Pathophysiology and treatment of painful diabetic neuropathy of the lower extremity

BACKGROUND: Symptomatic peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 62% of Americans with diabetes. METHODS: We reviewed the literature using the National Library of Medicine's MEDLINE search service. In total, we reviewed 54 articles. RESULTS: Hyperglycemia leads to increased activity in the polyol pathway in nerve cells; this ultimately results in abnormal nerve function. Numerous pharmacologic agents have been used to treat symptomatic peripheral neuropathy, but all of these drugs can be associated with adverse side effects. Recent work has indicated that subsensory electrical stimulation may be preferred to pharmacotherapy, since it is equally effective and has a more favorable safety profile. CONCLUSION: Although the pathophysiology of diabetic neuropathy is well understood, treatment of the symptoms associated with this condition can be challenging. Additional research is needed to reveal a safe and effective treatment for this debilitating sequela of diabetes mellitus.     

Bilateral Comparison of Aluminum Fixed-Point Cells Using Standard Platinum Resistance Thermometer

The objective of Project EURAMET 1114 (Bilateral comparison of a freezing point of aluminum) in the field of thermometry is to compare realization of a freezing point of aluminum (660.323???C) between the Dutch national laboratory VSL and the Slovenian national laboratory MIRS/UL-FE/LMK using a long-stem 25 ?? standard platinum resistance thermometer (SPRT). Both laboratories had participated in a number of inter-comparisons on the level of EURAMET and also on BIPM CCT level (VSL). MIRS/UL-FE/LMK laboratory recently acquired a new fixed-point cell which had to be validated in the process of intercomparison. A quartz-sheathed SPRT was selected and calibrated at MIRS/UL-FE/LMK at the aluminum freezing point and at the water triple point. A second set of measurements was made on the same SPRT and at the same fixed points at VSL (NL). After its return, the SPRT was again recalibrated at MIRS/UL-FE/LMK. In the comparison the W value of the SPRT was used. The results of the internal and external intercomparisons confirmed that the new aluminum cell of the MIRS/UL/FE-LMK realizes a temperature that agrees with the VSL aluminum fixed point within the uncertainty limits of both laboratories. Furthermore, the results of this bilateral-comparison were compared with results that both laboratories achieved in the EURAMET K4 (Project 820) and were found to be in agreement.     

Understanding regional variation in entrepreneurial activity and entrepreneurial attitude in Europe

Differences in entrepreneurial activity and entrepreneurial attitude are substantial and persistent across nations and regions. However, studies on entrepreneurship that encompass regions and countries at the same time are lacking. This paper explains both national and regional differences in entrepreneurial attitude and activity for 127 regions in 17 European countries, based on Global Entrepreneurship Monitor (GEM) data. We reveal the importance of institutional factors and economic and demographic attributes to variations in regional entrepreneurial attitude and activity. Our findings point at the relevance of distinguishing between components of entrepreneurial attitudes, i.e. fear of failure in starting business, perceptions on start-up opportunities and self-assessment of personal capabilities to start a firm. We find different determinants of these components, suggesting that they reflect different aspects of entrepreneurial attitude. In explaining regional prevalence rates of phases in entrepreneurial activity (nascent, baby business, established business) we find significant contributions of entrepreneurial attitude components. Urban regions and regions with high levels of nearby start-up examples show relatively high rates of early-stage entrepreneurship. A large number of start-up procedures does not discourage early-stage entrepreneurship.     

Ceramic Capillary Suspensions: Novel Processing Route for Macroporous Ceramic Materials

We introduce a novel method to produce macroporous ceramics by capillary suspensions. Adding a small amount (~1 vol%) of an immiscible secondary phase to a low concentration (~20 vol%) suspension can increase the yield stress by several orders of magnitude. This drastic change in flow behavior is induced by the creation of a sample‐spanning particle network in the suspension controlled by capillary forces. This strong network may persist even if the primary bulk phase is removed. Accordingly, capillary suspensions can be used as a precursor for manufacturing porous materials. Here, we focus on the specific features of this universal, low‐cost processing route for porous ceramics. An Al₂O₃ model system is used to demonstrate how to adjust porosity and pore size. With this system, we were able to achieve open porosities higher than 60% with an average pore size below 10 μm.     

Splice-site mutations: a novel genetic mechanism of Crigler-Najjar syndrome type 1

Crigler-Najjar syndrome type 1 (CN-1) is a recessively inherited, potentially lethal disorder characterized by severe unconjugated hyperbilirubinemia resulting from deficiency of the hepatic enzyme bilirubin-UDP-glucuronosyltransferase. In all CN-1 patients studied, structural mutations in one of the five exons of the gene (UGT1A1) encoding the uridinediphosphoglucuronate glucuronosyltransferase (UGT) isoform bilirubin-UGT1 were implicated in the absence or inactivation of the enzyme. We report two patients in whom CN-1 is caused, instead, by mutations in the noncoding intronic region of the UGT1A1 gene. One patient (A) was homozygous for a G-->C mutation at the splice-donor site in the intron, between exon 1 and exon 2. The other patient (B) was heterozygous for an A-->G shift at the splice-acceptor site in intron 3, and in the second allele a premature translation-termination codon in exon 1 was identified. Bilirubin-UGT1 mRNA is difficult to obtain, since it is expressed in the liver only. To determine the effects of these splice-junction mutations, we amplified genomic DNA of the relevant splice junctions. The amplicons were expressed in COS-7 cells, and the expressed mRNAs were analyzed. In both cases, splice-site mutations led to the use of cryptic splice sites, with consequent deletions in the processed mRNA. This is the first report of intronic mutations causing CN-1 and of the determination of the consequences of these mutations on mRNA structure, by ex vivo expression.     

Ideal Bend Contour Trajectories for Single-Mode Operation of Low-Loss Overmoded Waveguides

Bend designs for single-mode operation of low-loss overmoded waveguides are presented. A class of contour trajectories for minimum radiation loss is derived analytically, and numerical optimization is used to find ideal trajectory parameters. Three-dimensional finite-difference time-domain simulations predict bend losses below 0.1 dB for 180deg-bends of overmoded silicon-on-insulator waveguides with a radius of R=1.5 mum. These findings are supported experimentally     

Subsurface melting of nylon by friction-induced vibrations

Dry sliding of nylon on steel may lead to subsurface recrystallization of the polymer. This phenomenon is described and explained by subsurface melting due to internal heating as a result of the dissipation of frictioninduced vibrations at frequencies above 10 kHz. A vibration model relating the distribution of stress and temperature is proposed. Calculations based on this model show reasonable agreement with experimental observations.     

New method for hydroxylating long-chain unsaturated fatty acids,esters, alcohols,and hydrocarbons

Summary A new method for hydroxylating long-chain unsaturated compounds is described which involves addition of formic acid at its boiling point to the double bond followed by hydrolysis of the intermediate formate esters. The addition reaction proceeds slowly in the absence of catalysts, but strongly acidic substances, such as perchloric acid, sulfuric acid, and boron fluoride-acetic acid complex, speed up the addition tremendously. Monohydroxystearic acids can be prepared in good yield by addition of 90–100% formic acid to the double bond of oleic or elaidic acids, methyl oleate, or the unreacted olefinic material separated from the hydrolyzed reaction product of oleic acid with formic acid, followed by hydrolysis. Similarly prepared are dihydroxyoctadecanes from oleyl alcohol, monohydroxyoctadecenoic and dihydroxystearic acids from linoleic acid, monohydroxyhendecanoic acids (isolated as methyl esters) from 10-hendecenoic (undecylenic) acid, and secondary hexanols from 1-hexene. Triglycerides are readily formylated if a small amount of mutual cosolvent is employed. Acetic acid in the presence of acidic catalysts also adds to the double bond at its normal boiling point, but yields are lower than with formic acid. Presented at the Fall Meeting of the American Oil Chemists’ Society, Cincinnati, O., Oct. 20–22, 1952. One of the laboratories of the Bureau of Agricultural and Industrial Chemistry, Agricultural Research Administration, U. S. Department of Agriculture.     

A Sub-millikelvin Calibration Facility in the Range 0 $$^{\circ }$$C to 30 $$^{\circ }$$C

A new sub-millikelvin calibration facility for the range 0 \(^{\circ }\)C to 30 \(^{\circ }\)C is described, that allows calibration of customer thermometers, other than standard platinum resistance thermometers, with an uncertainty lower than 1 millikelvin. The improvements with respect to the traditional calibration facility are reported with particular emphasis on the temperature control (better than 0.2 mK), resistance measurement and calibration procedure. The new facility was validated by using 6 standard platinum resistance thermometers and the calibration uncertainty in the range from 0 \(^{\circ }\)C to 30 \(^{\circ }\)C amounted to 0.31 mK–0.35 mK. To demonstrate the potentiality of this facility, two oceanographic thermometers, Sea-Bird Electronics SBE 3 and SBE 35, were calibrated with an expanded uncertainty of 0.8 mK (\(k=2\)).     

Development of the High-Temperature Dew-Point Generator Over the Past 15 Years

At VSL a humidity generator was designed and constructed in the early 1990s. This generator was of the re-circulating-single-pressure type. Over the years, the generator has been thoroughly revised and several critical components have been replaced. Among others the pre-saturator and the change from re-circulation to single-pass mode. Validating experiments showed that the range of the new setup could be extended from \(70\,{^{\circ }}\hbox {C}\) to \(95\,{^{\circ }}\hbox {C}\) dew-point temperature, and the last modification allows an uncertainty of \(0.048\,{^{\circ }}\hbox {C}\) (k = 2) at the maximum temperature. In 2009 the setup was used in the Euramet-T-K8 humidity intercomparison at temperatures up to \(95\,{^{\circ }}\hbox {C}\). In the period from 2003 to 2015, four state-of-the-art chilled mirror hygrometers were regularly calibrated with the generator. One of these was also calibrated with the primary dew-point standards of several other European National Metrology Institutes, which made it possible to link the VSL generator to the generators used in these institutes. An analysis of the results of these calibrations shows an agreement in calibration capabilities within \(0.01\,{^{\circ }}\hbox {C}\) with PTB and NPL.