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Background: PSA kinetics after curative radiotherapy for prostate cancer is an important part of the posttreatment evaluation. We analysed PSA bounce occurrence after combined high dose rate brachytherapy (HDR-BT) and external radiotherapy (ERT)., Material & Methods: We analysed 623 patients treated from 1995 to 2008. The median age was 66 years (47-79). The median initial PSA was 12 ng/ml (0.1-224). Neoadjuvant endocrine therapy was given to 429 patients. ERT was given with 2 Gy fractions to 50 Gy and HDR-BT in two 10 Gy fractions. The median follow-up was 11 years (range 2-266 months). PSA bounce was defined as a temporary rise in PSA >0.2 ng/ml. PSA failure was defined according to the Phoenix definition., Results: PSA bounce occurred in 159 patients (26%), where 56 patients had a bounce amplitude >2 ng/ml and 31 patients had multiple bounces. Median time to bounce peak was 15 (3-103) months with a median bounce value of 1.5 (0.3-12)ng/ml. Younger age and lower Gleason scores were associated with PSA bounce. In a Cox regression analysis with PSA bounce as a time-dependent covariate and adjusted for other prognostic factors, PSA bounce was associated with a lower risk for PSA failure (HR = 0.42; 95% confidence interval 0.26-0.70)., Conclusion: PSA bounce after HDR-BT combined with ERT is common and associated with a good prognosis. As the relapse risk after an early bounce is very low, the findings should alert clinicians not to initiate salvage treatment too early. Research in prospective identification of PSA bounce is clinically relevant., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Secondary mechanical hyperalgesia to punctate mechanical stimuli and light touch (allodynia) are prominent symptoms in neuropathic pain states. In a combined microneurographic and psychophysical study, we investigated the role of mechano-insensitive (silent) nociceptors regarding induction. Electrical thresholds of mechano-sensitive and silent nociceptors were assessed by microneurography with two closely spaced intracutaneous electrodes (i.c.) and a transcutaneous configuration (t.c.) in the foot dorsum. For t.c. stimulation there was a marked difference between silent (median, quartiles; 60, 50-70 mA, n = 63) and mechano-sensitive fibers (3, 2-5 mA, n = 107). In silent fibers, thresholds were lower for i.c. stimulation (16, 14-19 mA, n = 8), but higher in mechano-sensitive units (6, 5-6 mA, n = 13). Corresponding psychophysical tests showed no difference between the stimulation configuration for pain thresholds, but lower thresholds for the i.c. stimulation in axon reflex erythema (12 vs. 21 mA), punctate hyperalgesia (9 vs. 15 mA) and allodynia (15 vs. 18 mA). Punctate hyperalgesia was evoked at very low stimulation frequencies of 1/20 Hz (7/7 subjects), whereas the induction of an axon reflex flare required stimulation at 1/5 Hz. Electrical stimulation which is sufficient to excite mechano-insensitive C nociceptors can induce secondary mechanical hyperalgesia even at low frequencies supporting a role of such low-level input to clinical pain states. Thus, differential nociceptor class-specific input to the spinal cord adds to the complexity of modulatory mechanisms that determine nociceptive processing in the spinal cord., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: High-dose-rate brachytherapy (HDR-BT) has optimal prerequisites in radiotherapy of prostate cancer (PC) with a conformal dose distribution and high doses per fraction giving a biological dose escalation. We report the outcome after HDR-BT and external beam radiotherapy (EBRT) after 20 years of experience., Material and Methods: The study includes 623 patients, median age of 66 years, treated from 1995 to 2008 and a median follow up of 11 years (range 2-266 months). Androgen deprivation therapy was given to 429 patients (69%). The HDR-BT was given with two 10 Gy fractions and the EBRT with 2 Gy fractions to 50 Gy., Results: The 10-year PC-specific survival was 100%, 92%, 91%, and 75% for low-, intermediate-, high- and very high-risk patients respectively, and the 10-year probability of PSA relapse was 0%, 21%, 33%, and 65% respectively. The 10-year actuarial prevalence for ≥grade 2 GU- and GI-toxicities were 28% and 12% respectively and for ≥grade 3, 4% and 1% respectively. Urethral stricture was the most frequent GU complication with a 10-year actuarial incidence of 10%. Treatment without dose constraints for the urethra conferred a higher incidence 18%, compared to 5% after 2003 (p < 0.001). Sixteen patients experienced grade 4 GU toxicity, of which 13 were treated before 2003. No grade 4 rectal toxicity was seen., Conclusion: The combination of EBRT and HDR-BT with adequate dose constraints to risk organs provides satisfactory long-term tumour control even in high-risk patients. GI toxicity stabilised but GU toxicity progressed during the 10-year follow up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In connection with the Chernobyl fallout and the subsequent deposition of radionuclides in Sweden, Swedish municipalities launched a measurement program to monitor the external radiation exposure. This program encompasses measurements of the ambient dose equivalent rate 1 m above ground at selected locations, and repeats those measurements at the same locations at 7-month intervals. Measurement data compiled from the seven locations with the highest deposition were combined with data from aerial surveys since May 1986 of ground deposition of 137 Cs, high-resolution gamma spectrometry performed at four locations in May 1986, and measurements from fixed continuous air gamma rate monitoring stations from 28 April to 15 May 1986. Based on these datasets, a model of the time pattern of the external dose rate in terms of ambient dose equivalent rate from the Chernobyl fallout was developed. The decrease in the ambient dose equivalent rate could, on average, be described by a four-component exponential decay function with effective half-times of 6.8 ± 0.3 d, 104 ± 26 d, 1.0 ± 0.02 y and 5.5 ± 0.09 y, respectively. The predominant contributions to the external dose rate in the first month were from short-lived fission products superseded by 134 Cs and then 137 Cs. Integrated over 70 y and using extrapolation of the curve fits, our model predicts that 137 Cs contributes about 60% and 134 Cs contributes about 30% of the external effective dose at these seven locations. The projected time-integrated 70 y external effective dose to an unshielded person from all nuclides per unit total activity deposition of 137 Cs is estimated to be 0.29 ± 0.0.08 mSv/(kBq m -2 ). These results are in agreement with those found in Chernobyl contaminated Russian forest areas, and emphasize the usefulness of maintaining a long-term and regular measurement program in contaminated areas., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The central role of the mitochondrion for cellular and organismal metabolism is well known, yet its functional role in evolution has rarely been featured in leading international conferences. Moreover, the contribution of mitochondrial genetics to complex disease phenotypes is particularly important, and although major advances have been made in the field of genomics, mitochondrial genomic data have in many cases been overlooked. Accumulating data and new knowledge support a major contribution of this maternally inherited genome, and its interactions with the nucleus, to both major evolutionary processes and diverse disease phenotypes. These advances encouraged us to assemble the first Mitochondrial Genomics and Evolution (MGE) meeting-an SMBE satellite and Israeli Science foundation international conference (Israel, September 2017). Here, we report the content and outcome of the MGE meeting (https://www.mge2017.com/; last accessed November 5, 2017)., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Objectives: To determine the internal consistency and the underlying components of our translated and adapted Swedish version of the General Medical Council's multisource feedback questionnaires (GMC questionnaires) for physicians and to confirm which aspects of good medical practice the latent variable structure reflected., Methods: From October 2015 to March 2016, residents in family medicine in Sweden were invited to participate in the study and to use the Swedish version to perform self-evaluations and acquire feedback from both their patients and colleagues. The validation focused on internal consistency and construct validity. Main outcome measures were Cronbach's alpha coefficients, Principal Component Analysis, and Confirmatory Factor Analysis indices., Results: A total of 752 completed questionnaires from patients, colleagues, and residents were analysed. Of these, 213 comprised resident self-evaluations, 336 were feedback from residents' patients, and 203 were feedback from residents' colleagues. Cronbach's alpha coefficients of the scores were 0.88 from patients, 0.93 from colleagues, and 0.84 in the self-evaluations. The Confirmatory Factor Analysis validated two models that fit the data reasonably well and reflected important aspects of good medical practice. The first model had two latent factors for patient-related items concerning empathy and consultation management, and the second model had five latent factors for colleague-related items, including knowledge and skills, attitude and approach, reflection and development, teaching, and trust., Conclusions: The current Swedish version seems to be a reliable and valid tool for formative assessment for resident physicians and their supervisors. This needs to be verified in larger samples.

Heparan sulfate (HS) mediates the activity of various growth factors including TGF-β. Heparanase is an endo-glucuronidase that specifically cleaves and modifies HS structure. In this study, we examined the effect of heparanase expression on TGF-β1-dependent signaling activities. We found that overexpression of heparanase in human tumor cells (i.e., Fadu pharyngeal carcinoma, MCF7 breast carcinoma) attenuated TGF-β1-stimulated Smad phosphorylation and led to a slower cell proliferation. TGF-β1-stimulated Akt and Erk phosphorylation was also affected in the heparanase overexpression cells. This effect involved the enzymatic activity of heparanase, as overexpression of mutant inactive heparanase did not affect TGF-β1 signaling activity. Analysis of HS isolated from Fadu cells revealed an increase in sulfation of the HS that had a rapid turnover in cells overexpressing heparanase. It appears that the structural alterations of HS affect the ability of TGF-β1 to signal via its receptors and elicit a growth response. Given that heparanase expression promotes tumor growth in most cancers, this finding highlights a crosstalk between heparanase, HS, and TGF-β1 function in tumorigenesis.

Objective: To evaluate histologically the progressive development and underlying mechanisms of chronic tympanic membrane perforation (TMP) in a rat model using a two-weeks ventilation tube (VT) treatment combined with topical application of mitomycin C/dexamethasone (VT-M/D), compared with normal tympanic membrane and acute TMPs., Methods: Fifty male Sprague-Dawley rats were divided into three experimental groups: a normal control group (n = 5), an acute TMP group (n = 5) (i.e. 3 days post-myringotomy) and a VT-M/D group (n = 40). The TMs were regularly assessed by otoscopy. The normal control animals were sacrificed on day 0 and the acute TMP group was sacrificed 3 days post-myringotomy for histological and immunohistochemical evaluations. The VT-M/D group was sacrificed at various time points - 14 and 17 days, 3, 4, 6, 8 and 10 weeks., Results: On longitudinal histological examination, compared with normal TM and acute TMP, the perforation edges at the later time points illustrated thickened stratified squamous epithelium rimming around the edges, significant increase in keratin and collagen deposition, increased macrophage infiltration as well as reduced cellular proliferation. Three phases of TMP healing process were identified - the acute healing phase (3-17 days), the transition phase (3-4 weeks) and the chronic phase (6-10 weeks)., Conclusion: Based on the histological results of this study, the progressive development of chronic TMPs appeared to be associated with increased epidermal thickening, collagen and keratin deposition, macrophage infiltration and reduced cellular proliferation. After the 3-4 weeks of transition phase, the TMPs seemed to have transformed into a non-healing chronic TMP between 6 and 10 weeks., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The acoustic and mechanical properties of silk membranes of different thicknesses were tested to determine their suitability as a repair material for tympanic membrane perforations. Membranes of different thickness (10-100μm) were tested to determine their frequency response and their resistance to pressure loads in a simulated ear canal model. Their mechanical rigidity to pressure loads was confirmed by tensile testing. These membranes were tested alongside animal cartilage, currently the strongest available myringoplasty graft as well as paper, which is commonly used for simpler procedures. Silk membranes showed resonant frequencies within the human hearing range and a higher vibrational amplitude than cartilage, suggesting that silk may offer good acoustic energy transfer characteristics. Silk membranes were also highly resistant to simulated pressure changes in the middle ear, suggesting they can resist retraction, a common cause of graft failure resulting from chronic negative pressures in the middle ear. Part of this strength can be explained by the substantially higher modulus of silk films compared with cartilage. This allows for the production of films that are much thinner than cartilage, with superior acoustic properties, but that still provide the same level of mechanical support as thicker cartilage. Together, these in vitro results suggest that silk membranes may provide good hearing outcomes while offering similar levels of mechanical support to the reconstructed middle ear., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Hypothesis: In the literature several surgical methods have been reported that aim to improve hearing in patients with isolated malleus fractures; however, it is still not clear which method gives the best results., Background: In this study, laser Doppler vibrometry (LDV) was used to compare the outcome of different surgical methods on malleus fractures in fresh frozen human temporal bones., Methods: Fractured malleus shafts of defrosted human temporal bones were repaired with bone cement, with a malleus prosthesis from cortical bone, or with a partial ossicular replacement prosthesis (PORP) from cortical bone, and LDV measurements were obtained for analysis., Results: The best result was achieved with the bone cement only, applied directly at the site of the fracture. The malleus prosthesis and the PORP gave similar results., Conclusion: All three surgical methods gave good results, but when the distal end of the fractured malleus can be attached close to the proximal end, the technique using only cement tends to be the best option. If the parts are too far apart, a malleus prosthesis or a PORP would be good options.

To evaluate coping strategies among patients with Amyotrophic lateral sclerosis starting with diagnosis and during the disease progression, as well as investigate changes and correlations between coping strategies, emotional well-being and physical function. A total of 36 patients participated in the study. The patients filled out the Hospital Anxiety and Depression Scale and the Motor Neuron Disease Coping Scale. Physical function was measured using the revised ALS functional rating scale. Data were collected regularly from diagnosis and over a two years period. As a way to cope with the disease patients relied on both problem focused and emotional focused strategies. The use of coping strategies remained stable. Both physical disabilities and emotional well-being was related to some coping strategies, with some variation during the disease progression. Moreover, some coping strategies were related to symptoms of anxiety and depression. Irrespective of whether the coping strategies affect the emotional well-being or vice versa, the results show the importance of early and continuous evaluation of coping and emotional well-being to ease the emotional distress and provide support to the patient so that he/she can cope with the disease during the disease progression., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Chronic tympanic membrane perforation (TMP) in a clinical setting may attract surgical intervention. With the advent of modern biomaterials, new options are available for myringoplasty but safety and efficacy need evaluation in a chronic TMP animal model. The aim of this study was to evaluate the efficacy of ventilation tube (VT) insertion in conjunction with topical application of mitomycin C/dexamethasone (M/D) for the creation of chronic TMP in rats., Methods: Thirty male Sprague-Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were divided into three experimental groups: spontaneous healing (myringotomy control), VT insertion for 2 weeks and VT insertion for 2 weeks in conjunction with topical application of M/D (VT-M/D). All TMs were regularly assessed by otoscopy for 10 weeks and then animals were sacrificed for histological evaluation., Results: In the VT-M/D group, seven out of ten (70%) perforations were patent at 10 weeks (mean patency, 57.9 days; P<0.01). The VT group had two out of ten (20%) perforations patent at 10 weeks (mean patency, 26.5 days; P<0.01), while all TMPs from the myringotomy control group were closed by day 9 (mean patency, 7.2 days). Histologically, the TMPs patent at week 10 had a stratified squamous epithelialized rim, keratinocyte layer thickening around the perforation edge as well as increased collagen deposition and macrophage infiltration., Conclusion: Chronic TMP in a rat model was successfully created by VT insertion and the efficacy was increased in combination with topical application of M/D., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

GTPases typically switch between an inactive, OFF conformation and an active, ON conformation when a GDP ligand is replaced by GTP. Their ON/OFF populations and activity thus depend on the stabilities of four protein complexes, two apo-protein forms, and GTP/GDP in solution. A complete characterization is usually not possible experimentally and poses major challenges for simulations. We review the most important methodological challenges and we review thermodynamic data for two GTPases involved in translation of the genetic code: archaeal Initiation Factors 2 and 5B (aIF2, aIF5B). One main challenge is the multiplicity of states and conformations, including those of GTP/GDP in solution. Another is force field accuracy, especially for interactions of GTP/GDP with co-bound divalent Mg(2+) ions. The calculation of electrostatic free energies also poses specific challenges, and requires careful protocols. For aIF2, experiments and earlier simulations showed that it is a "classic" GTPase, with distinct ON/OFF conformations that prefer to bind GTP and GDP, respectively. For aIF5B, we recently proposed a non-classic mechanism, where the ON/OFF states differ only in the protonation state of Glu81 in the nucleotide binding pocket. This model is characterized here using free energy simulations. The methodological analysis should help future studies, while the aIF2, aIF5B examples illustrate the diversity of ATPase/GTPase mechanisms. This article is part of a Special Issue entitled Recent developments of molecular dynamics., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In 2011, the IFCC Task Force on Clinical Applications of Cardiac Bio-Markers (TF-CB) was formed, with the purpose of providing evidence based educational materials to assist all biomarker users, i.e. laboratorians, clinicians, researchers, in-vitro diagnostics and regulatory agencies, in better understanding important analytical and clinical aspects of established and novel cardiac biomarkers for use in clinical practice and research. The goal of the task force was to promulgate the same information conjointly through the in vitro diagnostic industry to the laboratory, emergency department and cardiologists. The initial undertaking of the TF-CB, which is comprised of laboratory medicine scientists, emergency medicine physicians and cardiologists, was to address two key issues pertaining to implementing high-sensitivity cardiac troponin (hs-cTn) assays in clinical practice: the 99th percentile upper reference limit (URL) and calculating serial change values in accord with the Universal Definition of AMI. The highlights of both concepts from IFCC statements are described., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: This study deals with serious malpractice claims within Swedish Healthcare Direct, the national telephone helpline in Sweden. At least 33 claims of malpractice have been filed since the service was created in 2003. Although a low number, consequences have been tragic. Research in Swedish telenursing on contributing systemic and organizational factors and consequences of malpractice claims is sparse., Objective: The objective was to explore the direct experience of telenurses' and call center managers' involvement in actual malpractice claims-with focus on factors that may have contributed to the claims-and on the consequences of the claims., Methods: Six telenurses and five managers agreed to participate in open-ended interviews. A directed content analysis approach was chosen to analyze the transcribed interview texts., Results: Stress, shiftwork, fatigue, multitasking, understaffing, and factors embedded in the system could have contributed to the malpractice claims. Safety management was treated locally, with no attempts at organizational reforms., Discussion: The solitary nature of the telenursing task emphasizes the importance of an organization, which works toward providing an environment where telenurses can feel safe and supported. This may require, in turn, a change in both organizational and professional attitudes toward safety and risk of error. The greatest hinder may be healthcare providers themselves. If the difficulties in recruiting participants for this study are any indication, reaching out to healthcare providers who remain silent may be the greatest challenge.

Autism spectrum disorder is characterized by social impairments and behavioural inflexibility. In this pilot study, the feasibility and outcomes of a 6-week acceptance and commitment therapy-based skills training group were evaluated in a special school setting using a quasi-experimental design (acceptance and commitment therapy/school classes as usual). A total of 28 high-functioning students with autism spectrum disorder (aged 13-21 years) were assessed using self- and teacher-ratings at pre- and post-assessment and 2-month follow-up. All participants completed the skills training, and treatment satisfaction was high. Levels of stress, hyperactivity and emotional distress were reduced in the treatment group. The acceptance and commitment therapy group also reported increased prosocial behaviour. These changes were stable or further improved at the 2-month follow-up. Larger studies are needed to further evaluate the benefits of acceptance and commitment therapy for autism spectrum disorder., (© The Author(s) 2013.)

Looking at Open Science and Open Data from a broad perspective. This is the idea behind "Scientific data sharing: an interdisciplinary workshop", an initiative designed to foster dialogue between scholars from different scientific domains which was organized by the Istituto Italiano di Antropologia in Anagni, Italy, 2-4 September 2013.We here report summaries of the presentations and discussions at the meeting. They deal with four sets of issues: (i) setting a common framework, a general discussion of open data principles, values and opportunities; (ii) insights into scientific practices, a view of the way in which the open data movement is developing in a variety of scientific domains (biology, psychology, epidemiology and archaeology); (iii) a case study of human genomics, which was a trail-blazer in data sharing, and which encapsulates the tension that can occur between large-scale data sharing and one of the boundaries of openness, the protection of individual data; (iv) open science and the public, based on a round table discussion about the public communication of science and the societal implications of open science. There were three proposals for the planning of further interdisciplinary initiatives on open science. Firstly, there is a need to integrate top-down initiatives by governments, institutions and journals with bottom-up approaches from the scientific community. Secondly, more should be done to popularize the societal benefits of open science, not only in providing the evidence needed by citizens to draw their own conclusions on scientific issues that are of concern to them, but also explaining the direct benefits of data sharing in areas such as the control of infectious disease. Finally, introducing arguments from social sciences and humanities in the educational dissemination of open data may help students become more profoundly engaged with Open Science and look at science from a broader perspective.

Purpose: To discuss treatment modalities for aggressive posterior retinopathy of prematurity (AP-ROP)., Methods: The medical charts of all infants with AP-ROP at Uppsala University Hospital, Sweden, during a 2-year period (2009 and 2010) were reviewed. Eight infants (16 eyes) with a mean gestational age of 23.8 weeks and a mean birth weight of 592 g were treated with laser and/or intravitreal injections of bevacizumab (0.4 and 0.625 mg). RetCam photography was used to document the retinal appearance before and after treatment., Results: All infants (16 eyes) had AP-ROP in zone I. Mean time at initial treatment was 34 weeks postmenstrual age. Two eyes (one infant) were only treated with laser, and six eyes (three infants) were treated with laser therapy or cryopexy and, because of lack of regression, with bevacizumab as salvage therapy. Eight eyes (four infants) were treated with a first-line bevacizumab injection and four of these eyes (two infants) with additional laser ablation for continued disease progression in zone II. Macular dragging occurred in one eye of one infant primarily treated with laser., Conclusions: Given the high complication rate of the extensive laser treatment for zone I ROP, it is worth considering anti-vascular endothelial growth factor treatment as an alternative therapy. Further knowledge concerning side effects and long-term ocular and systemic outcome is warranted before this drug becomes general clinical practice., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

Neuroinflammation is typically observed in neurodegenerative diseases such as Alzheimer's disease, as well as after traumatic injury and pathogen infection. Resident immune cells, microglia and astrocytes, are activated and joined by blood-borne monocytes that traverse the blood-brain barrier and convert into activated macrophages. The activated cells express various cytokines, chemokines and proteolytic enzymes. To study the role of heparan sulfate proteoglycans in neuroinflammation, we employed a transgenic mouse overexpressing heparanase, an endoglucuronidase that specifically degrades heparan sulfate side chains. Neuroinflammation was induced by systemic challenge with lipopolysaccharide, or by localized cerebral microinjection of aggregated amyloid-β peptide, implicated in Alzheimer's disease. Lipopolysaccharide-treated control mice showed massive activation of resident microglia as well as recruitment of monocyte-derived macrophages into the brain parenchyma. Microinjection of aggregated amyloid-β elicited a similar inflammatory response, albeit restricted to the injection site, which led to dispersion and clearance of the amyloid. In the heparanase-overexpressing mice, all aspects of immune cell recruitment and activation were significantly attenuated in both inflammation models, as was amyloid dispersion. Accordingly, an in vitro blood-brain barrier model constructed from heparanase-overexpressing cerebral vascular cells showed impaired transmigration of monocytes compared to a corresponding assembly of control cells. Our data indicate that intact heparan sulfate chains are required at multiple sites to mediate neuroinflammatory responses, and further point to heparanase as a modulator of this process, with potential implications for Alzheimer's disease.

Private health information websites run by laypeople are more often visited than websites of official agencies. Understanding the role of weblogs in dietetic communication-i.e., sharing personal perceptions on healthy eating-is still lacking. This study aims to describe the nature of noncommercial Swedish blogs with fruits and vegetables (F&V)-related content and to identify different blogger types. A qualitative content analysis with abduction was performed on 50 weblogs. Most bloggers presented themselves as women. Only one-third reported their age (range 17 to over 50 years). The bloggers had either an active or passive influential purpose, and they approached F&V through either lived or mediated experiences. From these two dimensions, four F&V blogger ideal types were identified: the Persuader, the Authority, the Exhibitionist, and the Mediator. Particularly women wrote about their lived experiences close to the personal level, whereas men were more equally distributed across the different ideal types. Self-expression (typical for the Exhibitionist) and purpose to influence others' diets (typical for the Persuader and the Authority) were frequently expressed in these weblogs. The current findings on blogging purposes, approaches, and F&V blogger types may help to improve online dietetic communication, which sets new challenges for media strategies of health and nutritional professionals.

The neurosteroid dehydroepiandrosterone (DHEA) is formed locally in the CNS and has been implicated in several processes essential for CNS function, including control of neuronal survival. An important metabolic pathway for DHEA in the CNS involves the steroid hydroxylase CYP7B1. In previous studies, CYP7B1 was identified as a target for estrogen regulation in cells of kidney and liver. In the current study, we examined effects of estrogens on CYP7B1-mediated metabolism of DHEA in primary cultures of rat astrocytes and co-cultures of rat CNS cells. Astrocytes, which interact with neurons in several ways, are important for brain neurosteroidogenesis. We found that estradiol significantly suppressed CYP7B1-mediated DHEA hydroxylation in primary mixed CNS cultures from fetal and newborn rats. Also, CYP7B1-mediated DHEA hydroxylation and CYP7B1 mRNA were markedly suppressed by estrogen in primary cultures of rat astrocytes. Interestingly, diarylpropionitrile, a well-known agonist of estrogen receptor β, also suppressed CYP7B1-mediated hydroxylation of DHEA. Several previous studies have reported neuroprotective effects of estrogens. The current data indicate that one of the mechanisms whereby estrogen can exert protective effects in the CNS may involve increase of the levels of DHEA by suppression of its metabolism., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Significant progress has been made in understanding the functional organisation of the cell nucleus. Still many questions remain to be answered about the relationship between the spatial organisation of the nucleus and the regulation of the genome function. There are many conflicting data in the field making it very difficult to merge published results on mammalian cells into one model on subnuclear chromatin organisation. The fission yeast, Schizosaccharomyces pombe, over the last decades has emerged as a valuable model organism in understanding basic biological mechanisms, especially the cell cycle and chromosome biology. In this review we describe and compare the nuclear organisation in mammalian and fission yeast cells. We believe that fission yeast is a good tool to resolve at least some of the contradictions and unanswered questions concerning functional nuclear architecture, since S. pombe has chromosomes structurally similar to that of human. S. pombe also has the advantage over higher eukaryotes in that the genome can easily be manipulated via homologous recombination making it possible to integrate the tools needed for visualisation of chromosomes using live-cell microscopy. Classical genetic experiments can be used to elucidate what factors are involved in a certain mechanism. The knowledge we have gained during the last few years indicates similarities between the genome organisation in fission yeast and mammalian cells. We therefore propose the use of fission yeast for further advancement of our understanding of functional nuclear organisation.

Backgrounds: In a recent small study, patients with autoantibodies to cardiac troponin (cTnaAb) had higher cardiac troponin I (cTnI) release during an episode of acute coronary syndrome (ACS) than patients without cTnaAb and continued to have higher long-term levels of cTnI. However, the prognostic importance of the occurrence of cTnaAb is unknown., Methods: In 957 nonST-elevation ACS patients cTnaAb and cTnI were analyzed at randomization and after 6 months. Outcomes were assessed through 5 years., Results: Seven and 11% of the patients were cTnaAb positive at inclusion and 6months, respectively. The cardiac troponin I (cTnI) concentration at inclusion was independently associated with the development of cTnaAb (OR 1.53, 95% CI 1.25-1.88). The presence of cTnaAb was associated with an increased cTnI level at 6 months (OR 2.39, 95% CI 1.50-3.81). cTnaAb was not independently associated with death and AMI during follow-up (HR 0.97, 95% CI 0.61-1.54)., Conclusion: Development of cTnaAb after an episode of nonST-elevation ACS is associated with the acute myocardial damage, but occurs only in a minority of patients. Furthermore, the presence of cTnaAb is associated with chronically elevated cTnI concentrations. However, the occurrence of cTnaAb is not associated with an adverse long-term prognosis., (2010 Elsevier B.V. All rights reserved.)

Gaining knowledge in the field of health promotion may help physiotherapists acquire a new understanding of the way movement promotes health, as related to environmental influences. The aim of the present study was to describe how physiotherapists working in a programme of health promotion in compulsory school understand and approach their work. Seven physiotherapists in primary care, working partly with health promotion in compulsory school, were interviewed. A descriptive design of qualitative content analysis was chosen to analyse interviews that had already been conducted in a local evaluation of the programme. This resulted in a main theme, described as Perceiving and Supporting Coherence. This understanding and approach were discussed in relation to challenges of a historically embedded constitution of physiotherapy when entering the area of health promotion in compulsory school.

Objectives: This study sought to evaluate the analytical and clinical performance of the novel hypersensitive cardiac troponin I (cTnI) prototype assay from Beckman Coulter (Fullerton, California)., Background: Studies on patients with acute coronary syndromes and on seemingly healthy subjects have shown that even very minor elevations of cardiac troponins are associated with an increased risk of death. However, the normal plasma levels of cardiac troponins are still not known., Methods: cTnI plasma levels were measured in 542 healthy subjects, 319 men (age 59.9 +/- 11.8 years) and 213 women (age 59.8 +/- 13.1 years), and in 1,503 randomly selected patients of the GUSTO IV (Global Utilization of Strategies To open Occluded arteries IV) cohort with unstable angina and non-ST-segment elevation myocardial infarctions (MIs)., Results: The cTnI levels at 10% coefficient of variation and 20% coefficient of variation imprecision were 0.0033 and 0.0016 microg/l, respectively. The cTnI levels were measurable in >95% of the healthy subjects. The median level of healthy subjects <60 years of age was 0.0032 microg/l (range 0.0011 to 0.0079 microg/l) with the 99th percentile being 0.010 microg/l. No sex differences were observed. A receiver-operator characteristic curve analysis showed an optimal discrimination between healthy subjects and patients at 0.0064 microg/l with a sensitivity of 84.8% (95% confidence interval: 82.8% to 86.6%) and specificity of 89.7% (95% confidence interval: 86.8% to 92.2%). Outcomes as to death and/or MI were significantly different at this level (p < 0.01) in the GUSTO IV cohort., Conclusions: The novel high-sensitivity cTnI prototype assay from Beckman Coulter allows for the first time the measurement of cTnI levels in almost all healthy subjects. Our data indicate that the assay may be a powerful aid in the diagnosis and outcome prediction of patients with suspected myocardial ischemia and question any definition of myocardial infarction.

Aims: Previous studies have indicated the negative effects of socioeconomic deprivation on health status and morbidity. Nevertheless, the economic assignment systems for pharmaceutical benefits in Sweden do not take socioeconomic status (SES) into account. The aim of the study was, therefore, to compare reimbursement for subsidized drugs at primary healthcare centres (HCCs) with differing socioeconomic conditions in relation to real costs. The word reimbursement is used to denote economic compensation to the HCCs from the county council for drug benefit costs., Methods: The numbers of individuals dispensed drugs, total costs and reimbursement at five HCCs with different socioeconomic conditions were compared. A socioeconomic index was calculated for each HCC on the basis of information from the municipality registries on income (with negative sign), assistance allowance, education, foreign background, and unemployment. Register data on drug benefit costs were retrieved from the National Corporation of Pharmacies (Apoteket AB) and the Swedish Prescribed Drug Register at the National Board of Health and Welfare. Data on listed and unlisted citizens at the Kalmar County Council and on public statistics from registers at the HCC municipalities where the HCCs were situated were retrieved., Results: There was an almost inverse linear relationship between total cost compensation and the socioeconomic index (n = 5; r =-0.99; p = 0.001). The HCCs with the lowest SES received lower cost compensation., Conclusions: HCCs responsible for citizens with lower SES appeared to be disadvantaged by the prevalent reimbursement system in Sweden, thereby increasing differences in the state of health of the citizens. This, in turn, hampers health preventing programmes and lifestyle interventions. An HCC-specific standardized summary of socioeconomic burden is presented.

In this study, we examined whether 1alpha,25-dihydroxyvitamin D(3) (calcitriol), phenobarbital, and the antiretroviral drug efavirenz, drugs used by patient groups with high incidence of low bone mineral density, could affect the 25-hydroxylase activity or expression of human 25-hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells. Fibroblasts express the 25-hydroxylating enzymes CYP2R1 and CYP27A1. LNCaP cells were found to express two potential vitamin D 25-hydroxylases-CYP2R1 and CYP2J2. The presence in different cells of nuclear receptors vitamin D receptor (VDR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR) was also determined. Phenobarbital suppressed the expression of CYP2R1 in fibroblasts and CYP2J2 in LNCaP cells. Efavirenz suppressed the expression of CYP2R1 in fibroblasts but not in LNCaP cells. CYP2J2 was slightly suppressed by efavirenz, whereas CYP27A1 was not affected by any of the two drugs. Calcitriol suppressed the expression of CYP2R1 in both fibroblasts and LNCaP cells but had no clear effect on the expression of either CYP2J2 or CYP27A1. The vitamin D(3) 25-hydroxylase activity in fibroblasts was suppressed by both calcitriol and efavirenz. In LNCaP cells, consumption of substrate (1alpha-hydroxyvitamin D(3)) was used as indicator of metabolism because no 1alpha,25-dihydroxyvitamin D(3) product could be determined. The amount of 1alpha-hydroxyvitamin D(3) remaining in cells treated with calcitriol was significantly increased. Taken together, 25-hydroxylation of vitamin D(3) was suppressed by calcitriol and drugs. The present study provides new information indicating that 25-hydroxylation of vitamin D(3) may be regulated. In addition, the current results may offer a possible explanation for the impaired bone health after treatment with certain drugs.

The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A recent study demonstrated the association of TNFSF4 haplotypes located in the upstream region with risk for or protection from systemic lupus erythematosus (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality-control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904 (pooled OR=1.38, P=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This first replication study confirms the association of genetic variation in the upstream region of TNFSF4 with susceptibility to SLE.

Object: There is currently no biologic therapy to repair or restore a degenerated intervertebral disc. A potential solution may rest with embryonic stem cells (ESCs), which have a potential to grow indefinitely and differentiate into a variety of cell types in vitro. Prior studies have shown that ESCs can be encouraged to differentiate toward specific cell lineages by culture in selective media and specific growth environment. Among these lineages, there are cells capable of potentially producing nucleus pulposus (NP) in vivo. In this investigation, the authors studied ESCderived chondroprogenitors implanted into a degenerated disc in a rabbit. For this purpose, a rabbit model of disc degeneration was developed., Methods: A percutaneous animal model of disc degeneration was developed by needle puncture of healthy intact discs in 16 New Zealand white rabbits. Series of spine MR imaging studies were obtained before disc puncture and after 2, 6, and 8 weeks. Prior to implantation, murine ESCs were cultured with cis-retinoic acid, transforming growth factor beta, ascorbic acid, and insulin-like growth factor to induce differentiation toward a chondrocyte lineage. After confirmation by MR imaging, degenerated disc levels were injected with chondrogenic derivatives of ESCs expressing green fluorescent protein. At 8 weeks post-ESC implantation, the animals were killed and the intervertebral discs were harvested and analyzed using H & E staining, confocal fluorescent microscopy, and immunohistochemical analysis. Three intervertebral disc groups were analyzed in 16 rabbits, as follows: 1) Group A, control: naïve, nonpunctured discs (32 discs, levels L4-5 and L5-6); 2) Group B, experimental control: punctured disc (16 discs, level L2-3); and 3) Group C, experimental: punctured disc followed by implantation of chondroprogenitor cells (16 discs, level L3-4)., Results: The MR imaging studies confirmed intervertebral disc degeneration at needle-punctured segments starting at approximately 2 weeks. Postmortem H & E histological analysis of Group A discs showed mature chondrocytes and no notochordal cells. Group B discs displayed an intact anulus fibrosus and generalized disorganization within fibrous tissue of NP. Group C discs showed islands of notochordal cell growth. Immunofluorescent staining for notochordal cells was negative for Groups A and B but revealed viable notochordal-type cells within experimental Group C discs, which had been implanted with ESC derivatives. Notably, no inflammatory response was noted in Group C discs., Conclusions: This study illustrates a reproducible percutaneous model for studying disc degeneration. New notochordal cell populations were seen in degenerated discs injected with ESCs. The lack of immune response to a xenograft of mouse cells in an immunocompetent rabbit model may suggest an as yet unrecognized immunoprivileged site within the intervertebral disc space.

Aim: This paper is a report of a study to describe the different ways of understanding work among a group of Swedish telenurses., Background: Telenursing is an expanding service in many western countries and telenursing work is likely to be understood in a variety of ways. The way in which a person understands work influences how work is performed. Telenursing demands high levels of competence., Method: A qualitative interview study was conducted during 2004-2005. Twelve of the 20 telenurses working at a call centre in Sweden were interviewed, five of them twice because of organizational changes. The 17 interviews were analysed using a phenomenographic approach., Findings: Five different categories were identified in the data: (1) Assess, refer and give advice to the caller (2) Support the caller (3) Strengthen the caller (4) Teach the caller and (5) Facilitate the caller's learning. The first category can be seen as a base for telenursing work and was the only category used by some telenurses. The second category has components of traditional caring and the third is a coaching function. The fourth category contains a teaching component, but the fifth is the only category where the caller's learning is in focus. Telenurses who reported the fifth way also included all other ways of understanding work. Hence, this seems to be the most comprehensive way of understanding work., Conclusion: The categories together constitute a telenursing 'workmap'. This 'workmap' can be used for reflection to expand telenurses' current understanding of work, and hence promote competence development. Telenurses need to be aware of their role in public health education.

CYP7B1, a cytochrome P450 enzyme, metabolizes several steroids involved in hormonal signaling including 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), an estrogen receptor agonist, and dehydroepiandrosterone, a precursor for sex hormones. Previous studies have suggested that CYP7B1-dependent metabolism involving dehydroepiandrosterone or 3beta-Adiol may play an important role for estrogen receptor beta-mediated signaling. However, conflicting data are reported regarding the influence of different CYP7B1-related steroids on estrogen receptor beta activation. In the present study, we investigated CYP7B1-mediated conversions of dehydroepiandrosterone and 3beta-Adiol in porcine microsomes and human kidney cells. As part of these studies, we compared the effects of 3beta-Adiol (a CYP7B1 substrate) and 7alpha-hydroxy-dehydroepiandrosterone (a CYP7B1 product) on estrogen receptor beta activation. The data obtained indicated that 3beta-Adiol is a more efficient activator, thus lending support to the notion that CYP7B1 catalysis may decrease estrogen receptor beta activation. Our data on metabolism indicate that the efficiencies of CYP7B1-mediated hydroxylations of dehydroepiandrosterone and 3beta-Adiol are very similar. The enzyme catalyzed both reactions at a similar rate and the K(cat)/K(m) values were in the same order of magnitude. A high dehydroepiandrosterone/3beta-Adiol ratio in the incubation mixtures, similar to the ratio of these steroids in many human tissues, strongly suppressed CYP7B1-mediated 3beta-Adiol metabolism. As the efficiencies of CYP7B1-mediated hydroxylation of dehydroepiandrosterone and 3beta-Adiol are similar, we propose that varying steroid concentrations may be the most important factor determining the rate of CYP7B1-mediated metabolism of dehydroepiandrosterone or 3beta-Adiol. Consequently, tissue-specific steroid concentrations may have a strong impact on CYP7B1-dependent catalysis and thus on the levels of different CYP7B1-related steroids that can influence estrogen receptor beta signaling.

Progress in our understanding of the roles of genetics in pain and its management is described. New techniques are discussed, along with some potential uses of gene therapy. Relative gene expression, polymorphisms, and specific genes that influence interindividual responses to pharmacotherapy for pain are described.

Purpose: To evaluate the effect of a 7-week Qigong intervention on subjects with Fibromyalgia Syndrome (FMS)., Methods: The study was a controlled randomized study with repeated measures. Fifty-seven FMS female subjects were randomly assigned to an intervention group (n = 29) or a waiting-list control group (n = 28). After completion of the experimental part, the control group received the same intervention. Collection of data was made at pre- and post-treatment and at 4-month follow-up for both groups., Results: During the experimental part of the study, significant improvements were found for the intervention group, at posttreatment, regarding different aspects of pain and psychological health and distress. Almost identical results were found for the combined group. At 4-month follow-up, the majority of these results were either maintained or improved., Conclusion: The overall results show that Qigong has positive and reliable effects regarding FMS. A high degree of completion, 93%, and contentment with the intervention further support the potential of the treatment. The results of the study are encouraging and suggest that Qigong intervention could be a useful complement to medical treatment for subjects with FMS.

Colorectal cancer is the third most common cancer worldwide and the second most common cancer in Europe. Cumulative relative survival curves for both cancer of the colon and cancer of the rectum generally plateau after approximately 6-8 years. When this occurs, "population" or "statistical" cure is reached. We analyzed data from the Finnish Cancer Registry over a 50-year period using methods that simultaneously estimate the proportion of patients cured of disease (the cure fraction) and the survival time distribution of the "uncured" group. Our primary aim was to investigate temporal trends in the cure fraction and median survival of the uncured by age group for both cancer of the colon and rectum. For both cancers, the cure fraction has increased dramatically over time for all age groups. However, the difference in the cure fraction between age groups has reduced over time, particularly for cancer of the colon. Median survival in the uncured has also increased over time in all age groups but there still remains an inverse relationship between age and median survival, with shorter median survival with increasing age. The reasons for these impressive increases in patient survival are complex, but are highly likely to be strongly related to many improvements in cancer care over this same time period., (Copyright (c) 2007 Wiley-Liss, Inc.)

It has been proposed that as a result of human adaptation to different climates, mitochondrial genes have been affected by natural selection. To further study the selective pressure on human mitochondrial DNA, we have analysed polymorphism at the gene, domain and nucleotide site level in four geographic regions. The ratio of non-synonymous relative to synonymous substitutions is elevated for ATP6 in North Asia, ND3 in Africa and cytb in Europe relative to other mitochondrial genes. In addition, non-synonymous substitutions appear nearly five times more frequently outside core functional domains as compared with within functional domains. Therefore, a large part of the rate variation between mitochondrial genes is explained by differences in the length of the functional domain relative to the length of the gene. The accumulation of non-synonymous substitutions in the ATP6 gene among sequences from North Asia has been a gradual process over many thousands of years, consistent with relaxed purifying selection rather than recent strong selective sweeps. It is not necessary to invoke adaptive selection to explain the pattern of polymorphism in mitochondrial genes, when the most parsimonious explanation is relaxed purifying selection and the action of genetic drift.

The introduction of various techniques for minimally invasive parathyroidectomy (MIP) and minimally invasive thyroid surgery (MITS) have changed both the conceptual and surgical approach to parathyroid disease and single thyroid nodules. Perceived advantages of minimally invasive surgery both among clinicians and patients, have been a major factor in the development of new surgical techniques, as well as refinement in preoperative localisation techniques. Worldwide the number of patients being operated on using MIP or MITS has steadily increased. At some major centres as many as 70% of patients with primary hyperparathyroidism have their operation using MIP. In this review we discuss the underlying pathology and investigative procedures, as well as the various techniques used, all of which now have excellent outcomes at a minimal cost and with minimal complications. Based on our own experience we recommend the use of a lateral focused mini-incision for both MIP and MIT since they both use standard equipment and standard dissection techniques familiar to all experienced endocrine surgeons.

An integrated model for the regulation of glucose and insulin concentrations following intravenous glucose provocations in healthy volunteers and type 2 diabetic patients was developed. Data from 72 individuals were included. Total glucose, labeled glucose, and insulin concentrations were determined. Simultaneous analysis of all data by nonlinear mixed effect modeling was performed in NONMEM. Integrated models for glucose, labeled glucose, and insulin were developed. Control mechanisms for regulation of glucose production, insulin secretion, and glucose uptake were incorporated. Physiologically relevant differences between healthy volunteers and patients were identified in the regulation of glucose production, elimination rate of glucose, and secretion of insulin. The model was able to describe the insulin and glucose profiles well and also showed a good ability to simulate data. The features of the present model are likely to be of interest for analysis of data collected in antidiabetic drug development and for optimization of study design.

The present article reports on an empirical intervention aimed at testing the modern theory of competence at work. Competence is primarily defined as a way of understanding one's work and work tasks. In this study, a pretest and posttest design was used to measure job satisfaction, organizational climate, and prevalence of stress-related symptoms. In terms of these outcome variables, several aspects of job satisfaction increased significantly, whereas organizational climate and stress-related symptoms remained stable.

Objective: To determine whether low birth weight increases the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood and early adolescence., Method: In a population-based sample of 1,480 twin pairs born in the period 1985-1986 ascertained from the Swedish Twin Registry, birth weight was collected prospectively through the Medical Birth Registry. ADHD symptoms were measured with a 14-item checklist covering DSM-III-R criteria (parental rating) at age 8 to 9 years and 13 to 14 years. We used both a dichotomous approach for birth weight (>400 g or 15% weight difference) and ADHD (eight or more symptoms) and continuous measures to investigate between- and within-twin pair effects., Results: Our results showed that low birth weight was a risk factor for symptoms of ADHD and the associations did not diminish when we controlled for genetic influence. The lighter twin in birth weight-discordant pairs had on average 13% higher ADHD symptom score at age 8 to 9 years (p = .006) and 12% higher ADHD score at age 13 to 14 years (p = .018) compared with the heavier twin. The genetic correlations suggest modest or no genetic overlap between birth weight and ADHD., Conclusions: The hypothesis that low birth weight is associated with the development of ADHD symptoms was supported in this prospective twin study. Fetal growth restriction seems to represent a modest but fairly consistent environmental influence on the development of ADHD symptoms.

Patients with cancer have an increased risk of developing venous thromboembolism (VTE) due to a hypercoagulable state associated with malignancy. This risk is further complicated in patients undergoing cancer-related surgery due to immobility, other cancer treatments, and biologic changes associated with surgery. Despite this relatively high risk of VTE, many patients are not prescribed adequate prophylaxis in the pre- or post-operative periods. This article reviews available measures for thromboprophylaxis in light of current guidelines., ((c) 2007 Wiley-Liss, Inc.)

Studies of the polysaccharide hyaluronan (hyaluronic acid) started more than a century ago in Uppsala. This article describes the general development of hyaluronan research from an Uppsala point of view and is thus strongly biased. The readers are referred to other reviews for a more objective description of the history.

The objective of this study was to investigate the long-term psychological and mental health outcomes among survivors of a disastrous hotel fire. A 25-year follow-up investigation among adolescent and young adult survivors of a fire disaster was conducted in Borås, Sweden. A self-evaluation questionnaire and four self-rating scales - the IES-22, PTSS-10, GHQ-28 and SoC - were sent by mail to the participants. The results from the self-reported data showed low levels of psychiatric illness. Moreover, the respondents reported a low level of traumatic stress symptoms. More than 50% of the participants stated that the fire had a determining effect on their lives. Sixteen (21.3%) respondents indicated that the fire still had an impact on their daily lives. Differences between men and women were reported in most of the self-rating scales. The results indicate that a traumatizing experience (such as a fire disaster) still had a small effect on psychological health in a long-term perspective.

Variation inherent to each session in any recording situation has to be mastered to obtain informative mean values and differences. Variation due to time trend and unsteady consecutive readings versus inter-arm variations in blood pressure (BP) in the operator-initiated, self-initiated, and sleep recordings were studied by oscillometry. They were small in operator-initiated recordings, increased in self-recordings, and were paramount in sleep. A passive supine patient and simultaneous recordings with cuffs placed in equal horizontal positions are essential conditions for the estimation of a real mean inter-arm difference. The relative variation of pulse pressure (PP), compared with other components, was largest within each situation. Most of the systolic BP (SBP)/diastolic BP (DBP) variation in sleep was due to unequal vertical cuff distances to the heart level. Only sleep PP was independent of the vertical position of cuffs. A plot of inter-arm differences can visualize systematic errors in sequences of sleep SBP/DBP. As is well known, every doubling of variation (SD) requires quadrupling the number of independent recordings in order to retain the same size of confidence interval (CI) for a mean value.