An item response theory analysis of DSM-IV conduct disorder.
We examined DSM-IV conduct disorder (CD) symptom criteria in a community sample of male and female adolescents to evaluate the extent to which DSM-IV criteria characterize the range of severity of adolescent antisocial behavior within and across sex. Interviews were conducted with 3,208 adolescents between the ages of 11 and 18 years using the Diagnostic Interview Schedule for Children. Item response theory analyses were performed to obtain severity and discrimination parameters for each of the lifetime DSM-IV CD symptom criteria. In addition, item response theory-based differential item functioning analyses were conducted to examine the extent to which the symptom criteria function similarly across sex. The DSM-IV CD symptom criteria are useful and meaningful indicators of severe adolescent antisocial behavior. A single item ("Steal without Confrontation") was a poor indicator of severe antisocial behavior. The CD symptom criteria function similarly across sex; however, three items had significantly different severity parameters. The DSM-IV CD criteria are informative as categorical and continuous measures of severe adolescent antisocial behavior; however, some CD criteria display sex bias.


Reliability of a food frequency questionnaire to assess dietary antioxidant intake.
Epidemiologic evidence of a role for antioxidants in the prevention of chronic disease has been inconclusive, in part due to the difficulty of measuring past diets of free-living populations. The purpose of the current study was to examine the reliability of a 19-item, self-administered, semiquantitative, food frequency questionnaire to assess intake of the major dietary antioxidants. Reliability was established by administering the food frequency questionnaire a second time by telephone. The subjects comprised 151 participants in the Melbourne Visual Impairment Project, a study of the distribution and determinants of eye disease in Melbourne residents aged 40 and over. Spearman correlation coefficients ranged from 0.39 for spinach to 0.76 for yoghurt, and all were highly significant (all p = 0.001). The reliability of the instrument was not influenced by gender, English speaking ability, or the number of days between the first and second administration of the questionnaire. In conclusion, we have shown this 19-item food frequency questionnaire to be highly reliable. It should be useful for anyone involved in the study of the relationship of dietary antioxidant intake to health outcomes in large populations where limitations of time and money prohibit the collection of more detailed dietary intake information.


Screening of key methylation-driven genes CDO1 in breast cancer based on WGCNA.
With the rapid development of genomics and molecular biology, not only have biochemical indicators been used as tumour markers, but many new molecular markers have emerged. Epigenetic abnormalities are a new type of molecular marker, and DNA methylation is an important part of epigenetics. This study used weighted gene coexpression network analysis (WGCNA) to analyse key methylation-driven genes in breast cancer. The RNA-seq transcriptome data, DNA methylation data, and clinical information data of breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database, and the MethylMix R package was used to screen methylation-driven genes in breast cancer. The ClusterProfiler package and enrichplot package in R software were used to further analyse the function and signalling pathway of methylation-driven genes. Through univariate and multivariate Cox regression analyses, methylation-driver genes related to prognostic were obtained, a prognostic model was constructed and prognostic characteristics were analysed. The 17 methylation-driven genes related to prognosis were obtained by the WGCNA method in breast cancer, and the prognostic significance of these methylation-driven genes was determined by transcriptome and methylation combined survival analysis. Analysis of functions and signalling pathways showed that these genes were mainly enriched in biological processes and signalling pathway. Through univariate and multivariate Cox regression analyses, a prognostic model of 5 methylation-driven genes was constructed. The AUC of the receiver operating characteristic (ROC) curve of this model was 0.784, showing that the model had a good prediction effect. Based on WGCNA screening, it was found that only CDO1 was the key methylation-driven gene for prognosis in breast cancer, indicating that CDO1 may be an important indicator of the prognosis of breast cancer patients.


[Diffuse lung disease in children].
Diffuse lung disease in children represents a heterogeneous group of respiratory disorders with high morbidity and mortality. Typical features include tachypnoea, failure to thrive, diffuse radiological and histopathological abnormalities. Advances in genetics and pathophysiology, combined with a recent paediatric classification have improved our understanding of these disorders. The workup, diagnosis and management of these rare paediatric pulmonary diseases are difficult and require centralised, interdisciplinary team approach in experienced paediatric pulmonary centres.


A spontaneous intramural hematoma of the bowel presenting as obstruction in a child receiving low-molecular-weight heparin.
Low-molecular-weight heparin (LMWH) is a safe and effective alternative to unfractionated heparin and coumadin in the treatment and prophylaxis of thrombosis in children. When compared with these more established anticoagulants, it is easier to achieve therapeutic levels and the incidence of hemorrhagic complications is equivalent or lower. In children there is less published experience than in adults, but the low frequency of significant bleeding appears to be similar. The authors describe a child on therapeutic doses of LMWH for a deep vein thrombosis who spontaneously developed an intramural hemorrhage in his small bowel, leading to infarction and a partial bowel resection.


Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin.
To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis (FVA) in a Chinese Han family. Pars plana vitrectomy (PPV) surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment, without evidence of cardiac, renal, gastrointestinal, central nervous system or peripheral nervous system dysfunction. During the surgery, the patient presented with a gray-white dense and thick cotton wool-like change in the vitreous body, accompanied by complete retinal detachment. Additionally, hard, free and movable yellow-white deposits were observed in the posterior pole and surrounding retina, the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination, and whole exome sequencing was performed on blood samples from the patient and her cousin. During the operation, it was discovered that there was a complete detachment of the retina and a significant amount of hard, free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina. This is an exceedingly rare ocular manifestation. Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining, as well as elevated vascular endothelial growth factor (VEGF) expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination. The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin (TTR) gene, resulting in a substitution of glycine (Gly) at position 103 with arginine (Arg). FVA may present with various ocular manifestations, but panretinal detachment is a rare occurrence. In cases where retinal detachment persists for an extended period of time, amyloid deposits may form under the retina through retinal tears, leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis. Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state, necessitating careful postoperative follow-up. The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.


Determination of Death Anxiety and Death-Related Depression Levels in the Elderly During the COVID-19 Pandemic.
The aim of the study is to determine the levels of death anxiety and death-related depression in the elderly during the COVID-19 pandemic. The sample of the descriptive-relational study includes 344 elderly people registered in a family health center. It was determined that the most dreaded fear reported by the elderly who got COVID-19 infection was death, and there was a highly significant positive correlation between death anxiety and death-related depression ratings of the elderly and that as the average death anxiety score of the elderly rises, so does the degree of death-related depression.


The prevalence of trimetazidine use in athletes in Poland: excretion study after oral drug administration.
Stimulants, together with anabolic androgenic steroids, are regarded as one of the most popular doping substances in sport. Owing to a great variety of these substances and new designer drugs being introduced to the market, each year the World Anti-Doping Agency (WADA) updates the list of substances and methods prohibited in sport. On 1 January 2014, a new doping agent - trimetazidine (TMZ) - was added to the WADA Prohibited List. TMZ, a substance prohibited in competition, is classified in the S6b Specified Stimulant Group. TMZ is used as a well-known cardiologic drug with confirmed biochemical and clinical activity. According to knowledge of the pharmacology and mechanism of TMZ action, TMZ can be used by athletes to improve physical efficiency, especially in the case of endurance sports. This study presents the phenomena of TMZ use by Polish athletes involved in anti-doping control in the WADA-accredited laboratory in Warsaw (Poland) between 2008 and 2013. Samples were taken from the athletes of such disciplines as cycling, athletics, and triathlon. Moreover, the elimination study of TMZ has been conducted to establish the change of TMZ concentration in urine sample after oral administration of a single or double (during the long-term therapy) dose. TMZ was monitored in urine samples by gas chromatography-mass spectrometry-nitrogen phosphorus detection (GC-MS-NPD).


Hepatic vessels segmentation using deep learning and preprocessing enhancement.
Liver hepatic vessels segmentation is a crucial step for the diagnosis process in patients with hepatic diseases. Segmentation of liver vessels helps to study the liver internal segmental anatomy that helps in the preoperative planning of surgical treatment. Recently, the convolutional neural networks (CNN) have been proved to be efficient for the task of medical image segmentation. The paper proposes an automatic deep learning-based system for liver hepatic vessels segmentation of Computed Tomography (CT) datasets from different sources. The proposed work focuses on the combination of different steps; it starts by a preprocessing step to improve the vessels appearance within the liver region of interest in the CT scans. Coherence enhancing diffusion filtering (CED) and vesselness filtering methods are used to improve vessels contrast and intensity homogeneity. The proposed U-net based network architecture is implemented with modified residual block to include concatenation skip connection. The effect of enhancement using filtering step was studied. Also, the effect of data mismatch used in training and validation is studied. The proposed method is evaluated using many CT datasets. Dice similarity coefficient (DSC) is used to evaluate the method. The average DSC score achieved a score 79%. The proposed approach succeeded to segment liver vasculature from the liver envelope accurately, which makes it as potential tool for clinical preoperative planning.


Generation of flattop beams from a distorted optical field by the wavefront shaping technique.
Uniform laser beams with controllable patterns are crucial for various applications, including laser processing and inertial confinement fusion. While some methods have been proposed to generate flattop beams, they often require complex optical systems that can become ineffective because of the misalignment of the system or the imperfection of optical elements. To overcome these issues, we utilized feedback-based wavefront shaping (FWS) technology to generate flattop beams with desired patterns from a disordered light. To solve the multi-goal optimization problem, we propose some modifications based on the Non-dominated Sorting Genetic Algorithm II (NSGA2) and successfully generate focal beams with a uniform intensity distribution and controllable beam shape from the disordered light field.


Investigation on the clinical efficacy and safety of meloxicam (Metacam) in the treatment of non-infectious locomotor disorders in pigs.
The clinical efficacy and safety of meloxicam (Metacam 20 mg/ml) in the treatment of non-infectious locomotor disorders in pigs was investigated in a randomised double-blind, placebo controlled, multi-centre field study. A total of 220 pigs were examined, 211 pigs were suitable for evaluation. Treatment was performed on Day 1 with meloxicam (0.4 mg meloxicam/kg) or placebo by intramuscular injection. If necessary, treatment was optionally repeated on Day 2. Clinical examinations were conducted daily from Day 1 (immediately prior to initiation of therapy) to Day 4. The primary parameter, mean "Clinical Lameness Score" (CLS, a sum of the scores of "Lameness at Rest" and "Lameness at Walk"; range 2 to 11) improved from 6.8 and 6.3 on Day 1, to 3.5 and 4.7 on Day 4 in the meloxicam and placebo groups respectively (p < 0.001). At the final examination mean changes from baseline for CLS (Day 1) were 3.25 for meloxicam treated animals and 1.7 for placebo treated animals (p < 0.001). Behaviour score and feed intake improved during the study period with statistically significant differences in favour of meloxicam at all time points after initiation of therapy. Significantly fewer pigs received a second treatment in the meloxicam group than in the placebo group, 46% versus 73% (p < 0.001). A 'very good' or 'good' clinical efficacy assessment was recorded in 83% of the meloxicam cases compared to 42% of the placebo controls at the final examination (p < 0.001). No adverse events were reported due to the use of meloxicam. Furthermore safety of meloxicam in pregnant sows was demonstrated. It is concluded that intramuscular injection of meloxicam (Metacam) at a dosage of 0.4 mg/kg is efficacious and safe for the treatment of non-infectious locomotor disorders in pigs.


P1A1/A2 polymorphism of platelet glycoprotein IIIa and risk of acute coronary syndromes in heterozygous familial hypercholesterolemia.
Familial hypercholesterolemia (FH) is an autosomal inherited disorder caused by different mutations in the low density lipoprotein (LDL) receptor gene. It has been demonstrated that there is an increased risk of coronary heart disease (CHD) in heterozygous FH subjects, although this excess CHD is not only explained by the LDL-cholesterol concentration or the class of the LDL-receptor mutation. To investigate if a common polymorphism at the platelet glycoprotein (GP) IIIa gene locus could be related to CHD phenotypic variation in heterozygous FH. we have carried out a case-control study. We have studied 40 cases and 40 controls matched for age, sex and genetic defect in the LDL-receptor gene. Allele frequency of PI(A2) polymorphism for cases and controls was 20 and 22.5%, respectively, and the difference was not significant. In conclusion, our data do not support any association between the GP IIIa polymorphism and the increased prevalence of acute coronary syndromes in the heterozygous FH subjects.


Gender dynamics and the challenges for HIV prevention.
Information on the transmission of the human immunodeficiency virus (HIV), leading to acquired immunodeficiency syndrome (AIDS), has been widely disseminated since the early 1980s, and yet curbing new infections remains a major public health dilemma. In response to the global challenge of HIV/AIDS, most control and prevention interventions have targeted "core groups' with messages which include:- 1. Reduction of individual risk through responsible sexual behaviour or behaviour change, such as, delayed sexual debut, abstinence, monogamy and condom use. 2. Communal (as a society) adoption of a risk reduction strategy e.g. reduced rate of sexual partner change and avoiding multiple partners. 3. Improved, early and aggressive STD treatment programmes. However, data from sub-Saharan Africa and elsewhere shows how the epidemic, in the general population, appears to thrive unabatted. Large proportions of women and some men, in none of the traditional high risk core groups, are increasingly becoming infected with HIV. Most of the women appear to be at risk of infection not so much because of their own behaviour, but that of their partners of husbands. In this continuum, our response has been fragmented and non-strategic. Few programme activities have been developed that address men as a critical core group potentially propagating or sustaining the epidemic. The preoccupation with female sex workers and other core groups (e.g. truck drivers) could have overshadowed the need for programmes and interventions that make men, in general, aware of HIV risk and less likely to infect their sexual partners. Challenges posed by HIV require innovative strategies that foster behavioural and social change in the situation of men at risk and their partners.


Ethanol treatment of nanoPGA/PCL composite scaffolds enhances human chondrocyte development in the cellular microenvironment of tissue-engineered auricle constructs.
A major obstacle for tissue engineering ear-shaped cartilage is poorly developed tissue comprising cell-scaffold constructs. To address this issue, bioresorbable scaffolds of poly-ε-caprolactone (PCL) and polyglycolic acid nanofibers (nanoPGA) were evaluated using an ethanol treatment step before auricular chondrocyte scaffold seeding, an approach considered to enhance scaffold hydrophilicity and cartilage regeneration. Auricular chondrocytes were isolated from canine ears and human surgical samples discarded during otoplasty, including microtia reconstruction. Canine chondrocytes were seeded onto PCL and nanoPGA sheets either with or without ethanol treatment to examine cellular adhesion in vitro. Human chondrocytes were seeded onto three-dimensional bioresorbable composite scaffolds (PCL with surface coverage of nanoPGA) either with or without ethanol treatment and then implanted into athymic mice for 10 and 20 weeks. On construct retrieval, scanning electron microscopy showed canine auricular chondrocytes seeded onto ethanol-treated scaffolds in vitro developed extended cell processes contacting scaffold surfaces, a result suggesting cell-scaffold adhesion and a favorable microenvironment compared to the same cells with limited processes over untreated scaffolds. Adhesion of canine chondrocytes was statistically significantly greater (p ≤ 0.05) for ethanol-treated compared to untreated scaffold sheets. After implantation for 10 weeks, constructs of human auricular chondrocytes seeded onto ethanol-treated scaffolds were covered with glossy cartilage while constructs consisting of the same cells seeded onto untreated scaffolds revealed sparse connective tissue and cartilage regeneration. Following 10 weeks of implantation, RT-qPCR analyses of chondrocytes grown on ethanol-treated scaffolds showed greater expression levels for several cartilage-related genes compared to cells developed on untreated scaffolds with statistically significantly increased SRY-box transcription factor 5 (SOX5) and decreased interleukin-1α (inflammation-related) expression levels (p ≤ 0.05). Ethanol treatment of scaffolds led to increased cartilage production for 20- compared to 10-week constructs. While hydrophilicity of scaffolds was not assessed directly in the present findings, a possible factor supporting the summary data is that hydrophilicity may be enhanced for ethanol-treated nanoPGA/PCL scaffolds, an effect leading to improvement of chondrocyte adhesion, the cellular microenvironment and cartilage regeneration in tissue-engineered auricle constructs.


Barriers to healthcare seeking, beliefs about cancer and the role of socio-economic position. A Danish population-based study.
Cancer-related health behaviours may be affected by barriers to healthcare seeking and beliefs about cancer. The aim was to assess anticipated barriers to healthcare seeking and beliefs about cancer in a sample of the Danish population and to assess the association with socio-economic position. A population-based telephone interview with 3000 randomly sampled persons aged 30 years or older was performed using the Awareness and Beliefs about Cancer measure from 31 May to 4 July 2011. The Awareness and Beliefs about Cancer measure includes statements about four anticipated barriers to healthcare seeking and three positively and three negatively framed beliefs about cancer. For all persons, register-based information on socio-economic position was obtained through Statistics Denmark. Two anticipated barriers, worry about what the doctor might find and worry about wasting the doctor's time, were present among 27% and 15% of the respondents, respectively. Overall, a high proportion of respondents concurred with positive beliefs about cancer; fewer concurred with negative beliefs. Having a low educational level and a low household income were strongly associated with having negative beliefs about cancer. The fact that worry about what the doctor might find and worry about wasting the doctor's time were commonly reported barriers call for initiatives in general practice. The association between low educational level and low household income and negative beliefs about cancer might to some degree explain the negative socio-economic gradient in cancer outcome.


The Role of Electron Microscopy in Studying the Continuum of Changes in Membranous Structures during Poliovirus Infection.
Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles. This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories. Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis. In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection. Temporal and spatial membrane modifications throughout the infection cycle are discussed. Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis. These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes.


Presentation of pericardial hydatid cyst as acute cardiac tamponade.
We report a case of a 47-year-old man with isolated pericardial hydatid cyst (without myocardial involvement) that presented as acute pericardial tamponade. After initial investigation and transthoracic echocardiography, emergent pericardial drainage was performed for downgrading the urgency of a definitive treatment for a hydatid cyst. A computed tomography examination after the pericardial drainage showed a pericardial cyst without heart muscle involvement, making the treatment possible through anterior thoracotomy and without performing cardiopulmonary bypass. Complete surgical removal of the cyst was performed. The postoperative course was uneventful. The patient received postoperative albendazole treatment. He remained asymptomatic and no recurrence was observed during a 1-year follow-up period.


Diagnostic value of CA 15-3 antibody in detecting metastatic adenocarcinoma.
To determine the diagnostic value of CA 15-3 in detecting metastatic adenocarcinoma in body fluids using PreservCyt solution (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) as collection fluid. Cytospin slides prepared from 72 cases with unequivocally benign or malignant diagnosis were studied. Of the cases studied, 34 were breast carcinomas, and 17 were benign pleural effusions. Slides were stained for CA 15-3 by using the avidin-biotin complex method. Cases were evaluated for the presence of membranous or cytoplasmic staining. The percentage of cells exhibiting strong staining was estimated for both breast carcinoma and all adenocarcinomas as a group. These results were compared with CA 15-3 staining exhibited by benign mesothelium. Ninety-one percent of the breast cancer cases studied showed a positive reaction with CA 15-3, while 6% of the benign mesothelium cases were positive (p < 0.01). The sensitivity of CA 15-3 was 91 % for breast carcinoma and 80% for all adenocarcinomas. Specificity was 94% for breast carcinoma and for all adenocarcinoma. CA 15-3 is a sensitive and specific marker for diagnosing adenocarcinoma in cytologic specimens using PreservCyt solution as collection fluid.


[Investigation on intestinal absorption ingredients and their absorption characteristics in Pterocephali Herba by everted intestinal sac method].
The intestinal absorption characteristics of ten iridoid glycosides and phenolic acids in the Pterocephali Herba were evaluated via rat intestinal valgus model. The intestinal sac fluids at different time after administration of high,medium and low concentrations of Pterocephali Herba extract were collected and ten chemical components in fluid samples were detected by UPLC-PDA. Accumulative absorbed doses( Q) and absorption rate constants( Ka) of ten chemical constituents were calculated,while proportions between Pterocephali Herba extract and intestinal absorption liquid were compared. The results showed that the intestinal absorption of 10 chemical components was linear absorption( R2>0. 9) at different concentrations,which accorded with the zero-order absorption rate. The absorption rate constant was related to the concentration of the drug and the intestinal site,which indicated that intestinal adsorption mechanism of the components were passive diffusion and active transport. Proportions of chemical constituents in intestinal sac fluid were different from those in Pterocephali Herba extract. Therefore,those ten chemical components in Pterocephali Herba extract can be absorbed in whole intestine. Everted intestinal sac model can be used to evaluate intestinal absorption characteristics of ingredients in Pterocephali Herba extract effectively.


Personalized body segment parameters from biplanar low-dose radiography.
Body segment parameters are essential data in biomechanics. They are usually computed with population-specific predictive equations from literature. Recently, medical imaging and video-based methods were also reported for personalized computation. However, these methods present limitations: some of them provide only two-dimensional measurements or external measurements, others require a lot of tomographic images for a three-dimensional (3-D) reconstruction. Therefore, an original method is proposed to compute personalized body segment parameters from biplanar radiography. Simultaneous low-dose frontal and sagittal radiographs were obtained with EOS system. The upper leg segments of eight young males and eight young females were studied. The personalized parameters computed from the biplanar radiographic 3-D reconstructions were compared to literature. The biplanar radiographic method was consistent with predictive equations based on gamma-ray scan and dual energy X-ray absorptiometry.


Maternal pattern of reproduction and risk of breast cancer in daughters: results from the Utah Population Database.
Several studies have found that daughters born to older mothers have an elevated risk of breast cancer, and an endocrine hypothesis, among others, has been developed to explain these findings. Three recent studies have failed to find a consistent maternal age effect, indicating a need for further exploration of this issue. We used Utah breast cancer records linked to genealogical records to investigate maternal and paternal age and other maternal reproductive factors in relationship to the daughter's risk of breast cancer. The study group consisted of 2414 breast cancer case patients and 9138 individually matched control subjects. Breast cancer diagnoses were ascertained through the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The case patients and control subjects were born between 1875 and the end of 1947, and the mean age at diagnosis of the case patients was 65.9 years. No consistent effect for maternal or paternal age was found, except possibly among women who were firstborn children (odds ratio [OR] = 1.42 for a 10-year differential in maternal age; 95% confidence interval [CI] = 1.00-2.00). Further examination of the data indicated that mothers of case patients experienced long intervals between marriage and their first birth but not between subsequent births, and they went on to have fewer children. For each year of delay between the mother's marriage and first birth, the odds of breast cancer in the daughter increased 1.05-fold (95% CI = 1.01-1.10). We found no evidence of a consistent maternal age effect with regard to breast cancer risk in the daughter, but we did find evidence that the mothers of women who go on to get breast cancer have a reproductive pattern that could suggest some form of underlying infertility. These findings widen the epidemiologic support for the fetal antigen hypothesis, which is an immunogenetic explanation for the relationships between reproductive factors and breast cancer risk. That hypothesis provides strategies for the identification of breast cancer genes and the eventual development of a breast cancer vaccine.


Analytical evaluation of the Dade Behring Dimension RxL automated N-Terminal proBNP (NT-proBNP) method and comparison with the Roche Elecsys 2010.
Methods to quantify B-type natriuretic peptide (BNP) and N-terminal-propeptide (NT-proBNP) in plasma or serum samples are well established. We assessed the analytical performance of the Dimension RxL NT-proBNP method (Dade-Behring). Evaluation of different sample types was carried out. Controls and heparin plasma pools were used to determine the detection limit, precision, and linearity. Sample stability and the effect of interfering substances on the NT-proBNP concentrations were evaluated. Agreement between Dimension RxL and Elecsys 2010 (Roche Diagnostics) NT-proBNP methods was assessed. The influence of age and sex on NT-proBNP concentrations was evaluated in healthy subjects. Heparin plasma should be the matrix of choice. The detection limit was 2.0 ng/L. The total imprecision was 2.6-3.6% for concentrations from 231 to 9471 ng/L; mean NT-proBNP concentrations of 21 and 15 ng/L were associated with coefficients of variation of 9.9% and 14.7%, respectively. The method was linear up to 32,650 ng/L. There was no effect of temperature, freeze-thaw cycles and interfering substances. A bias was detected when Dimension RxL and Elecsys 2010 NT-proBNP methods were compared. Age and sex were significantly and independently related to NT-proBNP concentrations. The Dimension RxL NT-proBNP method, like the Elecsys 2010, is suitable for routine use in the diagnosis of heart failure.


Decreased expression of full-length mRNA for cBCD541 does not correlate with spinal muscular atrophy phenotype severity.
Spinal muscular atrophy (SMA) is characterized by degeneration of spinal cord anterior horn cells and muscular atrophy and has three phenotypes based on clinical severity and age of onset. One of the responsible genes for SMA is the survival motor neuron (SMN) gene, which is homozygously absent or interrupted in more than 90% of SMA patients. The cBCD541 (BCD) gene is a highly homologous copy of the SMN gene, which has a single synonymous transition in the coding region and may compensate for the loss of the SMN gene. To evaluate the effects of the BCD gene expression on the phenotypes of SMA, we examined lymphocyte mRNA from 9 SMA patients lacking the SMN gene, 10 asymptomatic parents, and 15 control subjects. We amplified mRNA fragments containing exon 7 of the SMN or BCD genes using reverse transcription-polymerase chain reaction since the transcript lacking exon 7 encodes a putative protein with a different C-terminal end. We used glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcript as an internal control, and the relative expression level of the SMN or BCD gene was shown as the ratio of SMN or BCD transcript to GAPDH transcript (S/G ratio). The mean S/G ratios of the patients were significantly lower than that of the parents and controls. However, among the patients examined in this study, there was no relationship between the S/G ratios and phenotypes of SMA. The results showed that the BCD gene expression was not related to the phenotypes of SMA. Furthermore, there was an overlap between the S/G ratios in patients and controls. As our discrimination study showed that the S/G ratio reflected the expression of the BCD transcripts in patients and the SMN transcripts in controls, this finding suggested that the BCD gene expression per se does not compensate for the loss of the SMN gene.


Digestible methionine+cysteine in the diet of commercial layers and its influence on the performance, quality, and amino acid profile of eggs and economic evaluation.
This work aimed at evaluating the effects of 4 digestible Met+Cys levels on the diet of commercial layers and their influence on the productive performance, quality, and amino acid profile of eggs and economic viability of the activity. A total of 576 white Lohmann LSL-Lite layers was distributed into 6 replicates of 24 birds for each diet. The experimental design was completely randomized, with 4 treatments defined by levels evaluated in the feed (0.465, 0.540, 0.581, and 0.647%). The productive performance was measured for 30 weeks. The quality (34 and 50 wk old) and the amino acid profile of eggs (43 wk old) also were evaluated. A linear positive response was observed at higher Met+Cys levels for feed intake, number of eggs per housed bird, and digestible Met+Cys intake. Egg production, egg weight, egg mass, feed efficiency, and weight gain had their optimal values determined by the quadratic regression model at 0.638, 0.654, 0.647, 0.644, and 0.613% digestible Met+Cys, respectively. In the 34th wk, eggshell thickness decreased linearly at higher Met+Cys levels. In the 50th week, the optimal levels detected for eggshell thickness and percentage were 0.571 and 0.570% digestible Met+Cys, respectively. The percentages of proteins, branched-chain amino acids (leucine, isoleucine, and valine), histidine, and proline in eggs (albumen+yolk) showed a linear negative response in function of higher Met+Cys levels. Higher digestible Met+Cys levels (>0.630%) led to a good performance of layers, while lower Met+Cys levels improved the eggshell quality of layers in peak production. Optimal Met+Cys levels may change according to the price of the synthetic amino acid.


Laboratory-based reporting of AIDS.
To improve the speed and completeness of AIDS reporting, the Philadelphia Board of Health adopted regulations requiring medical laboratories to report directly to the Department of Public Health all results indicative of AIDS-defining diagnoses. Reports were used to focus active AIDS surveillance on physicians who had requested laboratory reports whose results were likely to have diagnosed AIDS recently. One year after implementation, laboratories provided the first lead to 20% of all AIDS reports. Reports originating with laboratories reach our data base sooner after diagnosis and ascertain a slightly higher proportion of women than do other reports. Laboratory-based reporting offers a practical way to focus the limited resources available for active surveillance on health providers likely to have an AIDS diagnosis to report.


Clinical Characteristics and Risk Factors for Mortality in Critical COVID-19 Patients Aged 50 Years or Younger During Omicron Wave in Korea: Comparison With Patients Older Than 50 Years of Age.
The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group. We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality. Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m² or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043-1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584-14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042-8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691-98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294-10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison. Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients.


Vitamin B12 in plasma in patients with continent ileostomy and long observation time.
Plasma cobalamins (vitamin B12) were determined by a microbiological method in 235 patients with continent ileostomies and postoperative observation times of 3-13 years (mean, 6 years). The influence of the reservoir on the vitamin B12 values could not be evaluated in 22 patients (9%)--because of prophylactic treatment in 6%, subnormal B12 values before the operation in 1%, and 'treatment' of various neurological symptoms not caused by vitamin B12 deficiency in 2%. Fourteen (7%) of the remaining 213 patients had developed subnormal plasma levels of vitamin B12 and another 14 patients (7%) had 'borderline' values (130-200 pmol/l). The median time interval between reservoir operation and the development of subnormal values was 7.5 years (range, 3-11 years). A small-bowel resection had been added to the proctocolectomy in 11 out of 14 patients with subnormal values and in 8 out of 14 patients with borderline values. Subnormal or borderline values were seen in 27% of patients with Crohn's disease and in 12% of patients with ulcerative colitis. No patient had anaemia or neurological symptoms caused by B12 deficiency. The study shows that most patients with continent ileostomies do not develop B12 deficiency, and there is therefore no need for general prophylaxis. Since at least 7% developed subnormal values, the plasma levels of vitamin B12 should, however, be followed up regularly in all patients with continent ileostomies.


Hormonal control of myosin heavy chain genes during development of skeletal muscles.
A pattern of myosin heavy chain (MHC) switching is a hallmark of developing muscles. Factors responsible for these changes in gene expression include endogenous signals, motoneurons and hormones, especially thyroid hormones. After perturbing the innervation and/or thyroid hormone levels we have examined the neonatal-IIb MHC transition during rat development. First, denervation does not qualitatively affect the transition at either the transcriptional or translational level. Second, hypothyroidism prevents the appearance of IIb MHC and its mRNA in the innervated limb; in the denervated hypothyroid limb IIb MHC is synthesized at moderately high levels. Third, hyperthyroidism causes a precocious increase in IIb MHC in both innervated and denervated muscles. These results suggest that the transition from neonatal to adult IIb myosin synthesis is endogenously programmed during development, but is closely orchestrated by the changing neuronal and hormonal status of the animal. Thyroid hormone may exert its influence by effects both on the muscle fibre and on the developing motoneuron. In the guinea-pig the temporalis muscle is sexually dimorphic: it contains a fast-red MHC in the female but a fast-white MHC in the male. This dimorphism has been shown to be mediated by testosterone, since the castrated male synthesizes the fast-red MHC while the testosterone-supplemented female contains the fast-white MHC. During development male and female muscles initially synthesize the fast-red isoform. The male switches to the fast-white form at puberty.


Mechanisms of insulin-like growth factor-I-induced accelerated recovery in experimental ischemic acute renal failure.
Exogenous administration of recombinant human insulin-like growth factor I (rhIGF-I) to normal rats or humans increases renal blood flow and glomerular filtration rate (GFR). In rats with ischemic acute renal failure (iARF) the peptide accelerates the recovery of renal function and tubular integrity. These latter effects may be caused by renal hemodynamic actions of IGF-I or may result from direct actions of IGF-I on injured tubular cells. To examine this hypothesis, in vivo studies were performed in rats with iARF and in vitro experiments were conducted using a model of anoxia/reoxygenation injury in primary cultures of rat proximal tubular cells. In rats with iARF, IGF-I ameliorates the rise in serum creatinine, improves GFR, increases the rate of bromodeoxyuridine (BrdU) incorporation and the mitosis score, and reduces the number of apoptotic bodies. In acutely injured proximal tubular cells, IGF-I receptor mRNA levels decrease, but the remaining receptors are functional as indicated by ligand-induced phosphorylation of the IGF-I receptor beta-subunit. In anoxia/reoxygenation-injured cells, exogenous rhIGF-I improves ATP repletion, increases 3H-thymidine and BrdU incorporation and reduces the incidence of apoptosis as determined by the TUNEL method. We conclude that rhIGF-I accelerates the recovery of renal function in rats with iARF probably through hemodynamic effects, but in addition through direct metabolic, mitogenic and antiapoptotic actions on injured tubules.


Regulation of scapula development.
The scapula is a component of the shoulder girdle. Its structure has changed greatly during evolution. For example, in humans it is a large quite flat triangular bone whereas in chicks it is a long blade like structure. In this review we describe the mechanisms that control the formation of the scapula. To assimilate our understanding regarding the development of the scapula blade we start by addressing the issue concerning the origin of the scapula. Experiments using somite extirpation, chick-quail cell marking system and genetic cell labelling techniques in a variety of species have suggested that the scapula had its origin in the somites. For example we have shown in the chick that the scapula blade originates from the somite, while the cranial part, which articulates with the upper limb, is derived from the somatopleure of the forelimb field. In the second and third part of the review we discuss the compartmental origin of this bone and the signalling molecules that control the scapula development. It is very interesting that the scapula blade originates from the dorsal compartment, dermomyotome, which has been previously been associated as a source of muscle and dermis, but not of cartilage. Thus, the development of the scapula blade can be considered a case of dermomyotomal chondrogenesis. Our results show that the dermomyotomal chondrogenesis differ from the sclerotomal chondrogenesis. Firstly, the scapula precursors are located in the hypaxial domain of the dermomyotome, from which the hypaxial muscles are derived. The fate of the scapula precursors, like the hypaxial muscle, is controlled by ectoderm-derived signals and BMPs from the lateral plate mesoderm. Ectoderm ablation and inhibition of BMP activity interfers the scapula-specific Pax1 expression and scapula blade formation. However, only somite cells in the cervicothoracic transition region appear to be committed to form scapula. This indicates that the intrinsic segment specific information determines the scapula forming competence of the somite cells. Taken together, we conclude that the scapula forming cells located within the hypaxial somitic domain require BMP signals derived from the somatopleure and as yet unidentified signals from ectoderm for activation of their coded intrinsic segment specific chondrogenic programme. In the last part we discuss the new data that provides evidence that neural crest contributes for the development of the scapula.


KAAACI Evidence-Based Clinical Practice Guidelines for Chronic Cough in Adults and Children in Korea.
Chronic cough is common in the community and causes significant morbidity. Several factors may underlie this problem, but comorbid conditions located at sensory nerve endings that regulate the cough reflex, including rhinitis, rhinosinusitis, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease, are considered important. However, chronic cough is frequently non-specific and accompanied by not easily identifiable causes during the initial evaluation. Therefore, there are unmet needs for developing empirical treatment and practical diagnostic approaches that can be applied in primary clinics. Meanwhile, in referral clinics, a considerable proportion of adult patients with chronic cough are unexplained or refractory to conventional treatment. The present clinical practice guidelines aim to address major clinical questions regarding empirical treatment, practical diagnostic tools for non-specific chronic cough, and available therapeutic options for chronic wet cough in children and unexplained chronic cough in adults in Korea.


Treatment of Paget's disease of bone with porcine calcitonin: clinical and metabolic responses.
The clinical and metabolic responses of 12 patients with painful Paget's disease have been assessed before, during and after an 18-day course of treatment with purified porcine calcitonin, 160 MRC units i.m. daily. The indices of response included relief from pain, changes in concentration of serum alkaline phosphatase, calcium, magnesium, electrolytes and plasma inorganic phosphate; balance studies of calcium, phosphate, magnesium and in some cases sodium and potassium were undertaken. Urinary excretion of hydroxyproline was also measured. Remission of pain was complete in 11 of 15 courses of treatment. Coexistent osteoarthrosis was considered to be responsible where remission was incomplete. The mean duration of remission of pain was 12 months. Three patients who received a second course of treatment achieved further remission of pain. Side effects were not troublesome. Serum levels of alkaline phosphatase decreased to 67 per cent of the initial reading and the degree of suppression depended on the initial alkaline phosphatase activity. Urinary hydroxyproline correlated closely with the activity of serum alkaline phosphatase before, during and after treatment. The ratio of serum alkaline phosphatase:hydroxyproline excretion rose at the start and at the termination of treatment. Retention of calcium and inorganic phosphate occurred during the early phase of treatment only. Withdrawal of treatment resulted in a rebound retention of calcium and inorganic phosphate. The degree of calcium retention after treatment correlated with the level of plasma inorganic phosphate prevailing before treatment. The efficacy of these short courses of calcitonin are discussed and the metabolic observations related to theories of bone remodelling at a cellular and hormonal level.


Role of the research-subject locator (RSL) in the performance of a pediatric drug trial.
This article examines the feasibility, effectiveness, and ethical constraints relevant to appropriate financial compensation of the pediatric house officer who functions as a research-subject locator (RSL). When carefully trained and supervised, the RSL can facilitate timely enrollment of research subjects in pediatric drug trials, augment the house officer training experience, and advocate for children to increase therapeutic options available for pediatric care. When monitored within the clinical trial schema, the RSL has no direct link to the study outcome and thus performs within ethical standards for subject enrollment and study participation.


Trajectories of Suicidal Ideation among Adolescents Following Psychiatric Hospitalization.
Suicidal ideation (SI) is a common presenting problem for psychiatric hospitalizations in adolescents and often persists following discharge. This study examines whether distinct trajectories of SI could be delineated following hospitalization and the risk factors most strongly related to these trajectories. Adolescents (N = 104; 76 females; 28 males) were followed for 6 months after discharge from inpatient or partial hospitalization. Semi-parametric group modeling identified SI trajectory group membership. In all, 33.7% of adolescents fell in a Subclinical SI group, 43.3% in a Declining SI group, and 23.1% in a Chronic SI group. Multinomial logistic regression was utilized to examine baseline predictors of group membership. Emotion dysregulation differentiated Chronic SI from Declining SI. In multivariate analyses, adolescents endorsing greater non-acceptance of emotional responses (OR =1.18) and more limited access to emotion regulation strategies (OR =1.12) were more likely to belong to the Chronic SI than Declining SI trajectory. Those in the Chronic SI group also had the greatest number of suicide attempts and hospitalizations in the 6 months post-discharge. These results suggest that clinicians should closely monitor and address emotion dysregulation when assessing suicide risk. Greater dysregulation may require more intensive services in order to have an effect on chronic SI.


circ_ZFR Is Linked to Paclitaxel Resistance in Cervical Cancer via miR-944 Sponging and IL-10 Upregulation.
Cervical cancer (CC) has an elevated rate of invasion and death despite surgical treatment, radiotherapy, and chemotherapy. Several studies revealed that circRNAs have a key contribution to the resistance of drugs against different types of carcinomas. The goal of the existing study was to figure out what role circ_ZFR plays in paclitaxel (PTX) resistance in cervical cancer (CC) patients. Herein, two types of CC cells (SiHa/PTX and Hela/PTX) were utilized. The levels of IL-10 mRNA, miR-944, and circ_ZFR were measured using qRT-PCR analyses. The CCK-8 assay was used to determine PTX resistance. The IL-10 expression was measured via the ELISA technique. The combination of miR-944 and circ_ZFR or IL-10 was validated using a dual-luciferase reporter (DLR) assay. The amount of circ_ZFR was increased in PTX-resistant CC cells and tissues. In PTX-resistant CC cells, knocking down circ_ZFR expression decreased PTX resistance. circ_ZFR knockdown significantly reduced IL-10 expression via sponging miR-944, increasing PTX sensitivity in PTX-resistant CC cells. circ_ZFR knockdown has a considerable role in overwhelming CC-associated PTX resistance by modifying the axis of miR-944/IL-10 axis, suggesting that developing a circRNA target-based treatment could be considered prevent CC progression.


A Pathological Study of Acute Pulmonary Toxicity Induced by Inhaled Kanto Loam Powder.
The frequency and volume of Asian sand dust (ASD) (Kosa) are increasing in Japan, and it has been reported that ASD may cause adverse respiratory effects. The pulmonary toxicity of ASD has been previously analyzed in mice exposed to ASD particles by intratracheal instillation. To study the pulmonary toxicity induced by inhalation of ASD, ICR mice were exposed by inhalation to 50 or 200 mg/m³ Kanto loam powder, which resembles ASD in elemental composition and particle size, for 6 h a day over 1, 3, 6, 9, or 15 consecutive days. Histological examination revealed that Kanto loam powder induced acute inflammation in the whole lung at all the time points examined. The lesions were characterized by infiltration of neutrophils and macrophages. The intensity of the inflammatory changes in the lung and number of neutrophils in both histological lesions and bronchoalveolar lavage fluid (BALF) appeared to increase over time. Immunohistochemical staining showed interleukin (IL)-6- and tumor necrosis factor (TNF)-α-positive macrophages and a decrease in laminin positivity in the inflammatory lesions of the lung tissues. Electron microscopy revealed vacuolar degeneration in the alveolar epithelial cells close to the Kanto loam particles. The nitric oxide level in the BALF increased over time. These results suggest that inhaled Kanto loam powder may induce diffuse and acute pulmonary inflammation, which is associated with increased expression of inflammatory cytokines and oxidative stress.


Discontinuation of immunoglobulin replacement therapy in patients with secondary antibody deficiency.
Secondary immunodeficiency is becoming a greater medical concern as the usage of immunosuppressive and biological treatments has increased. Individuals with certain medical conditions, such as hematological malignancies, can also have secondary immunodeficiency. Immunoglobulin replacement therapy (IGRT), which has been used for decades in inherited or primary immunodeficiency, provides some protection to patients with acquired and predominant antibody deficiency, i.e. secondary antibody deficiency (SAD). However, IGRT is costly, and supplies are limited. Although there are clinical guidelines on when to initiate IGRT, there is no guideline on when to discontinue it. The authors reviewed existing literature and provided an overview of the current state of knowledge regarding IGRT discontinuation in SAD patients. Long-term supplementary immunoglobulin may not be necessary. Although it is possible to successfully transition away from IGRT in individuals with SAD, evidence-based practices are limited. Without clear guidelines and reliable prognostic markers, IGRT discontinuation practices are restricted to clinical judgment. For this reason, additional research should be conducted to identify markers that indicate the recovery of humoral immunity. Furthermore, the derivation and validation of a set of combined clinical and laboratory criteria to allow safe and timely IGRT discontinuation is warranted.


Path integral Monte Carlo simulations of dense carbon-hydrogen plasmas.
Carbon-hydrogen plasmas and hydrocarbon materials are of broad interest to laser shock experimentalists, high energy density physicists, and astrophysicists. Accurate equations of state (EOSs) of hydrocarbons are valuable for various studies from inertial confinement fusion to planetary science. By combining path integral Monte Carlo (PIMC) results at high temperatures and density functional theory molecular dynamics results at lower temperatures, we compute the EOSs for hydrocarbons from simulations performed at 1473 separate (ρ, T)-points distributed over a range of compositions. These methods accurately treat electronic excitation effects with neither adjustable parameter nor experimental input. PIMC is also an accurate simulation method that is capable of treating many-body interaction and nuclear quantum effects at finite temperatures. These methods therefore provide a benchmark-quality EOS that surpasses that of semi-empirical and Thomas-Fermi-based methods in the warm dense matter regime. By comparing our first-principles EOS to the LEOS 5112 model for CH, we validate the specific heat assumptions in this model but suggest that the Grüneisen parameter is too large at low temperatures. Based on our first-principles EOSs, we predict the principal Hugoniot curve of polystyrene to be 2%-5% softer at maximum shock compression than that predicted by orbital-free density functional theory and SESAME 7593. By investigating the atomic structure and chemical bonding of hydrocarbons, we show a drastic decrease in the lifetime of chemical bonds in the pressure interval from 0.4 to 4 megabar. We find the assumption of linear mixing to be valid for describing the EOS and the shock Hugoniot curve of hydrocarbons in the regime of partially ionized atomic liquids. We make predictions of the shock compression of glow-discharge polymers and investigate the effects of oxygen content and C:H ratio on its Hugoniot curve. Our full suite of first-principles simulation results may be used to benchmark future theoretical investigations pertaining to hydrocarbon EOSs and should be helpful in guiding the design of future experiments on hydrocarbons in the gigabar regime.


Nilotinib-induced interstitial lung disease.
Nilotinib is a second-generation tyrosine kinase inhibitor active in patients with chronic myeloid leukemia (CML) resistant to imatinib, and has been recently approved for newly diagnosed patients. We present a case of nilotinib-induced interstitial lung disease (ILD). A 67-year-old female patient was initially treated with imatinib for chronic-phase Philadelphia chromosome-positive (Ph(+)) CML. Imatinib was replaced by nilotinib because of hematological toxicity. The patient had received nilotinib for about 3 years without significant adverse effects. She visited the clinic due to chronic cough; chest X-ray revealed consolidations in both lung fields. Nilotinib-induced ILD was diagnosed based on intensive workup, including lung biopsy. She responded dramatically to corticosteroid therapy. To our knowledge, this is the first reported case of nilotinib-induced ILD in a patient with Ph(+) CML. We emphasize that if unexplained lung abnormalities progress in patients receiving nilotinib, physicians should consider this potentially fatal complication in their differential diagnoses.


Tuberculosis vaccine development.
If the end of the 20th century saw the flowering of genomics, the beginning of the 21st century is witnessing an equally rapid blossoming of proteomics. These twin technologies have had a dramatic influence on the study of tuberculosis (TB), and nowhere more so than in the development of new TB vaccines. Only a few years ago, it was generally accepted that clinical trials of new TB vaccines would not take place for at least a decade. However, the first trials are now scheduled to start within months. Much TB vaccine research has thus shifted from developing new vaccines, to selecting the best vaccines for human use from the increasing number of effective new candidates becoming available. This selection is being eased by the improved animal models that have been developed over the past few years and by our increasing understanding of immunity to TB.


Assessment of esthetic characteristics of the teeth and surrounding anatomical structures.
To determine the differences in the perception of aesthetic characteristics of the front teeth which include anatomic variations, appearance of the gums and dental arches, smiles and the lower third of the face between three groups of assessors. The study included 60 patients with permanent fully toothed dentition with no prosthetic work done and with Angle class I, whose lower third of the face was photographed while smiling. Collected photos were then assessed by people of the general population (21), graduate doctors of dental medicine (20) and specialists in dental prosthetics (20) using a modified OAS questionnaire (Orofacial aesthetic scale). General population assessors gave weakest scores to the appearance of teeth, tooth color and appearance of the dental arches, and they gave highest scores to the appearance of the gums. Specialists in dental prosthetics gave top scores (p <0.01) for the shape and color of teeth, the appearance of the dental arches and lips and general appearance of the lower third of the face, and gave the worst scores for the appearance of the gums (p <0.01). Male assessors and people aged 36-55 are the least critical in assessing the shape and the color of teeth, appearance of the arches and lips, and the general appearance of the lower third of the face. In assessing the gums the most tolerant assessors are patients over the age of 55 (p<0.01). Considering the age and gender it can be concluded that all the criteria contribute to the assessment of the aesthetics of the teeth and surrounding structures. The results of this study may help in the planning of dental prosthetics procedures.


Thermally triggered self-assembly of folded proteins into vesicles.
We report thermally triggered self-assembly of folded proteins into vesicles that incorporates globular proteins as building blocks. Leucine zipper coiled coils were combined with either globular proteins or elastin-like polypeptides as recombinant fusion proteins, which form "rod-coil" and "globule-rod-coil" protein complex amphiphiles. In aqueous solution, they self-assembled into hollow vesicles via temperature-responsive inverse phase transition. The characteristic of the protein vesicle membranes enables preferential encapsulation of simultaneously formed protein coacervate. Furthermore, the type of encapsulated cargo extends to small molecules and nanoparticles. Our approach offers a versatile strategy to create protein vesicles as vehicles with biological functionality.


The pharmacology of fluparoxan: a selective alpha 2-adrenoceptor antagonist.
1. This paper describes the pharmacology of the novel alpha 2-adrenoceptor antagonist fluparoxan (GR 50360) which is currently being studied clinically as a potential anti-depressant. Idazoxan and yohimbine were included in many studies for comparison. 2. In the rat isolated, field-stimulated vas deferens and the guinea-pig isolated, field-stimulated ileum preparations, fluparoxan was a reversible competitive antagonist of the inhibitory responses to the alpha 2-adrenoceptor agonist UK-14304 with pKB values of 7.87 and 7.89 respectively. In the rat isolated anococcygeus muscle, fluparoxan was a much weaker competitive antagonist of the contractile response to the alpha 1-adrenoceptor agonist phenylephrine with a pKB of 4.45 giving an alpha 2: alpha 1-adrenoceptor selectivity ratio of greater than 2500. 3. In the conscious mouse, fluparoxan (0.2-3.0 mg kg-1) was effective by the oral route and of similar potency to idazoxan in preventing clonidine-induced hypothermia and antinociception. In the rat, UK-14304-induced hypothermia (ED50 = 1.4 mg kg-1, p.o. or 0.5 mg kg-1, i.v.) and rotarod impairment (ED50 = 1.1 mg kg-1 p.o. or 1.3 mg kg-1, i.v.) were antagonized by fluparoxan. Fluparoxan, 0.67-6 mg kg-1, p.o., also prevented UK-14304-induced sedation and bradycardia in the dog. 4. In specificity studies fluparoxan had low or no affinity for a wide range of neurotransmitter receptor sites at concentrations up to at least 1 x 10(-5) M. It displayed weak affinity for 5-HT1A (pIC50 = 5.9) and 5-HT1B (pKi = 5.5) binding sites in rat brain. 5. We conclude that fluparoxan is a highly selective and potent alpha 2-adrenoceptor antagonist. The density of rat brain [3H]-dihydroalprenolol binding sites was reduced by 26% when fluparoxan was administered chronically for 6 days at a dose of 12 mg kg- 1 orally twice daily. The down-regulation of beta-adrenoceptors by fluparoxan is consistent with its antidepressant potential.


Role of gamma-glutamyltranspeptidase on the response of poorly and moderately differentiated rhabdomyosarcoma cell lines to buthionine sulfoximine-induced inhibition of glutathione synthesis.
Glutathione (GSH) is involved in many cellular functions, including cell growth and differentiation. GSH also plays an important role in the protection of cells against oxidative damage and hence in determining the sensitivity of cells to the cytotoxicity of anticancer agents. Because of this, induction of GSH depletion has been proposed as a good strategy for sensitizing tumor cells to antitumor agents. The aim of the present work is to study the effect of buthionine sulfoximine (BSO, a specific cellular GSH-depleting agent) in two rat tumor cell lines derived from the same rhabdomyosarcoma tumor model, the moderately differentiated and low metastatic F21 cell line, and the poorly differentiated and high metastatic S4MH cell line, to investigate the influence of the degree of differentiation in the induction of GSH depletion-based therapy. We observed that, whereas in the S4MH cell line BSO induced a dose-dependent inhibition of both cell growth in vitro and tumorigenic potential in vivo, in F21 cells the administration of moderate doses of BSO enhanced tumor growth and only at high doses was there a slight reduction of their tumorigenic potential. These effects were in consonance with the fact that the activity of gamma-glutamyltranspeptidase (gamma-GT) present in the F21 cells was 4 times higher than in the S4MH cells. Indeed, inhibition of gamma-GT activity by acivicin not only abrogated the BSO-induced increase of GSH content and of cell growth, but also the combination of acivicin + BSO significantly decreased intracellular GSH levels and cell proliferation, and induced F21 cells to apoptosis. These studies suggest that, as occurs in the rhabdomyosarcoma tumor model, gamma-GT levels and the degree of differentiation of tumor cells might influence the response of tumor cells to inducers of GSH depletion, and should be taken into account in therapies based on GSH metabolism.


Prenatal risk assessment and obstetric care in a small rural hospital: comparison with guidelines.
An assessment was made of the potential usefulness in a small rural hospital of the guidelines for prenatal risk assessment and management of the Newfoundland and Labrador Prenatal Record, a form similar to that in use in other provinces. A retrospective chart review was done for 266 pregnancies followed at the Baie Verte Peninsula Health Centre prior to the introduction of the guidelines. The pattern of practice was to request consultation and to transfer patients for delivery less often than was suggested by the guidelines; only 32% of patients at risk were assessed by an obstetrician. By the time of delivery only 39% of the patients were at no predictable risk according to the guidelines. Nevertheless, neonatal morbidity was present in this group (4% of the infants had an Apgar score of 6 or less at 1 or 5 minutes), though less often than in those at risk (18% of the infants had a low Apgar score). However, the group at no predictable risk required nonelective intervention in 40% of cases, approximately the same rate as that for the group at risk. It is necessary for some small hospitals to have the facilities and the trained staff to handle the problems that occur even in low-risk patients. To maintain the delivery rate necessary to retain skills, the guidelines may help family practitioners and consulting obstetricians to select some patients at risk who can be managed in small hospitals.


Law enforcement in the trauma bay: a survey of members of the American Academy for the Surgery of Trauma.
Trauma patients frequently come into contact with law enforcement officers (LEOs) during the course of their medical care, but little is known about how LEO presence affects processes of care. We surveyed members of the American Association for the Surgery of Trauma (AAST) to assess their perspectives on frequency, circumstances, and implications of LEO presence in trauma bays nationwide. Survey items addressed respondents' experience with the frequency and context of LEO presence and their perspectives on the impact of LEO presence for patients, clinical care, and public safety. Respondent demographics, professional characteristics, and practice setting were collected. The survey was distributed electronically to AAST members in September and October of 2020. Responses were compared by participant age, gender, race, ethnicity, urban versus rural location using χ2 tests. Of 234 respondents, 189 (80.7%) were attending surgeons, 169 (72.2%) identified as white, and 144 (61.5%) as male. 187 respondents (79.9%) observed LEO presence at least weekly. Respondents found LEO presence was most helpful for public safety, followed by clinical care, and then for patients. Older respondents rated LEO presence as helpful more often than younger respondents regarding the impact on patients, clinical care, and public safety (p<0.001 across all domains). When determining LEO access, respondents assessed severity of the patient's condition, the safety of emergency department staff, the safety of LEOs, and a patient's potential role as a threat to public safety. Respondents described a wide range of perspectives on the impact and consequence of LEO in the trauma bay, with little policy to guide interactions. The overlap of law enforcement and healthcare in the trauma bay deserves attention from institutional and professional policymakers to preserve patient safety and autonomy and patient-centered care. IV, survey study.


[Blood levels of nitrogenous substances in dairy cows with high and low production].
In blood serum of dairy cows of the Slovak Pied breed with high and low performance, the levels of total protein, urea, amino nitrogen, non-protein nitrogen and uric acid were studied over the period of four to six weeks after calving. Total protein was determined by the Bio-La-test, amino nitrogen by means of ninhydrin, non-protein nitrogen by Berthelot agent and uric acid by Benedict agent. In comparison with dairy cows with low performance, the dairy cows with high performance had a statistically significantly higher level of total protein, urea, amino nitrogen and non-protein nitrogen. The differences in uric acid content were statistically insignificant.


Defense mechanisms in schizotypal, borderline, antisocial, and narcissistic personality disorders.
Numerous authors have theorized that defense mechanisms play a role in personality disorders. We reviewed theoretical writings and empirical studies about defenses in schizotypal, borderline, antisocial, and narcissistic personality disorders, developing hypotheses about these differential relationships. We then examined these hypotheses using dynamic interview data rated for defenses in a study of participants (n = 107) diagnosed with these four personality disorder types. Overall, the prevalence of immature defenses was substantial, and all four disorders fit within the broad borderline personality organization construct. Defenses predicted the most variance in borderline and the least variance in schizotypal personality disorder, suggesting that dynamic factors played the largest role in borderline and the least in schizotypal personality. Central to borderline personality were strong associations with major image-distorting defenses, primarily splitting of self and other's images, and the hysterical level defenses, dissociation and repression. Narcissistic and antisocial personality disorders shared minor image-distorting defenses, such as omnipotence or devaluation, while narcissistic also used splitting of self-images and antisocial used disavowal defenses like denial. Overall, differential relationships between specific defenses and personality disorder types were largely consistent with the literature, and consistent with the importance that the treatment literature ascribes to working with defenses.


Significance of admission hypoalbuminemia in acute intracerebral hemorrhage.
Low levels of serum albumin may increase the risk of infections and mortality in critically ill patients. We tested the hypothesis that admission hypoalbuminemia predicted infectious complications and poor outcome in subjects with acute intracerebral hemorrhage (ICH). We analyzed a single center cohort of ICH patients collected between 1994 and 2015. Pneumonia, urinary tract infection and sepsis were retrospectively identified, according to validated criteria. Serum albumin was measured on admission and hypoalbuminemia was defined as total albumin ≤3.5 g/dL. The association between albumin levels, infections, and mortality at 90 days was tested with multivariable logistic regression analyses. A total of 2010 patients were included (median age 74 years, 54.5% males) of whom 444 (22.1%) had hypoalbuminemia on admission and 763 (38%) died within 90 days. The frequency of pneumonia, urinary tract infection, and sepsis was 19.9, 15.1, and 2.7%, respectively. Hypoalbuminemic patients had lower admission Glasgow coma scale, higher frequency of intraventricular hemorrhage and were more likely to have a history of chronic kidney or liver disease. After adjustment for potential confounders, hypoalbuminemia was an independent predictor of pneumonia [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.34-2.33, p < 0.001] and sepsis (OR 2.29, 95% CI 1.22-4.30, p = 0.010). Low levels of albumin were also independently associated with higher mortality at 90 days (OR 1.78, 95% CI 1.30-2.44, p < 0.001). In conclusion, early hypoalbuminemia is common and predicts poor outcome in ICH patients. Increased susceptibility to pneumonia and sepsis may be the pathophysiological mechanism underlying this association.


Available electron and energetic yields in fermentation processes.
Microbial growth and product yields have been investigated for several cultures. Available electron and free energy balances may be used to examine the efficiency of microbial energetics. Energetic yields based on free energy analysis were obtained and compared with yields from available electron analysis. Estimates of true growth yields under anaerobic conditions have been obtained using statistical methods and the results were compared with theoretical maximum yields.


Effects of chloride channel blockers on hypoxic injury in rat proximal tubules.
These studies examined the pathways and consequences of chloride uptake into proximal tubule cells during in vitro hypoxia. The chloride channel blocker diphenylamine-2-carboxylate (DPC) markedly reduced the degree of hypoxia-induced membrane damage as measured by the release of lactate dehydrogenase (LDH). DPC reduced the release of LDH from hypoxic tubules from 38 +/- 2.7% to 16 +/- 1.7% after 30 minutes of hypoxia (P < 0.001, N = 16) and also reduced 36Cl- uptake by hypoxic tubules. The reduction in LDH release was not associated with better preservation of cell ATP content or with protection against hypoxia-induced DNA damage. Other Cl- channel blockers, such as niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and 2-[(2-cyclopentyl-6,7-dichloro-2,3-dihyrdo-2-methyl-1-oxo-1H-in den-5-yl)oxy] acetic acid (IAA-94) provided even greater protection than DPC and were as effective as 2 mM glycine. The Cl- channel blockers appear to act late in the course of hypoxic injury since DNA damage, an early manifestation of injury, is not prevented by the blockers and since addition of the Cl- channel blocker after the hypoxic injury has begun reduces further membrane damage. These results support the conclusion that transport through Cl- channels contributes to hypoxic cell injury in proximal tubular cells.


21st century natural product research and drug development and traditional medicines.
Natural products and related structures are essential sources of new pharmaceuticals, because of the immense variety of functionally relevant secondary metabolites of microbial and plant species. Furthermore, the development of powerful analytical tools based upon genomics, proteomics, metabolomics, bioinformatics and other 21st century technologies are greatly expediting identification and characterization of these natural products. Here we discuss the synergistic and reciprocal benefits of linking these 'omics technologies with robust ethnobotanical and ethnomedical studies of traditional medicines, to provide critically needed improved medicines and treatments that are inexpensive, accessible, safe and reliable. However, careless application of modern technologies can challenge traditional knowledge and biodiversity that are the foundation of traditional medicines. To address such challenges while fulfilling the need for improved (and new) medicines, we encourage the development of Regional Centres of 'omics Technologies functionally linked with Regional Centres of Genetic Resources, especially in regions of the world where use of traditional medicines is prevalent and essential for health.


A biodegradable polyurethane-ascorbic acid scaffold for bone tissue engineering.
A novel, nontoxic, biodegradable, sponge-like polyurethane scaffold was synthesized from lysine-di-isocyanate (LDI) and glycerol. Ascorbic acid (AA) was copolymerized with LDI-glycerol. Our hypothesis was that the AA-containing polymer foam would enhance the biological activity of the osteoblastic precursor cell (OPCs). The LDI-glycerol-AA matrix degraded in aqueous solution to the nontoxic products of lysine, glycerol, and AA. The degradation products did not significantly affect the solution pH. The physical properties of the polymer network supported the cell growth in vitro. Mouse OPCs attached to the polymer matrix and remained viable. OPCs produced multilayered confluent cultures, a characteristic typical of bone cells. Furthermore, AA release stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis. Cells grown on the LDI-glycerol-AA matrix also showed an enhancement of mRNA expression for pro-alpha1 (I) collagen and transforming growth factor-alpha1 after 1 week. Data were tested for significance with an analysis of variance model and multiple comparison test (Fisher's Protected Least Significant Difference) at p < or = 0.05. The observations suggest that AA-containing polyurethane may be useful in bone tissue engineering applications.


HI-6 in man: efficacy of the oxime in poisoning by organophosphorus insecticides.
The efficacy of the oxime HI-6 was studied as a treatment for organophosphorus poisoning. HI-6 was given four times daily as a single intramuscular injection of 500 mg accompanied by atropine and diazepam therapy. Oxime treatment was started on admission and continued for a minimum of 48 h and a maximum of 7 d. HI-6 rapidly reactivated human blood acetylcholinesterase inhibited by dimethoxy organophosphorus compounds, while the dimethoxy-inhibited enzyme was mainly resistant to the treatment by HI-6. Although both HI-6 and pralidoxime chloride reactivated the red blood cell cholinesterase in quinalphos-poisoned subjects, the return of enzyme activities was more rapid following the use of HI-6. The general improvement of poisoned patients, which was sometimes more rapid than the rise of acetylcholinesterase activity, pointed to direct pharmacological effects of HI-6. No undesirable side-effects were noted in patients when HI-6 plasma concentrations were maintained at levels far above the 'therapeutic' concentration for up to 7 d.


Adaptive responsiveness of some central receptors to the denervation of heterologous afferent fibers: functional significance and possible behavioral consequences.
As shown in the rat brain, the development of the classical "denervation supersensitivity" of receptors does not always occur despite the complete destruction of the corresponding afferent fibers. This is due to the concomitant destruction of heterologous fibers which directly or indirectly contribute to the regulation of the denervated receptors. In this review, on the basis of data obtained in rats with lesions of ascending DA neurons, three examples of hetero-regulation of receptors will be provided. In the prefrontal cortex, the concomitant destruction of afferent noradrenergic fibers (NA) prevents the development of the denervation supersensitivity of DA receptors of the D1 type. In the nucleus accumbens, the development of the denervation supersensitivity of D1 receptors seems to be dependent on the state of activity of the cortico-nucleus accumbens glutamatergic projection. Finally, in cortico-limbic structures, the prolonged interruption of DA transmission leads to an increased density of 125I-neurotensin binding sites. These hetero-regulations reflect the existence of possible functional relationships between the two types of neuronal populations under investigation. As an example, it will be shown that some dysfunctions seen following the degeneration of the mesocortico-prefrontal and mesolimbic DA neurons disappear following the combined destruction of ascending NA neurons.


Eyelid lymphedema following neck dissection and radiotherapy.
Chronic eyelid lymphedema following neck dissection and radiotherapy is rare with 1 report in the literature. The authors report 3 cases and review the literature. Two cases had bilateral neck dissection and developed bilateral eyelid lymphedema and 1 case had unilateral neck dissection (left side) and developed ipsilateral lymphedema. Two patients underwent surgical debulking of lymphedema with significant improvement in symptoms. One patient declined surgical intervention, and the lymphedema remained unchanged. Chronic eyelid lymphedema following neck dissection and radiotherapy occurs where predominant lymphatic drainage to the submandibular and deep cervical lymph node basin is removed. Lymphedema tends to persist when it occurs and in selected cases appearance can be effectively improved by debulking and excision of festoons.


Possible chromosomal and germline integration of human herpesvirus 7.
Human herpesvirus 7 (HHV-7) is a betaherpesvirus, and is phylogenetically related to both HHV-6A and HHV-6B. The presence of telomeric repeat sequences at both ends of its genome should make it equally likely to integrate into the human telomere as HHV-6. However, numerous studies have failed to detect germline integration of HHV-7, suggesting an important difference between the HHV-6A/-6B and HHV-7 genomes. In search of possible germline integrated HHV-7, we developed a sensitive and quantitative real-time PCR assay and discovered that primers designed against some parts of the HHV-7 genome can frequently miss HHV-7 positive clinical samples even though they work efficiently in cell-culture-derived HHV-7 positive materials. Using a primer pair against the U90 ORF of HHV-7, we identified a possible case of germline integration of HHV-7 with one copy of viral genome per cell in both peripheral blood cells and hair follicles. Chromosomal integration of HHV-7 in these individuals was confirmed by fluorescence in situ hybridization analysis. Germline integration of HHV-7 was further confirmed by detection of ~2.6 copies of HHV-7 in the hair follicles of one of the parents. Our results shed light on the complex nature of the HHV-7 genome in human-derived materials in comparison to cell-culture-derived materials and show the need for stringent criteria in the selection of primers for epidemiological HHV-7 studies.


Formation and early development of the corpus luteum in pigs.
Numerous corpora lutea form from the multiple follicles that ovulate during the oestrous cycle of pigs. Vascular elements invade the follicle from the theca compartment, first centripetally, and subsequently by lateral branching of centripetal veins and arteries. The vessels are the vehicle for dispersion of steroidogenic theca cells throughout the corpus luteum. Mitosis occurs in both the theca and granulosa layers before ovulation, and in luteal cells well into the luteal phase. Luteal cell proliferation undergoes gradual restriction as the corpus luteum matures, but the mechanisms of exit from the cell cycle are unknown. The extracellular ligands that direct luteinization and maintain the corpus luteum include LH, prolactin, insulin and insulin-like growth factors (IGFs). These ligands induce qualitative and quantitative changes in steroid output, with progesterone as the principal product. These changes upregulate the cholesterol synthetic pathways to increase substrate availability. The intracellular regulation of luteinization is complex. A model is presented in which LH stimulates arachidonic and lineoleic acid metabolism to produce ligands for the nuclear proteins of the peripheral peroxisome activator receptor family. These ligands have downstream effects on cell differentiation and exit from the cell cycle. Luteal function is maintained by interactions among ligands, cholesterol regulatory proteins and constitutively expressed and regulated transcription factors.


Excision of prolapse of thoracic intervertebral disc. A transthoracic technique.
A new technique for the transthoracic removal of a prolapsed intervertebral disc in the mid or lower thoracic spine is described. Investigations before operation include thoracic myelography, selective spinal angiography and CT scanning. Image intensification is used at operation to check the level of the prolapse. A tunnel in the coronal plane (vertebrotomy) is made through the posterolateral part of the disc and the adjacent vertebral bodies, to reach the spinal canal at the site of the prolapse. This gives good exposure and enables gentle removal of the disc prolapse and any associated osteophytes, under direct vision without need for retraction or pressure on the dura or spinal cord. Spinal stability is not compromised, and the blood supply of the cord is not disturbed. Five consecutive patients are reported, including one in whom the disc prolapse was calcified and had herniated into the spinal cord. All were treated successfully.


Breaking symmetry - cell polarity signaling pathways in growth cone guidance and synapse formation.
Directional and positional information is essential for the diverse neuronal morphology and connectivity during development. The direction of axon growth is critical for building the correct networks among neurons, sometimes from far away. Neuronal synapses are asymmetric cell-cell junctions with distinct presynaptic and postsynaptic structures to convey neural activity in a directional fashion. Recent studies show that some of the key asymmetry is mediated by highly conversed cell polarity signaling pathways. These pathways, planar cell polarity and apical-basal polarity, are not required for the global axon-dendrite polarity. Therefore, the apparent distinct types of morphological asymmetry in the nervous system, growth cone turning and synaptic junctions, are mediated by similar cell polarity signaling mechanisms widely used in cellular and tissue morphogenesis.


Dual-time point 18F-FDG-PET and PET/CT for Differentiating Benign From Malignant Musculoskeletal Lesions: Opportunities and Limitations.
In this review, we summarize the false-positive and false-negative results of standard 18F-FDG-PET/CT in characterizing musculoskeletal lesions and discussed the added value and limitations of dual-time point imaging (DTPI) and delayed imaging in differentiating malignant from benign musculoskeletal lesions, based on review of the peer-reviewed literature. The quantitative and semiquantitative parameters adopted for DTPI are standardized uptake value (mainly maximum standardized uptake value [SUVmax]) and retention index (RI), calculated as RI (%) = 100% × (SUV [maxD-Delayed] - SUV [maxE-Early])/SUV [maxE-Early], although the criteria and cutoff for diagnosing malignancy in studies have varied considerably. Also, there has been considerable heterogeneity in protocol (time point of delayed imaging), interpretation, and results in dual-time point (DTP) 18F-FDG-PET for differentiating malignant from benign musculoskeletal lesions in various research studies. The specificity of DTPI is a function of many factors such as the nature of the musculoskeletal lesion or malignancy in question, the prevalence of false-positive etiologies in the patient population, and the cutoff values (either SUVmax or RI) employed to define a malignancy. Despite the apparent conflicting reports on the performance, there have been certain common points of agreement regarding DTPI: (1) DTP PET increases the sensitivity of 18F-FDG-PET/CT due to continued clearance of background activity and increasing 18F-FDG accumulation in malignant lesions, when the same diagnostic criteria (as in the initial standard single-time point imaging) are used. Increased sensitivity for lesion detection can be viewed as a strong point of DTP and delayed-time point imaging. (2) The causes for false positives (such as active infectious or inflammatory lesions and locally aggressive benign tumors) and false negatives (eg, low-grade sarcomas) are the major hurdles accounting for reduced diagnostic value of the technique, with overlap of 18F-FDG uptake patterns between benign and malignant musculoskeletal lesions on DTPI. (3) DTPI, however, could still be potentially useful in increasing the confidence of interpretation such as differentiating malignancy from sites of inactive or chronic inflammation, post-treatment viable residue vs necrosis, and certain other benign lesions. (4) Consideration of diagnostic CT component of PET/CT and the patient's clinical picture can lead to increase in specificity of interpretation in a given case scenario. Further systematic research, adoption of uniform protocol, and interpretation criterion could evolve the specific indications and interpretation criteria of DTPI for improved diagnostic accuracy in musculoskeletal lesions and its clinical applications.


Prevalence and incidence studies of anxiety disorders: a systematic review of the literature.
To present the results of a systematic review of literature published between 1980 and 2004 reporting findings of the prevalence and incidence of anxiety disorders in the general population. A literature search of epidemiologic studies of anxiety disorders was conducted, using Medline and HealthSTAR databases, canvassing English-language publications. Eligible publications were restricted to studies that examined age ranges covering the adult population. A set of predetermined inclusion and exclusion criteria were used to identify relevant studies. Prevalence and incidence data were extracted and analyzed for heterogeneity. A total of 41 prevalence and 5 incidence studies met eligibility criteria. We found heterogeneity across 1-year and lifetime prevalence rates of all anxiety disorder categories. Pooled 1-year and lifetime prevalence rates for total anxiety disorders were 10.6% and 16.6%. Pooled rates for individual disorders varied widely. Women had generally higher prevalence rates across all anxiety disorder categories, compared with men, but the magnitude of this difference varied. The international prevalence of anxiety disorders varies greatly between published epidemiologic reports. The variability associated with all anxiety disorders is considerably smaller than the variability associated with individual disorders. Women report higher rates of anxiety disorders than men. Several factors were found to be associated with heterogeneity among rates, including diagnostic criteria, diagnostic instrument, sample size, country studied, and response rate.


Transcriptional profiling of the developmentally important signalling pathways in human embryonic stem cells.
Embryonic stem cells (ESC) maintain their 'stemness' by self-renewal. However, the molecular mechanisms underlying self-renewal of human embryonic stem cells (hESC) remain to be elucidated. In this study, expression profiles of the molecules of developmentally important signalling pathways were investigated to better understand the relationships of the signalling pathways for self-renewal in hESC. Two human ESC lines were cultured on mouse embryonic fibroblast (MEF) feeder cells. Gene expression was analysed by RT-PCR, real-time RT-PCR and Western blotting. In the bone morphogenetic protein (BMP4), transforming growth factor (TGF-beta) and fibroblast growth factor (FGF4) signalling pathways, ligands and antagonists were highly expressed in hESC compared with human embryoid body (hEB). Human ESC showed abundant transcripts of intracellular molecules in the Wnt, Hh and Notch signalling pathways. No difference was detected in the expression level of the JAK/STAT signalling molecules between hESC and hEB. Western blot analysis showed that the transcriptional levels of the signalling molecules in hESC were consistent with translational levels. From the real-time PCR analysis, expression levels of some genes, such as Oct3/4, Nodal and beta-catenin, were different between two hESC lines. The self-renewal of hESC is probably maintained by coordinated regulation of signalling-specific molecules and in a signalling-specific manner.


Anatomy of an occlusal splint.
Occlusal splints, also known as bite guards, oral orthotics, and oral appliances, are utilized frequently in dental practices. They are commonly used to relax jaw muscles, prevent temporomandibular jaw trauma, protect dentition, and control headaches. How well occlusal splints work is another matter. Numerous studies, when taken as a whole, suggest only a modest indication that they are useful. This review applies principles of neurophysiology to analyze the usefulness of several types of occlusal splint in relation to their design and function. A unique occlusal splint with a design based on neurophysiology is described.


Key to the fossil genus Largusoperla (Plecoptera: Perlidae), with description of two new species from mid-Cretaceous Burmese amber.
Two new species of the fossil stonefly genus Largusoperla (Plecoptera: Perlidae), Largusoperla dewalti sp. nov. and Largusoperla borisi sp. nov. are described and illustrated from mid-Cretaceous Burmese amber. The two new species are distinguished from other known congeners by the specifically modified paraprocts. In addition, an identification key to the known species of Largusoperla is provided.


Lattice distortion and magnetic quantum phase transition in CeFeAs(1-x)P(x)O.
We use neutron diffraction to study the structural and magnetic phase diagram of CeFeAs(1-x)P(x)O. We find that replacing the larger arsenic with smaller phosphorus in CeFeAs(1-x)P(x)O simultaneously suppresses the AFM order and orthorhombic distortion near x=0.4, thus suggesting the presence of a magnetic quantum critical point. Our detailed structural analysis reveals that the pnictogen height is an important controlling parameter for their electronic and magnetic properties, and may play an important role in electron pairing and superconductivity of these materials.