In-situ aerosol nanoparticle characterization by small angle X-ray scattering at ultra-low volume fraction.

State-of-the-art aerosol nanoparticle techniques all have one feature in common: for analysis they remove the nanoparticles from their original environment. Therefore, physical and chemical properties of the particles might be changed or cannot be measured correctly. To overcome these shortcomings, we apply synchrotron based small angle X-ray scattering (SAXS) as an in-situ measurement technique. Contrasting other aerosol studies using SAXS, we focus on particle concentrations which allow direct comparison to common aerosol nanoparticle analyzers. To this end, we analyze aerosol nanoparticles at ambient pressure and concentrations of slightly above ~106 cm-3. A differential mobility particle sizer (DMPS) is operated in parallel. We find that SAXS enables measurement of the primary particles and the aggregates, whereas the DMPS detects only aggregates. We conclude that in-situ nanoparticle characterization with ultra-low volume fractions of ~10-10 is feasible with SAXS. Our technique opens up a doorway to the in-situ analysis of aerosol nanoparticles under atmospheric conditions.

Superior outcomes of decompression with an interlaminar dynamic device versus decompression alone in patients with lumbar spinal stenosis and back pain: a cross registry study.

INTRODUCTION: Surgical decompression for lumbar spinal stenosis (LSS) has been associated with poorer outcomes in patients with pronounced low back pain (LBP) as compared to patients with predominant leg pain. This cross registry study assessed potential benefits of the interlaminar coflex® device as an add-on to bony decompression alone. METHODS: Patients with lumbar decompression plus coflex® (SWISSspine registry) were compared with decompressed controls (Spine Tango registry). Inclusion criteria were LSS and a preoperative back pain level of ≥5 points. 1:1 propensity score-based matching was performed. Outcome measures were back and leg pain relief, COMI score improvement, patient satisfaction, complication, and revision rates. RESULTS: 50 matched pairs without residual significant differences but age were created. At the 7-9 months follow-up interval the coflex® group had higher back (p=0.014) and leg pain relief (p<0.001) and COMI score improvement (p=0.029) than the decompression group. Patient satisfaction was 90% in both groups. No revision was documented in the coflex® and one in the decompression group (2.0%). DISCUSSION: In the short-term, lumbar decompression with coflex® compared with decompression alone in patients with LSS and pronounced LBP at baseline is a safe and effective treatment option that appears beneficial regarding clinical and functional outcomes. However, residual confounding of non-measured covariables may have partially influenced our findings. Also, despite careful inclusion and exclusion of cases the cross registry approach introduces a potential for selection bias that we could not totally control for and that makes additional studies necessary.

Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with increased liver enzymes in obese adolescents and metabolic syndrome in all ages.

BACKGROUND: Obesity is associated with non-alcoholic fatty liver disease (NAFLD), and the patatin-like phospholipase 3 (PNPLA3) rs738409 (Ile148Met, C>G) gene polymorphism is one of the most important genetic determinants of NAFLD. Carriers have been reported to better respond to lifestyle modification. AIM: To investigate the effect of rs738409 on overweight/obese adolescents and adults with and without metabolic syndrome (MetS). METHODS: Two hundred and eighty-eight overweight/obese and 209 normal weight participants of the STYJOBS/EDECTA cohort (NCT00482924) were analysed for PNPLA3 genotypes. RESULTS: Compared to overweight/obese without MetS, in overweight/obese study participants with MetS, the presence of the G allele (148Met) was significantly higher (CC: 5.0% vs. 9.2%, Spearman's correlation, 0.12; P = 0.038). Persons with CG (heterozygote for the risk allele) and with GG (homozygote for the risk allele) genotypes showed significantly higher ALT levels than those with CC genotypes. Even young individuals aged below 20 years had significantly increased ALT levels if they were homozygote with the G allele. CONCLUSIONS: The PNPLA3 rs738409 polymorphism is associated already in youths with increased ALT, and is more frequent in obese with MetS of all ages. Hence, overweight/obese rs738409 carriers should be identified early in life and treated with a rigorous life style intervention.

Automation of a portable extracorporeal circulatory support system with adaptive fuzzy controllers.

The presented work relates to the procedure followed for the automation of a portable extracorporeal circulatory support system. Such a device may help increase the chances of survival after suffering from cardiogenic shock outside the hospital, additionally a controller can provide of optimal organ perfusion, while reducing the workload of the operator. Animal experiments were carried out for the acquisition of haemodynamic behaviour of the body under extracorporeal circulation. A mathematical model was constructed based on the experimental data, including a cardiovascular model, gas exchange and the administration of medication. As the base of the controller fuzzy logic was used allowing the easy integration of knowledge from trained perfusionists, an adaptive mechanism was included to adapt to the patient's individual response. Initial simulations show the effectiveness of the controller and the improvements of perfusion after adaptation.

Automation of an extracorporeal support system with adaptive fuzzy controllers.

For patients suffering from cardiogenic shock cardiopulmonary resuscitation may not be sufficient to restore normal heart function. However, their chances of survival may be increased with the use of an extracorporeal support system. With this system the patient's organs are perfused while being transported to the nearest hospital for proper treatment. In the automation of an extracorporeal support system the patient's vital signals are constantly monitored and proper adjustments are performed to improve organ perfusion. In this paper, an adaptive fuzzy controller is proposed that uses the knowledge and expertise of a perfusionist as a starting point and reference for regulation. Furthermore it is able to adapt to the patient's specific reactions by manipulating the rule base of the fuzzy controller. The performance of the adaptive fuzzy controller is tested with a simulation model of the cardiovascular system.

Design of a fuzzy controller for the automation of an extracorporeal support system with the use of a simulation environment.

The automation of a portable extracorporeal support system may greatly help people who suffer from cardiogenic shock by providing them with an optimal oxygen perfusion and avoid mult-organ failure while being transported to a hospital. This however requires the creation of tools that help in the design of the ideal controller. In this paper a simulation environment is described were a cardiovascular model from the ISR Physiome database was used together with a model of a portable extracorporeal support system. Additionally a model of an oxygenator/blender model is introduced to allow the simulation of oxygen perfusion. Fuzzy controlling was used for automation since it allows a straightforward implementation of expert knowledge. Through the simulation environment different scenarios may be created where intensive testing is possible and constant repetition for control optimization. Initial simulation results are given of the fuzzy controller adjusting the extracorporeal flow rate and oxygen administration for a case of low cardiac output.

Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for haemophilia A.

The tail cut bleeding model (CUT) is routinely used in factor VIII-deficient mice to assess pharmacodynamic effects of therapeutic strategies for haemophilia A. Results from this model are highly variable, many modifications to the model are reported and at times the animals' wellbeing may be compromised by recording survival as an endpoint. We therefore investigated if the ferric chloride carotid occlusion model (COM) used for thrombosis research can be applied to enhance data quality and animal welfare in haemophilia A research. Relative dose effects and relative dose variations were calculated for the CUT and COM. The requisite sample sizes were estimated and the importance of survival rates to assess rebleeds during recovery was evaluated by correlating initial blood loss to mortality. Relative dose effects increased with higher doses in both models. The COM was more sensitive at lower doses than the CUT, had up to 82% less variation across doses and clearly showed superior accuracy. Only 5% of the sample size required for the CUT would be needed to establish non-inferiority between a specific therapeutic dose in haemophilia A mice and healthy wild-type animals. A strong statistically significant correlation was found between initial blood loss and mortality within 24 h. Our findings clearly suggest that the COM is a valid tool for assessing haemophilia A treatment in vivo. The highly reproducible data means that significantly fewer animals are required and a more humane endpoint can be used by directly assessing clot stability instead of survival rate.

[Relationship between morphological characteristics of the teat duct and prevalence of intramammary infections with Streptococcus agalactiae in dairy cows]. / Beziehungen zwischen morphologischen Eigenschaften des Strichkanales und der Prävalenz intramammärer Infektionen durch Sc. agalactiae bei Milchkühen.

The objective of the study was to determine the relationship between morphological findings of the surface of teat duct particularly the level of ceratosis and the prevalence of intramammary infections (IMI). The study was conducted on a commercial dairy herd housing about 3000 lactating dairy cows. We examined 891 quarters in the middle of lactation. Duplicate samples of quarter foremilk were collected monthly. The bacteriological status of quarters was determined according to the recommendations of IDF. At the same time teats were evaluated by clinical examinations. The appearance of teat skin lesions and the status of the teat duct especially the existence of hyperceratosis (HC) was documented. Four classes of teat duct hyperceratosis were defined: without, slight, medium and severe HC. The rate of IMI in different classes of hyperceratosis of teat duct was compared by Chi-square analysis. Prevalences of intramammary infections were determined three times (P1, P2 and P3) during the study period. Prevalence of infection was high for S. aureus (P1: 5.6% vs. P2: 4.5% vs. P3: 4.3%), Sc. agalactiae (P1: 2.7% vs. P2: 2.6% vs. P3: 2.8%) and CNS (P1: 10.7% vs. P2: 8.8% vs. P3: 9.6%). Furthermore we detected IMI caused by other streptococci, yeast, E. coli and mixed infections. A positive correlation between status of HC and prevalence of IMI for Sc. agalactiae was found. At the second and third sampling time the rate of intramammary infection with Sc. agalactiae in quarters with medium HC (P2: 9.21% and P3: 13.73%) differed significantly (p < 0.05) compared to groups without (P2: 1.56% and P3: 1.91%) and slight hyperceratosis (P2: 2.33% and P3: 2.56%). The results of our study indicate a correlation between morphology of teat duct surface, especially regarding to Sc. agalactiae. On one hand HC can cause high intramammary infection rate with Sc. agalactiae. On the other hand it is possible that HC is the consequence of a quarter infection with Sc. agalactiae. Further research is required.

[The clinical effectiveness of a post milking teat disinfection method with a foaming iodophor teat dip]. / Untersuchungen zur klinischen Wirksamkeit eines Zitzendesinfektionsverfahrens nach dem Melken mit einem schaumbildenden jodophoren Dippmittel.

The effect of postmilking teat dipping with a foaming iodophor agent on incidence of intramammary infections (IMI), incidence of clinical mastitis, somatic cell count and the characteristics of udder tissue and teat was investigated in a positively controlled field study. Two groups of animals were compared. Teats were dipped with a foaming iodophor in the treatment group (TG, 122 animals) while teats in the control group (CG, 121 animals) were dipped with a conventional iodophor teat dip with the same iodine content. A bacteriological examination of quarter milk samples divided the study period in two parts. The incidence of new IMI did not differ between the groups (1st part of trial: TG vs. CG: 6.84% vs. 9.16%, 2nd part of trial: 7.78% vs. 7.82%). There were no differences between the treatment groups regarding incidence of clinical mastitis. We detected 0.64 clinical cases per 100 days in the treatment group vs. 0.50 in the control group. The development of SCC was comparable in both groups. Teat skin and teat duct conditions showed variation during the study period. Clinical efficacy of postmilking teat disinfection with a foaming iodophor was comparable to the treatment with a conventional iodophor product.

[Prevention of intramammary infections in dairy cows by the use of a premilking teat dip method with a foaming iodophor dip agent]. / Prophylaxe von Infektionen der Milchdrüse beim Milchrind durch die Anwendung eines Zitzendippverfahrens vor dem Melken mit einem schaumbildenden, jodophoren Dippmittel.

In this study we investigated the efficacy of premilking teat dipping with a foaming iodophor teat dip in a negative controlled field study. Incidence of new intramammary infections (IMI), incidence of clinical mastitis, influence on somatic cell count (SCC) and the characteristics of udder tissue and teats were used as parameters to evaluate clinical efficacy. Predipping was compared with a negative control using a split-udder experimental design. Right teats were predipped with a foaming disinfectant containing 0.27% iodine while left teats served as controls. The latter were conventionally cleaned with damp cloth towels and dried manually with disposable paper towels ("best cleaning practice"). All teats were dipped after milking with the same dip. There were no differences between treated and control quarters with respect to incidence of new IMI during the study period (treated quarters: 6.6% vs. untreated: 6.95%), incidence of clinical mastitis (30 cases in the treatment group vs. 39 cases in the control group) and geometric mean of SCC of quarter milk samples. Spectrum of detected pathogens was also comparable. Condition of udder tissue and teat ducts did not differ between treated and control quarters.

Increased IkappaB kinase activity is associated with activated NF-kappaB in acute myeloid blasts.

NF-kappaB/Rel transcription factors are modulators of immune and inflammatory processes and are also involved in malignancy. Phosphorylation of the IkappaB inhibitors by the IkappaB kinase (IKK) complex leads to their proteasomal degradation, resulting in activated NF-kappaB. Here, we investigated the activation status of NF-kappaB and the IKK complex in acute myeloid leukemia (AML). Gelshift assays revealed an increased level of activated nuclear NF-kappaB in myeloid blasts. Both bone marrow and peripheral blood blasts from AML patients showed enhanced IKK activity relative to controls, whereas the IKK protein concentrations were comparable. In addition, an increased level of IkappaB-alpha was detected in AML blast cells, although this appeared to be insufficient to block nuclear translocation of NF-kappaB, also confirmed by immunofluorescence. In subtype M4 and M5 AML cells a more extensive NF-kappaB activation and higher IKK activity was found than in M1/M2 specimens. Isolated AML blasts cultured ex vivo responded to external stimulation (TNF, LPS) by further IKK activation, IkappaB degradation and NF-kappaB activation. Preincubation with the proteasome inhibitor PSI inhibited the NF-kappaB system in isolated AML blasts. This study established for the first time a dysregulation of IKK signaling in AML leading to increased NF-kappaB activity suggesting potential therapeutic avenues.

Efficacy of a herd-specific vaccine against Staphylococcus aureus to prevent post-partum mastitis in dairy heifers.

A placebo-controlled field study was performed to evaluate the effect of a herd-specific vaccine against Staphylococcus aureus on intramammary infection (IMI), somatic cell count (SCC) and clinical mastitis. Three hundred and twenty-one heifers were assigned to two groups. Heifers in the vaccination group (n = 164) were vaccinated twice, i.e. 5 and 2 weeks before their expected calving date. Animals of the control group (n = 157) received the same treatment with a placebo containing no bacterial antigen. Quarter milk samples were collected immediately after parturition prior to the first machine milking, 3-4 weeks after calving and before the onset of treatment in animals with signs of clinical mastitis during the first 3 months after calving. For comparison of SCC the data from the monthly milk test records were evaluated. The prevalence of S. aureus in quarter milk samples taken at calving and 3-4 weeks post-partum did not differ significantly between the vaccine and control group. Incidence of clinical mastitis during the first 3 months after calving and the prevalence of S. aureus in quarter milk samples taken before the onset of treatment did not differ significantly between the groups. The SCC was lower in vaccinated than in control heifers. However, the difference was only significant on the third milk test day. Regarding prevalence of IMI with S. aureus and incidence of clinical mastitis the use of a herd-specific vaccine against S. aureus did not prove to be efficient on this farm.

Effect of teat dipping with a germicide barrier teat dip in late gestation on intramammary infection and clinical mastitis during the first 5 days post-partum in primiparous cows.

The effect of teat dipping with a barrier teat dip prior to parturition on intramammary infection (IMI) and clinical mastitis during the first 5 days post-partum was investigated in a split udder trial in 149 Holstein-Frisian heifers. Their left front and right hind quarters were dipped three times weekly (i.e. Monday, Wednesday and Friday) with a barrier teat dip containing 0.1% polyvidon iodine from day 260 of gestation until parturition. The opposite quarters (right front and left hind quarter) served as untreated control. Bacteria were isolated from 52.2% of quarter milk samples collected immediately after parturition prior to first machine milking. Staphylococcus aureus and coagulase-negative staphylococci (CNS) were predominantly found in the samples (29.2 and 35.6% of the positive samples, respectively). At parturition 6.7% of the heifers showed signs of clinical mastitis and another 27.5% developed signs of clinical mastitis during the first five days of lactation. No significant differences were found between treated and control quarters regarding IMI and incidence of clinical mastitis. Teat dipping prior to parturition in primigravid dairy heifers did not improve udder health in this trial.

Meiotic segregation, synapsis, and recombination checkpoint functions require physical interaction between the chromosomal proteins Red1p and Hop1p.

In yeast, HOP1 and RED1 are required during meiosis for proper chromosome segregation and the consequent formation of viable spores. Mutations in either HOP1 or RED1 create unique as well as overlapping phenotypes, indicating that the two proteins act alone as well as in concert with each other. To understand which meiotic processes specifically require Red1p-Hop1p hetero-oligomers, a novel genetic screen was used to identify a single-point mutation of RED1, red1-K348E, that separates Hop1p binding from Red1p homo-oligomerization. The Red1-K348E protein is stable, phosphorylated in a manner equivalent to Red1p, and undergoes efficient homo-oligomerization; however, its ability to interact with Hop1p both by two-hybrid and coimmunoprecipitation assays is greatly reduced. Overexpression of HOP1 specifically suppresses red1-K348E, supporting the idea that the only defect in the protein is a reduced affinity for Hop1p. red1-K348E mutants exhibit reduced levels of crossing over and spore viability and fail to undergo chromosome synapsis, thereby implicating a role for Red1p-Hop1p hetero-oligomers in these processes. Furthermore, red1-K348E suppresses the sae2/com1 defects in meiotic progression and sporulation, indicating a previously unknown role for HOP1 in the meiotic recombination checkpoint.

Are screening serum creatinine levels necessary prior to outpatient CT examinations?

PURPOSE: To determine the percentage of outpatients with elevated serum creatinine levels (>/=2.0 mg/dL [177 micromol/L]) and associated reported risk factors for contrast material-induced nephrotoxic reactions (eg, diabetes, renal disease, male, age >/= 60 years, chemotherapy) who undergo computed tomography (CT) and to define a true high-risk population. MATERIALS AND METHODS: The serum creatinine levels were obtained in a total of 2,034 consecutive outpatients (969 male, 1,065 female) who underwent contrast material-enhanced CT. In addition, selected patient charts were reviewed to determine the presence of risk factors for contrast material-induced nephrotoxic reactions. RESULTS: Only 66 (3.2%) had an elevated serum creatinine level. Risk factors were identified in 64 of the 66 (97%) patients with an elevated serum creatinine level. Renal disease was present in 62 of the 66 (94%) patients. Two of the 66 patients with an elevated creatinine level had no identifiable risk factors, representing 0.1% of the total number of patients. CONCLUSION: The data suggest that the majority of patients with a serum creatinine level of at least 2.0 mg/dL (177 micromol/L) will be identified by screening for risk factors. Careful patient screening, especially for renal disease, at the time of scheduling could result in considerable savings in terms of radiology man-hours expended and laboratory costs.

Initial report of a cutaneous T-cell lymphoma appearing on the auricular helix.

We report a case of cutaneous T-cell lymphoma in which the first sign of disease was involvement of the superior auricular helix. A review of the literature reveals that T-cell lymphoma often presents cutaneously, but it usually does not involve the ear, and an auricular lesion is rarely the first sign. The uncommon nature of this presentation, in addition to the potential need for multiple biopsies for a tissue diagnosis, can lead to a delay in diagnosis. When evaluating skin lesions in the head and neck, a high index of suspicion for cutaneous T-cell lymphoma is a key factor in its early diagnosis.

Structural analysis and transcript processing of the bovine proteolipid protein (PLP) gene.

In this study we present the complete genomic structure of the bovine PLP gene and its assignment to the long arm of the X-chromosome (BTXq2.1). We determined a total of 18,767 bp of the bovine PLP gene and compared it to the human heterolog. A very high similarity was detected between the non-coding regions, interrupted primarily by several transposable elements. A deletion of 13 bp in the vicinity to the translation start signal in the promoter of the bovine PLP gene was found. Functional studies of the 3' region showed the use of several polyadenylation signals. Three main transcripts were detected in adult cattle in the range of 3200, 2400, and 1600 nucleotides using Northern blot analysis. An additional shorter transcript was detected in the cerebrum of calves.