Electrophysiologic studies in the Guillain-Barré syndrome: effects of plasma exchange and antibody rebound.
Nerve conduction studies (NCS) and antiperipheral nerve myelin antibody (A-PNM Ab) titers were measured serially in 29 patients with Guillain-Barré syndrome (GBS), of whom 21 were treated with plasmapheresis. Data were obtained from 3 to 6 days until 1 to 2 years after onset of symptoms. Within 3 to 6 days, mean NCS were abnormal. They improved some by 1 week and became maximally abnormal by 4 to 8 weeks, during which time A-PNM Ab fell to low levels. In 5 patients plasmapheresed, A-PNM Ab fell and then increased at 4 to 8 weeks, followed by significant deterioration of NCS (P = 0.01) compared with those without antibody rebound at 18 weeks. These results suggest that, in monophasic GBS, there may be two mechanisms of conduction dysfunction such as early paranodal retraction and later demyelination. In some patients plasmapheresed, A-PNM Ab may rebound associated with further conduction dysfunction. These patients may benefit from further plasmapheresis.


Evaluation of between- and within-breed variation in measures of weight-age relationships.
Variation between- and within-breeds was evaluated for accretion of weight from birth to 7 yr of age and hip height at 7 yr for 1,577 cows sired by Angus, Brahman, Brown Swiss, Charolais, Chianina, Gelbvieh, Hereford, Jersey, Limousin, Maine Anjou, Pinzgauer, Sahiwal, Simmental, South Devon, and Tarentaise and from either Angus or Hereford dams. Parameters from Wt = A (1 - Be-kt) were estimated by nonlinear regressions and provided estimates of mature body weight (A) and rate of weight accretion relative to change in age (k) for each cow. Actual weight at birth, linear adjusted weights at 200, 365, and 500 d of age, ratios of these weights to mature weight, and height at the hip at 7 yr were analyzed. Beyond 20 mo, weights were adjusted to a constant condition score within breed of sire. Variance and covariance components were derived for breed (sigma 2 b), sires within breed (sigma 2 s), and progeny within sire (sigma 2 w). For all traits, the sigma 2 b estimate of genetic variance ranged from two to four times greater than the variance component for sigma 2 s. Between-breed heritabilities were .91 +/- .27 and .54 +/- .17 for A and k, respectively. Estimates of within-breed heritability for these two traits were .61 +/- .11 and .27 +/- .09. Estimates, both between- and within-breed, of the genetic correlation between A and k were moderate to large and negative; those between A and weights at 200, 365, and 500 d and height at maturity were large and positive. Selection for immediate change in measures of growth would be most effective among breeds. Sufficient direct genetic variation exists between breeds to enhance breed improvement of growth characters through breed substitution. Greater opportunity to alter the shape of the growth curve exists through selection for within-breed selection than through breed substitution.


Two-photon excited highly polarized and directional upconversion emission from slab organic crystals.
Effective upconversion emission from an organic crystal of cyano-substituted oligo (p-phenylenevinylene) (CNDPASDB) based on two-photon absorption is presented. Frequency upconverted cavityless lasing, or amplified spontaneous emission, from the crystal pumped by a femtosecond laser of 800 nm was observed when the excitation energy exceeded the threshold of 1.3 mJpulse(-1)cm(-2). Its polarization contrast was estimated to be approximately 0.93. This large ratio is due to the unified unidirectional configuration of the molecular long axis in crystal, beneficial to the stimulated emission with a low threshold. These results indicate that the present CNDPASDB crystal has a potential for upconversion laser device application.


[Changes in Soil Microbial Carbon-Degrading Enzymes and Their Relationships with Carbon Pool Components During the Restoration Process of Robinia pseudoacacia].
To reveal the change in the characteristics of soil microbial C-degrading enzyme activities and the response to the components of C during the restoration process of Robinia pseudoacacia forests in the Loess Plateau, the components of the soil C pool, C-degrading enzyme activities, and microbial metabolic entropy of R. pseudoacacia in different restoration stages were studied, and the response relationship between C-degrading enzymes and soil C components was explored. The results showed that the microbial respiration (MR) first increased and then decreased with the restored years. We found that the microbial metabolic entropy (qCO2) decreased significantly with the restored years, but the microbial entropy (qMB) increased. Soil C-degrading enzymes increased significantly in the early-stage restoration of R. pseudoacacia; however, oxidizing enzymes (PO and PER) and cellobiohydrolase (CBH) decreased in the late stage of restoration. The soil organic C and recalcitrant organic C increased significantly with the restored years; however, there was no significant difference for the labile organic C. Correlation analysis and the partial least squares-path model (PLS-PM) showed that soil C-degrading enzymes and C components were significantly correlated with microbial respiration and entropy (qCO2 and qMB), respectively. The hydrolytic enzyme (BG+CBH) was significantly positively correlated with SOC, microbial biomass C, qMB, and recalcitrant and labile organic C. The oxidizing enzyme (PO+PER) was significantly positively correlated with the soil clay and qCO2. In addition, the recalcitrant organic C was the key driver of soil microbial metabolism affected by vegetation restoration. Overall, the ecosystem of R. pseudoacacia plantations would gradually stabilize with the increase in restored years and significantly increase the sequestration effect of soil C. These results will be helpful to understand the transformation rule and regulation mechanism of the soil C pool in vulnerable habitats and provide scientific basis for the restoration and management of vegetation in the Loess Plateau.


Long Noncoding RNA RMRP Contributes to Paclitaxel Sensitivity of Ovarian Cancer by Regulating miR-580-3p/MICU1 Signaling.
Ovarian cancer is a prevalent female malignancy affecting the health and life of an increasing population of women around the world. Paclitaxel (PTX) resistance is a significant clinical problem in the treatment of ovarian cancer. However, the regulation mechanism of PTX resistance remains unclear. In this investigation, we reported an innovative function of the long noncoding RNA RMRP in promoting PTX resistance and glycolysis of ovarian cancer cells. We observed that RMRP was highly expressed in the ovarian cancer samples, in which the expression of RMRP was elevated in the PTX-resistant patients compared with the PTX-sensitive patients. Meanwhile, RMRP was upregulated in PTX-resistant ovarian cancer cell lines. Functionally, we found that the silencing of RMRP by siRNA significantly enhanced the PTX sensitivity of PTX-resistant ovarian cancer cells, in which the IC50 of PTX was reduced by RMRP depletion. The RMRP knockdown reduced cell viabilities and enhanced cell apoptosis of PTX-resistant ovarian cancer cells. Moreover, we observed that glucose uptake was enhanced in PTX-resistant ovarian cancer cells. The depletion of RMRP decreased glucose uptake, lactate product, and ATP production in PTX-resistant ovarian cancer cells. About the mechanism, we identified that RMRP was able to sponge miR-580-3p to enhance mitochondrial calcium uptake 1 (MICU1) expression in PTX-resistant ovarian cancer cells. MICU1 overexpression and miR-580-3p repression could reverse the RMRP-inhibited proliferation of PTX-resistant ovarian cancer cells in vitro. Thus, we concluded that RMRP contributes to PTX resistance and glycolysis of ovarian cancer by enhancing MICU1 expression through sponging miR-580-3p. Targeting RMRP may serve as a potential therapeutic strategy for the treatment of PTX-resistant ovarian cancer patients.


Application of a subjective health and safety rating system to Iowa farm operations.
A rapid, subjective health and safety assessment tool was developed and applied to 121 farm operations visited during a cross-sectional, on-farm industrial hygiene (IH) study of the Iowa Farm Family Health and Hazard Surveillance Project (IFFHHSP). The study utilized a single field investigator who conducted visits of farm operations from August 1995 to July 1996. The farm operations visited were randomly selected from a stratified, two-stage cluster sample of Iowa farm operations. The tool developed and applied to each farm operation--the Site Rank System--was based on the average of scores assigned to four different farm characteristics, which we believed would predict the health and safety status of the farm operations. Two of these characteristics were based on an assessment of each farm's operator (operator attitude and operator practices) and the other two were based on weighted scores assigned to physical components of the farm operation (status of facilities and status of equipment). The Site Rank System was found to have been assigned consistently, but an analysis comparing the Site Rank System scores to initial in-depth medical and environmental data gathered from the visited farm operations via self-reported questionnaires showed little correlation with outcomes. However, self-reported injuries (11 total) which occurred to the principal farm operators of the farm operations visited during the on-farm IH study phase (August 1995 to July 1996) correlated with low Site Rank System scores.


[Laparoscopic surgery in tubal pregnancy].
The author accounts about twenty patients operated on tubal pregnancy established on ultrasonic and laparoscopy. He refers the history of the methods of surgical interventions and the difficulties of the diagnosis nowadays. He makes known the technics of the laparoscopical operation and the operated patients' postoperative status.


Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) open reading frame 36 protein is a serine protein kinase.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma. The nucleotide sequence of the KSHV open reading frame (ORF) 36 predicts a polypeptide with significant sequence homology to known protein kinases. In this paper, we show that KSHV ORF36 mRNA is expressed during lytic growth and that ORF36 protein is localized in the nucleus. To determine whether the KSHV ORF36 protein is a protein kinase, we expressed it as a glutathione S-transferase (GST) fusion protein (GST-ORF36). Affinity-purified preparations of the GST-ORF36 fusion protein revealed that the protein is autophosphorylated. Mutation of lysine-108 to glutamine dramatically decreased the protein kinase activity of the purified protein, supporting the hypothesis that the protein kinase activity is inherent to the ORF36 protein. Phosphoamino acid analysis showed that the KSHV ORF36 fusion protein is phosphorylated on a serine residue, implying that KSHV ORF36 encodes a serine protein kinase.


Exercise as a therapeutic option for acute kidney injury: mechanisms and considerations for the design of future clinical studies.
Acute kidney injury (AKI) is a known risk factor for chronic kidney disease (CKD) and end stage kidney disease (ESKD). The progression from AKI to CKD, despite being well recognised, is not completely understood, although sustained inflammation and fibrosis are implicated. A therapeutic intervention targeting the post AKI stage could reduce the progression to CKD, which has high levels of associated morbidity and mortality. Exercise has known anti-inflammatory effects with animal AKI models demonstrating its use as a therapeutic agent in abrogating renal injury. This suggests the use of an exercise rehabilitation programme in AKI patients following discharge could attenuate renal damage and improve long term patient outcomes. In this review article we outline considerations for future clinical studies of exercise in the AKI population.


Biologic agents in the treatment of inflammatory rheumatic diseases.
In 1998, further details on the treatment of patients with rheumatoid arthritis with biologic agents became available. Biologic agents with established efficacy, e.g., the chimeric tumor necrosis factor-alpha monoclonal antibody cA2, were tested in combination with methotrexate (MTX), with evidence of synergistic effects. These trials revealed new, important information on the incorporation of tumor necrosis factor-alpha blocking agents into a treatment regimen of rheumatoid arthritis using established disease-modifying antirheumatic drugs and innovative biologic agents. Clinical trials testing new agents, e.g., T-cell receptor peptides in a double-blind, placebo-controlled fashion represented new developments with regard to T cell-directed treatment principles. In addition, new developments in the preclinical phase are discussed.


Relationships between ATP depletion, membrane potential, and the release of neurotransmitters in rat nerve terminals. An in vitro study under conditions that mimic anoxia, hypoglycemia, and ischemia.
It is known that the extracellular accumulation of glutamate during anoxia/ischemia is responsible for initiating neuronal injury. However, little information is available on the release of monoamines and whether the mechanism of its release resembles that of glutamate, which may itself influence the release of monoamines by activating presynaptic receptors. This study was designed to characterize the release of both amino acids and monoamines under chemical conditions that mimic anoxia, hypoglycemia, and ischemia. The contents of synaptosomes in adenine nucleotides (ATP, ADP, and AMP), amino acids (aspartate, glutamate, taurine, and gamma-aminobutyric acid), and monoamines (dopamine, noradrenaline, and 5-hydroxytryptamine) were measured by high-performance liquid chromatography, after the synaptosomes were subjected to anoxia (KCN + oligomycin), hypoglycemia (2 mmol/L 2-deoxyglucose in glucose-free medium), and ischemia (anoxia plus hypoglycemia). The anoxia- and ischemia-induced release or noradrenaline, dopamine, 5-hydroxytryptamine, and glutamate correlated well with ATP depletion. The correlation observed between glutamate levels and the release of dopamine and 5-hydroxytryptamine in ischemic conditions suggests a functional linkage between the two transmitter systems. However, the antagonists of presynaptic glutamate receptors failed to alter the amount of monoamines released. The inhibition of Na+,K+-ATPase by ouabain had an effect similar to that produced by ischemia. The decrease in Na+ and K+ gradients resulting from the energy depletion of the synaptosomes under ischemic conditions or resulting from the inhibition of Na+, K+-ATPase by ouabain promotes the reversal of the neurotransmitter transporters. The decrease in uptake of neurotransmitters may also contribute to the rise in the extracellular concentration of different transmitters observed during brain ischemia.


[Follow-up of patients suspected of glaucoma using computer-assisted analysis of the optic disk].
The Optic Nerve Head Analyzer was used for longitudinal monitoring of glaucoma suspects. Forty-one patients (76 eyes) were monitored for more than 12 months and 29 patients (51 eyes) for more than 18 months. A significant (p less than or equal to 0.06) decrease in the neuroretinal rim area was found in 8 of 51 eyes monitored greater than 18 months. Thirty-eight of 19 healthy subjects served as the control group. Only 1 of these 38 healthy eyes showed a significant decrease in the neuroretinal rim area (p = 0.04); this decrease is perhaps an artifact caused by the limited accuracy of the Optic Nerve Head Analyzer. From our data we conclude that longitudinal monitoring of patients for glaucoma by means of the Optic Nerve Head Analyzer is an adequate method of detecting ongoing glaucoma damage.


Task-shifting to community health workers: evaluation of the performance of a peer-led model in an antiretroviral program in Uganda.
Task shifting to community health workers (CHW) has received recognition. We examined the performance of community antiretroviral therapy and tuberculosis treatment supporters (CATTS) in scaling up antiretroviral therapy (ART) in Reach Out, a community-based ART program in Uganda. Retrospective data on home visits made by CATTS were analyzed to examine the CATTS ability to perform home visits to patients based on the model's standard procedures. Qualitative interviews conducted with 347 randomly selected patients and 47 CATTS explored their satisfaction with the model. The CATTS ability to follow-up with patients worsened from patients requiring daily, weekly, monthly, to three-monthly home visits. Only 26% and 15% of them correctly home visited patients with drug side effects and a missed clinic appointment, respectively. Additionally, 83% visited stable pre-ART and ART patients (96%) more frequently than required. Six hundred eighty of the 3650 (18%) patients were lost to follow-up (LTFU) during the study period. The mean number of patients LTFU per CATTS was 40.5. Male (p = 0.005), worked for longer durations (p = 0.02), and had lower education (p = 0.005). An increased number of patients (p = 0.01) were associated with increased LTFU. Ninety-two percent of the CATTS felt the model could be improved by reducing the workload. CATTS who were HIV positive, female, not residing in the same village as their patients, more educated, married, on ART, and spent less time with the patients were rated better by their patients. The Reach-Out CHW model is labor-intensive. Triaged home visits could improve performance and allow CATTS time to focus on patients requiring more intensive follow-up.


Subpopulation Treatment Effect Pattern Plot (STEPP) analysis for continuous, binary, and count outcomes.
For the past few decades, randomized clinical trials have provided evidence for effective treatments by comparing several competing therapies. Their successes have led to numerous new therapies to combat many diseases. However, since their conclusions are based on the entire cohort in the trial, the treatment recommendation is for everyone, and may not be the best option for an individual. Medical research is now focusing more on providing personalized care for patients, which requires investigating how patient characteristics, including novel biomarkers, modify the effect of current treatment modalities. This is known as heterogeneity of treatment effects. A better understanding of the interaction between treatment and patient-specific prognostic factors will enable practitioners to expand the availability of tailored therapies, with the ultimate goal of improving patient outcomes. The Subpopulation Treatment Effect Pattern Plot (STEPP) approach was developed to allow researchers to investigate the heterogeneity of treatment effects on survival outcomes across values of a (continuously measured) covariate, such as a biomarker measurement. Here, we extend the Subpopulation Treatment Effect Pattern Plot approach to continuous, binary, and count outcomes, which can be easily modeled using generalized linear models. With this extension of Subpopulation Treatment Effect Pattern Plot, these additional types of treatment effects within subpopulations defined with respect to a covariate of interest can be estimated, and the statistical significance of any observed heterogeneity of treatment effect can be assessed using permutation tests. The desirable feature that commonly used models are applied to well-defined patient subgroups to estimate treatment effects is retained in this extension. We describe a simulation study to confirm that the proper Type I error rate is maintained when there is no treatment heterogeneity, and a power study to show that the statistics have power to detect treatment heterogeneity under alternative scenarios. As an illustration, we apply the methods to data from the Aspirin/Folate Polyp Prevention Study, a clinical trial evaluating the effect of oral aspirin, folic acid, or both as a chemoprevention agent against colorectal adenomas. The pre-existing R software package stepp has been extended to handle continuous, binary, and count data using Gaussian, Bernoulli, and Poisson models, and it is available on the Comprehensive R Archive Network. The extension of the method and the availability of new software now permit STEPP to be applied to the full range of clinical trial end points.


Effect of a High Proportion of Rye in Compound Feed for Reduction of Salmonella Typhimurium in Experimentally Infected Young Pigs.
Public health concerns and the potential for food-borne zoonotic transmission have made Salmonella a subject of surveillance programs in food-producing animals. Forty-two piglets (25 d of age and initially 7.48 kg) were used in a 28 d infection period to evaluate the effects of a high proportion of rye on reducing Salmonella Typhimurium. Piglets were divided into two diet groups: control diet (wheat 69%) and experimental diet (rye 69%). After a one-week adaptation period, all piglets were orally infected with Salmonella Typhimurium (107 log CFU/mL; 2mL/pig). Salmonella in fecal shedding were evaluated at day 1, 3, 5, 7 and then weekly after infection. At the end of the experimental period (at day 28 after infection), the piglets were euthanized to sample feces, cecal digesta contents and ileocecal lymph nodes to determine the bacterial counts of Salmonella. The results suggest that the bacterial counts in the experimental group fed rye diets showed evidence of reducing Salmonella fecal shedding from day 14 onwards and decreasing the number of Salmonella in cecal digesta. However, the translocation of Salmonella in ileocecal lymph nodes was not affected. Furthermore, feed intake, weight gain and feed conversion did not differ between the groups (p > 0.05).


Concurrent synthesis and degradation of alcohol dehydrogenase in elicitor-treated and wounded potato tubers.
The accumulation of alcohol dehydrogenase (ADH) in arachidonic acid-elicited potato (Solanum tuberosum L.) tuber discs was studied. In accordance with our previous report of the accumulation of Adh mRNA beginning 2 hours after elicitor treatment (DP Matton, CP Constabel, N Brisson [1990] Plant Mol Biol 14: 775-783), immunoprecipitation of ADH from in vivo labeled discs indicated that ADH synthesis occurred as early as 12 hours after treatment. However, levels of ADH activity and protein, as shown by enzyme assay and immunoblot, did not rise in parallel but decreased during the first 24 hours of treatment. After 24 hours, ADH activity and protein began to increase, reaching a several-fold increase at 96 hours after elicitation. Water-treated control discs showed a similar though delayed and less pronounced pattern. These results imply a turnover of ADH following elicitor treatment of potato tuber discs. As shown by nondenaturing gel electrophoresis, the synthesis and degradation involved the same ADH isozyme.


In Situ Synthesis of Dental Resin Matrix Containing Silver Nanoparticles.
In this work, we investigated the influence of different concentrations of silver 2-ethylhexanoate on the synthesis and characteristics of silver nanoparticles (AgNPs) in resin matrix, as well as the antibacterial performance, mechanical properties and biocompatibility of the silver containing resin matrix, in order to provide a scientific basis for the application of AgNPs in restoration resins. The concentration of silver salt in resin matrix was set ranging from 0.05 wt% to 0.30 wt%. AgNPs were successfully synthesized in resin matrix by reducing silver ions in situ through photoinitiation. The results demonstrated that silver salt with low concentrations (≤0.20 wt%) had little influence on the degree of conversion, Knoop hardness and cell viability of silver resin matrix. However, silver salt with low concentrations (≤0.15 wt%) had little antibacterial activities against Streptococcus mutans. Therefore, it suggested that 0.20 wt% was a proper concentration for silver salt to be added into resin matrix, since silver salt at this concentration could exert a significantly antimicrobial activity without compromising the mechanical properties and biocompatibility of resin matrix.


Oxidative stress and oxidative damage in carcinogenesis.
Carcinogenesis is a multistep process involving mutation and the subsequent selective clonal expansion of the mutated cell. Chemical and physical agents including those that induce reative oxygen species can induce and/or modulate this multistep process. Several modes of action by which carcinogens induce cancer have been identified, including through production of reactive oxygen species (ROS). Oxidative damage to cellular macromolecules can arise through overproduction of ROS and faulty antioxidant and/or DNA repair mechanisms. In addition, ROS can stimulate signal transduction pathways and lead to activation of key transcription factors such as Nrf2 and NF-kappaB. The resultant altered gene expression patterns evoked by ROS contribute to the carcinogenesis process. Recent evidence demonstrates an association between a number of single nucleotide polymorphisms (SNPs) in oxidative DNA repair genes and antioxidant genes with human cancer susceptibility. These aspects of ROS biology will be discussed in the context of their relationship to carcinogenesis.


[Basic and clinical examinations of 6059-S in pediatrics (author's transl)].
1. MIC of 6059-S against 92 strains of clinically isolated bacteria were measured. The compound was active against most of Gram-negative rods, but was not active against Staphylococcus aureus. 2. 20 mg/kg of 6059-S (newly synthesized oxacephem antibiotics) was administered to the pediatric patients and its blood concentration was measured by agar well method using E. coli 7437 as a test organism. 3. The mean blood concentrations were maximum at 15 minutes after intravenous one-bolus injection. Maximum levels were 94.5 mcg/ml in the patients of below 5 years old and 98.7 mcg/ml above 6 years old. Their half-life of the blood levels were 95.4 and 110.6 minutes respectively. 4. The mean blood concentrations were highest at the end of the infusion in the cases of 60 minutes drip injection. Maximum levels were 85.0 mcg/ml in the patients of below 5 years old and 64.8 mcg/ml above 6 years old. 5. Clinical efficacy of 6059-S in 6 cases pyelonephritis, 2 cases of sepsis, 1 case of meningitis, 1 case of intraperitoneal abscess, 9 cases pneumonia and 2 case of tonsillitis was 100%. In the case of urinary tract infection, 4 patients were treated successfully by the administration of 20 mg/kg/day of 6059-S. Other bacterial infections were treated with 55 to 200 mg/kg/day. 6. 100% of the causative organisms were eliminated by 6059-S. They were E. coli, Klebsiella pneumoniae, Serratia marcescens, H. influenzae and beta-Streptococcus. 7. No remarkable side effect was noticed during administration.


Dynamic and 2D NMR studies on hydrogen-bonding aggregates of cholesterol in low-polarity organic solvents.
Self-diffusion coefficients (D) are measured for normal (nondeuterated) and deuterated cholesterol-d(6) (C26 and C27 methyl groups deuterated) in 1-octanol, chloroform, and cyclohexane at concentrations of 1-700 mM by varying the impurity water concentration (>2 mM) and temperature (30-50 degrees C). The pulsed field gradient spin-echo (PGSE) (1)H and (2)H NMR were used, respectively, at 600 and 92 MHz. At 30 degrees C, the hydrodynamic radius (R) obtained at 20 mM from the D value and solvent viscosity is 5.09, 7.07, and 6.17 A, respectively, in 1-octanol, chloroform, and cyclohexane when the impurity water is negligible. The R value in 1-octanol is the smallest and comparable with the average length of the molecular axes for the cholesterol molecule. In 1-octanol, R is invariant against the concentration variation, whereas in chloroform, R is larger and increases almost linearly with cholesterol concentration. At the highest concentration, 700 mM, the R in chloroform is 13.5 and 16.7 A, respectively, when the impurity water is at negligible and saturated concentrations. The R value larger than that in hydrogen-bonding 1-octanol indicates that cholesterol forms an aggregate through hydrogen bonding. The aggregate structure is confirmed by comparing NOESY spectra in chloroform and 1-octanol. The NOESY analysis reveals the presence of one extra cross peak (C4-C19) in chloroform compared to 1-octanol. Because the carbon atoms related to the cross peak are close to the hydroxyl group (C3-OH), cholesterol molecules are considered to be not piled but are found to be OH-centered in the aggregate. This is supported also by larger rotational hydrodynamic radii measured on cholesterol deuterated at positions C2, C3, C4, and C6. This shows that the aggregate formation is driven by the hydrogen-bonding between cholesterol molecules.


Cutaneous sensory disorder.
Some patients only present with a cutaneous sensory complaint such as itching, burning, stinging, or other disagreeable sensations of unknown etiology. Frequently, these patients may not have any diagnosable dermatologic, neurologic, medical, or psychiatric diagnosis. Their suffering, however, is real. This article explains a practical approach to the treatment of patients with pure cutaneous sensory disorders.


Ocean acidification weakens the immune response of blood clam through hampering the NF-kappa β and toll-like receptor pathways.
The impact of pCO2 driven ocean acidification on marine bivalve immunity remains poorly understood. To date, this impact has only been investigated in a few bivalve species and the underlying molecular mechanism remains unknown. In the present study, the effects of the realistic future ocean pCO2 levels (pH at 8.1, 7.8, and 7.4) on the total number of haemocyte cells (THC), phagocytosis status, blood cell types composition, and expression levels of twelve genes from the NF-kappa β signaling and toll-like receptor pathways of a typical bottom burrowing bivalve, blood clam (Tegillarca granosa), were investigated. The results obtained showed that while both THC number and phagocytosis frequency were significantly reduced, the percentage of red and basophil granulocytes were significantly decreased and increased, respectively, upon exposure to elevated pCO2. In addition, exposure to pCO2 acidified seawater generally led to a significant down-regulation in the inducer and key response genes of NF-kappa β signaling and toll-like receptor pathways. The results of the present study revealed that ocean acidification may hamper immune responses of the bivalve T. granosa which subsequently render individuals more susceptible to pathogens attacks such as those from virus and bacteria.


Experimental and bioinformatic analysis of cultured Bovine Endometrial Cells (BEND) responding to interferon tau (IFNT).
In ruminants, embryo implantation depends on progesterone (P4) and interferon tau (IFNT) controlling endometrial function. IFNT antagonizes bovine endometrial cells (BEND) response to phorbol 12,13-dibutyrate (PDBU) through posttranscriptional regulation of gene expression. We have previously described microRNAs (miRNAs) profiles in bovine endometrium, detecting miR-106a, relevant for embryo maternal communication. In this study, we investigated the expression miR-106a and genes for prostaglandin-endoperoxide synthase 2 (PTGS2), phospholipase A2, group IVA (PLA2G4A), estrogen receptor 1 (ESR1) and progesterone receptor (PR) in response to IFNT in BEND cells and searched for interferon responsive factors (IRFs) binding sites in their promoter genomic regions. The aim of this study was to unravel the molecular mechanisms involved in IFNT signalling and its regulation of miR-106a. PTGS2 showed increased expression under PDBU, which was antagonized by IFNT. IFNT induced expression of PR and miR-106a and downregulation of ESR1 and PR. Bioinformatic analyses detected that PLA2G4A was associated to IRF-1 and IRF-6, while ESR1, PR and PTGS2 were associated to only IRF-6. All genes exhibit one motif per IRF, except miR-106a that had three binding sites for IRF-6. We report the IFNT regulatory effect on miR-106a expression through IRF-6 in bovine endometrial cells. We identified a set of potential binding sites for IRF-1 and IRF-6 within the bovine genome. A set of candidate gene regions could be characterized where IFNT can act via IRFs to regulate the expression of proteins and miRNAs. Future studies will use these data to detect new IFNT regulatory mechanisms in the endometrium.


Results of a five-drug combination chemotherapy in non-small cell lung cancer. A phase II trial.
Twenty-six non-small lung cancer patients entered a phase II trial of a 5-drug combination chemotherapy. On day 1, patients received vinblastine, bleomycin, methotrexate, 5-FU, cisplantinum, leucovorin, and a similar sequence with an increased dosage was administered on day 6. Out of 22 fully evaluable patients we observed 1 CR and 7 PR. Hematological toxicity was significant, including 15 cases of neutropenia grade 4 and four grade 3, with one death during aplasia. Our results are disappointing but they are similar to most current reports on drug combinations in advanced non-small cell lung cancer. A better scheduling might improve the efficiency toxicity ratio.


Influence of water on the surface of the water-miscible ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate: a sum frequency generation analysis.
Sum frequency generation spectroscopy (SFG) was used to study the influence of water on the surface of the water-miscible ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate. The orientation of the cation at the gas-liquid interface was analyzed as a function of ionic liquid concentration in water for concentrations from 0 to 1 mole fraction of the ionic liquid. The cation was found to be oriented with the imidazolium ring nearly parallel to the surface plane with a tilt angle > or = 70 degrees when the ionic liquid was dry. Furthermore, no noticeable change in the orientation was observed when high concentrations of water were mixed with the ionic liquid. The cation butyl chain is projecting into the gas phase with a CH(3) tilt angle of 54 +/- 2 degrees when the ionic liquid is dry and 46 +/- 4 degrees when mixed with water. Water is oriented at the surface only for concentration < or = 0.02 mole fraction of the ionic liquid. At higher ionic liquid concentrations (mole fractions > or = 0.05) the gas-liquid interface resembles that of the pure ionic liquid.


Treatment intensity for developmental language disorder: A systematic review.
Research on treatment intensity in children with developmental language disorder (DLD) has undergone substantial development over the last decade. The aim of the present review was to analyse available publications as related to methodological quality, degree of scientific evidence, and the areas/aspects of language involved. A systematic review of the scientific literature was conducted using the PRISMA guidelines. A total of 9 articles from 34 published investigations in the field were selected for review according to our inclusion criteria. The articles addressed the effects of treatment intensity primarily considering expressive morphology and vocabulary. The methodological quality and levels of evidence provided by the studies were high. In general, the effect sizes of dependent variables were considered large. The number of articles investigating treatment intensity in DLD is scarce. High variability of stimuli was associated with improvements in morphology, whereas vocabulary did not demonstrate the same association. Further research on treatment intensity is needed to address transference and generalisation of the treated abilities.


Role of inorganic chlorides in formation of PCDDs, PCDFs, and coplanar PCBs from combustion of plastics, newspaper, and pulp in an incinerator.
The total amounts of dioxins found in exhaust gases from combustion of polyethylene (PE), polystyrene (PS), and poly(ethylene terephthalate) (PET) with approximately 3% (w/ w) NaCl were 6.07, 17.7, and 28.9 ng/g, respectively. Plastics containing benzene rings produced more dioxins than plastic containing no benzene ring. The amounts of dioxin formed in the exhaust gases from the combustion of newspapers impregnated with CaCl2, KCl, and NaCl were 18.6, 28.6, and 49.0 ng/g, respectively. Dioxin formation was associated with the bond energy between metal atom and chlorine atom. When newspapers impregnated with four different amounts of NaCl were combusted, the highest NaCl content newspaper (chlorine content 4.08%, w/w; lignin content 19.8%, w/w) produced the greatest amount of dioxins (174 ng/g). Pulp with NaCl (chlorine content 4.25%, w/w; lignin content 0.69%, w/w) produced more dioxins (6.71 ng/g) than pulp alone (0.799 ng/g) did upon combustion. The lignin content in a combustion sample correlated with the amount of dioxin formation. The results exhibited that combustion conditions with low CO concentration (<2 ppm) produced much less dioxins than conditions with high CO concentration (159 ppm).


Very-Long-Chain Acyl-Co-Enzyme A Dehydrogenase Deficiency Presenting as Rhabdomyolysis: First Case Report from Sri Lanka.
Rhabdomyolysis can be either inherited or acquired such as in metabolic myopathies. Very-long-chain acyl-CoA dehydrogenase deficiency is a rare fatty acid oxidation disorder which presents with different phenotypes, and the mild adult form can present as intermittent rhabdomyolysis. Here, we present the first adult case of very-long-chain acyl-CoA dehydrogenase deficiency presenting as rhabdomyolysis in a Sri Lankan patient. Case Presentation. A 36-year-old Sri Lankan man who was born to consanguineous parents presented with severe generalized muscle pain, stiffness, and dark-coloured urine for three days following prolonged low-intensity activity. Since fourteen years of age, he has had multiple similar episodes, where one episode was complicated with acute kidney injury. His eldest brother also suffered from the similar episode. Examination revealed only generalized muscle tenderness without any weakness. His creatine phosphokinase level was above 50,000 IU/L, and he had myoglobinuria. Molecular genetic tests confirmed the diagnosis of very-long-chain acyl-CoA dehydrogenase deficiency. Following a successful recovery devoid of complications, he remained asymptomatic with lifestyle adjustments. Very-long-chain acyl-CoA dehydrogenase deficiency is a rare inherited cause of metabolic myopathy that gives rise to intermittent rhabdomyolysis in adults. Prompt diagnosis is essential to prevent complications and prevent its recurrence.


Infrared multiphoton dissociation spectroscopic analysis of peptides and oligosaccharides by using fourier transform ion cyclotron resonance mass spectrometry with a midinfrared free-electron laser.
The fragmentation of peptides and oligosaccharides in the gas phase was investigated by means of electrospray ionization Fourier transform ion cyclotron resonance (FTICR) mass spectrometry coupled with dissociation by a laser-cleavage infrared multiphoton dissociation (IRMPD) technique. In this technique, an IR free-electron laser is used as a tunable source of IR radiation to cause cleavage of the ionized samples introduced into the FTICR cell. The gas-phase IRMPD spectra of protonated peptides (substance P and angiotensin II) and two sodiated oligosaccharides (sialyl Lewis X and lacto-N-fucopentaose III) were obtained over the IR scan range of 5.7-9.5 microm. In the IRMPD spectra for the peptide, fragment ions are observed as y/b-type fragment ions in the range 5.7-7.5 microm, corresponding to cleavage of the backbone of the parent amino acid sequence, whereas the spectra of the oligosaccharides have major peaks in the range 8.4-9.5 microm, corresponding to photoproducts of the B/Y type.


Costunolide, a sesquiterpene lactone from Saussurea lappa, inhibits the VEGFR KDR/Flk-1 signaling pathway.
Costunolide (CT), a sesquiterpene lactone constituent isolated from Saussurea lappa (Compositae), exerted an antiangiogenic effect. CT selectively inhibited the endothelial cell proliferation induced by vascular endothelial growth factor (VEGF). Further, CT was also found to inhibit the VEGF-induced chemotaxis of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. From these results, we hypothesized that CT might inhibit angiogenesis by blocking the angiogenic factor signaling pathway. VEGF interacts with its cognate receptors, KDR/Flk-1 and Flt-1, and exerts its angiogenic effect. CT inhibited the autophosphorylation of KDR/Flk-1 without affecting that of Flt-1. Moreover, administration of CT reduced VEGF-induced neovascularization in a mouse corneal micropocket assay. These results suggest that CT may prove useful for the development of a novel angiogenesis inhibitor.


Transforming growth factor-beta1 regulation of C-type natriuretic peptide expression in human vascular smooth muscle cells: dependence on TSC22D1.
C-type natriuretic peptide (CNP) possesses nitric oxide-like signaling mechanisms and actions in the vasculature, including the inhibition of fibrosis and vascular remodeling through counterregulation of transforming growth factor-β (TGF-β) signaling. The leucine zipper protein transforming growth factor stimulated clone 22 domain 1 (TSC22D1), cloned via its presumed binding to a GC-rich element in the CNP promoter, was the first protein to be described as a CNP transcription factor, but the lack of supporting evidence since its discovery and its lack of a classical DNA-binding site have left in question its role in the regulation of CNP by TGF-β and other factors. To define a specific role for TSC22D1 in CNP transcription, we have examined the effects of the profibrotic growth factors TGF-β1 and PDGF-BB on CNP mRNA expression in cultured human vascular smooth muscle cells (SMC) in which TSC22D1 expression was suppressed with small interfering RNA. Results showed that TGF-β and PDGF-BB significantly increased CNP expression in all three SMC types. Twenty-four-hour TGF-β-induced elevations in CNP were strongly correlated with changes in TSC22D1 mRNA levels, and both genes exhibited their greatest response to TGF-β1 in coronary artery SMC. Furthermore, siRNA suppression of TSC22D1 expression in coronary artery and aortic SMC by ∼90% resulted in 45-65% reductions of both PDGF- and TGF-β-stimulated CNP expression, respectively. These results support a postulated role of TSC22D1 as an enhancer of CNP transcription and suggest that TGF-β-induced upregulation of CNP expression in SMC may be mediated in part by increased transcription of TSC22D1.


[Secondary abnormal development of the bronchial artery: report of a case].
A 65-year-old man was admitted to our hospital because of massive hemoptysis. The patient had suffered from pneumonia since 1999, but he had refused to undertake further examinations. In 2002, the patient was transferred to our emergency room because of massive hemoptysis. Following endotracheal intubation, the patient underwent bronchial artery embolization. The X-ray and computed tomography (CT) films on admission revealed localized bronchiectasis in the left upper lung. Bronchoscopic findings revealed massive bleeding from the left upper bronchus. Bronchial arteriography of the left bronchial artery showed peripherally hypervascular finding in the left upper lobe. A segmentectomy of the left upper division was performed as a radical therapy for localized lesions with massive hemoptysis. The pathological diagnosis was secondary abnormal development of the bronchial artery. We speculated that massive hemoptysis had occurred probably due to infection in the focus.


High prevalence of HBsAg during pregnancy in Asian communities at Cayenne Hospital, French Guiana.
We described hepatitis B surface antigen (HBsAg) prevalence among 2,347 pregnant women having delivered at the Cayenne hospital in 2007 according to ethnicity. With 11.0% HBsAg prevalence, Asian women (Hmong and Chinese) were the group with the highest risk of hepatitis B virus (HBV) perinatal transmission compared with other ethnic groups.


Mortality study of pesticide applicators and other employees of a lawn care service company.
In response to reports linking non-Hodgkin's lymphoma (NHL) and the herbicide 2,4-dichlorophenoxyacetic acid, a retrospective cohort mortality study of 32,600 employees of a lawn care company was conducted. The cohort was generally young with short-duration employment and follow-up. In comparison to the US population, the cohort had significantly decreased mortality from all causes of death combined (307 deaths), arteriosclerotic heart disease, and accidents. There were 45 cancer deaths (59.6 expected, standardized mortality ratio [SMR] = 0.76, 95% confidence interval [CI] = 0.55, 1.01). Bladder cancer mortality was significantly increased, but two of the three observed deaths had no direct occupational contact with pesticides. There were four deaths due to NHL (SMR = 1.14, CI = 0.31, 2.91); three were male lawn applicators (SMR = 1.63, CI = 0.33, 4.77), with two of the applicators employed for three or more years (SMR = 7.11, CI = 1.78, 28.42). No other cause of death was significantly elevated among lawn applicators as a group or among those employed for three or more years. Although based on very small numbers and perhaps due to chance, the NHL excess is consistent with several earlier studies.


C-terminal truncated HBx reduces doxorubicin cytotoxicity via ABCB1 upregulation in Huh-7 hepatocellular carcinoma cells.
Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx. [BMB Reports 2019; 52(5): 330-335].


Analysis of L5 incidence in normal population use of L5 incidence as a guide in reconstruction of lumbosacral alignment.
Cross-sectional study. To establish a statistic model defining the relationship between L5 incidence (L5I) and pelvic incidence (PI) in normal population and to illustrate the importance of L5I in maintaining the normal sagittal profile of spine. L5I was proposed for the evaluation of postoperative improvements in high-grade isthmic spondylolisthesis. It has been proven that a postoperative improvement in L5I was correlated with a better surgical outcome, indicating that the restoration of L5I is important in restoring normal sagittal balance and spinal morphology. This retrospective study recruited 138 healthy volunteers, who were stratified into 2 groups according to age: adolescent group (13-18 yr) and adult group (19-35 yr). Parameters including PI, pelvic tilt, sacral slope, lumbar lordosis (LL), upper arc of the LL, lower arc of the LL, L5I, lumbosacral angle, and height of L5-S1 disc were measured on the long-cassette standing upright lateral radiographs of the spine and pelvis. The relations between all parameters were determined via the Pearson correlation coefficient (r). Linear regression was applied to model the relationship between PI and L5I. This study demonstrated significant correlation between L5I and PI with a coefficient of 0.818, and a formula based on linear regression was established to estimate the ideal L5I from PI as follows: L5I = 0.725 PI - 12.757. Pelvic tilt, sacral slope, lumbosacral angle, LL, lower arc of the LL, and height of L5-S1 disc were also found strongly correlated with L5I, whereas no correlation was found between upper arc of the LL and L5I. Strong correlations were found between L5I and spinopelvic parameters in healthy subjects, indicating that L5I was an important parameter in local lumbosacral alignment. Ideal postoperative L5I could be mathematically calculated by PI according to the formula as follows: L5I = 0.725 PI - 12.757, suggesting that calculated ideal L5I could be regarded as a guide in surgical decision making. 3.


Enhancement of microtubule-associated protein-1 Alpha gene expression in osteoblasts by low level laser irradiation.
Low level laser irradiation (LLLI) stimulates bone regeneration. However, the molecular mechanisms leading to this is not yet understood. The stepwise subtractive cDNA cloning technology has been developed, coupled with DNA homology searched in DNA database is useful to identify the certain gene. In order to understand the mechanism, we attempted to identify genes whose expressions are enhanced by LLLI. MC3T3-E1 osteoblastic cells were irradiated with an 830 nm Ga-Al-As diode laser, and a cDNA library was constructed using subtractive gene cloning. The cDNA library of osteoblasts which was treated by LLLI was constructed. Nucleotide sequences were analyzed and homology searched in a DNA database using BLASTN program to identify the gene with altered expression. Altered mRNA levels by LLLI were confirmed by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. The DNA sequence of a subtracted gene clone MCL129 indicated high homology (99%) with the microtubule-associated protein 1A (MAP1A) gene. Increase in MAP-1A mRNA level by LLLI was successfully confirmed by RT-PCR and real-time PCR. MAP1A has been shown to promote microtubule assembly and its functional expression. Microtubules play an important role in cell division, cell shape and polarity, cell movement, intracellular transport, signal transduction, and synthesis and secretion of collagen. Thus, enhancement of MAP1A gene expression by LLLI may be one of the molecular mechanisms involved in accelerating bone formation by LLLI. LLLI irradiation enhances MAP1A gene expression and modulates microtubule assembly and the functional structure of microtubules, in turn, stimulates osteoblastic proliferation and differentiation.


[Use of ospen (a drug form of phenoxymethylpenicillin) in pediatric practice].
Ospen is a dosage form of phenoxymethylpenicilin. As a therapeutic and prophylactic agent it was shown efficient in treatment of patients with diseases of the otorhinolaryngological organs due to primary and secondary coccal infections. High antiinflammatory activity of ospen was observed in acute and aggravated chronic tonsillitis, otitis, sinusitis and acute respiratory virus infections as well as in prevention of complications after adenotonsillectomy and various manipulations connected with penetration into the inner cavities. Ospen was highly active as a prophylactic agent against hospital respiratory infections. It prevented its distribution and aggravation of the main diseases. Adverse reactions to the use of ospen were minimal and no toxic manifestations were recorded.


Risks of Single Fetal Demise after Laser for Twin-Twin Transfusion Syndrome.
The aim of the study was to determine if markers of donor placental insufficiency and recipient cardiac dysfunction increase the risk for single fetal demise (SFD) after laser for twin-twin transfusion syndrome (TTTS). Single-center retrospective review of patients who had laser for TTTS. Risk factors for donor and recipient demise within 1 week were compared in pregnancies with SFD and pregnancies with dual survival using χ2 or Fisher's exact test. Multivariate logistic regression was then performed. Of 398 procedures, 305 (76.6%) had dual survival, 36 (9.0%) had donor demise, 28 (7.0%) had recipient demise, and 9 (2.3%) had dual demise. The remaining 20 (5.0%) patients had complicated courses with pregnancy loss or further intervention. In the 64 pregnancies with SFD, 29 (81%) in the donor group and 20 (71%) in the recipient group occurred in the first postoperative week. For the donor demise group, estimated fetal weight (EFW) <10%, EFW <3%, EFW <1%, EFW discordance >25%, and EFW discordance >30% did not increase the risk for donor demise except in cases that also had umbilical artery absent or reversed end diastolic flow (AREDF). Donor AREDF was the only independent risk factor for early donor demise. For the recipient demise group, recipient abnormal venous Dopplers were associated with increased risk while EFW discordance >25% was associated with decreased risk of recipient loss. In our cohort, donor growth restriction did not increase the risk of early donor demise after laser unless there was also donor AREDF. Donor AREDF was an independent risk factor for donor demise likely due to the severity of placental insufficiency. Abnormal recipient venous Doppler indices increased the risk of early recipient loss while a large intertwin discordance decreased the risk. This may be explained by profound overload in cases with recipient abnormal venous Doppler velocimetry and a lower risk of substantial fluid shifts from a relatively smaller donor territory when there is a large discordance.


Noninvasive ventilation in chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis.
Although long-term oxygen therapy (LTOT) improves survival, it has little effect on hypoventilation and other outcomes in patients with hypercapnic respiratory failure due to chronic obstructive pulmonary disease (COPD). Recent studies have shown that the use of noninvasive positive-pressure ventilation, when used in combination with LTOT in selected stable COPD patients, controls hypoventilation and improves daytime arterial blood gases, sleep quality, health status and may have a benefit in reducing exacerbation frequency and severity. Patients who show the greatest reduction in overnight carbon dioxide tension in arterial blood with ventilation are most likely to benefit from long-term ventilatory support. Some benefits have also been shown in patients with chronic respiratory failure due to bronchiectasis and cystic fibrosis, though survival is inferior in this patient group. As most studies of noninvasive positive-pressure ventilation in chronic obstructive pulmonary disease have been relatively short term, large multicentre studies with survival, exacerbations and hospital admissions as the primary end points are required to evaluate longer term effects.


Effect of phasing-sector angular extent in FM reticles.
A technique is presented for increasing the useful power of the FM modulation signal from a spinning FM reticle with a phasing sector. Spinning FM reticles often determine a target location by using a combination of a phasing sector to establish the angular target location and a radial frequency variation to establish the radial target location. Typically, the phasing sector of this reticle type consists of a semicircular transmissive sector with the other semicircular sector which provides FM modulation. The power of the FM modulation signal is increased by matching the phased-sector geometry to the size that corresponds to the period of the modulation frequency. This type of reticle is compared and contrasted with the more typical semicircular phasing-sector reticle in both the time and frequency domains.


[A case of aortic valve rupture due to blunt chest trauma].
A case of aortic valve rupture due to blunt chest trauma is presented. 19-year-old man was in good health until he sustained traumatic injury in a traffic accident. He was admitted to a hospital elsewhere because of blunt chest trauma and fractures of the bilateral lower extremities. A heart murmur was detected and echocardiogram revealed marked aortic regurgitation. Then he was referred to our hospital. Progressive congestive heart failure developed. He underwent aortic valve replacement with 25 mm SJM prosthesis 9 days after the injury. The noncoronary cusp was found to be ruptured parallel to and 2 mm from its attachment. His postoperative course was uneventful and he is doing well 4 years and 6 months after operation.


Cancer Disparities in Rural Appalachia: Incidence, Early Detection, and Survivorship.
To document cancer-related health disparities in Appalachia. The current study investigated disparities in cancer incidence, mortality, and staging between rural Appalachians and those living outside of rural Appalachia. To accomplish this, mortality data for the United States from 1969 to 2011 were obtained from the National Center for Health Statistics (NCHS) using SEER* Stat. These data were used to compare trends in mortality between rural Appalachians, urban Appalachians, rural non-Appalachians, and urban non-Appalachians. Cancer incidence trends, staging, and survivorship data were compared across regions using the SEER-18 Program, which represented 28% of the US population and includes 2 Appalachian states: Georgia and Kentucky. Cancer mortality rates declined in all regions, but disparities remained such that rural Appalachia has the highest incidence, while urban non-Appalachia has the lowest. In all but 1 state, rural Appalachians had higher cancer mortality rates than urban non-Appalachians. Cancer incidence declined for all regions except rural Appalachia. Rural Appalachians had lower rates of early stage breast cancer diagnoses than their urban non-Appalachian counterparts. Finally, rural Appalachians had lower 3- and 5-year survival rates than their urban non-Appalachian counterparts. Rural Appalachians are faced with poorer cancer-related health outcomes across the continuum of cancer care. A systematic effort is needed to reduce the burden of cancer for rural Appalachia. Additional research should explore reasons for the disparities that were observed.


The effects of pore size in bilayered poly(lactide-co-glycolide) scaffolds on restoring osteochondral defects in rabbits.
Bilayered porous scaffolds have recently attracted interest because of their considerable promise for repairing osteochondral defects. However, determination of optimal pore size in bilayered porous scaffolds remains an important issue. This study investigated the in vivo effects of pore size in bilayered scaffolds using a rabbit model of osteochondral defects. We fabricated five types of integrated bilayered poly(lactide-co-glycolide) (PLGA) scaffolds with different pore sizes in the chondral and osseous layers (50-100 µm, 100-200 µm, 200-300 µm, and 300-450 µm). A subset of bilayered scaffolds seeded with or without allogenic bone marrow mesenchymal stem cells (BMSCs) was implanted in rabbit osteochondral defects. All of the cell/scaffold composite constructs supported the simultaneous regeneration of articular cartilage and subchondral bone, but the best results were observed in cell-seeded PLGA scaffolds with 100-200 µm pores in the chondral layer and 300-450 µm pores in the osseous layer. Our study supports the concept that the effects of pore size on osteochondral repair should be taken into consideration during scaffold design for tissue engineering.


[Vocal cord abductor paralysis in multiple system atrophy--paradoxical movement of vocal cords during sleep].
Bilateral vocal cord abductor paralysis (VCAP) is frequently associated with multiple system atrophy (MSA) and the early clinical manifestation of VCAP is nocturnal inspiratory stridor simulating heavy snoring observed in patients with obstructive sleep apnea syndrome. We examined six MSA patients with nocturnal stridor and four disease controls including sleep apnea syndrome. Vocal cord movements were analyzed by laryngofiberscopy during both wakefulness and sleep induced by intravenous administration of diazepam. The results were as follows: First, the stenotic portion in the upper airway tract was the larynx (the vocal cords) in MSA patients with stridor, while the soft palate or the pharynx in the disease controls. Second, in the MSA patients, while awake-laryngofiberscopy showed abduction restriction suggestive of VCAP in only one of the six patients, sleep-laryngofiberscopy showed obvious paradoxical movement of the vocal cord in all the rests, where the vocal cords abducted in expiration and adducted in inspiration. In addition, there were two patterns in the inspiratory vocal cord position during sleep: one pattern where vocal glottis was still opening at the posterior one-third area and the other pattern where vocal glottis was almost completely closed through total length of the cords. Tracheostomy should be considered in the latter stage of VCAP.


Mutator phenotype due to loss of heterozygosity in diploid yeast strains with mutations in MSH2 and MLH1.
Mutations in mismatch repair (MMR) genes predispose humans to cancer. Particularly prevalent are frameshift and point mutations in MSH2 and MLH1, two genes whose products are required for the early steps in MMR. In normal tissues of persons predisposed to hereditary non-polyposis colon cancer (HNPCC), these mutations are usually present in only one allele. In tumor cells of these patients, the second, wild type allele is typically found to be deleted or inactivated by point mutation. This suggests that loss of heterozygosity (LOH) results in a strong mutator phenotype that could eventually lead to the onset of disease. Here we demonstrate that diploid yeast strains that are heterozygous for MSH2 and MLH1 alleles have an elevated mutation rate. We further show that this effect results not from saturation of the MMR capacity of all cells in the population, but rather from loss of the wild type allele in a subpopulation of heterozygous cells. These results have implications for understanding the mechanisms of carcinogenesis in humans.


Deferred treatment of clinically localized low-grade prostate cancer: actual 10-year and projected 15-year follow-up of the Karolinska series.
To review the outcome in patients with clinically localized prostate cancer managed conservatively. A total of 122 patients with palpable, clinically localized, low-grade prostate cancer diagnosed from 1978 to 1982 at the Karolinska Hospital, Stockholm, Sweden, were prospectively followed in a surveillance protocol followed by treatment when the tumor progressed with symptoms. All patients but one had been observed for 10 years or more. No antitumoral therapy had been given to 58 (48%) patients at follow-up or before death. The chance of being untreated 5 and 10 years after diagnosis, if still alive, was 71% and 43%, respectively. The actual disease-specific survival rate at 10 years was 90%. Of the patients with a possible observation period of 15 years or more, 25% died of prostate cancer (ie, an actual disease-specific survival of 75%). Using a survival plot, the projected disease-specific survival rate at 15 years was 62%. The cumulative incidence of death from prostate cancer increased with possible observation time up to 15 years. Our data are mature up to 10 years of observation and, based on these data, deferred treatment is a valid option for patients with clinically localized low-grade prostate cancer with a life expectancy of 10 years or less. The data are not definitive beyond 10 years and firm conclusions will be speculative, but our findings indicate that there probably is room for efficacious local treatment in patients with localized prostate cancer and a life expectancy longer than 10 years.


Perceptions of junior doctors and undergraduate medical students as anatomy teachers: Investigating distance along the near-peer teaching spectrum.
Near-peer teaching involves more experienced students acting as tutors and has been widely used in anatomy education. This approach has many advantages for the learner due to the social and cognitive congruence they share with the teacher, however, the influence of distance between the teacher and learner on these congruences has yet to be explored. The aim of this study was to compare the attitudes and perceptions of the student learner towards neuroanatomy review sessions taught by either a senior medical student or a junior doctor. The students were randomly assigned to an allocated tutor. All tutors used standardized material and had access to identical resources. The type of allocated tutor was swapped between the two teaching sessions and 99 student feedback forms were collected in total. The rating for the overall quality of the teaching session was not significantly different between the junior doctors and senior medical students (P = 0.11). However, criteria closely relating to social and cognitive congruence such as "enjoyment of the session," "delivery of the teaching," and "was it a good use of time" were all rated significantly higher for the senior medical students (P < 0.05). The results of this study suggest that small increases in distance along the near-peer teaching spectrum have an impact upon the student's perception of their learning experience. While all teachers were suitable role models it appears that junior doctors are too far removed from their own undergraduate experiences to share congruences with pre-clinical medical students.


Blood Flow Imaging with Ultrafast Doppler.
The pulsed-Doppler effect is the main technique used in clinical echography to assess blood flow. Applied with conventional focused ultrasound Doppler modes, it has several limits. Firstly, a finely tuned signal filtering operation is needed to distinguish blood flows from surrounding moving tissues. Secondly, the operator must choose between localizing the blood flows or quantifying them. In the last two decades, ultrasound imaging has undergone a paradigm shift with the emergence of ultrafast ultrasound using unfocused waves. In addition to a hundredfold increase in framerate (up to 10000 Hz), this new technique also breaks the conventional quantification/localization trade-off, offering a complete blood flow mapping of the field of view and a simultaneous access to fine velocities measurements at the single-pixel level (down to 50 µm). This data continuity in both spatial and temporal dimensions strongly improves the tissue/blood filtering process, which results in an increase sensitivity to small blood flow velocities (down to 1 mm/s). In this method paper, we aim to introduce the concept of ultrafast Doppler as well as its main parameters. Firstly, we summarize the physical principles of unfocused wave imaging. Then, we present the Doppler signal processing main steps. Particularly, we explain the practical implementation of the critical tissue/blood flow separation algorithms and on the extraction of velocities from these filtered data. This theoretical description is supplemented by in vitro experiences. A tissue phantom embedding a canal with flowing blood-mimicking fluid is imaged with a research programmable ultrasound system. A blood flow image is obtained and the flow characteristics are displayed for several pixels in the canal. Finally, a review of in vivo applications is proposed, showing examples in several organs such as carotids, kidney, thyroid, brain and heart.


[Phytotherapeutic treatments of gynecological diseases and fertility disorders in cattle - a veterinary historical analysis].
Fertility problems are the main reasons for culling dairy cows. Diseases of the female genital tract are also often the cause of antibiotic or hormonal treatments in bovine practices. The use of medicinal plants could expand the available therapeutics. The aim of the work was to analyze historical literature before the introduction of antibiotics in veterinary reproductive medicine. Five books in German language, published in Germany and Switzerland between 1878 and 1921, and one handwritten therapy booklet by the rural veterinarian Carl Ammann-Honegger (1879-1960) were systematically examined regarding the descriptions (AW) on gynecological diseases. The herbal and additional ingredients of the recipe, the target animal species, the type of administration and the indication were recorded in detail for each AW. The six literature sources contained a total of 103 AW (79 administered orally, 13 locally, and 11 both orally and locally). Almost two thirds of the AW (61) were based on a mixture of different plants (two to seven plants), and one third of the AW (31) on a single plant. A total of 55 plants were recorded. The most frequently mentioned medical plants were plants of the genus Juniperus (J. communis L. (19 AW), J. sabina L. (13 AW)) and Linum usitatissimum L. (18 AW), Matricaria chamomilla L. (13 AW) and Gentiana lutea L. (12 AW). The treatment of the Retentio secundinarum was the most frequently mentioned indication (44 AW), followed by parturition preparation (17 AW) and endometritis treatment (15 AW). The most frequently recorded plants can be divided based on their ingredients and their effect into (a) energy- and protein-rich forage plants, (b) generally appetizing, digestive- and metabolism-enhancing plants, (c) medical plants with a specific gynecological organotrophic effect and (d) according to current knowledge, predominantly toxic plants. Besides the antimicrobial active immunity to defence against bacterial infections, a stable barrier funcion of the endometrium contributes to uterine health. The plants classified under (a) - (c) have at least the potential for a positive effect on the immune system and the endometrial barrier function and thus contribute indirectly to the uterine health.


The effect of ACGME duty hour restrictions on operative continuity of care.
Resident work restrictions limit participation in operations that address problems created by a prior operation, because complications occur at any time. We compared resident and attending surgeon staffing of operative complications. We reviewed all complications that required a second operation reported at our Morbidity and Mortality Conference over 1 year, noting surgeons present, their postgraduate year level, and call shift. Comparisons were done using chi2. Of 142 cases, 39 involved a second operation. The same attending surgeon was present for both in 79 per cent of cases, whereas the same resident was present in only 44 per cent (P = 0.002). Postgraduate year 4 to 5 were less likely to be present for second operations than attendings (48% vs 87%, P = 0.011). Resident shift (day, night float, and weekend) was known in 32 cases. When the first operation occurred during day hours, attendings and residents were equally likely to be present at the second (55% and 45%, P = 0.16). When original operations took place during night float or weekend shifts, residents were less likely to be present (33%) than attendings (83%) at second operations (P = 0.036). Duty hour restrictions interfere with operative continuity of care. Reoperations should be exempted from duty hour restrictions.


Sarcomatoid carcinoma (so-called pseudosarcoma) of the larynx simulating malignant giant cell tumor of soft parts. A case report.
A tumor of the larynx composed of a small infiltrating and well-differentiated squamous cell carcinoma and a large polypoid sarcomatous mass showing the histologic features of the malignant giant cell tumor of soft parts (MGCT) is reported. Other types of sarcomatous components have been described with squamous cell carcinoma (SCC) of the larynx and names such as pseudosarcoma, carcinosarcoma, and spindle cell carcinoma have been used for these peculiar tumors. Because most data support that the sarcomatous component is an unusual carcinoma transformation due to unknown factors the authors prefer the term sarcomatoid carcinoma. Sarcomatoid carcinomas having the features of MGCT have been described in multiple epithelial organs. Therefore, an extensive search for a carcinoma component always should be carried out in tumors arising in any organ, including the larynx, and showing the typical histologic features of MGCT.


Using artificial neural networks to identify patients with concussion and postconcussion syndrome based on antisaccades.
OBJECTIVEArtificial neural networks (ANNs) have shown considerable promise as decision support tools in medicine, including neurosurgery. However, their use in concussion and postconcussion syndrome (PCS) has been limited. The authors explore the value of using an ANN to identify patients with concussion/PCS based on their antisaccade performance.METHODSStudy participants were prospectively recruited from the emergency department and head injury clinic of a large teaching hospital in Toronto. Acquaintances of study participants were used as controls. Saccades were measured using an automated, portable, head-mounted device preprogrammed with an antisaccade task. Each participant underwent 100 trials of the task and 11 saccade parameters were recorded for each trial. ANN analysis was performed using the MATLAB Neural Network Toolbox, and individual saccade parameters were further explored with receiver operating characteristic (ROC) curves and a logistic regression analysis.RESULTSControl (n = 15), concussion (n = 32), and PCS (n = 25) groups were matched by age and level of education. The authors examined 11 saccade parameters and found that the prosaccade error rate (p = 0.04) and median antisaccade latency (p = 0.02) were significantly different between control and concussion/PCS groups. When used to distinguish concussion and PCS participants from controls, the neural networks achieved accuracies of 67% and 72%, respectively. This method was unable to distinguish study patients with concussion from those with PCS, suggesting persistence of eye movement abnormalities in patients with PCS. The authors' observations also suggest the potential for improved results with a larger training sample.CONCLUSIONSThis study explored the utility of ANNs in the diagnosis of concussion/PCS based on antisaccades. With the use of an ANN, modest accuracy was achieved in a small cohort. In addition, the authors explored the pearls and pitfalls of this novel approach and identified important future directions for this research.


Identification of functional segments within the beta2I-domain of integrin alphaMbeta2.
The alpha(M)beta(2) integrin plays an important role in leukocyte biology through its interactions with a diverse set of ligands. Efficient ligand binding requires the involvement of both the alpha(M) and beta(2) subunits. Past ligand binding studies have focused mainly on the alpha(M) subunit, with the beta(2) subunit being largely unexplored. Therefore, in this study we conducted homolog-scanning mutagenesis on the I-domain (residues 125-385) within the beta(2) subunit. We identified four noncontiguous sequences (Arg(144)-Lys(148), Gln(199)-Ala(203), Leu(225)-Leu(230), and Gly(305)-His(309)) that are critical for fibrinogen and C3bi binding to alpha(M)beta(2). Molecular modeling revealed that these four sequences reside within a narrow region on the surface of the beta(2)I-domain, in close proximity to three potential cation-binding sites. Among these sequences, Gln(199)-Ala(203), Leu(225)-Leu(230), and Gly(305)-His(309) are important for the binding of both ligands, whereas Arg(144)-Lys(148) is more critical for fibrinogen than for C3bi binding. These sequences within the beta(2)I-domain are directly involved in ligand binding, since 1) switching these segments to their corresponding beta(1) sequences destroyed ligand binding; 2) loss of function was not due to a nonspecific gross conformational change, since the defective alpha(M)beta(2) mutants reacted well with a panel of conformation-dependent mAbs; 3) mutation of these functional sequences did not effect Ca(2+) binding; and 4) synthetic peptides corresponding to sequences Gln(199)-Ala(203) and Gly(305)-His(309) blocked ligand binding to alpha(M)beta(2), and the peptides interacted directly with fibrinogen and C3bi. Given the similarity among all integrin beta subunits, our results may help us to understand the underlying mechanism of integrin-ligand interactions in general.


A chemometric approach to distribution of selenium in medicinal plants cultivated in poland.
The aim of this study was to evaluate the level of selenium (Se) in common raw plant materials (herbs, leaves, flowers, fruits, and roots) obtained from medicinal plants cultivated in Poland. Furthermore, the relationship between the morphological part of a plant and its species was examined, and the concentration of Se in it was measured. Spectrofluorimetric determination of Se in 148 samples of 44 plant species revealed that the majority of the plants contained Se at a level from several to several tens of μg/kg dry weight (d.w.). A relatively high Se concentration, in the order of 50 μg/kg d.w., was found in Majoranae herba, Crataegi fructus, and Lini semen. An especially high Se level, >100 μg/kg d.w., was found in only three plants-Equiseti herba, Farfarae folium, and Cichorii radix. Application of a nonparametric Kruskal-Wallis analysis of variance test indicates that the morphological variable influences the level of Se in the studied groups of raw plant materials. The mean concentration of Se in fruits differs significantly from that found in flowers and roots. However, there was no statistically significant difference between the Se content in herbs and leaves and its levels in fruits, flowers, and roots. Cluster analysis and principal component analysis calculations show that it is possible to relate the Se concentration in plant material to the plant species and botanical family of the medicinal plant in only a few cases. Analysis of average Se levels in the plant species showed that the plants belonging to the Apiaceae and Labiatae botanical families are more Se-rich than those belonging to Rosaceae.


Effectiveness of different types of hair traps for brown bear research and monitoring.
Non-invasive sampling by hair-trapping is increasingly used worldwide in wildlife research. Despite this rise and the potential of hair samples for ecology and conservation studies, the relative performance of hair collection devices has been rarely tested. Here, we compare the effectiveness of five types of hair traps for brown bears Ursus arctos in the Carpathian Mountains (SE Poland) and test the effects of trap type, season, number of days elapsed since trap installation and trap features on the trapping success in order to provide recommendations for optimal sampling in future studies. The trap types were corral, path-trap, "smola"(beechwood tar) tree-trap, turpentine tree-trap and natural rub. In 2010, we collected 858 hair samples during 2330 inspections of 175 hair traps and found that the most effective traps were smola tree-traps (mean percentage of successful inspections ± SD: 30.2% ± 26.0) and natural rubs (50.8% ± 16.7). Based on this finding, over the following 2 years we focused on 24 smola tree-traps and eight natural rubs. During this long-term survey (2010-2012, 969 inspections, 1322 samples collected) the trapping success increased with time and smola tree-traps achieved similar effectiveness to natural rubs (45.5% ± 29.7 and 45.9 ± 23.4, respectively). We show that when baiting smola tree-traps ten weeks prior to research or monitoring, sampling effectiveness can reach up to 30%. Taking into account the logistical and methodological constraints associated with detecting and using natural rubs for a proper survey design, we recommend using smola tree-traps baited in advance for hair sampling in wildlife studies.


Considerations about the Geographic Distribution of Histoplasma Species.
Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves immunocompetent and immunosuppressed human and other mammalian hosts, depending on particular circumstances. Histoplasmosis infection has been documented worldwide. The infection is acquired by inhaling infective mycelial propagules of the dimorphic fungus Histoplasma capsulatum. New reports of clinical cases of histoplasmosis in extreme latitudes could be related to human social adaptations and climate changes in the world, which are creating new favorable environments for this fungus and for bats, its major natural reservoirs and dispersers. Histoplasma has been isolated from most continents, and it is considered a complex of cryptic species, consisting of various groups of isolates that differ genetically and correlate with a particular geographic distribution. Based on updated studies, Histoplasma taxonomy is adjusting to new genetic data. Here, we have suggested that Histoplasma has at least 14 phylogenetic species distributed worldwide and new genotypes that could be under deliberation. Histoplasma's geographic radiation began in South America millions of years ago when the continents were joined and the climate was favorable. For fungal spreading, the role of bats and some birds is crucial, although other natural factors could also participate.


Approach to the patient: reninoma.
A reninoma is a functional tumour of afferent arteriolar juxtaglomerular cells that secretes the enzyme renin, leading to hyperactivation of the renin-angiotensin-aldosterone system. Reninoma is a potentially curable cause of pathological secondary hyperaldosteronism that results in often severe hypertension and hypokalemia. The lack of suppression of plasma renin contrasts sharply with the much more common primary aldosteronism, but diagnosis is often prompted by screening for that condition. The major differential diagnosis of reninoma is renovascular hypertension. Fewer than 200 cases of reninoma have been described. Reninomas have been reported across a broad demographic but have a 2:1 predilection for women, often of childbearing age. Aldosterone receptor blockade, angiotensin converting enzyme inhibitors or angiotensin receptor blockers offer effective medical management but are contraindicated in pregnancy, so that surgical curative resection is ideal. The current optimal imaging and biochemical workup of reninoma and management approach (ideally, tumour excision with subtotal renal resection) are described.


[Double contrast examination of the bile ducts (author's transl)].
Efficacy of double contrast X-ray study of the bile duct was studied. Using barium sulfate it was possible to demonstrate fine mucosal pattern (FMP) of the bile duct in the surgical specimen. Utilizing decompression catheter in 44 patients with extrahepatic jaundice, double contrast study was clinically performed. It was also possible to demonstrate FMP of the bile duct mucosa. Mucosal and intramural spread of bile duct carcinoma were revealed preoperatively. It was also useful in the differential diagnosis of the biliary tract diseases.


Endemic prevalence of hepatitis B and C in Mongolia: A nationwide survey amongst Mongolian adults.
In this study, a representative group of Mongolian adults was tested for hepatitis B virus (HBV) and hepatitis C virus (HCV). Screening was conducted at 17 different locations on a randomly sampled group, representing the Mongolian adult population. A total of 1158 adults, 500 (43.1%) men and 659 (56.9%) women were included. The prevalence estimates of HBV and HCV amongst the general Mongolian adult population were found to be 11.1%±1% (SE) and 8.5%±0.7% or 207 418 and 160 228 cases, respectively. For HCV, the majority of cases are concentrated in older age groups with a prevalence of 25.8% amongst those aged 50 years and above, whilst the prevalence of HBV does not vary significantly amongst age groups. For both, HBV and HCV, the data indicate a higher risk of infection and a higher mortality because of the hepatitis amongst men than amongst women. This study represents the first nationwide estimate of the prevalence of HBV in Mongolia and also considered the first for HCV since 2005 and confirm the position of Mongolia as one of the hot-spots of chronic hepatitis infection in the world with about 19.4% of the adult population being infected with either HBV or HCV.


Relationship between membrane potential oscillations and rhythmic discharges in identified hippocampal theta-related cells.
Intracellular recordings of cells, classified according to the criteria of Colom and Bland as phasic theta-ON or phasic theta-OFF cells, were carried out in the dorsal region of the hippocampal formation in urethan-anesthetized rats. Cells were studied during two spontaneously occurring hippocampal field conditions, asynchrony, termed large-amplitude irregular activity, and synchrony, termed theta. During the spontaneous cycling between these two field states, the effect of four levels of intracellular depolarizing and hyperpolarizing constant current injections on the amplitude and phase of membrane potential oscillations (MPOs) and the rate and pattern of cell discharges was assessed. Labeled CA1 pyramidal cells and bistratified cells met the criteria for classification as phasic theta-ON cells and labeled CA1 pyramidal layer basket cells, mossy hilar cells, and granule cells met the criteria for classification as phasic theta-OFF cells. MPOs were recorded in CA1 pyramidal cells, CA1 layer basket cells, mossy interneurons, and granule cells only during theta field activity, their onset in theta-ON cells signaled by a depolarizing shift of 5-10 mV and in theta-OFF cells by a hyperpolarizing shift of 5-10 mV, in membrane potential. The effect of current injections in phasic theta-ON and theta-OFF cells during the theta field condition revealed that MPO amplitude was voltage dependent and frequency was voltage independent. There were no phase changes observed in phasic theta-ON cells during current injections; however, amplitude analysis revealed an inverted U-shaped curve asymmetrically distributed around the average value of the membrane potential occurring during the spontaneous theta (no current) control condition. The occurrence and rate of rhythmical cell discharges in CA1 pyramidal phasic theta-ON cells during the theta condition was precisely controlled within a critical range of membrane potential values from approximately -57 to -68 mV, corresponding to a range of MPO amplitudes of approximately 4-7 mV. Outside the critical range, rhythmic cell discharges were abolished. Membrane potential oscillations in CA1 pyramidal layer basket cells underwent an approximate 180 degrees phase reversal when the membrane potential was depolarized above -65 mV. The occurrence and rate of rhythmic cell discharges in CA1 pyramidal layer basket cell phasic theta-OFF cells during the theta condition was precisely controlled within a critical range of membrane potential values from approximately -62 to -60 mV, corresponding to a range of MPO amplitudes of approximately 7-7.5 mV. Outside the critical range, cell discharges were absent or occurred singly.


Divergent simian T-cell lymphotropic virus type 3 (STLV-3) in wild-caught Papio hamadryas papio from Senegal: widespread distribution of STLV-3 in Africa.
Among eight samples obtained from a French primatology research center, six adult guinea baboons (Papio hamadryas papio), caught in the wild in Senegal, had a peculiar human T-cell leukemia virus type 2 (HTLV-2)-like Western blot seroreactivity (p24(+), GD21(+), K55(+/-)). Partial sequence analyses of the tax genes (433 bp) indicated that these baboons were infected by a novel divergent simian T-cell lymphotropic virus (STLV). Analyses of the complete proviral sequence (8,892 bp) for one of these strains (STLV-3/PPA-F3) indicate that this STLV was highly divergent from the HTLV-1 (61.6% of nucleotide similarity), HTLV-2 (61.2%), or STLV-2 (60.6%) prototype. It was, however, much more closely related to the few other known STLV-3 strains, exhibiting 87 and 89% of nucleotide similarity with STLV-3/PHA-PH969 (formerly PTLV-L/PH969) and STLV-3/CTO-604, respectively. The STLV-3/PPA-F3 sequence possesses the major HTLV or STLV open reading frames corresponding to the structural, enzymatic, and regulatory proteins. However, its long terminal repeat comprises only two 21-bp repeats. In all phylogenetic analyses, STLV-3/PPA-F3 clustered together in a highly supported single clade with the other known strains of STLV-3, indicating an independent evolution from primate T-cell lymphotropic virus type 1 (PTLV-1) and PTLV-2. The finding of a new strain of STLV-3 in a West African monkey (Guinea baboon) greatly enlarges the geographical distribution and the host range of species infected by this PTLV type in the African continent. The recent discovery of several different STLV-3 strains in many different African monkey species, often in contact with humans, strongly suggests potential interspecies transmission events, as it was described for STLV-1, between nonhuman primates but also to humans.


Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing.
Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline. Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.<br />.


[Etiology and prognosis of "internal medicine" acute renal failure in 1981-1990 and 1991-2000--an analysis of 510 cases in a single center].
Despite advanced techniques of renal replacement therapy as well as improved medical care and control over the last decade, the overall mortality of patients with "internal" nontraumatic acute renal failure (ARF) requiring replacement therapy is still high. In a retrospective study we compared causes of nontraumatic ARF, risk factors for the development of renal failure and mortality rates in patients with nontraumatic ARF, who received hemodialysis therapy from 1981 to 1990 and from 1991 to 2000. 510 patients with nontraumatic ANV requiring hemodialysis were evaluated, 278 patients in 1981-1990 and 232 patients in 1991-2000. In both groups the chronic risk factors for ANV such as hypertension, diabetes mellitus, chronic cardiac failure, chronic hepatic failure and pre-existing renal impairment and the causes of a traumatic ARF were compared. In addition, concomitant sepsis and multi-organ failure as prognostic parameters as well as mortality rates dependent on the causes of ARF were evaluated. In the latter period, there was a significant reduction in the prevalence of acute glomerulonephritis (3.0 versus 8.3%, p < 0.05) and acute interstitial nephritis (2.6 versus 7.6%, p < 0.05) as well as acute pancreatitis (1.7 versus 7.6%, p < 0.01) as causes of ARF. On the other hand, the prevalence of drug-induced ARF increased during the latter period (10.8 versus 4.7%, p < 0.05). Other etiologies of nontraumatic ARF did not significantly differ between the two decades. Patients treated from 1991 to 2000 had chronic risk factors for the development of ARF, namely diabetes (14.6 versus 6.8%), coronary artery disease (28.0 versus 9.3%) and pre-existing renal impairment (51.7 versus 17.6%, p < 0.001), more frequently than did patients dialysed from 1981-1990. The prevalence of sepsis and multi-organ failure was approximately the same in both periods. The overall mortality (41.8 versus 44.6%, NS) and mortality secondary to causes of nontraumatic ARF were similar in both periods. In summary: the prevalence of several causes of nontraumatic ARF has changed during the last decades. Furthermore, patients treated in the 90's had chronic risk factors for renal failure, namely diabetes and pre-existing renal impairment as well as coronary artery disease, more frequently than did subjects treated in the preceding time period. The prognosis of the patients has not been significantly improved.


[Pathomorphological observation of the hypertrophic scar induced by injury to conical structure in female red Duroc pig].
To further explore the relationship between hypertrophic scar and injury to conical structure of skin and the pathogenesis of hypertrophic scar, and to reproduce an optimal animal model of hypertrophic scar. The back of two FRDP pigs were shaved, and a piece of normal skin was harvested for the observation of conical structure of skin. Skin wounds with depth of 0.38 mm, 0.76 mm, 1.14 mm and 1.52 mm, respectively, were created by gas-driven dermatome. Eight wounds measuring 7.0 cm x 7.0 cm were created on each pig. The wounds were divided into 4 groups according to the wound depth with 4 wounds in each group, i.e. 0.38 mm group, 0.76 mm group, 1.14 mm group and 1.52 mm group. The 0.38 mm and 0.76 mm groups were designated as superficial wound groups and 1.14 mm and 1.52 mm groups as deep wound groups. The wounds were allowed to heal without treatment. Tissue samples from the wound were harvested on 0, 10, 30, 60, 90 and 150 post injury day (PID) , and they were sectioned for HE staining and staining for elastic fibers (VVG). The wound healing and the scar formation were observed with naked eye. The skin conical structures in normal and injured skin were also observed. The morphology of hypertrophic scar was observed, and the thickness of the scar tissue was determined and scored. The wounds in superficial wound groups healed within 3 weeks with flat surface without scar formation. The wounds in deep wound groups healed later than 4 weeks with thick, hairless, hard in texture, with depigmentation or pigmentation, finally forming contracture. The skin conical structure could be found on the back of FRDP with HE and VVG staining, and it was similar to that of human in terms of the structure. In superficial wound groups, the upper part of the skin conical structure was injured, but fat fornix and glands were intact. In deep wound groups, the lower part of the skin cone, together with the fat fornix and gland were all injured. On the 150th post injury day, the histological picture of the tissue in superficial wound groups was similar to that of normal skin. But the skin conical structure could not be found in deep wound groups, and the wounds were filled by a large accumulation of disarrayed and irregularly arranged collagen fibers. With passage of time, the scar became thicker and thicker, and the scar hypertrophy reached the zenith in 150th PID. The injury of skin conical structure can lead to the formation of hypertrophic scar. FRDP can be used to reproduce and ideal model of hypertrophic scar.


Immunosuppressive treatment for peripheral neuropathies in Sjogren's syndrome - a systematic review.
Sjogren's syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no consensus about peripheral neuropathy treatment in SS. Our aim is to identify studies proving the efficiency of immunosuppressive treatment on peripheral neuropathies in SS. The search was conducted on the PubMed (MEDLINE) database. Studies with patients diagnosed with SS and peripheral neuropathy were included. Treatment with one of the following was among inclusion criteria: glucocorticoids (GC), rituximab (RTX), azathioprine (AZA), mycophenolic acid (MMF), cyclophosphamide (CP), methotrexate (MTX), plasmapheresis or iv immunoglobulins (IV IG). A total of 116 results were found and abstracts were examined. 103 papers were excluded, and the remaining 13 papers were analyzed. They were 3 case series and 10 case reports, retrospective, totalizing 62 patients of which 22 (35.5%) received IV IG, 8 (13%) received RTX, 7 (11%) CP, and 5 (8%) received only GC. Drug associations containing corticosteroids were frequent. Of those 22 treated with IV IG, 18 patients improved (82%), and 4 stabilized (18%). IV IG was useful in sensory, motor and sensorimotor neuropathies. CP had good results in mononeuritis multiplex, while autonomic neuropathies responded well to GC or RTX. AZA, RTX, MTX, MMF or plasmapheresis were not used alone. Follow-up periods were heterogenous and the evaluation of the neuropathy was not systematic. There is only low level evidence (retrospective case reports and case series). In most cases, IV IG treatment in patients with peripheral neuropathies and SS resulted in clinical improvement, while other therapies, such as RTX, corticosteroids and CP proved to be useful in a handful of cases.