Mid-term results of endovascular abdominal aortic aneurysm repair: is it possible to predict sac shrinkage?
To evaluate the mid-term results of endovascular repair of abdominal aortic aneurysms and to predict subsequent sac shrinkage. From December 2006 to April 2010, 114 abdominal aortic aneurysms were treated with stent grafts. The intraoperative sac pressure was measured by a microcatheter. Correlations between the diameter change and relevant factors were determined by a logistic regression analysis. Stent grafts were deployed successfully in all patients. Type-2 endoleaks were noted in 25 patients (22%); there were no type-1 or type-3 endoleaks at discharge. The clinical success rate was 99%. The diameter was reduced in 40 patients (56%) but remained unchanged in 32 (44%). There were no aneurysms that increased in diameter. At 2 years after the repair the rate of cumulative survival was 87% and freedom from secondary intervention was 95%. The sac pressure index after stent grafting with a reduced diameter was 0.56 ± 0.11 and that of patients with an unchanged diameter was 0.52 ± 0.14. There were no significant differences between the two groups. Persistent type-2 endoleaks had a slightly negative effect on sac shrinkage (P = 0.052). The mid-term results of endovascular aneurysm repair were satisfactory. Although it was difficult to predict the fate of a sac after stent grafting, persistent type-2 endoleaks were observed to have a slightly negative impact on sac shrinkage.


Searching for epistasis and linkage heterogeneity by correlations of pedigree-specific linkage scores.
Recognizing that multiple genes are likely responsible for common complex traits, statistical methods are needed to rapidly screen for either interacting genes or locus heterogeneity in genetic linkage data. To achieve this, some investigators have proposed examining the correlation of pedigree linkage scores between pairs of chromosomal regions, because large positive correlations suggest interacting loci and large negative correlations suggest locus heterogeneity (Cox et al. [1999]; Maclean et al. [1993]). However, the statistical significance of these extreme correlations has been difficult to determine due to the autocorrelation of linkage scores along chromosomes. In this study, we provide novel solutions to this problem by using results from random field theory, combined with simulations to determine the null correlation for syntenic loci. Simulations illustrate that our new methods control the Type-I error rates, so that one can avoid the extremely conservative Bonferroni correction, as well as the extremely time-consuming permutational method to compute P-values for non-syntenic loci. Application of these methods to prostate cancer linkage studies illustrates interpretation of results and provides insights into the impact of marker information content on the resulting statistical correlations, and ultimately the asymptotic P-values.


[Assessment of 2 automated microdilution techniques compared to an agar dilution method in determining sensitivity to fosfomycin in strains of carbapenem-resistant Pseudomonas aeruginosa].
Carbapenems-resistance in Pseudomonas aeruginosa isolates has been widely reported. Fosfomycin has been shown to act synergistically with other antimicrobials. The agar dilution method was approved for susceptibility testing for fosfomycin and Pseudomonas aeruginosa. However, broth microdilution methods are the basis of systems currently used in clinical microbiology laboratories. The results of this study indicate that these methods are acceptable as susceptibility testing methods for fosfomycin against these organisms.


Determination of the sites of cAMP-dependent phosphorylation on the nicotinic acetylcholine receptor.
The nicotinic acetylcholine receptor is a substrate for cAMP-dependent protein kinase both in vitro and in vivo. Recently, it has been demonstrated that phosphorylation of the nicotinic receptor by this kinase increases its rate of rapid desensitization. We now report the identification of the cAMP-dependent phosphorylation sites on the gamma and delta subunits. Two-dimensional phosphopeptide mapping of the phosphorylated gamma and delta subunits, after limit proteolysis with thermolysin, indicated that each subunit is phosphorylated on a single site. Phosphoamino acid analysis of the 32P-labeled subunits demonstrates that phosphorylation had occurred exclusively on serine residues. Purified phosphorylated subunits were cleaved with cyanogen bromide and the resultant phosphopeptides were purified by reverse-phase high performance liquid chromatography. Shorter phosphopeptides, obtained by secondary digestion with trypsin, were purified and subjected to both automated gas-phase sequencing and manual Edman degradation. The results demonstrate that the gamma subunit was phosphorylated at Ser-353, contained within the sequence Arg-Arg-Ser(P)-Ser-Phe-Ile and that the delta subunit was phosphorylated at Ser-361, contained within the sequence Arg-Ser-Ser(P)-Ser-Val-Gay-Tyr-Ser-Lys. Determination of the sites phosphorylated within the structure of the gamma and delta subunits should contribute to the molecular characterization of the regulation of desensitization of the nicotinic acetylcholine receptor by protein phosphorylation.


Genetic connection of carotid atherosclerosis with coat color and body weight in an intercross between hyperlipidemic mouse strains.
Atherosclerosis in the carotid artery is a major cause of ischemic stroke and has a strong genetic component. The aim of this study was to identify genetic factors contributing to carotid atherosclerosis. One hundred fifty-four female F2 mice were generated from an intercross between LP/J and BALB/cJ Apoe-null (Apoe-/-) mice and fed 12 wk of Western diet. Atherosclerotic lesions, body weight, and coat color were measured and genotyping was performed using miniMUGA genotyping arrays. A significant quantitative trait locus (QTL) on chromosome (Chr) 7, named Cath20, and five suggestive QTL on Chr 6, 12, 13, 15, and X were identified for carotid lesions. Three significant QTL, Bwfq2, Bw1n, Bwtq6, on Chr 2, 7, and 15 were identified for body weight. Two significant QTL, Chop2 and Albc2, on Chr 4 and 7 were identified for coat color, with Tyr, encoding tyrosinase, being the causal gene of Albc2. Cath20 overlapped with or was close to QTL Bw1n and Albc2 on Chr7. Carotid lesion sizes were significantly correlated with body weight and graded coat color in F2 mice. Cath20 on Chr7 disappeared after adjustment for coat color but remained after adjustment for body weight. Tyr was abundantly expressed in atherosclerotic lesions. These results demonstrate genetic connections of carotid atherosclerosis with body weight and coat color in hyperlipidemic mice and suggest a potential role for Tyr in carotid atherosclerosis.


Surface-bound aspartate aminotransferase on collagen films. Compared properties with native enzyme.
Aspartate aminotransferase (L-aspartate : 2-oxoglutarate aminotransferase, EC 126.96.36.199) has been covalently bound to chemically activated collagen films. This enzyme had never previously been coupled to any other solid support. The coupling method, including acyl azide formation on the carrier, allowed coupling of many other enzymes. A systematic study of coupling conditions has been performed; influence of time of coupling and of concentration of coupling solution on the enzymatic activity retained on the film. Coupling solutions could be used for several successive couplings. To determine the yield of binding, N-[14C] ethylmaleimide-labelled enzyme was prepared fully active and bound to collagen films. After lyophilisation the film retained most of its activity when stored in buffer and the half-life of the enzymatic film was about ten months. pH Dependence and activation energy were about the same for soluble and coupled enzyme. Coupling protects against thermal denaturation and increases the stability of the enzyme; the enzymatic film could be used repeatedly. Kinetics were somewhat modified in the coupled enzyme as compared to the enzyme in solution. Glutamate appeared more available while oxaloacetate seemed to be limiting. These modifications might be due to the proteic support itself. The enzymatic films also revealed themselves as a good tool for industrial or clinical purposes as well as for studying the mechanism of enzyme action.


Comparison and analysis of inter-subject variability of simulated magnetic activity generated from gastric electrical activity.
Electrogastrograms (EGGs) produced from gastric electrical activity (GEA) are used as a non-invasive method to aid in the assessment of a subject's gastric condition. It has been documented that recordings of the magnetic activity generated from GEA are more reliable. Typically, with magnetic measurements of GEA, only activity perpendicular to the body is recorded. Also, external anatomical landmarks are used to position the magnetic recording devices, SQUIDs, (Superconducting Quantum Interference Devices) over the stomach with no allowance made for body habitus. In the work presented here, GEA and its corresponding magnetic activity are simulated. Using these data, we investigate the effects of using a standard SQUID location as well as a customized SQUID position and the contribution the magnetic component perpendicular to the body makes to the magnetic field. We also explore the effects of the stomach wall thickness on the resultant magnetic fields. The simulated results show that the thicker the wall, the larger the magnitude of the magnetic field holding the same signal patterns. We conclude that most of the magnetic activity arising from GEA occurs in a plane parallel to the anterior body. We also conclude that using a standard SQUID position can be suboptimal.


Antiepileptic potential and behavioral profile of L-pGlu-(2-propyl)-L-His-L-ProNH2, a newer thyrotropin-releasing hormone analog.
Thyrotropin-releasing hormone (TRH) and its analogs have a number of neurobiological functions and therapeutic uses in disorders of the central nervous system. In this study, the newly synthesized TRH analogs were evaluated for central nervous system activity in pentobarbital-induced sleeping in mice. The most potent TRH analog (L-pGlu-(2-propyl)-L-His-L-ProNH(2) coded as NP-647) was evaluated for its antiepileptic potential in various seizure models in mice in comparison with TRH. Intravenous pretreatment with NP-647 (10 and 20 micromol/kg body wt) significantly delayed the onset and reduced the frequency of convulsions in the pentylenetetrazole model, but not in the maximum electroshock seizure model. Also, it was found to be protective against picrotoxin- and kainic acid-induced seizures. However, NP-647 did not significantly affect theophylline-induced seizures. Further study of the effect of NP-647 on locomotor activity and a functional observational battery revealed that it did not significantly exhibit any undesirable effects as compared with vehicle and TRH. NP-647 did not significantly affect cerebral blood flow, whereas the native peptide TRH markedly increased cerebral blood flow. Furthermore, NP-647 exerted antiepileptic activity without significantly altering plasma thyroid-stimulating hormone levels and mean arterial blood pressure. This suggests that NP-647 is more selective for central nervous system activity and devoid of hormonal and cerebrovascular system effects. In contrast, TRH exhibited cardiac and endocrine effects as marked by significant elevation in mean arterial blood pressure and plasma thyroid-stimulating hormone levels. This study demonstrates that NP-647 has potential antiepileptic activity devoid of undesirable effects and, thus, can be exploited for the prevention and treatment of epilepsy.


Impact of age and gender on the coping styles and psychiatric morbidity faced by informal primary caregivers of HIV-infected individuals living in India.
Primary caregivers of HIV-infected patients face enormous burden, which if inappropriately coped, leads to psychiatric morbidity. Little is known of what role caregiver's age and gender play in this. To assess the socio-demographic profile and the influence of age and gender on coping strategies and psychiatric morbidity. Sixty caregivers were assessed on a semistructured sociodemographic proforma, a coping checklist, and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; [SCID-I]). Majority of the carers were young, equally from both genders, and used the same number of coping strategies which increased with age. "Avoidance" was preferred by males and older carers. Youngsters had maximum psychiatric morbidity, majority of the depressed were females, while 90% of nicotine dependants were males. Gender, but not age, decided the style of coping and extent of psychiatric morbidity hence gender-specific interventions will improve the quality of life of the carers and their wards.


Genetic Effects of Single Nucleotide Polymorphisms in the Goat GDF9 Gene on Prolificacy: True or False Positive?
Goat reproductive traits are complex quantitative traits controlled by polygenes and multipoint. To date, some high-fertility candidate genes in livestock have been unearthed and the growth differentiation factor 9 (GDF9) gene is one of them, which plays a crucial role in early folliculogenesis. According to the relevant previous studies and the National Center for Biotechnology Information Search database (NCBI), a total of 45 single nucleotide polymorphisms (SNPs) have been detected in the goat GDF9 gene, but which one or which ones have important effects on goat fecundity is still uncertain. Hence, in order to find effective molecular markers for goat genetic breeding and accelerate the goat improvement, this study summarized and classified the above 45 SNPs into four kinds, as well as compared and analyzed the same SNP effects and the different SNPs linkage effects on the reproductive traits in different goat breeds. Since there were many SNPs in the goat GDF9 gene, only 15 SNPs have been identified in more than 30 goat breeds worldwide and they showed different effects on the litter size. Therefore, this study mainly chose these 15 SNPs and discussed their relationship with goat productivity. Results showed that three non-synonymous SNPs A240V, Q320P, and V397I and three synonymous ones L61L, N121N, and L141L played a "true" role in the litter size trait in many goat breeds around the world. However, the regulatory mechanisms still need further research. These results provide an effective tool for follow-up research developing the goat molecular breeding strategies and improving the goat reproductive traits.


ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies.
Alpha-1,3-glucosyltransferase congenital disorder of glycosylation (ALG6-CDG) is a congenital disorder of glycosylation. The original patients were described with hypotonia, developmental disability, epilepsy, and increased bleeding tendency. Based on Euroglycan database registration, we approached referring clinicians and collected comprehensive data on 41 patients. We found hypotonia and developmental delay in all ALG6-CDG patients and epilepsy, ataxia, proximal muscle weakness, and, in the majority of cases, failure to thrive. Nine patients developed intractable seizures. Coagulation anomalies were present in <50 % of cases, without spontaneous bleedings. Facial dysmorphism was rare, but seven patients showed missing phalanges and brachydactyly. Cyclic behavioral change, with autistic features and depressive episodes, was one of the most significant complaints. Eleven children died before the age of 4 years due to protein losing enteropathy (PLE), sepsis, or seizures. The oldest patient was a 40 year-old Dutch woman. The most common pathogenic protein alterations were p.A333V and p.I299Del, without any clear genotype-phenotype correlation. ALG6-CDG has been now described in 89 patients, making it the second most common type of CDG. It has a recognizable phenotype and a primary neurologic presentation.


Clinical pharmacokinetics of prazosin--1985.
Prazosin is a selective alpha 1-adrenoceptor antagonist which is useful alone or in combination for the treatment of hypertension and heart failure. Unlike many other antihypertensive drugs, the action of prazosin appears to be closely related to its concentration in plasma or whole blood. Prazosin is variably absorbed, is subject to first-pass metabolism, and is eliminated almost entirely as metabolites of much lower hypotensive activity than the parent drug. Prazosin is highly bound to plasma and tissue proteins. The influences of renal, hepatic and cardiac disease on the disposition of prazosin are reviewed, as are the effects of pregnancy and ageing. The optimum use of prazosin in clinical practice depends on an understanding of the pharmacokinetic properties of the drug.


Gene expression profiling identifies genes associated with invasive intraductal papillary mucinous neoplasms of the pancreas.
The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of an associated invasive carcinoma in IPMNs. Using oligonucleotide microarrays, we performed a large-scale gene expression profiling of 12 IPMNs with or without an associated invasive carcinoma. A subset of genes identified was validated for the gene expression patterns in a large panel of IPMNs by reverse-transcription polymerase chain reaction and/or immunohistochemistry. A total of 673 transcripts were identified as expressed at significantly higher levels (P < 0.05 and at fivefold or greater) in IPMNs relative to normal pancreatic ductal epithelial samples. Of interest, many of the genes identified as overexpressed in IPMNs have also been previously reported to be highly expressed in infiltrating ductal adenocarcinoma of the pancreas. By analyzing genes overexpressed selectively in IPMNs with an associated invasive carcinoma (n = 7), we also identified a panel of genes potentially associated with the invasive phenotype of the neoplasms. Immunohistochemical validation revealed that claudin 4, CXCR4, S100A4, and mesothelin were expressed at significantly high frequency in invasive IPMNs than in noninvasive IPMNs. Notably, the expression of at least two of the four proteins was observed in 73% of 22 invasive IPMNs but in none of 16 noninvasive IPMNs (P < 0.0001). Our findings suggest that preoperative assessment of gene expression profiles may be able to differentiate invasive from noninvasive IPMNs.


Changes of apoptosis-related proteins in hippocampus of SAM mouse in development and aging.
Expression of Caspase and Bcl-2 proteins was examined in the hippocampus of senescence-accelerated mice (SAM, P8 and R1 strain) from E19 to 16 months of age. Immunoblotting analysis showed no upregulation of pro-apoptotic proteins (caspase-2L, -3, -6, -8, -9, and Bax) with age while all the anti-apoptotic proteins (caspase-2S, Bcl-2, and Bcl-XL) remained unchanged during aging. Terminal dUTP nick end labeling (TUNEL) and electron microscopy on the hippocampus of 3- and 16-month-old SAM revealed very few TUNEL positive cells in both groups. Morphometric study further showed neuronal loss in the hippocampus was not age-related. Our results suggest apoptosis and cell loss are minor events in the hippocampus of SAM mice and are unlikely to be the cause of functional decline during aging in SAM.


C13C4.5/Spinster, an evolutionarily conserved protein that regulates fertility in C. elegans through a lysosome-mediated lipid metabolism process.
Lipid droplets, which are conserved across almost all species, are cytoplasmic organelles used to store neutral lipids. Identification of lipid droplet regulators will be conducive to resolving obesity and other fat-associated diseases. In this paper, we selected 11 candidates that might be associated with lipid metabolism in Caenorhabditis elegans. Using a BODIPY 493/503-based flow cytometry screen, 6 negative and 3 positive regulators of fat content were identified. We selected one negative regulator of lipid content, C13C4.5, for future study. C13C4.5 was mainly expressed in the worm intestine. We found that this gene was important for maintaining the metabolism of lipid droplets. Biochemical results revealed that 50% of triacylglycerol (TAG) was lost in C13C4.5 knockout worms. Stimulated Raman scattering (SRS) signals in C13C4.5 mutants showed only 49.6% of the fat content in the proximal intestinal region and 86.3% in the distal intestinal region compared with wild type animals. The mean values of lipid droplet size and intensity in C13C4.5 knockout animals were found to be significantly decreased compared with those in wild type worms. The LMP-1-labeled membrane structures in worm intestines were also enlarged in C13C4.5 mutant animals. Finally, fertility defects were found in C13C4.5(ok2087) mutants. Taken together, these results indicate that C13C4.5 may regulate the fertility of C. elegans by changing the size and fat content of lipid droplets by interfering with lysosomal morphology and function.


DNAase I sensitivities in chromatin of the Xenopus laevis somatic and oocyte 5 S DNAs.
The DNAase I sensitivities of the somatic-type 5 S DNA and oocyte-type 5 S DNA have been compared in nuclei from adult somatic tissues of Xenopus laevis. Neither of these Type III genes is expressed in mature erythrocytes and only somatic-type 5 S DNA is expressed in liver. We find that somatic-type 5 S DNA is DNAase-I-sensitive in liver nuclei and less sensitive in erythrocyte nuclei, while oocyte-type 5 S DNA is insensitive in both tissues. The DNAase I sensitivity appears to be uniform across each active somatic-type 5 S DNA repeat. Two regions slightly hypersensitive to DNAase I are found only in liver somatic-type 5 S DNA. One of these regions is within the gene, overlapping with the binding site of the transcription factor (TF III A) required for 5 S RNA synthesis. Thus, the correlation between DNAase I sensitivity and gene activity previously seen for protein-coding genes also holds for these Type III genes. Our data lead us to suggest that the fully DNAase-I-sensitive chromatin conformation on 5 S DNA requires the presence both of transcription factors and RNA polymerase.


Reduced water-holding capacity of beef during refrigeration is associated within creased heme oxygenase 1 expression, oxidative stress and ferroptosis.
Low molecular weight iron (LMW-Fe)-mediated oxidative stress from heme degradation may reduce beef water-holding capacity (WHC). However, the underlying mechanism of heme degradation is still unknown. In the present study, we assessed the WHC, tissue morphology, reactive oxygen species (ROS), apoptosis, heme oxygenase(HMOX) 1 expression, and ferroptosis characteristics of beef chilled at 4 °C for 6 days. Results showed that water loss increased and WHC decreased during beef storage (P < 0.05). Increased protein and mRNA expression of HMOX1 promoted the decomposition of heme and facilitated the liberation of iron ions (P < 0.05), and excess LMW-Fe was associated with ROS formation, depletion of glutathione, and inhibition of glutathione peroxidase 4 activity (P < 0.05). Muscle tissue showed typical features of ferroptosis, including expression of ferroptosis-related genes, malondialdehyde accumulation, and structural damage to mitochondria (P < 0.05). It was also found that HMOX1 and the heme pathway-mediated ferroptosis were associated with structural changes in myofibrils and reduced WHC in chilled beef.


Production of a phosphatidylglycerol-like substance by genital flora bacteria.
Bacteria contaminating amniotic fluid have anecdotally been shown to produce a phosphatidylglycerol-like substance, thus giving false positive tests for phosphatidylglycerol in vaginal pool fluid from patients with premature rupture of the membranes. Isolates of Escherichia coli, Proteus mirabilis, Acinetobacter calcoaceticus, Klebsiella pneumoniae, Staphylococcus aureus, coagulase-negative Staphylococcus, Streptococcus faecalis, and Streptococcus agalactiae (group B streptococcus) were grown in broth and analyzed for the presence of phosphatidylglycerol-like material by one-dimensional thin-layer chromatography and also by a polyclonal, immunologic slide agglutination test (Amniostat-FLM). All species demonstrated a positive test result for phosphatidylglycerol by either thin-layer chromatography, slide agglutination, or both. The material migrated separately from cardiolipin and phosphatidylethanolamine as determined by chromatography, but identically with the phosphatidylglycerol control. Gram-negative species were more strongly positive than gram-positive organisms. Colony counts on the order of 10(8) colony-forming units per milliliter were necessary to give positive test results for phosphatidylglycerol. The possible clinical implications of these findings are discussed.


Mediastinal lymphangioma in adults: CT and MR imaging features.
Adult mediastinal lymphangiomas are rare lesions the diagnosis of which is difficult based on imaging studies. A retrospective study of CT, MR, and pathologic findings of mediastinal lymphangioma was performed in order to correlate pathological and imaging findings. Nine cases of adult lymphangiomas were identified in the records of our institution over a 12-year period. The CT, MR, and pathologic findings were reviewed. Lesions were classified pathologically as unilocular, cavernous, and intermediate types. Pathologic examination identified six cases of unilocular lesion, two cases of cavernous type, and one intermediate type. The CT features (n = 9) included a smoothly marginated non-enhancing mass of water attenuation (n = 7), a non-enhancing mass of soft tissue attenuation (n = 1), and an enhancing multiseptated mass (n = 1). Lesions were located in the anterior mediastinum (n = 2), right paratracheal (n = 4), subcarinal (n = 1), aortopulmonic window (n = 1) areas, and below the left hilum extending into the posterior mediastinum (n = 1). The MR features (n = 3) were characterized by an enhancing multicystic and multiseptated appearance, evocative of a cavernous type in two cases. The CT appearance of mediastinal thoracic lymphangioma is variable depending on the pathologic type. The most common unilocular type is a non-enhancing thin-walled mass on CT. A less frequent cavernous type can be suggested based on a multiseptated and loculated mass on CT and/or MR examination.


Rediscovering Einstein's legacy: How Einstein anticipates Kuhn and Feyerabend on the nature of science.
Thomas Kuhn and Paul Feyerabend promote incommensurability as a central component of their conflicting accounts of the nature of science. This paper argues that in so doing, they both develop Albert Einstein's views, albeit in different directions. Einstein describes scientific revolutions as conceptual replacements, not mere revisions, endorsing 'Kant-on-wheels' metaphysics in light of 'world change'. Einstein emphasizes underdetermination of theory by evidence, rational disagreement in theory choice, and the non-neutrality of empirical evidence. Einstein even uses the term 'incommensurable' specifically to apply to challenges posed to comparatively evaluating scientific theories in 1949, more than a decade before Kuhn and Feyerabend. This analysis shows how Einstein anticipates substantial components of Kuhn and Feyerabend's views, and suggests that there are strong reasons to suspect that Kuhn and Feyerabend were directly inspired by Einstein's use of the term 'incommensurable', as well as his more general methodological and philosophical reflections.


Impact of symptom resolution on medication adherence in first episode psychosis.
Adequate adherence to medication confers benefits on patients with psychotic illness, but is difficult to achieve. Efficacy of medication influences adherence in patients in advanced phases of illness and may have a similar influence on patients with a first episode of psychosis (FEP). We assessed medication adherence and efficacy in 216 FEP patients at program entry and at 3 and 6 months later. "Efficacy" was evaluated as the ability of medication to reduce positive or negative symptoms to below established thresholds for clinical remission at each evaluation. Adherence was defined as adequate (>75%) or not. Resolution of negative symptoms by month 3 of treatment was associated with inadequate adherence at months 3 and 6. In contrast, rapid resolution of positive symptoms showed no relationship to adherence. In a multivariate analysis taking into account other determinants of adherence in FEP, the role of early negative symptom remission was confirmed, and we found that a 3-month sustained remission of positive symptoms was associated with adequate adherence. Medication efficacy may promote adherence if it produces sustained remission of positive symptoms. However, many patients who benefit from medication, particularly those with rapid improvement of negative symptoms, fail to adhere to the treatment.


Uterine adenosarcoma in a boy with persistent müllerian duct syndrome: first reported case.
Persistent müllerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism. Bilateral fallopian tubes and a uterus occur with an otherwise normal male phenotype. Testicular neoplasm in PMDS has been reported, but malignant degeneration of the remnant female genitalia has only once been reported. We present imaging, surgical specimen, and surgical pathology of the first documented case of uterine adenosarcoma of a müllerian remnant in a 14-year-old boy with PMDS presenting with gross hematuria and increasing abdominal protuberance. The child died of metastatic disease after surgical resection.


MemBrain-contact 2.0: a new two-stage machine learning model for the prediction enhancement of transmembrane protein residue contacts in the full chain.
Inter-residue contacts in proteins have been widely acknowledged to be valuable for protein 3 D structure prediction. Accurate prediction of long-range transmembrane inter-helix residue contacts can significantly improve the quality of simulated membrane protein models. In this paper, we present an updated MemBrain predictor, which aims to predict transmembrane protein residue contacts. Our new model benefits from an efficient learning algorithm that can mine latent structural features, which exist in original feature space. The new MemBrain is a two-stage inter-helix contact predictor. The first stage takes sequence-based features as inputs and outputs coarse contact probabilities for each residue pair, which will be further fed into convolutional neural network together with predictions from three direct-coupling analysis approaches in the second stage. Experimental results on the training dataset show that our method achieves an average accuracy of 81.6% for the top L/5 predictions using a strict sequence-based jackknife cross-validation. Evaluated on the test dataset, MemBrain can achieve 79.4% prediction accuracy. Moreover, for the top L/5 predicted long-range loop contacts, the prediction performance can reach an accuracy of 56.4%. These results demonstrate that the new MemBrain is promising for transmembrane protein's contact map prediction. http://www.csbio.sjtu.edu.cn/bioinf/MemBrain/. Supplementary data are available at Bioinformatics online.


Cost-effective treatment of the infertile couple.
To review the published literature on the cost-effective approach to infertility treatment. The literature on the economics and cost-effectiveness of infertility treatments was reviewed. Studies related to this topic were identified through MEDLINE. Few cost-effectiveness studies about infertility treatment have been published. In the absence of tubal blockage and severe male factor, use of IUI and hMG-IUI is more cost-effective than IVF. In vitro fertilization is at least as cost-effective as tubal surgery. Although IVF costs are high, they fall well within the range of other accepted medical treatments and are below the general public's willingness to pay for these treatments. Cost-effectiveness analysis is an important means of improving quality of care while controlling costs. Further work regarding cost-effectiveness of treatments among different diagnostic groups is needed.


Effects of provision and receipt of social support on adjustment to laparoscopic radical prostatectomy.
Radical prostatectomy has a negative impact on prostate cancer patients' health-related quality of life (HRQoL). Social support may help patients adjust to their situation after surgery. We investigated patients' accounts of received social support as well as their spouses' accounts of provided social support as predictors of patients' HRQoL 6 months after surgery. Moreover, we tested whether patients with lower HRQoL at 2 weeks after surgery had the most benefit from spousal support. A total of 77 patients (M = 61.57 years, SD = 6.03) and their spouses (M = 58.46 years, SD = 7.52) completed questionnaires at 2 weeks and 6 months after laparoscopic radical prostatectomy. Received social support, spousal provided social support, and HRQoL were assessed 2 weeks after surgery, and HRQoL was assessed again 6 months later. Patients with lower HRQoL at 2 weeks after surgery benefited more from the receipt and their partners' provision of support in terms of HRQoL 6 months later than patients with a higher HRQoL at the beginning. Assessing patients' HRQoL might be one method to identify those individuals who are in special need of support from their spouses.


The test characteristics of physician clinical gestalt for determining the presence and severity of anaemia in patients seen at the emergency department of a tertiary referral hospital in Tanzania.
To evaluate the test characteristics of clinical gestalt for detecting the presence and severity of anaemia in emergency department patients at a tertiary referral hospital in Tanzania. This prospective study enrolled a convenience sample of emergency department patients who had a complete blood count ordered by the treating physician in the course of their clinical care. Physicians recorded their impression of the presence and severity of anaemia before viewing the laboratory results. To assess interobserver agreement, a second physician provided their blinded gestalt impression of the patient's haemoglobin level. We enrolled 216 patients and complete data were available for 210 patients (97%), 59% male, median age 30 years. The range of measured haemoglobin values was 1.5-15.4 g/dL. The physicians rated anaemia mild or absent in 74 (35%), moderate in 72 (34%) and severe in 64 patients (30%). These estimates were significantly concordant with the laboratory haemoglobin measurements (Kendall's τ b=0.63, 95% CI 0.57 to 0.69, p<0.0001). The test characteristics of physician gestalt estimates for severe anaemia were: sensitivity 64% (95% CI 53% to 74%), specificity 91% (95% CI 85% to 96%), positive likelihood ratio of 7.4 (95% CI 4.2 to 13.3) and negative likelihood ratio of 0.40 (0.3 to 0.5). The weighted Cohen's κ for interobserver agreement between physicians on the gestalt estimate of the degree of anaemia was 0.87 (95% CI 0.76 to 0.98). Physicians' estimates of the severity of anaemia were significantly concordant with laboratory haemoglobin measurements. Sensitivity of the gestalt estimate for severe anaemia was moderate. Interobserver agreement was 'almost perfect'.


Helical (spiral) CT of the thorax.
Helical CT should be used routinely for thoracic imaging both as a primary screening tool in patients assessed for metastatic disease or lung cancer and as a problem solving modality in more complex lesions (e.g., arteriovenous malformations). Greater confidence in diagnosis and improved accuracy of lesion detection are benefits resulting from the volumetric data acquisition of helical CT. Optimal use of intravenous contrast material during a short scan interval enhances the diagnosis of pulmonary thromboembolic disease and aortic pathology. The airways can be displayed in detail on axial, coronal, or minimum intensity projection images, which is useful when planning interventional or surgical procedures.


The influence of swelling and matrix degradation on the microstructural integrity of tendon.
Tendon is multi-level fibre composite material, responsible for the transmission of forces from muscles to the skeleton. It is composed of a hierarchical arrangement of collagenous units surrounded by a proteoglycan-rich matrix, arranged to support strain transfer, and thus contribute to the mechanical behaviour of tendon. This study examines the effect of swelling and enzymatic degradation on structural integrity at different levels of the tendon hierarchy. Biochemical and microstructural analysis are used to examine the effects of incubation on the composition and swelling of the matrix, prior to a mechanical characterisation of sample integrity. Results indicated significant swelling of tendon fibrils and interfibrillar matrix after incubation in phosphate buffered saline, leading to a reduction in ultimate tensile load, with failure initiated between fibrils and sub-fibrils. In contrast, incubation with the enzyme chondroitinase ABC resulted in a total removal of glycosaminoglycan from the samples, and a subsequent reduction in the extent of swelling. These fascicles also demonstrated an increase in failure loads, with failure predominating between fibres. The findings from this work confirm the importance of the non-collagenous matrix components in controlling strain transfer within tendon structures. It also highlights the necessity to maintain samples within a suitable and controlled environment prior to testing.


Statistical models for autocorrelated count data.
A generalized linear mixed model is an increasingly popular choice for the modelling of correlated, non-normal responses in a regression setting. A number of methods are currently available for fitting a generalized linear mixed model including Monte-Carlo Markov-Chain maximum likelihood algorithms, approximate maximum likelihood (PQL), iterative bias correction, and others. Of interest in this paper is to compare the parameter estimation of the various methods in the modelling of a count data set, the incidence of polio in the USA over the period 1970-1983, using a longlinear generalized linear mixed model with an autoregressive correlation structure. Despite the fact that all of these methods are considered valid modelling techniques, we find that parameter estimates and standard errors differ substantially between analyses, particularly in the estimation of the parameters describing the random effects distribution. A small simulation study is helpful in understanding some of these differences. The methods lead to reasonably similar predictions for future observations, with small differences observed in some monthly counts.


The effect of cloprostenol on human luteal steroid and prostaglandin secretion in vitro.
1 Human luteal tissue slices from days 18, 21 and 25 of the menstrual cycle were superfused in vitro with Medium 199 alone or containing cloprostenol (1 microgram/ml). Concentrations of progesterone, oestradiol-17beta and prostaglandins F2alpha and E2 were determined in the superfusate samples. 2 Secretion of steroids and prostaglandins was maintained at an approximately constant level throughout the experiments (21 h in one case) when the tissue was perfused with M199 alone. 3 Superfusion with cloprostenol (1 microgram/ml) resulted in an initial depression of progesterone and oestradiol-17beta but this was not maintained, levels returning to control values or showing an increase, while superfusion with cloprostenol continued. Cloprostenol is not therefore considered to be luteolytic at this dose and under these conditions for human luteal tissue in vitro. 4 Superfusion with cloprostenol (1 microgram/ml) also resulted in a large stimulation of secretion of endogenous prostaglandin F2 alpha following a short lag phase. This stimulation was possibly due to the initial depression of progesterone secretion. A short-lived stimulation of prostaglandin E2 secretion was also observed. 5 The significance of the increase in prostaglandin E2 secretion and the interrelationships between the various changes observed with cloprostenol are difficult to interpret.


Synthesis and biological studies of some imidazolinone derivatives.
A Series of 4-(1-Aryl-5-oxo-2-phenyl-2-imidazolin-4-yl) metheno-5-chloro-3-methyl-1-phenyl-3-pyrazole) were synthesised and tested for their antibacterial, antiinflammatory and analagesic activities. Some of the compounds showed significant antiinflammatory properties.


Saturation technique does not decrease cancer detection during followup after initial prostate biopsy.
It has been reported that the prostate cancer detection rate in men with prostate specific antigen 2.5 ng/ml or greater undergoing saturation (20 cores or greater) prostate biopsy as an initial strategy is not higher than that in men who undergo 10 to 12 core prostate biopsy. At a median followup of 3.2 years we report the cancer detection rate on subsequent prostate biopsy in men who underwent initial saturation prostate biopsy. Saturation prostate biopsy was used as an initial biopsy strategy in 257 men between January 2002 and April 2006. Cancer was initially detected in 43% of the patients who underwent saturation prostate biopsy. In the 147 men with negative initial saturation prostate biopsy followup including digital rectal examination and repeat prostate specific antigen measurement was recommended at least annually. Persistently increased prostate specific antigen or an increase in prostate specific antigen was seen as an indication for repeat saturation prostate biopsy. During the median followup of 3.2 years after negative initial saturation prostate biopsy 121 men (82%) underwent subsequent evaluation with prostate specific antigen and digital rectal examination. Median prostate specific antigen remained 4.0 ng/ml or greater in 57% of the men and it increased by 1 ng/ml or greater in 23%. Cancer was detected in 14 of 59 men (24%) undergoing repeat prostate biopsy for persistent clinical suspicion of prostate cancer. No significant association was demonstrated between cancer detection and initial or followup prostate specific antigen, or findings of atypia and high grade prostatic intraepithelial neoplasia on initial saturation prostate biopsy. Cancers detected on repeat prostate biopsy were more likely to be Gleason 6 and organ confined at prostatectomy than were those diagnosed on initial saturation prostate biopsy. Previous experience suggests that, while office based saturation prostate biopsy improves cancer detection in men who have previously undergone a negative prostate biopsy, it does not improve cancer detection as an initial biopsy technique. We now report that the false-negative rate on subsequent prostate biopsy after initial saturation prostate biopsy is equivalent to that following traditional prostate biopsy. These data provide further evidence against saturation prostate biopsy as an initial strategy.


The loss of alveolar processus, mandible density and bone tissue structure in reference to the computerized analysis of intraoral radiography.
98 patients treated in the Department of Dental and Maxillofacial Surgery, Medical University and Institute of Rural Medicine in Lublin had radiovisiographically tested premolar teeth area on the left side. Reviewing radiovisiographical picture, there were defined bone mineral density and mandible bone structure and degree of loss of alveolar processus. It was concluded that the degree of loss of alveolar processus is significantly correlated with the researched patients' age, and is inversely correlated with mineral density and equivalent of mandible bone mineral contents. The achieved results prove that demineralisation changes can significantly influence teeth loss.


Comparison of Single- and Five-fraction Regimens of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non-small-cell Lung Cancer: A Two-institution Propensity-matched Analysis.
To evaluate differences in local control (LC), disease-specific (DC), and overall survival (OS) of patients with early-stage non-small-cell lung cancer (NSCLC) treated with single- (SF) versus 5-fraction (FF) stereotactic body radiation therapy (SBRT) at 2 institutions. Peripheral early-stage NSCLC cases treated with a median dose of 30 Gy in SF or a median dose of 50 Gy in FF were included per institutional practice. Kaplan-Meier and Cox models were used to assess survival. A matched-pair analysis was performed to account for imbalances. Toxicities including Common Terminology Criteria for Adverse Events (CTCAE) grade 3 pneumonitis, chest wall pain requiring long-acting narcotics, and hospitalization for respiratory events 6 months posttreatment were recorded. A total of 163 lesions were treated between 2007 and 2015; 65 received SF SBRT and 98 received FF SBRT. Most tumors were T1 (n = 92) and T2 (n = 34) lesions and had adenocarcinoma (n = 77) and squamous cell carcinoma (n = 46) histologies, respectively. In the matched cohort, there were no differences in OS, LC, DC, or progression-free survival between the groups. LC and OS at 1 year in the matched cohort was 95% and 88%, and 87% and 84% in the SF and FF cohorts, respectively. There was 1 grade 3 pneumonitis in the FF group, and 9 total hospitalizations post-SBRT, 3 (5%) in the SF group and 6 (6%) in the FF group. No statistically significant differences were seen in LC or DC following SF or FF SBRT in this matched cohort of peripheral lesions. No grade 4 or higher toxicities were reported.


Human papillomavirus in cervical cancer.
Epidemiologic studies supported by molecular technology have provided sufficient evidence of the causal role of some human papillomavirus (HPV) infections in the development of cervical cancer. The finding is consistent universally, and HPV has been proposed as the first identified necessary cause of cervical cancer. Such recognition translates into the concept that cervical cancer does not develop without persistent presence of HPV DNA. In the developed parts of the world, cytologic screening programs could benefit from the addition of HPV testing to their protocols. Controlled studies and one randomized trial have shown that HPV testing is helpful in solving the ambiguous cases generated by cytology reading. In populations where cytology programs are not functional or efficient, HPV testing is being evaluated as an alternative means of primary screening. Prevention of exposure to high-risk HPV types, either by prophylactic vaccination or by combined prophylactic and therapeutic immunologic intervention, may prove to be the most efficient and logistically feasible option for the prevention of cervical cancer in developing populations.


The organization of digit contact timing during grasping.
While the process of hand preshaping during grasping has been studied for over a decade, there is relatively little information regarding the organization of digit contact timing (DCT). This dearth of information may be due to the assumption that DCT while grasping exhibits few regularities or to the difficulty in obtaining information through traditional movement recording techniques. In this study, we employed a novel technique to determine the time of digit contacts with the target object at a high precision rate in normal healthy participants. Our results indicate that, under our task conditions, subjects tend to employ a radial to ulnar pattern of DCT which may be modulated by the shape of the target object. Moreover, a number of parameters, such as the total contact time, the frequency of first contacts by the thumb and index fingers and the number of simultaneous contacts, are affected by the relative complexity of the target object. Our data support the notion that a great deal of information about the object's physical features is obtained during the early moments of the grasp.


Anti-hepatocarcinoma effect of cordycepin against NDEA-induced hepatocellular carcinomas via the PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB pathway in mice.
The purpose of the present study was to evaluate the effects of cordycepin (CA) on N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinomas (HCC) and explore its potential mechanisms. Mice were randomly assigned to four groups: control group, NDEA group, NDEA+CA (20mg/kg) group, NDEA+CA (40mg/kg) group. The animal of each group were given NDEA (100ppm) in drinking water. One hour later, CA, which was dissolved in PBS, were intragastrically administered for continuous seven days. The results showed that CA reduced the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver and serum. CA also reduced the levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), methane dicarboxylic aldehyde (MDA), and stored the activity of superoxygen dehydrogenises (SOD) in serum. CA could obviously attenuate the hepatic pathological alteration. Furthermore, CA effectively inhibited the phosphorylations of phosphatidylinositol 3 kinase(PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR). In conclusion, our research suggested that CA exhibited protective effects on NDEA-induced hepatocellular carcinomas via the PI3K/Akt/mTOR pathway.


Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin-Darby canine kidney cells.
The nitrogen-containing bisphosphonates used for management of the patients with osteoporosis were reported to influence the function of renal tubular cells. However, how nitrogen-containing bisphosphates exert any effects on ion currents remains controversial. The effects of ibandronate (Iban), a nitrogen-containing bisphosphonate, on ionic channels, including two types of Ca2+-activated K+ (KCa) channels, namely, large-conductance KCa (BKCa) and intermediate-conductance KCa (IKCa) channels, were investigated in Madin-Darby canine kidney (MDCK) cells. In whole-cell current recordings, Iban suppressed the amplitude of voltage-gated K+ current elicited by long ramp pulse. Addition of Iban caused a reduction of BKCa channels accompanied by a right shift in the activation curve of BKCa channels, despite no change in single-channel conductance. Ca2+ sensitivity of these channels was modified in the presence of this compound; however, the magnitude of Iban-mediated decrease in BKCa-channel activity under membrane stretch with different negative pressure remained unchanged. Iban suppressed the probability of BKCa-channel openings linked primarily to a shortening in the slow component of mean open time in these channels. The dissociation constant needed for Iban-mediated suppression of mean open time in MDCK cells was 12.2 μM. Additionally, cell exposure to Iban suppressed the activity of IKCa channels, and DC-EBIO or 9-phenanthrol effectively reversed its suppression. Under current-clamp configuration, Iban depolarized the cells and DC-EBIO or PF573228 reversed its depolarizing effect. Taken together, the inhibitory action of Iban on KCa-channel activity may contribute to the underlying mechanism of pharmacological or toxicological actions of Iban and its structurally similar bisphosphonates on renal tubular cells occurring in vivo.


Antithrombin III activity (residual thrombin activity) in plasma from non-medicated or heparinized horses.
Two synthetic substrate assays (fluorometric and chromogenic) were used to measure antithrombin-III (AT-III) activity (residual thrombin activity) in non-medicated and heparin (sodium) treated horses. In 18 non-medicated horses the fluorometric substrate assay (FSA) values were similar to previous reports but they reflected inconsistent trends and larger deviations in the heparin-treated groups (Group 2: 40 and 100 U/kg IV, n = 6; Group 3: 240 U/kg IV, n = 5; Group 4: 80 U/kg IV followed by 160 U/kg SC, n = 8) when compared to the chromogenic substrate assay (CSA) values. The CSA values for the 18 non-medicated horses indicated a higher AT-III activity (lower residual thrombin activity) than the FSA. AT-III activity was quantified in 18 non-medicated horses (29 mg/dl) and compared well with values for humans (30 mg/dl) and dogs (40 mg/dl). Plasma heparin concentrations, determined by the FSA, correlated well with the 'therapeutic range' (1.5 fold to 2.5 fold prolongation of the activated partial thromboplastin time (APTT) normal value) and values reported for humans. The effect of heparin therapy on AT-III activity in four treatment regimens was evaluated. AT-III activity was not significantly affected (with one exception) by a single dose of intravenous (IV) heparin (40 and 100 U/kg) nor by repeated subcutaneous (SC) injections of heparin (240 U/kg). A transient increase in residual thrombin activity was measured 12 h after an intravenous (80 U/kg) injection of heparin. Large doses of heparin (80 U/kg IV followed by 160 U/kg SC) given every 12 h produced a progressive prolongation of the APTT. In this group the APTT remained prolonged 48 h after the last treatment.


Honeycomb-like holey Co3O4 membrane triggered peroxymonosulfate activation for rapid degradation of organic contaminants.
Heterogeneous advanced oxidation processes (AOPs) are commonly employed for the degradation of recalcitrant contaminants, however, practical application of heterogeneous AOPs has been limited by their low activation efficiency and inefficient utilization of radicals. Herein, this study demonstrates for the first time that 2D honeycomb-like holey membranes assembled by Co3O4 nanosheets, serve as an excellent activator for peroxymonosulfate (PMS) and aid in rapid pollutant removal. The Co3O4 membrane achieved 100% target pollutant ranitidine removal and a membrane retention time of only ~385 ms with the degradation rate 3-5 orders of magnitude faster than that achieved by conventional heterogeneous catalysis. Ranitidine degradation was maintained at >90% for 13 h of continuous-flow operation at a high flux of 176 L m-2 h-1 bar-1. Furthermore, the Co3O4 membrane could also effectively degrade several recalcitrant pollutants, including pharmaceutical personal care products, phenols, and dyes. SO4•- and •OH were identified as the primary reactive oxygen species in the Co3O4 membrane/PMS system, with Co providing the active site for PMS activation. This strategy of membrane-based AOP treatment offers helpful guidance for the design of other efficient heterogeneous catalytic systems and presents a novel approach to overcoming the limitations of conventional heterogeneous catalysis.


1-(2H-1,3-Benzodioxol-5-yl)ethanone thio-semicarbazone.
In the title compound, C10H11N3O2S, the 1,3-benzodioxole and hydrazinecarbothio-amide fragments are nearly planar [(mean deviations from planarity for non-H atoms of 0.0325 (12) Å and 0.0707 (10) Å, respectively] and subtend a dihedral angle of 29.06 (5)°. In the crystal, mol-ecules are linked by pairs of almost linear N-H⋯S hydrogen bonds, forming inversion dimers. These dimers are additionally connected by weaker and strongly bent N-H⋯S inter-actions into chains along [101]. There is one additional weak N-H⋯O contact which, if considered as an inter-action, leads to the formation of a three-dimensional network.


Comparison of three concomitant boost techniques for early-stage breast cancer.
Whole breast radiotherapy (RT) followed by a tumor bed boost typically spans 5-6 weeks of treatment. Interest is growing in RT regimens, such as concomitant boost, that decrease overall treatment time, lessening the time/cost burden to patients and facilities. Computed tomography (CT) scans from 20 cases were selected for this retrospective, dosimetric study to compare three different techniques of concomitant boost delivery: (1) standard tangents plus an electron boost, (2) intensity-modulated RT (IMRT) tangents using custom compensators plus an electron boost, and (3) IMRT tangents plus a conformal photon boost. The equivalent uniform dose model was used to compare the plans. The average breast equivalent uniform dose value for the three techniques (standard, IMRT plus electrons, and IMRT plus photons) was 48.6, 47.9, and 48.3, respectively. The plans using IMRT more closely approximated the prescribed dose of 46 Gy to the whole breast. The breast volume receiving >110% of the dose was less with the IMRT tangents than with standard RT (p = 0.037), but no significant difference in the maximal dose or other evaluated parameters was noted. Although the IMRT techniques delivered the prescribed dose with better dose uniformity, the small improvement seen did not support a goal of improved resource use.


Influence of propranolol on high energy phosphate and tissue acidosis in regional ischemic myocardium of pigs: assessment with arterial pressure and respiration gated in vivo 31-phosphorus magnetic resonance spectroscopy.
In an attempt to define the metabolic abnormalities of the ischemic myocardium, the changes in high energy phosphates, inorganic phosphate and intracellular pH were serially and quantitatively evaluated in ischemic porcine hearts having no collateral circulation, using arterial pressure and respiration gated in vivo 31P magnetic resonance spectroscopy. The protocol was also modified for propranolol pretreatment (0.6 mg/kg intravenously) to define its effect on the metabolism of ischemic myocardium. In the non-treated group, creatine phosphate was rapidly depleted by 10 minutes after ischemia; by 40 minutes, ATP and intracellular pH gradually decreased to 10 +/- 11% of control and to 5.90 +/- 0.26, respectively, and inorganic phosphate rose to 303 +/- 43% of control. In the propranolol treated group, the concentrations of creatine phosphate and ATP were higher, and those of inorganic phosphate and tissue pH were similar compared with controls during 40 minutes of ischemia. This suggests that the beneficial effect of propranolol on the ischemic myocardium is due to the preservation of ATP, an essential energy resource for numerous enzymatic reactions in viable myocardium.


Relationship between erector spinae muscle oxygenation via in vivo near infrared spectroscopy and static endurance time in healthy males.
The purpose of the study was to confirm the trends in right and left side muscle blood volume (Mbv) and muscle oxygenation (Mox) during the Biering-Sorensen muscular endurance (BSME) test, compare right and left side Mbv and Mox responses, and predict BSME time via Mox variables. Research suggests that during moderate intensity (approximately 20% of maximal volitional contraction) muscle contraction blood flow will decrease as a result of increased intramuscular pressure. Moreover, decreased muscle oxygenation is believed to be associated with diminished musculoskeletal endurance time, but until the development of near infrared spectroscopy (NIRS) it was not possible to non-invasively monitor these changes in erector spinae muscle. Nineteen healthy males completed the BSME in a prone position. The NIRS probes were placed on the left and right erector spinae muscle at the third lumbar vertebra level. The test protocol was: 2 min resting baseline, BSME to volitional fatigue, and 4 min recovery. The results indicated Mbv initially increased reaching asymptote before returning to baseline at termination. The Mox increased then declined systematically until BSME termination, returning to near baseline in recovery. No significant difference between sides was noted for Mbv or Mox. Mox best predicted BSME time. In conclusion, Mbv increased and then reaches asymptote as indicated in previous research, and oxygen availability was associated with the duration of erector spinae static contraction. Thus, prolonged static postures using the erector spinae muscles may diminish muscle oxygenation increasing susceptible to fatigue and injury.


A mammalian lung's immune system minimizes tissue damage by initiating five major sequential phases of defense.
The mammalian lungs encounter several pathogens, but have a sophisticated multi-phase immune defense. Furthermore, several immune responses to suppress pulmonary pathogens can damage the airway epithelial cells, particularly the vital alveolar epithelial cells (pneumocytes). The lungs have a sequentially activated, but overlapping, five phase immune response to suppress most pathogens, while causing minimal damage to the airway epithelial cells. Each phase of the immune response may suppress the pathogens, but if the previous phase proves inadequate, a stronger phase of immune response is activated, but with an increased risk of airway epithelial cell damage. The first phase immune response involves the pulmonary surfactants, which have proteins and phospholipids with potentially sufficient antibacterial, antifungal and antiviral properties to suppress many pathogens. The second phase immune response involves the type III interferons, having pathogen responses with comparatively minimal risk of damage to airway epithelial cells. The third phase immune response involves type I interferons, which implement stronger immune responses against pathogens with an increased risk of damage to airway epithelial cells. The fourth phase immune response involves the type II interferon, interferon-γ, which activates stronger immune responses, but with considerable risk of airway epithelial cell damage. The fifth phase immune response involves antibodies, potentially activating the complement system. In summary, five major phases of immune responses for the lungs are sequentially initiated to create an overlapping immune response which can suppress most pathogens, while usually causing minimal damage to the airway epithelial cells, including the pneumocytes.


The thrombin inhibitor, argatroban, inhibits breast cancer metastasis to bone.
Breast cancer has the potential to metastasize to bone, causing debilitating symptoms. Although many tumor cells have thrombin-generating systems originating from tissue factor (TF), therapy in terms of the coagulation system is not well established. To elucidate the efficacy of the thrombin inhibitor, argatroban, on bone metastasis, we investigated TF activation and vascular endothelial growth factor (VEGF) secretion on treatment with thrombin and argatroban. MDA-231 breast cancer cells were treated with thrombin in presence or absence of argatroban, and TF activity was measured in the form of activated factor X. Enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF concentrations in the medium. MDA-231 cells were injected into the left heart ventricle of mice, and then argatroban or saline was administered intraperitoneally for 28 days. After 28 days, incidence of bone metastasis was evaluated in the limbs by radiography. TF activity and VEGF secretion were upregulated by thrombin. Argatroban inhibited the enhancement of TF activity and VEGF secretion induced by thrombin. In vivo analysis revealed that the number of metastasized limbs in the argatroban group was significantly lower compared with the saline group (P < 0.05). Thrombin not only enhances VEGF secretion but also has a positive feedback mechanism to reexpress TF. These results indicate that inhibition of thrombin is of great value in suppression of tumor metastasis. Argatroban is a noteworthy and useful thrombin inhibitor because it has already been used in the clinical setting and has antimetastatic effects in vivo.


Baculovirus AcMNPV induces type I interferons and NK/NKT cells-mediated protection against foot-and-mouth disease virus in mice.
Foot-and-mouth disease is a viral illness that affects cloven-hoofed animals causing serious economic losses. Inactivated vaccines against its causative agent, foot-and-mouth disease virus (FMDV), require approximately seven days to induce protection. Therefore, antiviral strategies are needed to provide earlier protection and to stop the spread of this highly contagious virus during outbreak situations. In this way, our group has previously demonstrated that the baculovirus (BV) Autographa californica multiple nucleopolyhedrovirus (AcMNPV), an insect virus with immunostimulant effects, induces a nonspecific antiviral status that protects C57BL/6 mice against a lethal challenge with FMDV A/Arg/01 at 3 hours or 3 days post inoculation. In this work, we studied the immunological mechanisms involved in this protection. Firstly, we compared the protection elicited by AcMNPV in wild type mice and in knock-out mice lacking the subunit IFNAR1 of the receptor for type I interferons (IFNs). Our results showed that type I IFNs are key to prevent the death of the animals after the FMDV challenge. On the other hand, we evaluated the role of NK and NKT cells by depleting these cell subsets with anti-NK1.1 monoclonal antibody. These cells proved to be necessary for the induction of IFN-γ by AcMNPV and to prevent the onset of a severe disease after the FMDV challenge. We propose BV as a novel tool for the development of antiviral strategies because of the high levels of IFNs induced and the NK/NKT cells-mediated immune response elicited.


Radiculopathy as a complication of ankylosing spondylitis.
A cauda equina syndrome in association with ankylosing spondylitis is well recorded. We report the occurrence of an upper limb radiculopathy which progressed to a cauda equina syndrome in association with ankylosing spondylitis.


An electrochemiluminescence sensor based on CsPbBr3 -zquantum dots and poly (3-thiophene acetic acid) cross-linked nanogold imprinted layer for the determination of benzo(a)pyrene in edible oils.
A novel quench molecularly imprinted electrochemiluminescence sensor (MIECLS) based on a covalent organic framework composite (COF-300-Au) with enhanced electrochemiluminescence (ECL) signal from CsPbBr3 quantum dots and cross-linked 3-thiopheneacetic acid functionalized AuNPs (3-TAA@AuNPs) was developed for the detection of the environmental pollutant benzo(a)pyrene (BaP). A composite material constructed of COF-300-Au with a large specific surface area served as the sensor's support substrate, providing more CsPbBr3 and imprint recognition sites. Electropolymerization was then employed to form an AuNPs three-dimensional imprinting layer with polythiophene cross-linked using BaP as a template and 3-TAA@AuNPs as a functional monomer. A specific cross-linked imprinting recognition effect was recorded on BaP along with the quenching effect of quinones. The density functional theory (DFT) evaluation of the binding mechanism between 3-TAA@AuNPs and BaP revealed powerful MIECLS toward the detection of BaP at concentrations ranging from 10-14 to 10-5M, with a detection limit of as low as 4.1 × 10-15 M.


Interaction of bacteriophage T4 RNA and DNA ligases in joining of duplex DNA at base-paired ends.
The joining of duplex DNA at base-paired ends by bacteriophage T4 DNA ligase was confirmed using either a synthetic duplex decamer or restriction endonuclease fragments of ColE1 DNA as substrates. The reaction was not linearly dependent on enzyme concentration but increased markedly at high enzyme concentrations. Although T4 RNA ligase did not catalyze this blunt end joining, it makedly stimulated the DNA ligase reaction particularly at low DNA ligase concentrations. The apparent Km for the decamer was 50 micronM in the presence or absence of RNA ligase. In the presence of RNA ligase, T4 DNA ligase had about the same turnover number for blunt end and cohesive end joining. The joining of duplex DNA at base-paired ends was proven by several techniques including restriction endonuclease cleavage of the products. The products of the ligation reaction using restriction enzyme fragments were mostly linear oligomers but included some circular duplexes. Escherichia coli DNA ligase in the presence or absence of RNA ligase did not catalyze blunt end joining. RNA ligase only moderately affected the joining of cohesive ends by T4 DNA ligase or E. coli DNA ligase and did not itself catalyze this reaction.


The Immunology of Breast Development.
The immune system is not normally viewed as a regulator of breast development. However, in this issue of Developmental Cell, Plaks et al. (2015) reveal that antigen-presenting cells and T cells have a key role in controlling the development of the mammary gland's epithelial ductal network.


Mental Health Care Education and Training in Pharmacy Programs in Arabic-Speaking Countries.
This study aimed to assess how entry-level pharmacy programs in Arab countries prepare graduates to provide mental health care, specifically examining the didactic curricula and experiential training in psychiatry in bachelor and PharmD programs. An electronic survey was sent to all entry-level pharmacy programs in the 22 Arab countries asking to report on the 2021-2022 academic year. The survey assessed teaching and learning (eg, psychiatric diseases taught and extent of the coverage; contact hours dedicated to psychiatric therapeutics, pharmacology, and medicinal chemistry), experiential training in psychiatry and its challenges, and graduates' preparedness to provide mental health. A descriptive analysis of the data was undertaken, and data were reported for bachelor and PharmD programs separately. Overall, 35 pharmacy programs completed the survey. All PharmD programs and 80% of bachelor programs covered psychiatric therapeutics, and most contact hours were dedicated to pharmacology, followed by psychiatric therapeutics and medicinal chemistry. Over half of the faculty considered that depression and anxiety disorders were covered sufficiently, and 56.2% of programs did not offer experiential training in psychiatry. Common challenges in psychiatry experiential training included a lack of sites and qualified preceptors. Overall, 26.4% of faculty positively rated graduates' preparedness to provide mental health care. Graduates who completed experiential training in psychiatry and PharmD graduates were rated higher. Pharmaceutical education in Arab countries could be improved by enhancing the teaching and assessment of mental health topics and expanding psychiatry experiential training. Such changes would improve entry-level pharmacists' competencies in mental health care provision.


Time-resolved MR angiography of the central veins of the chest.
The purpose of our study was to show the usefulness and limitations of contrast-enhanced time-resolved MR angiography (MRA) for imaging the central veins of the chest. Time-resolved MRA is highly sensitive for the detection of abnormalities and is particularly useful in conjunction with static high-spatial-resolution MRA. However, several intrinsic limitations must be kept in mind.


Heat enhances the cytotoxicity of cis-diamminedichloroplatinum(II) and its analogues cis-1,1-cyclobutane-dicarboxylato(2R)-2-methyl-1,4- butanediammineplatinum(II) and cis-diammine(glycolato)platinum in vitro.
cis-1,1-Cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammin eplatinum(II) (NK121) and cis-diammine(glycolato)platinum (254-S), analogues of cis-diamminedichloroplatinum (II) (CDDP) with reduced nephrotoxicity, are under clinical phase trial in Japan. Since CDDP has been shown to be more cytotoxic under conditions of an elevated temperature, we tested the cytotoxicity and cellular uptake of these analogues at 37 degrees and 43 degrees C using EMT6/KU cells in vitro. The cytotoxicity of CDDP was enhanced at 43 degrees C, and that of NK121 and 254-S was also enhanced, in a dose- and time-dependent manner. The 90% cytotoxic concentration (IC90) of each drug was reduced 2.9-fold for CDDP, 2.5-fold for NK121, and 2.2-fold for 254-S. Cytotoxicity was maximal when the two modalities were used simultaneously for all three drugs. The intracellular platinum concentration was assayed using flameless atomic absorption spectrophotometry. When exposed to IC90 drug concentration at 43 degrees C for 2 h simultaneously, the intracellular platinum concentration increased to 0.095 +/- 0.007 micrograms/10(7) cells (a 1.9-fold increase) for CDDP, to 0.198 +/- 0.012 micrograms/10(7) cells (a 1.3-fold increase) for NK121, and to 0.090 +/- 0.014 micrograms/10(7) cells (a 1.3-fold increase) for 254-S; respectively, as compared with the level measured after drug exposure at 37 degrees C (P < 0.05 for all drugs). The elevation in platinum concentration may be one of mechanism related to a synergistic effect of the two treatment modalities. The concomitant use of CDDP analogues and heat shows potential for possible clinical application.


Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study.
Zinc supplementation was hypothesized to have therapeutic potential against prostate cancer, but its influence on prostate cancer incidence especially at high doses is controversial. A total of 47,240 men from the Health Professionals Follow-up Study were followed from 1986 to 2016. Men reported their zinc supplement use at baseline and biennially thereafter. Clinical features of prostate cancer included stage, grade, lethal and aggressive (T4 or N1 or M1 or Gleason 8-10) outcome. Multivariable Cox proportional hazards models were used to evaluate the association between zinc supplement use and incidence of prostate cancer. During a median follow-up of 28.3 years, we documented 6,980 incident prostate cancer cases including 1,053 lethal and 1,143 aggressive. Zinc supplement use was not associated with overall, localized, low- and intermediate-grade prostate cancer. However, compared to never-users, men who used supplement zinc more than 75 mg/day were at higher risk for lethal (HR: 1.76, 95% CI: 1.16-2.66, Ptrend = 0.001) and aggressive prostate cancer (HR: 1.80, 95% CI: 1.19-2.73, Ptrend = 0.006). Similarly, men who took supplemental zinc for 15 or more years had a higher risk for lethal (HR: 1.91, 95% CI: 1.28-2.85, Ptrend <0.001) and aggressive prostate cancer (HR: 1.55, 95% CI: 1.03-2.33, Ptrend = 0.004). Zinc supplementation of more than 75 mg per day or over 15 years may substantially increase risk of lethal and aggressive prostate cancer. Caution is warranted regarding excessive usage of zinc supplements among adult men.


Preload-independent index of contractility for the assessment of left ventricular function.
We describe a method for the assessment of myocardial contractile force; it is based on the measurement of left ventricular pressure P and its first derivative dP/dt at two well-defined points on the isovolumic pressure curve. The slope Vs relating rise of dP/dt to rise of P is a measure of contractile element velocity. Vs values for normal children and adults, varying in body surface area from 0.18 to 2.14 m2 and in age from 1 day to 60 years, were in close agreement, indicating that this parameter is substantially independent of heart size. Ten children with myocardial disease all had lower Vs values than any of 24 children with normal left ventricular function. Within each of these two groups, the increase of dP/dt during isovolumic contraction was highly correlated with the increase of P, but the regression line for the normal group had a significantly steeper slope than that for the impaired group. The near zero intercepts of the two regression lines on both delta P and the delta dP/dt axes gave additional evidence that alterations of preload did not affect Vs.


Molecular Phylogeny, Diversity, and Bioprospecting of Endophytic Fungi Associated with wild Ethnomedicinal North American Plant Echinacea purpurea (Asteraceae).
The endophytic fungal community associated with the ethnomedicinal plant Echinacea purpurea was investigated as well as its potential for providing antifungal compounds against plant pathogenic fungi. A total of 233 endophytic fungal isolates were obtained and classified into 42 different taxa of 16 genera, of which Alternaria alternata, Colletotrichum dematium, and Stagonosporopsis sp. 2 are the most frequent colonizers. The extracts of 29 endophytic fungi displayed activities against important phytopathogenic fungi. Eight antifungal extracts were selected for chemical analysis. Forty fatty acids were identified by gas chromatography-flame-ionization detection (GC-FID) analysis. The compounds (-)-5-methylmellein and (-)-(3R)-8-hydroxy-6-methoxy-3,5-dimethyl-3,4-dihydroisocoumarin were isolated from Biscogniauxia mediterraneaEPU38CA crude extract. (-)-5-Methylmellein showed weak activity against Phomopsis obscurans, P. viticola, and Fusarium oxysporum, and caused growth stimulation of C. fragariae, C. acutatum, C. gloeosporioides, and Botrytis cinerea. (-)-(3R)-8-Hydroxy-6-methoxy-3,5-dimethyl-3,4-dihydroisocoumarin appeared slightly more active in the microtiter environment than 5-methylmellein. Our results indicate that E. purpurea lives symbiotically with different endophytic fungi, which are able to produce bioactive fatty acids and aromatic compounds active against important phytopathogenic fungi. The detection of the different fatty acids and aromatic compounds produced by the endophytic community associated with wild E. purpurea suggests that it may have intrinsic mutualistic resistance against phytopathogen attacks in its natural environment.


Multiple frequency bioelectrical impedance for the prediction of total body potassium in cystic fibrosis.
The use of multiple frequency bioelectrical impedance analysis (MFBIA) was compared with single frequency bioelectrical impedance analysis (SFBIA) and anthropometry to estimate the size of the body cell mass (BCM) in a paediatric cystic fibrosis population. BCM was independently determined from the accepted gold standard reference of total body potassium (TBK). MFBIA was used to measure the impedance of the body at 248 frequencies from 4 kHz to 1 MHz. Data were analysed using Cole-Cole plots of reactance versus resistance. The limits of agreement procedure was used to determine the reliability and precision of the different techniques to predict values for TBK, in an individual subject. The results indicate that MFBIA with a precision of 12% offers little improvement over single frequency BIA but is better and more accurate than anthropometry for the prediction of TBK in an individual patient.


Actin stress fibres and cell-cell adhesion molecules in tendons: organisation in vivo and response to mechanical loading of tendon cells in vitro.
Tendons consist of parallel longitudinal rows of cells separated by collagen fibres. The cells are in intimate contact longitudinally within rows, and laterally via sheet-like lateral cell processes between rows. At points of contact, they are linked by gap junctions. Since tendons stretch under load, such cell contacts require protection. Here we describe the organisation of the actin cytoskeleton and actin-based cell-cell interactions in vivo and examine the effect of cyclic tensile loading on tendon cells in vitro. Cells within longitudinal rows contained short longitudinally running actin stress fibres. Each fibre was aligned with similar fibres in the cells longitudinally on either side, and fibres appeared to be linked via adherens junctions. Overall, these formed long oriented rows of stress fibres running along the rows of tendon cells. In culture, junctional components n-cadherin and vinculin and the stress fibre component tropomyosin increased in strained cultures, whereas actin levels remained constant. These results suggest that: (1) cells are linked via actin-associated adherens junctions along the line of principal strain; and (2) under load, cells appear to attach themselves more strongly together, and assemble more of their cytoplasmic actin into stress fibres with tropomyosin. Taken together, this suggests that cell-cell contacts are protected during stretch, and also that the stress fibres, which are contractile, may provide an active mechanism for recovery from stretch. In addition, stress fibres are ideally oriented to monitor tensile load and thus may be important in mechanotransduction and the generation of signals passed via the gap junction network.


Fracture Risk in Patients with Hypoparathyroidism.
To summarize the recently published scientific evidence on fracture risk in hypoparathyroidism. Hypoparathyroidism is characterized by a low bone turnover and a high bone mineral density. Data on fracture risk are sparse and due to the rarity of the disease, available studies have only been able to include relatively few patients. Risk of non-vertebral fractures does not seem to be affected to any major degree, although epidemiological studies suggest a decreased risk of fractures at the humerus in postsurgical hypoparathyroidism, whereas an increased risk of fractures at the upper arm has been shown in non-surgical hypoparathyroidism. Several, but not all, studies have also pointed towards an increased risk of vertebral fractures, especially in non-surgical hypoparathyroidism. Fractures at the appendicular skeleton do not seem to be of specific concern in hypoparathyroidism, but emerging data suggest an increased risk of vertebral fractures, which needs to be clarified further in upcoming studies.


Improving practice with the Liverpool Care Pathway.
The Liverpool Care Pathway for the Dying Patient (LCP) is an evidence-based document that acts as a guide for health care professionals when caring for patients in the last days of their lives.


A case-crossover study on the effect of short-term exposure to moderate levels of air pollution on the risk of heart failure.
Exposure to high levels of air pollution in industrialized urban areas is associated with an increased risk of heart failure (HF). On most days, the majority of European cities are only moderately affected by air pollution. The aim of this study was to evaluate the association between short-term exposure to moderate levels of air pollution with the risk of HF in a city with good air quality. We recruited 576 patients (median age 82 years; 58.2% men) admitted to a large university hospital in Central Germany for HF to participate in a hospital-based, bidirectional, case-crossover study. Diagnosis of HF and symptom onset were verified individually. The effect of short-term exposure to nitrogen dioxide (NO2 ), particulate matter (PM10 ), and ozone (O3 ) on the risk of HF was estimated using linear and non-linear (categorized) multivariate analyses for three different lag times (1, 2, and 3 days before HF onset). Air pollution variables were adjusted to the date of HF symptom onset. During the study period, the average daily concentration of air pollutants was only moderate and reflects the average European background air pollution. In particular, the concentration of air pollutants ranged from 2 to 63.39 μg/m3 (median = 17.46 μg/m3 ) for NO2 , from 2 to 125.88 μg/m3 (median = 44.61 μg/m3 ) for O3 , and from 2.21 to 166.79 μg/m3 (median = 18.67 μg/m3 ) for PM10 . We did not find a linear or non-linear association between short-term exposure to NO2 , O3 , or PM10 and risk for HF at all lag times in the overall population and subgroups. In an area with only moderate air pollution, short-term exposure to major air pollutants does not increase the risk for HF. Future studies should focus on a potential threshold effect of air pollution on HF risk as a basis for evidence-based development of statutory limits in highly polluted areas.


Do locking screws work in plates bent at holes?
To assess whether plate bending at a hole significantly changes the biomechanical properties of a locked screw. Coronal plane bends of 5-, 15-, or 45-degree angles were placed in 3.5-mm locking compression plates with the apex at a locking hole. An additional 45-degree angle test group was created in which a threaded screw head insert was placed before bending. Ten plates were tested in each group and compared with nonbent controls in a stepwise cyclic loading protocol. Statistically significant differences in protocol survival were shown between the control group and the 15-degree angle (P = 0.006) and 45-degree angle (P = 0.0007) groups. An apparent decrease in protocol survival in the 5-degree angle group did not reach statistical significance (P = 0.17). The average number of cycles survived was significantly different between the control group and the 15-degree angle (P = 0.027) and 45-degree angle (P = 0.0002) groups. The mean cycles to failure for the 5-degree angle group was 16% lower than for controls but did not reach statistical significance (P = 0.37). The test group bent to an angle of 45 degrees after placement of a threaded screw head insert showed no difference in protocol survival or in mean number of cycles survived compared with the regular 45-degree angle group. Bending of a 3.5-mm locking compression plate by more than 5 degrees at a locking hole results in a statistically significant decrease in survival of the corresponding locked screw. This effect cannot be prevented by the placement of a threaded screw head insert before bending.


Re-Shaping the Pancreatic Cancer Tumor Microenvironment: A New Role for the Metastasis Suppressor NDRG1.
Pancreatic cancer (PaC) is a highly aggressive disease, with poor response to current treatments and 5-year survival rates of 10-15%. PaC progression is facilitated by its interaction with the complex and multifaceted tumor microenvironment (TME). In the TME, cancer cells and surrounding stromal cells constantly communicate with each other via the secretion and uptake of factors including cytokines, chemokines, growth factors, metabolites, and extracellular vesicles (EVs), reshaping the landscape of PaC. Recent studies demonstrated that the metastasis suppressor N-myc downstream regulated 1 (NDRG1) not only inhibits oncogenic signaling pathways in PaC cells but also alters the communication between PaC cells and the surrounding stroma. In fact, NDRG1 was found to influence the secretome of PaC cells, alter cancer cell metabolism, and interfere with intracellular trafficking and intercellular communication between PaC cells and surrounding fibroblasts. This review will present recent advancements in understanding the role of NDRG1 in PaC progression, with a focus on how this molecule influences PaC-stroma communication and its potential for re-shaping the PaC TME.


Early-Career Physician Burnout.
Early-career physicians face a broad range of challenges unique to their phase of life and career. Beginning in residency, anesthesiologists encounter stressors unique to their work environment, which, when coupled with their personal life demands, places significant burden and creates potential for burnout. In this article, the authors review the literature to explore the contributors of burnout in early-career anesthesiologists, evaluate the relationship between compassionate care and empathic distress, and propose strategies to prevent and treat burnout in this specific subset of anesthesiologists.


Cytotechnologist Performance for Screening Hürthle Cell Atypia in Indeterminate Thyroid Fine-Needle Aspirates.
We have previously shown that specimens diagnosed as containing Hürthle cells have a 12% chance of being malignant if they are classified as atypia of undetermined significance (AUS-HC). The identification of Hürthle cells by cytotechnologists (CTs) during screening can improve cytopathologist efficiency and may prevent diagnostic errors due to the oversights of focal findings. Here, we examine the performance of our institutional CTs when screening for Hürthle cell atypia in thyroid fine-needle aspiration (FNA) specimens. Information on 8,814 thyroid cytopathology specimens was retrieved for a 10-year period. Specimens were screened by 1 of 11 CTs. A subsample of cases was categorized either as AUS-HC or suspicious for Hürthle cell neoplasm. AUS-HC screening diagnoses were more likely to be downgraded to benign but less likely to be upgraded compared to AUS diagnoses with nuclear or microfollicular atypia. AUS-HC represents almost all papillary thyroid carcinoma (PTC) screening diagnoses downgraded to the AUS category, which suggests that even low levels of Hürthle cell atypia can result in PTC being included in the differential diagnosis. Overall, there are few major discrepancies between CT and pathologist diagnoses for specimens containing Hürthle cell atypia.


Polydioxanone-based bio-materials for tissue engineering and drug/gene delivery applications.
Since the commercialization of polydioxanone (PDX) as a biodegradable monofilament suture by Ethicon in 1981, the polymer has received only limited interest until recently. The limitations of polylactide-co-glycolide (PLGA) coupled with the growing need for materials with enhanced features and the advent of new fabrication techniques such as electrospinning have revived interest for PDX in medical devices, tissue engineering and drug delivery applications. Electrospun PDX mats show comparable mechanical properties as the major structural components of native vascular extracellular matrix (ECM) i.e. collagen and elastin. In addition, PDX's unique shape memory property provides rebound and kink resistance when fabricated into vascular conduits. The synthesis of methyl dioxanone (MeDX) monomer and copolymers of dioxanone (DX) and MeDX have opened up new perspectives for poly(ester-ether)s, enabling the design of the next generation of tissue engineering scaffolds for application in regenerating such tissues as arteries, peripheral nerve and bone. Tailoring of polymer properties and their formulation as nanoparticles, nanomicelles or nanofibers have brought along important developments in the area of controlled drug or gene delivery. This paper reviews the synthesis of PDX and its copolymers and provides for the first time an exhaustive account of its applications in the (bio)medical field with focus on tissue engineering and drug/gene delivery.


Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity.
Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful markers for cancer screening, surveillance, and prognosis. Our aim was to examine the clinical significance of MCM-2 and MCM-5 protein expression in colon cancer and to evaluate the association with various clinicopathological characteristics and tumor proliferative capacity. Immunohistochemical expression of MCM-2 and MCM-5 was performed on paraffin-embedded malignant tissue sections obtained from 96 patients with colon cancer. MCM-2 and MCM-5 expression was correlated with different clinicopathological characteristics, proliferative capacity (Ki-67 labeling index), and p53 cell-cycle regulator expression. MCM-2 and Ki-67 expression was significantly associated with the tumors' histological grade (P = 0.003), existence of nodular metastases (N) (P = 0.003 and P = 0.030, respectively), malignancy on adenoma (P = 0.029 and P = 0.024, respectively), and vascular invasion (P = 0.010 and P = 0.011, respectively). MCM-2 expression was additionally associated with Dukes' stage (P = 0.005). Significant positive relationships were found between the expression of MCM-2 or MCM-5 proteins and that of Ki-67 protein (r = 0.963, P-value < 0.001, and r = 0.738, P-value < 0.001, respectively), as well as between MCM-2 and MCM-5 proteins (r = 0.745, P-value < 0.001). Significant positive relationships were also observed between the expression of MCM-2 or MCM-5 proteins and that of p53 protein; however, they were consistently lower than the corresponding with Ki-67 protein. No significant association was observed between MCM-5 protein expression and the clinicopathological characteristics examined. The current data suggest that MCM-2 protein expression is significantly associated with important clinicopathological characteristics for patients' management, being correlated with the cell proliferation state in colon cancer.


Expression of Cdcrel-1 (Pnutl1), a gene frequently deleted in velo-cardio-facial syndrome/DiGeorge syndrome.
The murine Cdcrel-1 (Pnutl1) gene belongs to the family of septins, which are thought to be involved in cytokinesis in yeast, Drosophila and vertebrates. Recent studies implicate Cdcrel-1 in the regulation of vesicle transport in neurons of the adult brain. The human homologue, hCDCREL-1 maps to chromosome 22q11.2, a region commonly deleted in patients displaying velo-cardio-facial syndrome (VCFS) or DiGeorge syndrome (DGS). During development, Cdcrel-1 transcripts are expressed from E10.5 on in the nervous system such as the dorsal root ganglia and the cranial ganglia as well as the lateral layer of the neural tube, the area where terminally differentiated neurons are located. Low level expression is found in the mesenchyme of the frontonasal mass and the limb bud mesenchyme of E11.5 and E13.5 murine embryos. At E15.5, expression is detected in the nervous tissue and in the neural layer of the eye. Based on the expression pattern as well as clinical data, Cdcrel-1 may be involved in the etiology of VCFS/DGS.


Pregnancy outcome in women who use opiates.
Opiate use in pregnancy is on the increase. There are a number of complications associated with this problem but current data from UK centres are sparse. A retrospective study. A North of England Hospital. Maternal and neonatal case records were studied and a standard data set completed. Maternal and neonatal outcomes were classified by the woman's drug usage at the end of pregnancy. One hundred and ten babies born to 108 women were studied and 41% had evidence of previous exposure to the hepatitis C virus. Women who took heroin in later pregnancy were significantly more likely than women who were stabilised on methadone to have a baby who needed morphine (40% versus 19%), had higher mean maximum neonatal abstinence scores (NAS) (5.8 versus 4.7) and stayed in the neonatal unit significantly longer (mean 17.2 days versus 11.8 days). There were two neonatal deaths and the overall rate of prematurity was 29%. The outcome for pregnancy in women who use opiates is complicated by high rates of prematurity and neonatal death. Women who used heroin in later pregnancy had babies who developed more severe NAS and needed a longer hospital stay than women who used only methadone.


Ionic strength dependence of the hysteresis in the polyriboadenylate-polyribouridylate system.
The hysteresis observed in cyclic acid-base titrations of the three-standed polyribonucleotide helix poly (A)-2 POLY (U) strongly depends on ionic strength. For NaCl and at 25 degrees C, hysteresis occurs in the limited concentration range between 0.03 M and 1.0 M(NaCl). The transition points associated with the cyclic conversions between the triple helix and the poly (A)-poly (A) double helix and (free) poly (U) constitute a (pH ionic strength) phase diagram covering the ranges of stability and metastability of the hysteresis system. Variations with NaCl concentration of some hysteresis parameters can be quantitatively described in terms of polyelectrolyte theories based on the cylinder-cell model for rodlike polyions. The results of this analysis suggest that the metastability is predominantly due to dlectrostatic energy barriers preventing the equilibrium transition of the partially protonated triple helix above a critical pH value. Ultraviolet absorbance and potentiometric titration data of poly (A)in the acidic pH range can be analyzed in terms of two types of double-helical structures. Spectrophotometric titrations reveal isosbestic wavelengths for structural transitions of poly (A). "Time effects" commonly observed in poly (A) titrations are suggested to reflect helix transitions between the two acidic structures.


Arsenic species analysis by ion chromatography-bianode electrochemical hydride generator-atomic fluorescence spectrometry.
In this work, a novel hyphenated technique ion chromatography-bianode electrochemical hydride generator-atomic fluorescence spectrometry (IC-BAECHG-AFS) system was developed for on-line simultaneous analysis of arsenite (As(III)), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), and arsenate (As(V)). Parameters that might affect hydride generation efficiency were investigated and the interference of various ions was also examined. Under the optimal conditions, the hydride generation efficiency of bianode electrochemical hydride generator (BAECHG) was close to the hydride generation efficiency of chemical hydride generator (CHG). The linear ranges were 5-200 microg L(-1) for As(III), DMA and MMA and 10-200 microg L(-1) for As(V). The limits of detection (LOD, S/N=3) were 3.04, 4.27, 3.97 and 9.30 microg L(-1) for As(III), DMA, MMA and As(V), respectively. The relative standard deviations (RSD, n=7) of As(III), DMA, MMA and As(V) were 4, 3, 5 and 4%, respectively. The proposed method was also applied to the determination of the four arsenic species in dental pulp inactivative agent (type I). The recoveries of the four arsenic compounds were in the range of 91.6-103.2%.


Elevated TRAF2/6 expression in Parkinson's disease is caused by the loss of Parkin E3 ligase activity.
Parkinson's disease (PD) is the second leading neurodegenerative disease, and is known to be induced by environmental factors or genetic mutations. Among the verified genetic mutations of PD, Parkin, isolated from the PARK2 locus, shows an autosomal recessive inheritance pattern and is known to be an E3 ligase. However, the physiological target of Parkin and the molecular mechanism of Parkin-deficiency-induced PD have not been clearly demonstrated until now. It has recently been proposed that inflammation, suggesting as a causal factor for PD, is enhanced by Parkin deficiency. Thus, we examined the relationship between inflammation-related factors and Parkin. Here, we provide the evidence that Parkin suppresses inflammation and cytokine-induced cell death by promoting the proteasomal degradation of TRAF2/6 (TNF-α receptor-associated factor 2/6). Overexpression of Parkin can reduce the half-lives of TRAF2 and TRAF6, whereas si-Parkin can extend them. However, mutant Parkins did not alter the expression of TRAF2/6. Thus, loss of Parkin enhances sensitivity to TNF-α- or IL-1β-induced JNK activation and NF-κB activation. Indeed, si-Parkin-induced apoptosis is suppressed by the knockdown of TRAF6 or TRAF2. We also observed elevated expression levels of TRAF6 and a reduction of IκB in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mouse model. Moreover, elevated expression levels or aggregation of TRAF6 were detected in approximately half of the human PD tissues (7/15 cases) and 2 cases, respectively. In addition, TRAF6 and Parkin expression levels show a reverse relationship in human PD tissues. Our results strongly suggest that the reduction of Parkin or overexpression of TRAF2/6 by chronic inflammation would be the reason for occurrence of PD.