Genetic variability of Echinococcus granulosus sensu stricto in Europe inferred by mitochondrial DNA sequences.
The genetic diversity of Echinococcus granulosus sensu stricto (s.s.) metacestodes from four European countries was evaluated by the DNA sequence analysis of the cytochrome c oxidase subunit 1 (cox1) mitochondrial gene. Of the 312 organisms investigated, 132 were from Bulgaria, 35 from Hungary, 89 from Italy and 56 from Romania. Considerable intraspecific variation was observed in the mitochondrial cox1 sequences: 24 haplotypes were detected in the Eastern European population and seven in the Italian population. The Eastern European population parsimony network displayed a star-like features consisting of the most common haplotype EG1 (G1 genotype) and the three major haplotypes: EG2, EG3 and EG4. The EG1 was also the major haplotype in the Italian population network, though with a higher prevalence (73%) compared to the Eastern European network. The percentage of the population constituted by the G1 genotype was used as an indirect index to evaluate the genetic diversity within E. granulosus s.s. populations of Eurasia. A clinal correlation between the percentage of the G1 genotype and the geographical regions of Eurasia was observed: the G1 genotype is highly represented in the Mediterranean Basin; it decreases in Eastern Europe and South-West Asia and increases in China. This clinal correlation could reflect the spreading of livestock domestication from Southern-Western Asia during the Neolithic period, beginning around 12,000 BC.


Regulation of nitrogen fixation in Rhizobium spp. Isolation of mutants of Rhizobium trifolii which induce nitrogenase activity.
This communication describes the isolation and characterization of mutants of Rhizobium trifolii which can induce nitrogenase activity in defined liquid medium. Two procedures were used for the isolation of these mutants from R. trifolii strain DT-6: (1) following chemical mutagenesis, slow growing mutants were selected which were unable to utilize NH+4 as sole source of nitrogen; (2) as spontaneous mutants resistant to the glutamate analogue L-methionine-DL-sulfoximine. Mutants (DT-71, DT-125) isolated by these procedures induced nitrogenase activity in the free-living state, whereas the parent strain lacked this property. Induction of nitrogenase activity in these mutants occurred during the late exponential phase of growth when the rate of protein synthesis was decreasing. The addition of NH+4 to a medium containing glutamate as the nitrogen-source resulted in a 50--70% reduction (repression?) of nitrogenase activity; in contrast, the rate of protein synthesis or the rate of respiration was not influenced by exogenous NH+4. Biochemical analysis showed that these mutants (strains DT-71 and DT-125) have defects in both nitrogen and carbon metabolism. The levels of glutamate synthase (both NADP+ -and NAD+ -dependent activities) and glutamate dehydrogenase (NAD+-dependent activity) were markedly lower. In addition, the mutants were found to have no detectable ribitol dehydrogenase or beta-galactosidase activity. These findings are discussed in relation to a mechanism of regulation of symbiotic nitrogen fixation.


Design, construction, and validation of an in-situ groundwater trace element analyzer with applications in carbon storage.
It is estimated that carbon emissions should reach net-zero by 2050 to meet important climate targets. Carbon capture is likely necessary to reach these targets, requiring a long-term storage solution such as geological carbon sequestration. However, as with any subsurface activity, leakage can occur, potentially impacting groundwater quality near the storage site. Rapid detection is essential to mitigate damage to this resource. Since CO2 will acidify groundwater, the concentrations of acid soluble minerals and associated cations will increase. Thus, an in-situ, real-time element analysis system based on laser-induced breakdown spectroscopy (LIBS) is under development to monitor these elements. The system splits the traditional LIBS system into a miniature, all-optical sensor head built around a passively Q-switch laser fiber coupled to a control unit. Previous work has validated the LIBS technique for use at high pressure as well as the split system design. In this work, a fieldable prototype sensor is developed and tested in an onsite monitoring well where trace elements concentrations (approx. 0-3 ppm) were tracked over 20 days. These concentrations varied in response to local rainfall, diluting with increased rain, demonstrating the ability of a LIBS-based sensor to track trace elements under real-world conditions.


Phospholipase A activities in rat placentas of 14 days' gestation.
1. Homogenates and subcellular fractions of placentas obtained from rats on the 14th day of gestation were assayed for enzymes characteristic of various subcellular organelles. Based on these assays it seemed the placental lysosomes (acid phosphatase activity) were distributed equally among the subcellular particulate fractions and that the cytosol was not contaminated by mitochondria or microsomes. 2. The placental preparations were assayed for phospholipase A activity using 2-[14-C] phosphatidylethanolamine. We found phospholipases A with pH optima of 4.0, 7.0, and 8.5. These enzymes had Ca-2+ requirements and subcellular localizations similar to those reported for adult rat liver (Waite, M., Scherphof, G.L., Boshouivers, F.M.G. and van Deenen, L.L.M. (1969) J. Lipid Res. 10, 411.) 3. The majority of the placental phospholipase A activity was found in the cytosol. We think this activity represents enzyme(s) solubilized from the plasma membranes of placental cells and speculate that this enzyme may be active in a placental transport mechanism.


Nutritional support of the obese patient.
Overweight and obesity is the most common chronic disease in the United States and is associated with an increased risk for morbidity and mortality. For the hospitalized patient, the mechanical, metabolic, and inflammatory physiologic changes induced by obesity necessitate additional considerations for care. Calculation of nutritional requirements is problematic and challenging due to difficulty in measuring body composition and energy expenditure. Provision of selective hypocaloric feeding in this population may be particularly beneficial in reducing complications of hyperglycemia, fluid overload, and reduction in fat mass. Clinical care should incorporate a team approach that addresses the special nutritional and metabolic needs of this population.


Obstructive jaundice secondary to multiple hepatic artery aneurysms in a 14-year-old boy with neurofibromatosis type 1.
Neurofibromatosis type 1 is the most common inherited disorder of the nervous system, affecting approximately 1 in 3,000 people. A small but significant subset of these patients develop vasculopathies. We present the first reported case of neurofibromatosis type 1 presenting with obstructive jaundice secondary to multiple hepatic artery aneurysms. Therapy included staged coil embolization of the hepatic artery aneurysms and resection of a large retroperitoneal neurofibroma.


An allometric model for predicting blood ethanol elimination in mammals.
The relationship of ethanol elimination kinetics in mammals was estimated using the allometric principle. The hypothesis of relationships between parameters obtained from the compartment model with Michaelis-Menten elimination kinetics and body weight can lead to common equations of blood ethanol elimination in mammals. The maximum elimination velocity (g/hr) and the apparent volume of distribution (L) were significantly proportional to the 0.71 and 0.93 powers of body weight (r = 0.994, P < 0.01 and r = 0.998, P < 0.001), respectively. There was no significant relationship between the Michaelis constant and body weight. In the differential equations of the two-compartment model, the kinetics parameters were substituted for the obtained power functions. Good fitting of these equations for the real data showed that ethanol elimination kinetics in mammals can be predicted quantitatively.


A case of red-cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan.
A case of red cell adenosine deaminase (ADA) overproduction associated with hereditary hemolytic anemia is reported here. This appears to be the second report. Proband is a 38-year-old Japanese male who had hemoglobin, 15.8 g/100 ml; reticulocyte count, 4.5%; serum indirect bilirubin, 4.9 mg/100 ml; 51Cr-labeled red cell half-life, 12 days; red cells showed moderate stomatocytosis. His red cell ADA activity showed 40-fold increase while that of the mother showed 4-fold increase. The mother was hematologically normal. The father had a normal enzyme activity. The proband and the mother showed slightly high serum uric acid levels. The proband's red cell showed: ATP, 628 nmoles/ml (normal, 1,010--1,550); adenine nucleotide pool, 46% of the normal mean; 2,3-diphosphoglycerate content, 3,782 nmoles/ml (normal 4,170--5,300); increased oxygen affinity of hemoglobin, P50 of intact erythrocytes being 21.8 mmHg (normal, 24.1--26.1). Red cell glycolytic intermediates in the proband were low in general, and the rate of lactate production was low. Kinetic studies using crude hemolysate revealed a normal Km for adenosine, normal electrophoretic mobility but slightly abnormal pH curve and slightly low utilization of 2-deoxyadenosine. The ADA activity of lymphocytes was nearly normal.


The hypolipidemic activity of chitosan nanopowder prepared by ultrafine milling.
The hypolipidemic activities of high and low molecular weights of chitosan nanopowders (HMW-chitosan-NP: 315 kDa; LMW-chitosan-NP: 51 kDa) prepared by ultrafine milling were evaluated in rats. The results showed that the hypolipidemic activity of chitosan nanopowder was better than ordinary chitosan, and LMW-chitosan-NP was superior to HMW-chitosan-NP in hypolipidimic activity. Compared with ordinary chitosan, chitosan nanopowder increased the fecal lipids and the activities of serum and liver lipoprotein lipase (LPL) and hepatic lipase (HL) of rats. Rats receiving LMW-chitosan-NP excreted less lipids in feces, but showed higher serum and liver LPL and HL activities compared with those fed HMW-chitosan-NP. These results suggested that compared with ordinary chitosan, the increased hypolipidemic activity of chitosan nanopowder might be attributed to its ability on increasing fecal lipid excretions and stimulating LPL and HL activities, and the better stimulation of LMW-chitosan-NP in activities of these lipases might help it to exceed HMW-chitosan-NP in hypolipidemic activity.


A quick investigation of the detrimental effects of environmental pollutant polycyclic aromatic hydrocarbon fluoranthene on the photosynthetic efficiency of wheat (Triticum aestivum).
The present study describes the effects of polycyclic aromatic hydrocarbon pollutant fluoranthene (FLT) on photochemical efficiency of plants and hence their growth. Chlorophyll a fluorescence measurements were performed in order to get quick and reliable information about the effects of fluoranthene. The number of active reaction centres decreased by more than 20% in FLT treated samples. The results show that FLT affects the overall primary photochemistry by inhibiting the number of active reaction centres (RC) while the efficiency of each of the active reaction centres is not affected. We propose that the effect of fluoranthene is mainly on the absorption and trapping of the light energy by the RC rather than the actual electron transport. The results may be applicable to a wide range of plants provided other environmental and physiological conditions are taken into account carefully.


Microchimeric fetal cells cluster at sites of tissue injury in lung decades after pregnancy.
Fetal cells trafficking into maternal blood during pregnancy engraft tissues and persist for decades in marrow and bone. While persistent fetal cells were initially implicated in autoimmune disease, animal studies suggest that microchimeric fetal cells play a broader role in response to tissue injury. This study investigated whether fetal cells participate in tissue repair after human pregnancy. Specimens were obtained from women undergoing surgery for suspected lung cancer. Y-fluorescence in-situ hybridization was performed on paraffin-embedded sections, with the investigator blinded to medical histories. Male cells were identified in lung/thymus tissue from all women with known male pregnancies, but not in those without sons. The frequency of male microchimeric cells was seven-fold greater in lung/thymus tissues than marrow and was two-fold greater than normal bone from the same women. Nested-polymerase chain reaction for sex determining region Y confirmed male DNA in tissues. Male cells in lung were clustered in tumour rather than surrounding healthy tissues. In conclusion, male presumed-fetal cells were identified in pathological post-reproductive tissues, where they were more likely to be located in diseased tissues at several-fold higher frequency than normal tissues. It is suggested that fetal cells are present at sites of tissue injury and may be stem cells, either recruited from marrow or having proliferated locally.


Attention-deficit/hyperactivity disorder with oppositional defiant disorder in Swedish children - an open study of collaborative problem solving.
To evaluate collaborative problem solving (CPS) in Swedish 6-13-year-old children with attention-deficit/hyperactivity disorder and oppositional defiant disorder (ODD). Seventeen families completed 6-10 sessions of CPS training. Primary outcome measures were SNAP-IV [attention-deficit/hyperactivity disorder (ADHD) and ODD scores] and Clinical Global Impression-Improvement (CGI-I) scores at baseline, post-intervention and 6 months later. Secondary outcome measures were the Conners' 10-item scale and the Family Burden of Illness Module (FBIM). All 17 participants completed the intervention. The whole group had significant reductions in SNAP-IV ODD, ADHD, total Conners' and FBIM scores, both at post-intervention and at 6-month follow-up. Eight of the children, although significantly improved on ODD scores and the Conners' emotional lability subscale at post-intervention, had almost no improvement in hyperactivity/impulsivity. Post-intervention, this group received stimulant medication for their ADHD. CGI-I scores of much improved or very much improved were reached by 53% (9/17) of all at post-intervention, and by 81% (13/16) at 6-month follow-up. Collaborative problem solving significantly reduced ODD, ADHD and emotional lability symptoms. A subgroup improved in their ADHD symptoms only after adding stimulant medication.


Identification of characteristic aroma components of butter from Chinese butter hotpot seasoning.
The potent aroma compounds in butter from four kinds of Chinese butter hotpot seasoning were first investigated by analyzing the isolates from solid-phase microextraction. A total of 49 aroma compounds were identified, and 23 of them were highly correlated with the aroma profiles of the butter by partial least squares regression analysis. Aroma extract dilution analysis and odor activity value calculations were applied to further reveal the dominant odorants. Fifty-three odorants with flavor dilution factors between 1 and 1024 were identified and OAVs of 17 odorants were greater than 1. Finally, an aroma recombination experiment was prepared by mixing the aroma-active compounds (OAVs > 1), and the aroma profile of the recombination showed good agreement with that of the original sample. Omission tests showed that 2-furfurylthiol, 2-acetylthiazole, anethole, (E)-2-decenal, and 1,8-cineole were the key odorants for the overall aroma of butter.


[Innervation of the anterior byssus retractor muscle (ABRM) in Mytilus edulis L. and in Mytilus galloprovincialis Lmk. V. Cytochemical localization of cholinesterase activities (author's transl)].
Specific and non specific cholinesterase activities were demonstrated in the ABRM of Mytilus edulis L. and Mytilus galloprovincialis L. by means of different techniques. The results were found identical for both species: neuromuscular junctions "en grappe"-type scarely distributed within the ABRM, contain AChE. According to the histochemical inhibition tests, (a) the eserine inhibits AChE activity of the ABRM with a level of 5-10(-5) M or higher, (b) the ChE non specific activities are inhibited by iso-OMPA level between 5.10(-5) to 10(-4) M. The histo- and cytochemical observations were completed by showing the existence of neuromuscular junctions containing small clear vesicles: they probably are the morphological support for ACh presence. Moreover, specific and non specific ChE activities were localized in the glio-interstitial cells. AChE precipitates were developed along the ABRM sarcolemma, some muscle mitochondria and in the intercellular spaces remain enigmatic.


[Morphofunctional state of the blood microcirculatory bed in the injured gastrocnemius muscle in rats during pharmacological stimulation].
The state of hemomicrocirculatory bed and of local peripheral circulation was studied after the operational injury of rat gastrochnemius muscle without pharmacologic treatment and following a combined administration of alpha-tocopherol and methyluracil. Local circulation in the regenerate of the treated animals was shown to increase not only as a result of increase of capillary density, but also due to the elevation in the number of functioning capillaries and veins.


Magnetic anisotropy reversal driven by structural symmetry-breaking in monolayer α-RuCl3.
Layered α-RuCl3 is a promising material to potentially realize the long-sought Kitaev quantum spin liquid with fractionalized excitations. While evidence of this state has been reported under a modest in-plane magnetic field, such behaviour is largely inconsistent with theoretical expectations of spin liquid phases emerging only in out-of-plane fields. These predicted field-induced states have been largely out of reach due to the strong easy-plane anisotropy of bulk crystals, however. We use a combination of tunnelling spectroscopy, magnetotransport, electron diffraction and ab initio calculations to study the layer-dependent magnons, magnetic anisotropy, structure and exchange coupling in atomically thin samples. Due to picoscale distortions, the sign of the average off-diagonal exchange changes in monolayer α-RuCl3, leading to a reversal of spin anisotropy to easy-axis anisotropy, while the Kitaev interaction is concomitantly enhanced. Our work opens the door to the possible exploration of Kitaev physics in the true two-dimensional limit.


The cost of misadventures in colonic surgery. A model for the analysis of adverse outcomes in standard procedures.
Analysis revealed an impressive number of patients transferred to intensive care at the Peter Bent Brigham Hospital after misadventures in standard medical and surgical procedures. The model explored here is that of colon surgery, a therapy standardized for decades. The courses of sixteen patients were studied, wherein adverse outcomes appeared to have been preventable. Failure to diagnose colonic leakage and failure to provide colostomy (or to do so safely) were the major underlying causes. Nephrotoxic antibiotics and immunosuppression were sometimes in the background. Nine patients died, all with severe sepsis. Multiple organ failure occurred in the majority of cases. The mortality was tenfold, the cost sevenfold, and the length of hospitalization fourfold that expected after uneventful operation. Current interest in cost-benefit analysis should be broadened standard medical and surgical procedures. Litigious potential should not be allowed to impede such analyses.


Atenolol-imprinted polymer: a DFT study.
The purpose of this work was to investigate, via DFT calculations, the molecularly imprinted polymer (MIP) for atenolol (ATL) β-blocker evaluating distinct functional monomers (FMs), solvents, and cross-linker agents (CLAs). As the main result, we could determine from structural and thermodynamic data the best MIP synthesis protocol as being: p-vinyl benzoic acid (APV) as FM, toluene as solvent, and pentaerythritol triacrylate (PETRA) as CLA. We believe this rational design can be very useful for experimentalists in an attempt to perform an efficient synthesis of a MIP for this important β-blocker drug.


Inhibition of primary and secondary nucleation alongwith disruption of amyloid fibrils and alleviation of associated cytotoxicity: A biophysical insight of a novel property of Chlorpropamide (an anti-diabetic drug).
Aggregation of physiologically synthesized soluble proteins to insoluble, cytotoxic fibrils is a pre-requisite for pathogenesis of amyloid associated disorders including Alzheimer's disease, non-systemic amyloidosis, Parkinson's disease, etc. Considerable advancement has been made to understand the mechanism behind aggregation process but till date we have no efficient cure and preventive therapy for associated diseases. Strategies to prevent protein aggregation are nevertheless many which have been proved promisingly successful in vitro. One of those is repurposing already approved drugs that saves time and money too and has been employed in this study. Here, for the first time we are reporting the effectiveness of an anti-diabetic drug chlorpropamide (CHL) under dosage conditions, a novel property to inhibit aggregation in human lysozyme (HL) in vitro. Spectroscopic (Turbidity, RLS, ThT, DLS, ANS) and microscopic (CLSM) results demonstrates that CHL has the potency to suppress aggregation in HL up to 70 %. CHL is shown to affect the elongation of fibrils with IC50 value of 88.5 μM as clear from the kinetics results, may be by interacting near/with aggregation prone regions of HL. Hemolytic assay also revealed the reduced cytotoxicity in the presence of CHL. Disruption of amyloid fibrils and inhibition of secondary nucleation in the presence of CHL was also evidenced by ThT, CD and CLSM results with reduced cytotoxicity as confirmed by hemolytic assay. We also performed preliminary studies on α-synuclein fibrillation inhibition and surprisingly found that CHL is not just inhibiting the fibrillation but also stabilizing the protein in its native state. These findings insinuate that CHL (anti-diabetic) possess multiple roles and can be a promising drug for developing therapeutic against non-systemic amyloidosis, Parkinson's disease and other amyloid associated disorders.


Hydroalcoholic extract of Tagetes minuta L. inhibits inflammatory bowel disease through the activity of pheophytins on the NF-κB signalling pathway.
Species of the genus Tagetes are well known for their anti-inflammatory properties. Tagetes minuta "Huacatay" is an endemic species of South America that has been used in traditional medicine since ancient times as a remedy for stomach and intestinal discomfort. The aim of this study is to investigate the anti-inflammatory activity of the aqueous and hydroalcoholic extracts of the Huacatay, identifying the compounds responsible for this activity. Anti-inflammatory activity of the compounds, fractions and extracts was evaluated in Hs 746T (stomach), HIEC-6 (intestine) and THP-1 (monocytes peripheral blood) cells by measuring their inhibitory capacity against the NF-κB production. Aqueous and hydroalcoholic extracts of Tagetes minuta displayed anti-inflammatory activity in vitro, the hydroalcoholic extract being the most active (IC50 between 59.72 and 66.42 μg/mL) in all cell lines. Bio-guided hydroalcoholic extract fractionation led to the isolation and characterisation of two pheophytins, pheophytin a (1) and 132-hydroxy pheophytin a (2). Both compounds inhibited the production of NF-κB with IC50 values in the low micromolar range, with an IC50 between 12.32 and 16.01 μM for compound 1 and 7.91-9.87 μM for compound 2. The two pheophytins isolated in this study inhibit the production of NF-κB, thus showing that the traditional anti-inflammatory use of Tagetes minuta can be proved through pharmacological assays. This contributes to understanding the anti-inflammatory activity of the Huacatay extracts and their use in the treatment of stomach and intestinal discomfort.


Photosynthetic acclimation and water-use efficiency of three species of understory herbaceous bamboo (Gramineae) in Panama.
To assess the role of photosynthetic acclimation in the response of tropical understory herbs to treefall light gaps, photosynthetic response curves were determined for three species of herbaceous bamboo growing in treatments of sun and shade at Barro Calorado Island, Panama. Increased maximum photosynthetic capacity did not always accompany higher ramet production in the sun treatment. Pharus latifolius reproduced abundantly in both treatments, and produced more ramets and developed higher maximum photosynthetic capacity under higher irradiance. Streptochaeta spicata also produced a high percentage of reproductive ramets in both treatments and produced more ramets in the sun, did not show any significant differences in photosynthetic parameters between treatments. Streptochaeta sodiroana did not change maximum photosynthetic capacity in the sun, and had higher photosynthetic efficiency and lower mortality in the shade. Stable carbon isotope composition of leaves indicated that all three species developed higher water-use efficiency under higher irradiance. Photosynthetic flexibility may contribute to the ability of P. latifolius to reproduce in treefall gaps, whereas S. spicata and S. sodiroana may maintain the ability to fix carbon efficiently in low irradiance even when growing or persisting in gaps.


From life insurance to safer sex--reflections of a marketing man.
Much of the writing on health in developing countries focuses on the public sector rather than the private market, and on providers rather than on consumers. A more consumer-oriented perspective would regard the transactions by which most people in most poor countries buy healthcare as the norm, just one among many purchases of a personal service which all of us, as consumers, have to make. This paper contends that asymmetric information is not confined to health and medicine, but is a common problem for consumers whatever the GDP of the country they live in, and however rich and poor they may be. Understanding how consumers overcome these problems yields insights into the ways in which providers have to market their services, and into what, if anything, governments and donors can do to extend, improve or regulate the private healthcare market.


[Rare syndromes in intensive care medicine : Presentation of two cases].
This article presents two cases of young women with spontaneous life-threatening bleeding events. Both had a history of gastrointestinal rupture or arterial dissection. Based on their medical history and genetic testing, Ehlers-Danlos syndrome (EDS) IV (vascular type) was diagnosed. In this very rare disorder which accounts for only 5 % of all EDS cases, fibroblasts synthesize reduced and abnormal procollagen type III. This is caused by mutations in the COL3A1 gene coding for type III procollagen. Life expectancy in these patients is significantly reduced. In many cases spontaneous arterial ruptures or dissections and organ ruptures are the first manifestations of this disease. More than 80 % of patients with EDS IV suffer from a severe complication before 40 years of age. Treatment options are very limited. Most important is to avoid invasive procedures (open surgery as well as endovascular interventions) because of its high morbidity and mortality. Celiprolol, a cardioselective β‑blocker, seems to have a beneficial effect by reducing the incidence of vascular complications.


Dissipation kinetics of fenamidone, propamocarb and their metabolites in ambient soil and water samples and unknown screening of metabolites.
A fenamidone and propamocarb dissipation study was carried out applying ultra high-performance liquid chromatography coupled to Orbitrap mass spectrometry (UHPLC-Orbitrap-MS). Dissipation kinetics were evaluated in different types of soils and in water under different conditions (sunlight or darkness). In addition, a plant protection product containing both compounds was applied at two doses: (i) single and (ii) double dose in soils, and (i) single and (ii) fivefold dose in water. The fenamidone and propamocarb concentration decreased during the monitored period (100 days), obtaining high persistence in the case of water studies (DT50 > 50 days) and low to medium persistence in soils (DT50 < 50 days). No Observed Effect Concentration (NOEC) and concentration causing 50% lethality (EC50) were calculated and showed that fenamidone could cause toxic effects in soil and water organisms due to very high NOEC values (0.013 mg/L for aquatic invertebrates) while propamocarb did not cause any lethality. Fenamidone and propamocarb metabolites were also monitored with acetophenone and RPA-411639 ((5)-5-methyl-2-(methylthio)-3-(4-S nitrophenyl)amino-5-phenyl-3,5-dihydro-4H-imidazole-4-one) being the main metabolites for fenamidone. These metabolites obtained concentration values of up to 25% initial fenamidone content which can be a risk for the environment and fauna but, despite the toxicity of these compounds, they have not been studied yet. Metabolite 175 m/z and propamocarb n-desmethyl were the main propamocarb metabolites with values of 3% of initial propamocarb content. Three new propamocarb metabolites were detected in water samples and one in soil, highlighting the capabilities of the proposed methodology for monitoring known metabolites and identifying new ones in environmental studies.


The Thickness of the Retinal Nerve Fiber Layer (RNFL) as a Biomarker in Uveitis.
To study the changes of the retinal nerve fiber layer (RNFL) thickness during and following uveitis flares. This was a retrospective study of patients with uveitis diagnosed in the ophthalmology service of Torrevieja hospital. We analyzed RNFL thickness during and after the acute episode. We included 29 patients. Most patients (55.2%) had anterior uveitis; followed by posterior, intermediate and panuveitis. Mean RNFL thickness was significantly higher during the flare (132.17±35.54μm vs 107.66±17.10μm). RNFL thickness had no difference between groups with or without macular edema. The RNFL thickens during flares in most patients with uveitis. It can be measured by optical coherence tomography in a non-invasive way, representing an objective marker of inflammation. This can favor earlier detection of flares, resolution, and recurrence of uveitis. More studies are needed to determine the evolution of RNFL over time and in different types of uveitis.


Variant Chinese hamster cells resistant to the proline analog L-azetidine 2-carboxylic acid.
Variants resistant to the toxic effects of the proline analog L-azetidine 2-carboxylic acid (AZCA) have been isolated from the Chinese hamster tissue culture line G3 by a three-step selection procedure using increasing concentrations of AZCA. Cells surviving each of the three selective steps have been examined for AZCA resistance and for proline uptake, biosynthesis, and degradation. The largest increment in AZCA resistance is acquired in the third step and is due to overproduction of proline as a result of increased activity of the enzyme system responsible for the conversion of glutamic acid to glutamic gamma-semialdehyde. It is not accompanied by an increase in the rate of formation of proline from ornithine or in the rate of proline uptake or degradation.


X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis.
X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant clinical phenotype. Among 25 symptomatic patients diagnosed with XIAP deficiency, we identified 17 patients who initially presented with manifestations other than HLH. These included Crohn-like bowel disease (n=6), severe infectious mononucleosis (n=4), isolated splenomegaly (n=3), uveitis (n=1), periodic fever (n=1), fistulating skin abscesses (n=1) and severe Giardia enteritis (n=1). Subsequent manifestations included celiac-like disease, antibody deficiency, splenomegaly and partial HLH. Screening by flow cytometry identified 14 of 17 patients in our cohort. However, neither genotype nor protein expression nor results from cell death studies were clearly associated with the clinical phenotype. Only mutation analysis can reliably identify affected patients. XIAP deficiency must be considered in a wide range of clinical presentations.


Comparison of regional brain 5-HT and 5-HIAA content in flexor and extensor rats.
Hindlimb extension (HLE) induced by maximal electroshock seizures (MES) can be markedly affected by drugs which affect CNS 5-hydroxytryptamine (5-HT). Consequently, it has been proposed that the natural resistance of certain rats (flexor rats) to HLE is due to elevated levels of 5-HT. We have tested the hypothesis that the increased resistance of flexor rats to MES-induced HLE is due to elevated serotonergic levels in some region(s) of the CNS by examining 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in 8 regions of the CNS in rats classified by MES as either flexors or extensors. Furthermore, we compared the in vivo synthesis rate of 5-HT between flexor and extensor rats in 6 regions of the brain by measuring the accumulation of 5-HTP following aromatic amino acid decarboxylase inhibition with NSD-1015. All neurochemical analyses were carried out on rats sacrificed one week after their last seizure test. No differences in 5-HT, 5-HIAA or 5-HTP synthesis rate were detected between flexor and extensor rats for any of the regions examined, suggesting that enhanced serotonergic levels are not responsible for the unusual resistance of flexor rats to HLE.


A new method to obtain isofemale lines for monitoring Chilo suppressalis resistance to Bt toxin.
Cost-effective Bt resistance monitoring programmes exist to manage insect resistance to Bt crops. F2 screening is widely used in detecting rare resistant alleles. One way to establish numerous isofemale lines for F2 bioassays is acquiring many field-trapped copulated females. However, it is difficult to obtain sufficient Chilo suppressalis isofemale lines because females have low mating rates and fecundity. We developed a new method to establish C. suppressalis isofemale lines with field-collected egg masses. No significant difference in detection ability was observed in the F2 screen between the old and new methods. Moreover, the new method is economical, convenient and efficient.


Small extracellular vesicles delivering lncRNA WAC-AS1 aggravate renal allograft ischemia‒reperfusion injury by inducing ferroptosis propagation.
Ferroptosis is a predominant contributor to renal ischemia reperfusion injury (IRI) after kidney transplant, evoking delayed graft function and poorer long-term outcomes. The wide propagation of ferroptosis among cell populations in a wave-like manner, developing the "wave of ferroptosis" causes a larger area of tubular necrosis and accordingly aggravates renal allograft IRI. In this study, we decipher a whole new metabolic mechanism underlying ferroptosis and propose a novel spreading pathway of the "wave of ferroptosis" in the renal tissue microenvironment, in which renal IRI cell-secreted small extracellular vesicles (IRI-sEVs) delivering lncRNA WAC-AS1 reprogram glucose metabolism in adjacent renal tubular epithelial cell populations by inducing GFPT1 expression and increasing hexosamine biosynthesis pathway (HBP) flux, and consequently enhances O-GlcNAcylation. Additionally, BACH2 O-GlcNAcylation at threonine 389 in renal tubular epithelial cells prominently inhibits its degradation by ubiquitination and promotes importin α5-mediated nuclear translocation. We present the first evidence that intranuclear BACH2 suppresses SLC7A11 and GPX4 transcription by binding to their proximal promoters and decreases cellular anti-peroxidation capability, accordingly facilitating ferroptosis. Inhibition of sEV biogenesis and secretion by GW4869 and knockout of lncRNA WAC-AS1 in IRI-sEVs both unequivocally diminished the "wave of ferroptosis" propagation and protected against renal allograft IRI. The functional and mechanistic regulation of IRI-sEVs was further corroborated in an allograft kidney transplant model and an in situ renal IRI model. In summary, these findings suggest that inhibiting sEV-mediated lncRNA WAC-AS1 secretion and targeting HBP metabolism-induced BACH2 O-GlcNAcylation in renal tubular epithelial cells may serve as new strategies for protecting against graft IRI after kidney transplant.


Clinical Characteristics, Treatments, and Concurrent Mutations in Non-Small Cell Lung Cancer Patients With NF1 Mutations.
Metastatic non-small cell lung cancer (mNSCLC) is characterized by complex genomic alterations. NF1 mutations may confer distinct clinical characteristics within NSCLC, and real-world evidence on concurrent mutations, treatment patterns, and health outcomes is lacking. This retrospective study was performed in patients with mNSCLC treated in the Flatiron Health network who underwent the FoundationOne tumor-sequencing. Anticancer therapies, concurrent mutations, real-world progression-free survival (rwPFS), and overall survival (OS) were assessed. Of the 1663 patients, 103 patients were identified with NF1 mutation. Concurrent mutations with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (16.5%) and epidermal growth factor receptor fusion (6.8%) were the most frequent. In patients with NF1 mutation only (n = 57), 42% were women, 86% patients had smoking history, and 70% had non-squamous cell carcinoma type. Most (51%) of the patients with NF1 mutations received a single line of therapy versus other mutations and the overall treated population (44%). Platinum-based chemotherapy was the predominant first-line therapy, with programmed cell death-1/programmed cell death-ligand-1 inhibitors as subsequent lines of therapy. The NF1 mutation only group had numerically the shortest median rwPFS (82 days) than other mutation groups. Median OS for the NF1 mutation group in first, second, and third lines of therapy was 321, 498, and 210 days, respectively. NF1 mutations confer distinct clinical characteristics in patients with mNSCLC. These patients may have different trajectories for progression and survival than seen for other mutations, experience less systemic therapy after first-line therapy, and may have shorter survival.


Human mismatch repair: reconstitution of a nick-directed bidirectional reaction.
Bidirectional mismatch repair directed by a strand break located 3' or 5' to the mispair has been reconstituted using seven purified human activities: MutSalpha, MutLalpha, EXOI, replication protein A (RPA), proliferating cell nuclear antigen (PCNA), replication factor C (RFC) and DNA polymerase delta. In addition to DNA polymerase delta, PCNA, RFC, and RPA, 5'-directed repair depends on MutSalpha and EXOI, whereas 3'-directed mismatch correction also requires MutLalpha. The repair reaction displays specificity for DNA polymerase delta, an effect that presumably reflects interactions with other repair activities. Because previous studies have suggested potential involvement of the editing function of a replicative polymerase in mismatch-provoked excision, we have evaluated possible participation of DNA polymerase delta in the excision step of repair. RFC and PCNA dramatically activate polymerase delta-mediated hydrolysis of a primer-template. Nevertheless, the contribution of the polymerase to mismatch-provoked excision is very limited, both in the purified system and in HeLa extracts, as judged by in vitro assay using nicked circular heteroplex DNAs. Thus, excision and repair in the purified system containing polymerase delta are reduced 10-fold upon omission of EXOI or by substitution of a catalytically dead form of the exonuclease. Furthermore, aphidicolin inhibits both 3'- and 5'-directed excision in HeLa nuclear extracts by only 20-30%. Although this modest inhibition could be because of nonspecific effects, it may indicate limited dependence of bidirectional excision on an aphidicolin-sensitive DNA polymerase.


Association between ground reaction force in sit-to-stand motion and falls in community-dwelling older Japanese individuals.
Ground reaction force (GRF) during sit-to-stand motion is associated with lower extremity strength and balance function. The relationship between GRF and experience of falls has been reported; however, there are no reports on whether GRF can predict the incidence of future falls. We aimed to evaluate the ability of GRF to predict falls and compare GRF with existing predictors. This prospective observational cohort study enrolled 456 community-dwelling older adults living in Itabashi ward who participated in health check-ups in 2016 and 2017. Participants' physical and cognitive functions were assessed, and the maximum GRF (F), F/weight (F/W), rate of force development (RFD), RFD/W (RFD/weight), and time taken to stand up were evaluated. The following year, participants were asked to report the number of falls during the year. Cox proportional hazards regression was conducted to analyze the relationship between the lowest quintile of each GRF parameter as a predictive factor for falling and assess the annual incidence of falls. Twenty-three participants reported having two or more falls in the previous year. Of all GRF parameters evaluated, only F/W was lower in the fallers than in the non-fallers. After adjusting for sex, age, lifestyle, and comorbidities, F/W was associated with falls in 1 year, and the lowest F/W group had higher risks of falls than the highest F/W group (hazard ratio 2.72, 95 % confidence interval 1.11-6.68). Other measures were not associated with falls. GRF during the sit-to-stand motion might predict the incidence of future falls.


Simple fabrication of bimetallic platinum-rhodium alloyed nano-multipods: A highly effective and recyclable catalyst for reduction of 4-nitrophenol and rhodamine B.
Water pollution caused by organic pollutants has aroused great concern to earth sustainability in the last several decades. Herein, a facile one-pot solvothermal approach was developed to construct bimetallic platinum-rhodium alloyed nano-multipods (PtRh ANMPs) in oleylamine (OAm) by adopting creatinine and cetyltrimethylammonium chloride (CTAC) as the co-structure-directing agents. The as-fabricated nanocatalyst exhibited extraordinary catalytic behaviors towards 4-nitrophenol (4-NP) and rhodamine B (RhB) reduction by sodium borohydride (NaBH4). Impressively, the resultant catalyst showed highly facilitated rate constant (k: 0.209/0.354 min-1) and turnover frequency (TOF: 1.0 × 10-3/0.44 × 10-3 mol g-1 min-1) towards 4-NP and RhB reduction in comparison with commercial Pt black under the same conditions. This research offers some valuable insights for facile preparation of advanced nanostructures as efficient and recyclable catalyst in environmental remediation field.


Absorptive-mediated endocytosis of an adrenocorticotropic hormone (ACTH) analogue, ebiratide, into the blood-brain barrier: studies with monolayers of primary cultured bovine brain capillary endothelial cells.
The internalization of a neuromodulatory adrenocorticotropic hormone (ACTH) analogue, [125I]ebiratide (H-Met(O2)-Glu[125I]His-Phe-D-Lys-Phe-NH(CH2)2NH2), was examined in cultured monolayers of bovine brain capillary endothelial cells (BCEC). HPLC analysis of the incubation solution showed that [125I]ebiratide was not metabolized during the incubation with BCEC. The acid-resistant binding of [125I]ebiratide to BCEC increased with time for 120 min and showed a significant dependence on temperature and medium osmolarity. Pretreatment of BCEC with dansylcadaverine or phenylarsine oxide, endocytosis inhibitors, and 2,4-dinitrophenol, a metabolic inhibitor, decreased significantly the acid-resistant binding of [125I]ebiratide. The acid-resistant binding of [125I]ebiratide was saturable in the presence of unlabeled ebiratide (100 nM-1 mM). The maximal internalization capacity (Bmax) at 30 min was 7.96 +/- 3.27 pmol/mg of protein with a half-saturation constant (Kd) of 15.9 +/- 6.4 microM. The acid-resistant binding was inhibited by basic peptides such as poly-L-lysine, protamine, histone, and ACTH but was not inhibited by poly-L-glutamic acid, insulin, or transferrin. These results confirmed that ebiratide is transported through the blood-brain barrier via an absorptive-mediated endocytosis.


Cat infected by a variant of bat rabies virus in a 29-year disease-free urban area of southern Brazil.
After 29 years, rabies was detected in a cat in Curitiba, southern Brazil. The fluorescent antibody test (FAT) and mouse inoculation test (MIT) were performed on central nervous system (CNS) samples. Direct immunofluorescence was negative, but the biological test was positive and rabies virus was characterized as variant 4 (from Tadarida brasiliensis). Reappearance of rabies in domestic animals warns of sylvatic-aerial risk of infection and the necessity of monitoring bats in historically rabies-free areas.


Analysis of epidermal growth factor receptor (EGFR) status in endometrial stromal sarcoma.
Endometrial stromal sarcomas (ESSs) are rare neoplasms, which are currently treated by surgery, whereas effective adjuvant therapies have not yet been established. Recently, epidermal growth factor receptor (EGFR) expression has been described in ESS, and a potential role of EGFR-targeted adjuvant therapies has been proposed. The aim of this study was to analyze EGFR status in an ESS series and to evaluate their potential role as molecular targets. EGFR status was investigated in a total of ten cases of ESS, which included seven low-grade ESS and three undifferentiated ESS cases. EGFR expression levels were assessed by immunohistochemistry, and gene amplification analysis was performed with dual-color fluorescence in situ hybridization (FISH). Nine out of ten ESS cases showed positive immunostaining, whereas FISH analysis demonstrated constantly negative results. This study confirmed that EGFR is frequently overexpressed in ESS. FISH analysis did not show EGFR amplification in any of the tumors, therefore EGFR expression in ESS should be related to different genetic mechanisms.


Laparoscopic-based perivascular unilateral renal sympathetic nerve denervation for treating resistant hypertension: a case report.
A 38-year-old man with a history of resistant hypertension for more than 10 years underwent laparoscopic-based perivascular unilateral renal sympathetic nerve denervation in 2012. After the operation, the patient's blood pressure has been controllable while the antihypertensive drug intake has decreased over 6 years. Laparoscopic-based perivascular unilateral renal sympathetic nerve denervation may be a potentially feasible and effective option in treating patients with resistant hypertension.


Laser in situ keratomileusis for residual myopia after photorefractive keratectomy.
To evaluate the efficacy and safety of laser in situ keratomileusis (LASIK) for myopic regression and undercorrection after photorefractive keratectomy (PRK). The Eye Institute, Sydney, Australia. Fifty eyes of 32 patients were treated by LASIK for residual myopia following primary PRK. The mean spherical equivalent refraction (SEQ) was -2.92 diopters (D) +/- 1.57 (SD) (range -0.75 to -7.88 D). The mean refractive cylinder was 0.96 +/- 0.74 D (range 0 to 3.50 D). For analysis, the eyes were divided into 2 groups: those with 0 or low corneal haze (Group 1) and those with severe corneal haze (Group 2). In Group 1, the SEQ was -1.99 +/- 0.79 D (range -0.75 to -3.75 D) and in Group 2, -3.77 +/- 1.62 D (range -0.75 to -7.90 D). The procedure was performed using the Chiron Automated Corneal Shaper and the Summit Apex Plus laser. The mean interval between PRK and LASIK was 25 months (range 9 to 59 months). The following parameters were studied before and after LASIK retreatment: SEQ, mean refractive cylinder, uncorrected visual acuity (UCVA), and best corrected visual acuity (BCVA). Complications after LASIK retreatment were evaluated. Six months after LASIK, the mean SEQ in all eyes was -0.65 +/- 0.86 D (range +1.50 to -3.35 D); 70.0% of eyes were within +/-1.00 D of emmetropia and the UCVA was 6/12 or better in 72.5%. The mean SEQ in Group 1 was -0.22 +/- 0.55 D (range -0.88 to -1.50 D) and in Group 2, -0.97+/- 0.92 D (range 0.12 to -3.25 D); the UCVA was 6/12 or better in 94.0% of eyes in Group 1 and in 56.0% in Group 2. No statistically significant between-group difference was found in lines of Snellen acuity lost or gained at 6 months. No eye lost more than 1 line of BCVA. Laser in situ keratomileusis appears to be a safe, effective, and predictable procedure for treating eyes with 0 or low haze with residual myopia after PRK. It is less predictable in eyes with severe haze.


[Diagnostic possibilities of quantitative histochemical studies of epidermoid cancer of the lung].
The paper discusses the results of microspectrophotometric assay of DNA and free glycogen levels in the cells of 32 epidermoid tumors of the lung showing different degree of cell differentiation. Increased degree of tumor anaplasia was matched by a rise in DNA accumulation index and polyploidy in nuclei offset by a decrease in the glycogen level in tumor cell cytoplasm. It is suggested that DNA and free glycogen assays may contribute to the diagnostic assessment of cell differentiation involved in lung cancer.


Factors associated with academic burnout and its prevalence among university students: a cross-sectional study.
This study aimed to evaluate the current state of academic burnout among Chinese college students and its influencing factors. A cross-sectional study of 22,983 students was conducted using structured questionnaires and the Maslach Burnout Inventory General Survey on sociodemographic characteristics, educational process, and personal aspects. Multiple variables were statistically evaluated using logistic regression analysis. The total score of the students' academic burnout was 40.73 (± 10.12) points. The scores for the reduced personal accomplishment, emotional exhaustion, and cynicism were 23.63 (± 6.55), 11.20 (± 6.05), and 5.91 (± 5.31), respectively. Students with academic burnout accounted for 59.9% (13,753/22,983). Male students had higher burnout scores than female students, upper-grade students had higher burnout scores than lower-grade students, and students who smoked had higher burnout than non-smokers during the school day. More than half of students experienced academic burnout. Gender, grade, monthly living expenses, smoking, parents' education level, study and life pressures, and the current degree of professional knowledge interest significantly impacted academic burnout. An effective wellness program and an annual long-term burnout assessment may sufficiently reduce student burnout.


Benefit of adaptive CT-based treatment planning in high-dose-rate endorectal brachytherapy for rectal cancer.
In this planning study, we investigated the dosimetric benefit of repeat CT-based treatment planning at each fraction vs. the use of a single CT-based treatment plan for all fractions for high-dose-rate endorectal brachytherapy (HDREBT) for rectal cancer. We included 11 patients that received a CT scan with applicator in situ for all three fractions. The treatment plan of the first fraction was projected on the repeat CT scans to simulate the use of a single treatment plan. In addition, replanning was performed on the repeat CT scans, and these were compared to the corresponding projected treatment plans. Repeat CT-based treatment planning resulted on average in a 21% higher (p = 0.01) conformity index compared to single CT-based treatment planning. Projecting the initial treatment plan to the repeat CT scans of fraction two and three, 12/22 fractions reached a CTV D98 of 85% of the prescribed dose of 7 Gy, which increased to 14/22 using replanning. For the remaining fractions, median CTV D98 was 4.2 Gy, and an intervention would be necessary to correct applicator balloon setup or to remove remaining air and/or feces between the CTV and the applicator. Using a single CT-based treatment plan for all fractions may result in a suboptimal treatment at later fractions. Therefore, repeat CT imaging should be the minimal standard practice in HDREBT for rectal cancer to determine whether an intervention would be necessary. Replanning based on repeat CT imaging resulted in more conformal treatment plans and is therefore recommended.


Effects of lesioning the dorsal and intermediate acoustic striae on binaural interaction at the inferior colliculus.
Contralateral clicks normally activate units in the inferior colliculus of rats. Ipsilateral clicks usually inhibit this activity when their intensity just exceeds the contralateral intensity. When the contralateral dorsal and intermediate acoustic striae are lesioned as they pass over the restiform body, ipsilateral clicks inhibit even if they are substantially less intense than contralateral clicks. Contralateral click thresholds for unit activation are elevated by about 10 dB, but this shift in sensitivity cannot account for the marked advantage gained by the ipsilateral inhibitory input. These findings suggest that one or both of these pathways contributes heavily to binaural interaction at the inferior colliculus.


Transplantation of fetal mesencephalic and medullary raphe tissues into the cerebellum of denervated adult rats--an immunohistochemical study.
Pieces of mesencephalic and medullary raphe tissues were transplanted into the cerebella of 5,6-dihydroxytryptamine-treated adult rats. The extent of axonal outgrowth of serotonergic and dopaminergic neurons in the grafts was immunohistochemically studied. At 3 months after transplantation, numerous dopaminergic neurons with many processes extending within the graft were detected in the mesencephalic raphe graft, but not in the medullary raphe graft. In contrast, both the mesencephalic and medullary raphe grafts contained numerous serotonergic neurons and a dense plexus of their fibers. The outgrowing serotonergic fibers from the mesencephalic raphe graft showed a hyperinnervation pattern in the cerebellar cortex adjacent to the graft. Furthermore, a glomerulus-like accumulation of serotonergic fibers was observed in the granular layer. In the cases of medullary raphe grafts, the relatively abundant outgrowing serotonergic fibers showed a laminar organization in the cerebellar cortex near the graft, which was similar to the normal distributional pattern. These results indicate that serotonergic and dopaminergic neurons located within the mesencephalic raphe graft clearly differed from each other in their ability to extend their processes into the host cerebellum, which provides further evidence for the existence of specific interactions between outgrowing serotonergic fibers and their terminal fields (targets).


Mono- and binuclear complexes of copper(II) with dimethylaminomethyl derivatives of 2-naphthol and 6-quinolinol: synthesis and in vitro study of antitumor properties.
1-(Dimethylamino)methyl-6-quinolinol scaffold, a structural moiety of the molecule of anticancer drug topotecan, was modified into copper-containing products to study cytotoxic properties. New mononuclear and binuclear Cu(II) complexes with 1-(N,N-dimethylamino)methyl-6-quinolinol were synthesized for the first time. The same way Cu(II) complexes with 1-(dimethylamino)methyl-2-naphtol ligand were synthesized. The structures of mono- and binuclear Cu(II) complexes with 1-aminomethyl-2-naphtol were confirmed by X-ray diffraction. The obtained compounds were examined for in vitro cytotoxic activity against Jurkat, K562, U937, MDA-MB-231, MCF7, T47D, and HEK293 cells. The induction of apoptosis and the effect of novel Cu complexes on the cell cycle were investigated. The cells showed a higher sensitivity to mononuclear Cu(II) complex with 1-(N,N-dimethylamino)methyl-6-quinolinolligand. All synthesized Cu(II) complexes had higher antitumor activity than the drugs topotecan, camptothecin, and platinum containing cisplatin.


Ulnar lengthening using a half-ring sulcated external fixator for ulnar longitudinal deficiency: a case report.
Ulnar longitudinal deficiency (ULD) is a rare condition of the upper limbs. Although radius lengthening for radial longitudinal deficiencies (RLD) was found to be successful, no ulnar lengthening for ULD without RLD and hand deformities has been reported. Herein, we present a Bayne type II ULD case report of the ulnar lengthening and gradual reduction of the dislocated radial head in an 11-year-old boy using a half-ring sulcated external fixator. For ulnar lengthening/radial longitudinal traction for radial head reduction, transverse osteotomy in mid ulna was performed and half-ring sulcated external fixator was used for ulnar distraction lengthening. Radial longitudinal traction and stabilization of external fixator were achieved by transverse pins through ulna and radius. Distraction (1 mm/day) began at 5th day and was completed at 95th postoperative day. External fixator was applied for 7 months. Successful ulnar lengthening (81 mm; 62% gain) was achieved 1-year after the surgery and the range of elbow motion at 2 years was >40°. Forearm rotation and wrist extension/flexion were also preserved with no complaints of pain. We concluded that ulnar distraction lengthening and gradual reduction of radial head could improve appearance of the arm and were of significant benefit to the patient.


Changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries.
Over the last two decades, noninvasive ventilation (NIV) has been proposed in various causes of acute respiratory failure (ARF) but some indications are debated. Current trends in NIV use are unknown. Comparison of three multicenter prospective audits including all patients receiving mechanical ventilation and conducted in 1997, 2002, and 2011 in francophone countries. Among the 4132 patients enrolled, 2094 (51%) required ventilatory support for ARF and 2038 (49 %) for non-respiratory conditions. Overall NIV use was markedly increased in 2010/11 compared to 1997 and 2002 (37% of mechanically ventilated patients vs. 16% and 28%, P < 0.05). In 2010/11, the use of first-line NIV for ARF had reached a plateau (24% vs. 16% and 23%, P < 0.05) whereas pre-ICU and post-extubation NIV had substantially increased (11% vs. 4% and 11% vs. 7%, respectively, P < 0.05). First-line NIV remained stable in acute-on-chronic RF, continued to increase in cardiogenic pulmonary edema, but decreased in de novo ARF (16% in 2010/11 vs. 23% in 2002, P < 0.05). The NIV success rate increased from 56% in 2002 to 70% in 2010/11 and remained the lowest in de novo ARF. NIV failure in de novo ARF was associated with increased mortality in 2002 but not in 2010/11. Mortality decreased over time, and overall, NIV use was associated with a lower mortality. Increases in NIV use and success rate, an overall decrease in mortality, and a decrease of the adverse impact NIV failure has in de novo ARF suggest better patient selection and greater proficiency of staff in administering NIV. Clinicaltrials.gov Identifier NCT01449331.


Blood cadmium and moderate-to-severe glomerular dysfunction in Korean adults: analysis of KNHANES 2005-2008 data.
The objective of this study was to evaluate the association between blood cadmium (Cd) and moderate-to-severe glomerular dysfunction in a Korean population using a representative sample. A cross-sectional study was used to evaluate the association between blood Cd and glomerular dysfunction. Based on the Korean National Health and Nutrition Examination Survey (2005-2008), individual blood Cd was measured in 2,992 adults, aged between 20 and 65. After adjusting for survey years, age, sociodemographic factors, and health behaviors, the odds ratio for moderate-to-severe glomerular dysfunction (<60 mL/min per 1.73 m(2)) was 1.97 (95% CI: 1.28-3.07) when comparing the highest with the lowest blood Cd quartile in Korean women. However, in Korean men, there was no association between blood Cd and moderate-to-severe glomerular dysfunction. These findings support the consideration of Cd as a risk factor for glomerular dysfunction in the female population. Furthermore, environmental heavy metal monitoring and an institutional strategy should be implemented to reduce Cd exposure in the general population.


Measuring Balance and Mobility after Traumatic Brain Injury: Validation of the Community Balance and Mobility Scale (CB&M).
To further investigate the construct validity of the Community Balance and Mobility Scale (CB&M), developed for ambulatory individuals with traumatic brain injury (TBI). A convenience sample of 35 patients with TBI (13 in-patients, 22 outpatients) was recruited. Analyses included a comparison of CB&M and Berg Balance Scale (BBS) admission and change scores and associations between the CB&M and measures of postural sway, gait, and dynamic stability; the Community Integration Questionnaire (CIQ); and the Activities-specific Balance Confidence (ABC) Scale. Mean admission scores on the BBS and the CB&M were 53.6/56 (SD=4.3) and 57.8/96 (SD=23.3) respectively. Significant correlations were demonstrated between the CB&M and spatiotemporal measures of gait, including walking velocity, step length, step width, and step time; measures of dynamic stability, including variability in step length and step time; and the ABC (p<0.05). Significant correlations between the CB&M and CIQ were revealed with a larger data set (n=47 outpatients) combined from previous phases of research. In patients with TBI, the CB&M is less susceptible to a ceiling effect than the BBS. The construct validity of the CB&M was supported, demonstrating associations with laboratory measures of dynamic stability, measures of community integration, and balance confidence.


A source for measurement of the absolute intensities of 226Ra gamma-radiation in equilibrium with decay products.
The design and production techniques of a gamma-ray spectrometric source of 226Ra in equilibrium with its daughter decay products have been developed. The radon emanation coefficient of the source did not exceed 0.1%. The 226Ra activity in the gamma-ray spectrometric source was measured relative to that in an alpha-particle spectrometric source by comparison of the intensities of the main gamma rays using a semiconductor gamma-ray spectrometer. The total uncertainty of the activity measurement results was 0.5% for a coverage factor of k = 2.


Vascular malformations syndromes: an update.
To provide an update of vascular malformation syndromes by reviewing the most recent articles on the topic and following the new International Society for the Study of Vascular Anomalies (ISSVA) 2018 classification. This review discusses the main features and diagnostic approaches of the vascular malformation syndromes, the new genetic findings and the new therapeutic strategies developed in recent months. Some vascular malformations can be associated with other anomalies, such as tissue overgrowth. PIK3CA-related overgrowth spectrum (PROS) is a group of rare genetic disorders with asymmetric overgrowth caused by somatic mosaic mutations in PI3K-AKT-mTOR pathway that encompass a heterogeneous group of rare disorder that are associated with the appearance of overgrowth. CLOVES syndrome and Klippel-Trénaunay syndrome are PROS disease. Proteus syndrome is an overgrowth syndrome caused by a somatic activating mutation in AKT1. CLOVES, Klippel-Trénaunay and Proteus syndromes are associated with high risk of thrombosis and pulmonary embolism. Hereditary hemorrhagic telangiectasia is an autosomic dominant disorder characterized by the presence of arteriovenous malformations. New therapeutic strategies with bevacizumab and thalidomide have been employed with promising results.


Fractalkine deficiency attenuates LPS-induced acute kidney injury and podocyte apoptosis by targeting the PI3K/Akt signal pathway.
Podocyte injury is a major biomarker of primary glomerular disease, which leads to massive proteinuria and kidney failure. The increased production of the chemokine, fractalkine (FKN, CX3CL1), is a hallmark of multiple inflammatory diseases. However, the underlying mechanism of FKN in podocyte injury remains unknown. In this study, we performed an LPS infusion model in FKN knockout (FKN-/-, FKN-KO) mice. In cultured podocytes, we used plasmids to knockdown FKN and treated the podocytes with PI3K/Akt inhibitor (LY294002). Haematoxylin and eosin (HE) staining, Western Bolt, Co-immunoprecipitation (Co-IP), Immunofluorescence staining and flow cytometric analysis were employed to establish the role of FKN in podocyte injury. LPS stimulation resulted in kidney damage, increased the expression of the Bcl-2 family apoptosis protein, and decreased podocyte marker protein (nephrin, podocin and WT1) abundance compared with the WT mice. LPS-induced FKN-KO mice exhibited reduced lethality and inflammatory cell infiltration, podocyte apoptosis, and PI3K/Akt signal pathway inhibition compared to WT mice. In cultured podocytes, the interaction between FKN and the PI3K/Akt signalling pathway was well confirmed. FKN knockdown reduced podocyte apoptosis by regulating the Bcl-2 family; however, this protective effect was reversed by the co-administration of a PI3K/Akt inhibitor (LY294002). Overall, these findings reveal a novel mechanistic property of FKN, PI3K/Akt signalling, and podocyte apoptosis.


Extramedullary plasmacytoma of the adenoids.
Extramedullary plasmacytomas are extremely rarely diagnosed in children. We report two cases of extramedullary plasmacytoma detected coincidentally in the adenoidectomy specimens of children younger than 4 years. We show that these children are disease-free after local excision as the only treatment. Surgical treatment without anti-neoplastic therapy in pediatric plasma cell dyscrasias of the pharyngeal lymphoid tissue may be a sufficient curative therapy.


Evaluating renal iron overload in diabetes mellitus by blood oxygen level-dependent magnetic resonance imaging: a longitudinal experimental study.
Iron overload plays a critical role in the pathogenesis of diabetic nephropathy. Non-invasive evaluation of renal iron overload in diabetes in the management and intervention of diabetic nephropathy is of great significance. This study aimed to explore the feasibility of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in evaluating renal iron overload in diabetes using a rabbit model. The rabbits were randomly divided into control, iron-overload (I), diabetes (D), and diabetes with iron-overload (DI) groups (each n = 19). The diabetes models were generated by injecting intravenous alloxan solution, and the iron-overload models were generated by injecting intramuscular iron-dextran. BOLD MRI was performed immediately (week 0) and at week 4, 8, and 12 following modeling. The differences in renal cortex (CR2*) and outer medulla R2* (MR2*) and the ratio of MR2*-CR2* (MCR) across the different time points were compared. Iron was first deposited in glomeruli in the I group and in proximal tubular cells in renal cortex in the D group. In the DI group, there was iron deposition in both glomeruli and proximal tubular cells at week 4, and the accumulation increased subsequently. The degree of kidney injury and iron overload was more severe in the DI group than those in the I and D groups at week 12. At week 8 and 12, the CR2* and MR2* in the DI group were higher than those in the I and D groups (all P < 0.05). The MCR in the I, D, and DI groups decreased from week 0 to 4 (all P < 0.001), and that in the I group increased from week 8 to 12 (P = 0.034). CR2* and MR2* values displayed different trends from week 0-12. Dynamic MCR curves in the D and DI groups were different from that in the I group. It presents interactions between diabetes and iron overload in kidney injury, and BOLD MRI can be used to evaluate renal iron overload in diabetes.


Denaturing gradient gel electrophoresis and direct sequencing of PCR amplified genomic DNA: a rapid and reliable diagnostic approach to beta thalassaemia.
The analysis of polymerase chain reaction (PCR)-amplified beta-globin DNA with allele-specific oligonucleotide (ASO) probes reveals a very heterogeneous spectrum of beta-thalassaemia in the Netherlands. However about 20% of the beta-thalassemia mutations cannot be identified with this approach. The combination of specific amplification of certain regions of the beta-globin gene with denaturing gradient gel electrophoresis (DGGE) allowed us to rapidly localize several of these mutations to specific regions of the gene, which were again amplified and directly sequenced. We believe that the combination of DGGE and the direct sequence determination of PCR amplified genomic DNA represents a valid alternative to the 'ASO probes' approach, especially in countries where a very heterogeneous spectrum of beta-thalassaemia mutations occurs.


Pancreas-preserving total gastrectomy for proximal gastric cancer.
Lymph node (LN) dissection along the upper border of the pancreas is one of the essential parts of curative surgery for gastric cancer, and the distal portion of the pancreas was frequently resected for complete removal of LNs along the splenic artery. However, pancreatic juice leakage, subphrenic abscess, and postoperative diabetes were common complications in patients treated by pancreatic resection. To avoid these problems a new surgical procedure, the pancreas-preserving operation, was developed by Maruyama in 1979. We found that lymphatic channels from the stomach did not flow into the pancreas parenchyma, and that the spleen, splenic artery, and fatty connective tissue including nodes could be removed completely without dissection of the pancreas parenchyma and splenic vein. The preserved pancreas receives its arterial blood supply through the transverse pancreatic artery, and its preservation prevents postoperative diabetes. A total of 299 patients were treated by this procedure. The operative mortality rate was 0.3%, the hospital death rate 1.6%, and the surgical complications rate 19.6%. The cumulative 5-year survival rate for those with stage II was 70.5% and for those with stage III 54.1%. These results were superior to those of the pancreas resection group.


The state of hormonal contraception today: overview of unintended pregnancy.
Each year in the United States about 1 in 20 women experiences an unintended pregnancy. Understanding the impact of consistent, appropriate, and effective contraception on this major health care concern is key to overcoming this societal and economic burden. In addition to available family-planning services, women need ongoing support in choosing and using methods based on her overall life situation, as well as strategies to address the logistic and cost barriers to effective birth control.


Comparing the Efficacy and Safety of Combination Triamcinolone Acetonide and 5-Fluorouracil versus Monotherapy Triamcinolone Acetonide or 5-Fluorouracil in the Treatment of Hypertrophic Scars and Keloids: A Systematic Review and Meta-Analysis.
Keloids and hypertrophic scars cause physical and psychosocial problems. Combination 5-fluorouracil (5-FU) with triamcinolone acetonide (TAC) may enhance the treatment of pathological scars, although the evidence base is limited. We aimed to evaluate the efficacy and complication rates of combination intralesional TAC and 5-FU in comparison to monotherapy intralesional TAC or 5-FU for the treatment of keloids and hypertrophic scars. EMBASE, MEDLINE and CENTRAL were searched by two independent reviewers. The primary outcome was treatment efficacy (51% to 100% improvement). Study quality and risk of bias were assessed using Cochrane's risk of bias tool, respectively. Of 277 articles screened, 13 studies were included comprising 12 randomised control trials (RCT) and 1 non-randomised study. There were six and nine studies comparing combination intralesional therapy versus monotherapy 5-FU and monotherapy TAC, respectively. The combined group demonstrated superior objective treatment efficacy compared to the monotherapy TAC group (OR 3.45, 95% C.I: [2.22-5.35], I 2=0%, P<0.00001) and monotherapy 5-FU group (OR 4.17, 95% C.I: [2.21-7.87], I 2=0%, P<0.0001). Telangiectasia was less frequent in combination therapy (OR 0.24, 95% CI: [0.11-0.52], I 2=0%, P=0.0003) compared to monotherapy TAC. Combined intralesional TAC and 5-FU administration demonstrated superior treatment efficacy outcomes compared to monotherapy TAC or 5-FU. Patient-reported outcome measures, lacking here, should be incorporated in the design of future research to justify clinical recommendations.


Introduction the revolving scarf osteotomy for treating severe hallux valgus with an increased distal metatarsal articular angle: a retrospective cohort study.
Hallux valgus(HV) with an increased distal metatarsal articular angle (DMAA) is one of the most common foot deformities among adults. Double metatarsal osteotomy (DMO) is effective in treating severe HV deformity with an increased DMAA. However, this technique presents the risk of avascular necrosis (AVN) of the metatarsal head and transfer metatarsalgia due to shortening of the first metatarsal. The aim of this study was to introduce a surgical procedure defined as revolving scarf osteotomy (RSO) and compare the clinical and radiological results of RSO and DMO performed for treating severe HV with an increased DMAA. First metatarsal osteotomies and Akin osteotomy were performed in 56 patients (62 ft) with severe HV with an increased DMAA in Honghui Hospital from January 2015 to December 2017. RSO was performed in 32 ft and DMO was performed in 30 ft. The Akin osteotomy was performed in both groups. The American Orthopedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) score, the hallux valgus angle (HVA), intermetatarsal angle (IMA), DMAA, and first metatarsal length (FML) and the rates of complications were compared preoperatively and postoperatively in the two groups. The mean AOFAS score, VAS score, HVA, IMA, and DMAA showed significant improvements in both groups after surgery, but with no significant differences between the two groups. The postoperative FML was significantly larger in the RSO group than in the DMO group (p < 0.001). One of the 30 ft (3.3%) in the DMO group exhibited transfer metatarsalgia at 12 months postoperatively, while another foot (3.3%) in same group had avascular necrosis of the metatarsal head. One of the 30 ft (3.1%) in the RSO group had hallux varus. No differences in the clinical and radiographic results were observed between the two groups with severe HV and an increased DMAA. However, RSO does not cause shortening of the metatarsal and AVN of the metatarsal head. A long-term, randomized, controlled prospective study with a larger sample would provide higher-level evidence for confirming the clinical efficacy and safety of RSO.


Transurethral resection of the prostate. A review of 1111 cases.
A review of 1111 transurethral resections of the prostate (TURP) revealed a mortality of 0.5% (6 patients). A stricture frequency of 3% was observed as a complication after the operation. A supplementary resection was done within one year in 9%. Transurethral resection syndrome of the prostate (TURP syndrome) occurred in two patients. Cancer incidence was 18%. Blood transfusions were given to 20% of the patients. The weight of resected prostatic tissue ranged from 4 to 115 g (mean 25 g), and was less than 20 g in 60%. Peroperative bleeding amounting to over 1800 ml occurred in 3.3% (37 patients).


Cat Ownership and Rural Residence Are Associated with Lyme Disease Prevalence in the Northeastern United States.
Lyme disease (LD) is the most common vector-borne disease in the USA. Beyond its tick-borne nature, however, risk factors for LD are poorly understood. We used an online questionnaire to compare LD patients and non-LD counterparts and elucidate factors associated with LD. We investigated demographic, lifestyle, and household characteristics and use of prevention measures. Associations with LD were modeled using logistic regression, and average marginal effects were estimated. In total, 185 active or past LD patients and 139 non-patients participated. The majority of respondents were white (95%) and female (65%). Controlling for age, sex, and type of residential area, pet ownership was associated with an 11.1% (p = 0.038) increase in the probability of LD. This effect was limited to cat owners (OR: 2.143, p = 0.007; dog owners, OR: 1.398, p = 0.221). Living in rural areas was associated with a 36% (p = 0.001) increase in the probability of LD compared to living in an urban area. Participants who reported knowing someone with Lyme Disease were more likely to wear insect repellant and perform tick checks. This study suggests opportunities for improved LD prevention, including advising cat owners of their increased risk. Although patterns in adoption of LD prevention methods remain poorly understood, concern about LD risk does motivate their use.


[Angiographic study of facial paralyses (author's transl)].
Many arguments lead us to think that a possible etiologic factor in idiopathic Bell's palsy is the ischemia of the facial nerve and that angiography could help in diagnosis: (1) the rapid progress of the paralysis; (2) the correlation between Bell's palsy occurring after embolization of the internal maxillary artery, the middle meningeal artery, the occipital or posterior auricular artery, and their participation in the blood supply of the facial nerve; (3) the already known ischemic third nerve paralysis reported in diabetes and extending further to the facial nerve. Even if it is technically impossible to study Bell's palsy by angiography, it is interesting to understand and consider some complications of embolization and perhaps to envisage a new kind of treatment.


Flow cell within an LED: a proposal for an optical absorption detector.
Droplets formed at the tip of a tube under the same conditions possess extreme uniformity of form, volume and weight. These properties of liquid drop formation have been known for a long time and consequently many applications for the drop have been found in instrumentation and chemical analysis methods. In the present paper, we report on the analytical use of a dynamic LED-based flow-through optical absorption detector with optical path length controlled by continuous dropping of a solution. This arrangement consists of a flow cell built within a high-intensity red LED (lambda(max) = 630 nm). The feasibility of the detector is demonstrated by colorimetric determination of methylene blue, and ammonium by Berthelot's reaction, in a flow-injection system. For ammonium, the reaction forms a blue dye (indophenol) with a maximum absorption at 630-650 nm. The detection limit, considered as 3 times the signal of the blank, is better than 125 microg l(-1). The small flow cell represents a good combination of optical path length, low volume and fast washout. This detector can be used advantageously in automated methods and can represent a solution to problems of optical detection involving gas bubbles and precipitation of particles in turbidimetric applications.


Formed and preformed metabolite excretion clearances in liver, a metabolite formation organ: studies on enalapril and enalaprilat in the single-pass and recirculating perfused rat liver.
Single-pass and recirculating rat liver perfusion studies were conducted with [14C]enalapril and [3H]enalaprilat, a precursor-product pair, and the data were modeled according to a physiological model to compare the different biliary clearances for the solely formed metabolite, [14C]enalaprilat, with that of preformed [3H]enalaprilat. With single-pass perfusion, the apparent extraction ratio (or biliary clearance) of formed [14C]enalaprilat was 15-fold the extraction ratio of preformed [3H]enalaprilat, an observation attributed to the presence of a barrier for cellular entry of the metabolite. Upon recirculation of bolus doses of [14C]enalapril and [3H]enalaprilat, the biliary clearance, estimated conventionally as metabolite excretion rate/midtime metabolite concentration, for formed [14C]enalaprilat was again 10- to 15-fold higher than the biliary clearance for preformed [3H]enalaprilat, but this decayed with perfusion time and gradually approached values for preformed [3H]enalaprilat. The decreasing biliary clearance of formed enalaprilat with recirculation was explained by the dual contribution of the circulating and intrahepatic metabolite (formed from circulating drug) to excretion. Physiological modeling predicted (i) an influx barrier (from blood to cell) at the sinusoidal membrane as the rate-limiting process in the overall removal of enalaprilat, (ii) a 15-fold greater extraction ratio or biliary clearance for formed [14C]enalaprilat over [3H]enalaprilat during single-pass perfusion, and (iii) the time-dependent and declining behaviour of the biliary clearance for formed [14C]enalaprilat during recirculation of the medium. In the absence of a direct knowledge of eliminating organs in vivo, this variable pattern for excretory clearance of the formed metabolite within the organ is indicative of a metabolite formation organ.


Review of proteomics approach to eye diseases affecting the anterior segment.
Visual impairment and blindness is a major health burden worldwide, and major ocular diseases causing visual impairment pertain to the anterior segment of the eye. Anterior segment ocular diseases are common, yet complex entities. Although many treatment options and surgical techniques are available for these ailments, the underlying cause and pathogenesis is still unclear. Finding ways to fundamentally treat these patients and rectify the underlying dysregulations leading to the disease may help cure patients completely without major complications. Proteomics approaches are a novel way to distinguish dysregulated proteins in a variety of biological tissues in a hypothesis-free manner, thus helping to find the responsible pathways leading to a certain disease. The aim of the current study is to review the available knowledge in scientific literature regarding the proteomics studies done on anterior segment eye diseases and suggest potential clinical implications to exploit the results of these studies. SIGNIFICANCE: Anterior segment ocular diseases are responsible for a major proportion of visual impairment and blindness worldwide. Although ophthalmologists have several treatment options that can alleviate or control the progression of these diseases, no definite cure is available for most of them. Moreover, because these diseases are progressive, prompt diagnosis is of utmost important. Proteomics studies enable us to identify and quantify the dysregulated proteins in a biological specimen in a hypothesis-free manner. Understanding the dysregulated protein pathways shines a light on the pathogenesis of the disease. Moreover, these dysregulated proteins may act as biomarkers to help in diagnosis and treatment follow-up. Hence, in this article we sought out to review the available scientific literature regarding the proteomics studies of anterior segment ocular diseases and to identify potential applications of proteomic studies in clinic.


Cholecystokinin stimulates and inhibits lordosis behavior in female rats.
Recently, IP CCK-8 has been shown to inhibit lordosis in sexually experienced, estradiol benzoate (EB) and progesterone (P) primed rats. However, receptivity is influenced by prior sexual experience and/or exposure to sex steroids, as well as the steroid dosage administered before testing. Thus, we examined the effect of CCK-8 (3 micrograms/kg; IP) on lordosis in rats with different degrees of receptivity. Three weeks after ovariectomy, females were treated with EB followed 48 hr later with P, or with EB alone. CCK-8 significantly facilitated lordosis in rats given 5 micrograms EB. Following a 5 week nonexperimental period, animals were more receptive and CCK-8 significantly inhibited lordosis in the 5 or 10 micrograms EB groups. In a separate experiment, rats were ovariectomized, adrenalectomized, and treated with EB alone. As in the first experiment, CCK-8 facilitated and inhibited lordosis. CCK-8's effects were highly dependent on the female's receptivity, facilitating lordosis when receptivity was low and inhibiting lordosis when receptivity was high (but not maximal). In conclusion, IP CCK-8 modulates lordosis behavior independent of P, but its effects depend on the female's degree of receptivity.


Body dissatisfaction and restrained eating in male juvenile and adult athletes.
Athletes of light-weight sport classes are under a constant strain to control eating and body shape, which can make them prone to develop eating disorders. In the present study, cognitive control of eating (restrained eating) and body dissatisfaction were investigated in male elite athletes of light-weight and heavy-weight classes at different ages. Body dissatisfaction was assessed under hunger and satiety. Adult light-weight rowers had extremely high scores of restrained eating and a more pronounced body dissatisfaction under hunger compared to satiety in contrast to heavy-weight rowers. Juvenile light-weight rowers had a pronounced cognitive control of eating behavior while body dissatisfaction was not affected by weight-class or hunger. The results suggest that extensive participation in a light-weight sport increases the cognitive control of eating behavior but not the disinhibition of cognitive control of eating. High levels of cognitive control of eating in the adult lightweight rowers are accompanied with body dissatisfaction under hunger but not under satiety.


Isolated hypoglycorrachia: leptomeningeal carcinomatosis causing subacute confusion.
We report a 76-year-old caucasian man who presented with a 3-week history of progressive confusion. His past medical history included a left nephro-uretectomy for poorly differentiated transitional cell carcinoma 9 years previously. Besides his confusion, his clinical and neurological examination was unremarkable. Extensive investigation revealed only isolated hypoglycorrachia and mildly elevated CSF protein. Cerebral CT and MRI scans without contrast did not reveal any abnormalities. As his condition continued to decline, an MRI scan of the brain with gadolinium was performed which revealed extensive nodular enhancement of the surface of the cerebellum and brainstem and both temporal lobe convexities. Repeat lumbar puncture showed malignant cells in the CSF and confirmed the diagnosis of leptomeningeal carcinomatosis. This case illustrates that leptomeningeal carcinomatosis should be considered in the differential diagnosis of cognitive decline in the elderly, after other common aetiologies have been excluded. The index of suspicion should be increased in patients with a prior history of cancer.


Intraoperative evoked potential monitoring of the spinal cord: enhanced stability of cortical recordings.
Intraoperative EP monitoring of spinal cord function depends upon a quickly obtained, reproducible EP. The records must be obtained in a hostile environment where artifacts and other sources of electrical noise cannot easily be eliminated: records are obtained continuously without interrupting the surgery. We studied EP reproducibility by measuring cortical EP amplitude range and latency range within individual patients. Reproducibility was enhanced by several changes in the stimulus and recording parameters: (1) Bipolar recording near the vertex (Cz-Pz, E1-E2) eliminated a significant amount of the artifacts and random variations seen in referential recordings. Bipolar recordings sacrifice some amplitude but the improved reproducibility is worthwhile. (2) Restricted filters (especially 30-3000 Hz) improve reproducibility still further, compared to the traditional open filters (1-1000 Hz). (3) Fast stimulation rates improve monitoring up to rates of about 5 stimuli/sec. At even faster rates too much amplitude attenuation usually occurs. Using these techniques stable intraoperative EPs were recorded from all 115 patients except those in whom EPs were abnormal even before surgery. Advantages and disadvantages compared to epidural recording techniques were discussed. Several further observations were made, including (1) monitoring could be done equally as well with stimulation either at the peroneal or at the posterior tibial nerve; (2) balanced nitrous oxide and narcotic anesthesia did attenuate EPs by about 60%, although this is not so much as to interfere seriously with monitoring.


Clinical significance of cavernous carotid calcifications encountered on head computed tomography scans performed on patients seen in the emergency department.
To determine whether the presence of calcification in the cavernous segment of the internal carotid artery seen on head computed tomography (CT) performed in the emergency department shows any relationship to the existence of systemic disease. Significant and consistent relationships could be used as predictors in suggesting the presence of systemic disease in those patients receiving head CTs for unrelated symptoms. A retrospective investigation was performed on 295 consecutive patients presenting to the Massachusetts General Hospital emergency department for head CT scan during the course of 1 month. Head CT images were analyzed for carotid siphon calcifications. Data regarding multiple predictors of disease including gender, age, hypertension, diabetes, smoking, hypercholesterolemia, cardiac disease, and alcohol and intravenous drug abuse were abstracted from the medical record for each patient. Strong univariate correlation was noted in the comparison between the presence of carotid siphon calcification and gender, age, diabetes, hypertension, smoking, and cardiac disease while alcohol and intravenous drug abuse correlated poorly. Multivariate models including categorized age and gender demonstrated a consistently strong interaction with diabetes, cardiac disease, and smoking while hypertension and hypercholesterolemia showed a loss of significance. Interaction term analysis indicated a strong (ie, significant) interaction between gender and both hypertension and hypercholesterolemia. Carotid siphon calcifications are strong predictors of existing medical disease in simple cases. In patients with a combination of diseases, a strong interaction between covariates is noted, suggesting a more complex interaction contributing to the formation of carotid siphon disease.


Consent in paediatric research: an evaluation of the guidance provided in the 2007 NHMRC National statement on ethical conduct in human research.
In 2007, the National Health and Medical Research Council (NHMRC) released a revised National statement on ethical conduct in human research. Public submissions in the review process leading to the 2007 statement highlighted four main areas of concern: children's competence to consent, mature minors and the requirement for parental consent, whether children can refuse to participate, and the provision of information to children. A useful addition to the statement is the concept of levels of maturity, which help determine whether a child or young person's consent is necessary and/or sufficient for participation in research. Changes in terminology ("capacity" instead of "competence" and introduction of the term "vulnerability") have the potential to create confusion, as the new terms are not clearly defined, and capacity is used in several senses.


Pharmacokinetics of intravenous mexiletine in patients with acute myocardial infarction.
Acute myocardial infarction (AMI) is known to alter the pharmacokinetics of several antiarrhythmic agents. To study the effects of AMI on the kinetics of mexiletine (MEX), a single intravenous dose of 200 mg MEX HCl was infused over 30 min in 11 patients with AMI. The study was performed within 24 h of the onset of pain (study I) and repeated about 2 weeks later in seven patients at discharge (study II). MEX was quantitated in plasma and urine samples by a gas-liquid chromatographic method. The decline of MEX in plasma was three-exponential, with a terminal half-life of 14.7 +/- 3.4 (mean +/- SE) h in study I and 11.3 +/- 2.4 h (p less than 0.05) in study II, in the seven patients studied in both phases. The steady-state volume of distribution averaged 578 +/- 97 L in study I and 415 +/- 33 L in study II (p less than 0.05). The total plasma clearance, renal clearance, and recovery of MEX in urine were similar in the two studies, as was the plasma protein binding of MEX (64 +/- 2 vs. 57 +/- 3%, NS). Thus, an increase in the volume of distribution with consequent prolongation of the elimination half-life of MEX occurs in the acute phase of AMI, whereas the rate of elimination remains unchanged.


The microbiome of a shell mound: ancient anthropogenic waste as a source of Streptomyces degrading recalcitrant polysaccharides.
Metagenome amplicon DNA sequencing and traditional cell culture techniques are helping to uncover the diversity and the biotechnological potential of prokaryotes in different habitats around the world. It has also had a profound impact on microbial taxonomy in the last decades. Here we used metagenome 16S rDNA amplicon sequencing to reveal the microbiome composition of different layers of an anthropogenic soil collected at a shell mound Sambaqui archeological site. The Samabaqui soil microbiome is mainly composed by phyla Acidobacteria, Rokubacteria, Proteobacteria and Thaumarchaeota. Using culture-dependent analysis we obtained few Streptomyces isolates from the Sambaqui soil. One of the isolates, named Streptomyces sp. S3, was able to grow in minimal medium containing recalcitrant polysaccharides including chitin, xylan, carboxymethylcellulose or microcrystalline cellulose as sole carbon sources. The activities of enzymes degrading these compounds were confirmed in cell free supernatants. The genome sequence revealed not only an arsenal of genes related to polysaccharides degradation but also biosynthetic gene clusters which may be involved in the production of biotechnologically interesting secondary metabolites.


To quantify the small-molecule kinase inhibitors ceritinib, dacomitinib, lorlatinib, and nintedanib in human plasma by liquid chromatography/triple-quadrupole mass spectrometry.
Multiple small-molecule kinase inhibitors with specific molecular targets have recently been developed for the treatment of cancer. This article reports the development and validation of an ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method to simultaneously analyse the small-molecule kinase inhibitors dacomitinib, ceritinib, lorlatinib, and nintedanib in human plasma. For chromatographic analyte separation, an Acquity UPLC® BEH C18 column 1.7 μm, 50 mm x 2.1 mm was used with a binary gradient of pure water/formic acid/ammonium formate (100:0.1:0.02, v/v/v) and methanol/formic acid (100:0.1, v/v). Calibration curves for all small-molecule kinase inhibitors were 5.00-500 ng/mL. Validation of this method met all requirements of the Food and Drug administration. Additionally, clinical applicability was demonstrated by quantification of multiple samples from a pharmacokinetic study in patients with lung cancer.


[Bacterial endocarditis from the stimulatory unit of a cardiac pacemaker].
Cardiac device endocarditis is an infrequent complication of permanent pacemaker and implantable cardioverter-defibrillator. A personal observation had been valued noteworthy in relation to the relatively low rates and clinical features. An old man presented recurrent fevers throughout 17 months before transesophageal echocardiography detection of intracardiac vegetations. The removal and replacement of the infected device via open thoracotomy had been successful, and subsequently confirmed in a prolonged follow-up.


Postoperative pancreatic fistula: Microbial growth determines outcome.
Postoperative pancreatic fistula is a dangerous complication in pancreatic surgery. This study assessed the impact of microbiologic pathogens detected in postoperative pancreatic fistula on clinical outcomes after partial pancreatoduodenectomy and distal pancreatectomy. Microorganisms in postoperative pancreatic fistula were identified by microbiologic analyses from abdominal drains or intraoperative swabs during relaparotomy. Demographic, operative, and microbiologic data, as well as postoperative outcomes were examined. Of 2,752 patients undergoing partial pancreatoduodenectomy and distal pancreatectomy, 256 patients with clinically relevant postoperative pancreatic fistula (International Study Group of Pancreatic Surgery [ISGPS] grades B and C) were identified (9.3%) and microbiologic cultures were positive in 210 patients (82.0%), with a higher rate after partial pancreatoduodenectomy (95.8%) than after distal pancreatectomy (64.3%; P < .001). Microbiologic spectra differed distinctively between partial pancreatoduodenectomy and distal pancreatectomy. Detection of microorganisms in postoperative pancreatic fistula resulted in a higher morbidity and mortality, including postpancreatectomy hemorrhage (42.4% vs 21.7%; P = .009), sepsis (38.1% vs 6.5%; P < .001), wound infection (30.0% vs 6.5%; P = .001), reoperation (48.1% vs 10.9%; P < .001), hospital stay (median 42 vs 26 days; P < .001), and overall 90-day mortality (19.5% vs 4.3%; P = .013) and was identified as an independent risk factor for sepsis, wound infection, and reoperation in the multivariate analysis. Detection of microorganisms in postoperative pancreatic fistula is frequent after pancreatic resection and indicates a turning point in the development of postoperative pancreatic fistula into a life-threatening condition. Whether early anti-infective therapy in combination with interventional measures or a surgical reintervention are warranted, has yet to be elucidated.