Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: results from the PIPA cohort study.

OBJECTIVES: Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment. METHOD: This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay. RESULTS: In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of -11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes. CONCLUSION: Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

Nailfold capillaroscopy as diagnostic test in patients with psoriasis and psoriatic arthritis: A systematic review.

Up to 30 % of patients with psoriasis (PsO) develop psoriatic arthritis (PsA), and diagnosis can be difficult. Nailfold capillaroscopy (NC) is an easily applicable, non-invasive procedure to assess skin microcirculation. This systematic review investigates NC as diagnostic tool for PsO and PsA, including correlations between NC outcome measures to clinical and laboratory outcome measures. This systematic review was built on the PICO and PRISMA guidelines. In total 22 relevant studies were found Searching in the Web of Science, PubMed and Embase, latest update June 13th, 2022. The following NC outcome measures are found to be significantly more prevalent in PsO patients than healthy controls: reduced density, reduced length and more abnormal morphology. Likewise, in PsA patients, reduced density, more abnormal morphology, more microhaemorrhages and fewer hairpin shapes are found to be significantly more prevalent. Results were non-conclusive in terms of disease activity and duration with NC findings. Random-effects meta-analysis showed a significant reduction of density in PsO patients compared to healthy controls (studies: 6, n = 249; SMD = -0.91; 95 % CI [-1.41, -0.40], p = 0.0058, heterogeneity I2=74 %, AUC = 0.740) and in PsA patients compared to healthy controls (studies: 5, n = 130; SMD = -1.22; 95 % CI [-2.38, -0.06], p = 0.0432, heterogeneity I2=89 %, AUC = 0.806). No NC outcome measures were overall conclusive in differentiating PsO from PsA. Considering the conflicting results and small sample sizes further large-scale research on the identification of capillaroscopic changes in PsO and PsA and correlations with standardised clinical and laboratory outcome measures are necessary.

Increased prevalence of sleep disturbance in psoriatic arthritis is associated with inflammatory and non-inflammatory measures.

OBJECTIVES: To examine the prevalence of sleep disturbances, quantified by the Pittsburgh Sleep Quality Index (PSQI), in patients with psoriatic arthritis (PsA), psoriasis (PsO) and healthy controls (HCs), explore associations between PSQI and clinical and patient-reported outcomes, and evaluate the effect of treatment on PSQI. METHOD: Patients were included from the Parker Institute's PsA patient cohort to evaluate the prevalence of sleep disturbances. Univariate and multivariate regression analyses were used to explore associations between sleep disturbance and outcome measures. Treatment effect in PsA patients was assessed with a mixed-effect model for repeated measures. RESULTS: In total, 109 PsA patients, 20 PsO patients, and 20 HCs were included. Sleep disturbances were reported by 66.1% of PsA patients, 45.0% of PsO patients, and 15.0% of HCs. Univariate regression analyses revealed statistically significant associations (p < 0.001) between PSQI and Disease Activity Score (DAS28CRP), tender points, visual analogue scale (VAS) patient global and pain, Psoriatic Arthritis Impact of Disease fatigue, Health Assessment Questionnaire (HAQ), and painDETECT score. Multivariate regression analysis demonstrated VAS patient global, VAS pain, and tender points as being independently associated with PSQI. The mixed-effect model revealed no effect of treatment. CONCLUSION: More PsA patients than PsO patients and HCs reported sleep disturbances. Sleep disturbances were associated with inflammatory and non-inflammatory measures possibly explaining the limited effect of treatment. This demonstrates the need for interdisciplinary approaches to improve the management of sleep disturbance in PsA.Trial registration: ClinicalTrials.gov (NCT02572700).

2021 international consensus statement on optical coherence tomography for basal cell carcinoma: image characteristics, terminology and educational needs.

BACKGROUND: Despite the widespread use of optical coherence tomography (OCT) for imaging of keratinocyte carcinoma, we lack an expert consensus on the characteristic OCT features of basal cell carcinoma (BCC), an internationally vetted set of OCT terms to describe various BCC subtypes, and an educational needs assessment. OBJECTIVES: To identify relevant BCC features in OCT images, propose terminology based on inputs from an expert panel and identify content for a BCC-specific curriculum for OCT trainees. METHODS: Over three rounds, we conducted a Delphi consensus study on BCC features and terminology between March and September 2020. In the first round, experts were asked to propose BCC subtypes discriminable by OCT, provide OCT image features for each proposed BCC subtypes and suggest content for a BCC-specific OCT training curriculum. If agreement on a BCC-OCT feature exceeded 67%, the feature was accepted and included in a final review. In the second round, experts had to re-evaluate features with less than 67% agreement and rank the ten most relevant BCC OCT image features for superficial BCC, nodular BCC and infiltrative and morpheaphorm BCC subtypes. In the final round, experts received the OCT-BCC consensus list for a final review, comments and confirmation. RESULTS: The Delphi included six key opinion leaders and 22 experts. Consensus was found on terminology for three OCT BCC image features: (i) hyporeflective areas, (ii) hyperreflective areas and (iii) ovoid structures. Further, the participants ranked the ten most relevant image features for nodular, superficial, infiltrative and morpheaform BCC. The target group and the key components for a curriculum for OCT imaging of BCC have been defined. CONCLUSION: We have established a set of OCT image features for BCC and preferred terminology. A comprehensive curriculum based on the expert suggestions will help implement OCT imaging of BCC in clinical and research settings.

Influence of pre-treatment structural brain measures on effects of action-based cognitive remediation on executive function in partially or fully remitted patients with bipolar disorder.

Cognitive impairment is an emerging treatment target in patients with bipolar disorder (BD) but so far, no evidence-based treatment options are available. Recent studies indicate promising effects of Cognitive Remediation (CR) interventions, but it is unclear who responds most to these interventions. This report aimed to investigate whether pre-treatment dorsal prefrontal cortex (dPFC) thickness predicts improvement of executive function in response to Action-Based Cognitive Remediation (ABCR) in patients with BD. Complete baseline magnetic resonance imaging (MRI) data were available from 45 partially or fully remitted patients with BD from our randomized controlled ABCR trial (ABCR: n = 25, control group: n = 20). We performed cortical reconstruction and volumetric segmentation using FreeSurfer. Multiple linear regression analysis was conducted to assess the influence of dPFC thickness on ABCR-related executive function improvement, reflected by change in the One Touch Stocking of Cambridge performance from baseline to post-treatment. We also conducted whole brain vertex wise analysis for exploratory purposes. Groups were well-matched for demographic and clinical variables. Less pre-treatment dPFC thickness was associated with greater effect of ABCR on executive function (p = 0.02). Further, whole-brain vertex analysis revealed an association between smaller pre-treatment superior temporal gyrus volume and greater ABCR-related executive function improvement. The observed associations suggest that structural abnormalities in dPFC and superior temporal gyrus are key neurocircuitry treatment targets for CR interventions that target impaired executive function in BD.

Recent advances in solid oxide cell technology for electrolysis.

In a world powered by intermittent renewable energy, electrolyzers will play a central role in converting electrical energy into chemical energy, thereby decoupling the production of transport fuels and chemicals from today's fossil resources and decreasing the reliance on bioenergy. Solid oxide electrolysis cells (SOECs) offer two major advantages over alternative electrolysis technologies. First, their high operating temperatures result in favorable thermodynamics and reaction kinetics, enabling unrivaled conversion efficiencies. Second, SOECs can be thermally integrated with downstream chemical syntheses, such as the production of methanol, dimethyl ether, synthetic fuels, or ammonia. SOEC technology has witnessed tremendous improvements during the past 10 to 15 years and is approaching maturity, driven by advances at the cell, stack, and system levels.

Basal cell carcinoma treated with combined ablative fractional laser and ingenol mebutate - an exploratory study monitored by optical coherence tomography and reflectance confocal microscopy.

BACKGROUND: Basal cell carcinomas (BCCs) have previously been treated off-label with ingenol mebutate (IM). Ablative fractional laser (AFL) may improve efficacy of IM by increasing drug uptake in the tumour. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) detect BCC non-invasively. Our aim was to investigate BCC response and tolerability after combined AFL and IM treatment of low-risk BCCs. METHODS: Twenty patients with histologically verified superficial (n = 7) and nodular (n = 13) BCCs were treated with combined fractional CO2 -laser (10 600 nm) and IM 0.015% or 0.05%, the concentration depending on anatomical location. BCC response was evaluated clinically, by OCT and RCM at day 29 and 90 after first treatment, and histologically at day 90. Treatment was repeated at day 29 if BCC persisted. Local skin reactions (LSRs) were assessed using LSR scale at all visits. RESULTS: At day 29, 18/20 patients received a second treatment due to residual BCC detected clinically, by OCT or RCM. OCT and RCM presented subclinical BCCs in five of 20 cases (25%). At day 90, overall histological cure rate was 70%, corresponding to clinical (65%) and OCT/RCM (60%) cure rates, and agreement between evaluation methods was substantial (kappa ≥ 0.796, P < 0.0001). Clearance rates were similar for sBCCs and nBCCs (P = 0.354) and for lesions treated with IM 0.015% and 0.05% (P = 0.141). LSRs were tolerable, but scarring was observed in the majority of cleared patients. CONCLUSION: Two treatments of combined AFL and IM show potential to treat low-risk BCCs with acceptable tolerability. OCT and RCM show promise to detect subclinical BCCs at short-term follow-up.

Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing.

BACKGROUND: Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified. METHODS: Fresh-frozen tissue from primary tumours, synchronous liver metastases and adjacent normal liver was collected from 21 patients and analysed by whole-exome sequencing on the Illumina HiSeq 2500 platform. Gene variants designated as 'damaging' or 'potentially damaging' by Ingenuity software were used for the subsequent comparative analysis. BAM files were used as the input for the analysis of CNAs using NEXUS software. RESULTS: Shared mutations between the primary tumours and the synchronous liver metastases varied from 50 to 96%. Mutations in APC, KRAS, NRAS, TP53 or BRAF were concordant between the primary tumours and the metastases. Among the private mutations were well-known driver genes such as PIK3CA and SMAD4. The number of mutations was significantly higher in patients with right- compared to left-sided tumours (102 vs. 66, p = 0.004). Furthermore, right- compared to left-sided tumours had a significantly higher frequency of private mutations (p = 0.023). Similarly, CNAs differed between the primary tumours and the metastases. The difference was mostly comprised of numerical and segmental aberrations. However, novel CNAs were rarely observed in specific CRC-relevant genes. CONCLUSION: The examined primary colorectal tumours and synchronous liver metastases had multiple private mutations, indicating a high degree of inter-tumour heterogeneity in the individual patient. Moreover, the acquirement of novel CNAs from primary tumours to metastases substantiates the need for genomic profiling of metastases in order to tailor metastatic CRC therapies. As for the mutational status of the KRAS, NRAS and BRAF genes, no discordance was observed between the primary tumours and the metastases.

In vivo characterization of pustules in Malassezia Folliculitis by reflectance confocal microscopy and optical coherence tomography. A case series study.

BACKGROUND AND OBJECTIVE: Malassezia Folliculitis (MaF) is an inflammatory condition of hair follicles caused by Malassezia yeast. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) are imaging technologies enabling in vivo visualization of superficial skin layers. This study explores morphology of pustules in MaF imaged by OCT and RCM. METHODS: Patients with microscopically verified MaF were included in this case series. Morphology was evaluated qualitatively with RCM and OCT, focusing on shape, border and content of selected pustules. RESULTS: Nine patients with MaF were included. Clinically, six patients presented monomorphic MaF with multiple superficial pustules, while three patients showed more polymorph MaF appearance. In total 13 pustules were investigated by RCM and OCT. In RCM images, pustules varied from having a well-defined border with homogenous content to ill-defined borders with heterogeneous content. A distinct black halo was occasionally observed around pustules as were dilated vessels. In OCT images, pustules appeared polymorphic, showing both well- and ill-defined structures with oval or irregular shape and more or less homogenous content. Malassezia fungi were not discernible by either RCM or OCT. Specific morphological image features in RCM and OCT did not reflect different clinical manifestations of MaF. CONCLUSION: RCM and OCT images identify morphological aspects of MaF pustules, and confirm that MaF is a folliculitis with clinical as well as morphological variance.

Suction blister lesions and epithelialization monitored by optical coherence tomography.

BACKGROUND/PURPOSE: Our objective was to assess epithelialization of suction blister lesions by optical coherence tomography (OCT) and benchmark it to histology using epidermal thickness (ET) as the primary outcome. METHODS: Thirty-two healthy volunteers were recruited to Study 1 and 2. One 10-mm suction blister was raised on each buttock, and the blister roof was excised. Lesions were covered with moisture-retaining dressing. In Study 1, the lesions were OCT-scanned on day 0 (D0), D2 and D4 and excised for histological examination. In Study 2, the progress of epithelialization and skin barrier function were monitored to D14. RESULTS: ET increased from D0 to D2 by 46 µm (P<.001) and from D2 to D4 by 19 µm (P=.004). Compared with histology, OCT overestimated the presence of the epithelium (P<.0001) and ET on D4. Reliable measurements were obtained when the ET of the lesions reached the ET of the normal epidermis from D5-D7 and onwards. The ET development was reflected in decreased transepidermal water loss. CONCLUSION: We found that the OCT technique was poorly discriminative with respect to the neoepithelium and the moist lesion surface material in the early postinjury period. In the later stages, OCT seemed valuable for estimating the advancement of epithelialization.

Diagnostic accuracy of optical coherence tomography in actinic keratosis and basal cell carcinoma.

BACKGROUND: Early diagnosis of non-melanoma skin cancer (NMSC) is potentially possible using optical coherence tomography (OCT) which provides non-invasive, real-time images of skin with micrometre resolution and an imaging depth of up to 2mm. OCT technology for skin imaging has undergone significant developments, improving image quality substantially. The diagnostic accuracy of any method is influenced by continuous technological development making it necessary to regularly re-evaluate methods. OBJECTIVE: The objective of this study is to estimate the diagnostic accuracy of OCT in basal cell carcinomas (BCC) and actinic keratosis (AK) as well as differentiating these lesions from normal skin. METHODS: A study set consisting of 142 OCT images meeting selection criterea for image quality and diagnosis of AK, BCC and normal skin was presented uniformly to two groups of blinded observers: 5 dermatologists experienced in OCT-image interpretation and 5 dermatologists with no experience in OCT. During the presentation of the study set the observers filled out a standardized questionnaire regarding the OCT diagnosis. Images were captured using a commercially available OCT machine (Vivosight ®, Michelson Diagnostics, UK). RESULTS: Skilled OCT observers were able to diagnose BCC lesions with a sensitivity of 86% to 95% and a specificity of 81% to 98%. Skilled observers with at least one year of OCT-experience showed an overall higher diagnostic accuracy compared to inexperienced observers. CONCLUSIONS: The study shows an improved diagnostic accuracy of OCT in differentiating AK and BCC from healthy skin using state-of-the-art technology compared to earlier OCT technology, especially concerning BCC diagnosis.

Growth pattern of colorectal liver metastasis as a marker of recurrence risk.

Despite improved therapy of advanced colorectal cancer, the median overall survival (OS) is still low. A surgical removal has significantly improved survival, if lesions are entirely removed. The purpose of this retrospective explorative study was to evaluate the prognostic value of histological growth patterns (GP) in chemonaive and patients receiving neo-adjuvant therapy. Two-hundred-fifty-four patients who underwent liver resection of colorectal liver metastases between 2007 and 2011 were included in the study. Clinicopathological data and information on neo-adjuvant treatment were retrieved from patient and pathology records. Histological GP were evaluated and related to recurrence free and OS. Kaplan-Meier curves, log-rank test and Cox regression analysis were used. The 5-year OS was 41.8% (95% CI 33.8-49.8%). Growth pattern evaluation of the largest liver metastasis was possible in 224 cases, with the following distribution: desmoplastic 63 patients (28.1%); pushing 77 patients (34.4%); replacement 28 patients (12.5%); mixed 56 patients (25.0%). The Kaplan-Meier analyses demonstrated that patients resected for liver metastases with desmoplastic growth pattern had a longer recurrence free survival (RFS) than patients resected for non-desmoplastic liver metastases (p=0.05). When patients were stratified according to neo-adjuvant treatment in the multivariate Cox regression model, hazard ratios for RFS compared to desmoplastic were: pushing (HR=1.37, 95% CI 0.93-2.02, p=0.116), replacement (HR=2.16, 95% CI 1.29-3.62, p=0.003) and mixed (HR=1.70, 95% CI 1.12-2.59, p=0.013). This was true for chemonaive patients as well as for patients who received neo-adjuvant treatment.

Imaging of collagen deposition disorders using optical coherence tomography.

BACKGROUND: Collagen deposition disorders such as hypertrophic scars, keloids and scleroderma can be associated with significant stigma and embarrassment. These disorders often constitute considerable impairment to quality of life, with treatment posing to be a substantial challenge. Optical coherence tomography (OCT) provides a non-invasive, easily applicable bedside optical imaging method for assessment of the skin. It is hypothesized that OCT imaging may be useful in assessing fibrosis to avoid additional biopsies that could potentially worsen the scarring. METHOD: Thirty-three patients with ordinary scars, hypertrophic scars, keloid scarring, lichen sclerosus et atrophicus and localized or systemic scleroderma were recruited for this pilot study. Affected tissue and adjacent healthy skin were scanned using OCT and digitally photographed. Density measurements were performed in ImageJ on OCT images from scleroderma patients, both systemic and morphea (10 patients), keloid patients (10 patients) and healthy skin adjacent to keloids (10 patients). RESULTS: OCT images of scarring diseases showed varying degrees of disruption to the skin architecture. OCT characteristics were identified for each lesion type. Hypertrophic scars displayed an increased vascularity and signal-rich bands correlating to excessive collagen deposition. Keloids depicted a disarray of hyper-reflective areas primarily located in the upper dermis. Additionally, the dermis displayed a heterogeneous morphology without indications of any vascular supply or lymphatic network. In contrast to keloids, scleroderma displayed a more cohesive backscattering indicating a difference in density of collagen or other dermal structures. OCT images demonstrated no significant differences between mean density measurements in OCT images of scleroderma, keloid and healthy skin (P = 0.07). CONCLUSION: The OCT imaging appears to identify different scarring mechanisms, and therefore be of potential use in the assessment of outcomes following non-invasive therapy of e.g. early or progressive lesions.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing photodynamic therapy reveals subclinical residual lesions.

BACKGROUND: Photodynamic therapy with methyl aminolaevulinate (MAL-PDT) is a widely used non-invasive treatment modality for non-melanoma skin cancer (NMSC). The outcome of MAL-PDT is usually primarily evaluated clinically. Optical coherence tomography (OCT) is a non-invasive imaging technology based on interferiometry. OCT has been proven to provide high accuracy in identifying NMSC lesions and performing thickness measurements of thin tumours. OBJECTIVES: To describe the OCT morphology in in-vivo NMSC lesions during MAL-PDT treatment and to investigate the use of OCT in evaluating the response of MAL-PDT treated NMSC lesions. METHODS: A total of 18 biopsy-proven basal cell carcinomas and actinic keratoses were monitored by OCT during 2 sessions of MAL-PDT treatment. At 3-months follow-up the patients were assessed both by OCT and clinically. If the clinical and OCT evaluation came to different conclusions on recurrence of the lesion, patients were followed more closely at clinical appointments for up to one year after the PDT treatment. RESULTS: All lesions displayed at least one OCT characteristic before MAL-PDT treatment. At 3 months follow-up, recurrence was suspected clinically in 5/18 cases, with OCT in 7/18 cases. OCT correctly identified all of the partial responses also found by the clinical examinations. In both cases where recurrence was only found in OCT, this was subsequently confirmed by histology. CONCLUSIONS: Our study suggests that OCT identified 29% more recurrences than clinical examination alone. OCT can detect subclinical residual NMSC lesions after MAL-PDT treatment and may therefore be an accurate tool for early detection of residual lesional tissue.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing imiquimod therapy.

PURPOSE: To explore the application of optical coherence tomography (OCT) imaging of basal cell carcinomas (BCC) and actinic keratosis (AK) before, during and after imiquimod treatment and the ability of OCT to predict treatment outcome. METHODS: The study subjects were 20 patients with biopsy-verified BCC (9) or AK (11). Patients were OCT-scanned before, after 1 and 4 weeks of imiquimod treatment and after 3 months. Lesions were identified clinically and with OCT. Thickness and morphology of the lesions were recorded at each visit. Any remaining lesions were biopsied at follow-up. RESULTS: Complete data sets were available for 16 patients (8 women and 8 men aged 52-82 years), four in-compliant patients were excluded. OCT identified all lesions. Previously suggested OCT-criteria identified 5/8 BCCs. Crusting, ulceration and active treatment significantly reduced image quality. All BCCs cleared, but at follow-up residual structures were seen clinically in 4 cases. OCT and histology both ruled out residual BCC. For AKs significant thinning occurred after 1 week of treatment (P = 0.04). Imiquimod cleared 2/8 AKs, and significantly decreased the thickness of all lesions (P = 0.02). CONCLUSIONS: OCT could identify superficial BCC and AK before treatment. Monitoring during imiquimod treatment revealed impaired image quality most likely caused by inflammation, crusting and ulceration. On follow-up, OCT showed thinning of AKs indicating effect of treatment. All treated BCCs cleared, but where residual tissue was suspected clinically this could be ruled out by OCT.

Improved controlled atmosphere high temperature scanning probe microscope.

To locally access electrochemical active surfaces and interfaces in operando at the sub-micron scale at high temperatures in a reactive gas atmosphere is of great importance to understand the basic mechanisms in new functional materials, for instance, for energy technologies, such as solid oxide fuel cells and electrolyzer cells. Here, we report on advanced improvements of our original controlled atmosphere high temperature scanning probe microscope, CAHT-SPM. The new microscope can employ a broad range of the scanning probe techniques including tapping mode, scanning tunneling microscopy, scanning tunneling spectroscopy, conductive atomic force microscopy, and Kelvin probe force microscopy. The temperature of the sample can be as high as 850 °C. Both reducing and oxidizing gases such as oxygen, hydrogen, and nitrogen can be added in the sample chamber and the oxygen partial pressure (pO2) is monitored by an oxygen sensor. We present here some examples of its capabilities demonstrated by high temperature topography with simultaneously ac electrical conductance measurements during atmosphere changes, electrochemical impedance spectroscopy at various temperatures, and measurements of the surface potential. The improved CAHT-SPM, therefore, holds a great potential for local sub-micron analysis of high-temperature and gas induced changes of a wide range of materials.

High temperature and pressure electrochemical test station.

An electrochemical test station capable of operating at pressures up to 100 bars and temperatures up to 400 °C has been established. It enables control of the partial pressures and mass flow of O2, N2, H2, CO2, and H2O in a single or dual environment arrangement, measurements with highly corrosive media, as well as localized sampling of gas evolved at the electrodes for gas analysis. A number of safety and engineering design challenges have been addressed. Furthermore, we present a series of electrochemical cell holders that have been constructed in order to accommodate different types of cells and facilitate different types of electrochemical measurements. Selected examples of materials and electrochemical cells examined in the test station are provided, ranging from the evaluation of the ionic conductivity of liquid electrolytic solutions immobilized in mesoporous ceramic structures, to the electrochemical characterization of high temperature and pressure alkaline electrolysis cells and the use of pseudo-reference electrodes for the separation of each electrode contribution. A future perspective of various electrochemical processes and devices that can be developed with the use of the established test station is provided.

The influence of age and aerobic fitness: effects on mitochondrial respiration in skeletal muscle.

AIM: Mitochondrial function has previously been studied in ageing, but never in humans matched for maximal oxygen uptake ((V)·O2max). Furthermore, the influence of ageing on mitochondrial substrate sensitivity is not known. METHODS: Skeletal muscle mitochondrial respiratory capacity and mitochondrial substrate sensitivity were measured by respirometry in young (23 ± 3 years) and middle-aged (53 ± 3 years) male subjects with similar (V)·O2max. Protocols for respirometry included titration of substrates for complex I (glutamate), complex II (succinate) and both (octanoyl carnitine) for calculation of substrate sensitivity (C(50) ). Myosin heavy chain (MHC) isoforms, citrate synthase (CS) and ß-hydroxy-acyl-CoA-dehydrogenase (HAD) activity, mitochondrial DNA (mtDNA) content, protein levels of complexes I-V and antioxidant defence system [manganese superoxide dismutase (MnSOD)] were measured. RESULTS: No differences were found in maximal mitochondrial respiration or C(50) with glutamate (2.0 ± 0.3 and 1.8 ± 0.3 mm), succinate (3.7 ± 0.2 and 3.8 ± 0.4 mm) or octanoyl carnitine (47 ± 8 and 56 ± 7 µm) in young and middle-aged subjects respectively. Normalizing mitochondrial respiration to mtDNA young subjects had a higher (P < 0.05) respiratory capacity per mitochondrion compared to middle-aged subjects. HAD activity and mtDNA per mg tissue were higher in middle-aged compared to young subjects. Middle-aged had a higher MHC I isoform and a lower MHC IIX isoform content compared to young subjects. CONCLUSION: Mitochondrial substrate sensitivity is not affected by ageing. When young and middle-aged men are carefully matched for (V)·O2max, mitochondrial respiratory capacity is also similar. However, per mitochondrion respiratory capacity was lower in middle-aged compared to young subjects. Thus, when matched for (V)·O2max, middle-aged seem to require a higher mitochondrial content than young subjects.

Neuroradiologic correlates of cognitive impairment in adult Moyamoya disease.

BACKGROUND AND PURPOSE: MMD has been shown to result in impairment of executive functioning in adults. The purpose of this study was to correlate presurgical neuropsychological assessments with the severity of primary MMD as measured by CBF and CVR and with secondary damage from MMD as estimated by cortical stroke and WMD. MATERIALS AND METHODS: A retrospective analysis of 31 adult patients with MMD was performed. Xe-CT was used to obtain CBF and CVR, and MRI was reviewed to grade cortical stroke and WMD. Two tests of executive functioning (FAS and TMT-B) were correlated with imaging findings. A multiple regression analysis was performed. RESULTS: There was a significant overall positive relationship between mean CBF and FAS (P = .038) and TMT-B scores (P = .014). A significant negative relationship was present between the WMD score and the FAS (P = .009) and TMT-B scores (P = .015). Per-region analysis demonstrated that FAS and TMT-B scores were significantly decreased by the presence of a posterior stroke (P < .0001 and P = .001) or WMD (P = .006 and P = .004). All patients with posterior parieto-occipital WMD or stroke also had secondary disease in the anterior regions. CONCLUSIONS: Impaired executive functioning in adults with MMD is most strongly associated secondary damage in the form of WMD or cortical stroke. The effect is most profound with parieto-occipital lobe involvement, likely a reflection of overall disease severity. Increasing global WMD burden may be a better indicator of cognitive decline than cortical infarction. Patients with higher baseline CBF seem to have better cognitive functioning.