Risk factors for multiple sclerosis, neuromyelitis optica and transverse myelitis.
Little is known about risk factors for neuromyelitis optica (NMO) or transverse myelitis (TM). The objective of this paper is to evaluate whether established multiple sclerosis (MS) risk factors, including smoking history, a history of infectious mononucleosis (IM), anti-EBNA1 Ab titers and HLA-DR15 are associated with NMO or TM. We conducted a case-control study among participants in the Accelerated Cure Project for Multiple Sclerosis (ACP) Repository, which includes patients with MS, NMO and TM. Controls include related and unrelated individuals without evidence of demyelinating disease. Analyses included 1237 cases of MS, 98 cases of NMO, 133 cases of TM and 488 healthy controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the association between smoking, HLA-DR15, anti-EBNA1 Ab titers and a history of IM adjusting for gender, study site and ethnicity. Overall, the association between smoking, IM, HLA-DR15 and anti-EBNA1 Ab titers and odds of MS were as expected and no significant interactions were observed. However, there was little evidence of association between these MS risk factors and odds of NMO or TM. Established MS risk factors do not appear to be associated with susceptibility to TM or NMO and, among MS patients, these risk factors appear to act independently.


Constancy scaling and conflict when the Zöllner illusion is seen in three dimensions.
If a standard Zöllner illusion is seen as a staircase in depth, pairs of long lines flanking convex stair edges appear to diverge as usual, but divergence in pairs flanking concave edges can appear reduced. If the stair is reversed perceptually in the manner of the Schröder staircase, convex and concave shapes exchange and the extent of apparent divergence in the long line pairs exchanges with them. The effect is enhanced if explicit stair edges are added, and reduced if the standard Zöllner pattern is replaced by one in which segments of the long lines are offset in the direction of the usual illusory effect. The observations suggest that the three-dimensional potential of the pattern cannot be excluded from explanations of the illusion, and are compatible with the view of Gregory and Harris that inappropriate constancy scaling is its primary cause, triggered 'bottom-up' by pattern properties or 'top-down' by cognitive inference. However, these two mechanisms would have to be acting in conflict to generate suppression of divergence in the concave steps. Pattern processing for properties, such as orientation, that are not associated with the potential of the Zöllner illusion as a three-dimensional configuration, but that have been suggested as sources of the illusion in recent studies, could also be acting in opposition to hypothesis scaling in the concave steps.


Induction of the rainbow trout MHC class I pathway during acute IHNV infection.
Interferons are essential for establishing cytotoxic T-lymphocyte immunity against viral pathogens through different mechanisms including the modulation of antigen presentation to T-cell subsets. At the present time, interferons have yet to be isolated from teleost fish. We have developed a salmonid model to examine whether MHC gene regulation is modulated during acute viral infection in trout, an event attributable to interferons in mammals. During peak infection with infectious hematopoietic necrosis virus, induction of STAT-1, PSMB9A and ABCB2 mRNA was evident in all tissues within infected fish, as compared with controls. In addition, MHC class Ia and beta(2) microglobulin (beta(2)m) transcript levels were enhanced within the experimental group but surprisingly, splenic and pronephric class IIB mRNA expression was virtually absent. A time-course study looking at 24, 72 and 192 h post-infection was then performed to determine the overall kinetics of this response. STAT-1 and PSMB9A message levels increased early during the immune response and remain at relatively high levels until the final time point. MHC class Ia expression is not consistently upregulated until midway in the response. MHC class IIB transcripts are downregulated by 72 h in the spleen and pronephros and then partially restored by 192 h. Finally, analysis of the putative promoter regions for PSMB9A and ABCB2 identified interferon (IFN) regulatory factory (IRF-1) and INF-gamma (GAS) activation sites that may be involved in the regulation of these genes during viral infection.


Healthcare-Associated Legionella Disease: A Multi-Year Assessment of Exposure Settings in a National Healthcare System in the United States.
Healthcare facilities are high-risk environments for Legionella disease (LD), including Legionnaires' disease, but transmission in these settings is often overlooked. We used the LD database at the U.S. Department of Veterans Affairs (VA) national healthcare system to assess the type of healthcare exposure for LD cases. Cases were extracted from the database for 1 September 2012 through 31 July 2019, focusing on cases with an overnight stay at a VA facility during the 10-day exposure window prior to symptom onset. Patient medical charts were reviewed for demographics and types of healthcare setting exposure(s). There were 99 LD cases in the cohort: 31.3% were classified as having definite VA exposure, 37.4% were classified as possible VA with inpatient exposure, and 31.3% were classified as possible VA with both inpatient and outpatient exposure. For definite VA LD cases, 67.7% had some type of exposure in the long-term care setting. While 63% of the 99 cases had exposure in the acute care setting only, both the long-term care and acute care settings contributed substantially to the total number of exposure days. A review of patient movement during the exposure period showed the variable and sometimes extensive use of the VA system, and it provides insights useful for epidemiologic investigations and potential preventive actions.


Total Synthesis of Laucysteinamide A, a Monomeric Congener of Somocystinamide A.
Laucysteinamide A (4) is a marine natural product isolated from the cyanobacterium Caldora penicillata and contains structural motifs found in promising cancer drug leads. The first total synthesis of 4 and its analogues was achieved, which also enabled a concise formal synthesis of somocystinamide A (3), a dimeric congener of 4 that previously showed extremely potent antiproliferative activities. This work provides further insights on structure-activity relationships in this class of natural products.


Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway.
Urocortin (UCN) is a peptide related to hypothalamic corticotrophin-releasing hormone and binds with high affinity to corticotrophin-releasing hormone receptor-2beta, which is expressed in the heart. In this study, we report that UCN prevented cell death when administered to primary cardiac myocyte cultures both prior to simulated hypoxia/ischemia and at the point of reoxygenation after simulated hypoxia/ischemia. UCN-mediated cell survival was measured by trypan blue exclusion, 3'-OH end labeling of DNA (TUNEL), annexin V, and fluorescence-activated cell sorting. To explore the mechanisms that could be responsible for this effect, we investigated the involvement of MAPK-dependent pathways. UCN caused rapid phosphorylation of ERK1/2-p42/44, and PD98059, which blocks the MEK1-ERK1/2-p42/44 cascade, also inhibited the survival-promoting effect of UCN. Most important, UCN reduced damage in isolated rat hearts ex vivo subjected to regional ischemia/reperfusion, with the protective effect being observed when UCN was given either prior to ischemia or at the time of reperfusion after ischemia. This suggests a novel function of UCN as a cardioprotective agent that could act when given after ischemia, at reperfusion.


Brain-computer communication: unlocking the locked in.
With the increasing efficiency of life-support systems and better intensive care, more patients survive severe injuries of the brain and spinal cord. Many of these patients experience locked-in syndrome: The active mind is locked in a paralyzed body. Consequently, communication is extremely restricted or impossible. A muscle-independent communication channel overcomes this problem and is realized through a brain-computer interface, a direct connection between brain and computer. The number of technically elaborated brain-computer interfaces is in contrast with the number of systems used in the daily life of locked-in patients. It is hypothesized that a profound knowledge and consideration of psychological principles are necessary to make brain-computer interfaces feasible for locked-in patients.


Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension.
Thiazolidinediones are a new class of antidiabetic agent that improve insulin sensitivity and reduce plasma glucose and blood pressure in subjects with type 2 diabetes. Although these agents can bind and activate an orphan nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), there is no direct evidence to conclusively implicate this receptor in the regulation of mammalian glucose homeostasis. Here we report two different heterozygous mutations in the ligand-binding domain of PPARgamma in three subjects with severe insulin resistance. In the PPARgamma crystal structure, the mutations destabilize helix 12 which mediates transactivation. Consistent with this, both receptor mutants are markedly transcriptionally impaired and, moreover, are able to inhibit the action of coexpressed wild-type PPARgamma in a dominant negative manner. In addition to insulin resistance, all three subjects developed type 2 diabetes mellitus and hypertension at an unusually early age. Our findings represent the first germline loss-of-function mutations in PPARgamma and provide compelling genetic evidence that this receptor is important in the control of insulin sensitivity, glucose homeostasis and blood pressure in man.


Isolation and characterization of male flower cDNAs from maize.
Differential screening of two libraries made from whole, immature maize tassels was used to isolate six cDNAs which show enhanced levels of expression in male flowers. MFS1, MFS2, MFS4, MFS10 and MFS18, which were isolated from a 5 cm tassel library, are expressed throughout tassel growth up until mature pollen is produced in the anthers. MFS14, which was isolated from a 10-12 cm tassel library, has a narrower window of expression associated with microsporogenesis and declines as mature pollen is produced. MFS18 mRNA accumulates in the glumes and in anther walls, paleas and lemmas of mature florets. MFS18 mRNA is particularly associated with the vascular bundle in the glumes and encodes a polypeptide of 12 kDa, rich in glycine, proline and serine that has similarities with other plant structural proteins. In contrast, MFS14 mRNA accumulates in the tapetum and encodes a polypeptide of 13 kDa that is rich in alanine. The MFS14 and MFS18 proteins are basic (isoelectric points of 11.56 and 9.54, respectively) and both have hydrophobic N-termini which display all the characteristics of signal peptides, indicating that these proteins may be secreted.


Prognosis and Management in Subsequent Rh Alloimmunized Pregnancies.
Background: RhD alloimmunization remains a severe problem worldwide, but its management has been revolutionized by two important discoveries: the possibility to establish fetal Rh genotype non-invasively by using a maternal blood sample, and using of Doppler velocimetry to monitor early signs of affected fetuses. Materials and methods: We performed a literature review by searching PubMed for relevant information about diagnosis, prognosis, and management of secondary affected Rh alloimmunized pregnancies. Results:The risk to develop fetal anemia and hydrops seems to increase with increasing concentrations of Rh antibodies, and studies show it is higher for subsequent pregnancies. Individuals presenting the DEL phenotype with the types 1, 2 or 3 can be considered RhD positive and anti-D immune globulin is not indicated. Discussions: Medical algorithm involves previous pregnancy history together with serum parameters. Follow-up in a department of maternal fetal medicine is desired and encouraged in these cases. Depending on the severity and woman's previous pregnancy history, especially condition prior to 24 weeks of gestation, several therapies such as plasmaphereses, intravenous immune globulin or intrauterine transfusions can be conducted. Intrauterine transfusions have a better prognosis when performed earlier and on fetuses without hydrops. Conclusion:Although the incidence of hemolytic disease of the fetus and newborn has decreased and is no longer a major cause of perinatal mortality, vigilance is still required. There is a strong argument for reunite the management of these cases in dedicated maternal fetal medicine centers that perform invasive procedures in order to improve knowledge, gain skills and enhance clinical management.


Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation.
Tofisopam (1-(3,4-dimethoxyphenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodiazepine) has been shown to be an effective anxiolytic agent in the wide-ranging clinical practice. A high sensitive gas chromatography nitrogen phosphorous detection (GC-NPD) bioanalytical method was developed and validated for the purpose of pharmacokinetic study of tofisopam. A liquid-liquid extraction method was used for the sample preparation. The mean recovery for tofisopam was 69.8% and the inter- and intra-day precision values were well below the 15% limit established for bioanalytical methods. A similar compound, girizopam was used as internal standard. The assay was linear in the 5-500 ng/ml range corresponding to therapeutically relevant plasma levels. The concentrations of the compound were measured in the plasma samples of 12 healthy male volunteers and the pharmacokinetic parameters were determined from the plasma concentration-time data. A rapid absorption and distribution, relatively short biological half-life and considerable inter-individual variation in the plasma concentration levels of parent compound were the main characteristics of the pharmacokinetics of tofisopam. According to these results, the new (GC-NPD) bioanalytical method proved to be capable of measuring concentration of tofisopam in human plasma and was successfully applied in a single dose pharmacokinetic study.


Body composition and metabolic syndrome in patients with primary gout in Vietnam.
To characterize the body composition, to determine the prevalence of metabolic syndrome (MetS), and to examine the association between body composition and the components of MetS in Vietnamese patients with primary gout. A total of 107 males with gout and 107 age-matched healthy males underwent physical examination, body composition assessment by dual-energy X-ray absorptiometry and blood tests. Both the original and revised National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP) III criteria were used to define MetS. Means of total body and trunk fat mass in patients with gout were higher (P<0.001) than those in controls: 20.9 vs 13.3 kg and 11.4 vs 6.1 kg, respectively. The prevalence of MetS according to the original and revised NCEP/ATP III criteria in patients with gout was also higher (P<0.001) than in controls (33.6 vs 15.9% and 56.1 vs 23.4%), respectively. In patients with gout, total fat mass was strongly correlated with BMI (r=0.86, P<0.001), while trunk fat mass was strongly correlated with waist circumference (r=0.91, P<0.001). Total fat mass, trunk fat mass and trunk fat mass/legs fat mass ratio were positively correlated (P<0.05) with glycaemia, triglyceridaemia, blood pressure and negatively correlated (P<0.05) with high-density liproprotein cholesterol levels. Patients with gout had significantly higher fat mass, especially in the trunk region, and higher prevalence of MetS than healthy controls. Therefore, management of weight and MetS should be emphasized in patients with gout to reduce their risk of cardiovascular diseases.


Thermoelectrically Cooled GaAIAs Laser Illuminator.
Required operating wavelengths in GaAs injection lasers have generally determined the operating temperature, preventing the use of optimum refrigeration systems. Recent advances in GaAIAs injection lasers have produced high efficiency lasers with selectable wavelengths from 0.8 microm to 0.9 microm. This paper discusses the refrigeration considerations for GaAIAs lasers. The basis for selecting the thermoelectric refrigerator is presented and the solution of the optical-electronic interface problems are discussed. Finally, the actual design and performance characteristics of the individual laser arrays and a thermoelectrically cooled, GaAIAs illuminator are described.


Management of infectious complications of intraventricular reservoirs in cancer patients: low incidence and successful treatment without reservoir removal.
At the time of analysis, the first 30 patients with Ommaya reservoirs (OR) at the Children's Orthopedic Hospital and Medical Center in Seattle, Washington had had 32 reservoirs for a mean duration of 28 months. In all, the reservoir chambers had been punctured for either diagnostic or therapeutic purposes a total of 1,287 times with a mean of 40 injections per reservoir and 1.4 injections per month. Six reservoir infections were diagnosed in five patients--a rate of one infection for every 153 reservoir-months. Four infections were attributed to reservoir use--a rate of one infection for every 322 reservoir entries, and less than one infection in 900 entries when a standard aseptic protocol for sampling and injection was applied. There was no correlation between infectious complications and the frequency with which reservoirs were injected, but there was evidence that some of the infections resulted from incomplete compliance with recommended technique for skin preparation and reservoir entry. Four infections were treated successfully with intravenous and intra-reservoir antibiotics without reservoir removal. Only one reservoir had to be removed because of persistent infection. Two other reservoirs were removed because of trauma and malfunction. Twenty-seven patients (90%) retained their original reservoir, up to 9.5 years after implantation. Intraventricular chemotherapy via an indwelling subcutaneous reservoir is a preferred method for delivery of intrathecal chemotherapy, with an acceptable infection risk relative to the benefits of patient comfort and therapeutic efficacy.


Transplant outcomes in mucopolysaccharidoses.
The mucopolysaccharidoses (MPSs) are inherited metabolic disorders (IMDs) caused by single-gene defects leading to progressive cellular accumulation of glycosaminoglycans (GAGs) and damage to multiple organs, including the central nervous, musculoskeletal, cardiorespiratory, and other systems. Hurler syndrome (MPS IH), the most severe form, is the prototypical model. Enzyme replacement therapy (ERT), available for MPS I, II, and VI, is beneficial in some patients. However, ERT does not improve neurocognitive function because of its inability to cross the blood-brain barrier. In contrast, allogeneic hematopoietic stem cell transplantation (HSCT) allows donor-derived, enzyme-producing cells to migrate to the brain and other organs to provide permanent enzyme therapy and thus help somatic organs, improve neurocognitive function and quality of life, and prolong survival, particularly when performed early in the course of the disease. Bone marrow has been the graft source in the past. However, in the last 5 years many patients have been treated with unrelated donor (URD) umbilical cord blood transplant (UCBT), allowing rapid and increased access to transplantation with favorable outcomes. This review describes published and our institutional clinical experiences, discusses the current status of the field, and provides therapy guidelines for patients with MPS.


Rocking the world of innate immunity: an interview with Luke O'Neill.
Luke O'Neill is professor of biochemistry in the School of Biochemistry and Immunology at Trinity College Dublin, and his main research focus is innate immunity and its key output, inflammation. His work has explored the key sensors and mediators of infection, including the Toll-like receptors, inflammasomes and cytokines in the interleukin-1 (IL-1) family. Luke received the Royal Irish Academy Gold Medal for Life Sciences in 2012 and the European Federation of Immunology Societies Medal in 2014. He was elected a member of the European Molecular Biology Organisation (EMBO) in 2005 and a Fellow of the Royal Society in 2016. In this interview, Luke talks about the necessary collaboration between immunologists and cancer scientists, inflammaging, and his rock-star alter-ego as frontman of The Metabollix.


Increased lipase and amilase levels in critically ill patients: retrospective study.
Elevated lipase and amylase are commonly found in patients in intensive care unit without a previously recognized pancreatic illness, constituting a diagnostic and therapeutic challenge. The authors therefore proposed to determine the frequency of asymptomatic high serum lipase in critically ill patients, involved risk factors and outcome. Retrospective study of patients admitted in an intensive care unit from January 1 to December 31, 2006, excluding admissions for acute pancreatitis, history of pancreatic disease, renal insufficiency or lacking of data. Patients were divided in two groups (with and without high serum lipase) that were compared for clinical, laboratory and radiological variables. SPSS 13; Student's t test and Chi-square test (CI 95%) with statistical significance if p< 0.05). 102 patients were included with high serum lipase was present in 39.2% of patients, mean lipase of 797U/L. Patients with high serum lipase had longer hospital stay (p< 0.001), parenteral nutrition (p< 0.001), ventilator support (p=0.04), fever (p< 0.001), hyperamylasemia (p<0.05), hyperbilirrubinemia (p=0.003) and rise of transaminases (p=0.001), with no significant differences in diagnosis, gender, age, APACHE II, SOFA, SAPS, mortality, hypotension, alkaline phosphatase, hemoglobin, lactate, tolerance to enteral nutrition and use of propofol. Imaging study revealed pancreatic alterations in two patients with high serum lipase. Elevated lipase was commonly found in critical patients, it related with longer length of stay but was not accompanied by increased clinical severity or mortality. It was more frequent with parenteral nutrition. A minority of patients met the criteria of acute pancreatitis.


Cryoscanning electron microscopy of loaded articular cartilage with special reference to the surface amorphous layer.
The surface layer (i.e. the surface lamina) of articular cartilage, which is devoid of a collagen fibril network or cells, was investigated in the pig and human. It overlies the collagenous main part of the articular cartilage which contains chondrocytes and is thought to be important biomechanically. In order to examine morphological changes in this layer when under load, knee articular cartilage of the pig, along with the underlying subchondral bone, was compressed with a cylindrical indenter. The specimen was frozen by immersion in liquid nitrogen to maintain the loaded condition and was then freeze-fractured at the indented region. The fracture face was examined with a cryoscanning electron microscope. The surface layer was compressed beneath the indenter regardless of loading pressure or period and was expanded around the indenter to form a triangular bulge in cross section. The height of the bulge was related to the applied pressure and not to the loading period. Recovery of the cartilage from indentation was also examined. Immediately after removal of the indenter, the bulge of the surface layer moved back into the previously indented region. The region was covered by a thick surface layer after 2 s. The response of the surface layer to and recovery from indentation was largely instantaneous and elastic. Under heavy load conditions, the main part of the cartilage under the indenter was observed to have a striped pattern which was made up of bands of densely packed collagen fibrils with fibrillar networks remaining between them. These morphological findings agree well with previously reported biomechanical hypotheses and can be explained by the flow of interstitial fluid provoked by stress application.


Exclusion of aortic tear in the unstable trauma patient: the utility of transesophageal echocardiography.
The goal of this study was to investigate the value of biplanar transesophageal echocardiography (TEE) as a screening tool for aortic tear in unstable trauma patients. During a 1-year period, a prospective trial to exclude aortic tear was conducted at a level I trauma center. Ten of 53 patients (19%) sustaining severe blunt thoracic trauma were deemed too unstable to undergo safe transport to aortography and underwent TEE. Mechanism of injury was motor vehicle crash in eight patients and pedestrians struck in two. Patients had a mean Injury Severity Score = 34 (range, 17 to 59) and mean age = 43 years (range, 18 to 77). Indications for aortic tear evaluation were chest x-ray findings in seven and mechanism of injury alone in three. Patients were not transportable because of hemodynamic instability in five individuals, severe unstable head injury in three individuals, and unstable cervical spine fracture in two individuals. Transesophageal echocardiography was performed in the emergency department in one instance, in the operating room in one instance, and in the surgical intensive care unit in the remaining eight instances. Patients underwent the procedure less than 8 hours after admission in seven and more than 48 hours after admission in three. One patient had a complication during TEE (ventricular dysrhythmias). In one of ten patients, TEE was positive. This patient required medical management (beta-blockade) for aortic tear until severe hypoxia secondary to pulmonary contusion improved after 36 hours. Repair of aortic tear was then successfully performed. The TEE procedure is valuable in identifying aortic injury in high-risk trauma patients who are too unstable to undergo transport to the aortography suite.


Targeting E2F1 and c-Myc expression by microRNA-17-5p represses interferon-stimulated gene MxA in peripheral blood mononuclear cells of pediatric systemic lupus erythematosus patients.
Elevated type I interferon (IFN) is believed to be one of the crucial factors involved in the pathogenesis of systemic lupus erythematosus (SLE). Its expression was recently found to be governed by the transcription factor E2F1 which is involved in an autoregulatory triad along with c-Myc and the microRNA polycistron miR-17-92. However, this intricate triad has seldom been investigated in SLE patients. Therefore, the current study was undertaken to investigate the expression pattern of the E2F1/c-Myc/miR-17-5p triad in peripheral blood of SLE patients as well as to examine the impact of manipulating this triad using miR-17-5p mimics and inhibitors on IFN signature in SLE patients. Expression of the E2F1/c-Myc/miR-17-5p triad and the IFN-stimulated gene MxA was analyzed using real time qPCR. Peripheral blood mononuclear cells from SLE patients and controls were transfected with miR-17-5p mimics and antagomirs using the HiPerfect transfection reagent. E2F1 transcripts and miR-17-5p were significantly downregulated while c-Myc and MxA transcripts were significantly upregulated in SLE. Also, transfection of SLE PBMCs with miR-17-5p mimics led to a substantial repression of E2F1 and c-Myc expression. The overall change in this triad upon miR-17-5p mimicking resulted in lowering the transcript levels of the IFN-inducible gene MxA in SLE. This may advocate the manipulation/use of the E2F1/c-Myc/miR-17-5p trinity to effectively control the aberrantly high levels of type I IFN activity in lupus patients.


Population genetic structure of cotton pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae) using mitochondrial cytochrome oxidase I (COI) gene sequences from India.
Pink bollworm (PBW), Pectinophora gossypiella is one of the most destructive pest's globally inflicting huge economic losses in cotton even during later stages of crop growth. In the present investigation, the population genetic structure, distribution, and genetic diversity of P. gossypiella in cotton growing zones of India using partial mitochondrial DNA cytochrome oxidase-I (COI) gene was addressed. The overall haplotype (Hd), number of nucleotide differences (K), and nucleotide diversity (π) were 0.3028, 0.327, and 0.00047, respectively which suggest that entire population exhibited low level of genetic diversity. Zone-wise clustering of population revealed that central zone recorded low level of Hd (0.2730) as compared to north (0.3619) and south (0.3028) zones. The most common haplotype (H1) reported in all 19 locations could be proposed as ancestral/original haplotype. This haplotype with one mutational step formed star-like phylogeny connected with 11 other haplotypes. The phylogenetic relationship studies revealed that most haplotypes of populations are closely related to each other. Haplotype 5 was exclusively present in Dharwad (South zone) shared with populations of Hanumangarh and Bathinda (North zone). The result indicated that there is no isolation by distance effect among the Indian populations of PBW. The present study reports a low genetic diversity among PBW populations of India and H1, as ancestral haplotype from which other haplotypes have evolved suggests that the migration and dispersal over long distance and invasiveness are major factors.


Hyperuricemia and Cardiovascular Disease.
Purine metabolism in the circulatory system yields uric acid as its final oxidation product, which is believed to be linked to the development of gout and kidney stones. Hyperuricemia is closely correlated with cardiovascular disease, metabolic syndrome, and chronic kidney disease, as attested by the epidemiological and empirical research. In this review, we summarize the recent knowledge about hyperuricemia, with a special focus on its physiology, epidemiology, and correlation with cardiovascular disease. This review also discusses the possible positive effects of treatment to reduce urate levels in patients with cardiovascular disease and hyperuricemia, which may lead to an improved clinical treatment plan.


[Hepatitis E infection in dialysis and after transplantation].
Hepatitis E virus (HEV) causes epidemics of acute hepatitis in developing countries, and also appears to be an emerging agent in industrialized countries. HEV infection is transmitted via the fecal-oral route, and may be a zoonosis in industrialized countries. HEV infection was thought to be responsible for acute hepatitis that does not become chronic. However, it has been recently reported that HEV infection can evolve to chronic hepatitis and to cirrhosis, at least in solid-organ transplant patients. The reduction of immunosuppressive drugs could be considered as a first-line therapeutic option.


Mining and visualizing the chemical content of large databases.
The shift in the drug discovery paradigm that has resulted in increased dependence on large volumes of information for decision making has created new challenges and opportunities in chemoinformatics research. The large volumes of data that are now available present an opportunity for the development of better predictive models, for the selection of more promising drug candidates, and for more comprehensive decisions to be made by researchers in chemistry and biology. The progress of this approach in drug discovery has also introduced challenges associated with the need to develop better tools to manage the large volumes of data. For chemistry-related research in particular, there is a need for more effective retrieval methods and better tools for data analysis that incorporate good interface design to facilitate the use of such systems by the non-expert scientist. This article reviews recent developments in the mining of large volumes of chemistry data, with a focus on chemoinformatics tools for small-molecule drug discovery and tools developed for analysis and in-depth mining. External sources of data, such as a variety of web services, further expand the volume of data to be analyzed during any small-molecule discovery project. The impact of the generation of large volumes of data and the related research factors is reshaping chemoinformatics work.


Long non-coding RNA CASC15 is upregulated in hepatocellular carcinoma and facilitates hepatocarcinogenesis.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for one-sixth of all malignant tumors, and the mortality rate of HCC ranks second among all cancer-related deaths. Increasing evidence has recently shown that long non-coding RNAs (lncRNAs) play an important role in cancer occurrence and progression, including HCC. Cancer susceptibility candidate 15 (CASC15), a lncRNA, has been reported to be involved in melanoma progression and phenotype switching. However, the function of CASC15 in human HCC is still unknown. In the present study, we evaluated expression of CASC15 and its potential functions in HCC. The expression of CASC15 in HCC tissues was quantitated by the reverse-transcription quantitative polymerase chain reaction, which showed that CASC15 was overexpressed in 59% (48/82) of HCC tissues compared with corresponding adjacent normal tissues, and the CASC15 expression level was significantly correlated with metastasis (P=0.012), tumor size (P=0.037), and TNM stage (P=0.013). Kaplan-Meier survival curves showed that high CASC15 expression was associated with poor prognosis in HCC patients (P<0.05). Moreover, a knockdown model of CASC15 was established, which showed that CASC15 significantly impaired HCC cell proliferation, migration, and invasion. CASC15 knockdown also induced cell apoptosis in vitro and impaired tumor growth in vivo. In conclusion, CASC15 plays an important role in the progression of HCC, acting as an oncogene. High expression of CASC15 is correlated with a poor prognosis, suggesting that CASC15 may be a predictive biomarker of HCC.


Assays for testing Pneumocystis carinii viability.
A series of classical vital stains and fluorescent indicator compounds were evaluated as viability assays of P. carinii. The combination of the acetoxymethyl ester of calcein with either ethidium homodimer or propidium iodide distinguished between live, dead and moribund organisms and provided high fluorescence intensity and low bleaching enabling photodocumentation at high magnifications.


An approach toward public hospital performance assessment.
Public hospitals have come under heavy scrutiny across the world owing to rising expenditures. However, much of the focus has been on cutting down costs to raise efficiency levels. Although not denying the importance of efficiency measures, this article targets a performance issue that is relevant to address the quality of services rendered in public hospitals. Thus, it is important to focus on the effectiveness of resource utilization in these hospitals. Consequently, this article seeks to examine the impact of average length of stay (ALOS) and bed turnover rates (BTR) on bed occupancy rates (BOR). Public hospital inpatient utilization records during the period 2006 to 2013 were gathered from the Ministry of Health, Malaysia. A 2-step generalized method of moments (GMM) statistical method was used to analyze the data. BOR was adopted as the dependent variable, whereas BTR and ALOS were used as the explanatory variables. The logarithm of total bed count (BED), admission (ADM), and patient days (PD) was deployed as control variables. Three regression models were developed to explore the correlates of BOR as a hospital performance measure. Ethics committee approval was waived because no patients were identified in the study. The statistical analyses show that ALOS and BTR are inversely correlated with BOR, with both coefficients significant at 1%. The control variables of BED, ADM, and PD had the right positive signs and they were significant in both sets of equations. Hence, reducing ALOS and BTR can help raise performance of public hospitals in Malaysia. In light of the robust results obtained, this study offers implications for improving public hospital performance. It shows a need to reduce ALOS and BTR in public hospitals to improve BOR.


COMT genotype predicts BOLD signal and noise characteristics in prefrontal circuits.
Prefrontal dopamine (DA) is catabolized by the COMT (catechol-O-methyltransferase) enzyme. Literature suggests that the Val/Met single nucleotide polymorphism (SNP) in the COMT gene predicts executive cognition in humans with Val carriers showing poorer performance due to less available synaptic DA. Recent fMRI studies are thought to agree with these studies having demonstrated prefrontal hyperactivation during n-back and attention-requiring tasks. This was interpreted as "less efficient" processing due to impaired signal-to-noise ratio (SNR) of neuronal activity. However, electrophysiological studies of neuronal SNR in primates and humans imply that prefrontal cortex should show a diminished prefrontal BOLD response in Val carriers. In the present study, we addressed the question of whether the prefrontal SNR of the BOLD response is decreased in Val carriers using a visual oddball task and an approach to analysis of fMRI data that maximizes noise characterization. We investigated N=17 homozygous Met carriers compared with N=24 Val carriers matched for age, sex, education, IQ, reaction time (variability) and head motion. Event-related fMRI was conducted presenting 160 visual stimuli (40 targets, checkerboard reversal). Subjects had to respond as quickly as possible to targets by button press. In the fMRI GLM [y(t)=beta*x(t)+c+e(t)] analysis, voxel-by-voxel 'activation' [y(t)] as well as residual noise variance [e(t)=sigma2] were calculated using a conservative full-width half maximum (FWHM=6 mm). As compared to Val carriers, we observed a stronger and more extended BOLD responses in homozygous Met carriers in left supplementary motor area (SMA) extending to ACC and dorsolateral prefrontal cortex. Vice versa, increased levels of noise were seen in Val carriers surrounding the peak activation maximum. In line with our expectations from prior electrophysiological studies, we observed a diminished BOLD response and increased noise in Val carriers. This suggests that the DA stabilizes cortical microcircuits by sharpening the signal and suppressing surrounding noise.


CranialVault and its CRAVE tools: a clinical computer assistance system for deep brain stimulation (DBS) therapy.
A number of methods have been developed to assist surgeons at various stages of deep brain stimulation (DBS) therapy. These include construction of anatomical atlases, functional databases, and electrophysiological atlases and maps. But, a complete system that can be integrated into the clinical workflow has not been developed. In this paper we present a system designed to assist physicians in pre-operative target planning, intra-operative target refinement and implantation, and post-operative DBS lead programming. The purpose of this system is to centralize the data acquired a the various stages of the procedure, reduce the amount of time needed at each stage of the therapy, and maximize the efficiency of the entire process. The system consists of a central repository (CranialVault), of a suite of software modules called CRAnialVault Explorer (CRAVE) that permit data entry and data visualization at each stage of the therapy, and of a series of algorithms that permit the automatic processing of the data. The central repository contains image data for more than 400 patients with the related pre-operative plans and position of the final implants and about 10,550 electrophysiological data points (micro-electrode recordings or responses to stimulations) recorded from 222 of these patients. The system has reached the stage of a clinical prototype that is being evaluated clinically at our institution. A preliminary quantitative validation of the planning component of the system performed on 80 patients who underwent the procedure between January 2009 and December 2009 shows that the system provides both timely and valuable information.


Automated Retinal Layer Segmentation Using Spectral Domain Optical Coherence Tomography: Evaluation of Inter-Session Repeatability and Agreement between Devices.
Retinal and intra-retinal layer thicknesses are routinely generated from optical coherence tomography (OCT) images, but on-board software capabilities and image scaling assumptions are not consistent across devices. This study evaluates the device-independent Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) for automated intra-retinal layer segmentation and image scaling for three OCT systems. Healthy participants (n = 25) underwent macular volume scans using a Cirrus HD-OCT (Zeiss), 3D-OCT 1000 (Topcon), and a non-commercial long-wavelength (1040nm) OCT on two occasions. Mean thickness of 10 intra-retinal layers was measured in three ETDRS subfields (fovea, inner ring and outer ring) using the Iowa Reference Algorithms. Where available, total retinal thicknesses were measured using on-board software. Measured axial eye length (AEL)-dependent scaling was used throughout, with a comparison made to the system-specific fixed-AEL scaling. Inter-session repeatability and agreement between OCT systems and segmentation methods was assessed. Inter-session coefficient of repeatability (CoR) for the foveal subfield total retinal thickness was 3.43μm, 4.76μm, and 5.98μm for the Zeiss, Topcon, and long-wavelength images respectively. For the commercial software, CoR was 4.63μm (Zeiss) and 7.63μm (Topcon). The Iowa Reference Algorithms demonstrated higher repeatability than the on-board software and, in addition, reliably segmented all 10 intra-retinal layers. With fixed-AEL scaling, the algorithm produced significantly different thickness values for the three OCT devices (P<0.05), with these discrepancies generally characterized by an overall offset (bias) and correlations with axial eye length for the foveal subfield and outer ring (P<0.05). This correlation was reduced to an insignificant level in all cases when AEL-dependent scaling was used. Overall, the Iowa Reference Algorithms are viable for clinical and research use in healthy eyes imaged with these devices, however ocular biometry is required for accurate quantification of OCT images.


[Studies on the effects of Siwu Mixture on reversing multidrug resistance of human erythrocyte leukemic cell line K562/ADM].
To study the effects of Siwu Mixture on reversing the multidrug resistance (MDR) of human erythrocyte leukemic cell line K562/ADM. With verapamil set as a positive control, MTT assay was applied to evaluate the resistant factor of cell line K562/ADM to anticancer drugs and the reversal index of Siwu Mixture on MDR of the cells. The concentration of adriamycin(ADM) in the cells was measured by reversal-phase high performance liquid chromatography. The immunofluorescence method was used to determine the expression of P-glucoprotein(Pgp) on cell membrane. When ADM was combined with Siwu Mixture, its concentration in the cells and the reversal index of MDR were significantly higher than those of blank control (P < 0.01). However, the expression of Pgp on cell membrane showed little difference ( P > 0.05). In case of noncytotoxic dose, Siwu Mixture showed significant effect on reversing MDR of cell line K562/ADM. The effect might be related to decreasing efflux of anticancer drugs in the cells and increasing their concentration in the cells. Nevertheless, it had no influence on the expression of Pgp on cell membrane.


Reactive oxygen generated by NADPH oxidase 1 (Nox1) contributes to cell invasion by regulating matrix metalloprotease-9 production and cell migration.
A mediating role of the reactive oxygen species-generating enzyme Nox1 has been suggested for Ras oncogene transformation phenotypes including anchorage-independent cell growth, augmented angiogenesis, and tumorigenesis. However, little is known about whether Nox1 signaling regulates cell invasiveness. Here, we report that the cell invasion activity was augmented in K-Ras-transformed normal rat kidney cells and attenuated by transfection of Nox1 small interference RNAs (siRNAs) into the cells. Diphenyleneiodonium (DPI) or Nox1 siRNAs blocked up-regulation of matrix metalloprotease-9 at both protein and mRNA levels in K-Ras-transformed normal rat kidney cells. Furthermore, DPI and Nox1 siRNAs inhibited the activation of IKKalpha kinase and the degradation of IkappaB alpha, suppressing the NFkappaB-dependent matrix metalloprotease-9 promoter activity. Additionally, epidermal growth factor-stimulated migration of CaCO-2 cells was abolished by DPI and Nox1 siRNAs, indicating the requirement of Nox1 activity for the motogenic effect of epidermal growth factor. This Nox1 action was mediated by down-regulation of the Rho activity through the low molecular weight protein-tyrosine phosphatase-p190RhoGAP-dependent mechanism. Taken together, our findings define a mediating role of Nox1-generated reactive oxygen species in cell invasion processes, most notably metalloprotease production and cell motile activity.


Nitrate absorption by corn roots : inhibition by phenylglyoxal.
Nitrate transport in excised corn (Zea mays L.) roots was inhibited by phenylglyoxal, but not by 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) or fluorescein isothiocyanate (FITC). Inhibition of nitrate uptake by a 1-hour treatment with 1 millimolar phenylglyoxal was reversed after 3 hours, which was similar to the time needed for induction of nitrate uptake. If induction of nitrate uptake occurs by de novo synthesis of a nitrate carrier, then the resumption of nitrate uptake in the inhibitor-treated roots may occur because of turnover of phenylglyoxal-inactivated nitrate carrier proteins. All three chemicals inhibited chloride uptake to varying degrees, with FITC being the strongest inhibitor. While inhibition due to DIDS was reversible within 30 minutes, both FITC and phenylglyoxal showed continued inhibition of chloride uptake for up to 3 hours after removal from the uptake solution. Assuming that the anion transporter polypeptide(s) carries a positive charge density at or near the transport site, the results indicate that the nitrate carrier does not carry any lysyl residues that are accessible to DIDS or FITC, whereas the chloride carrier does. Both chloride and nitrate carriers, however, seem to possess arginyl residues that are accessible to phenylglyoxal.


STUDENTS' PERCEPTION ABOUT THE CLINICO-ANATOMICAL CONFERENCES AS A TEACHING METHODOLOGY.
Anatomy has always been considered as an essential basis for clinical sciences. In recent decades there has been an increased trend towards incorporation of clinical problems in the teaching of anatomy. To promote clinical knowledge clinico-anatomical conferences have been conducted in our department for the last five years. This study has been undertaken to determine perception of medical students regarding these conferences and to formulate recommendations for their improvement based on feedback obtained from students. A cross-sectional study was conducted from December 2013 to January 2014 at the Lahore Medical & Dental College (LMDC), Lahore. A sample of 200 students of first and second year MBBS classes was selected for the study through convenience sampling technique. A 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree) was used to determine students' perception about clinic-anatomical conferences, using a self-administered questionnaire. Data was analysed using SPSS-19.0. Out of total 144 (72%) students were of the opinion that clinico-anatomical conferences were a good source of clinical knowledge, 126 (63%) opined that these conferences promoted understanding rather than memorization, 122 (61%) found them interesting, and 15 (30%) found improvement in their grades in the subject of anatomy after attending the conferences. The clinico-anatomical conferences were found interesting and reported to be a good source of clinical knowledge. It is recommended that these conferences should be conducted frequently, made interactive and patients should be presented as case studies during the conferences


Prolonged Intermittent Renal Replacement Therapy for Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome.
Patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 frequently develop severe acute kidney injury (AKI). Although continuous renal replacement therapy is the standard of care for critically ill patients, prolonged intermittent renal replacement therapy (PIRRT) may be a feasible option. We aimed to describe the tolerability and security of PIRRT treatments in COVID-19 patients with ARDS who required mechanical ventilation and developed severe AKI. We prospectively analyzed patients who underwent PIRRT treatments at a COVID-19 reference hospital in Mexico City. Intradialytic hypotension was defined as a systolic blood pressure decrease of ≥20 mm Hg or an increase of 100% in vasopressor dose. We identified 136 AKI cases (60.7%) in 224 patients admitted to the intensive care unit. Among them, 21 (15%) underwent PIRRT (130 sessions) due to stage 3 AKI. The median age of the cohort was 49 (range 36-73) years, 17 (81%) were male, 7 (33%) had diabetes, and the median time between symptoms onset and PIRRT initiation was 12 (interquartile range [IQR] 7-14) days. The median of PIRRT procedures for each patient was 5 (IQR 4-9) sessions. In 108 (83%) PIRRT sessions, the total ultrafiltration goal was achieved. In 84 (65%) PIRRT procedures, there was a median increase in norepinephrine dose of +0.031 mcg/kg/min during PIRRT (IQR 0.00 to +0.07). Intradialytic hypotensive events occurred in 56 (43%) procedures. Fifteen (12%) PIRRT treatments were discontinued due to severe hypotension. Vasopressor treatment at PIRRT session onset (OR 6.2, 95% CI 1.4-28.0, p: 0.02) and a pre-PIRRT lactate ≥3.0 mmol/L (OR 4.63, 95% CI 1.3-12.8, p: 0.003) were independently and significantly associated with the risk of hypotension during PIRRT. During follow-up, 11 patients (52%) recovered from AKI and respiratory failure and 9 (43%) died. Several adaptations to our PIRRT protocol during the COVID-19 outbreak are presented. PIRRT was feasible in the majority of COVID-19 patients with ARDS and severe AKI, despite frequent transitory intradialytic hypotensive episodes. PIRRT may represent an acceptable alternative of renal replacement therapy during the COVID-19 outbreak.


[Need for a substance abuse medicine qualified acute inpatient treatment program in alcohol dependence].
Based on the fact that alcoholism is a mainly psychiatric/psychotherapeutic problem, qualified treatment regimens for the detoxification of addicts have been established at different places. However, a standard treatment hasn't emerged yet, neither for clinical application nor as a basis for discussion between health insurances and clinics. The following article describes essential quality criteria of a qualified acute treatment regimen for addicts. We use existing models and our own experiences of two clinics for the treatment of substances abuse with between 1300 and 1500 admissions each per year.


Establishment and Persistence of Baculovirus penaei Infections in Cultured Pacific White Shrimp, Penaeus vannamei
The time course for establishment of a baculovirus (BP) infection and the persistence of infections in larvae and postlarvae of the Pacific white shrimp, Penaeus vannamei was investigated. In two preliminary studies, postlarvae were inoculated with BP and the prevalence of infections was monitored over 138- and 73-day periods. Viral polyhedra characteristic of patent infections first appeared 24 hr after inoculation, were present in all shrimp examined 14-17 days postinoculation (p.i.), and then decreased in prevalence during the remainder of each study. BP infections could not be detected by in situ hybridization in shrimp collected during the final day of each study. In a third and more comprehensive study, PCR-based diagnostic procedures were used to detect BP in experimentally infected shrimp over a 120-day period. In that study, BP was first detected in viral exposed mysis stage shrimp 12 hr p.i., was present in all shrimp examined by 72 hr p.i., and decreased in prevalence during the remainder of the study. BP infections could not be detected by PCR-based diagnostics in shrimp collected on the final day of the study. Only 1 of 10 previously infected shrimp collected at 31 days p.i. and diagnosed for BP by bioassay was infected. Results of this study indicate similarities between P. vannamei and some species of insects in the time required for establishment and loss of a patent baculovirus infection.


TERC telomerase subunit gene copy number in different disease stages of non-hodgkin lymphoma and in hepatitis C.
ABSTRACT Focal amplification of specific regions of the genome creates high copy number and expression of oncogenes in tumors. By applying fluorescence in situ hybridization (FISH) to leukocytes of hepatitis C (HCV) patients and non-Hodgkin lymphoma (NHL) patients, we estimated gene dosage of the TERC gene at 3q26.3. Higher TERC copy numbers were found in NHL at diagnosis compared to HCV patient groups. Higher TERC copy numbers were also observed in NHL patient at diagnosis and relapse compared to patients in remission. We believe that the TERC gene amplification is involved in the process of genetic instability leading to tumor genesis such as in NHL.


Apoptosis of hepatitis B virus-infected hepatocytes prevents release of infectious virus.
Apoptosis of infected cells is critically involved in antiviral defense. Apoptosis, however, may also support the release and spread of viruses. Although the elimination of infected hepatocytes is required to combat hepatitis B virus (HBV) infection, it is still unknown which consequences hepatocyte apoptosis has for the virus and whether or not it is advantageous to the virus. To study this, we designed a cell culture model consisting of both HBV-producing cell lines and primary human hepatocytes serving as an infection model. We showed that the release of mature, enveloped virions was 80% to 90% reduced 24 h after the induction of apoptosis in HBV-replicating hepatoma cells or HBV-infected hepatocytes. Importantly, HBV particles released from apoptotic hepatocytes were immature and nonenveloped and proved not to be infectious. We found an inverse correlation between the strength of an apoptotic stimulus and the infectivity of the virus particles released: the more potent the apoptotic stimulus, the higher the ratio of nonenveloped capsids to virions and the lower their infectivity. Furthermore, we demonstrated that HBV replication and, particularly, the expression of the HBx protein transcribed from the viral genome during replication do not sensitize cells to apoptosis. Our data clearly reject the hypothesis that the apoptosis of infected hepatocytes facilitates the propagation of HBV. Rather, these data indicate that HBV needs to prevent the apoptosis of its host hepatocyte to ensure the release of infectious progeny and, thus, virus spread in the liver.


Asbestos fibers in human lung: forensic significance.
Asbestos is a fibrous mineral which, because of its unique properties, has innumerable applications in many industries and is used in a large variety of consumer products. It has become ubiquitous and is woven, literally and figuratively, into the fabric of our present-day civilization. However, its presence is sometimes unknown and unsuspected by those who are exposed to asbestos by virtue of occupation or environment and inhale its fibers. Exposed workers and even urban dwellers may have a variable lung burden of asbestos fibers. There is indisputable clinical, pathological, experimental and epidemiological proof that, after varying periods of latency, asbestos may cause benign and malignant disease often leading to disability or death. Forensic investigation of suspected asbestos-related deaths includes a life-time occupational history, a complete autopsy, and identification of the asbestos fiber tissue burden. The latter usually requires special procedures.


Paraneoplastic acquired haemophilia A in extensive-stage small cell lung cancer (ES-SCLC) in the era of immunotherapy.
Small cell lung cancer (SCLC) is a deadly and rapidly progressive disease that can present with various paraneoplastic syndromes on initial workup. Acquired factor VIII (FVIII) deficiency, also known as acquired haemophilia A (AHA), has been identified as a rare paraneoplastic syndrome in SCLC. Here, we present a 61-year-old woman with a massive gastrointestinal bleed and prolonged activated partial thromboplastin time (PTT) in the emergency department. She was diagnosed with rare paraneoplastic AHA secondary to extensive-stage SCLC (ES-SCLC). She was treated with high-dose steroids and factor bypassing agents, which led to the resolution of bleeding and undetectable FVIII inhibitor levels. She was subsequently treated for ES-SCLC with carboplatin, etoposide and atezolizumab. This case report highlights a rare clinical presentation of paraneoplastic AHA that necessitates prompt recognition in patients with SCLC with ongoing bleeding and elevated PTT.


Development of isotope dilution cold vapor inductively coupled plasma mass spectrometry and its application to the certification of mercury in NIST standard reference materials.
An isotope dilution cold vapor inductively coupled plasma mass spectrometry (ID-CV-ICPMS) method featuring gaseous introduction of mercury via tin chloride reduction has been developed and applied to the quantification and certification of mercury in various NIST standard reference materials: SRM 966 Toxic Metals in Bovine Blood (30 ng x mL(-1)); SRM 1641d Mercury in Water (1.6 microg x mL(-1)); and SRM 1946 Lake Superior Fish Tissue (436 ng x g(-1)). Complementary mercury data were generated for SRMs and NIST quality control standards using cold vapor atomic absorption spectroscopy (CVAAS). Certification results for the determination of mercury in SRM 1641d using two independent methods (ID-CV-ICPMS and CVAAS) showed a degree of agreement of 0.3% between the methods. Gaseous introduction of mercury into the ICPMS resulted in a single isotope sensitivity of 2 x 10(6) counts x s(-1)/ng x g(-1) for 201Hg and significantly reduced the memory and washout effects traditionally encountered in solution nebulization ICPMS. Figures of merit for isotope ratio accuracy and precision were evaluated at dwell times of 10, 20, 40, 80, and 160 ms using SRM 3133 Mercury Spectrometric Solution. The optimum dwell time of 80 ms yielded a measured 201Hg/202Hg isotope ratio within 0.13% of the theoretical natural value and a measurement precision of 0.34%, on the basis of three replicate injections of SRM 3133.


Location of the nonidentical two reactive lysine residues in the myosin molecule.
We previously reported ((1979) J. Biochem. 85, 747-753) that both of the burst and nonburst heads contain one reactive lysine residue per head, and that only the reactive lysine residue in the burst head is trinitrophenylated in the presence of PP1 whereas both reactive lysine residues are modified in the absence of PP1. In the present study, subfragment one (S-1) prepared from trinitrophenyl (TNP) myosin was subjected to a limited tryptic digestion, a BrCN cleavage, and a thorough tryptic and alpha-chymotryptic digestion, and the TNP peptides thus obtained were analyzed by SDS-gel electrophoresis and by gel filtration. In the limited digestion, it was found that the reactive lysine residues are both located in the tryptic peptide of 25-27 K daltons containing the N-terminus of the heavy chain and not in the 19-21 K peptide containing reactive thiols. In the BrCN cleavage, it was found that the reactive lysine residues are not located in the 17 K peptide containing the essential arginine residues (Morkin, E., et al. (1979) J. Biol. Chem. 254, 12647-12652). In the thorough digestion, S-1 prepared from myosin modified in the absence of PP1 gave two equimolar fractions of TNP peptides in Sephadex G-25 column chromatography, whereas that of S-1 prepared from myosin modified in the presence of PP1 gave a single fraction of TNP peptide which corresponds in size to one of two fractions of TNP peptides obtained above. These findings strongly suggest that the chemical structure around the reactive lysine residue in the burst head is different from that in the nonburst head.


[Hypokinesia: a health related risk factor].
Results of numerous epidemiological and experimental studies show that insufficient physical activity (hypokinesia) is an important factor in development of chronic degenerative diseases. It has been proved that insufficient physical activity aggravates insulin resistance, a latent and asymptomatic metabolic disorder that causes hyperinsulinemia. On the other hand, there are multiyear, multidiscipline, prospective clinical studies which have established a significant correlation between general physical ability (measured by maximal oxygen consumption: VO2max) and the capability of metabolic system to produce energy: physical fitness=metabolic fitness. It is possible to precisely diagnose the newest, up to now inaccessible risk factor for health. Our attitude is that measurement of VO2max has to be a standard practice. Quantification means precise diagnosis of hypokinesia. Physical activity for preventive and therapeutic purposes is rational, effective and optimal way. It makes it possible to choose adequate therapy programs and their dosage (intensity, volume, form and duration). We can follow-up therapy effects, achievements and maintain our goal (medium level of general aerobic ability). Low aerobic ability should be treated as a significant independent risk factor for development of insulin-independent diabetes and arteriosclerosis. At the same time this risk factor can easily be affected using natural, physiological mechanisms which are favorable, but simple, inexpensive and practically lifelong.


Immune dysregulation in the aging human lung.
Aging has been associated with diminished lung function and increased susceptibility to lung infection. To determine whether changes suggestive of immune dysregulation and inflammation appear in the lungs of clinically normal individuals as a function of advancing age, we performed bronchoalveolar lavage (BAL) on discontinuous age groups (20-36, 45-55, and 65-78 yr old) of clinically normal volunteer subjects. We measured immunoglobulin (IgG, IgA, IgM), albumin, interleukin-6 (IL-6), and interleukin-10 concentrations in BAL fluid. Bronchoalveolar cell profiles, cell surface antigen expression, and superoxide anion production were also measured. A significant increase in total cell concentration, neutrophils, and BAL immunoglobulin content was observed in the oldest age group compared with the youngest age group. Mean lymphocyte subset (CD4+/CD8+) ratios were significantly increased in blood (2.6 +/- 0.4 versus 1.6 +/- 0.1; p<0.03) and to a greater degree in BAL (4.8 +/- 1.0 versus 1.9 +/- 0.2; p<0.01) for the oldest versus youngest age groups. Similarly, BAL-derived cells displayed significantly increased phorbol myristate acetate-stimulated release of superoxide anion (8.8 +/- 1.3 versus 4.5 +/- 0.7 nmol/5 x 10 5 cells/h; p<0.01) for the oldest versus youngest subject group, and mean BAL IL-6 concentrations were significantly elevated in the oldest age group (0.86 +/- 0.13 ng/ml) compared with the youngest age group (0.53 +/- 0.03 ng/ml; p<0.01). Our observations suggest that altered inflammatory cell profiles and low-grade inflammation exist in the lower respiratory tracts of many asymptomatic, clinically normal volunteers of advanced age.


[Efficacy and adverse effects of film coated praziquantel for treatment of schistosomiasis japonica].
To understand the adverse and curative effects of film coated praziquantel for treatment of schistosomiasis japonica. A questionnaire survey was conducted among 6 to 65 years old inhabitants from epidemic areas of schistosomiasis japonica in Jiangxi, Anhui and Hubei provinces, while indirect haemagglutination assay (IHA) was also administrated. The Serological positives were tested by Kato-Katz technique. A total of 509 habitats of serological positives and healthy persons were given praziquantel. 460 targets with no relative symptoms were followed up for adverse effect of drugs in one month and efficacy evaluation of praziquantel was carried out in 104 parasitological positives 3 months post-treatment. The 84.7% (144/170) individuals thought film coated tablets were no smell or only with little smell while 92.9%(315/339) targets in control group fell that tablets smelled bad. The total side effect rates of film coated praziquantel group and control group in 1-2 hours post-treatment were 20.30% (27/133) and 83.18% (272/327) respectively. There was significantly different between two groups (chi(2) = 164.316, P < 0.05). The adverse effect rates of film coated praziquantel group in neuromuscular system, digestive system and cardiovascular system were 15.79% (21/133), 9.77% (13/133), 2.26% (3/133) individually which were significantly lower than those of control groups with 81.65% (267/327), 49.24% (161/327), 12.84% (42/327) in corresponding systems (chi(2)(neuromuscular system) = 175.188, chi(2)(digestive system) = 62.601, chi(2)(cardiovascular system) = 12.010, P < 0.05). And the adverse effect rate of allergic reaction of film coated group was no significant difference with control group (2.26%(3/133) versus 0.92% (3/327), chi(2) = 1.315, P = 0.235). One day after treatment, the adverse effect rate of film coated tablets of praziquantel decreased to 3.01% (4/133), significantly lower than that of control group (P < 0.05). There was no significant difference after 2 weeks treatment while the adverse effect rates decreased to 0.75%(1/133), 0.61% (2/327) in film coated praziquantel group and control group respectively (chi(2) = 0.029, P = 0.642). The curative rates 3 months post treatment were 84.91% (45/51) in film coated tablets of praziquantel group and 82.35% (42/53) in control group without significant difference (chi(2) = 1.536, P = 0.215). The smell and adverse effects of film coated tablets of praziquantel were decreased significantly and its efficacy for treatment of schistosomiasis japonica was equal to the control tablets. The film coated tablets of praziquantel might be applied in field widely after a further verification.


Increased risk of stroke in patients with coronary artery disease and sleep apnea: a 10-year follow-up.
The effect of sleep apnea on mortality and cardiovascular morbidity is mainly unknown. We aimed to study whether sleep apnea is related to stroke, death, or myocardial infarction in patients with symptomatic coronary artery disease. A total of 392 men and women with coronary artery disease referred for coronary angiography were examined by use of overnight sleep apnea recordings. Sleep apnea, defined as an apnea-hypopnea index >or=5, was recorded in 54% of the patients. All patients were followed up prospectively for 10 years, and no one was lost to follow-up. Stroke occurred in 47 (12%) of 392 patients during follow-up. Sleep apnea was associated with an increased risk of stroke, with an adjusted hazard ratio of 2.89 (95% confidence interval 1.37 to 6.09, P=0.005), independent of age, body mass index, left ventricular function, diabetes mellitus, gender, intervention, hypertension, atrial fibrillation, a previous stroke or transient ischemic attack, and smoking. Patients with an apnea-hypopnea index of 5 to 15 and patients with an apnea-hypopnea index >or=15 had a 2.44 (95% confidence interval 1.08 to 5.52) and 3.56 (95% confidence interval 1.56 to 8.16) times increased risk of stroke, respectively, than patients without sleep apnea, independent of confounders (P for trend=0.011). Death and myocardial infarction were not related to sleep apnea. Intervention in the form of coronary artery bypass grafting or percutaneous coronary intervention was related to a longer survival but did not affect the incidence of stroke. Sleep apnea is significantly associated with the risk of stroke among patients with coronary artery disease who are being evaluated for coronary intervention.


Medically induced labor: Epidural analgesia and women's perceptions of pain in early labor.
Approximately 25% of all deliveries in Denmark are medically induced, typically characterized by more intense uterine contractions. The aim of this paper is to investigate the differences in the administration of epidural analgesia and pain experience between spontaneous and medically induced labor in nulliparous and multiparous women. This is a prospective case-controlled study of 100 participating women in labor. The primary outcome was the timing of administration of epidural analgesia, by delivery progression and frequency. Pain scores were indicated by the McGill Pain Questionnaire and the duration of pain was also notified. In nulliparous and multiparous women, medically induced labor was associated with earlier administration of epidural analgesia in relation to the onset of labor pain, compared to women with a spontaneous onset of labor (10.4 vs 26.10 hours, p=0.0). There was a trend, however not statistical, in the use of epidural analgesia in relation to delivery progression, assessed as dilation of the cervix (3 cm vs 4.5 cm, p=0.07) and towards higher frequency for medically induced labor (51.5% vs 32.8%, p=0.07). In nulliparous women, a reduced period of labor pain was shown in medically induced deliveries compared to spontaneous deliveries (9.30 vs 19.00 hours, p=0.03). However, no significant differences in experienced pain were shown (Score: 28.70 vs 29.60, p=0.194). Epidural analgesia was administered earlier, and duration of experienced pain was shorter in medically induced labor, in comparison to spontaneous deliveries. However, the experienced pain was not different, possibly explained by a more intense labor process.


Self-association of naphthalene at the air-ice interface.
We present a molecular dynamics study of the interactions between two molecules of naphthalene present at air-water versus air-ice interfaces. In agreement with the inference from our previous experimental work [Kahan, T. F.; Donaldson, D. J. J. Phys. Chem. A 2007, 111, 1277], the results suggest that self-association of the molecules is more likely to take place on the ice surface than on the water surface. A shorter average distance between the two naphthalene molecules, in conjunction with a stronger interaction energy and free energy of association, point to a stronger tendency to self-associate on ice than on water. The distinct behavior at the two interfaces appears be due to more favorable interactions between naphthalene molecules on liquid water surfaces than on ice surfaces.


Diagnostic Concordance of Cytology and Histology in Samples Obtained via Endoscopic Ultrasound-Guided Fine-Needle Biopsy (EUS-FNB).
Introduction Endoscopic ultrasound (EUS)-guided fine-needle aspiration and biopsy (FNA/FNB) to obtain cytological aspirates and histological core samples, respectively, are the standard of care for diagnosing lesions in/adjacent to the upper/lower gastrointestinal tract. Due to the lack of standardization of tissue processing, it is unclear whether core samples should be sent only for histology (formalin) or cytology (CytoLyt), or both. The aim of this study was to investigate the diagnostic concordance rates between cytology and histology on EUS-FNB core samples. Methods A total of 227 patients underwent EUS-FNB between October-2017 and February-2019 by a single therapeutic endoscopist; 44 core-tissue samples (41 patients) were placed alternately in CytoLyt (cytology) and formalin (histology), with equal passes into each, to best achieve a proportionate sample amount. The patient's demographics, medical history, pertinent imaging, EUS indication/findings were reviewed. Main outcomes included concordance rates between cytology-histology and diagnostic accuracy for malignancy. Results Cytology and histology were discordant in five cases (11.5%); four with negative cytology but a definite diagnosis of malignancy achieved with histology. One case was suspected as neoplasm on cytology but further characterized as benign on histology. Cytology failed to sub-characterize an additional four mass-like pancreatic benign entities, due to inadequate tissue architecture assessment in the CytoLyt sample. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology for diagnosis of malignancy were 87.88% (95%CI: 71.8-96.6), 90.91% (95%CI: 58.7-99.7), 96.67% (95%CI: 81.6-99.4), and 71.43% (95%CI: 49.4-86.4). Discussion We observed 11.5% diagnostic discordance between cytology and histology on EUS-FNB core samples, with histology being superior. Future multicenter prospective randomized studies are needed to establish an accurate and cost-effective diagnostic process.


Peripheral arterial disease in diabetic patients with renal insufficiency: a review.
Peripheral arterial disease is common among diabetic patients with renal insufficiency, and most of the diabetic patients with end-stage renal disease (ESRD) have peripheral arterial disease. Ischaemia is probably overrepresented as an etiological factor for a diabetic foot ulcer in this group of patients compared with other diabetic patients. ESRD is a strong risk factor for both ulceration and amputation in diabetic patients. It increases the risk of nonhealing of ulcers and major amputation with an OR of 2.5-3. Renal disease is a more important predictor of poor outcome after revascularizations than commonly expected. Preoperative vascular imaging is also affected by a number of limitations, mostly related to side effects of contrast agents poorly eliminated because of kidney dysfunction. Patients with renal failure have high perioperative morbidity and mortality. Persistent ischaemia, extensive infection, forefoot and heel gangrene, poor run-off, poor cardiac function, and the length of dialysis-dependent renal failure all affect the outcome adversely. Despite dismal overall outcome, recent data indicate that by proper selection, favourable results can be obtained even in ESRD patients, with the majority of studies reporting 1-year limb salvage rates of 65-75% after revascularization among survivors. High 1-year mortality of 38% reported in a recent review has to be taken into consideration, though. The preferential use of endovascular-first approach is attractive in this vulnerable multimorbid group of patients, but the evidence for endovascular treatment is very scarce. The need for complete revascularization of the foot may be even more important than in other patients with ischaemic ulcerated diabetic foot because there are a number of factors counteracting healing in these patients. Typically, half of the patients are reported to lose their legs despite open bypass. To control tissue damage and improve chances of ulcer healing, one should understand that early referral to vascular consultation is necessary.


Current Management of Patients With Acquired Solitary Kidney.
Persons with acquired solitary kidney, including those who have had a unilateral nephrectomy for living kidney donation, renal malignancies, or trauma, have decreased renal mass that leads to increased intraglomerular pressure and glomerular hyperfiltration. These physiologic adaptations of solitary kidney may exacerbate other preexisting and genetic conditions that could create a predisposition to or worsen glomerular pathologies, leading to unfavorable renal outcomes. Hence, these persons may benefit from special care and lifestyle modifications, including nutritional interventions. There is a lack of consensus and evidence for proper surveillance and management after nephrectomy, and misconceptions in both directions of having a "normal" versus "abnormal" kidney status may cause confusion among patients and healthcare providers pertaining to long-term kidney health monitoring and management. We have reviewed available data on the impact of lifestyle modifications, particularly nutritional measures, and pharmacologic interventions, on short- and long-term outcomes after nephrectomy. We recommend avoidance of excessively high dietary protein intake (>1 g/kg per day) and high dietary sodium intake (>4 grams/d), adequate dietary fiber intake from plant-based foods, a target body mass index of <30 kg/m2 (in non-athletes and non-bodybuilders), and judicious management of risk factors of progressive chronic kidney disease (CKD), and future studies should help to better determine optimal care practices for these persons.


Role of splenectomy in incidence and severity of acute graft-versus-host disease: a multicenter study of 157 patients.
Allogeneic bone marrow transplantation is a therapeutic option for many hematological malignancies. Graft-versus-host disease (GVHD) remains one of the major complications and has a high mortality rate. The pathophysiological mechanisms involved are poorly understood and GVHD prevention regimens still give disappointing results. This study concerned 157 patients with diverse diagnoses from Bordeaux, Grenoble and Marseille who had undergone an HLA-matched transplantation without T cell depletion. Thirty-one patients (20%) had been splenectomized before transplantation. The role of splenectomy in the incidence and severity of acute GVHD was investigated using a univariate and multivariate analysis of 11 risk factors including splenectomy. Univariate analysis found three significant risk factors linked with GVHD incidence: splenectomy, age of recipient and GVHD prevention by monotherapy versus a combination of methotrexate plus cyclosporin. Multivariate analysis retained only the effects of age and GVHD prevention on GVHD incidence and showed that splenectomy was the most important factor in GVHD severity. One explanation for the role of splenectomy could be the spleen's possible function as a filter of activated T lymphocytes from the transplant. We therefore concluded that it would be preferable to abstain from splenectomizing patients before transplantation although splenectomy is still advisable in certain malignancies after transplantation.


Effects of Exercise on Parkinson's Disease: A Meta-Analysis of Brain Imaging Studies.
Exercise is increasingly recognized as a key component of Parkinson's disease (PD) treatment strategies, but the underlying mechanism of how exercise affects PD is not yet fully understood. The activation likelihood estimation (ALE) method is used to study the mechanism of exercise affecting PD, providing a theoretical basis for studying exercise and PD, and promoting the health of patients with PD. Relevant keywords were searched on the PubMed, Cochrane Library, and Web of Science databases. Seven articles were finally included according to the screening criteria, with a total sample size of 97 individuals. Using the GingerALE 3.0.2 software, an ALE meta-analysis was performed using seven studies that met the requirements, and the probability of the cross-experiment activation of each voxel was calculated. The meta-analysis produced seven clusters, and major activations were found in the cerebellum, occipital lobe, parietal lobe, and frontal lobe brain regions. Exercise for PD mainly results in the enhanced activation of the cerebellum, occipital lobe, parietal lobe, and frontal lobe. Exercise for PD does not cause a change in the activation of a single brain area, and the observed improvement may result from coordinated changes in multiple brain areas.


Beyond drug-induced alteration of glutamate homeostasis, astrocytes may contribute to dopamine-dependent intrastriatal functional shifts that underlie the development of drug addiction: A working hypothesis.
The transition from recreational drug use to compulsive drug-seeking habits, the hallmark of addiction, has been shown to depend on a shift in the locus of control over behaviour from the ventral to the dorsolateral striatum. This process has hitherto been considered to depend on the aberrant engagement of dopamine-dependent plasticity processes within neuronal networks. However, exposure to drugs of abuse also triggers cellular and molecular adaptations in astrocytes within the striatum which could potentially contribute to the intrastriatal transitions observed during the development of drug addiction. Pharmacological interventions aiming to restore the astrocytic mechanisms responsible for maintaining homeostatic glutamate concentrations in the nucleus accumbens, that are altered by chronic exposure to addictive drugs, abolish the propensity to relapse in both preclinical and, to a lesser extent, clinical studies. Exposure to drugs of abuse also alters the function of astrocytes in the dorsolateral striatum, wherein dopaminergic mechanisms control drug-seeking habits, associated compulsivity and relapse. This suggests that drug-induced alterations in the glutamatergic homeostasis maintained by astrocytes throughout the entire striatum may interact with dopaminergic mechanisms to promote aberrant plasticity processes that contribute to the maintenance of maladaptive drug-seeking habits. Capitalising on growing evidence that astrocytes play a fundamental regulatory role in glutamate and dopamine transmission in the striatum, we present an innovative model of a quadripartite synaptic microenvironment within which astrocytes channel functional interactions between the dopaminergic and glutamatergic systems that may represent the primary striatal functional unit that undergoes drug-induced adaptations eventually leading to addiction.


Diagnostic Accuracy of Fecal Calprotectin for Pediatric Inflammatory Bowel Disease in Primary Care: A Prospective Cohort Study.
In specialist care, fecal calprotectin (FCal) is a commonly used noninvasive diagnostic test for ruling out inflammatory bowel disease (IBD) in children with chronic gastrointestinal symptoms. The aim of this study was to evaluate the diagnostic accuracy of FCal for IBD in symptomatic children in primary care. We studied 2 prospective cohorts of children with chronic diarrhea, recurrent abdominal pain, or both: children initially seen in primary care (primary care cohort) and children referred to specialist care (referred cohort). FCal (index test) was measured at baseline and compared with 1 of the 2 reference standards for IBD: endoscopic assessment or 1-year follow-up. Physicians were blinded to FCal results, and values greater than 50 μg/g feces were considered positive. We determined specificity in the primary care cohort and sensitivity in the referred cohort. None of the 114 children in the primary care cohort ultimately received a diagnosis of IBD. The specificity of FCal in the primary care cohort was 0.87 (95% CI, 0.80-0.92). Among the 90 children in the referred cohort, 17 (19%) ultimately received a diagnosis of IBD. The sensitivity of FCal in the referred cohort was 0.99 (95% CI, 0.81-1.00). The findings of this study suggest that a positive FCal result in children with chronic gastrointestinal symptoms seen in primary care is not likely to be indicative of IBD. A negative FCal result is likely to be a true negative, which safely rules out IBD in children in whom a primary care physician considers referral to specialist care.


Identification of Shared Genes and Pathways in Periodontitis and Type 2 Diabetes by Bioinformatics Analysis.
It is well known that the presence of diabetes significantly affects the progression of periodontitis and that periodontitis has negative effects on diabetes and diabetes-related complications. Although this two-way relationship between type 2 diabetes and periodontitis could be understood through experimental and clinical studies, information on common genetic factors would be more useful for the understanding of both diseases and the development of treatment strategies. Gene expression data for periodontitis and type 2 diabetes were obtained from the Gene Expression Omnibus database. After preprocessing of data to reduce heterogeneity, differentially expressed genes (DEGs) between disease and normal tissue were identified using a linear regression model package. Gene ontology and Kyoto encyclopedia of genes and genome pathway enrichment analyses were conducted using R package 'vsn'. A protein-protein interaction network was constructed using the search tool for the retrieval of the interacting genes database. We used molecular complex detection for optimal module selection. CytoHubba was used to identify the highest linkage hub gene in the network. We identified 152 commonly DEGs, including 125 upregulated and 27 downregulated genes. Through common DEGs, we constructed a protein-protein interaction and identified highly connected hub genes. The hub genes were up-regulated in both diseases and were most significantly enriched in the Fc gamma R-mediated phagocytosis pathway. We have identified three up-regulated genes involved in Fc gamma receptor-mediated phagocytosis, and these genes could be potential therapeutic targets in patients with periodontitis and type 2 diabetes.


Digital image DNA cytometry: a useful tool for the evaluation of malignancy in biliary strictures.
Cytologic evaluation of the biliary tract strictures is nowadays widely used for distinguishing between benign and malignant lesions but remains a challenge for some problematic cases. Digital Image cytometry (DNA-cytometry) helps cytopathologists to resolve some unclear situations. We have analysed 41 specimens of bile duct brushings obtained from patients during ERCP (11 benign cases, 7 suspicious for malignancy cases and 23 malignant cases) by DNA-cytometry and correlated them with the histological biopsy counterpart. All eleven cytological and histological benign cases were DNA-diploid and among 22 patients with malignant cytological and histological diagnosis 21 were DNA-aneuploid. One case considered malignant by the cytopathologist revealed DNA-aneuploid but malignancy could not be confirmed by histology. The analysis of the suspicious for malignancy cases revealed that all DNA-aneuploid cases were malignant and all DNA-diploid cases were benign referring to the follow-up of the patients. The comparison between cytology alone and cytology combined with DNA-cytometry related to the histological diagnosis (gold standard) resulted in a sensitivity of 100% and a specificity of 79% for cytology alone; a specificity of 94% and a sensitivity 92% for DNA-cytometry and a specificity of 93% and a sensitivity of 100% with combined analyses. The positive predictive value was 90% for cytology, 96% for DNA-cytometry and for both analyses. The negative predictive value showed 100% for cytology, 89% for DNA-cytometry and 100% for combined studies. Despite the limited number of patients involved in the study, the results obtained indicate an increased of specificity and of positive predictive value using DNA-cytometry. These results confirm the pertinence of these method for challenging cases, in conjunction with other available diagnostic tools.


The role of vacuolar digestive system in preventing cadmium poisoning in Acanthamoeba castellanii.
Constituents showing cadmium affinity were found in digestive residues of the vacuolar digestive system in Acanthamoeba. Cadmium was detected by means of X-ray analysis in complexes appearing both in residues included within the digestive vacuoles and in those egested outside the cell. The digestive vacuolar system in Acanthamoeba castellanii is characterized by a particularly high turnover rate (4). Confronted with this fact, results of the present study suggest that the system is able to egest rapidly the ligand-bound cadmium. In this way protects the amoeba against serious toxic effects of the Cd-polluted environment.


Vulnerable narcissism: commentary for the special series "Narcissistic personality disorder--new perspectives on diagnosis and treatment".
Comments on the articles by A. E. Skodol et al. (see record 2013-24395-001), E. Ronningstam (see record 2014-42878-005), D. Diamond et al. (see record 2014-42878-004), and A. L. Pincus et al. (see record 2014-01439-001). The tie that binds these four articles together is the respective authors' emphasis on the vulnerability- emotional, self-esteem/ego, interpersonal- that they consider to be central to pathological narcissism. The current authors agree that it is important that the field acknowledge both grandiose and vulnerable aspects of narcissism (e.g., Miller & Campbell, 2008), but they wonder whether the pendulum is now swinging too far back in the direction of vulnerability.


Effect of the Hemin Molecular Complexes on the Structure and Properties of the Composite Electrospun Materials Based on Poly(3-hydroxybutyrate).
The creation of innovative fibrous materials based on biodegradable semicrystalline polymers and modifying additives is an urgent scientific problem. In particular, the development of biomedical materials based on molecular complexes and biopolymers with controlled properties is of great interest. The paper suggests an approach to modifying the structure and properties of the composite materials based on poly(3-hydroxybutyrate) (PHB) obtained by the electrospinning method using molecular complexes of hemin. The introduction of 1-5 wt. % of hemin has a significant effect on the supramolecular structure, morphology and properties of PHB-based fibers. Changes in the supramolecular structure intensified with the increasing hemin concentration. On the one hand, a decrease in the fraction of the crystalline phase by 8-10% was observed. At the same time, there is a decrease in the density of the amorphous phase by 15-70%. Moreover, the addition of hemin leads to an improvement in the strength characteristics of the material: the elongation at break increased by 1.5 times, and in the tensile strength, it increased by 3 times. The antimicrobial activity of the hemin-containing composite materials against Escherichia coli and Staphylococcus aureus was confirmed. The obtained materials are proposed to be used in the creation of composite systems for regenerative medicine.


Abandonment of antiretroviral therapy among HIV-positive patients attended at the reference center for HIV/AIDS in Vitória, Brazil.
This study evaluates the risk factors for the abandonment of antiretroviral therapy (ART) among patients receiving care in an AIDS clinic in Vitória, Brazil. We conducted a case-control study of patients with AIDS attending a reference center for sexually transmitted disease (STD)/AIDS. A total of 62 patients, who abandoned therapy in 2008, and 188 HIV-infected patients answered an interview including demographic, social, and clinical characteristics. Risk factors associated with abandon in univariate analysis were entered into logistic regression models. A total of 250 patients were included in the study. Groups were similar regarding age, gender, and monthly income. In the final multivariate model, illicit drug use (adjusted odds ratio [AOR], 2.3; 95% confidence interval [CI], 1.03-5.07), previous abandon of medication (AOR 38.6; 95% CI 10.49-142.25), last CD4 count <200 cells/mm(3) (AOR 1.5; 95% CI 1.03-2.10), and viral load higher than 1000 copies/mL (AOR 2.0 (95% CI 1.34-3.09) were independent predictors of abandonment of ART. In addition to the clinical indicators, behavioral factors remained important throughout the multivariate analysis in our study.


Does Man Marking Influence Running Outputs and Intensity During Small-Sided Soccer Games?
Aasgaard, M and Kilding, AE. Does man marking influence running outputs and intensity during small-sided soccer games? J Strength Cond Res 34(11): 3266-3274, 2020-Small-sided games (SSGs) are considered an effective training tool for physical development in soccer. Small-sided games can be modified in several ways to manipulate the physical demands to best match the game demands, player characteristics, and session objectives. The aim of this study was to compare the physiological, perceptual, and Global Positioning System (GPS)-derived time-motion characteristics of man marking (MM) vs. non-man marking (NMM) in 2v2, 3v3, and 4v4 SSGs. In an acute crossover design, 8 amateur soccer players (mean age ± SD: 23.6 ± 3.3 years) played 2v2, 3v3, and 4v4 SSGs consisting of 4 × 4-minute bouts, with 2-minute passive recovery. During all SSGs, players wore a heart rate (HR) monitor and GPS unit and reported their rating of perceived exertion (RPE). Average percent HR (%HRave) induced small to moderate effects with MM compared with NMM (%Δ = 1-2.7%; effect size [ES] = 0.22-0.65). Comparisons between MM formats indicated a decrease in %HRave with increased player numbers (%Δ = 1.6-3.5%; ES = 0.39-0.86). Perceptual load increased with MM compared with NMM (%Δ = 6.7-17.6%; ES = 0.66-2.09), whereas increases in player numbers (MM only) reduced RPE output (%Δ = 9.4-24.3%; ES = 1.14-3.61). Time-motion characteristics revealed substantially greater total distance covered in MM irrespective of player number (%Δ = 6.8-14.7%; ES = 1.34-2.82). There were very likely increases in distances covered at striding (13.1-17.8 km·h) (%Δ: 23.4-33.2; ES = 2.42-4.35) and high-intensity running (HIR) (17.9-21 km·h) (%Δ: 47.3-104; ES = 0.91-1.68) for MM compared with NMM irrespective of player number. In conclusion, MM substantially elevated perceptual load and distances from striding to HIR regardless of player number, whereas differences between NMM and MM for internal load remain unclear. Use of MM may allow coaches to condition for particularly demanding phases of the game and prescription of larger SSG formats to increase distance covered at higher velocities.


Lipase-catalyzed preparation of S-propranolol in presence of hydroxypropyl beta-cyclodextrins.
A simple method for the preparation of S-propranolol catalyzed by a Rhizopus niveus lipase in an aqueous medium is described. Hydroxypropyl-beta-cyclodextrin was used for the first time to increase the solubility of (R,S)-O-butyryl propranolol thus permitting the reaction to be carried out in water. The formation of an inclusion complex between (R,S)-O-butyryl propranolol and hydroxypropyl-beta-cyclodextrin was studied and a stoichiometry of 1:1 was determined. The influences of the hydroxypropyl-beta-cyclodextrin concentration, pH and percentage of ethanol on the enzymatic activity were also investigated. Under the conditions presented in this paper, values of ee(s) of 90% and E=48 were obtained.


Long-term results of chest wall reconstruction with DualMesh.
The aim of this study was to evaluate the clinical outcomes of chest wall reconstruction using a new, expanded polytetrafluoroethylene prosthesis, 'DualMesh'. Between December 2005 and March 2010, chest wall reconstruction using 2-mm DualMesh was performed in 11 patients. The indication for resection was primary lung cancer in six patients, malignant mesothelioma in one patient, recurrent lung cancer in one patient, recurrent invasive thymoma in one patient, postirradiated osteomyelitis in one patient, and chondro-hamartoma in one patient. The mean observation period was 23 months, and four cases were observed for more than three years. There were no operative deaths and no wound infections. There were two postoperative complications: prolonged air leakage occurred in a patient with pulmonary emphysema who underwent right lower lobectomy, and slight paradoxical respiration occurred in the patient who underwent resection of the entire sternal body for osteomyelitis. Follow-up chest computed tomography was performed routinely. No dehiscence occurred in any cases. Chest wall reconstruction using DualMesh demonstrated acceptable durability and biocompatibility, even after long-term follow-up. DualMesh has the potential to become an ideal prosthesis for the bony chest wall as an alternative to conventional polytetrafluoroethylene or polypropylene grafts.


Infrarenal aortic coarctation and diffuse hypoplasia of the aortoiliac-femoral system.
Infrarenal aortic coarctation and diffuse hypoplasia is a very uncommon vascular disease. It has been named as hypoplasia of the abdominal aorta, mid-aortic dysplasia, mid-aortic syndrome, atrophy of aorta, atresia of the terminal aorta, and atypical coarctation. The pathogenesis is still controversial. This is in part due to the fact that among the reported cases pathological studies have been rarely carried out. We recently came across an autopsy case of an adult patient with coarctation of the infrarenal aorta and severe hypoplasia of the aortoiliac-femoral system. The pathological findings found explain the pathogenesis of this particular case.


Pancreas vs. islet transplantation: a call on the future.
The aim of this article is to review recent reports on whole pancreas and islet cell transplantation. It focuses on 'what the call to the future looks like' for both therapies as treatment options for those type 1 diabetes patients who do not respond well to conventional therapy. The major benefit of pancreas transplantation is the reversal of diabetes improvement of diabetes complications. Although the procedure requires major surgery and life-long immunosuppression, it remains the gold standard for a specific population of patients who suffer from type 1 diabetes and who do not respond to conventional therapy. Allogeneic islet transplantation is a promising alternative to pancreas transplantation, but patient outcomes remain less than optimal and significant progress is required in order for this procedure to be considered a reliable therapy. Several factors have to be taken into consideration before making the decision of which of these procedures would better suit a patient with type 1 diabetes.