284 research outputs found
Vascular anomalies of the celiac trunk and implications in treatment of HCC with TACE. Description of a case and review of the literature
Knowledge of the vascular anatomy of the upper abdomen is important in the daily practice of surgeons specialized in the hepatobiliary and pancreatic area, and for general surgeons and radiologists, mainly those involved in interventional radiology. Since anatomical variants of the celiac axis and hepatic arteries are common, an accurate description of vascularization is required before procedures to avoid iatrogenic vascular changes. We reported a case of a young male patient with HBV related cirrhosis, who came to our institution for the treatment of 2 HCC nodules. The preprocedural contrast-enhanced CT examination showed combined variations of celiac trunk, hepatic arteries, gastroduodenal artery, and right inferior phrenic artery. The careful pre- and intraprocedural evaluation of vascularization allowed us to perform transarterial chemoembolization of the 2 nodules without complications. The incidence and developmental and clinical significance of this variation is discussed with a detailed review of the literature. Knowledge of such a case has important clinical significance in abdominal operations or invasive arterial procedures
Экспериментальное определение и сравнительный анализ характеристик прочности полимеров PPH030GP, ABS и PLA при различных скоростях деформации
Nowadays the field of application of products made from polymer materials is constantly increasing. These products find their wide application in the most high-tech industries such as automotive, aerospace and medical industry. Modern trends in the development of the automotive industry predicts that 75 % of the total car mass will be replaced with polymer materials by 2020 and other industries demonstrate similar trends. Regarding to this information, engineering companies that design parts of the automotive industry should have polymer material characteristics over an entire range of deformations up to destruction for their performance prediction. However, strength characteristics of products from polymers are different and depend not only on a polymer grade but also on technology used for part production. Existing literature review on this problematic area is rather rare. The purpose of this paper is to determine and analyze mechanical characteristics of widely used PPH030GP polymer obtained by extrusion and ABS, PLA polymers applied while manufacturing samples using an additive method (3D-printing) depending on the rate of high-elastic deformation. All the samples have been made according to the requirements of GOST 11262–80 and subjected to uniaxial stretching on a tensile machine UIT STM 050/300 at different speeds of clamp expansion. According to experimental results, stretching diagrams in conditional coordinates s–e have been obtained up to the point of failure for different rates of clamp expansion. It has been shown that while using the additive method, a direction of layers and adhesion between them, which depends on 3D-print parameters, have a significant effect on the part strength. Printing settings are indicated in accordance with the selected mode and a 3D-printer model. As a result of data processing, strength characteristics of PPH030GP polymer and ABS and PLA polymers have been determined to a sufficient extent, depending on the direction of printing layers and rate of high-elastic deformation. These data can be used to calculate strength of products by numerical methods and a finite element method in various software products.Сегодня область применения изделий из полимерных материалов постоянно увеличивается. Такие изделия находят широкое применение в наиболее наукоемких отраслях, таких как автомобильная, аэрокосмическая и медицинская отрасли. Современные тенденции развития автомобильной промышленности прогнозируют к 2020 году 75 % общей массы автомобиля заменить полимерными материалами. Схожие тренды демонстрируют и другие отрасли. В связи с этим инженерным компаниям, проектирующим детали автомобильной промышленности, для прогнозирования их работоспособности необходимо иметь характеристики полимерных материалов во всем диапазоне деформаций – вплоть до разрушения. Однако прочностные характеристики изделий из полимеров различны и зависят не только от марки полимера, но и от технологии производства детали. Подробная информация в отечественной литературе встречается достаточно редко и в сжатом виде. Авторами статьи была поставлена задача определить и проанализировать механические характеристики широко применяемого полимера PPH030GP, полученного экструзивным методом, и полимеров ABS и PLA, применяемых при изготовлении образцов аддитивным методом (3D-печать) в зависимости от скорости деформации. Для этого были выполнены образцы согласно требованиям ГОСТ 11262–80 и подвергнуты одноосному растяжению на разрывной машине UIT STM 050/300 при разных скоростях раздвижения зажимов. По результатам экспериментальных исследований получены диаграммы растяжения в условных координатах s–e вплоть до момента разрушения для различных скоростей раздвижения зажимов. Показано, что при аддитивном методе значительное влияние на прочность изделия оказывают направление слоев и адгезия между ними, которая зависит от параметров 3D-печати. Параметры печати указаны в зависимости от выбранного режима и конструкции 3D-принтера. В результате обработки данных в достаточно полной мере определены прочностные характеристики полимеров PPH030GP, ABS и PLA в зависимости от направления слоев печати и скорости деформации. Эти данные можно применять для расчета прочности изделий численным методом и методом конечных элементов в различных программных продуктах
High-Throughput Assay for Enantiomeric Excess Determination in 1,2- and 1,3-Diols and Direct Asymmetric Reaction Screening
A simple and efficient method for determination of the yield, enantiomeric/diasteriomeric excess (ee/de), and absolute configuration of crude chiral diols without the need of work-up and product isolation in a high throughput setting is described. This approach utilizes a self-assembled iminoboronate ester formed as a product by dynamic covalent self-assembly of a chiral diol with an enantiopure fluorescent amine such as tryptophan methyl ester or tryptophanol and 2-formylphenylboronic acid. The resulting diastereomeric boronates display different photophysical properties and allow for fluorescence-based ee determination of molecules containing a 1,2- or 1,3-diol moiety. This method has been utilized for the screening of ee in a number of chiral diols including atorvastatin, a statin used for the treatment of hypercholesterolemia. Noyori asymmetric hydrogenation of benzil was performed in a highly parallel fashion with errors <1 % ee confirming the feasibility of the systematic examination of crude products from the parallel asymmetric synthesis in real time and in a high-throughput screening (HTS) fashion.</p
Toward fluorescence-based high-throughput screening for enantiomeric excess in amines and amino acid derivatives
A highly accurate and reliable screening method for enantiomeric excess of amine derivatives in the presence of water is reported. The fluorescence-based screening system has been realized by self-assembly of chiral diol-type dyes (BINOL, VANOL and VAPOL), 2-formylphenylboronic acid, and chiral amines forming iminoboronate esters. The structure and chirality of the amine analytes determine the stability of the diastereomeric iminoboronate esters, which in turn display differential fluorescence. The fluorescence signal reflects the enantiomeric purity of the chiral amines and was utilized in high-throughput arrays. The arrays were able to recognize enantiomeric excess of amines, amino esters, and amino alcohols. In addition to qualitative analysis, quantitative experiments were successfully performed. Studies of the role of additives such as water or citrate were carried out to gain insight into the stability of the iminoboronate esters. It is shown that the above additives destabilize less stable esters while the stable esters remain unchanged. Thus, the presence of water and citrate leads to increased difference between the diastereomeric iminoboronates and contributes to the enantiodiscrimination of the chiral amines.</p
РАК ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ И НАСЛЕДСТВЕННЫЕ СИНДРОМЫ
The aim of this study is to assess relative risk of prostate cancer (PC) and other tumors in families of patients with multiple primary malignancies (MPM) and the syndrome of hereditary nonpolyposis colorectal cancer (HNPCC). The study is based on data from the cancer register of families that includes information on 560 patients with MPM, 126 families with HNPCC and their first-degree relatives. Incidence of these diseases in population served as the control.Among 560 probands with PPN 217 (38.7%) were male and 343 (61.3%) – female. Only 12 (2.1%) male patients had tumor in the prostate. In these patients 24 tumors were identified. Two patients had synchronous tumors, other ten patients had metachronous. Eight patients with prostate cancer had tumors of other organs: 5 – in rectum, 2 – in colon and 1 – in bladder. As a second tumor prostate cancer was diagnosed in 4 patients, three of them had rectal cancer and one – colon cancer. Only 2 (0.3%) patients had prostate cancer as a primary tumor. Clinical and genealogical information achieved from 543 patients with MPM, including in 206 male probands. Among 3637 first-degree relatives of probands with MPM prostate cancer was diagnosed in 2 (0.11±2.3%) patients that was 1.7 times higher than in population (0.063±0.0019%). The relative risk of prostate cancer for relatives of patients from families with HNPCC syndrome was 0.8 ± 6.3% that was 12/7 times higher than in the control group (p <0.05). The estimation of the relative risk in families of male probands was perfprmed. Among 1460 male relatives with MPM only 1 (0.14%) case of prostate cancer was diagnosed (son of proband). Among 42 families of male probands with HNPCC syndrome, prostate cancer was detected in 2 (1.3%) brothers that exceeds population risk 20.6 times. Although the molecular mechanisms and pathogenesis of prostate cancer in such families is unknown, its association with a HNPCC-syndrome and possibly MPM-syndrome is obvious.Higher relative risk of developing prostate cancer for male relatives of probands with MPM and HNPCC syndrome presupposes inherited genetically determined predisposition to disease development. Further molecular and genetic studies are needed to determine the genetic basis of predisposition to prostate cancer in these families.Цель исследования — оценить относительный риск рака предстательной железы (РПЖ) и других (внепростатных) опухолей в семьях больных с первично-множественными злокачественными новообразованиями (ПМЗН) и с синдромом наследственного неполипозного колоректального рака (HNPCC). Материалом для исследования послужили данные регистра раковых семей, включающий сведения о 560 больных с ПМЗН, 126 семей с HNPCC и их родственников первой степени родства. В качестве контроля служили популяционные частоты указанных заболеваний.Среди 560 пробандов с ПМЗН было 217 (38.7%) мужчин и 343 (61.3%) женщин. Только у 12 (2.1%) пациентов-мужчин одна из опухолей поражала ПЖ. У них выявлены 24 опухоли. У двух из них опухоли были синхронными, а у 10 — метахронными. У 8 пациентов с РПЖ вторые опухоли локализовались: в прямой кишке (5), ободочной кишке (2) и мочевом пузыре (1). В качестве второй опухоли РПЖ наблюдали у 4 пациентов: у 3 с раком прямой кишки и у 1 — раком ободочной кишки. Только у 2 (0.3%) пациентов первой опухолью был РПЖ. Клинико-генеалогические сведения удалось получить у 543 пациентов с ПМЗН, в том числе у 206 пробандов-мужчин. Среди 3637 родственников первой степени родства пробандов с ПМЗН РПЖ выявлен у 2 (0.11±2.3%), что в 1.7 раза превышает популяционный риск (0.063±0.0019%). Относительный риск РПЖ для родственников пациентов из семей с синдромом HNPCC составляет 0.8±6.3% и превышает таковой в контрольной группе в 12.7 раз (р<0.05). Проведена оценка относительного риска в семьях пробандов-мужчин. Среди 1460 родственников-мужчин с ПМЗН выявлен 1 (0.14%) случай РПЖ — у сына. В 42 семьях пробандов-мужчин с синдромом HNPCC РПЖ был выявлен у 2 (1.3%) братьев, что превышает популяционный риск в 20.6 раза. Хотя молекулярный механизм и патогенез РПЖ в описанных семьях остается неизвестным, его ассоциация с синдромом HNPCC и, возможно, с синдромом полинеоплазий, очевидна. Высокий относительный риск заболеть РПЖ для кровных родственников-мужчин пробандов с ПМЗН и синдромом HNPCC предполагает наличие унаследованной генетически обусловленной предрасположенности к развитию болезни. Необходимы молекулярно-генетические исследования, чтобы определить генетическую основу подверженности к раку предстательной железы в этих семьях. Не исключено, что это может быть связано с общими этиологическими факторами
Uma área de relevante interesse biológico, porém pouco conhecida: a Reserva Florestal do Morro Grande
Molecular surveillance of Plasmodium vivax dhfr and dhps mutations in isolates from Afghanistan
<p>Abstract</p> <p>Background</p> <p>Analysis of dihydrofolate reductase (<it>dhfr</it>) and dihydropteroate synthase (<it>dhps</it>) mutations in <it>Plasmodium vivax </it>wild isolates has been considered to be a valuable molecular approach for mapping resistance to sulphadoxine-pyrimethamine (SP). The present study investigates the frequency of SNPs-haplotypes in the <it>dhfr </it>and <it>dhps </it>genes in <it>P. vivax </it>clinical isolates circulating in two malaria endemic areas in Afghanistan.</p> <p>Methods</p> <p><it>P. vivax </it>clinical isolates (n = 171) were collected in two different malaria endemic regions in north-west (Herat) and east (Nangarhar) Afghanistan in 2008. All collected isolates were analysed for SNP-haplotypes at positions 13, 33, 57, 58, 61, 117 and 173 of the <it>pvdhfr </it>and 383 and 553 of the <it>pvdhps </it>genes using PCR-RFLP methods.</p> <p>Results</p> <p>All 171 examined isolates were found to carry wild-type amino acids at positions 13, 33, 57, 61 and 173, while 58R and 117N mutations were detected among 4.1% and 12.3% of Afghan isolates, respectively. Based on the size polymorphism of <it>pvdhfr </it>genes at repeat region, type B was the most prevalent variant among Herat (86%) and Nangarhar (88.4%) isolates. Mixed genotype infections (type A/B and A/B/C) were detected in only 2.3% (2/86) of Herat and 1.2% (1/86) of Nangarhar isolates, respectively. The combination of <it>pvdhfr </it>and <it>pvdhps </it>haplotypes among all 171 samples demonstrated six distinct haplotypes. The two most prevalent haplotypes among all examined samples were wild-type (86%) and single mutant haplotype I<sub>13</sub>P<sub>33</sub>F<sub>57</sub>S<sub>58</sub>T<sub>61</sub><b>N </b><sub>117</sub>I<sub>173/</sub>A<sub>383</sub>A<sub>553 </sub>(6.4%).</p> <p>Double (I<sub>13</sub>P<sub>33</sub>S<sub>57</sub><b>R</b><sub>58</sub>T<sub>61</sub><b>N</b><sub>117</sub>I<sub>173</sub>/A<sub>383</sub>A<sub>553</sub>) and triple mutant haplotypes (I<sub>13</sub>P<sub>33</sub>S<sub>57</sub><b>R </b><sub>58</sub>T<sub>61</sub><b>N</b><sub>117</sub>I<sub>173</sub>/<b>G</b><sub>383</sub>A<sub>553</sub>) were found in 1.7% and 1.2% of Afghan isolates, respectively. This triple mutant haplotype was only detected in isolates from Herat, but in none of the Nangarhar isolates.</p> <p>Conclusion</p> <p>The present study shows a limited polymorphism in <it>pvdhfr </it>from Afghan isolates and provides important basic information to establish an epidemiological map of drug-resistant vivax malaria, and updating guidelines for anti-malarial policy in Afghanistan. The continuous usage of SP as first-line anti-malarial drug in Afghanistan might increase the risk of mutations in the <it>dhfr </it>and <it>dhps </it>genes in both <it>P. vivax </it>and <it>Plasmodium falciparum </it>isolates, which may lead to a complete SP resistance in the near future in this region. Therefore, continuous surveillance of <it>P. vivax </it>and <it>P. falciparum </it>molecular markers are needed to monitor the development of resistance to SP in the region.</p
Mitochondrial cardiomyopathies: how to identify candidate pathogenic mutations by mitochondrial DNA sequencing, MITOMASTER and phylogeny
Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. Owing to a high mutation rate, mtDNA defects may occur at any nucleotide in its 16 569 bp sequence. Complete mtDNA sequencing may detect pathogenic mutations, which can be difficult to interpret because of normal ethnic/geographic-associated haplogroup variation. Our goal is to show how to identify candidate mtDNA mutations by sorting out polymorphisms using readily available online tools. The purpose of this approach is to help investigators in prioritizing mtDNA variants for functional analysis to establish pathogenicity. We analyzed complete mtDNA sequences from 29 Italian patients with mitochondrial cardiomyopathy or suspected disease. Using MITOMASTER and PhyloTree, we characterized 593 substitution variants by haplogroup and allele frequencies to identify all novel, non-haplogroup-associated variants. MITOMASTER permitted determination of each variant's location, amino acid change and evolutionary conservation. We found that 98% of variants were common or rare, haplogroup-associated variants, and thus unlikely to be primary cause in 80% of cases. Six variants were novel, non-haplogroup variants and thus possible contributors to disease etiology. Two with the greatest pathogenic potential were heteroplasmic, nonsynonymous variants: m.15132T>C in MT-CYB for a patient with hypertrophic dilated cardiomyopathy and m.6570G>T in MT-CO1 for a patient with myopathy. In summary, we have used our automated information system, MITOMASTER, to make a preliminary distinction between normal mtDNA variation and pathogenic mutations in patient samples; this fast and easy approach allowed us to select the variants for traditional analysis to establish pathogenicity
Analysis of the dihydrofolate reductase-thymidylate synthase gene sequences in Plasmodium vivax field isolates that failed chloroquine treatment
<p>Abstract</p> <p>Background</p> <p>To use pyrimethamine as an alternative anti-malarial drug for chloroquine-resistant malaria parasites, it was necessary to determine the enzyme's genetic variation in dihydrofolate reductase-thymidylate syntase (DHFR-TS) among Korean strains.</p> <p>Methods</p> <p>Genetic variation of <it>dhfr-ts </it>genes of <it>Plasmodium vivax </it>clinical isolates from patients who did not respond to drug treatment (<it>n </it>= 11) in Korea were analysed. The genes were amplified using the polymerase chain reaction (PCR) with genomic DNA as a template.</p> <p>Results</p> <p>Sequence analysis showed that the open reading frame (ORF) of 1,857 nucleotides encoded a deduced protein of 618 amino acids (aa). Alignment with the DHFR-TS genes of other malaria parasites showed that a 231-residue DHFR domain and a 286-residue TS domain were seperated by a 101-aa linker region. This ORF shows 98.7% homology with the <it>P. vivax </it>Sal I strain (XM001615032) in the DHFR domain, 100% in the linker region and 99% in the TS domain. Comparison of the DHFR sequences from pyrimethamine-sensitive and pyrimethamine-resistant <it>P. vivax </it>isolates revealed that nine isolates belonged to the sensitive strain, whereas two isolates met the criteria for resistance. In these two isolates, the amino acid at position 117 is changed from serine to asparagine (S117N). Additionally, all Korean isolates showed a deletion mutant of THGGDN in short tandem repetitive sequences between 88 and 106 amino acid.</p> <p>Conclusions</p> <p>These results suggest that sequence variations in the DHFR-TS represent the prevalence of antifolate-resistant <it>P. vivax </it>in Korea. Two of 11 isolates have the Ser to Asn mutation in codon 117, which is the major determinant of pyrimethamine resistance in <it>P. vivax</it>. Therefore, the introduction of pyrimethamine for the treatment of chloroquine-resistant vivax malaria as alternative drug in Korea should be seriously considered.</p
- …
