Advanced portable micro-SORS prototype coupled with SERDS for heritage science.

We investigate the subsurface composition of turbid materials at the micro scale by means of a portable non-invasive technique, micro-spatially offset Raman spectroscopy (micro-SORS), combined with shifted excitation Raman difference spectroscopy (SERDS). This combination enables the microscale layer analysis and allows to deal effectively with highly fluorescing samples as well as ambient light, all in a form of an in-house portable prototype device optimised for applications in heritage science. The instrument comprises ability to simultaneously collect multiple spectra by means of an optical fibre bundle, thus reducing the dead time and simplifying the ease of deployment of the technique. The performance of the synergy between micro-SORS and 785 nm SERDS dual-wavelength diode laser is demonstrated on a stratified mock-up painting samples including highly fluorescing painted layers. This instrumental approach could be ground-breaking in heritage science, due to the largely unmet need of analysing the molecular composition of subsurface of artworks non-invasively and in situ, and in the presence of fluorescent background and ambient light. Moreover, many other fields are expected to benefit from this technological advancement such as solar energy, forensic and food analytical areas.

SARS-CoV-2 viral RNA load dynamics in the nasopharynx of infected children.

It is important to understand the temporal trend of the paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined the differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. Serial cycle threshold values of SARS-CoV-2 from the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral loads (mean cycle threshold on day 7 of illness 28.6 vs. 36.7, P = 0.02). Peak SARS-CoV-2 viral loads occurred around day 2 of illness in infected children. Although we were unable to directly demonstrate infectivity, the detection of significant amount of virus in the upper airway of asymptomatic children suggest that they have the potential to shed and transmit SARS-CoV-2. Our study highlights the importance of contact tracing and screening for SARS-CoV-2 in children with epidemiological risk factors regardless of their symptom status, in order to improve containment of the virus in the community, including educational settings.

[Inpatient multimodal pain therapy : Additive value of neuromuscular core stability exercises for chronic back pain]. / Die stationäre multimodale Schmerztherapie : Additiver Wert eines sensomotorischen Stabilisationstrainings bei chronischem Rückenschmerz.

INTRODUCTION: The medical and healthcare economic burden caused by chronic lumbar back pain (CLBP) requires the use of interdisciplinary treatment approaches. The present study aimed to evaluate whether the effectiveness of inpatient multimodal pain therapy (MPT, operations and procedures (OPS) coding 8-918.02), can be increased by implementing additional neuromuscular core stability exercises (NCSE). MATERIAL AND METHODS: As part of a prospective controlled study, subjects with CLBP (n = 48, 17 males, 58.2 ± 11.7 years) were allocated to one of two groups. One group received standard care (SC, n =23) encompassing manual, pharmacological and psychological therapy in addition to passive physiotherapeutic applications. The intervention group (IG, n =25) additionally completed NCSE. On the day of admission and on discharge as well as 1 and 6 weeks after inpatient care, pain intensity (numeric rating scale), pain-related routine daily functions (Oswestry disability index), well-being (SF-12 Health Survey) and motor function parameters (trunk strength, endurance and postural control) were assessed. Data analysis was performed using statistical inference methods. In addition, effect sizes (Cohen's d) of intergroup differences were calculated. RESULTS: Both groups showed significant reductions in pain intensity (p < 0.05, d > 0.6) at all measurement points (MP). Physical well-being and disability (p < 0.05, d > 0.6) were improved 1 week after discharge in the intervention group only. Overall, no systematic differences between groups were detected (p > 0.05). In relation to the motor outcomes, no significant changes over time nor between groups were verified (p > 0.05). DISCUSSION: Despite the use of an additional NCSE, no significant added value in individuals with CLBP could be detected, although a systematic pre-post effect in daily functions and physical well-being (one week after discharge) was observed for the IG only. Therefore, on the basis of the study results, the implementation of additional NCSE into the inpatient MPT cannot be clearly recommended. To further delineate the therapeutic relevance, studies with larger sample sizes are needed.

Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study.

BACKGROUND: Patients with severe oral lichen planus refractory to standard topical treatment currently have limited options of therapy suitable for long-term use. Oral alitretinoin (9-cis retinoic acid) was never systematically investigated in clinical trials, although case reports suggest its possible efficacy. OBJECTIVES: To assess the efficacy and safety of oral alitretinoin taken at 30 mg once daily for up to 24 weeks in the treatment of severe oral lichen planus refractory to standard topical therapy. METHODS: We conducted a prospective open-label single arm pilot study to test the efficacy and safety of 30 mg oral alitretinoin once daily for up to 24 weeks in severe oral lichen planus. Ten patients were included in the study. Primary end point was reduction in signs and symptoms measured by the Escudier severity score. Secondary parameters included pain and quality of life scores. Safety parameters were assessed during a follow-up period of 5 weeks. RESULTS: A substantial response at the end of treatment, i.e. >50% reduction in disease severity measured by the Escudier severity score, was apparent in 40% of patients. Therapy was well tolerated. Adverse events were mild and included headache, mucocutaneous dryness, musculoskeletal pain, increased thyroid-stimulating hormone and dyslipidaemia. CONCLUSIONS: Alitretinoin given at 30 mg daily reduced disease severity of severe oral lichen planus in a substantial proportion of patients refractory to standard treatment, was well tolerated and may thus represent one therapeutic option for this special group of patients.

Single-pass UV generation at 222.5 nm based on high-power GaN external cavity diode laser.

We demonstrate a compact system for single-pass frequency doubling of high-power GaN diode laser radiation. The deep UV laser light at 222.5 nm is generated in a ß-BaB2O4 (BBO) crystal. A high-power GaN external cavity diode laser (ECDL) system in Littrow configuration with narrowband emission at 445 nm is used as pump source. At a pump power of 680 mW, a maximum UV power of 16 µW in continuous-wave operation at 222.5 nm is achieved. This concept enables a compact diode laser-based system emitting in the deep ultraviolet spectral range.

400 mW external cavity diode laser with narrowband emission at 445 nm.

A high-power external cavity diode laser (ECDL) system with narrowband emission is presented. The system is based on a commercially available high-power GaN laser diode. For the ECDL, a maximum optical output power of 400 mW in continuous-wave operation with narrowband emission is achieved. Longitudinal mode selection is realized by using a surface diffraction grating in Littrow configuration. A spectral width of 20 pm at 445 nm with a side-mode suppression ratio larger than 40 dB is achieved. This concept enables diode laser systems suitable for subsequent nonlinear frequency conversion into the UV spectral range.

Systemic corticosteroids for subcutaneous panniculitis-like T-cell lymphoma.

BACKGROUND: Primary cutaneous γ/δ T-cell lymphoma (PCGD-TCL) is aggressive and has a poor prognosis. In contrast, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) of the α/ß T-cell receptor phenotype is known to follow an indolent course and have a more favourable prognosis. In the past, PCGD-TCL and SPTCL were often considered to be a manifestation of the same disease, and aggressive systemic polychemotherapy has commonly been the first-line therapy for both. Given the understanding that SPTCL is a separate and less aggressive entity, clinical data exclusively evaluating the efficacy of conservative treatment in SPTCL are needed. OBJECTIVES: To assess the overall clinical response to systemic corticosteroids in the treatment of SPTCL. METHODS: This was a retrospective cross-sectional study based on a patient data repository from two tertiary care university hospitals in Zürich (Switzerland) and Tübingen (Germany). The repository spanned 13 years. RESULTS: In four of the five patients (80%) with SPTCL, treatment with systemic corticosteroids induced a complete remission. CONCLUSIONS: Systemic corticosteroids may be an excellent first-line single-agent therapy for SPTCL.

[MRSA bloodstream infections according to the German obligation for notification - data and experience of the MDRO Network Rhine-Main, Germany, 2011]. / Meldepflicht MRSA in Blutkulturen - Daten und Erfahrungen des MRE-Netz Rhein-Main, 2011.

BACKGROUND: Since July 1st, 2009 in accord with the statuary order based on the German law for infectious diseases (Infektionsschutzgesetz), MRSA in blood and liquor have to be notified to the public health authorities. The aim of this extension of the notification to report is to improve the surveillance of nosocomial infections and the prevention of nosocomial MRSA infections. In this paper data of the notifications in the year 2011 within the MDRO-Net Rhine-Main, an association of 7 public health authorities in the region, are reported in order to investigate whether the aims of the obligation for notification could be achieved. RESULTS: In 2011, 138 MRSA bloodstream infections, including 1 MRSA in liquor culture, were notified to the 7 health protection authorities, resulting in an incidence rate of 5.6/100,000 inhabitants. In urban regions with more hospitals available, the incidence rate was higher than in rural districts with less medical facilities (6.9 vs. 4.4/100,000 inhabitants). Only 46 (35%) of the patients with MRSA cultured in their blood had been detected via anamnesis as patients on risk for MRSA, and 59 (45%) had been screened for MRSA on admission. The incidence rate in the different hospitals was 0.041 ± 0.031/1,000 patient days (range 0-0.145/1,000 patient days). CONCLUSIONS: For the first time, data on notification of MRSA cultures in blood specimen are published from a whole MRE Network in Germany encompassing >2.1 million inhabitants. Incidence rates per 100,000 inhabitants alone do not seem adequate to cope with the aims of the obligation for notification. Instead, reference to patient days in the respective clinic enables an external comparison to other medical institutions in the region and is a better base for discussion with these institutions on improvements of surveillance, screening and hygiene.

Early implementation of antifungal therapy in the management of febrile neutropenia is associated with favourable outcome during induction chemotherapy for acute leukaemias.

BACKGROUND: Mortality related to induction chemotherapy during the treatment of acute leukaemias (AL) has been estimated at 5-20%, and this increases with age. Fungal infection remains one of the major causes of morbidity and mortality and is considered an obstacle to the successful management of acute leukaemias. METHODS: We retrospectively analysed all patients treated for acute leukaemias at a single institution between July 2006 and January 2009, to assess the impact of early antifungal therapy on outcome during induction chemotherapy. There were 44 episodes of induction chemotherapy, with a median age of patients of 61 years (range 18-81), including 29 patients with acute myeloid leukaemia, 9 with acute lymphoblastic leukaemia and 6 with relapsed AL. The median age was 61 years (range 18-81), and 20 patients were over the age of 60 years. RESULTS: All patients who developed febrile neutropenia received broad-spectrum antibiotics. Early empirical antifungal treatment was commenced with voriconazole (15 patients) or caspofungin (12 patients) if the febrile neutropenia did not resolve after 72 h of antibiotic therapy, in conjunction with radiological changes consistent with possible fungal infection. None of the patients succumbed during induction chemotherapy. The 120-day mortality rate after the induction therapy was 2.2%, without any incidence of invasive fungal disease. CONCLUSION: Our analysis shows that early empirical treatment for fungal infection with voriconazole or caspofungin is associated with a favourable outcome of induction therapy for acute leukaemias. Further studies to confirm this finding are warranted.

Tumour heterogeneity of mucosal melanomas during treatment with imatinib.

A comparison of in vitro and in vivo characteristics of tumour cells derived from patients with mucosal melanoma treated with imatinib was performed with respect to KIT mutations. Three patients with mucosal melanoma were treated with imatinib. Patient-derived tumour material was used to establish melanoma cell cultures ex vivo. We evaluated tumour material and cell cultures for KIT protein expression and KIT mutation status. In addition, proliferation assays with melanoma cell cultures were performed with imatinib. Expression of KIT protein and KIT mutation was shown in two patients who responded to imatinib in vivo. Cells derived from a third patient who did not respond to imatinib did not express KIT and lacked a KIT mutation. Patient-derived melanoma cells did not show any KIT mutations, nor did they respond to imatinib in vitro. Our study underlines that melanoma consists of a heterogeneous cell population, making it imperative to use the mapping of involved activating tumour growth-driving pathways in order to improve response to therapy with kinase inhibitors.

Speciation, thermodynamics and structure of Np(V) oxalate complexes in aqueous solution.

The speciation, thermodynamics and structure of the Np(v) (as the NpO2+ cation) complexes with oxalate (Ox2-) are studied by different spectroscopic techniques. Near infrared absorption spectroscopy (Vis/NIR) is used to investigate complexation reactions as a function of the total ligand concentration ([Ox2-]total), ionic strength (Im = 0.5-4.0 mol kg-1 Na+(Cl-/ClO4-)) and temperature (T = 20-85 °C) for determination of the complex stoichiometry and thermodynamic functions (log ß0n(T), ΔrH0n, ΔrS0n). Besides the solvated NpO2+ ion, two NpO2+ oxalate species (NpO2(Ox)n1-2n; n = 1, 2) are identified. With increasing temperature a decrease of the molar fractions of the 1 : 1 - and 1 : 2 - complexes is observed. Application of the law of mass action yields the temperature dependent conditional stability constants log ß'n(T) at a given ionic strength which are extrapolated to IUPAC reference state conditions (Im = 0) according to the specific ion interaction theory (SIT). The log ß0n(T) values of both complex species (log ß01(25 °C) = 4.53 ± 0.12; log ß02(25 °C) = 6.22 ± 0.24) decrease with increasing temperature confirming an exothermic complexation reaction. The temperature dependence of the thermodynamic stability constants is described by the integrated van't Hoff equation yielding the standard reaction enthalpies (ΔrH01 = -1.3 ± 0.7 kJ mol-1; ΔrH02 = -8.7 ± 1.4 kJ mol-1) and entropies (ΔrS01 = 82 ± 2 J mol-1 K-1; ΔrS02 = 90 ± 5 J mol-1 K-1) for the complexation reactions. In addition, the sum of the specific binary ion-ion interaction coefficients Δε0n(T) for the complexation reactions are obtained from SIT modelling as a function of the temperature. The structure of the complexes and the coordination mode of oxalate are investigated using EXAFS spectroscopy and quantum chemical calculations. The results show, that in case of both species NpO2(Ox)- and NpO2(Ox)23-, chelate complexes with 5-membered rings are formed.

Invasive paediatric Elizabethkingia meningoseptica infections are best treated with a combination of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or fluoroquinolone.

OBJECTIVES: Elizabethkingia meningoseptica is a multi-drug-resistant organism that is associated with high mortality and morbidity in newborn and immunocompromised patients. This study aimed to identify the best antimicrobial therapy for treating this infection. METHODS: A retrospective descriptive study was conducted from 2010 to 2017 in a tertiary paediatric hospital in Singapore. Paediatric patients aged 0 to 18 years old with a positive culture for E. meningoseptica from any sterile site were identified from the hospital laboratory database. The data collected included clinical characteristics, antimicrobial susceptibility and treatment, and clinical outcomes. RESULTS: Thirteen cases were identified in this study. Combination therapy with piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluoroquinolone resulted in a cure rate of 81.8  %. The mortality rate was 15.4  % and neurological morbidity in patients with bacteraemia and meningitis remained high (75 %). CONCLUSIONS: Treatment with combination therapy of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluroquinolone was effective in this study, with low mortality rates being observed.

Quantitative NMR spectroscopy for gas analysis for production of primary reference gas mixtures.

Due to its direct correlation to the number of spins within a sample quantitative NMR spectroscopy (qNMR) is a promising method with absolute comparison abilities in complex systems in technical, as well as metrological applications. Most of the samples studied with qNMR are in liquid state in diluted solutions, while gas-phase applications represent a rarely applied case. Commercially available NMR equipment was used for purity assessment of liquid and liquefied hydrocarbons serving as raw materials for production of primary reference gas standards. Additionally, gas-phase studies were performed within an online NMR flow probe, as well as in a high-pressure NMR setup to check feasibility as verification method for the composition of gas mixtures.

Versican upregulation in Sézary cells alters growth, motility and resistance to chemotherapy.

Sézary syndrome (SéS) represents a leukemic variant of cutaneous T-cell lymphoma, whose etiology is still unknown. To identify dyregulated genes in SéS, we performed transcriptional profiling of Sézary cells (SCs) obtained from peripheral blood of patients with SéS. We identified versican as the highest upregulated gene in SCs. VCAN is an extracellular matrix proteoglycan, which is known to interfere with different cellular processes in cancer. Versican isoform V1 was the most commonly upregulated isoform in SCs. Using a lentiviral plasmid, we overexpressed versican V1 isoform in lymphoid cell lines, which altered their growth behavior by promoting formation of smaller cell clusters and by increasing their migratory capacity towards stromal cell-derived factor 1, thus promoting skin homing. Versican V1 overexpression exerted an inhibitory effect on cell proliferation, partially by promoting activation-induced cell death. Furthermore, V1 overexpression in lymphoid cell lines increased their sensitivity to doxorubicin and gemcitabine. In conclusion, we confirm versican as one of the dysregulated genes in SéS and describe its effects on the biology of SCs. Although versican overexpression confers lymphoid cells with increased migratory capacity, it also makes them more sensitive to activation-induced cell death and some chemotherapeutics, which could be exploited further for therapeutic purposes.

Impact of urbanization on detection rates of eating disorders.

OBJECTIVE: The purpose of this study was to examine the incidence of anorexia nervosa and bulimia nervosa among patients in primary care and to evaluate the impact of urbanization, age and sex differences, and changes over time. METHOD: During 1985-1989, 58 general practitioners, trained in diagnosing eating disorders, registered all of their patients who had diagnoses of anorexia nervosa and/or bulimia nervosa according to strict criteria. The study population (N = 151,781) was 1% of the population of the Netherlands; the distribution of sexes, ages, geographical locations, and degrees of urbanization in the study group was representative of the Dutch population. Main outcome measures were rates of newly detected cases and age-adjusted rate ratios. RESULTS: The crude annual incidence rate of detected cases in primary care per 100,000 person-years was 8.1 for anorexia nervosa and 11.5 for bulimia nervosa. The incidence of bulimia nervosa was lowest in rural areas, intermediate in urbanized areas, and highest in large cities (6.6, 19.9, and 37.9, respectively, per 100,000 females per year); no rural-urban differences for anorexia nervosa were found. Pronounced sex and age differences in incidence rates were observed. Over the 5-year period, there was no time trend in the incidence of anorexia nervosa, but the incidence of bulimia nervosa tended to increase. CONCLUSIONS: The incidence rates of eating disorders--as defined by detection rates in primary care--are higher than previously reported. Urbanization seems to be a risk factor for bulimia nervosa but not for anorexia nervosa.

Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia: clinical and biochemical studies.

We performed a case-control study to investigate the role of recent infection as stroke risk factor and to identify pathogenetic pathways linking infection and stroke. We examined 166 consecutive patients with acute cerebrovascular ischemia and 166 patients hospitalized for nonvascular and noninflammatory neurologic diseases. Control subjects were individually matched to patients for sex, age, and season of admission. We assessed special biochemical parameters in subgroups of stroke patients with and without recent infection (n = 21) who were similar with respect to demographic and clinical parameters. Infection within the preceding week was a risk factor for cerebrovascular ischemia in univariate (odds ratio [OR] 3.1; 95% confidence interval (CI), 1.57 to 6.1) and age-adjusted multiple logistic regression analysis (OR 2.9; 95% CI, 1.31 to 6.4). The OR of recent infection and age were inversely related. Both bacterial and viral infection contributed to increased risk. Infection elevated the risk for cardioembolism and tended to increase the risk for arterioarterial embolism. Stroke patients with and without preceding infection were not different with respect to factor VII and factor VIII activity, fibrin monomer, fibrin D-dimer, von Willebrand factor, C4b-binding protein, protein S, anticardiolipin antibodies, interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor, interleukin-6, interleukin-8, and neopterin. In conclusion, recent infection is an independent risk factor for acute cerebrovascular ischemia. Its role appears to be more important in younger age groups. The pathogenetic linkage between infection and stroke is still insufficiently understood.

Patient assessment of self-measurement of blood pressure: results of a telephone survey in Germany.

OBJECTIVE: To obtain information on the adoption of self-measurement of blood pressure by hypertensives and their attending physicians. METHODS: Callers to the Cardiovascular Hotline Heidelberg revealing themselves to have high blood pressure were interviewed about self-recording of blood pressure. RESULTS: Among the callers about 70% practised self-measurement. Half of them bought a device on their own initiative, one-third on recommendation or prescription by their physician. A quarter of those practising the technique were introduced to it by experienced personnel and a comparable number were adequately informed about the aims and objectives. Nevertheless, more than half of those practising self-measurement claimed to be coping better with the disease. CONCLUSIONS: The data indicate that self-monitoring is widely practised by hypertensives in Germany. In contrast to this finding, too few physicians have adopted home-recording as a useful tool in the treatment of hypertension.

Histology of intestinal Whipple's disease revisited. A study of 48 patients.

Whipple's disease is an infectious disorder with intestinal and extra-intestinal manifestations. We reinvestigated the intestinal histology in a series of 48 patients (10 females, 38 males; mean age 56.5 years, standard deviation of the mean +/- 11.2 years). A total of 126 biopsy samples, obtained prior to, during, and after therapy, were evaluated by light microscopy. In 43 patients (90%), histology was consistent with common descriptions, while it was uncommon in 3 patients (6%), and non-diagnostic in 2 patients (4%). During treatment, several alterations occurred. Apart from a continuous decrease in PAS-positive macrophages, the pattern of mucosal infiltration changed from diffuse to patchy. Moreover, the cytological aspects of PAS-positive macrophages changed substantially, and this change was used to propose four different subtypes. Initially, subtype 1 macrophages predominated (74%), but showed a gradual decrease within a few months of therapy. After 15 months, subtype 3 and subtype 4 macrophages predominated (< 80%). In 7 of 9 patients followed over long periods some subtype 3 or subtype 4 macrophages persisted. It is concluded that at diagnosis and during treatment the intestinal histology of Whipple's disease is heterogeneous. A few PAS-positive macrophages commonly persist at long-term follow-up. This and other features suggest the presence of a persistent immune defect.