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1.
J Anim Sci ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38898575

ABSTRACT

The study objective was to investigate the effect of repeated hypothalamic-pituitary-adrenal (HPA) axis stimulation using synthetic adrenocorticotropic hormone (ACTH) intramuscular injections on hair cortisol concentration, growth, and behavior in preweaned dairy calves. Twenty-seven Holstein calves were assigned to nine triads (based on sex and birth order) and randomly assigned to 1 of 3 treatments: 1) control (CON; 2 mL saline weekly); 2) moderate (MOD; alternating Cosyntropin [2 mcg/kg body weight (BW)] and saline weekly); or 3) frequent (FREQ; Cosyntropin [2 mcg/kg BW] weekly). Calves received their first injection on study day 0 (7±1 d of age). Hair was collected from the tail switch between days -5 and -3 (baseline), 21, and 49 and analyzed for cortisol concentration. To verify the endogenous cortisol release by Cosyntropin during the treatment period, saliva was collected on days 0, 14, 28, and 42 before injection and every 15 min for 2 h after injection for analysis of salivary cortisol concentration. Calves were fitted with accelerometers to continuously monitor lying time, number of lying bouts, and lying bout duration throughout the study. Growth measures (BW, hip height, hip width) were recorded weekly. Data were analyzed using repeated measures ANOVA (SAS, Version 9.4), and models included the fixed effects of treatment, time (min or study day), and interaction between treatment and time. Temperature humidity index was included as a continuous covariate in all models. We observed a treatment × min interaction (P < 0.0001), whereby salivary cortisol concentration was lower in CON calves compared to MOD and FREQ calves 15 to 120 min post injection. While hair cortisol concentration was not influenced by treatment, concentration decreased from day 21 (1.28±0.03 ng/mL) to 49 (0.93±0.03 ng/mL). Average body weight was similar across treatments (CON [59.4±1.09 kg], MOD [58.6±0.98 kg], and FREQ [57.6±0.96 kg]; P=0.50). There was no evidence to suggest a difference in average daily lying time (CON [18.5±0.23 h/d], MOD [18.6±0.23 h/d], and FREQ [18.5±0.23 h/d]; P=0.99). These results suggest that repeated HPA axis stimulation through Cosyntropin administration increased salivary cortisol concentration, but did not influence hair cortisol concentration, growth, or behavior in preweaned dairy calves.

3.
AJNR Am J Neuroradiol ; 44(9): 1090-1095, 2023 09.
Article in English | MEDLINE | ID: mdl-37620154

ABSTRACT

BACKGROUND AND PURPOSE: Despite its rarity in Western countries, kernicterus resulting from severe neonatal hyperbilirubinemia and its associated neurologic consequences still persists. Subtle MR imaging patterns may be overlooked, leading to diagnostic and prognostic uncertainties. The study systematically analyzes MR imaging pattern over time. MATERIALS AND METHODS: A retrospective MR imaging study was conducted in Departments of Pediatric Neurology at the University Children's Hospitals in Leipzig, Germany, or Tübingen, Germany, between 2012 and 2022 in patients who presented beyond the neonatal period suspected of having chronic kernicterus. RESULTS: Eight patients with a total of 15 MR images were identified. The clinical diagnosis of kernicterus was confirmed in all cases on the basis of typical MR imaging findings: Bilateral, diffuse hyperintensity of the globus pallidus was observed in the neonatal period on T1WI (1 MR imaging, at 2 weeks), in infancy on T2WI (4 MR images, at 9-26 months). In children 2 years of age and older, bilateral hyperintensity on T2WI was limited to the borders of the globus pallidus (8 MR images, at 20 months -13 years). Notably, 2 children exhibited normal initial MR imaging findings at 2 months of age. Hence, MR imaging depiction of kernicterus pathology evolves with time, first evident on T1WI, subsequently on T2WI, with a "blind window" during early infancy. The T2WI signal change initially involves the entire globus pallidus and later is limited to the borders. Kernicterus had not been diagnosed in any except 2 patients by previous investigators. CONCLUSIONS: All patients presented with a characteristic clinical history and signs and an evolving MR imaging pattern. Nonetheless, the diagnosis of kernicterus was frequently missed. Abnormalities on later MR images appear to be underrecognized.


Subject(s)
Kernicterus , Child , Infant, Newborn , Humans , Kernicterus/diagnostic imaging , Globus Pallidus/diagnostic imaging , Retrospective Studies , Germany , Magnetic Resonance Imaging
4.
Clin Oncol (R Coll Radiol) ; 35(6): e352-e361, 2023 06.
Article in English | MEDLINE | ID: mdl-37031075

ABSTRACT

AIMS: Clinical equipoise exists regarding early-stage lung cancer treatment among patients as trials comparing stereotactic body radiation therapy (SBRT) and surgical resection are unavailable. Given the potential differences in treatment effectiveness and side-effects, we sought to determine the associations between treatment type, decision regret and depression. MATERIALS AND METHODS: A multicentre, prospective study of patients with stage IA-IIA non-small cell lung cancer (NSCLC) with planned treatment with SBRT or surgical resection was conducted. Decision regret and depression were measured using the Decision Regret Scale (DRS) and Patient Health Questionnaire-4 (PHQ-4) at 3, 6 and 12 months post-treatment, respectively. Mixed linear regression modelling examined associations between treatment and decision regret adjusting for patient sociodemographics. RESULTS: Among 211 study participants with early-stage lung cancer, 128 (61%) patients received SBRT and 83 (39%) received surgical resection. The mean age was 73 years (standard deviation = 8); 57% were female; 79% were White non-Hispanic. In the entire cohort at 3 months post-treatment, 72 (34%) and 57 (27%) patients had mild and severe decision regret, respectively. Among patients who received SBRT or surgery, 71% and 46% of patients experienced at least mild decision regret at 3 months, respectively. DRS scores increased at 6 months and decreased slightly at 12 months of follow-up in both groups. Higher DRS scores were associated with SBRT treatment (adjusted mean difference = 4.18, 95% confidence interval 0.82 to 7.54) and depression (adjusted mean difference = 3.49, 95% confidence interval 0.52 to 6.47). Neither patient satisfaction with their provider nor decision-making role concordance was associated with DRS scores. CONCLUSIONS: Most early-stage lung cancer patients experienced at least mild decision regret, which was associated with SBRT treatment and depression symptoms. Findings suggest patients with early-stage lung cancer may not be receiving optimal treatment decision-making support. Therefore, opportunities for improved patient-clinician communication probably exist.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiosurgery , Humans , Female , Aged , Male , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Prospective Studies , Treatment Outcome , Radiosurgery/adverse effects , Emotions , Neoplasm Staging
6.
Eur J Paediatr Neurol ; 47: 118-130, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38284996

ABSTRACT

BACKGROUND: Acute cerebellitis (AC) in children and adolescents is an inflammatory disease of the cerebellum due to viral or bacterial infections but also autoimmune-mediated processes. OBJECTIVE: To investigate the frequency of autoantibodies in serum and CSF as well as the neuroradiological features in children with AC. MATERIAL AND METHODS: Children presenting with symptoms suggestive of AC defined as acute/subacute onset of cerebellar symptoms and MRI evidence of cerebellar inflammation or additional CSF pleocytosis, positive oligoclonal bands (OCBs), and/or presence of autoantibodies in case of negative cerebellar MRI. Children fulfilling the above-mentioned criteria and a complete data set including clinical presentation, CSF studies, testing for neuronal/cerebellar and MOG antibodies as well as MRI scans performed at disease onset were eligible for this retrospective multicenter study. RESULTS: 36 patients fulfilled the inclusion criteria for AC (f:m = 14:22, median age 5.5 years). Ataxia was the most common cerebellar symptom present in 30/36 (83 %) in addition to dysmetria (15/36) or dysarthria (13/36). A substantial number of children (21/36) also had signs of encephalitis such as somnolence or seizures. In 10/36 (28 %) children the following autoantibodies (abs) were found: MOG-abs (n = 5) in serum, GFAPα-abs (n = 1) in CSF, GlyR-abs (n = 1) in CSF, mGluR1-abs (n = 1) in CSF and serum. In two further children, antibodies were detected only in serum (GlyR-abs, n = 1; GFAPα-abs, n = 1). MRI signal alterations in cerebellum were found in 30/36 children (83 %). Additional supra- and/or infratentorial lesions were present in 12/36 children, including all five children with MOG-abs. Outcome after a median follow-up of 3 months (range: 1 a 75) was favorable with an mRS ≤2 in 24/36 (67 %) after therapy. Antibody (ab)-positive children were significantly more likely to have a better outcome than ab-negative children (p = .022). CONCLUSION: In nearly 30 % of children in our study with AC, a range of abs was found, underscoring that autoantibody testing in serum and CSF should be included in the work-up of a child with suspected AC. The detection of MOG-abs in AC does expand the MOGAD spectrum.


Subject(s)
Autoantibodies , Encephalitis , Adolescent , Child , Child, Preschool , Humans , Ataxia , Cerebellum/diagnostic imaging , Encephalitis/diagnostic imaging , Inflammation , Retrospective Studies
9.
Br J Dermatol ; 185(4): 745-755, 2021 10.
Article in English | MEDLINE | ID: mdl-33942286

ABSTRACT

BACKGROUND: Bruton tyrosine kinase (BTK) inhibition targets B-cell and other non-T-cell immune cells implicated in the pathophysiology of pemphigus, an autoimmune disease driven by anti-desmoglein autoantibodies. Rilzabrutinib is a new reversible, covalent BTK inhibitor demonstrating preclinical efficacy as monotherapy in canine pemphigus foliaceus. OBJECTIVES: To evaluate the efficacy and safety of oral rilzabrutinib in patients with pemphigus vulgaris in a multicentre, proof-of-concept, phase II trial. METHODS: Patients with Pemphigus Disease Area Index severity scores 8-45 received 12 weeks of oral rilzabrutinib 400-600 mg twice daily and 12 weeks of follow-up. Patients initially received between 0 and ≤ 0·5 mg kg-1 prednisone-equivalent corticosteroid (CS; i.e. 'low dose'), tapered after control of disease activity (CDA; no new lesions, existing lesions healing). The primary endpoints were CDA within 4 weeks on zero-to-low-dose CS and safety. RESULTS: In total, 27 patients with pemphigus vulgaris were included: nine newly diagnosed (33%) and 18 relapsing (67%); 11 had moderate disease (41%) and 16 moderate to severe (59%). The primary endpoint, CDA, was achieved in 14 patients (52%, 95% confidence interval 32-71): 11 using low-dose CS and three using no CS. Over 12 weeks of treatment, mean CS doses reduced from 20·0 to 11·8 mg per day for newly diagnosed patients and from 10·3 to 7·8 mg per day for relapsing patients. Six patients (22%) achieved complete response by week 24, including four (15%) by week 12. Treatment-related adverse events were mostly mild (grade 1 or 2); one patient experienced grade 3 cellulitis. CONCLUSIONS: Rilzabrutinib alone, or with much lower CS doses than usual, was safe, with rapid clinical activity in pemphigus vulgaris. These data suggest that BTK inhibition may be a promising treatment strategy and support further investigation of rilzabrutinib for the treatment of pemphigus.


Subject(s)
Pemphigus , Protein Kinase Inhibitors/therapeutic use , Agammaglobulinaemia Tyrosine Kinase , Autoantibodies , Humans , Pemphigus/drug therapy , Prednisone
10.
Stud Health Technol Inform ; 264: 1777-1778, 2019 Aug 21.
Article in English | MEDLINE | ID: mdl-31438339

ABSTRACT

The goal of this study was to determine a consensual proposition for the development of computer tools in primary care. A Delphi study using colored abaci was conducted among 23 French experts, some of whom were patients. The tools expected by the experts were: a customizable knowledge database integrated into an efficient clinical support system, a follow-up calendar designed as a collaborative patient-focused tool, and an information exchange data system.


Subject(s)
Information Technology , Motivation , Delphi Technique , Humans , Information Systems , Primary Health Care
11.
Stud Health Technol Inform ; 264: 1949-1950, 2019 Aug 21.
Article in English | MEDLINE | ID: mdl-31438422

ABSTRACT

My Little Smart Personal Assistant is a co-designed remote connected device with an interactive vocal assistant that provides a panel of social/medical services for the rural European elderly population. The aim is to create a new patient-centered solution to improve quality of life, self-autonomy, and integration within local community. This should improve aging-well at home in rural settings.


Subject(s)
Aging , Rural Health Services , Aged , Humans , Quality of Life , Rural Population
12.
J Dent Res ; 98(9): 994-1001, 2019 08.
Article in English | MEDLINE | ID: mdl-31329045

ABSTRACT

Enamel formation and quality are dependent on environmental conditions, including exposure to fluoride, which is a widespread natural element. Fluoride is routinely used to prevent caries. However, when absorbed in excess, fluoride may also lead to altered enamel structural properties associated with enamel gene expression modulations. As iron plays a determinant role in enamel quality, the aim of our study was to evaluate the iron metabolism in dental epithelial cells and forming enamel of mice exposed to fluoride, as well as its putative relation with enamel mechanical properties. Iron storage was investigated in dental epithelial cells with Perl's blue staining and secondary ion mass spectrometry imaging. Iron was mainly stored by maturation-stage ameloblasts involved in terminal enamel mineralization. Iron storage was drastically reduced by fluoride. Among the proteins involved in iron metabolism, ferritin heavy chain (Fth), in charge of iron storage, appeared as the preferential target of fluoride according to quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry analyses. Fluorotic enamel presented a decreased quantity of iron oxides attested by electron spin resonance technique, altered mechanical properties measured by nanoindentation, and ultrastructural defects analyzed by scanning electron microscopy and energy dispersive x-ray spectroscopy. The in vivo functional role of Fth was illustrated with Fth+/- mice, which incorporated less iron into their dental epithelium and exhibited poor enamel quality. These data demonstrate that exposure to excessive fluoride decreases ameloblast iron storage, which contributes to the defective structural and mechanical properties in rodent fluorotic enamel. They raise the question of fluoride's effects on iron storage in other cells and organs that may contribute to its effects on population health.


Subject(s)
Ameloblasts/metabolism , Amelogenesis , Fluorosis, Dental/metabolism , Iron/metabolism , Animals , Epithelial Cells/metabolism , Fluorides , Fluorosis, Dental/physiopathology , Male , Mice , Mice, Inbred BALB C
13.
BMC Med Inform Decis Mak ; 19(1): 45, 2019 03 18.
Article in English | MEDLINE | ID: mdl-30885183

ABSTRACT

BACKGROUND: Heterogeneous healthcare instance data can hardly be integrated without harmonizing its schema-level metadata. Many medical research projects and organizations use metadata repositories to edit, store and reuse data elements. However, existing metadata repositories differ regarding software implementation and have shortcomings when it comes to exchanging metadata. This work aims to define a uniform interface with a technical interlingua between the different MDR implementations in order to enable and facilitate the exchange of metadata, to query over distributed systems and to promote cooperation. To design a unified interface for multiple existing MDRs, a standardized data model must be agreed on. The ISO 11179 is an international standard for the representation of metadata, and since most MDR systems claim to be at least partially compliant, it is suitable for defining an interface thereupon. Therefore, each repository must be able to define which parts can be served and the interface must be able to handle highly linked data. GraphQL is a data access layer and defines query techniques designed to navigate easily through complex data structures. RESULTS: We propose QL4MDR, an ISO 11179-3 compatible GraphQL query language. The GraphQL schema for QL4MDR is derived from the ISO 11179 standard and defines objects, fields, queries and mutation types. Entry points within the schema define the path through the graph to enable search functionalities, but also the exchange is promoted by mutation types, which allow creating, updating and deleting of metadata. QL4MDR is the foundation for the uniform interface, which is implemented in a modern web-based interface prototype. CONCLUSIONS: We have introduced a uniform query interface for metadata repositories combining the ISO 11179 standard for metadata repositories and the GraphQL query language. A reference implementation based on the existing Samply.MDR was implemented. The interface facilitates access to metadata, enables better interaction with metadata as well as a basis for connecting existing repositories. We invite other ISO 11179-based metadata repositories to take this approach into account.


Subject(s)
Health Information Interoperability , Medical Informatics Applications , Metadata , Humans
15.
Br J Dermatol ; 177(6): 1683-1692, 2017 12.
Article in English | MEDLINE | ID: mdl-28703393

ABSTRACT

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare, potentially devastating autoimmune disease of the skin. IgG autoantibodies directed against type VII collagen (Col7), the major component of anchoring fibrils, induce skin fragility leading to cutaneous and mucocutaneous blister formation, which is mostly of a scarring phenotype. Thus, powerful and reproducible diagnostic assays are critical to establish the diagnosis of EBA early to avoid irreversible sequelae. OBJECTIVES: The present international, retrospective multicentre study included a large cohort of patients with EBA and evaluated the diagnostic power of four different diagnostic assays for the detection of anti-Col7 IgG autoantibodies. METHODS: Overall, 95 EBA sera and 200 control sera consisting of 100 bullous pemphigoid sera, 50 pemphigus vulgaris sera and 50 sera of healthy controls were tested for anti-Col7 IgG autoantibodies using indirect immunofluorescence (IIF), two commercial enzyme-linked immunosorbent assay (ELISA) systems and Western blot (WB) analysis. EBA sera were taken from patients with positive direct immunofluorescence and IgG reactivity in at least one of the immunoserological assays (IIF, ELISA, WB). RESULTS: A Col7-NC1/NC2 ELISA (MBL, Nagoya, Japan) showed the highest sensitivity (97·9%), followed by a Col7-NC1 ELISA (Euroimmun, Lübeck, Germany) (89·5%), WB with Col7-NC1 (85·3%), and IIF on saline-split human skin (74·7%). The specificities of both ELISA systems were comparable (NC1 98·7%, NC1/NC2 99·3%). Furthermore, WB was more sensitive than IIF, which was more specific. CONCLUSIONS: The two commercially available ELISA systems allow for a highly sensitive and specific diagnosis of EBA. The sensitivity of the Col7-NC1/NC2 ELISA is significantly higher compared with the ELISA based on the Col7-NC1 domain only.


Subject(s)
Autoantibodies/metabolism , Collagen Type VII/immunology , Epidermolysis Bullosa Acquisita/diagnosis , Immunoglobulin G/metabolism , Blister/immunology , Blotting, Western , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/immunology , Microscopy, Fluorescence , Retrospective Studies
16.
Public Health ; 145: 30-38, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28359387

ABSTRACT

OBJECTIVES: Opportunistic screening for type 2 diabetes (T2D) has not been adopted as part of routine practice. The aim of the study was to investigate the yield of opportunistic target screening for T2D in Croatia and to evaluate the process of screening by using data from electronic medical record. STUDY DESIGN: We conducted opportunistic screening in 23 general practitioners (GPs) in a population of 13,344 patients aged 45-70 years. METHODS: First, after excluding patients with T2D, patients with risk factors for T2D were derived from the electronic medical record and GP's assessment during the preconsultation phase. Second, those with data about normoglycemia in past three years were excluded. Remaining patients started the consultation phase during their usual visit, when they were offered capillary fasting plasma glucose testing in the next consultation. RESULTS: Prevalence of T2D was 10.9% (new 1.4%). A total of 5568 (46.1%) patients had risks and 2849 (51.2%) had data about normoglycemia in the last three years. Using those data, number needed to invite to screening (NNI) was reduced to half: from 46.1% to 22.5%. One hundred eighty-four patients were screened positive for T2D in two capillary fasting plasma glucose tests (yield 9.8%). Number needed to screen (NNS) in order to detect one T2D was 10.3 patients. Among risks for T2D, overweight was the best predictive factor for undiagnosed T2D (odds ratio [OR]: 2.11, confidence interval [CI]:1.41-3.15, P < .001). Logistic regression showed that in targeted population, overweight patients with a family history in fold were 2.5 times more likely to have T2D (OR: 2.54, CI 1.78-.61, P < .001). CONCLUSIONS: Total yield in targeted population was 1,4%. By using data about normoglycemia from EMRs, NNI was reduced by half and NNS was 10.3 patients. Our findings suggest the model for improvement in opportunistic screening.


Subject(s)
Diabetes Mellitus, Type 2/diagnosis , Electronic Health Records , General Practitioners , Mass Screening/methods , Primary Health Care/methods , Adult , Aged , Croatia/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Female , Health Services Needs and Demand , Humans , Male , Middle Aged , Odds Ratio , Outcome Assessment, Health Care , Overweight , Prediabetic State/blood , Prediabetic State/diagnosis , Prediabetic State/epidemiology , Prediabetic State/etiology , Prevalence , Prospective Studies , Regression Analysis , Risk Factors
17.
Ann Vasc Surg ; 42: 214-221, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28389293

ABSTRACT

BACKGROUND: Cigarette smoking is strongly associated with atherosclerotic disease. It is incumbent on vascular surgeons to provide smoking cessation counseling (SCC) to their patients. The objective of this study was to determine the association of SCC and improvement in quality of care. METHODS: As a quality project using retrospective data, the study received institutional review board exemption status. A retrospective review of prospectively maintained database from April 2014 through March 2015 of outpatient encounters in a vascular surgery clinic was performed of current smokers. Through the quality support team, providers were encouraged to counsel smokers to quit, document the discussion, and bill specific Evaluate and Management codes (99406 and 99407). The number of outpatients by smoking status, documentation and billing of SCC, demographics of current smokers, and monetary collections were collected. Data were compared using a correlation coefficient calculated and tested for statistical significant using two-tailed t-test. RESULTS: A sample of 1,077 visits by 612 currently smoking patients accounted for 24% of all outpatient vascular surgery visits. The average age was 61 years, and 64% were male. Comorbidities included 77% with hypertension, 32% with diabetes mellitus, and 14% with chronic kidney disease. Medically, 72% were on aspirin, 71% on statin, and 48% on beta blocker. A total of 208 (34%) never underwent a vascular intervention, and 183 (30%) had an intervention during the study period (44% for peripheral artery disease, 10% for carotid stenosis, 14% amputations, and 10% abdominal aortic aneurysm). Documentation improved from 65% of encounters during the first month to 89% in the peak month and 79% of total encounters. All-cause mortality rate was 2%, and this cohort demonstrated 75% SCC for 28 encounters. Fifty-five patients (9%) quit smoking for more than 30 days at the end of the study period, and this cohort had 69% of their 97 encounters with documented SCC. Increased SCC was correlated with decreased 30-day readmissions during the concurrent month (r = -0.711, P = 0.009) and the following month (r = -0.719, P = 0.008). There was a weak correlation with decreased amputations the following month (r = -0.5, P = 0.08). From a financial perspective, $1,373 was collected for 33 patients with a potential for collection of $7,460 predicted for minimum Medicare payment of 1 visit per patient. CONCLUSIONS: Advising vascular patients in the arduous process of smoking cessation benefits both the patient and the health system. Proper documentation and billing decreases costs of early readmissions and increases departmental revenue.


Subject(s)
Counseling/economics , Process Assessment, Health Care/economics , Quality Improvement/economics , Quality Indicators, Health Care/economics , Smoking Cessation/economics , Vascular Diseases/economics , Vascular Diseases/surgery , Vascular Surgical Procedures/economics , Aged , Aged, 80 and over , Comorbidity , Cost Savings , Cost-Benefit Analysis , Databases, Factual , Fees and Charges , Female , Health Care Costs , Humans , Income , Male , Middle Aged , Retrospective Studies , Risk Factors , Smoking/adverse effects , Smoking/economics , Smoking Cessation/methods , Treatment Outcome , Vascular Diseases/diagnosis , Vascular Diseases/mortality , Vascular Surgical Procedures/adverse effects , Vascular Surgical Procedures/mortality
18.
Faraday Discuss ; 194: 621-638, 2016 12 16.
Article in English | MEDLINE | ID: mdl-27711803

ABSTRACT

The ultra-bright femtosecond X-ray pulses provided by X-ray Free Electron Lasers (XFELs) open capabilities for studying the structure and dynamics of a wide variety of biological and inorganic systems beyond what is possible at synchrotron sources. Although the structure and chemistry at the catalytic sites have been studied intensively in both biological and inorganic systems, a full understanding of the atomic-scale chemistry requires new approaches beyond the steady state X-ray crystallography and X-ray spectroscopy at cryogenic temperatures. Following the dynamic changes in the geometric and electronic structure at ambient conditions, while overcoming X-ray damage to the redox active catalytic center, is key for deriving reaction mechanisms. Such studies become possible by using the intense and ultra-short femtosecond X-ray pulses from an XFEL, where sample is probed before it is damaged. We have developed methodology for simultaneously collecting X-ray diffraction data and X-ray emission spectra, using an energy dispersive spectrometer, at ambient conditions, and used this approach to study the room temperature structure and intermediate states of the photosynthetic water oxidizing metallo-protein, photosystem II. Moreover, we have also used this setup to simultaneously collect the X-ray emission spectra from multiple metals to follow the ultrafast dynamics of light-induced charge transfer between multiple metal sites. A Mn-Ti containing system was studied at an XFEL to demonstrate the efficacy and potential of this method.


Subject(s)
Crystallography, X-Ray , Electrons , Lasers , Catalysis , X-Rays
19.
Br J Dermatol ; 175(1): 142-9, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26800395

ABSTRACT

BACKGROUND: Two pemphigus severity scores, Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI), have been proposed to provide an objective measure of disease activity. However, the use of these scores in clinical practice is limited by the absence of cut-off values that allow differentiation between moderate, significant and extensive types of pemphigus. OBJECTIVES: To calculate cut-off values defining moderate, significant and extensive pemphigus based on the ABSIS and PDAI scores. METHODS: In 31 dermatology departments in six countries, consecutive patients with newly diagnosed pemphigus were assessed for pemphigus severity, using ABSIS, PDAI, Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores. Cut-off values defining moderate, significant and extensive subgroups were calculated based on the 25th and 75th percentiles of the ABSIS and PDAI scores. The median ABSIS, PDAI, PGA and DLQI scores of the three severity subgroups were compared in order to validate these subgroups. RESULTS: Ninety-six patients with pemphigus vulgaris (n = 77) or pemphigus foliaceus (n = 19) were included. The median PDAI activity and ABSIS total scores were 27·5 (range 3-84) and 34·8 points (range 0·5-90·5), respectively. The respective cut-off values corresponding to the first and third quartiles of the scores were 15 and 45 for the PDAI, and 17 and 53 for ABSIS. The moderate, significant and extensive subgroups were thus defined, and had distinguishing median ABSIS (P < 0·001), PDAI (P < 0·001), PGA (P < 0·001) and DLQI (P = 0·03) scores. CONCLUSIONS: This study suggests cut-off values of 15 and 45 for PDAI and 17 and 53 for ABSIS, to distinguish moderate, significant and extensive pemphigus forms. Identifying these pemphigus activity subgroups should help physicians to classify and manage patients with pemphigus.


Subject(s)
Pemphigus/diagnosis , Severity of Illness Index , Skin Diseases, Vesiculobullous/diagnosis , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Prospective Studies , Reference Values
20.
Skin Res Technol ; 21(1): 61-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25066249

ABSTRACT

PURPOSE: The aim of this study was to demonstrate the feasibility of a custom-made phased-array microcoil within a 400 MHz animal system for the morphological characterization of human skin tissue in correlation with histopathology. MATERIALS AND METHODS: A dedicated 7-channel microcoil-based MR detector arranged in a phased-array geometry was developed to combine the advantages of both a large field of view and a high signal-to-noise ratio. Standard gradient echo sequences were adapted for the characterization of skin morphology ex vivo. RESULTS: In this study, the feasibility of using this type of microdetector, combined with specially manufactured sample holders, to achieve high-resolution MR images of fresh and formalin-fixed, normal and hidradenitis suppurativa diseased skin was successfully demonstrated. The setup presented in this work allows reliable acquisitions of high-resolution images with in-plane resolution up to 25 × 25 µm², and 100 µm in the orthogonal direction, thereby allowing the differentiation of typical layers of the skin, sebaceous glands and hair follicle. CONCLUSION: This study demonstrates that MR microscopy on skin biopsies can be applied at low cost on a standard animal MR imaging system. The successful imaging of different skin structures ex vivo is a prerequisite for non-invasive, in vivo application of skin MR microscopy for accurate complementary disease diagnosis in dermatology.


Subject(s)
Hidradenitis Suppurativa/pathology , Magnetic Resonance Imaging/instrumentation , Magnetics/instrumentation , Microscopy/instrumentation , Skin/pathology , Specimen Handling/instrumentation , Dermoscopy/instrumentation , Equipment Design , Equipment Failure Analysis , Humans , Image Enhancement/instrumentation , In Vitro Techniques , Miniaturization , Reproducibility of Results , Sensitivity and Specificity
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