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1.
BMC Psychol ; 11(1): 409, 2023 Nov 23.
Article En | MEDLINE | ID: mdl-37996858

AIMS: To perform the first psychometric analysis of the Norwegian version of the eHLQ using confirmative factor analysis (CFA) procedures in a population of patients admitted to hospital using a cross-sectional design. The eHLQ consists of 35 items capturing the 7-dimensional eHealth Literacy Framework (eHLF) which describes users' attributes, user's interaction with technologies and user's experience with digital health systems. METHODS: The 7 independent scales of the eHLQ was translated from Danish and culturally adapted into the Norwegian language following a standardised protocol. Assessment of construct validity of the eHLQ was undertaken using data from a cross-sectional survey of 260 patients hospitalized at a Norwegian University Hospital in the Oslo area during a two-week period in June 2021. The analysis included using correlation analysis (Pearsons R), internal consistency (Cronbach's alpha) and confirmatory factor analysis (CFA). RESULTS: All factor loadings were high to acceptable (i.e. > 0.6), except for five items which had somewhat lower loadings. Regarding internal consistency, alpha ranged from 0.73 to 0.90. For optimal CFA fit for the different scale models, correlated residuals were required for five of the seven scales. Overall our analysis shows an intermediate fit of the orginal construct. Scale intercorrelations were all below 0.8, indicating an overall acceptable discriminant validity between the 7 dimensions. CONCLUSIONS: The results from the CFA analysis indicate that for almost all 7 eHLQ scales, an acceptable model fit was achieved. The 260 hospitalized patients included in this study represented a variety of diagnoses, recruited from a geographically limited area. Further studies on psychometric properties of the Norwegian version of eHLQ in larger samples, diverse settings and by using more comprehensive approaches are warranted.


Literacy , Telemedicine , Humans , Cross-Sectional Studies , Reproducibility of Results , Surveys and Questionnaires , Language , Telemedicine/methods , Norway , Factor Analysis, Statistical , Psychometrics/methods
2.
Virchows Arch ; 483(6): 873-878, 2023 Dec.
Article En | MEDLINE | ID: mdl-37428268

Papillary mesothelioma in situ (PMIS) is a rare and enigmatic disease. Most instances manifest as lesions of the peritoneal serosa. The pathogenesis and behavior of peritoneal PMIS are still poorly understood, and separation from benign well differentiated peritoneal mesothelial tumors (WDPMT) may be challenging. We describe the 15-year long course of a PMIS in an adult male in which inactivating mutations of BAP1, encoding BRCA1 associated protein 1 (BAP1), were identified. Tumor samples were obtained on 2 occasions more than 8y apart. In both samples, the tumor cells were bland, with occasional focal infiltration into the stalks of larger papillary lesions. However, no invasion into subserosal adipose tissue was identified. In both samples the tumor cells did not express nuclear BAP1. Comprehensive genomic analysis of the initial tumor sample revealed a somatic inactivating mutation in BAP1 (predicted effect, Y223*) and a somatic variant of IRS2 (A701_V702insAA). An additional inactivating mutation in BAP1 (predicted effect, T69fs*5) was detected in the later sample. The patient did not receive any treatment and is still alive 15 years after initial presentation. Our experience supports the view that peritoneal PMIS may follow an indolent course for many years and prompts the question whether these tumors should uniformly be treated aggressively.


Mesothelioma, Malignant , Peritoneal Neoplasms , Adult , Humans , Male , Biomarkers, Tumor/analysis , Mutation , Peritoneal Neoplasms/pathology , Peritoneum/pathology , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/metabolism
3.
Georgian Med News ; (335): 54-59, 2023 Feb.
Article En | MEDLINE | ID: mdl-37042589

The purpose of this study was to analyze the effects of cadmium toxicity on rat embryogenesis when exposed to other heavy metal citrates. Despite the variety of scientific publications discussing the influence of cadmium on mammalian postnatal development, the effect of this metal on embryogenesis has not yet been sufficiently studied. In this experimental study, cadmium chloride was administered to experimental pregnant female Wistar rats at a daily dose of 1.0 mg/kg. Rats were allocated at random into groups receiving either cadmium chloride alone or additional zinc citrate, cerium citrate, or nanocomposite (based on iodine, sulfur, and selenium citrate). The control group received distilled water at an equivalent volume. In each group, operational intervention occurred at the 13th and 20th day of gestation to assess numbers of live fetuses, corpora lutea, pre-implantation losses, post-implantation losses, and total implantation losses. When cadmium chloride alone was administered, a pronounced embryotoxic effect was observed, manifested as a significant decrease in the number of live fetuses. Experimental groups which received cadmium chloride with zinc citrate, cerium citrate, or nanocomposite had an increased number of live fetuses and corpora lutea, as well as a decreased number of implantation losses, compared to the group which only received cadmium chloride. Each combination of cerium, zinc, and selenium nanocomposite citrates demonstrated a compensatory effect on all measures of embryogenesis impacted by cadmium embryotoxicity. Thus, administration of the citrates of cerium, zinc, and selenium nanocomposite reduces cadmium embryotoxicity and its accumulation in the body.


Cadmium Chloride , Citrates , Embryonic Development , Metals, Heavy , Animals , Female , Pregnancy , Rats , Cadmium Chloride/toxicity , Citrates/pharmacology , Embryo Implantation/drug effects , Mammals , Rats, Wistar , Chronic Disease , Embryonic Development/drug effects , Metals, Heavy/pharmacology , Metals, Heavy/toxicity , Cerium/pharmacology , Nanocomposites , Zinc Compounds/pharmacology , Selenium Compounds/pharmacology , Iodine Compounds/pharmacology , Sulfur Compounds/pharmacology
4.
Skin Health Dis ; 1(2): e17, 2021 Jun.
Article En | MEDLINE | ID: mdl-35664978

Objective: To explore health literacy (HL) profiles within a cohort of people with psoriasis. A cluster approach identifies groups of individuals that have similar HL profiles. The method unmasks sub-groups with particular HL strengths, or subgroups with limitations, which require tailored healthcare services to improve. Methods: A cross-sectional sample of 792 patients from the Norwegian Climate Helio Therapy Programme in Gran Canaria participated. The HL questionnaire assessed nine HL dimensions. Using Ward's Hierarchical Clustering Method (Stata version 16), we looked for subgroups of patients across the dimensions. We also explored whether these clusters had specific demographic features and associations to outcomes such as psoriasis knowledge, quality of life and self-management capacity. Result: The analysis revealed four unique clusters identifying clinically meaningful subgroups. Two groups stood out as especially interesting. One cluster representing 26.6% of the sample presented severe HL limitations associated with lower psoriasis knowledge, quality of life, self-management and self-efficacy. HL domains connected to cooperation with healthcare professionals showed deficient scores. The other cluster included a smaller percentage (7.7%) with high HL compared to the total sample. This cluster was associated with higher self-management, quality of life and better self-efficacy. Conclusion: The cluster analysis revealed substantial differences in HL profiles within the sample. These results support the importance of a holistic understanding of the HL needs and the vulnerabilities within a psoriasis cohort. Implementing one size fits all approaches, may not be sufficient in psoriasis context to target HL.

5.
Scand J Pain ; 20(3): 491-498, 2020 07 28.
Article En | MEDLINE | ID: mdl-32101532

Background and aims Psoriasis is a common chronic skin condition, causing skin lesions with thickened and scaling skin, as well as erythema and inflammation that may involve painful sores, cracks, and pustules. Previously psoriasis was regarded as a painless skin condition. However, over the past decade studies show that skin pain is a frequently reported and bothersome symptom in patients with psoriasis. There is however a lack of rich narratives describing the experience of skin pain in these patients. The aims of this qualitative study were therefore to explore in depth how patients experience psoriasis-related skin pain, and how they deal with it. Methods Thirteen patients with psoriasis were recruited from a dermatology ward and outpatient clinic. One of the investigators (TML) performed individual, semi-structured interviews at an undisturbed room in the hospital. Interviews were thematically analyzed using the method of Systematic Text Condensation as described by Malterud (2012). Results Three main themes were identified from the interviews. First, the skin pain experience was complex. Patients used a variety of adjectives and metaphors to describe their pain, and their skin was sensitive to stimuli of every-day activities. Itch was a common cosymptom, and could both mask pain but also cause severe pain due to excessive scratching and damage to the skin. Second, skin pain had a negative impact on patients' life. Skin pain reduced their physical activity level, impaired their sleep, and made them irritable, depressed, unconcentrated on tasks, as well as withdrawn from other people and social activities. Third, patients dealt with their skin pain in various ways. Although some took action to relieve the pain and distract themselves from pain, most of the patients applied maladaptive and passive coping strategies such as put up with it, avoid painful activities, become fearful or trivialize their pain. Conclusions The experience of psoriasis related skin pain is complex. The pain has a major negative impact on patients' life in terms of physical, emotional, cognitive, and social functions. Patients use a variety of adaptive but most frequently maladaptive coping strategies in order to deal with their skin pain. Implications This study provides new and in-depth knowledge on psoriasis related skin pain. This information is valuable for further work on pain assessment tools and pain management recommendations customized for skin pain experienced by patients with psoriasis.


Pain/psychology , Psoriasis/psychology , Quality of Life , Adaptation, Psychological , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pain/etiology , Pain Management/methods , Pain Management/psychology , Psoriasis/complications , Qualitative Research , Skin/physiopathology
6.
Qual Life Res ; 28(10): 2641-2650, 2019 Oct.
Article En | MEDLINE | ID: mdl-31187410

PURPOSE: Quality of life (QOL) is an important concept in the field of health and medicine. QOL is a complex concept that is interpreted and defined differently within and between disciplines, including the fields of health and medicine. The aims of this study were to systematically review the literature on QOL in medicine and health research and to describe the country of origin, target groups, instruments, design, and conceptual issues. METHODS: A systematic review was conducted to identify research studies on QOL and health-related quality of life (HRQOL). The databases Scopus, which includes Embase and MEDLINE, CINAHL, and PsycINFO were searched for articles published during one random week in November 2016. The ten predefined criteria of Gill and Feinstein were used to evaluate the conceptual and methodological rigor. RESULTS: QOL research is international and involves a variety of target groups, research designs, and QOL measures. According to the criteria of Gill and Feinstein, the results show that only 13% provided a definition of QOL, 6% distinguished QOL from HRQOL. The most frequently fulfilled criteria were: (i) stating the domains of QOL to be measured; (ii) giving a reason for choosing the instruments used; and (iii) aggregating the results from multiple items. CONCLUSION: QOL is an important endpoint in medical and health research, and QOL research involves a variety of patient groups and different research designs. Based on the current evaluation of the methodological and conceptual clarity of QOL research, we conclude that the majority QOL studies in health and medicine have conceptual and methodological challenges.


Environmental Health/standards , Medicine/standards , Quality of Life/psychology , Humans
7.
Br J Dermatol ; 180(6): 1506-1516, 2019 06.
Article En | MEDLINE | ID: mdl-30597532

BACKGROUND: Health literacy (HL) - the ability to seek, understand and utilize health information - is important for good health. Suboptimal HL has been associated with poorer health outcomes in other chronic conditions, although this has not previously been studied in patients with psoriasis. OBJECTIVES: To investigate the HL strengths and weaknesses of a cohort of patients with moderate-to-severe psoriasis. Another aim was to examine possible associations between patients' quality of life, their demographic, clinical and self-management characteristics, and dimensions of HL. METHODS: A cross-sectional study was conducted. Data were collected from a cohort of patients with psoriasis who had received climate helio therapy from 2011 to 2016 (n = 825). HL was assessed by the Health Literacy Questionnaire (HLQ). The association between HL domains, demographic, clinical and self-management variables were analysed using bivariate correlation and a four-step linear multiple regression model. RESULTS: The scores on all HLQ dimensions indicated lower health literacy than other populations. The linear regression models showed a significant association between HL, quality of life and self-management variables, with higher HL predicting higher quality of life, self-efficacy and psoriasis knowledge. Sex, educational attainment, age and disease severity had less influence on health literacy. CONCLUSIONS: Improving HL may be a useful strategy for reducing disparities in self-management skills for patients with psoriasis. Interventions that aim to reduce disease severity and increase psoriasis knowledge, self-efficacy and quality of life may positively increase HL.


Health Literacy , Patient Education as Topic , Psoriasis/therapy , Self-Management , Adult , Aged , Aged, 80 and over , Chronic Disease/therapy , Cohort Studies , Cross-Sectional Studies , Feasibility Studies , Female , Humans , Male , Middle Aged , Psoriasis/diagnosis , Quality of Life , Severity of Illness Index , Young Adult
8.
Nat Commun ; 8(1): 1187, 2017 10 30.
Article En | MEDLINE | ID: mdl-29084962

Current neuromodulatory strategies to enhance motor recovery after stroke often target large brain areas non-specifically and without sufficient understanding of their interaction with internal repair mechanisms. Here we developed a novel therapeutic approach by specifically activating corticospinal circuitry using optogenetics after large strokes in rats. Similar to a neuronal growth-promoting immunotherapy, optogenetic stimulation together with intense, scheduled rehabilitation leads to the restoration of lost movement patterns rather than induced compensatory actions, as revealed by a computer vision-based automatic behavior analysis. Optogenetically activated corticospinal neurons promote axonal sprouting from the intact to the denervated cervical hemi-cord. Conversely, optogenetically silencing subsets of corticospinal neurons in recovered animals, results in mistargeting of the restored grasping function, thus identifying the reestablishment of specific and anatomically localized cortical microcircuits. These results provide a conceptual framework to improve established clinical techniques such as transcranial magnetic or transcranial direct current stimulation in stroke patients.


Motor Cortex/physiopathology , Pyramidal Tracts/physiopathology , Stroke/therapy , Transcranial Direct Current Stimulation/methods , Algorithms , Animals , Axons/physiology , Biomechanical Phenomena/physiology , Female , Humans , Nerve Regeneration/physiology , Neurons/physiology , Optogenetics/methods , Rats, Long-Evans , Recovery of Function/physiology , Stroke/physiopathology
9.
Brachytherapy ; 16(2): 373-377, 2017.
Article En | MEDLINE | ID: mdl-28039010

PURPOSE: The aim of this study was to compare the organ-at-risk doses to the rectum and the bladder in postoperative endometrial cancer patients who receive high-dose-rate vaginal brachytherapy (HDR-VB), when using three different methods of treatment planning: (Workflow A) individualized treatment planning before every fraction, (Workflow B) individualized treatment planning for first fraction only), and (Workflow C) using a template plan based on applicator choice and prescription specifics without patient-specific imaging or planning (standardized template approach). METHODS AND MATERIALS: Alternative plans were retrospectively created using workflows B and C for 22 patients who previously received postoperative HDR-VB using a vaginal cylinder and planned using Workflow A for endometrial cancer. The rectum and bladder were contoured on the CTs used for each fraction for dose comparison between the three methods. D50, D2cc, D1cc, D0.1cc, and V100 of the bladder and the rectum were compared using the two-sided Wilcoxon signed-rank test. RESULTS: A total of 123 fractions were available for comparison. For Workflow A vs. Workflow B, there was no significant difference for any rectal or bladder dosimetric parameter. For Workflow A vs. Workflow C, Workflow A delivered a significantly higher median dose to the rectum than Workflow C for D50, D2cc, D1cc, and V100. Workflow C delivered a significantly higher dose to the bladder than Workflow A: D2cc, D1cc, D0.1cc, and V100. However, the magnitudes of the differences were small; the dose index difference was >75 cGy for only two fractions. CONCLUSION: Plan standardization in HDR-VB may result in considerable time and cost savings with minimal organ-at-risk dose differences.


Brachytherapy/methods , Endometrial Neoplasms/radiotherapy , Organs at Risk , Radiation Dosage , Radiotherapy Planning, Computer-Assisted/methods , Brachytherapy/adverse effects , Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/surgery , Female , Humans , Radiotherapy Dosage , Radiotherapy, Adjuvant/adverse effects , Rectum/diagnostic imaging , Retrospective Studies , Tomography, X-Ray Computed , Urinary Bladder/diagnostic imaging , Vagina , Workflow
10.
Metab Eng ; 30: 130-140, 2015 Jul.
Article En | MEDLINE | ID: mdl-26037463

In microbial processes for production of proteins, biomass and nitrogen-containing commodity chemicals, ATP requirements for nitrogen assimilation affect product yields on the energy producing substrate. In Saccharomyces cerevisiae, a current host for heterologous protein production and potential platform for production of nitrogen-containing chemicals, uptake and assimilation of ammonium requires 1 ATP per incorporated NH3. Urea assimilation by this yeast is more energy efficient but still requires 0.5 ATP per NH3 produced. To decrease ATP costs for nitrogen assimilation, the S. cerevisiae gene encoding ATP-dependent urease (DUR1,2) was replaced by a Schizosaccharomyces pombe gene encoding ATP-independent urease (ure2), along with its accessory genes ureD, ureF and ureG. Since S. pombe ure2 is a Ni(2+)-dependent enzyme and Saccharomyces cerevisiae does not express native Ni(2+)-dependent enzymes, the S. pombe high-affinity nickel-transporter gene (nic1) was also expressed. Expression of the S. pombe genes into dur1,2Δ S. cerevisiae yielded an in vitro ATP-independent urease activity of 0.44±0.01 µmol min(-1) mg protein(-1) and restored growth on urea as sole nitrogen source. Functional expression of the Nic1 transporter was essential for growth on urea at low Ni(2+) concentrations. The maximum specific growth rates of the engineered strain on urea and ammonium were lower than those of a DUR1,2 reference strain. In glucose-limited chemostat cultures with urea as nitrogen source, the engineered strain exhibited an increased release of ammonia and reduced nitrogen content of the biomass. Our results indicate a new strategy for improving yeast-based production of nitrogen-containing chemicals and demonstrate that Ni(2+)-dependent enzymes can be functionally expressed in S. cerevisiae.


Cation Transport Proteins/biosynthesis , Gene Expression , Nickel/metabolism , Saccharomyces cerevisiae , Schizosaccharomyces pombe Proteins/biosynthesis , Urease/biosynthesis , Cation Transport Proteins/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Schizosaccharomyces/genetics , Schizosaccharomyces/metabolism , Schizosaccharomyces pombe Proteins/genetics , Urease/genetics
11.
Br J Radiol ; 87(1043): 20140362, 2014 Nov.
Article En | MEDLINE | ID: mdl-25226047

OBJECTIVE: A new dosimetric variable, dose-dropping speed (DDS), was proposed and used to evaluate normal tissue sparing among stereotactic radiosurgery (SRS) plans with different prescription isodose lines. METHODS: 40 plans were generated for 8 intracranial SRS cases, prescribing to isodose levels (IDLs) ranging from 50% to 90% in 10% increments. Whilst maintaining similar coverage and conformity, plans at different IDLs were evaluated in terms of normal tissue sparing using the proposed DDS. The DDS was defined as the greater decay coefficient in a double exponential decay fit of the dose drop-off outside the planning target volume (PTV), which models the steep portion of the drop-off. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. RESULTS: Among all plans, the DDS was found to be the lowest for the prescription at 90% IDL and the highest for the prescription at 60% or 70%. The beam profile slope change in the penumbra and its field size dependence were explored and given as the physical basis of the findings. CONCLUSION: A variable was proposed for SRS plan quality evaluation. Using this measure, prescriptions at 60% and 70% IDLs were found to provide best normal tissue sparing. ADVANCES IN KNOWLEDGE: A new variable was proposed based on which normal tissue sparing was quantitatively evaluated, comparing different prescription IDLs in SRS.


Brain Neoplasms/surgery , Radiosurgery/methods , Humans , Radiotherapy Dosage , Treatment Outcome
12.
Br J Dermatol ; 171(6): 1458-69, 2014 Dec.
Article En | MEDLINE | ID: mdl-25143061

BACKGROUND: Psoriasis is a common skin disease with extensive comorbidity risks, which may affect multiple aspects of life. Self-management is essential for skin treatment and lifestyle choices, but few disease-specific tailored self-management and educational programmes appear to be available. OBJECTIVES: To evaluate the effects of a 3-month individual motivational interviewing intervention in patients with psoriasis (with a total follow-up of 6 months) after climate therapy/heliotherapy (CHT). METHODS: A randomized controlled trial with 169 patients with psoriasis was conducted in the context of CHT at Gran Canaria, Spain. The main outcome measures were Self-Administered Psoriasis Area and Severity Index (SAPASI) and Health Education Impact Questionnaire (heiQ), and the secondary outcomes were illness perception, psoriasis knowledge and lifestyle change assessments. Outcomes were measured at baseline, after 3 weeks of CHT, and 3 months and 6 months later. RESULTS: There were significant overall treatment effects in the study group in terms of the SAPASI score, three self-management domains of heiQ and the self-efficacy scores (P < 0∙05). The lifestyle change parameters were significantly better in the study group. Illness perception differed between the groups at 3 months (P = 0∙014), and psoriasis knowledge was significantly better in the study group at 6 months (P = 0∙017). CONCLUSIONS: A 3-month motivational interviewing intervention following CHT had positive overall effects on disease severity, self-efficacy, psoriasis knowledge and health behaviour change. This approach has the potential to be an important complement to medical management, self-management and education in patients with psoriasis.


Motivational Interviewing/methods , Psoriasis/therapy , Self Care/methods , Telephone , Adult , Aged , Attitude to Health , Female , Humans , Male , Middle Aged , Patient Education as Topic/methods , Psoriasis/psychology , Risk Reduction Behavior , Risk-Taking , Treatment Outcome , Young Adult
13.
Science ; 344(6189): 1250-5, 2014 Jun 13.
Article En | MEDLINE | ID: mdl-24926013

The brain exhibits limited capacity for spontaneous restoration of lost motor functions after stroke. Rehabilitation is the prevailing clinical approach to augment functional recovery, but the scientific basis is poorly understood. Here, we show nearly full recovery of skilled forelimb functions in rats with large strokes when a growth-promoting immunotherapy against a neurite growth-inhibitory protein was applied to boost the sprouting of new fibers, before stabilizing the newly formed circuits by intensive training. In contrast, early high-intensity training during the growth phase destroyed the effect and led to aberrant fiber patterns. Pharmacogenetic experiments identified a subset of corticospinal fibers originating in the intact half of the forebrain, side-switching in the spinal cord to newly innervate the impaired limb and restore skilled motor function.


Motor Cortex/physiopathology , Myelin Proteins/antagonists & inhibitors , Pyramidal Tracts/injuries , Pyramidal Tracts/physiology , Recovery of Function , Stroke Rehabilitation , Animals , Female , Immunotherapy/methods , Nogo Proteins , Physical Conditioning, Animal , Prosencephalon/physiopathology , Rats , Rats, Long-Evans
14.
Scand J Psychol ; 54(6): 508-14, 2013 Dec.
Article En | MEDLINE | ID: mdl-24111658

This study investigated the mental health of people with psoriasis undergoing patient education in climate therapy. A prospective design included a baseline assessment and two follow-ups after a 3-week patient education program. Participants were 254 adults. Positive mental health was measured by the mental health continuum short form (0-70), and negative mental health by the emotional distress subscale (1-4) of the health education impact questionnaire. Paired-samples t-tests were used to evaluate changes in mental health from baseline to follow-up. Multiple linear regression was used to analyse the ability of socio-demographic and clinical variables and emotional distress to predict changes in positive mental health. To predict change in negative mental health we repeated the same analysis but with a change in negative mental health as a dependent variable and positive mental health as an independent variable. The results show that positive mental health and health-related emotional distress improved significantly from before to after the intervention by 7.1 points, p < 0.001 and 0.21 points, p < 0.001) respectively. At the second follow-up, health-related emotional distress remained significantly improved compared with baseline levels by 0.11 points, p = 0.004. The longer participants had lived with psoriasis ( ß = 146, p = 0.027), and the presence of co-morbid health problems (ß  =  111, p = 0.051) the greater the improvement in the positive mental health immediately after the intervention. No predictors were identified for negative mental health. This study indicates that the promotion of positive mental health needs to be integrated into the climate therapy program, and sustained in their home context.


Climatotherapy , Mental Health , Psoriasis/psychology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Patient Education as Topic , Prospective Studies , Psoriasis/therapy , Quality of Life/psychology , Surveys and Questionnaires , Treatment Outcome , Young Adult
15.
Mucosal Immunol ; 5(5): 555-66, 2012 Sep.
Article En | MEDLINE | ID: mdl-22569301

Intestinal immune cells are important in host defense, yet the determinants for human lymphoid homeostasis in the intestines are poorly understood. In contrast, lymphoid homeostasis has been studied extensively in mice, where the requirement for a functional common γ-chain molecule has been established. We hypothesized that humanized mice could offer insights into human intestinal lymphoid homeostasis if generated in a strain with an intact mouse common γ-chain molecule. To address this hypothesis, we used three mouse strains (non-obese diabetic (NOD)/severe-combined immunodeficient (SCID) (N/S); NOD/SCID γ-chain(-/-) (NSG); and Rag2(-/-) γ-chain(-/-) (DKO)) and two humanization techniques (bone marrow liver thymus (BLT) and human CD34(+) cell bone marrow transplant of newborn mice (hu)) to generate four common types of humanized mice: N/S-BLT, NSG-BLT, NSG-hu, and DKO-hu mice. The highest levels of intestinal human T cells throughout the small and large intestines were observed in N/S-BLT mice, which have an intact common γ-chain molecule. Furthermore, the small intestine lamina propria T-cell populations of N/S-BLT mice exhibit a human intestine-specific surface phenotype. Thus, the extensive intestinal immune reconstitution of N/S-BLT mice was both quantitatively and qualitatively better when compared with the other models tested such that N/S-BLT mice are well suited for the analysis of human intestinal lymphocyte trafficking and human-specific diseases affecting the intestines.


Bone Marrow Cells/immunology , Interleukin Receptor Common gamma Subunit/metabolism , Intestines/immunology , T-Lymphocytes/immunology , Transplantation Chimera , Animals , Animals, Newborn , Antigens, CD34/metabolism , Bone Marrow Transplantation , DNA-Binding Proteins , Disease Models, Animal , Homeostasis , Humans , Interleukin Receptor Common gamma Subunit/genetics , Mice , Mice, Inbred NOD , Mice, Knockout , Mice, SCID
16.
Nuklearmedizin ; 51(3): 101-10, 2012.
Article En | MEDLINE | ID: mdl-22446512

PURPOSE: To evaluate the calibration of an adaptive thresholding algorithm (contrast-oriented algorithm) for FDG PET-based delineation of tumour volumes in eleven centres with respect to scanner types and image data processing by phantom measurements. METHODS: A cylindrical phantom with spheres of different diameters was filled with FDG realizing different signal-to-background ratios and scanned using 5 Siemens Biograph PET/CT scanners, 5 Philips Gemini PET/CT scanners, and one Siemens ECAT-ART PET scanner. All scans were analysed by the contrast-oriented algorithm implemented in two different software packages. For each site, the threshold SUVs of all spheres best matching the known sphere volumes were determined. Calibration parameters a and b were calculated for each combination of scanner and image-analysis software package. In addition, "scanner-type-specific" calibration curves were determined from all values obtained for each combination of scanner type and software package. Both kinds of calibration curves were used for volume delineation of the spheres. RESULTS: Only minor differences in calibration parameters were observed for scanners of the same type (Δa ≤4%, Δb ≤14%) provided that identical imaging protocols were used whereas significant differences were found comparing calibration parameters of the ART scanner with those of scanners of different type (Δa ≤60%, Δb ≤54%). After calibration, for all scanners investigated the calculated SUV thresholds for auto-contouring did not differ significantly (all p>0.58). The resulting sphere volumes deviated by less than -7% to +8% from the true values. CONCLUSION: After multi-centre calibration the use of the contrast-oriented algorithm for FDG PET-based delineation of tumour volumes in the different centres using different scanner types and specific imaging protocols is feasible.


Algorithms , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Positron-Emission Tomography/instrumentation , Positron-Emission Tomography/standards , Radiotherapy Planning, Computer-Assisted/standards , Calibration , Equipment Failure Analysis/standards , Germany , Humans , Radiotherapy Dosage , Reference Standards , Reproducibility of Results , Sensitivity and Specificity
17.
J Eur Acad Dermatol Venereol ; 26(1): 29-35, 2012 Jan.
Article En | MEDLINE | ID: mdl-21385220

BACKGROUND: Patients with psoriasis commonly report severe sensory skin symptoms, sleep disturbance, psychological distress and impaired health related quality of life (HRQoL). However, the complex associations among these factors are poorly investigated in this patient group. OBJECTIVES: The purpose of this study was to investigate the association between skin pain or skin discomfort and HRQoL, and explore whether sleep disturbance and psychological distress were mediators of these associations. METHODS: A total of 139 psoriasis patients from a university hospital setting participated in this exploratory, cross-sectional study. Data were obtained through interviews and questionnaires (Dermatology Life Quality Index, General Sleep Disturbance Scale, Illness Perception Questionnaire) and analysed using a series of multiple regression analyses. HRQoL was the dependent variable. Independent variables and assumed mediators were entered into the model in a predefined order. RESULTS: Skin pain, skin discomfort, sleep disturbance and psychological distress were significantly associated with HRQoL (all P < 0.05). Sleep disturbance was a partial mediator for the association between skin pain and HRQoL. No such mediation effect was found in terms of psychological distress. The total model explained 40% of the variance in HRQoL. CONCLUSION: In this study, skin pain and skin discomfort were significantly related to HRQoL when controlling for demographic and clinical characteristics. In addition, sleep disturbance mediated the association between skin pain and HRQoL. An understanding of the complex association among physiological and psychological factors, and HRQoL is clinically important in order to provide proper treatment and care of patients with psoriasis.


Pain/physiopathology , Psoriasis/physiopathology , Quality of Life , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pain/etiology , Psoriasis/complications , Psoriasis/psychology , Severity of Illness Index , Stress, Psychological
18.
Med Phys ; 39(6Part13): 3750, 2012 Jun.
Article En | MEDLINE | ID: mdl-28517317

PURPOSE: To demonstrate that standardization in documentation format can significantly reduce manual data entry error in patient chart. METHOD AND MATERIALS: Due to lack of direct data link between CT on rail imaging registration software and patient R&V system, therapists have to manually enter translation correction of patient position into R&V system after performing imaging registration between CT image taken just before treatment delivery and treatment planning CT image. Approximately six months after CT on rail was placed into clinical service, we started requiring therapists to use a standard format to document the shifts when they manually enter data to reduce manual data entry error rate. The therapist manual data entry errors in R&V system before (551 entries) and after the format standardization (1645 entries) are the subjects of statistical analysis. The errors are divided into two categories (recoverable and non-recoverable errors) depending on whether a human being can recover the translation shifts in lateral, longitudinal, and vertical directions from the therapist notes. Fisher's exact test is performed to test the statistical significance of therapist's data entry error reduction after our imposing the documentation format requirement. Temporal information on when the errors were made is also analyzed to find out when errors are more likely to happen. RESULTS: Statistical analysis indicated that reductions in the numbers of recoverable, non-recoverable, and total errors after standardization in document format are all statistically significant with p values less than 0.05. CONCLUSION: A simple and low cost measure like standardization in document format can significantly reduce the errors operators introduce to patient R&V system when they perform manual data entry. We hope our experience will convince people to follow more disciplined documentation rule to reduce the error rate and therefore potentially can improve the quality of patient care when manual data entry is involved.

19.
Biotechnol Bioeng ; 108(11): 2691-704, 2011 Nov.
Article En | MEDLINE | ID: mdl-21618469

Lactate and ammonia are the most important waste products of central carbon metabolism in mammalian cell cultures. In particular during batch and fed-batch cultivations these toxic by-products are excreted into the medium in large amounts, and not only affect cell viability and productivity but often also prevent growth to high cell densities. The most promising approach to overcome such a metabolic imbalance is the replacement of one or several components in the culture medium. It has been previously shown that pyruvate can be substituted for glutamine in cultures of adherent Madin-Darby canine kidney (MDCK) cells. As a consequence, the cells not only released no ammonia but glucose consumption and lactate production were also reduced significantly. In this work, the impact of media changes on glucose and glutamine metabolism was further elucidated by using a high-throughput platform for enzyme activity measurements of mammalian cells. Adherent MDCK cells were grown to stationary and exponential phase in six-well plates in serum-containing GMEM supplemented with glutamine or pyruvate. A total number of 28 key metabolic enzyme activities of cell extracts were analyzed. The overall activity of the pentose phosphate pathway was up-regulated during exponential cell growth in pyruvate-containing medium suggesting that more glucose-6-phosphate was channeled into the oxidative branch. Furthermore, the anaplerotic enzymes pyruvate carboxylase and pyruvate dehydrogenase showed higher cell specific activities with pyruvate. An increase in cell specific activity was also found for NAD(+)-dependent isocitrate dehydrogenase, glutamate dehydrogenase, and glutamine synthetase in MDCK cells grown with pyruvate. It can be assumed that the increase in enzyme activities was required to compensate for the energy demand and to replenish the glutamine pool. On the other hand, the activities of glutaminolytic enzymes (e.g., alanine and aspartate transaminase) were decreased in cells grown with pyruvate, which seems to be related to a decreased glutamine metabolism.


Enzymes/metabolism , Epithelial Cells/physiology , Stress, Physiological , Adaptation, Physiological , Animals , Cell Culture Techniques , Cell Line , Dogs , Epithelial Cells/metabolism , Kidney/cytology , Kidney/metabolism , Metabolic Networks and Pathways
20.
J Phys Condens Matter ; 23(5): 052201, 2011 Feb 09.
Article En | MEDLINE | ID: mdl-21406900

Magnetic properties of a series of (La(0.7)Sr(0.3)MnO(3)/SrRuO(3)) superlattices, where the SrRuO(3) layer thickness is varying, are examined. A room-temperature magnetocaloric effect is obtained owing to the finite size effect which reduces the T(C) of La(0.7)Sr(0.3)MnO(3) layers. While the working temperature ranges are enlarged, - ΔS(M)(max) values remain similar to the values in polycrystalline La(0.7)Sr(0.3)MnO(3). Consequently, the relative cooling powers are significantly improved, the microscopic mechanism of which is related to the effect of the interfaces at La(0.7)Sr(0.3)MnO(3)/SrRuO(3) and higher nanostructural disorder. This study indicates that artificial oxide superlattices/multilayers might provide an alternative pathway in searching for efficient room-temperature magnetic refrigerator for (nano) micro-scale systems.

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