Happiness across the borders-A cross-sectional study among patients with psoriasis and atopic dermatitis in Europe.

BACKGROUND: Dermatological research has traditionally concentrated on evaluating mental comorbidities, neglecting positive concepts like happiness. Initial studies indicate that psoriasis and atopic dermatitis (AD) impair the happiness of those affected. Considering global happiness variations, this study aimed to explore the disease- and country-specific differences in disease-related quality of life and happiness, and potential influential factors on heuristic happiness among psoriasis and AD patients in Europe. METHODS: A cross-sectional multicentre study was conducted in dermatology departments of university-affiliated hospitals in eight European countries (Austria, Germany, Italy, Malta, Poland, Portugal, Romania and Ukraine) between October 2021 and February 2023. Adult psoriasis and AD patients completed a standardized questionnaire in their native languages, providing data on demographics, disease-related characteristics, disease-related quality of life (Dermatology Life Quality Index, DLQI), heuristic happiness, positive affect (PA), negative affect (NA) and satisfaction with life (SWL). Descriptive analysis and quantile regression were performed. RESULTS: Between psoriasis (n = 723) and AD (n = 316) patients almost no differences were observed in happiness, SWL and NA, except for DLQI and small differences in PA, with AD patients reporting greater impact than psoriasis patients. Country-wise variation emerged in DLQI, heuristic happiness, PA, NA and SWL with Austrian patients displaying the highest levels of happiness, satisfaction and positivity, coupled with higher treatment care and lower disease severity. Quantile regression revealed varying coefficients for predictor variables across quantiles, indicating, for example positive effects on heuristic happiness associated with current or previous receipt of systemic therapies at different quantiles. CONCLUSION: This study shows notable happiness differences across European countries and significant disease-related variations, particularly with AD patients being more impaired than psoriasis patients. The findings highlight the need for equality in treatment access and support the development of targeted positive psychological interventions to enhance happiness considering country-specific distinctions in future research and health policies for psoriasis and AD patients.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

Complete response of advanced cutaneous squamous cell and basal cell carcinomas with sequential cemiplimab and sonidegib therapy.

A 78-year-old woman was referred to our skin cancer centre with three previous incomplete resections in the left cavum conchae of a deep-infiltrating locally advanced, but still asymptomatic basal cell carcinoma (BCC). The patient noted furthermore two rapidly growing exophytic lesions in the left preauricular and cervical area in the last weeks. The clinical and histological distinction of locally advanced from metastatic cutaneous squamous cell carcinoma (CSCC) lesions was challenging. Imaging analysis with CT scans showed, however, an involvement of the parotid gland as well as multiple small lymph node metastases. The interdisciplinary tumour board decision at our institution recommended a systemic treatment with the PD1-antibody cemiplimab. After 13 cycles with cemiplimab at a dose of 350 mg intravenously every 3-weeks, the patient showed a complete response of the two CSCC lesions with histological confirmation. However, the BCC of the left ear appeared to be unchanged and still asymptomatic. The interdisciplinary tumour board considered this tumour to be no candidate for a curative resection or irradiation. Therefore, the patient was exposed to the hedgehog inhibitor sonidegib with a conventional dose of 200 mg orally per day. After 3 months of treatment, the tumour showed a markable regression and a complete response was confirmed by 3-punch biopsies from this preoperated lesion. Both cemiplimab and sonidegib were excellently tolerated with almost no adverse events apart from a mild fatigue (CTC grade 1) over the first 3 weeks of the cemiplimab therapy. There were no laboratory abnormalities found.

Pilot study of peer modeling with psychological inoculation to promote coronavirus vaccination.

Promoting coronavirus vaccination is deterred by misinformation, ranging from elaborate conspiracy theories about sinister purposes to exaggeration of side effects, largely promulgated by social media. In this pilot study, we tested the effects of different messages on actions leading to vaccination. Two theory-based advertisements were produced for Facebook, which provided video testimonials from peer role models recommending vaccination and its benefits while providing psychological inoculation through the models' acknowledging misinformation, rejecting it and receiving the vaccine. These ads were paid to appear on Facebook users' feeds in rural counties in South Texas, along with a generic vaccine promotion ad from the CDC without peer models or psychological inoculation. Ad viewers could click a link to 'find a vaccine near you'; these responses served as the outcome variable for assessing experimental effects. Ads featuring peer modeling with psychological inoculation yielded a significantly higher rate of positive responses than CDC ads (30.5 versus14.9/1000 people reached in English and 49.7 versus 31.5/1000 in Spanish; P < 0.001 for both English and Spanish rate comparisons). This provides useful pilot data supporting the hypothesis that theory-based communication, i.e. peer modeling with psychological inoculation, may be more effective than more traditional forms of advertising for promoting coronavirus vaccination.

[COVID-19 and the central and peripheral nervous system]. / COVID-19: Auswirkungen auf das zentrale und periphere Nervensystem.

The health effects of coronavirus disease 2019 (COVID-19) caused by the infection of SARS-CoV­2 (severe acute respiratory syndrome coronavirus 2) are becoming increasingly clear as the pandemic spreads. In addition to the lungs, other organs are also affected, which can significantly influence morbidity and mortality. In particular, neurological symptoms involving the central nervous system can lead to acute or long-term consequences. The mechanisms of this neuropathogenesis of SARS-CoV­2 infection and its relation to acute and chronic neurological symptoms are the subject of current studies investigating a potential direct and indirect viral infection of the nervous system. The following review summarizes the current status of neuropathological manifestations, molecular pathogenesis, possible infection pathways in the nervous system, and systemic effects. In addition, an overview of the Germany-wide CNS-COVID19 registry and collaborations is presented, which should contribute to a better understanding of the neurological symptoms of COVID-19.

An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 was one of the first disease-specific questionnaires developed in 1996 to assess quality of life (QoL) in patients with breast cancer (BC). However, since 1996 major changes in BC treatment have occurred, requiring an update of the EORTC BC module. This study presents the results of the phase I-III update of the QLQ-BR23 questionnaire. PATIENTS AND METHODS: The update of the EORTC QLQ-BR23 module followed standard EORTC guidelines. A systematic literature review revealed 83 potential relevant QoL issues during phases I and II. After shortening the issues list and following interviews with patients and health care providers, 15 relevant issues were transformed into 27 items. The preliminary module was pretested in an international, multicentre phase III study to identify and solve potential problems with wording comprehensibility and acceptability of the items. Descriptive statistics are provided. Analyses were qualitative and quantitative. We provide a psychometric structure of the items. RESULTS: The phase I and II results indicated the need to supplement the original QLQ-BR23 with additional items related to newer therapeutic options. The phase III study recruited a total of 250 patients (from 12 countries). The final updated phase III module contains a total of 45 items: 23 items from the QLQ-BR23 and 22 new items. The new items contain two multi-item scales: a target symptom scale and a satisfaction scale. The target symptom scale can be divided into three subscales: endocrine therapy, endocrine sexual and skin/mucosa scale. CONCLUSION: Our work has led to the development of a new EORTC QLQ-BR45 module that provides a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients' QoL. The final version of the EORTC QLQ-BR45 is currently available for use in clinical practice. The final phase IV study is underway to confirm psychometric properties of the module.

An integrative correlation of myopathology, phenotype and genotype in late onset Pompe disease.

AIMS: Pompe disease is caused by pathogenic mutations in the alpha 1,4-glucosidase (GAA) gene and in patients with late onset Pome disease (LOPD), genotype-phenotype correlations are unpredictable. Skeletal muscle pathology includes glycogen accumulation and altered autophagy of various degrees. A correlation of the muscle morphology with clinical features and the genetic background in GAA may contribute to the understanding of the phenotypic variability. METHODS: Muscle biopsies taken before enzyme replacement therapy were analysed from 53 patients with LOPD. On resin sections, glycogen accumulation, fibrosis, autophagic vacuoles and the degree of muscle damage (morphology-score) were analysed and the results were compared with clinical findings. Additional autophagy markers microtubule-associated protein 1A/1B-light chain 3, p62 and Bcl2-associated athanogene 3 were analysed on cryosections from 22 LOPD biopsies. RESULTS: The myopathology showed a high variability with, in most patients, a moderate glycogen accumulation and a low morphology-score. High morphology-scores were associated with increased fibrosis and autophagy highlighting the role of autophagy in severe stages of skeletal muscle damage. The morphology-score did not correlate with the patient's age at biopsy, disease duration, nor with the residual GAA enzyme activity or creatine-kinase levels. In 37 patients with LOPD, genetic analysis identified the most frequent mutation, c.-32-13T>G, in 95%, most commonly in combination with c.525delT (19%). No significant correlation was found between the different GAA genotypes and muscle morphology type. CONCLUSIONS: Muscle morphology in LOPD patients shows a high variability with, in most cases, moderate pathology. Increased pathology is associated with more fibrosis and autophagy.

Outcomes and outcome measures used in evaluation of communication training in oncology - a systematic literature review, an expert workshop, and recommendations for future research.

BACKGROUND: Communication between health care provider and patients in oncology presents challenges. Communication skills training have been frequently developed to address those. Given the complexity of communication training, the choice of outcomes and outcome measures to assess its effectiveness is important. The aim of this paper is to 1) perform a systematic review on outcomes and outcome measures used in evaluations of communication training, 2) discuss specific challenges and 3) provide recommendations for the selection of outcomes in future studies. METHODS: To identify studies and reviews reporting on the evaluation of communication training for health care professionals in oncology, we searched seven databases (Ovid MEDLINE, CENTRAL, CINAHL, EMBASE, PsychINFO, PsychARTICLES and Web of Science). We extracted outcomes assessed and the respective assessment methods. We held a two-day workshop with experts (n = 16) in communication theory, development and evaluation of generic or cancer-specific communication training and/or outcome measure development to identify and address challenges in the evaluation of communication training in oncology. After the workshop, participants contributed to the development of recommendations addressing those challenges. RESULTS: Out of 2181 references, we included 96 publications (33 RCTs, 2 RCT protocols, 4 controlled trials, 36 uncontrolled studies, 21 reviews) in the review. Most frequently used outcomes were participants' training evaluation, their communication confidence, observed communication skills and patients' overall satisfaction and anxiety. Outcomes were assessed using questionnaires for participants (57.3%), patients (36.0%) and observations of real (34.7%) and simulated (30.7%) patient encounters. Outcomes and outcome measures varied widely across studies. Experts agreed that outcomes need to be precisely defined and linked with explicit learning objectives of the training. Furthermore, outcomes should be assessed as broadly as possible on different levels (health care professional, patient and interaction level). CONCLUSIONS: Measuring the effects of training programmes aimed at improving health care professionals' communication skills presents considerable challenges. Outcomes as well as outcome measures differ widely across studies. We recommended to link outcome assessment to specific learning objectives and to assess outcomes as broadly as possible.

Expression profile of pattern recognition receptors in skeletal muscle of SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients.

AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non-neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis-associated speck-like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are early events in ALS, we hypothesized that PRRs might be abnormally expressed in muscle fibre degeneration. METHODS: Western blot analysis, real-time PCR and immunohistochemistry were performed with muscle tissue from presymptomatic and early-symptomatic male SOD1(G93A) mice and with muscle biopsies of control and sporadic ALS (sALS) patients. Analysed PRRs include nucleotide-binding oligomerization domain-like (NOD-like) receptor protein 1 (NLRP1), NLR protein 3 (NLRP3), NLR family CARD domain-containing 4 (NLRC4) and absent in melanoma 2. Additionally, expression levels of ASC, caspase 1, interleukin 1 beta (IL1ß) and interleukin 18 (IL18) were evaluated. RESULTS: Expression of PRRs and ASC was detected in murine and human tissue. The PRR NLRC4, caspase 1 and IL1ß were significantly elevated in denervated muscle of SOD1(G93A) mice and sALS patients. Furthermore, levels of caspase 1 and IL1ß were already increased in presymptomatic animals. CONCLUSION: Our findings suggest that increased inflammasome activation may be involved in skeletal muscle pathology in ALS. Furthermore, elevated levels of NLRC4, caspase 1 and IL1ß reflect early changes in the skeletal muscle and may contribute to the denervation process.

Novel SBF2 mutations and clinical spectrum of Charcot-Marie-Tooth neuropathy type 4B2.

Biallelic SBF2 mutations cause Charcot-Marie-Tooth disease type 4B2 (CMT4B2), a sensorimotor neuropathy with autosomal recessive inheritance and association with glaucoma. Since the discovery of the gene mutation, only few additional patients have been reported. We identified seven CMT4B2 families with nine different SBF2 mutations. Revisiting genetic and clinical data from our cohort and the literature, SBF2 variants were private mutations, including exon-deletion and de novo variants. The neuropathy typically started in the first decade after normal early motor development, was predominantly motor and had a rather moderate course. Electrophysiology and nerve biopsies indicated demyelination and excess myelin outfoldings constituted a characteristic feature. While neuropathy was >90% penetrant at age 10 years, glaucoma was absent in ~40% of cases but sometimes developed with age. Consequently, SBF2 mutation analysis should not be restricted to individuals with coincident neuropathy and glaucoma, and CMT4B2 patients without glaucoma should be followed for increased intraocular pressure. The presence of exon-deletion and de novo mutations demands comprehensive mutation scanning and family studies to ensure appropriate diagnostic approaches and genetic counseling.

One in two cancer patients is significantly distressed: Prevalence and indicators of distress.

OBJECTIVE: Psychological distress is common in cancer patients, and awareness of its indicators is essential. We aimed to assess the prevalence of psychological distress and to identify problems indicative of high distress. METHODS: We used the distress thermometer (DT) and its 34-item problem list to measure psychological distress in 3724 cancer patients (mean age 58 years; 57% women) across major tumor entities, enrolled in an epidemiological multicenter study. To identify distress-related problems, we conducted monothetic analyses. RESULTS: We found high levels of psychological distress (DT ≥ 5) in 52% of patients. The most prevalent problems were fatigue (56%), sleep problems (51%), and problems getting around (47%). Sadness, fatigue, and sleep problems were most strongly associated with the presence of other problems. High distress was present in 81.4% of patients reporting all 3 of these problems (DT M = 6.4). When analyzing only the subset of physical problems, fatigue, problems getting around, and indigestion showed the strongest association with the remaining problems and 76.3% of patients with all 3 problems were highly distressed (DT M = 6.1). CONCLUSIONS: Our results show a high prevalence of psychological distress in cancer patients, as well as a set of problems that indicate the likely presence of other problems and high distress and can help clinicians identify distressed patients even if no routine distress screening is available.

[The Development of Quality Standards for the Psychosocial Outpatient Care of Cancer Patients - Results of a Delphi Survey]. / Die Entwicklung von Qualitätsstandards für die ambulante psychosoziale Krebsberatung ­ Ergebnisse einer Delphibefragung.

BACKGROUND: The psychosocial outpatient care of cancer patients and their families is a central element of oncological care. To date, the provision of care to this group is very heterogeneous in terms of the spectrum of services offered and quality of care. The aim of this study was to develop a multidimensional classification of quality standards for psychosocial outpatient cancer counseling. METHOD: We conducted a study using the Delphi method. 97 experts from more than 10 different fields of action or institutional contexts (e. g. mental health care professionals, cancer societies, self-help groups) were included in 3 rounds of Delphi assessment. Finally, 134 single criteria within 9 quality areas (e. g. staff, range of services, documentation) were generated and evaluated for their relevance, clarity, comprehensiveness and level of obligation. RESULT: A total of 119 individual criteria (88.8%) achieved consensus within the 3 Delphi rounds. Hereof, 94 were basic criteria (79%) and 25 optional criteria (21%). The highest number of individual criteria referred to the service spectrum (26 individual criteria), documentation (21) as well as staff and accessibility (16 each). Fifteen criteria (11.2%) achieved no consensus and were removed. CONCLUSION: For the first time, criteria for assessing the quality of psychosocial outpatient cancer counseling with expert consensus are available, facilitating the evaluation of psychosocial outpatient cancer counseling.

HIV encephalopathy: glial activation and hippocampal neuronal apoptosis, but limited neural repair.

OBJECTIVES: HIV infection affects the central nervous system (CNS), frequently causing cognitive impairment. Hippocampal injury impedes the ability to transfer information into memory. Therefore, we aimed to examine neuronal injury and repair in the hippocampal formation in HIV encephalopathy. METHODS: We compared neuropathological findings in 14 autopsy cases after death from systemic complications of HIV infection and in 15 age-matched HIV-negative control cases after sudden death from nonneurological causes using immunohistochemistry. RESULTS: The density of apoptotic granule cells in the dentate gyrus was higher in HIV-infected than in control cases (P = 0.048). Proliferation of neural progenitor cells in the dentate gyrus was increased in HIV infection (P = 0.028), whereas the density of recently generated TUC-4 [TOAD (turned on after division)/Ulip/CRMP family 4]-expressing neurons in this region was not significantly elevated in HIV-infected cases (P = 0.13). HIV infection caused microglial activation and astrocytosis in the neocortex and hippocampal formation. Conversely, we were unable to detect more pronounced axonal injury in HIV-infected than in control cases. CONCLUSIONS: As in other infections involving the CNS, apoptosis of hippocampal neurons accompanied by microglial activation and astrocytosis is a prominent feature of HIV encephalopathy. The regenerative potential, assessed using the density of young neurons in the hippocampal dentate gyrus, in HIV infection appears to be lower than in acute bacterial meningitis and septic encephalitis.

[Structures and Practice of Psychological Services in Oncological and Diabetological Rehabilitation: Results of a Nationwide Survey]. / Strukturen und Praxis der psychologischen Abteilungen in der onkologischen und diabetologischen Rehabilitation: Ergebnisse einer bundesweiten Befragung.

OBJECTIVE: To study the structural frame conditions and the contents of psychological activity in oncological rehabilitation as well as in rehabilitation of patients with type 2 diabetes. METHODS: We conducted a nationwide survey of psychological services in rehabilitation facilities treating oncological patients and patients with type 2 diabetes. RESULTS: 71 (of 145) oncological and 21 (of 63) diabetological rehabilitation facilities participated in the survey. In both indication areas an average of 1.1 psychologists is in charge of 100 patients. Between some rehabilitation facilities, however, there are considerable differences concerning the psychologist/patient ratio (in oncological rehabilitation facilities: standard deviation (SD)=0.52; in diabetological rehabilitation facilities: SD=0.35). Moreover, there is large heterogeneity among rehabilitation facilities as to the percentages of patients obtaining psychological interventions and the way in which psychological services allocate their working time. CONCLUSION: The general set-up of psychological services in oncological and diabetological rehabilitation facilities (especially the low psychologist/patient ratio in many facilities) can partly be considered insufficient. The heterogeneity with respect to the structural frame conditions and practice of psychological services reveals the low degree of standardization of psychological activity in both indication areas.

Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis.

Intracellular accumulations of mutant, misfolded proteins are major pathological hallmarks of amyotrophic lateral sclerosis (ALS) and related disorders. Recently, mutations in Sigma receptor 1 (SigR1) have been found to cause a form of ALS and frontotemporal lobar degeneration (FTLD). Our goal was to pinpoint alterations and modifications of SigR1 in ALS and to determine how these changes contribute to the pathogenesis of ALS. In the present study, we found that levels of the SigR1 protein were reduced in lumbar ALS patient spinal cord. SigR1 was abnormally accumulated in enlarged C-terminals and endoplasmic reticulum (ER) structures of alpha motor neurons. These accumulations co-localized with the 20s proteasome subunit. SigR1 accumulations were also observed in SOD1 transgenic mice, cultured ALS-8 patient's fibroblasts with the P56S-VAPB mutation and in neuronal cell culture models. Along with the accumulation of SigR1 and several other proteins involved in protein quality control, severe disturbances in the unfolded protein response and impairment of protein degradation pathways were detected in the above-mentioned cell culture systems. Furthermore, shRNA knockdown of SigR1 lead to deranged calcium signaling and caused abnormalities in ER and Golgi structures in cultured NSC-34 cells. Finally, pharmacological activation of SigR1 induced the clearance of mutant protein aggregates in these cells. Our results support the notion that SigR1 is abnormally modified and contributes to the pathogenesis of ALS.

Comparison of human metapneumovirus, respiratory syncytial virus and Rhinovirus respiratory tract infections in young children admitted to hospital.

Respiratory Syncytial Virus (RSV), Human metapneumovirus (HMPV), and Rhinoviruses (RV) are frequent causes of respiratory tract infections in young children. We compared laboratory and clinical findings in children with comparable age distribution and hospitalized due to RSV, HMPV or RV infections. Viral pathogens were detected by a quantitative real time PCR from nasopharyngeal aspirates. No significant differences in the admission diagnosis, laboratory parameters, patient demographics and treatment measures between the three viral causes of respiratory illness were found. No correlation between viral load and disease severity was observed however, there was a significantly lower concentration of the nasopharyngeal interleukin 8 (IL-8) in children with RV compared to HMPV and RSV, indicating a milder proinflammatory reaction. Moreover, RV-infected children had significantly lower body temperature, higher leucocyte counts in peripheral blood, and a tendency to have a shorter stay in hospital than children with either HMPV or RSV infection. Taken together, clinical presentation of the infections with RSV, HMPV, and RV is similar among children of the same age group and not clearly distinguishable by standard clinical or laboratory findings. Therefore, virus specific testing should be included regularly for routine diagnosis of children with respiratory tract infections.

Elevation of plasma 1-deoxy-sphingolipids in type 2 diabetes mellitus: a susceptibility to neuropathy?

BACKGROUND AND PURPOSE: Diabetic distal sensorimotor polyneuropathy (DSPN) is a frequent, disabling complication of diabetes mellitus. There is increasing evidence that sphingolipids play a role in insulin resistance and type 2 diabetes (T2DM). Whether neurotoxic 1-deoxy-sphingolipids are elevated in DSPN patients' plasma and whether levels correlate to the DSPN stage were examined. METHODS: The plasma profile of 12 sphingoid bases in patients with DSPN and T2DM(n = 39) were cross-sectionally compared to other nerve disorders including chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 13), transthyretin-related familial amyloid polyneuropathy (FAP) (n = 10), amyotrophic lateral sclerosis (ALS) (n = 13) and small fibre neuropathy (n = 12) by liquid chromatography mass spectrometry. Correlations to the DSPN stage were additionally performed. Furthermore, the sphingoid base distribution in sural nerve specimens was measured in patients with DSPN (n = 6) compared to CIDP (n = 3). RESULTS: A significantly increased amount of 1-deoxy-sphingolipids [1-deoxy-sphinganine (0.11 ± 0.06 µmol/l), 1-deoxy-sphingosine (0.24 ± 0.16 µmol/l)] in patients with DSPN was observed compared to age-matched healthy controls (0.06 ± 0.03 µmol/l; 0.12 ± 0.05 µmol/l) and to the other groups. (Para)clinical parameters including sensory loss, neuropathic pain, weakness, vibration perception, nerve conduction velocity, sensory nerve action potentials (sural nerve) and duration of T2DM did not correlate with plasma 1-deoxy-sphingolipid levels, neither did the clinical stage according to the Dyck classification for DSPN. Sphingolipid levels in sural nerve biopsies showed no differences between DSPN and CIDP. Contrarily, patients with a small fibre neuropathy had decreased C20-sphingosine plasma levels. CONCLUSION: 1-deoxy-sphingolipid plasma levels are significantly elevated in DSPN. They are already detectable in early disease stages but do not correlate with the clinical course. Further knowledge on 1-deoxy-sphingolipids might lead to a better pathophysiological understanding and future treatment options in DSPN.

In situ studies of growth of carbon nanotubes on a local metal microheater.

Using electron microscopy and in situ Raman spectroscopy we investigate carbon nanotube growth from ethylene on iron catalyst islands patterned on top of Mo electrodes, using a highly localized resistive on-chip-heating technique. A clear transition is observed between multi-walled and single-walled nanotube growth as the local temperature of the heater is increased. This can be rationalized in terms of the balance between incoming carbon flux and diffusion through the catalyst particle. The observed changes in heater performance on exposure to the hydrocarbon gas are explored and related to the formation of molybdenum carbide, leading to a rapid change in resistivity and heating power that increases the local temperature of the heater by up to 100 °C. This provides optimum conditions for nanotube growth after an incubation time that depends on the carbon flux.