Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

Pressure release of containments during severe accidents in Switzerland

As required by the Swiss Federal Nuclear Safety Inspectorate (HSK) all Switzerland's five nuclear power plants have to install a containment filtered venting system. The integrity of the containment (the last barrier for radioactive releases to the environment) can be threatened by overpressure due to inadequate heat removal. Design requirements have been provided for a specific class of severe accident scenarios. In general the capacity of the system is considered sufficient if it is able to vent the steam production corresponding to a decay heat level of 1% of the thermal reactor power. The mitigation capacity for the reduction of released radioactive material is specified by a retention factor of 1000 for aerosols to prevent or limit a long term ground contamination and a factor of 100 for elementary iodine for prevention or limiting of thyroid doses and to avoid short term evacuation. Besides existing requirements for design, maintenance and operation, additional claims such as passivity and operability at any pressure conditions inside the containment have to be met. Passivity implies that the system can be initiated after a severe accident without any operator action. The system also has to allow early manual venting. Various filtered venting systems are presently available. The nuclear power plants of Beznau, Gosgen, Leibstadt and Muhleberg have already selected such systems and already implemented them or are going to install them step by step. Beznau selected the Sulzer-EWI system which is using a water pool with nozzles-baffle plates and mixing elements to achieve the required filtration of the aerosols. In both Beznau units, the systems are installed and in standby mode. Gosgen, a pressurized water reactor as well as Beznau, is going to implement a filter system developed by Siemens-KWU, known as sliding pressure venting process, combining a venturi scrubber in a water pool and a mesh filter. The boiling water reactor of Leibstadt also selected the same system as Beznau while Müheberg choose the ABB system but not in the common design. The venturi pipes are thereby integrated in the water pool of the outer torus. The system in all five nuclear power plants is fully operable and in standby mode since December 1993.     

Complications following major abdominal surgery in cirrhotic patients

The morbidity and mortality associated with major abdominal surgical interventions in 34 histologically proven cirrhotic patients are analyzed by the authors. The surgical interventions were carried out as urgent, absolute and elective indications. Thirty-seven general and surgical complications were observed following major abdominal surgery in 34 cirrhotics. Seven out of 34 patients died, giving a mortality rate of 21%. Suture-line insufficiency, peritonitis, sepsis and other inflammatory processes turned out to be the most common complications. Statistical analysis showed that the Child criteria, prothrombin level and white blood cell count were useful prognostic factors.     

Supraclavicular abscess caused by Salmonella enteritidis in patient without gastrointestinal symptoms

Soft tissue infections are among the rare manifestations of extra intestinal salmonellosis and occur more frequently in immunocompromised patients. Herein we report a case of a 51-year-old white male with type II. diabetes mellitus, diagnosed with supraclavicular abscess caused by Salmonella enteritidis. The patient denied any gastrointestinal symptoms, and stool cultures were negative. After incision, drainage, and administration of intravenous ampicillin (4 x 1.5 g/day for two weeks) the patient recovered completely. To our knowledge, this is the first reported case of cervical soft tissue abscess caused by Salmonella enteritidis without preceding gastrointestinal symptoms. We feel that the presence of diabetes was a risk factor for developing the infection.     

Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.     

Addition of ferulic acid,ethyl ferulate,and feruloylated monoacyl- and diacylglycerols to salad oils and frying oils

To determine antioxidative effects of ferulic acid and esterified ferulic acids, these compounds were added to soybean oils (SBO), which were evaluated for oxidative stability and frying stability. Additives included feruloylated MAG and DAG (FMG/FDG), ferulic acid, ethyl ferulate, and TBHQ. After frying tests with potato chips, oils were analyzed for retention of additives and polar compounds. Chips were evaluated for hexanal and rancid odor. After 15 h frying, 71% of FMG/FDG was retained, whereas 55% of ethyl ferulate was retained. TBHQ and ferulic acid levels were 6% and <1%, respectively. Frying oils with ethyl ferulate or TBHQ produced significantly less polar compounds than SBO with no additives. Chips fried in SBO with TBHQ or ferulic acid had significantly lower amounts of hexanal and significantly less rancid odor after 8 d at 60°C than other samples. Oils were also aged at 60°C, and stability was analyzed by PV, hexanal, and rancid odor. Oils with TBHQ or FMG/FDG had significantly less peroxides and hexanal, and a lower rancid odor intensity than the control. FMG/FDG inhibited deterioration at 60°C, whereas ethyl ferulate inhibited the formation of polar compounds in frying oil. Ferulic acid acted as an antioxidant in aged fried food. TBHQ inhibited oil degradation at both temperatures. Presented at the 94th AOCS Meeting & Expo, Kansas City, MO, May 4–7, 2003.     

Generating Rare Association Rules Using the Minimal Rare Itemsets Family

Rare association rules correspond to rare, or infrequent, itemsets, as opposed to frequent ones that are targeted by conventional pattern miners. Rare rules reflect regularities of local, rather than global, scope that can nevertheless provide valuable insights to an expert, especially in areas such as genetics and medical diagnosis where some specific deviations/illnesses occur only in a small number of cases. The work presented here is motivated by the long-standing open question of efficiently mining strong rare rules, i.e., rules with high confidence and low support. We also propose an efficient solution for finding the set of minimal rare itemsets. This set serves as a basis for generating rare association rules.     

Approximation Bounds for Minimum Information Loss Microaggregation

The NP-hard microaggregation problem seeks a partition of data points into groups of minimum specified size k, so as to minimize the sum of the squared euclidean distances of every point to its group's centroid. One recent heuristic provides an O(k³) guarantee for this objective function and an O(k²) guarantee for a version of the problem that seeks to minimize the sum of the distances of the points to its group's centroid. This paper establishes approximation bounds for another microaggregation heuristic, providing better approximation guarantees of O(k²) for the squared distance measure and O(k) for the distance measure.