566).
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http://dx.doi.org/10.1186/s12871-020-00959-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055106PMC
March 2020

To initiate the conversation - Public health nurses' experiences of working with obesity in persons with mobility disability.

J Adv Nurs 2019 Oct 21;75(10):2156-2166. Epub 2019 Jul 21.

Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden.

Aim: Developing a theory explaining how public health nurses accomplish and adapt counselling in lifestyle habits to decrease obesity in people with mobility disability.

Design: Empirical research - qualitative.

Method: Classic grounded theory with face-to-face interviews, 2017-2018, using inductive approach to understand public health nurses' intervening experiences with obesity patients.

Results: To initiate the conversation emerged as the main concern meaning having difficulties initiating conversations about obesity with patients. Public health nurses' facilitators to communicate lifestyle changes emerged as the pattern generating the theory, which consists of the categories; person-centeredness in the situation, experience and knowledge, strengthening conditions, access to other professionals and prioritization in everyday work.

Conclusions: Public health nurses hesitate to raise topics of obesity in patients with mobility disability. They advocate increased integration with lifestyle changes in everyday work including multi-professional cooperation. The implication is testing the emerged theory at primary health care centres.

Impact: Obesity is more common in people with mobility disability than in those without. There is a need to understand how public health nurses adapt counselling in lifestyle habits. Public health nurses hesitate to talk about obesity with patients in fear of offending anyone. Public health nurses did not distinguish between patients with or without mobility disability. Several facilitators could be helpful initiating conversation with the patients. Public health nurses need more time and resources to facilitate conversation with patients with mobility disability to counsel lifestyle changes.
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http://dx.doi.org/10.1111/jan.14081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851847PMC
October 2019

'Having to learn this so late in our lives…' Swedish elderly patients' beliefs, experiences, attitudes and expectations of e-health in primary health care.

Scand J Prim Health Care 2019 Mar 8;37(1):41-52. Epub 2019 Feb 8.

d Department of Health Sciences , Lund University , Lund , Sweden.

Objective: The elderly are an increasing group and large consumers of care in Sweden. Development of mobile information technology shows promising results of interventions for prevention and treatment of chronic diseases. Exploring the elderly patients' beliefs, attitudes, experiences and expectations of e-health services helps us understand the factors that influence adherence to such tools in primary care.

Material And Methods: We conducted focus group interviews with 15 patients from three primary health care centers (PHCCs) in Southern Sweden. Data were analysed with thematic content analysis with codes and categories emerged from data during analysis.

Results: We found one comprehensive theme: 'The elderly's ambivalence towards e-health:  reluctant curiosity, a wish to join and need for information and learning support'. Eight categories emerged from the text during analysis: 'E-health - a solution for a non-existing problem?', 'The elderly's experiences of e-health', 'Lack of will, skills, self-trust or mistrust in the new technology', 'Organizational barriers', 'Wanting and needing to move forward', 'Concerns to be addressed for making e-health a good solution', 'Potential advantages with e-health versus ordinary health care' and 'Need for speed, access and correct comprehensive information'.

Conclusions: Elderly patients in Sweden described feelings of ambivalence towards e-health, raising concerns as accessibility to health care, mistrust in poor IT systems or impaired abilities to cope with technology. They also expressed a wish and need to move forward albeit with reluctant curiosity. Successful implementation of e-health interventions should be tailored to target different attitudes and needs with a strong focus on information and support for the elderly. Key points Exploring the elderly patients' beliefs, experiences, attitudes and expectations of the fast developing e-health services helps us understand the factors that influence adherence to such tools in primary care. Elderly patients in Sweden reported ambivalence and different experiences and attitudes towards e-health, raising concerns as accessibility to health care, costs and mistrust in poor IT systems or impaired abilities to cope with technology. They also expressed a wish and need to move forward albeit with reluctant curiosity. Successful implementation of e-health interventions should be tailored to target different attitudes and needs with a strong focus on information and support for the elderly.
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http://dx.doi.org/10.1080/02813432.2019.1570612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452815PMC
March 2019

The complexity of reaching and maintaining a healthy body weight - the experience from adults with a mobility disability.

BMC Obes 2018 3;5:33. Epub 2018 Dec 3.

Department of Health Sciences, Lund University, P.O. Box 157, 221 00 Lund, SE Sweden.

Background: People with a disability affecting their mobility are more likely to be overweight or obese than those without a mobility disability. The guidelines on how to prevent and treat overweight/obese adults in the general population have not been adapted to the needs of people with a mobility disability. A reasonable useful first step in the process of adapting such guidelines is to conduct a qualitative study of the perceived needs of these people.

Aim: The aim was to explore the experienced importance of body weight among adults with a mobility disability and their perceived needs and actions to reach and maintain a healthy weight.

Method: This was an explorative qualitative study based on individual interviews and qualitative content analysis. An inductive analysis of the interviews formed the basis for the establishment of sub-categories, main categories and, finally, a main theme. The twenty participants included in the study have had a mobility disability for more than two years before being recruited.

Results: The overall theme, "The complex trajectory to a healthy weight", included four main categories. In the category (i) , the participants perceived that everything was harder with the combination of a mobility disability and being overweight/obese with one factor making the other worse. In (ii) , the participants talked about different ways of attempting to reach or maintain a healthy weight. In (iii) , they spoke of awareness and motivation as contributory factors. In (iv) , they spoke about feelings that their weight problems were not given high priority in primary health care. They found it difficult to get advice designed for persons with a mobility disability and felt that competence was lacking among health professionals. The participants asked for a team of professionals with adequate knowledge concerning mobility disabilities.

Conclusions: People with a mobility disability combined with being overweight/obese have a complex living situation and health needs. The experiences communicated by participants may facilitate adaption of existing intervention programs or development of a new evidence-based obesity prevention program for primary health care settings.
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http://dx.doi.org/10.1186/s40608-018-0212-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276247PMC
December 2018

Is care based on comprehensive geriatric assessment with mobile teams better than usual care? A study protocol of a randomised controlled trial (The GerMoT study).

BMJ Open 2018 10 10;8(10):e023969. Epub 2018 Oct 10.

The Swedish Institute for Health Economics, Lund, Sweden.

Introduction: Comprehensive geriatric assessment (CGA) is a multidimensional, interdisciplinary diagnostic process used to determine the medical, psychological and functional capabilities of frail older people. The primary aim of our current study is to confirm whether CGA-based outpatient care is superior than usual care in terms of health-related outcomes, resource use and costs.

Methods And Analysis: The Geriatric Mobile Team trial is designed as a single-centre randomised, controlled, assessor-blinded (at baseline) trial. All participants will be identified via local healthcare registries with the following inclusion criteria: age ≥75 years, ≥3 different diagnoses and ≥3 visits to the emergency care unit (with or without admittance to hospital) during the past 18 months. Nursing home residency will be an exclusion criterion. Baseline assessments will be done before the 1:1 randomisation. Participants in the intervention group will, after an initial CGA, have access to care given by a geriatric team in addition to usual care. The control group receives usual care only. The primary outcome is the total number of inpatient days during the follow-up period. Assessments of the outcomes: mortality, quality of life, health care use, physical functional level, frailty, dependence and cognition will be performed 12 and 24 months after inclusion. Both descriptive and analytical statistics will be used, in order to compare groups and for analyses of outcomes over time including changes therein. The primary outcome will be analysed using analysis of variance, including in-transformed values if needed to achieve normal distribution of the residuals.

Ethics And Dissemination: Ethical approval has been obtained and the results will be disseminated in national and international journals and to health care leaders and stakeholders. Protocol amendments will be published in ClinicalTrials.gov as amendments to the initial registration NCT02923843. In case of success, the study will promote the implementation of CGA in outpatient care settings and thereby contribute to an improved care of older people with multimorbidity through dissemination of the results through scientific articles, information to politicians and to the public.

Trial Registration Number: NCT02923843; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-023969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252639PMC
October 2018

Genomic analysis of transcriptional networks directing progression of cell states during MGE development.

Neural Dev 2018 09 14;13(1):21. Epub 2018 Sep 14.

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 94143, USA.

Background: Homeodomain (HD) transcription factor (TF) NKX2-1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. NKX2-1 defines MGE regional identity in large part through transcriptional repression, while specification and maturation of GABAergic and cholinergic fates is mediated in part by transcriptional activation via TFs such as LHX6 and LHX8. Here we analyze the signaling and TF pathways, downstream of NKX2-1, required for GABAergic and cholinergic neuron fate maturation.

Methods: Differential ChIP-seq analysis was used to identify regulatory elements (REs) where chromatin state was sensitive to change in the Nkx2-1cKO MGE at embryonic day (E) 13.5. TF motifs in the REs were identified using RSAT. CRISPR-mediated genome editing was used to generate enhancer knockouts. Differential gene expression in these knockouts was analyzed through RT-qPCR and in situ hybridization. Functional analysis of motifs within hs623 was analyzed via site directed mutagenesis and reporter assays in primary MGE cultures.

Results: We identified 4782 activating REs (aREs) and 6391 repressing REs (rREs) in the Nkx2-1 conditional knockout (Nkx2-1cKO) MGE. aREs are associated with basic-Helix-Loop-Helix (bHLH) TFs. Deletion of hs623, an intragenic Tcf12 aRE, caused a reduction of Tcf12 expression in the sub-ventricular zone (SVZ) and mantle zone (MZ) of the MGE. Mutation of LHX, SOX and octamers, within hs623, caused a reduction of hs623 activity in MGE primary cultures.

Conclusions: Tcf12 expression in the SVZ of the MGE is mediated through aRE hs623. The activity of hs623 is dependent on LHX6, SOX and octamers. Thus, maintaining the expression of Tcf12 in the SVZ involves on TF pathways parallel and genetically downstream of NKX2-1.
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http://dx.doi.org/10.1186/s13064-018-0119-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138899PMC
September 2018

How best to support individuals with IDD as they become frail: Development of a consensus statement.

J Appl Res Intellect Disabil 2019 Jan 27;32(1):35-42. Epub 2018 Jun 27.

Department of Nursing, University of Manitoba, Winnipeg, MB, Canada.

Background: While higher rates and earlier onset of frailty have been reported among adults with intellectual and developmental disabilities (IDD), research on how best to support these individuals is lacking.

Method: An international consultation relied on three consensus building methods: the Nominal Group Technique, an NIH consensus conference approach, and a Delphi survey.

Results: There is agreement that person-centered planning and aging in place should be guiding principles. Frailty must be considered earlier than in the general population with the recognition that improvement and maintenance are viable goals. Intersectoral collaboration is needed to coordinate assessments and actions. Safety and planning for the future are important planning considerations, as are the needs of caregivers. Ongoing research is needed.

Conclusion: The statement offers guidance to respond to frailty among adults with IDD and fosters ongoing exchange internationally on best practice. As new evidence emerges, the statement should be revisited and revised.
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http://dx.doi.org/10.1111/jar.12499DOI Listing
January 2019

The experiences of pre- and in-hospital care in patients with hip fractures: A study based on Critical incidents.

Int J Orthop Trauma Nurs 2018 Aug 15;30:8-13. Epub 2018 May 15.

Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden. Electronic address:

Background: Hip fractures are described to have a significant impact on patients' well-being and different fast-track concepts could result in a reduction of the patient's psychological and emotional reactions before pre- and intrahospital care.

Aims And Objectives: This study aimed to elucidate perceived situations of significance experienced by patients with hip fracture during the prehospital- and in-hospital care.

Design: The study used a qualitative approach using a critical incident technique (CIT), 14 patients with hip fractures were included.

Methods: All informants had undergone surgery for a hip fracture, were able to communicate in Swedish and had no cognitive impairment.

Results: The main area Oscillating between being satisfied and to endure a new demanding situation emerged from five categories: Pain and pain management, Feeling fear and satisfaction in perioperative care, Experiencing continuity in care, Considering information and Felling confirmed.

Conclusion: Experiences of prehospital care shows a positive impact though the patients experienced this part of the pathway professionally. However, the patients described critical incidents according to their experiences of pain seems to have significant damagingly impact on the patients' well-being. The patient also describe a sense of uncertainty in their individual involvement of care.
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http://dx.doi.org/10.1016/j.ijotn.2018.05.003DOI Listing
August 2018

Fall-risk-increasing drugs and falls requiring health care among older people with intellectual disability in comparison with the general population: A register study.

PLoS One 2018 19;13(6):e0199218. Epub 2018 Jun 19.

Center for Primary Health Care Research, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.

Background: Falls are the most common cause of injury for older people in the general population as well as among those with intellectual disability. There are many risk factors for falls, including a range of drugs which are considered to be fall-risk-increasing (FRIDs). The aim of the present study was to describe prescription patterns of FRIDs in itself as well as in relation to falls requiring health care among older people with intellectual disability and their age-peers in the general population. Moreover, to investigate possible differences between the two groups.

Methods: A cohort of people with intellectual disability and a referent cohort, one-to-one-matched by sex and year of birth, were established. Each cohort comprised 7936 people aged 55+ years at the end of 2012. Register data were collected for 2006-2012 on prescription of antidepressants, anxiolytics, hypnotics and sedatives, opioids, and antipsychotics, as well as for fall-related health care contacts. Analyses were performed on yearly data, using repeated measures models.

Results: People with intellectual disability were more likely to be prescribed at least one FRID (Relative Risk [RR] 2.31). The increase was highest for antipsychotics (RR 25.0), followed by anxiolytics (RR 4.18), antidepressants (RR 2.72), and hypnotics and sedatives (RR 1.42). For opioids, however, a lower prevalence (RR 0.74) was found. In both cohorts, those with prescription of at least one FRID were more likely to have a fall-related injury that required health care. The increased risk was higher in the referent cohort (RR 3.98) than among people with intellectual disability (RR 2.27), although people with intellectual disability and prescription still had a higher risk of falls than those with prescription in the referent cohort (RR 1.27). A similar pattern was found for all drug groups, except for opioids, where prescription carried the same risk of having a fall-related injury that required health care in both cohorts.

Conclusions: With or without prescription of FRIDs, older people with ID have a higher risk of falls requiring health care than their age-peers in the general population. It is important to be aware of this when prescribing drugs that further increase the risk of falls.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199218PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007903PMC
April 2019

Cortical interneuron development: a tale of time and space.

Development 2017 11;144(21):3867-3878

Department of Psychiatry, University of California, San Francisco, CA 94158, USA

Cortical interneurons are a diverse group of neurons that project locally and are crucial for regulating information processing and flow throughout the cortex. Recent studies in mice have advanced our understanding of how these neurons are specified, migrate and mature. Here, we evaluate new findings that provide insights into the development of cortical interneurons and that shed light on when their fate is determined, on the influence that regional domains have on their development, and on the role that key transcription factors and other crucial regulatory genes play in these events. We focus on cortical interneurons that are derived from the medial ganglionic eminence, as most studies have examined this interneuron population. We also assess how these data inform our understanding of neuropsychiatric disease and discuss the potential role of cortical interneurons in cell-based therapies.
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http://dx.doi.org/10.1242/dev.132852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702067PMC
November 2017

Prescription of potentially inappropriate medications among older people with intellectual disability: a register study.

BMC Pharmacol Toxicol 2017 10 25;18(1):68. Epub 2017 Oct 25.

Center for Primary Health Care Research, Department of Clinical Sciences in Malmö, Lund University, 221 00, Lund, SE, Sweden.

Background: Older people have a greater disease burden and are more likely than younger to be prescribed medications. They are also more sensitive to adverse effects. With this in mind, a range of medications have been suggested inappropriate in this population. People with intellectual disability (ID) have a higher disease burden than the general population, putting them at even greater risk of prescription of such medications. The aim of this study was to describe prescription of potentially inappropriate medications among older people with ID in relation to prescriptions among their age peers in the general population.

Methods: We established an administrative cohort of people with ID (ID cohort; n = 7936), using a Swedish national register. A referent cohort from the general population (gPop) was matched one-to-one by sex and year of birth. Data regarding prescription of potentially inappropriate medications were collected from the Swedish prescribed drug register for the years 2006-2012.

Results: People with ID were more likely than the general population to be prescribed medications with anticholinergic effects, intermediate- or long-acting benzodiazepines, and antipsychotics at least once during the study period, and also had more number of years with prescription. Except for benzodiazepines, those in the ID cohort with at least one prescription had larger amounts prescribed than those in the gPop cohort. People in the ID cohort were less likely than the general population to be prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Among those with at least one prescription of NSAIDs, those in the ID cohort had prescriptions during fewer years and in lower amounts than those in the gPop cohort.

Conclusions: Although prescription of potentially inappropriate medications overall is more common among people with ID than in the general population, the opposite pattern is found for medications for pain management. This may be a result of pain being under-recognized and under-treated in this population. Thus, there is a need for training as well as increased knowledge and awareness among care and health care professionals regarding signs of adverse effects and the need of continuous evaluation of treatment in this vulnerable group.
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http://dx.doi.org/10.1186/s40360-017-0174-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657112PMC
October 2017

Is Obesity More Than a Double Burden among People with Mobility Disability? The Effect of Obesity on HRQoL and Participation in Society.

Healthcare (Basel) 2017 Oct 24;5(4). Epub 2017 Oct 24.

Department of Health Sciences, Lund University, P.O. Box 157, Lund SE-221 00, Sweden.

Obesity is more common in individuals with mobility disability than in those without this condition. Individuals with mobility disability also have lower health-related quality of life (HRQoL) and are limited in their participation in society. Therefore, this study aimed to investigate the body mass index (BMI) status and the association of overweight or obesity on HRQoL and participation in society among those with mobility disability in comparison to those without mobility disability. This cross-sectional study was based on a health survey conducted in Sweden in 2012 ( = 18,322; age, 18-64 years). Logistic regression with and without interaction analysis was applied. Effect modification by overweight status was significant for, moderate pain. For obesity, effect modification was seen for low general health, pain (moderate and severe), and not participating in work. BMI was higher among those with mobility disability, but no associations between overweight or obesity and HRQoL or participation in society were observed for those with mobility disability. Overweight and obesity did not add an additional burden to mobility disability, probably because mobility disability is associated with low HRQoL and low participation in society. Despite these results, population obesity prevention strategies are still needed.
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http://dx.doi.org/10.3390/healthcare5040079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746713PMC
October 2017

and control subtype and laminar identity of MGE-derived neocortical interneurons.

Development 2017 08 10;144(15):2837-2851. Epub 2017 Jul 10.

Department of Psychiatry, Neuroscience Program and the Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94158, USA

Distinct cortical interneuron (CIN) subtypes have unique circuit functions; dysfunction in specific subtypes is implicated in neuropsychiatric disorders. Somatostatin- and parvalbumin-expressing (SST and PV) interneurons are the two major subtypes generated by medial ganglionic eminence (MGE) progenitors. Spatial and temporal mechanisms governing their cell-fate specification and differential integration into cortical layers are largely unknown. We provide evidence that and ( and ) transcription factor expression in an arc-shaped progenitor domain within the MGE promotes time-dependent survival of this neuroepithelium and the time-dependent specification of layer V SST CINs. and autonomously repress PV fate in MGE progenitors, in part through directly driving expression. These results have identified, in mouse, a transcriptional pathway that controls SST-PV fate.
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http://dx.doi.org/10.1242/dev.150664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560044PMC
August 2017

Gender differences in psychiatric diagnoses in older people with intellectual disability: a register study.

BMC Psychiatry 2017 05 22;17(1):192. Epub 2017 May 22.

Department of Health Sciences, Lund University, SE-221 00, Lund, Sweden.

Background: Gender differences regarding psychiatric ill-health are well known in the general population. However, not much research is done on people with intellectual disability, and especially not among older people with intellectual disability.

Methods: People with intellectual disability aged 55+ years in 2012 in Sweden were identified through a register containing information on those receiving support and service for this type of disability. The cohort comprised 3609 women and 4327 men with mean age 65 and 64 years, respectively. Information on psychiatric diagnoses was collected from the National Patient Register for the period 2002-2012. Potential gender differences were evaluated both for diagnostic categories (e.g. affective disorders) and single diagnoses (e.g. depressive episodes).

Results: The most common diagnoses among women were in the diagnostic category affective disorders, and among men in psychotic disorders. The majority of both women (72%) and men (71%) had diagnoses in only one diagnostic category. Women were more likely than men to have at least one diagnosis of dementia (odds ratio 1.40, 95% confidence interval 1.06-1.83) or affective disorders (1.33, 1.21-1.58) during the study period. They were, however, less likely to have at least one diagnosis of alcohol/substance use related disorder (0.59, 0.43-0.80). No gender differences were found for diagnoses of psychotic (1.04, 0.86-1.27) or anxiety disorders (1.15, 0.94-1.40). Regarding single diagnoses, women were more likely than men to have had at least one diagnosis of unspecified nonorganic psychosis (1.75, 1.23-2.50), depressive episode (1.47, 1.19-1.82), recurrent depressive disorder (1.53, 1.06-2.22), other anxiety disorder (1.34, 1.06-1.69), or dementia in Alzheimer disease (2.50, 1.40-4.49), but less likely to be diagnosed with psychiatric and behavioral disorders due to use of alcohol (0.41, 0.27-0.61).

Conclusions: As in the general population, there seem to be gender differences with respect to several types of psychiatric diagnoses among older people with intellectual disability. More research is needed to establish if this is due to gender differences in the occurrence of disease, inclination to seek care, health care utilization patterns, or ability to correctly identify disorders.
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http://dx.doi.org/10.1186/s12888-017-1353-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441013PMC
May 2017

Effects on leisure activities and social participation of a case management intervention for frail older people living at home: a randomised controlled trial.

Health Soc Care Community 2017 07 12;25(4):1416-1429. Epub 2017 Mar 12.

Research Group Older People's Health and Person-Centred Care, Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden.

Frailty causes disability and restrictions on older people's ability to engage in leisure activities and for social participation. The objective of this study was to evaluate the effects of a 1-year case management intervention for frail older people living at home in Sweden in terms of social participation and leisure activities. The study was a randomised controlled trial with repeated follow-ups. The sample (n = 153) was consecutively and randomly assigned to intervention (n = 80) or control groups (n = 73). The intervention group received monthly home visits over the course of a year by nurses and physiotherapists working as case managers, using a multifactorial preventive approach. Data collections on social participation, leisure activities and rating of important leisure activities were performed at baseline, 3, 6, 9 and 12 months, with recruitment between October 2006 and April 2011. The results did not show any differences in favour of the intervention on social participation. However, the intervention group performed leisure activities in general, and important physical leisure activities, to a greater extent than the control group at the 3-month follow-up (median 13 vs. 11, P = 0.034 and median 3 vs. 3, P = 0.031 respectively). A statistically significantly greater proportion of participants from the intervention group had an increased or unchanged number of important social leisure activities that they performed for the periods from baseline to 3 months (93.2% vs. 75.4%, OR = 4.48, 95% CI: 1.37-14.58). Even though statistically significant findings in favour of the intervention were found, more research on activity-focused case management interventions is needed to achieve clear effects on social participation and leisure activities.
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http://dx.doi.org/10.1111/hsc.12442DOI Listing
July 2017

Somatic healthcare utilisation patterns among older people with intellectual disability: an 11-year register study.

BMC Health Serv Res 2016 11 9;16(1):642. Epub 2016 Nov 9.

Department of Health Sciences, Faculty of Medicine, Lund University, P.O. Box 157, SE-221 00, Lund, Sweden.

Background: People with intellectual disabilities (ID) are known to have more diseases and are believed to start aging earlier than the general population. The population of older people with ID is growing, but knowledge about their use of healthcare is limited. This study aimed to explore somatic healthcare utilisation patterns among people with ID living in Sweden, in comparison with the general population from 2002 to 2012.

Methods: Participants were a group of people with ID (n = 7936) aged 55 years and older in 2012, and an equal-sized, birth year and sex matched, general population sample (n = 7936). Participants were divided into age groups of 5-year intervals. Data regarding in- and outpatient care were collected from the Swedish National Patient Register.

Results: In the younger age groups, the ID group had higher healthcare utilisation compared with the general population sample, with higher risks for planned and unplanned somatic in- and outpatient care, particularly for unplanned inpatient registrations. Decreasing patterns were seen with age; with lower risks in the ID group for the oldest age groups. This was most evident in planned somatic in- and outpatient care. In those with at least one registration, the ID group had a longer unplanned length of stay in the younger age groups, but fewer planned visits to physicians in somatic outpatient care compared with the control group.

Conclusions: Compared with the general population, people with ID show higher healthcare utilisation in younger age groups. Healthcare utilisation decreases with age, and in old age, fewer people with ID use healthcare compared with the general population. The barriers to accessing planned healthcare for older people with ID need more investigation.
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http://dx.doi.org/10.1186/s12913-016-1880-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103402PMC
November 2016

Subpallial Enhancer Transgenic Lines: a Data and Tool Resource to Study Transcriptional Regulation of GABAergic Cell Fate.

Neuron 2016 Oct;92(1):59-74

Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA. Electronic address:

Elucidating the transcriptional circuitry controlling forebrain development requires an understanding of enhancer activity and regulation. We generated stable transgenic mouse lines that express CreER and GFP from ten different enhancer elements with activity in distinct domains within the embryonic basal ganglia. We used these unique tools to generate a comprehensive regional fate map of the mouse subpallium, including sources for specific subtypes of amygdala neurons. We then focused on deciphering transcriptional mechanisms that control enhancer activity. Using machine-learning computations, in vivo chromosomal occupancy of 13 transcription factors that regulate subpallial patterning and differentiation and analysis of enhancer activity in Dlx1/2 and Lhx6 mutants, we elucidated novel molecular mechanisms that regulate region-specific enhancer activity in the developing brain. Thus, these subpallial enhancer transgenic lines are data and tool resources to study transcriptional regulation of GABAergic cell fate.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063253PMC
http://dx.doi.org/10.1016/j.neuron.2016.09.027DOI Listing
October 2016

Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons.

Neuron 2016 Sep;91(6):1260-1275

Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. Here, we dissected the molecular functions of NKX2-1 by defining its chromosomal binding, regulation of gene expression, and epigenetic state. NKX2-1 binding at distal regulatory elements led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, NKX2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub-ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach provides a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.
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http://dx.doi.org/10.1016/j.neuron.2016.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319854PMC
September 2016

Patterns of Somatic Diagnoses in Older People with Intellectual Disability: A Swedish Eleven Year Case-Control Study of Inpatient Data.

J Appl Res Intellect Disabil 2017 Jan 6;30(1):157-171. Epub 2015 Nov 6.

Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden.

Background: Knowledge about diagnoses patterns in older people with intellectual disabilities is limited.

Methods: The case group (n = 7936) comprised people with intellectual disabilities aged 55 years and older. The control group (n = 7936) was age matched and sex matched. Somatic inpatient diagnoses (2002-2012) were collected retrospectively.

Results: Several diagnoses were in several years significantly more common in the case group, particularly infections [odds ratio (OR) 1.78-4.08]; nervous system (OR 2.06-31.75); respiratory (OR 1.78-4.08) and genitourinary diseases (1.59-11.50); injuries, unspecified symptoms (OR 1.56-4.27); and external causes of morbidity (OR 1.53-4.08). The oldest in the case group had significantly less occurrence of tumours (OR 0.26-0.51), cardiovascular (OR 0.42-0.72), and musculoskeletal diseases (OR 0.32-0.53) than controls.

Conclusions: Older people with intellectual disabilities have higher numbers of some diagnoses, but lower numbers of others. Further research on the reasons for the unique pattern of diagnoses in this group is required.
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http://dx.doi.org/10.1111/jar.12230DOI Listing
January 2017

Lhx6 and Lhx8 promote palate development through negative regulation of a cell cycle inhibitor gene, p57Kip2.

Hum Mol Genet 2015 Sep 12;24(17):5024-39. Epub 2015 Jun 12.

Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY 10010, USA,

Cleft palate is a common birth defect in humans. Therefore, understanding the molecular genetics of palate development is important from both scientific and medical perspectives. Lhx6 and Lhx8 encode LIM homeodomain transcription factors, and inactivation of both genes in mice resulted in profound craniofacial defects including cleft secondary palate. The initial outgrowth of the palate was severely impaired in the mutant embryos, due to decreased cell proliferation. Through genome-wide transcriptional profiling, we discovered that p57(Kip2) (Cdkn1c), encoding a cell cycle inhibitor, was up-regulated in the prospective palate of Lhx6(-/-);Lhx8(-/-) mutants. p57(Kip2) has been linked to Beckwith-Wiedemann syndrome and IMAGe syndrome in humans, which are developmental disorders with increased incidents of palate defects among the patients. To determine the molecular mechanism underlying the regulation of p57(Kip2) by the Lhx genes, we combined chromatin immunoprecipitation, in silico search for transcription factor-binding motifs, and in vitro reporter assays with putative cis-regulatory elements. The results of these experiments indicated that LHX6 and LHX8 regulated p57(Kip2) via both direct and indirect mechanisms, with the latter mediated by Forkhead box (FOX) family transcription factors. Together, our findings uncovered a novel connection between the initiation of palate development and a cell cycle inhibitor via LHX. We propose a model in which Lhx6 and Lhx8 negatively regulate p57(Kip2) expression in the prospective palate area to allow adequate levels of cell proliferation and thereby promote normal palate development. This is the first report elucidating a molecular genetic pathway downstream of Lhx in palate development.
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http://dx.doi.org/10.1093/hmg/ddv223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527495PMC
September 2015

Cost-utility analysis of case management for frail older people: effects of a randomised controlled trial.

Health Econ Rev 2015 Dec 30;5(1):51. Epub 2015 May 30.

Department of Health Sciences, Faculty of Medicine, Lund University, P.O. Box 157, SE-221 00, Lund, Sweden,

Background: To evaluate the effects of a case management intervention for frail older people (aged 65+ years) by cost and utility.

Materials And Methods: One hundred and fifty-three frail older people living at home were randomly assigned to either an intervention (n = 80) or a control group (n = 73). The 1-year intervention was carried out by nurses and physiotherapists working as case managers, who undertook home visits at least once a month. Differences in costs and quality-adjusted life years (QALYs) based on the health-related quality-of-life instruments EQ-5D and EQ-VAS, and also the incremental cost-effectiveness ratio were investigated. All analyses used the intention-to-treat principle.

Results: There were no significant differences between the intervention group and control group for total cost, EQ-5D-based QALY or EQ-VAS-based QALY for the 1-year study. Incremental cost-effectiveness ratio was not conducted because no significant differences were found for either EQ-5D- or EQ-VAS-based QALY, or costs. However, the intervention group had significantly lower levels of informal care and help with instrumental activities of daily living both as costs (3,927 vs. 6,550, p = 0.037) and provided hours (200 vs. 333 hours per year, p = 0.037).

Conclusions: The intervention was cost neutral and does not seem to have affected health-related quality of life for the 1-year study, which may be because the follow-up period was too short. The intervention seems to have reduced hours and cost of informal care and help required with instrumental activities of daily living. This suggests that the intervention provides relief to informal caregivers.
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http://dx.doi.org/10.1186/s13561-015-0051-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449349PMC
December 2015

Effects on healthcare utilization of case management for frail older people: a randomized controlled trial (RCT).

Arch Gerontol Geriatr 2015 Jan-Feb;60(1):71-81. Epub 2014 Oct 18.

Department of Clinical Sciences in Malmö, Faculty of Medicine, Lund University, SE-205 02 Malmö, Sweden; Center for Primary Health Care Research, Faculty of Medicine, Lund University, SE-205 02 Malmö, Sweden.

Objectives: Various healthcare interventions have been launched targeting the growing population of older people. The objective of this study was to investigate the of a case management intervention for frail old people (aged 65+ years) effects on healthcare utilization.

Materials And Methods: The study was conducted in a municipality in southern Sweden and included people aged 65+ years who lived in their ordinary homes, were dependent in two or more activities of daily living (ADL), and had at least two hospital admissions, or four physician visits, in the previous year. One-hundred-fifty-three participants were randomly assigned to either an intervention (n=80) or a control group (n=73). The one-year intervention comprised home visits, at least once a month, by case managers. Group differences were investigated 6-12 and 0-6 months before, and 0-6 and 6-12 months after, baseline.

Results: The intervention group had, compared to the control group, significant lower mean number (0.08 vs. 0.37, p=0.041) and proportion (17.4 vs. 46.9%, p=0.016) of ED visits not leading to hospitalization 6-12 months after baseline. The intervention group also had a significantly lower mean number of visits to physicians in outpatient care 6-12 months after baseline (4.09 vs. 5.29, p=0.047).

Conclusion: The effect on ED visits not leading to hospitalization meant that those in the control group were more likely to visit the ED for reasons that did not require hospitalization, suggesting that they may have been less monitored than the intervention group. The intervention has the potential to reduce the burden on outpatient care and ED.
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http://dx.doi.org/10.1016/j.archger.2014.10.009DOI Listing
June 2015

Loneliness and health care consumption among older people.

Scand J Caring Sci 2015 Sep 14;29(3):435-43. Epub 2014 May 14.

Center for Primary Health Care Research, Department of Clinical Sciences in Malmö, Faculty of Medicine, Lund University, Malmö, Sweden.

Few studies have investigated loneliness in relation to health care consumption among frail older people. The aim of this study was to examine loneliness, health-related quality of life (HRQoL), and health complaints in relation to health care consumption of in- and outpatient care among frail older people living at home. The study, with a cross-sectional design, comprised a sample of 153 respondents aged from 65 years (mean age 81.5 years) or older, who lived at home and were frail. Data was collected utilising structured interviews in the respondent's home assessing demographic data, loneliness, HRQoL and health complaints. Patient administrative registers were used to collect data on health care consumption. Loneliness was the dependent variable in the majority of the analyses and dichotomised. For group comparisons Student's t-test, Mann-Whitney U-test and Chi-square test were used. The results showed that 60% of the respondents had experienced loneliness during the previous year, at least occasionally. The study identified that lonely respondents had a lower HRQoL (p = 0.022), with a higher total number of reported health complaints (p = 0.001), and used more outpatient services including more acute visits at the emergency department, compared to not lonely respondents (p = 0.026). Multiple linear regression analysis showed that a depressed mood was independently associated to total use of outpatient care (B = 7.4, p < 0.001). Therefore, it might not be loneliness, per se, that is the reason for seeking health care. However, reasons for using health care services are difficult to determine due to the complex situation for the frail older person. To avoid emergency department visits and to benefit the well-being of the frail older person, interventions targeting the complex health situation, including loneliness, are suggested.
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http://dx.doi.org/10.1111/scs.12147DOI Listing
September 2015

Lhx6 directly regulates Arx and CXCR7 to determine cortical interneuron fate and laminar position.

Neuron 2014 Apr;82(2):350-64

Department of Psychiatry, Neuroscience Program and the Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address:

Cortical GABAergic interneurons have essential roles for information processing and their dysfunction is implicated in neuropsychiatric disorders. Transcriptional codes are elucidating mechanisms of interneuron specification in the MGE (a subcortical progenitor zone), which regulate their migration, integration, and function within cortical circuitry. Lhx6, a LIM-homeodomain transcription factor, is essential for specification of MGE-derived somatostatin and parvalbumin interneurons. Here, we demonstrate that some Lhx6⁻/⁻ MGE cells acquire a CGE-like fate. Using an in vivo MGE complementation/transplantation assay, we show that Lhx6-regulated genes Arx and CXCR7 rescue divergent aspects of Lhx6⁻/⁻ cell-fate and laminar mutant phenotypes and provide insight into a neonatal role for CXCR7 in MGE-derived interneuron lamination. Finally, Lhx6 directly binds in vivo to an Arx enhancer and to an intronic CXCR7 enhancer that remains active in mature interneurons. These data define the molecular identity of Lhx6 mutants and introduce technologies to test mechanisms in GABAergic interneuron differentiation.
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http://dx.doi.org/10.1016/j.neuron.2014.02.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261952PMC
April 2014

Case management for frail older people - a qualitative study of receivers' and providers' experiences of a complex intervention.

BMC Health Serv Res 2014 Jan 10;14:14. Epub 2014 Jan 10.

Department of Health Sciences, Faculty of Medicine, Lund University, P,O, Box 157, Lund SE-221 00, Sweden.

Background: Case management interventions have been widely used in the care of frail older people. Such interventions often contain components that may act both independently of each other and interdependently, which makes them complex and challenging to evaluate. Qualitative research is needed for complex interventions to explore barriers and facilitators, and to understand the intervention's components. The objective of this study was to explore frail older people's and case managers' experiences of a complex case management intervention.

Methods: The study had a qualitative explorative design and interviews with participants (age 75-95 years), who had received the case management intervention and six case managers who had performed the intervention were conducted. The data were subjected to content analysis.

Results: The analysis gave two content areas: providing/receiving case management as a model and working as, or interacting with, a case manager as a professional. The results constituted four categories: (1 and 2) case management as entering a new professional role and the case manager as a coaching guard, as seen from the provider's perspective; and (3 and 4) case management as a possible additional resource and the case manager as a helping hand, as seen from the receiver's perspective.

Conclusions: The new professional role could be experienced as both challenging and as a barrier. Continuous professional support is seemingly needed for implementation. Mutual confidence and the participants experiencing trust, continuity and security were important elements and an important prerequisite for the case manager to perform the intervention. It was obvious that some older persons had unfulfilled needs that the ordinary health system was unable to meet. The case manager was seemingly able to fulfil some of these needs and was experienced as a valuable complement to the existing health system.
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http://dx.doi.org/10.1186/1472-6963-14-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897947PMC
January 2014

SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

Proc Natl Acad Sci U S A 2013 Apr 15;110(18):7330-5. Epub 2013 Apr 15.

Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.

The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.
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http://dx.doi.org/10.1073/pnas.1220010110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645538PMC
April 2013

Mechanistic differences in the transcriptional interpretation of local and long-range Shh morphogen signaling.

Dev Cell 2012 Nov;23(5):1006-19

Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.

Morphogens orchestrate tissue patterning in a concentration-dependent fashion during vertebrate embryogenesis, yet little is known of how positional information provided by such signals is translated into discrete transcriptional outputs. Here we have identified and characterized cis-regulatory modules (CRMs) of genes operating downstream of graded Shh signaling and bifunctional Gli proteins in neural patterning. Unexpectedly, we find that Gli activators have a noninstructive role in long-range patterning and cooperate with SoxB1 proteins to facilitate a largely concentration-independent mode of gene activation. Instead, the opposing Gli-repressor gradient is interpreted at transcriptional levels, and, together with CRM-specific repressive input of homeodomain proteins, comprises a repressive network that translates graded Shh signaling into regional gene expression patterns. Moreover, local and long-range interpretation of Shh signaling differs with respect to CRM context sensitivity and Gli-activator dependence, and we propose that these differences provide insight into how morphogen function may have mechanistically evolved from an initially binary inductive event.
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http://dx.doi.org/10.1016/j.devcel.2012.09.015DOI Listing
November 2012

Prevalence and predictors of healthcare utilization among older people (60+): focusing on ADL dependency and risk of depression.

Arch Gerontol Geriatr 2012 May-Jun;54(3):e349-63. Epub 2012 Mar 13.

Department of Health Sciences, Faculty of Medicine, Lund University, P.O. Box 157, SE-221 00 Lund, Sweden.

The aim of this study was to investigate healthcare utilization patterns over a six-year period among older people (60+), classified as dependent/independent in Activities of Daily Living (ADL) and/or at/not at risk of depression and to identify healthcare utilization predictors. A sample (n=1402) comprising ten age cohorts aged between 60 and 96 years was drawn from the Swedish National study on Aging and Care (SNAC). Baseline data were collected between 2001 and 2003. Number and length of hospital stays were collected for six years after baseline year. Group differences and mean changes over time were investigated. Healthcare utilization predictors were explored using multiple linear regression analysis. The results revealed that 21-24% had at least one hospital stay in the six years after baseline, 29-37% among ADL dependent subjects and 24-33% among those at risk of depression. There was a significant increase of hospital stays in all groups over time. ADL-dependent subjects and those at risk of depression had significant more hospital stays, except for those at/not at risk of depression in years 2, 4 and 5. The healthcare utilization predictors 5-6 years after baseline were mainly age, previous healthcare utilization and various symptoms and, in 1-2 and 3-4 years after baseline, age, various diagnostic groups and various physical variables. Thus healthcare utilization patterns seem to be similar for the different groups, but it is difficult to find universal predictors. This suggests that different variables should be considered, including both ADL and psychosocial variables, when trying to identify future healthcare users.
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http://dx.doi.org/10.1016/j.archger.2012.02.006DOI Listing
August 2012

SoxB1 transcription factors and Notch signaling use distinct mechanisms to regulate proneural gene function and neural progenitor differentiation.

Development 2008 May 16;135(10):1843-51. Epub 2008 Apr 16.

Ludwig Institute for Cancer Research, Karolinska Institute, Box 240, SE-171 77 Stockholm, Sweden.

The preservation of a pool of neural precursors is a prerequisite for proper establishment and maintenance of a functional central nervous system (CNS). Both Notch signaling and SoxB1 transcription factors have been ascribed key roles during this process, but whether these factors use common or distinct mechanisms to control progenitor maintenance is unsettled. Here, we report that the capacity of Notch to maintain neural cells in an undifferentiated state requires the activity of SoxB1 proteins, whereas the mechanism by which SoxB1 block neurogenesis is independent of Notch signaling. A common feature of Notch signaling and SoxB1 proteins is their ability to inhibit the activity of proneural bHLH proteins. Notch represses the transcription of proneural bHLH genes, while SoxB1 proteins block their neurogenic capacity. Moreover, E-proteins act as functional partners of proneural proteins and the suppression of E-protein expression is an important mechanism by which Notch counteracts neurogenesis. Interestingly, in contrast to the Hes-dependent repression of proneural genes, suppression of E-protein occurs in a Hes-independent fashion. Together, these data reveal that Notch signaling and SoxB1 transcription factors use distinct regulatory mechanisms to control proneural protein function and to preserve neural cells as undifferentiated precursors.
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http://dx.doi.org/10.1242/dev.020180DOI Listing
May 2008
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