Spectroscopic view on the interaction between the psoralen derivative amotosalen and DNA.

Psoralens are eponymous for PUVA (psoralen plus UV-A radiation) therapy, which inter alia can be used to treat various skin diseases. Based on the same underlying mechanism of action, the synthetic psoralen amotosalen (AMO) is utilized in the pathogen reduction technology of the INTERCEPT® Blood System to inactivate pathogens in plasma and platelet components. The photophysical behavior of AMO in the absence of DNA is remarkably similar to that of the recently studied psoralen 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT). By means of steady-state and time-resolved spectroscopy, intercalation and photochemistry of AMO and synthetic DNA were studied. AMO intercalates with a higher affinity into A,T-only DNA (KD = 8.9 × 10-5 M) than into G,C-only DNA (KD = 6.9 × 10-4 M). AMO covalently photobinds to A,T-only DNA with a reaction quantum yield of ΦR = 0.11. Like AMT, it does not photoreact following intercalation into G,C-only DNA. Femto- and nanosecond transient absorption spectroscopy reveals the characteristic pattern of photobinding to A,T-only DNA. For AMO and G,C-only DNA, signatures of a photoinduced electron transfer are recorded.

Lesions of the lateral pterygoid muscle-an overestimated reason for temporomandibular dysfunction: a 3T magnetic resonance imaging study.

The aim of this study was to examine the lateral pterygoid muscle (LPM) parenchyma, myotendinous junction, and tendon in temporomandibular disorder (TMD) patients using 3T magnetic resonance imaging (MRI). Results were compared with findings reported in the literature, in which the LPM has been attributed a major role in triggering TMD. 3T MRI was used for temporomandibular joint (TMJ) imaging. The MRI images of 63 patients were analysed for muscle contracture and atrophy, tendon rupture, signal alterations of the tendon, tendon contrast enhancement, and peritendinous fluid collection. Descriptive statistics and the coefficient estimate method were used for statistical analysis. Focus was placed on the association between LPM tendon pathology and TMJ lesions like osteoarthritis and disc displacement. Severe lesions of the LPM tendon and muscle parenchyma, like rupture or fibrosis, were detected in very few cases. Only moderate signs of tendinosis were found in TMD patients. In contrast, there was a clear correlation between tendon lesions and osteoarthritis or anterior disc displacement. These results indicate the need to discuss and question the role of the LPM and its tendon in TMD. Data suggest that LPM and tendon lesions are part of complex degenerative changes of the TMJ, and it seems less likely that a LPM disorder is causative in TMD.

Inguinal microbiome in patients undergoing an endovascular aneurysm repair: Application of next-generation sequencing of the 16S-23S rRNA regions.

BACKGROUND: Surgical site infection (SSI) remains a hazardous complication after vascular surgery. In this pilot study we investigated the inguinal microbiome in skin biopsies using histology and 16S-23S rDNA Next Generation Sequencing (NGS). Our hypothesis was that causative microorganisms of SSI are present in the inguinal microbiome. METHODS: Data on surgical site infections and skin samples from the Percutaneous in Endovascular Repair versus Open (PiERO) trail were evaluated. Two patients with SSI were matched for age and comorbidity to eight matching patients of the PiERO trial. All patients were treated for an abdominal aortic aneurysm with endovascular repair. Nasal and perineal cultures were taken preoperatively to detect Staphylococcus aureus carriage. After disinfection with chlorhexidine, groin biopsies were taken to identify bacteria in deeper skin layers. All samples were subjected to histological analysis and culture-free 16S-23S rDNA NGS. RESULTS: Staphylococcus aureus species were cultured in 5 out of 20 preoperative nasal and perineal swaps. Histology detected only a few bacteria. NGS of the 16S-23S rRNA regions identified DNA of bacterial species in all biopsies (20/20). Most identified genera and species proved to be known skin flora bacteria. No relation was found between SSIs and the preoperative microbiome. CONCLUSION: In this pilot study, an innovative analysis of the preoperative microbiome using 16S-23S rDNA NGS did not show a relation with the occurrence of a surgical site infection. No pathogenic bacterial species were present in the inguinal skin after disinfection with chlorhexidine.

Potential Source Apportionment and Meteorological Conditions Involved in Airborne 131I Detections in January/February 2017 in Europe.

Traces of particulate radioactive iodine (131I) were detected in the European atmosphere in January/February 2017. Concentrations of this nuclear fission product were very low, ranging 0.1 to 10 µBq m-3 except at one location in western Russia where they reached up to several mBq m-3. Detections have been reported continuously over an 8-week period by about 30 monitoring stations. We examine possible emission source apportionments and rank them considering their expected contribution in terms of orders of magnitude from typical routine releases: radiopharmaceutical production units > sewage sludge incinerators > nuclear power plants > spontaneous fission of uranium in soil. Inverse modeling simulations indicate that the widespread detections of 131I resulted from the combination of multiple source releases. Among them, those from radiopharmaceutical production units remain the most likely. One of them is located in Western Russia and its estimated source term complies with authorized limits. Other existing sources related to 131I use (medical purposes or sewage sludge incineration) can explain detections on a rather local scale. As an enhancing factor, the prevailing wintertime meteorological situations marked by strong temperature inversions led to poor dispersion conditions that resulted in higher concentrations exceeding usual detection limits in use within the informal Ring of Five (Ro5) monitoring network.

Environmental consequences of uranium atmospheric releases from fuel cycle facility: II. The atmospheric deposition of uranium and thorium on plants.

Uranium and thorium isotopes were measured in cypress leaves, wheat grains and lettuce taken in the surroundings of the uranium conversion facility of Malvési (South of France). The comparison of activity levels and activity ratios (namely (238)U/(232)Th and (230)Th/(232)Th) in plants with those in aerosols taken at this site and plants taken far from it shows that aerosols emitted by the nuclear site (uranium releases in the atmosphere by stacks and (230)Th-rich particles emitted from artificial ponds collecting radioactive waste mud) accounts for the high activities recorded in the plant samples close to the site. The atmospheric deposition process onto the plants appears to be the dominant process in plant contamination. Dry deposition velocities of airborne uranium and thorium were measured as 4.6 × 10(-3) and 5.0 × 10(-3) m s(-1), respectively.

Ratio of marked and excised sentinel lymph nodes and scintigraphic appearance time in melanoma patients with negative sentinel lymph node.

AIM: Metastases can occur in up to 15% of all melanoma patients with negative sentinel lymph node examination (SN -). We retrospectively investigated the number of preoperatively marked sentinel lymph nodes (SNs) with lymphoscintigraphy and effectively surgically removed SNs in SN--patients with cutaneous melanoma >or=0.5 mm. Ratio of these parameters was calculated and impact of this ratio as well as impact of scintigraphic appearance time (SAT) on disease progression was studied. MATERIALS AND METHODS: Data on 122 SN--patients--70 women (58%), mean age 56.5 years--were analyzed. Mean follow-up time was 58 months. RESULTS: Mean tumour thickness of all patients was 2.3 mm. In 51 patients (42%) the number of SNs marked in lymphoscintigraphy was higher than excised in surgery, in 47 patients (38%) the same number as marked was excised and in 24 patients (20%) a lower number was marked than excised. Metastases occurred in 17 patients (14%) after a mean time of 24.8 months. Mean tumour thickness (5.4 mm) was significantly higher in these patients than in the other patients (p = 0.000). Ratio of marked and excised SNs had no influence on disease progression; the only parameter influencing outcome was tumour thickness (p = 0.000). Short SAT was significantly associated with higher tumour thickness (p = 0.004). CONCLUSION: Our study indicates that, in routine clinical practice, it suffices to harvest the first SN, as the ratio of marked and excised SNs has no impact on disease progression.

Monitoring the soot emissions of passing cars.

We report on the first application of a novel fast on-road sensing method for measurement of particulate emissions of individual passing passenger cars. The studywas motivated by the shift of interest from gases to particles in connection with strong adverse health effects. The results correspond very much to findings by Beaton et al. (Science, May 19,1995) for gaseous hydrocarbon and CO emissions: A small percentage of "superpolluters" (here 5%) account for a high percentage (here 43%) of the pollution (here elemental carbon). We estimate that up to 50% of the particulate emissions of vehicles could be avoided on the basis of the present legislation, if on-road monitoring would be applied to enforce maintenance. Our fast sensing method for particles is based on photoelectron emission from the emitted airborne soot particles in combination with a CO2 sensor delivering a reference.

[Outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in the Rijnmond region: the largest outbreak in the Netherlands]. / Uitbraak van meticillineresistente Staphylococcus aureus (MRSA) in de regio Rijnmond: grootste MRSA-epidemie in Nederland.

UNLABELLED: EPIDEMIC: The annual number of new MRSA isolates in the Netherlands tripled in 2002 compared with previous years. This increase was in part due to a MRSA outbreak in the Rijnmond region. The outbreak occurred in two merged hospitals and is the largest ever to occur in the Netherlands. From November 2001 till June 2003 MRSA was isolated from 381 patients and 113 hospital employees. The worst affected departments were Surgery and Internal Medicine. One MRSA strain (pulsed-field gel electroforesis (PFGE) type 16) remained initially unrecognised and was therefore able to spread unnoticed. Soon two additional epidemic MRSA strains (types 37 and 38) were discovered. DISCUSSION: Multiple factors played a role in the extent and duration of the outbreak. Because of the delayed detection and rapid spread of MRSA type 16, the outbreak grew too large once recognised to be resolved within the available infrastructure. Investments were needed at various fields, including the infection-control service and the microbiology laboratory. Employees had to be informed and motivated, and a separate MRSA ward and OPD were provided. New MRSA outbreaks occurred, despite extensive MRSA (contact) screening among patients and employees. The numbers of isolates began falling as from the beginning of 2003.

Effect of smoking on global cognitive function in nondemented elderly.

BACKGROUND: Contrary to early case-control studies that suggested smoking protects against Alzheimer disease (AD), recent prospective studies have shown that elderly who smoke may be at increased risk for dementia. OBJECTIVE: To examine prospectively the effect of smoking on cognition in nondemented elderly. METHOD: In a multicenter cohort, the European Community Concerted Action Epidemiology of Dementia (EURODEM), including the Odense, Personnes Agées Quid (Paquid), Rotterdam, and Medical Research Council: Ageing in Liverpool Project-Health Aspects (MRC ALPHA) Studies, 17,610 persons aged 65 and over were screened and examined for dementia. After an average 2.3 years of follow-up, 11,003 nondemented participants were retested. Excluding incident dementia cases and those without baseline information on smoking gave an analytical sample of 9,209 persons. Average yearly decline in Mini-Mental State Examination (MMSE) score was compared among groups, adjusting for age, sex, baseline MMSE, education, type of residence, and history of myocardial infarction or stroke. RESULTS: MMSE score of persons who never smoked on average declined 0.03 point/year. The adjusted decline of former smokers was 0.03 point greater and of current smokers 0.13 point greater than never smokers (p < 0.001). Higher rates of decline by smoking were found in men and women, persons with and without family history of dementia, and in three of four participating studies. Higher cigarette pack-year exposure was correlated with a significantly higher rate of decline. CONCLUSION: Smoking may accelerate cognitive decline in nondemented elderly.

BIOMarkers for occupational diesel exhaust exposure monitoring (BIOMODEM)--a study in underground mining.

Methods for the assessment of exposures to diesel exhaust were evaluated, including various biomarkers of internal exposure and early biological effects. The impact of possible biomarkers of susceptibility was also explored. Underground workers (drivers of diesel-powered excavators) at an oil shale mine in Estonia were compared with surface workers. Personal exposures to particle-associated 1-nitropyrene (NP) were some eight times higher underground than on the surface. Underground miners were also occupationally exposed to benzene and polycyclic aromatic hydrocarbons, as indicated by excretion of urinary metabolites of benzene and pyrene. In addition, increased O(6)-alkylguanine DNA adducts were detected in the white blood cells of underground workers, suggesting higher exposure to nitroso-compounds. However, no differences between underground and surface workers were observed in the levels of other bulky DNA adducts determined by 32P-postlabelling, or in DNA damage. The study indicated that smoking, diet and residential indoor air pollution are important non-occupational factors to consider when interpreting biomonitoring results.

Osmotic stress response in Dictyostelium is mediated by cAMP.

DokA, a homolog of bacterial hybrid histidine kinases, is essential for hyperosmotic stress resistance in Dictyostelium: We show that a transient intracellular cAMP signal, dependent on the presence of DokA, is generated in response to an osmotic shock. This variation of cAMP levels contributes to survival under hypertonic conditions. In contrast to the low cAMP levels observed in dokA(-) strains, overexpression of the receiver domain of DokA causes an increase in cAMP levels, resulting in a rapidly developing phenotype. We present biochemical and cell biological data indicating that the DokA receiver domain is a dominant-negative regulator of a phosphorelay, which controls the intracellular cAMP phosphodiesterase RegA. The activity of the DokA receiver domain depends on a conserved aspartate, mutation of which reverses the developmental phenotype, as well as the deregulation of cAMP metabolism.

An epidemiological study on the occurrence of Staphylococcus aureus in superficial abscesses of patients presenting for surgery in a teaching hospital in Khartoum, Sudan.

A group of patients (n=86) suffering from superficial abscesses was recruited in the Khartoum Teaching Hospital, Sudan. Detailed clinical and socio-economic data were collected. It appeared that 83% of all patients were younger than 40. Labourers were most prevalent (28%), followed by students (23%) and housewives (16%). The head and neck were most often affected (22%), with hands being second (19%). In 92% of all pus cultures a microbial agents was identified, the large majority being Staphylococcus aureus (69%). Among patients, 47% were nasal carriers of S. aureus, similar to the carriage rate measured among controls, suggesting that nasal carriage is no risk factor for abscess development. Multivariate logistic regression analysis revealed that a history of abscess, recent traditional medical treatment, poor hygiene and low socio-economic status were significantly and independently associated with the occurrence of superficial abscesses.

Prevalence and determinants of fecal colonization with vancomycin-resistant Enterococcus in hospitalized patients in The Netherlands.

OBJECTIVE: To determine the prevalence and determinants of fecal carriage of vancomycin-resistant enterococci (VRE) in intensive care unit (ICU), hematology-oncology, and hemodialysis patients in The Netherlands. DESIGN: Descriptive, multicenter study, with yearly 1-week point-prevalence assessments between 1995 and 1998. POPULATION: All patients hospitalized on the testing days in ICUs and hematology-oncology wards in nine hospitals in The Netherlands were included. METHODS: Rectal swabs obtained from 1,112 patients were screened for enterococci in a selective broth and subcultured on selective media with and without 6 mg/L vancomycin. Resistance genotypes were determined by polymerase chain reaction. Further characterization of VRE strains was done by pulsed-field gel electrophoresis (PFGE). We studied possible determinants of VRE colonization with a logistic regression analysis model. Determinants analyzed included gender, age, and log-transformed length of prior hospital stay. RESULTS: The results showed that 614 (55%) of 1,112 patients were colonized with vancomycin-sensitive enterococci, and 15 (1.4%) of 1,112 carried VRE. No increase in VRE colonization was observed from 1995 to 1998. Eleven strains were identified as Enterococcus faecium and four as Enterococcus faecalis. All E faecium and one E faecalis carried the vanA gene; the other E faecalis strains harbored the vanB gene. PFGE revealed that three vanB VRE isolated from patients hospitalized in one single ICU were related, suggesting nosocomial transmission. Though higher age seemed associated with VRE colonization, exclusion of patients with the nosocomial strain from the regression analysis decreased this relation to nonsignificant. Duration of hospital stay was not associated with VRE colonization. CONCLUSION: VRE colonization in Dutch hospitals is an infrequent phenomenon. Although nosocomial spread occurs, most observed cases were unrelated, which suggests the possibility of VRE acquisition from outside the hospital. Prolonged hospital stay, age, and gender proved unrelated to VRE colonization.

Education and the risk for Alzheimer's disease: sex makes a difference. EURODEM pooled analyses. EURODEM Incidence Research Group.

The hypothesis that a low educational level increases the risk for Alzheimer's disease remains controversial. The authors studied the association of years of schooling with the risk for incident dementia and Alzheimer's disease by using pooled data from four European population-based follow-up studies. Dementia cases were identified in a two-stage procedure that included a detailed diagnostic assessment of screen-positive subjects. Dementia and Alzheimer's disease were diagnosed by using international research criteria. Educational level was categorized by years of schooling as low (< or =7), middle (8-11), or high (> or =12). Relative risks (95% confidence intervals) were estimated by using Poisson regression, adjusting for age, sex, study center, smoking status, and self-reported myocardial infarction and stroke. There were 493 (328) incident cases of dementia (Alzheimer's disease) and 28,061 (27,839) person-years of follow-up. Compared with women with a high level of education, those with low and middle levels of education had 4.3 (95% confidence interval: 1.5, 11.9) and 2.6 (95% confidence interval: 1.0, 7.1) times increased risks, respectively, for Alzheimer's disease. The risk estimates for men were close to 1.0. Finding an association of education with Alzheimer's disease for women only raises the possibility that unmeasured confounding explains the previously reported increased risk for Alzheimer's disease for persons with low levels of education.

[Therapy of lymphomatoid papulosis with balneo-PUVA-photochemotherapy]]. / Therapie der lymphomatoiden Papulose mit Bade-PUVA-(Balneo-) Photochemotherapie.

Lymphomatoid papulosis is a rare lymphoproliferative disorder of the skin. The standard therapeutic regimen is systemic (oral) photochemotherapy (PUVA). We examined the efficacy of PUVA-bath photochemotherapy in a patient requiring heart transplantation because of idiopathic dilatated cardiomyopathy and a relative contraindication against systemic 8-methoxypsoralen. The 42-years old male patient had suffered for 15 years with itching papules and plaques which clinically, immunohistochemically and molecular biologically were diagnosed as lymphomatoid papulosis. PUVA-bath photochemotherapy with 8-MOP was initiated. After 29 treatments the plaques disappeared completely. After 44 sessions (cumulative UV-A dose 206 J/cm2) the patient's skin almost was clear. PUVA-bath photochemotherapy proved to be a therapeutic alternative to systemic PUVA-treatment in this case of lymphomatoid papulosis.

Is age-related maculopathy associated with Alzheimer's Disease? The Rotterdam Study.

The authors examined the relation between age-related maculopathy and Alzheimer's disease in the Rotterdam Study, a prospective population-based study in the Netherlands. From 1990 to mid-1993, subjects aged 75 years or older (n = 1,438) were screened for the presence of age-related maculopathy and Alzheimer's disease, and follow-up examinations were conducted from mid-1 993 to the end of 1994. Subjects with advanced age-related maculopathy at baseline showed an increased risk of incident Alzheimer's disease (relative risk = 2.1, 95% confidence interval: 1.1, 4.3; adjusted for age and gender), but this risk decreased after additional adjustment for smoking and atherosclerosis (relative risk = 1.5, 95% confidence interval: 0.6, 3.5). These findings suggest that the neuronal degeneration occurring in age-related maculopathy and Alzheimer's disease may, to some extent, have a common pathogenesis.

Burden of mortality and morbidity from dementia.

The purpose of this study was to estimate severity-specific mortality and to quantify the global health burden of dementia by assessing the time spent disabled with dementia and the life years lost due to dementia. We used mortality data from the Rotterdam study, a population-based prospective study in the 55+-year age range to calculate overall and severity-specific excess mortality for the demented. Lost life years were calculated by decomposing the (mixed) Dutch life table of 1990-1992 in two populations, the demented and the healthy, using prevalence and excess (all cause) mortality. Healthy life loss was calculated by a modified Sullivan technique, weighting for disease severity. Our results indicated that mortality was increased in the demented, in all age, sex, and severity groups. Mortality rate ratios were 2.1 (men) and 2.3 (women), with ranges of 1.7-3.4 (men) and 2.0-3.1 (women), depending on severity. Fifty-five-year-old men lose 1.2 life years due to morbidity and mortality and 0.7 life years due to mortality resulting from dementia. Women lose 3.1 and 1.9 life years, respectively. This population-based study provides evidence that mortality is increased in the demented at all stages, including minimal dementia. The quantified health impact on the general population is in the same order as that of lung cancer or stroke.

Rearrangement of cortex proteins constitutes an osmoprotective mechanism in Dictyostelium.

Dictyostelium responds to hyperosmotic stress of 400 mOsm by a rapid reduction of its cell volume to 50%. The reduced cell volume is maintained as long as these osmotic conditions prevail. Dictyostelium does not accumulate compatible osmolytes to counteract the osmotic pressure applied. Using two-dimensional gel electrophoresis, we demonstrate that during the osmotic shock the protein pattern remains unaltered in whole-cell extracts. However, when cells were fractionated into membrane and cytoskeletal fractions, alterations of specific proteins could be demonstrated. In the crude membrane fraction, a 3-fold increase in the amount of protein was measured upon hyperosmotic stress. In the cytoskeletal fraction, the proteins DdLIM and the regulatory myosin light chain (RMLC) were shown to be regulated in the osmotic stress response. The elongation factors eEF1alpha (ABP50) and eEF1beta were found to increase in the cytoskeletal fraction, suggesting a translational arrest upon hyperosmotic stress. Furthermore, the two main components of the cytoskeleton, actin and myosin II, are phosphorylated as a consequence of the osmotic shock, with a tyrosine residue as the phosphorylation site on actin and three threonines in the case of the myosin II heavy chain.

[Disseminated ischemic necrosis and livedo racemosa in a chronic dialysis patient with calciphylaxis]. / Disseminierte ischämische Nekrosen und Livedo racemosa bei einer Patientin mit Kalziphylaxie nach Langzeitdialyse.

Calciphylaxis occurred in a 40-year old female patient with end-stage renal failure. The patient developed livedo racemosa ("livedo reticularis") with painful skin necrosis and ulcers involving multiple areas of the hip and legs after 22 years of hemodialysis. X-ray-examinations revealed calcinosis of peripheral arteries, especially of the pelvis, thigh and hands, while histological examinations showed a fibrosis and calcinosis of small subcutaneous arteries. A generalized cutaneous microangiopathy could be demonstrated by transcutaneous oxygen pressure measurements. Laboratory data showed a moderate secondary hyperparathyroidism with mild elevation of calcium-phosphate product. In addition to the hemodialysis an attempt was made to improve the microcirculation by vasoactive drugs. The clinical course was characterized by slow healing of the ulcers and occurrence of new areas of cutaneous necrosis. Calciphylaxis is a rare late complication in patients with advanced, often end-stage renal failure. It has characteristic histopathological features and is frequently, but not always, associated with a disturbed calcium and phosphorus metabolism and mildly elevated levels of parathyroid hormone. Calciphylaxis is classified as a special type of metastatic calcinosis.