Conventional Ultrasound, Immunohistochemical Factors and BRAFV600E Mutation in Predicting Central Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma.
The study was aimed at evaluating the correlation between central cervical lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients and ultrasound (US) features, immunohistochemical factors and BRAFV600E mutation. A total of 225 consecutive patients (225 PTCs) who had undergone surgery were included. All PTCs were pre-operatively analysed by US with respect to size, components, echogenicity, shape, margins, microcalcification, multiple cancers or not, internal vascularity and capsule contact or involvement. The presence of four immunohistochemical factors, including cytokeratin 19, human bone marrow endothelial cell 1, galectin-3 and thyroid peroxidase, and BRAFV600E mutation was also evaluated. Univariate and multivariate analyses were performed to identify the risk factors for central CLNM, and a risk model was established. Pathologically, 44% (99/225) of the PTCs had central CLNMs. Multivariate analysis revealed that size ≤10mm, microcalcification, internal vascularity, capsule contact or involvement and BRAFV600E mutation were independent risk factors for central CLNM. The risk score for central CLNM was calculated as follows: risk score = 1.5 × (if lesion size ≤10 mm) + 1.9 × (if microcalcification) + 0.8 × (if internal flow) + 3.0 × (if capsule contact or involvement) + 1.5 × (if BRAFV600E mutation). The rating result was divided into six stages, and the relevant risk rates of central CLNM were 0% (0/1), 0% (0/22), 7.4% (4/54), 48.6% (34/70), 71.2% (42/59) and 100% (19/19), respectively. In conclusion, PTC ≤10mm, microcalcification, internal vascularity, capsule contact or involvement and BRAFV600E mutation are risk factors for central CLNM. The risk model may be useful in treatment planning and management of patients with PTCs.


optCluster: An R Package for Determining the Optimal Clustering Algorithm.
There exist numerous programs and packages that perform validation for a given clustering solution; however, clustering algorithms fare differently as judged by different validation measures. If more than one performance measure is used to evaluate multiple clustering partitions, an optimal result is often difficult to determine by visual inspection alone. This paper introduces optCluster, an R package that uses a single function to simultaneously compare numerous clustering partitions (created by different algorithms and/or numbers of clusters) and obtain a "best" option for a given dataset. The method of weighted rank aggregation is utilized by this package to objectively aggregate various performance measure scores, thereby taking away the guesswork that often follows a visual inspection of cluster results. The optCluster package contains biological validation measures as well as clustering algorithms developed specifically for RNA sequencing data, making it a useful tool for clustering genomic data. This package is available for free through the Comprehensive R Archive Network (CRAN) at http://cran.rproject.org/web/packages/optCluster/.


High-Content Surface and Total Expression siRNA Kinase Library Screen with VX-809 Treatment Reveals Kinase Targets that Enhance F508del-CFTR Rescue.
The most promising F508del-CFTR corrector, VX-809, has been unsuccessful as an effective, stand-alone treatment for CF patients, but the rescue effect in combination with other drugs may confer an acceptable level of therapeutic benefit. Targeting cellular factors that modify trafficking may act to enhance the cell surface density of F508-CFTR with VX-809 correction. Our goal is to identify druggable kinases that enhance F508del-CFTR rescue and stabilization at the cell surface beyond that achievable with the VX-809 corrector alone. To achieve this goal, we implemented a new high-throughput screening paradigm that quickly and quantitatively measures surface density and total protein in the same cells. This allowed for rapid screening for increased surface targeting and proteostatic regulation. The assay utilizes fluorogen-activating-protein (FAP) technology with cell excluded and cell permeant fluorogenic dyes in a quick, wash-free fluorescent plate reader format on live cells to first measure F508del-CFTR expressed on the surface and then the total amount of F508del-CFTR protein present. To screen for kinase targets, we used Dharmacon's ON-TARGET plus SMARTpool siRNA Kinase library (715 target kinases) with and without 10 μM VX-809 treatment in triplicate at 37 °C. We identified several targets that had a significant interaction with VX-809 treatment in enhancing surface density with siRNA knockdown. Select small-molecule inhibitors of the kinase targets demonstrated augmented surface expression with VX-809 treatment.


Predictors and timing of amputations in military lower extremity trauma with arterial injury.
Military lower extremity arterial injuries present threats to life and limb. These injuries are common and limb salvage is a trauma system priority. Understanding the timing and predictors of amputation through the phases of casualty evacuation can help inform future limb salvage efforts. This study characterizes limbs undergoing amputation at different operationally relevant time points. A retrospective cohort study of casualties with lower extremity arterial injuries undergoing initial vascular limb salvage in Iraq and Afghanistan was undertaken. Amputations were grouped as having been performed early (in theater at Role 2 or 3) or late (after evacuation to Role 4 or 5). Further distinction was made between late and delayed (after discharge from initial hospitalization) amputations. Four hundred fifty-five casualties met inclusion criteria with 103 amputations (23%). Twenty-one (20%) were performed in theater and 82 (80%) were performed following overseas evacuation. Twenty-one (26% of late amputations) were delayed, a median of 359 days from injury (interquartile range, 176-582). Most amputations were performed in the first 4 days following injury. Amputation incidence was highest in popliteal injuries (28%). Overall, amputation was predicted by higher incidence of blast mechanism and fracture and greater limb and casualty injury severity. Early amputations had higher limb injury severity than late amputations. Delayed amputations had greater incidence of motor and sensory loss and contracture than early amputations. Casualty and limb injury severity predict predictors and timing of amputation in military lower extremity arterial injury. Amputation following overseas evacuation was more common than in-theater amputation, and functional loss is associated with delayed amputation. Future limb salvage efforts should focus on postevacuation and rehabilitative care. Epidemiologic study, level III.


Vocal tract discomfort in teachers after teaching activity.
Purpose To evaluate the vocal tract discomfort (VTD) reported by teachers, comparing their vocal self-assessment at three different times: before teaching, after four hours of teaching, and after eight hours of teaching. Methods The study sample was composed of 50 teachers: 42 women and eight men. The participating teachers were divided into two groups according to the cutoff value of the Voice Symptom Scale (VoiSS): Vocal Risk Group (VRG) and Vocally Healthy Group (VHG). The List of Vocal Signs and Symptoms (LVSS) was used to identify the number of vocal symptoms in each group. The groups were evaluated at three specific moments (before (BT) and after four (4HT) and eight (8HT) hours of teaching) by means of the Vocal Tract Discomfort Scale (VTD scale) and vocal self-assessment. Results The VRG presented more vocal signs and symptoms of the LVSS than the VHG (total: VHG=0.56/VRG=1.60, p<0.001; work-related VHG=0.79/VRG=2.49, p<0.001). The VHG did not report change in discomfort for both frequency (p=1.132) and severity (p=0.431) and showed better vocal self-assessment (BT=0.67; 4HT=0.96; 8HT=0.96, p=0.007). However, the VRG presented vocal tract discomfort after four and eight hours of teaching for both frequency (BT=1.60; 4HT=2.49; 8HT=2.95, p<0.001) and severity (BT=1.79; 4HT=2.52; 8HT=3.12, p<0.001) and worse voice self-assessment (BT=2.00; 4HT=2.42; 8HT=3.00, p<0.001). Conclusion Teachers at vocal risk present worse vocal self-assessment and increased vocal tract discomfort throughout the teaching working day.


Feigning acute intermittent porphyria.
Acute intermittent porphyria (AIP) is an autosomal dominant genetic defect in heme synthesis. Patients with this illness can have episodic life-threatening attacks characterized by abdominal pain, neurological deficits, and psychiatric symptoms. Feigning this illness has not been reported in the English language literature to date. Here, we report on a patient who presented to the hospital with an acute attack of porphyria requesting opiates. Diligent assessment of extensive prior treatment records revealed thirteen negative tests for AIP.


Incidence of medical error and adverse outcomes on a pediatric general surgery service.
The Institute of Medicine has identified medical error as a leading cause of death and injury, with deaths resulting from medical error exceeding those caused by motor vehicle collisions, breast cancer, or AIDS. The authors examined the incidence and sources of medical error in relation to adverse events on a pediatric general surgery service. All intensive care unit (ICU) and ward admissions to 2 staff pediatric general surgeons during a 1-month period were identified prospectively and in-patient care was reviewed daily by a 3-person panel consisting of a staff surgeon, a surgical fellow, and a nonmedical observer. Medical errors, identified through daily patient encounters, nursing rounds, medical rounds, and chart examinations, were evaluated based on type, hospital setting, personnel involved, and outcome. Adverse outcomes were evaluated based on type and contributing factors. Our study group included 64 patients. A total of 108 errors were identified; 28% of these errors resulted in adverse outcomes. One or more medical errors were identified in the care of two thirds of patients (43 of 64), with medical error contributing to adverse outcomes in one third of patients (21 of 64). Errors occurred most frequently in communication, postoperative monitoring and care, and diagnosis, with errors in postoperative care and diagnosis having the highest likelihood of resulting in an adverse outcome. Seventy-four adverse outcomes were identified in 31 patients; 35 (47%) of these outcomes, occurring in 21 patients, were attributable to medical error. The most common adverse outcomes identified were additional nonoperative procedures, of which, 92% resulted from medical error. There were no deaths. Medical error occurs in more than one half of hospital admissions on a general pediatric surgery service and contributes to a substantial number of adverse outcomes.


MCA sarcomas induced in scid mice are more immunogenic than MCA sarcomas induced in congenic, immunocompetent mice.
With the aim of studying possible T-cell mediated selection of the cells in growing tumours, 108 mice of the C.B-17 strain, either immunocompetent C.B-17 mice or histocompatible immunodeficient C.B-17 severe combined immune deficiency (scid) were treated with 3-methylcholanthrene (MCA) in two different dosages. A total of 51 tumours were obtained, 44 of which were established as uncloned tumour cell lines, and used for further study. Tumour incidence correlated with carcinogen-dosage in that more tumours developed in groups treated with a high MCA dose than in groups treated with a low MCA dose, but not with immune status of the tumour host. No significant difference in the level of MHC class I molecule expression was found between the two groups of tumours. The rate of rejection after transplantation to syngeneic immunocompetent hosts was significantly higher for the scid tumours than for the non-scid tumours. The authors suggest that this reflects an immunoselection performed by T cells in the immunocompetent host in which the tumour originated, which has eliminated highly immunogenic tumour cells, leaving non-immunogenic tumour cells to grow.


Immunoreactive corticotropin-releasing factor in rat plasma.
Immunoreactive ACTH (I-ACTH) levels in the rat anterior pituitary and plasma, and immunoreactive corticotropin-releasing factor (I-CRF) concentrations in the median eminence (ME) and plasma were determined after adrenalectomy and in insulin-induced hypoglycemia. I-CRF was detected in plasma from normal rats (mean +/- SD, 5.6 +/- 0.9 pg/ml; n = 6). Gel filtration chromatography of I-CRF from pooled plasma of these rats revealed a single peak which eluted in the position of authentic rat CRF. I-CRF levels in ME and I-ACTH levels in anterior pituitary decreased immediately after adrenalectomy, then gradually increased to high levels 14 days after surgery. Plasma I-CRF and I-ACTH concentrations increased immediately after surgery, slightly decreased to near the control levels at 24 h, and then increased to high concentrations 14 days after surgery. Plasma and ME I-CRF levels 14 days after adrenalectomy, followed by daily dexamethasone replacement, were almost the same as control levels. In insulin-induced hypoglycemia, plasma I-ACTH and I-CRF concentrations increased and ME I-CRF content decreased at 30 and 60 min. These results suggest that plasma I-CRF levels reflect changes in hypothalamic CRF levels.


Effect of chondroitin sulfate and hyaluronic acid on gene expression in a three-dimensional culture of chondrocytes.
The effect of glycosaminoglycan addition on a three-dimensional (3D) culture of porcine chondrocyte cells was investigated with a view to use in cartilage regenerative medicine. Chondroitin sulfate C increased the mRNA expression of type 2 collagen, while chondroitin sulfate A did not. Hyaluronic acid of high molecular weight markedly decreased the mRNA expression of both aggrecan and type 2 collagen, although hyaluronic acid of low molecular weight showed no apparent effect.


Arsenic affects inflammatory cytokine expression in Gallus gallus brain tissues.
The heavy metal arsenic is widely distributed in nature and posses a serious threat to organism's health. However, little is known about the arsenic-induced inflammatory response in the brain tissues of birds and the relationship and mechanism of the inflammatory response. The purpose of this study was to explore the effects of dietary arsenic on the expression of inflammatory cytokines in the brains of Gallus gallus. Seventy-two 1-day-old male Hy-line chickens were divided into a control group, a low arsenic trioxide (As2O3)-treated (7.5 mg/kg) group, a middle As2O3-treated (15 mg/kg) group, and a high As2O3-treated (30 mg/kg) group. Arsenic exposure caused obvious ultrastructural changes. The mRNA levels of the transcription factor nuclear factor-κB (NF-κB) and of pro-inflammatory cytokines, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E synthase (PTGEs), in chicken brain tissues (cerebrum, cerebellum, thalamus, brainstem and myelencephalon) on days 30, 60 and 90, respectively, were measured by real-time PCR. The protein expression of iNOS was detected by western blot. The results showed that after being treated with As2O3, the levels of inflammatory-related factor NF-κB and pro-inflammatory cytokines in chicken brain tissues increased (P < 0.05). Arsenic exposure in the chickens triggered host defence and induced an inflammatory response by regulating the expression of inflammatory-related genes in the cerebrum, cerebellum, thalamus, brainstem and myelencephalon. These data form a foundation for further research on arsenic-induced neurotoxicity in Gallus gallus.


Coupled Cluster Theory with Induced Dipole Polarizable Embedding for Ground and Excited States.
In this work, we present the theory and implementation of the coupled cluster single and double excitations (CCSD) method combined with a classical polarizable molecular mechanics force field (MMPol) based on the induced dipole model. The method is developed to compute electronic excitation energies within the state specific (SS) and linear response (LR) formalisms for the interaction of the quantum mechanical and classical regions. Furthermore, we consider an approximate expression of the correlation energy, originally developed for CCSD with implicit solvation models, where the interaction term is linear in the coupled cluster density. This approximation allows us to include the explicit contribution of the environment to the CC equations without increasing the computational effort. The test calculations on microsolvated systems, where the CCSD/MMPol method is compared to full CCSD calculations, demonstrates the reliability of this computational protocol for all interaction schemes (errors < 2%). We also show that it is important to include induced dipoles on all atom centers of the classical region and that too diffuse functions in the basis set may be problematic due to too strong interaction with the environment.


Bronchopleurobiliary fistula. A complication of intrahepatic biliary stent migration.
We describe the management of bronchopleurobiliary fistula in a 56-year-old woman who underwent a (L) mastectomy with postoperative radio- and chemotherapy for advanced breast carcinoma and required insertion of inhabiliary Silastic stents for the relief of severe obstructive jaundice. During restaging of her carcinoma for further chemotherapy, she complained of dyspnea, right chest pain and productive cough with yellow sputum. Her chest x-ray film and thoraco-abdominal CT scan demonstrated right pleural effusion with a stent protruding through the right hemidiaphragm. The objective evidence of bile in the pleural aspirate with history of bile-stained sputum established the diagnosis of bronchopleurobiliary fistula resulting from biliary stent migration.


In silico study of carvone derivatives as potential neuraminidase inhibitors.
Recent outbreaks of highly pathogenic influenza strains have highlighted the need to develop new anti-influenza drugs. Here, we report an in silico study of carvone derivatives to analyze their binding modes with neuraminidase (NA) active sites. Two proposed carvone analogues, CV(A) and CV(B), with 36 designed ligands were predicted to inhibit NA (PDB ID: 3TI6) using molecular docking. The design is based on structural resemblance with the commercial inhibitor, oseltamivir (OTV), ligand polarity, and amino acid residues in the NA active sites. Docking simulations revealed that ligand A18 has the lowest energy binding (∆Gbind) value of -8.30 kcal mol-1, comparable to OTV with ∆Gbind of -8.72 kcal mol-1. A18 formed seven hydrogen bonds (H-bonds) at residues Arg292, Arg371, Asp151, Trp178, Glu227, and Tyr406, while eight H-bonds were formed by OTV with amino acids Arg118, Arg292, Arg371, Glu119, Asp151, and Arg152. Molecular dynamics (MD) simulation was conducted to compare the stability between ligand A18 and OTV with NA. Our simulation study showed that the A18-NA complex is as stable as the OTV-NA complex during the MD simulation of 50 ns through the analysis of RMSD, RMSF, total energy, hydrogen bonding, and MM/PBSA free energy calculations.


Green Accelerated Synthesis, Antimicrobial Activity and Seed Germination Test of Quaternary Ammonium Salts of 1,2-bis(4-pyridyl)ethane.
A family of fifteen quaternary ammonium salts (QAs), bearing the 1,2-bis(4-pyridyl)ethane core, were obtained using for the first time two different green methods, such as microwave (MW) and ultrasounds (US) irradiation, with very good yields and in much shorter times compared to the classical method, and an assay on their antimicrobial action against Escherichia coli (E. coli) was carried out. While 12 to 24 hours were required for complete alkylation of 1,2-bis(4-pyridyl)ethane by reactive halogenated derivatives in anhydrous solvent under reflux conditions, MW and US irradiation reduced the reaction time and the desired products were achieved in a few min. One of the aims of this study was to evaluate the antibacterial potential of the synthesized QAs against pathogenic bacteria, along with their impact on germination activity of wheat seeds (Triticum aestivum L.). The antibacterial activity of the QAs against Escherichia coli was explored by determining the minimum inhibitory concentration (MIC). The MIC values varied from 0.312 to 2.5 mg/mL, highlighting the lowest values attained for the derivatives containing methoxy, chlorine and benzofurane functional groups. The viability of aerobic bacteria was determined with the Tetrazolium/Formazan Test, a method that was found to be the best alternative approach with respect to the difuzimetric method. Seeds of Triticum aestivum L. were used for the evaluation of the germination indicators, such as seed germination (SG), the relative seed germination (RSG), the relative radicle growth (RRG), and the seed germination index (GI). The toxicity studies of QAs 1, 4 and 7, at two different concentrations, showed no inhibitory effect on seed germination.


Foxk2 inhibits non-small cell lung cancer epithelial-mesenchymal transition and proliferation through the repression of different key target genes.
Increasing evidence suggests that numerous fork-head transcription factors are required to repress the mammalian cells phenotype. Among them, Foxk2 is a ubiquitously expressed family member, but the role of Foxk2 in mediating tumor metastasis in non-small cell lung cancer has not been explored. In this investigation reduced Foxk2 expression was found in lung adenocarcinoma tissues compared with the adjacent non-tumor tissues, and was associated with better overall survival. Low expression was also found in the NSCLC cell lines such as A549, NCI-H520, H1299, H358 and H460 cells. Recombinant lentivirus expressing Foxk2 constructs or ShFoxk2 were developed and transfected into A549 cells or NCI-H520 cells, immunofluorescence assay, qRT-PCR, and western blot analysis were used to measure the change of the epithelial markers, E-cadherin and α-catenin, and mesenchymal markers N-cadherin and vimentin. Wound healing assay and Transwell assay were used to measure the relative cell invasion ability. MTT assay, Edu assay, and cell cycle distribution analysis were used to confirm the effect of Foxk2 on cell proliferation. ChIP-seq, qChIP, as well as luciferase reporter gene assays were used to detect the target genes regulated by Foxk2, Bioinformatics predicated the potential miRNAs that could target Foxk2. Our study demonstrated that Foxk2 played major roles in NSCLC EMT by directly targeting N-cadherin and Snail, we found that Foxk2 regulated NSCLC cell growth by suppressing the expression of cyclin D1 and CDK4, which suggested that Foxk2 might be a multifunctional regulator in NSCLC. The expression of Foxk2 may be regulated by miR-1271, which could serve as a promising therapeutic target for NSCLC.


A qPCR-based metric of Th2 airway inflammation in asthma.
Using microarray profiling of airway epithelial cells, we previously identified a Th2-high molecular phenotype of asthma based on expression of periostin, CLCA1 and serpinB2 and characterized by specific inflammatory, remodeling, and treatment response features. The goal of the current study was to develop a qPCR-based assay of Th2 inflammation to overcome the limitations of microarray-based methods. Airway epithelial brushings were obtained by bronchoscopy from two clinical studies comprising 44 healthy controls and 62 subjects with asthma, 39 of whom were studied before and after a standardized 8 week course of inhaled corticosteroids (ICS). The qPCR-based expression of periostin, CLCA1 and serpinB2 were combined into a single metric. In asthma, the three-gene-mean of periostin, CLCA1 and serpinB2 correlated with FeNO (r = 0.75, p = 0.0002), blood eosinophils (r = 0.58, p = 0.003) and PC20 methacholine (r = -0.65, p = 0.0006), but not total serum IgE (r = 0.33, p = 0.1). Higher baseline three-gene-mean correlated with greater improvement in FEV1 with ICS at 2, 4 and 8 weeks (all p < 0.05). By ROC analysis, the area under the curve (AUC) of the three-gene-mean for FEV1 improvement with ICS at 4 and 8 weeks was 0.94 and 0.87, respectively, which are higher than the AUCs of FeNO, blood eosinophils, IgE or PC20. Th2 airway inflammation as measured by this three-gene-mean also had predictive capacity for an improvement in symptoms. The three-gene-mean of periostin, CLCA1 and serpinB2 in airway epithelial brushings identifies Th2-high and low populations, is correlated with other Th2 biomarkers, and performs well for prediction of FEV1 improvement with ICS. The three-gene-mean provides a measurement of Th2 airway inflammation that is clinically relevant and that can serve as a valuable tool to evaluate non-invasive biomarkers to predict treatment responses to existing and emerging asthma therapies.


Immune monitoring after kidney transplantation.
During the last decennium, research in the field of organ transplantation changed from studying mechanisms of acute rejection shortly after transplantation to understanding why patients benefit from their grafts only for a limited time, because of irreversible chronic rejection and serious side effects of immunosuppression. To avoid side effects, tapering or even withdrawal of immunosuppression in transplant recipients is warranted, provided this is not accompanied with graft loss. Noninvasive cell mediated immune tests could be helpful to identify transplant recipients in whom the immunosuppressive load can be safely reduced, and to identify patients at risk for chronic rejection. In the present report, we describe cellular assays to determine donor-specific responses in peripheral blood mononuclear cells from transplant recipients taken before transplantation and during tapering or withdrawal of immunosuppression.


A comprehensive examination of health conditions associated with obesity in older adults.
Over 70% of older adults in the United States are overweight or obese. To examine the overall health burden of obesity in older adults, the Vitamins and Lifestyle cohort study of western Washington State recruited 73,003 adults aged 50 to 76 who completed a self-administered questionnaire on current height and weight, medical history, and risk factors. Cross-sectional analysis of body mass index (BMI) and health conditions was performed using data collected in 2000 to 2002. Participants were categorized as normal weight, overweight, obese I, or obese II/III using BMI cut-points. Health conditions included 7 serious diseases, 2 conditions associated with cardiovascular disease risk, 23 medical conditions, and 11 health complaints. Odds ratios (ORs) from logistic regression models were used to examine associations of the four BMI categories with each health condition. Analyses were gender stratified and adjusted for age, education, race/ethnicity, and smoking status. Among women, 34% were overweight, 16% in the obese I category, and 10% in obese categories II/III. Among men, 49% were overweight, 18% in the obese I category, and 6% in obese categories II/III. Overall, 37 of 41 conditions examined for women and 29 of 41 conditions examined for men were associated with increased levels of BMI (trend p <0.05 for all models). For women and men, respectively, the highest ORs comparing obese II/III to normal weight were diabetes (OR=12.5 and 8.3), knee replacement (OR=11.7 and 6.1), and hypertension (OR=5.4 and 5.6). Obesity also increased the odds of several rare diseases such as pancreatitis (OR=1.9 and 1.5) and health complaints such as chronic fatigue (OR=3.7 and 3.5) and insomnia (OR=3.5 and 3.1). A broad range of diseases and health complaints are associated with obesity. Clinicians should be aware of the diverse ways in which being overweight or obese may affect the health of their patients when counseling them about weight loss.


Familial co-aggregation and shared genetics of cardiometabolic disorders and traits: data from the multi-generational Lifelines Cohort Study.
It is unclear to what extent genetics explain the familial clustering and the co-occurrence of distinct cardiometabolic disorders in the general population. We therefore aimed to quantify the familial (co-)aggregation of various cardiometabolic disorders and to estimate the heritability of cardiometabolic traits and their genetic correlations using the large, multi-generational Lifelines Cohort Study. We used baseline data of 162,416 participants from Lifelines. Cardiometabolic disorders including type 2 diabetes (T2D), cardiovascular diseases, hypertension, obesity, hypercholesterolemia, and metabolic syndrome (MetS), were defined in adult participants. Fifteen additional cardiometabolic traits indexing obesity, blood pressure, inflammation, glucose regulation, and lipid levels were measured in all included participants. Recurrence risk ratios (λR) for first-degree relatives (FDR) indexed familial (co-)aggregation of cardiometabolic disorders using modified conditional Cox proportional hazards models and were compared to those of spouses. Heritability (h2), shared environment, and genetic correlation (rg) were estimated using restricted maximum likelihood variance decomposition methods, adjusted for age, age2, and sex. Individuals with a first-degree relative with a cardiometabolic disorder had a higher risk of the same disorder, ranging from λFDR of 1.23 (95% CI 1.20-1.25) for hypertension to λFDR of 2.48 (95% CI 2.15-2.86) for T2D. Most of these were higher than in spouses (λSpouses < λFDR), except for obesity which was slightly higher in spouses. We found moderate heritability for cardiometabolic traits (from h2CRP: 0.26 to h2HDL: 0.50). Cardiometabolic disorders showed positive familial co-aggregation, particularly between T2D, MetS, and obesity (from λFDR obesity-MetS: 1.28 (95% CI 1.24-1.32) to λFDR MetS-T2D: 1.61 (95% CI 1.52-1.70)), consistent with the genetic correlations between continuous intermediate traits (ranging from rg HDL-Triglycerides: - 0.53 to rg LDL-Apolipoprotein B: 0.94). There is positive familial (co-)aggregation of cardiometabolic disorder, moderate heritability of intermediate traits, and moderate genetic correlations between traits. These results indicate that shared genetics and common genetic architecture contribute to cardiometabolic disease.


14N Hyperfine Structure in the Pure Rotational Spectrum of 24Mg14N12C
The pure rotational spectrum of 24Mg14N12C, between 11.9 and 23.9 GHz, has been measured using a pulsed jet Fourier transform microwave spectrometer. The hyperfine structure due to the 14N nucleus has been measured, and the nuclear quadrupole coupling, Fermi contact, and dipole-dipole interaction constants have been determined. The ionic character of the metal-isocyanide bond has been investigated through the nuclear quadrupole and magnetic hyperfine parameters. Copyright 1998 Academic Press.


Irritable bowel syndrome and migraine: bystanders or partners?
Irritable bowel syndrome (IBS) and migraine are distinct clinical disorders. Apart from the characteristics of chronic and recurrent pain in nature, these pain-related disorders apparently share many similarities. For example, IBS is female predominant with community prevalence about 5-10%, whereas that of migraine is 1-3% also showing female predominance. They are often associated with many somatic and psychiatric comorbidities in terms of fibromyaglia, chronic fatigue syndrome, interstitial cystitis, insomnia and depression etc., even the IBS subjects may have coexisted migraine with an estimated odds ratio of 2.66. They similarly reduce the quality of life of victims leading to the social, medical and economic burdens. Their pathogeneses have been somewhat addressed in relation to biopsychosocial dysfunction, heredity, genetic polymorphism, central/visceral hypersensitivity, somatic/cutaneous allodynia, neurolimbic pain network, gonadal hormones and abuses etc. Both disorders are diagnosed according to the symptomatically based criteria. Multidisciplinary managements such as receptor target new drugs, melantonin, antispasmodics, and psychological drugs and measures, complementary and alternatives etc. are recommended to treat them although the used agents may not be necessarily the same. Finally, the prognosis of IBS is pretty good, whereas that of migraine is less fair since suicide attempt and stroke are at risk. In conclusion, both distinct chronic pain disorders to share many similarities among various aspects probably suggest that they may locate within the same spectrum of a pain-centered disorder such as central sensitization syndromes. The true pathogenesis to involve these disorders remains to be clarified in the future.


Optimizing Management of Heart Failure by Using Echo and Natriuretic Peptides in the Outpatient Unit.
Chronic heart failure (HF) is an important public health problem and is associated with high morbidity, high mortality, and considerable healthcare costs. More than 90% of hospitalizations due to worsening HF result from elevations of left ventricular (LV) filling pressures and fluid overload, which are often accompanied by the increased synthesis and secretion of natriuretic peptides (NPs). Furthermore, persistently abnormal LV filling pressures and a rise in NP circulating levels are well known indicators of poor prognosis. Frequent office visits with the resulting evaluation and management are most often needed. The growing pressure from hospital readmissions in HF patients is shifting the focus of interest from traditionally symptom-guided care to a more specific patient-centered follow-up care based on clinical findings, BNP and echo. Recent studies supported the value of serial NP measurements and Doppler echocardiographic biomarkers of elevated LV filling pressures as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of echo and pulsed-wave blood-flow and tissue Doppler with NPs appears valuable in guiding ambulatory HF management, since they are potentially useful to distinguish stable patients from those at high risk of decompensation.


Lotus Leaf Aqueous Extract Reduces Visceral Fat Mass and Ameliorates Insulin Resistance in HFD-Induced Obese Rats by Regulating PPARγ2 Expression.
Objectives: Lotus leaf is a kind of traditional Chinese medicine. We aimed to explore the effects of lotus leaf aqueous extract (LLAE) on peroxisome proliferative activated receptor γ2 (PPARγ2) expression in preadipocytes and adipocytes and further investigate its effects on high fat diet (HFD)-induced obese rats. Methods: pGL3-Enhancer-PPARγ2 (625 bp)-Luc plasmid, a luciferase reporter gene expression plasmid containing PPARγ2 promoter, was stably transfected into 3T3-L1 preadipocytes. PPARγ2 promoter activities were determined by assaying the luciferase activities. Then PPARγ2 promoter activities in preadipocytes and PPARγ2 mRNA levels in human subcutaneous adipocytes were measured after the administration with LLAE. Additionally, the effects of LLAE on body weight, fat mass, glucose and lipid metabolism and the expression of PPARγ2, insulin receptor substrate 1 and glucose transporter 4 (GLUT4) in visceral adipose tissue (VAT) were measured in HFD-induced obese rats treated with low or high dose [0.5 or 3.0 g crude drug/(kg.d)] LLAE for 6 weeks. Results: Ten μg/ml LLAE significantly increased the luciferase activities in 3T3-L1 cells and the stimulatory action reached 2.51 folds of controls when LLAE was 1000 μg/ml (P < 0.01). After treating 3T3-L1 cells with 100 μg/ml LLAE, the stimulatory role peaked at 32 h where it was 2.58 folds of controls (P < 0.01). Besides, 100 μg/ml LLAE significantly increased PPARγ2 mRNA levels in human adipocytes to 1.91 folds of controls (P < 0.01). In HFD-induced obese rats, administration with both low and high dose LLAE notably reduced visceral fat mass by 45.5 and 58.4%, respectively, and significantly decreased fasting serum insulin levels (P < 0.05). The high dose LLAE also significantly decreased homeostasis model assessment of insulin resistance in obese rats (P < 0.05). Furthermore, the mRNA levels of PPARγ2 and GLUT4 in VAT of obese rats were significantly increased when compared with control rats, and were notably suppressed by LLAE intervention for 6 weeks (P < 0.05). Conclusion: LLAE significantly reduces visceral fat mass and ameliorates insulin resistance in HFD-induced obese rats. These beneficial effects of LLAE may associate with its role in stimulating PPARγ2 expression in preadipocytes and subcutaneous adipocytes and suppressing PPARγ2 and GLUT4 expression in VAT.


ONRAB® oral rabies vaccine is shed from, but does not persist in, captive mammals.
ONRAB® is a human adenovirus rabies glycoprotein recombinant vaccine developed to control rabies in wildlife. To support licensing and widespread use of the vaccine, safety studies are needed to assess its potential residual impact on wildlife populations. We examined the persistence of the ONRAB® vaccine virus in captive rabies vector and non-target mammals. This research complements work on important rabies vector species (raccoon, striped skunk, and red fox) but also adds to previous findings with the addition of some non-target species (Virginia opossum, Norway rats, and cotton rats) and a prolonged period of post vaccination monitoring (41 days). Animals were directly inoculated orally with the vaccine and vaccine shedding was monitored using quantitative real-time PCR applied to oral and rectal swabs. ONRAB® DNA was detected in both oral and rectal swabs from 6 h to 3 days post-inoculation in most animals, followed by a resurgence of shedding between days 17 and 34 in some species. Overall, the duration over which ONRAB® DNA was detectable was shorter for non-target mammals, and by day 41, no animal had detectable DNA in either oral or rectal swabs. All target species, as well as cotton rats and laboratory-bred Norway rats, developed robust humoral immune responses as measured by competitive ELISA, with all individuals being seropositive at day 31. Similarly, opossums showed good response (89% seropositive; 8/9), whereas only one of nine wild caught Norway rats was seropositive at day 31. These results support findings of other safety studies suggesting that ONRAB® does not persist in vector and non-target mammals exposed to the vaccine. As such, we interpret these data to reflect a low risk of adverse effects to wild populations following distribution of ONRAB® to control sylvatic rabies.


Pd-Catalyzed Oxidative Heck Reaction of Grignard Reagents with Diaziridinone as Oxidant.
A novel Pd-catalyzed oxidative Heck reaction with readily available Grignard reagents using di- t-butyldiaziridinone as an oxidant has been developed. Various substituted olefins were obtained in 46-91% yields with high regioselectivity under mild reaction conditions.


Plasma-derived exosomal miR-183 associates with protein kinase activity and may serve as a novel predictive biomarker of myocardial ischemic injury.
Myocardial infarction (MI) is primarily caused by ischemic heart or coronary artery disease and is a major cause of mortality worldwide. Thus, it is necessary to establish reliable biochemical markers for the early diagnosis of MI. MicroRNAs (miRNAs or miR) have been demonstrated to circulate in biological fluids and are enclosed in extracellular vesicles, including exosomes. The current study assessed the differential expression of exosomal miRNAs in the plasma of patients with MI and healthy individuals, and the possible mechanism involved. Plasma-derived exosomes were isolated from patients with MI and healthy control individuals, and vesicles with a membrane were observed using transmission electron microscopy. Furthermore, an exosomal miRNA expression profile was compared between patients with MI and healthy individuals using a miRNA microarray. Significantly differentially expressed miRNAs were validated using reverse transcription-quantitative polymerase chain reaction. To the best of our knowledge, the present study was the first to demonstrate that miR-183 was markedly upregulated in patients with MI compared with healthy individuals. In addition, the relative exosomal miR-183 level increased with the degree of myocardial ischemic injury. Additionally, GO and KEGG analyses demonstrated that miR-183 is primarily involved in cell communication, protein kinase activity regulation and adrenergic signaling in cardiomyocytes. Furthermore, a protein-protein interaction network of all the miR-183 target genes was constructed. The results demonstrated that five core genes (PPP2CB, PPP2CA, PRKCA, PPP2CA, PPP2R5C and PPP2R2A) in the PPI network were also associated with protein kinase activity regulation and adrenergic signaling in cardiomyocytes. Taken together, these data demonstrate that exosomal miR-183 derived from the serum of patients with MI may be a novel diagnostic biomarker involved in the regulation of protein kinase activity. miR-183 may therefore be further developed for clinical use to benefit patients with coronary artery diseases.


Evidence for regional differences of semen quality among fertile French men. Fédération Francaise des Centres d'Etude et de Conservation des Oeufs et du Sperme humains.
The world literature on human semen quality indicates apparent geographical differences but these might primarily depend on variations among studies for subject recruitment strategy, semen analysis or data processing methods. A retrospective analysis on the quality of semen from 4710 healthy unselected fertile men, who were candidate semen donors to sperm banks in university hospitals in eight different French areas during the period 1973-1993, was undertaken. In these centres, all the men were referred under the same guidelines and all semen samples were analysed using similar methodologies. Significant differences were found between centres for seminal volume, sperm concentration, total number of spermatozoa in the ejaculate and percentage of motile spermatozoa (all P < 0.0001). Multiple regression analysis accounting for the age, sexual abstinence before semen collection and year of semen collection also showed regional differences: compared to Paris, the seminal volume was higher in Caen (P < 0.001) and lower in Toulouse (P < 0.01), the total number of spermatozoa was higher in Lille (P < 0.001) and lower in Toulouse (P < 0.05) and the percentage of motile spermatozoa was higher in Bordeaux and lower in Tours (both P < 0.001). This is the first study providing evidence for regional differences in the human semen quality.


Prevalence of the trichomycete fungus Harpella melusinae (Harpellales: Harpellaceae) in larval black flies (Diptera: Simuliidae) across a heterogeneous environment.
A total of 2063 mid- to late-instar larval black flies were collected from 64 stream sites in South Carolina and screened for the presence of the trichomycete fungus Harpella melusinae. Sixteen of 18 host species were colonized by H. melusinae on at least one occasion. Prevalence of H. melusinae in larvae of Simulium tuberosum cytospecies "A" was highest in acidic streams with low conductivity, whereas H. melusinae colonized larvae of Simulium verecundum most frequently in slower-moving streams. Ecological conditions, therefore, can serve as predictors of the prevalence of H. melusinae. Prevalence in host larvae was significantly lower in the Piedmont ecoregion than in the Mountain ecoregion. Prevalence did not differ in the host species S. verecundum across ecoregions, suggesting that different prevalences among host species might indicate some host preference. The prevalence of H. melusinae differed significantly between two univoltine host species (Simulium venustum and Prosimulium magnum) at the same site but not between two multivoltine host species (S. tuberosum cytospecies "FG" and S. tuberosum cytospecies "CDE"), suggesting that host life history could be important in determining fungal prevalence.


[Follow-up study on cytophagic histiocytic panniculitis with abnormal immunologic findings].
A 41-year-old patient suffering from multiple subcutaneous nodules of 9 years' duration subsequently left a well-demarcated region of atrophy. Histiocytic panniculitis was observed in biopsy specimens with cytophagocytosis. Histiocytosis was found in the bone marrow. These histiocytes were positive for lysozyme and platelets. He later developed fever and hepatomegaly. Laboratory examination revealed leukocytopenia, mild anemia, and liver disfunction as well as abnormal immunologic findings such as positive LE test and ANA, and an increase of serum IgA and complement levels. The patient was successfully treated with systemic administration of prednisolone and azathiopurine++.


CX(3)C chemokine fractalkine in pulmonary arterial hypertension.
Perivascular infiltrates composed of macrophages and lymphocytes have been described in lung biopsies of patients displaying pulmonary arterial hypertension (PAH), suggesting that circulating inflammatory cells can be recruited in affected vessels. CX(3)C chemokine fractalkine is produced by endothelial cells and promotes leukocyte recruitment, but unlike other chemokines, it can capture leukocytes rapidly and firmly in an integrin-independent manner under high blood flow. We therefore hypothesized that fractalkine may contribute to pulmonary inflammatory cell recruitment in PAH. Expression and function of the fractalkine receptor (CX(3)CR1) were studied by use of triple-color flow cytometry on circulating T-lymphocyte subpopulations in freshly isolated peripheral blood mononuclear cells from control subjects and patients with PAH. Plasma-soluble fractalkine concentrations were measured by enzyme-linked immunosorbent assay. Finally, fractalkine mRNA and protein expression were analyzed in lung samples by reverse transcriptase-polymerase chain reaction or in situ hybridization and immunohistochemistry, respectively. In patients with PAH, CX(3)CR1 expression and function are upregulated in circulating T-lymphocytes, mostly of the CD4+ subset, and plasma soluble fractalkine concentrations are elevated, as compared with control subjects. Fractalkine mRNA and protein product are expressed in pulmonary artery endothelial cells. We conclude that inflammatory mechanisms involving chemokine fractalkine and its receptor CX(3)CR1 may have a role in the natural history of PAH.


Sertraline Induced Galactorrhea.
There is limited literature reporting galactorrhea with antidepressants, including selective serotonin reuptake inhibitors. In this case report, a patient with adjustment disorder who developed galactorrhea with sertraline was presented.


Less toxic zinc(ii), diorganotin(iv), gallium(iii) and cadmium(ii) complexes derived from 2-benzoylpyridine N,N-dimethylthiosemicarbazone: synthesis, crystal structures, cytotoxicity and investigations of mechanisms of action.
Four metal complexes based on 2-benzoylpyridine N,N-dimethylthiosemicarbazone (Bp44mT) were designed. Free ligand and zinc(ii), diorganotin(iv), gallium(iii) and cadmium(ii) complexes all demonstrated pronounced activity, which was indicated using the growth inhibition test in vitro. Interestingly, most of the compounds were found to be selective against hepatocellular carcinoma (HepG2) cells but had little effect on normal hepatocyte (QSG7701) cells. In particular, Zn(Bp44mT)2 (1) exhibited toxicity on QSG7701 cells which approximately 12-fold lower than that on HepG2 cells. The studies of mechanisms of action indicated that 1 induced reactive oxygen species (ROS) generation in a dose-dependent manner via the mitochondria transduction pathway. Protein analyses showed that 1 significantly promoted p21 and p53 gene expression, causing caspase-3 activation.


Globally fixed-time synchronization of coupled neutral-type neural network with mixed time-varying delays.
This paper mainly studies the globally fixed-time synchronization of a class of coupled neutral-type neural networks with mixed time-varying delays via discontinuous feedback controllers. Compared with the traditional neutral-type neural network model, the model in this paper is more general. A class of general discontinuous feedback controllers are designed. With the help of the definition of fixed-time synchronization, the upper right-hand derivative and a defined simple Lyapunov function, some easily verifiable and extensible synchronization criteria are derived to guarantee the fixed-time synchronization between the drive and response systems. Finally, two numerical simulations are given to verify the correctness of the results.


Impact of a child with congenital anomalies on parents (ICCAP) questionnaire; a psychometric analysis.
The objective of this study was to validate the Impact of a Child with Congenital Anomalies on Parents (ICCAP) questionnaire. ICCAP was newly designed to assess the impact of giving birth to a child with severe anatomical congenital anomalies (CA) on parental quality of life as a result of early stress. At 6 weeks and 6 months after birth, mothers and fathers of 100 children with severe CA were asked to complete the ICCAP questionnaire and the SF36. The ICCAP questionnaire measures six domains: contact with caregivers, social network, partner relationship, state of mind, child acceptance, and fears and anxiety. Reliability (i.e. internal consistency and test-retest) and validity were tested and the ICCAP was compared to the SF-36. Confirmatory factor analysis resulted in 6 six a priori constructed subscales covering different psychological and social domains of parental quality of life as a result of early stress. Reliability estimates (congeneric approach) ranged from .49 to .92. Positive correlations with SF-36 scales ranging from .34 to .77 confirmed congruent validity. Correlations between ICCAP subscales and children's biographic characteristics, primary CA, and medical care as well as parental biographic and demographic variables ranged from -.23 to .58 and thus indicated known-group validity of the instrument. Over time both mothers and fathers showed changes on subscales (Cohen's d varied from .07 to .49), while the test-retest reliability estimates varied from .42 to .91. The ICCAP is a reliable and valid instrument for clinical practice. It enables early signaling of parental quality of life as a result of early stress, and thus early intervention.


A dental implant in the infratemporal fossa: case report.
This case report describes a rare displacement of a dental implant in the infratemporal fossa, which occurred during placement of the implant into the pterygoid process with computer-assisted technology. The implant was immediately removed by means of an intraoral approach to prevent any neurologic complications. Although computer-aided systems in implant surgery represent a reliable and effective tool, the surgeon should always instruct the patient on the necessary behavior during implant placement and the risks associated with a lack of adherence to these recommendations.


Acrokeratosis verruciformis of Hopf in family.
Acrokeratosis verruciformis of Hopf (AKV) is a rare disorder of keratinization inherited in an autosomal dominant fashion. A 15-year-old female presented with numerous skin-colored papular lesions over the neck as well as dorsa of the hands and feet of 7 years duration. Similar lesions were noted in her mother. Six other members of her family showed similar lesions with similar site of involvement. Presence of characteristic warty papules and histopathology led to diagnosis of a rare condition of acrokeratosis verruciformis.


Impact of relapse predictors on psychosocial functioning of SUD youth one year after treatment.
This investigation examined how personal, environmental and substance use factors predicted psychosocial functioning for youth with alcohol and drug problems. Four hundred twenty-four adolescents (M = 15.9, SD = 1.3) completed comprehensive assessments, including personal characteristics (e.g., Axis I diagnosis, motivation, self-esteem), environmental factors (e.g., family history, social supports) and substance use, at study intake and throughout the year following inpatient treatment. Treatment outcomes were assessed by measures of academic functioning, family relations, social functioning as well as health status and mental health treatment at one year. Aspects of the proposed model significantly predicted all treatment outcome domains, except family functioning, in the year following treatment. Psychosocial functioning at one year was predicted by age, gender, SES, comorbid psychopathology, family influence and nonusing social supports prior to treatment and relapse status after treatment. The utility of variables associated with substance use treatment outcomes in predicting psychosocial outcomes is considered.


Cardiovascular and metabolic responses during anoxic submergence in the bullfrog with and without maintained extracellular pH.
We studied metabolic, cardiovascular, and electrolyte responses of paralyzed bullfrogs to 6 hours of submerged anoxia at 15 degrees C, either with or without maintenance of extracellular pH at preanoxic values by NaHCO3 infusion. There were no differences in arterial PCO2 between acidemic and nonacidemic groups. Lactate appearance in arterial blood, as an indicator of anaerobic metabolic rate, was not significantly different between the anoxic groups, although both were significantly elevated over control. Heart rate in both anoxic groups was similar and significantly lower than in control. During anoxia, both systolic and diastolic pressures fell, and the group with maintained pH fell further. Plasma calcium concentration decreased in both anoxic groups, but the fall was more severe in the group in which pH was controlled. Survival was lower in this group, with a rapid decline in survival after 4 hours of anoxia. We conclude that the fall in extracellular pH seen during anoxia has a protective effect on cardiovascular function that may be partially due to maintenance of relatively high extracellular calcium levels.


[New methods for the evaluation of bone quality. DXA-based analysis of bone quality:trabecular bone score(TBS).]
Trabecular bone score(TBS)is a texture measure that evaluates pixel gray-level variations in lumbar spine DXA images, and provides skeletal information distinct from the standard BMD measurement. Recent clinical evidences show that TBS is associated with fracture risk in primary and secondary osteoporosis, and can be used together with FRAXR and BMD to adjust FRAX-probability of fracture in postmenopausal women and older men. However, athough treatment-related increases are reflected in the TBS, these are considerably smaller than the changes in BMD and there is insufficient evidence that TBS can be used to assess response to pharmacologic treatment.


Experimental evidence of short light pulse amplification using strong-coupling stimulated brillouin scattering in the pump depletion regime.
The energy transfer from a long (3.5 ps) pump pulse to a short (400 fs) seed pulse due to stimulated Brillouin backscattering in the strong-coupling regime is investigated. The two pulses, both at the same wavelength of 1.057 microm are quasicounterpropagating in a preformed underdense plasma. Relative amplification factors for the seed pulse of up to 32 are obtained. The maximum obtained amplified energy is 60 mJ. Simulations are in agreement with the experimental results and suggest paths for further improvement of the amplification scheme.


Acid-base and electrolyte abnormalities due to capreomycin.
We report a patient with tuberculosis treated with a five-drug regimen who experienced severe acid-base and electrolyte abnormalities including hypomagnesemia, hypokalemia, hypocalcemia, and a hypochloremic metabolic alkalosis. These disturbances are believed to be due to treatment with capreomycin, which produced renal magnesium wasting and possible tubular damage. Therefore, we recommend frequent determinations of serum electrolytes, magnesium, and calcium in patients treated with capreomycin.


Too much medicine? Scientific and ethical issues from a comparison between two conflicting paradigms.
The role of medicine in society appears to be focused on two views, which may be summarized as follows: "Doing more means doing better" (paradigm A) and "Doing more does not mean doing better" (paradigm B). I compared paradigms A and B both in terms of a single clinical condition and in the general context of a medical system. For a single clinical condition, I analyzed breast cancer screening. There are at least seven interconnected issues that influence the conflict between paradigms A and B in the debate on breast cancer screening: disconnection between research and practice; scarcity of information given to women; how "political correctness" can influence the choice of a health policy; professional interests; doubts about effectiveness; incommensurability between harms and benefits; and the difficulty in making dichotomous decisions with discrete variables. As a general approach to medicine, the main representative of paradigm A is systems medicine. As representatives of paradigm B, I identified the following approaches or movements: choosing wisely; watchful waiting; the Too Much Medicine campaign; slow medicine; complaints against overdiagnosis; and quaternary prevention. I showed that both as a single condition and as a general approach to medicine, the comparison was entirely reducible to a harm-benefit analysis; moreover, in both cases, the two paradigms are in many respects incommensurable. This transfers the debate to the ethical level; consequently, scientists and the public have equal rights and competence to debate on this subject. Moreover, systems medicine has many ethical problems that could limit its spread. I made some hypotheses about scenarios for the future of medicine. I particularly focused on whether systems medicine would become increasingly accessible and widespread in the population or whether it would be downsized because its promises have not been maintained or ethical problems will become unsustainable.


Apparatus for skidding sensitivity testing of energetic materials.
A remote-operated apparatus for testing the detonation sensitivity of energetic materials is detailed. Using an air ram and rotating disk, the normal force and transverse velocity of the impact plane are controlled independently, enabling the exploration of varying impact conditions over a wide parameter space. A microcontroller local to the apparatus is used to automate apparatus operation and ensure temporal alignment of the impacting ram head with the rotating disk. Calculation of the firing parameters and issuing of operational commands are handled by a remote computer and relayed to the local microcontroller for execution at the hardware level. Impact forces are taken from fast strain measurements obtained from gauges incorporated into the ram head. Infrared imaging of explosive samples provides insight into the peak thermal temperatures experienced at the sample surface during the impact event.


Topiramate induced bilateral angle-closure glaucoma.
Topiramate is a sulfamate-substituted monosaccharide and is used as an antiepileptic medication. It can also be used as a prophylactic agent for headache from migraine. The main purpose of this article is to create awareness among medical colleagues regarding severe ophthalmic side effect of topiramate. This is the first reported case of topiramate induced bilateral angle-closure glaucoma in Nepal. This case was managed successfully by discontinuing topiramate and by starting anti-glaucoma medication along with atropine eye drops which were tapered and eventually discontinued.


A reconsideration of immunological privilege within the anterior chamber of the eye.
The immunologically privileged status of the anterior chamber of the eye has been confirmed on the basis of skin and thyroid allografts with use of inbred strains of rats. Skin grafts, transplanted across both major and minor histocompatibility barriers, enjoy prolonged survival within the anterior chamber. However, several factors have been found to restrict the privilege exhibited by this site: the magnitude of the immunogenetic disparity between donor and recipient, graft size, type of tissue grafted, and, at least in the case of thyroid grafts, the endocrine status of the host. Although a defect in the afferent limb of the immune response has been the popular explanation offered for immunological privilege in an alymphatic site, this was not the basis of the privilege encountered in the anterior chamber. Furthermore, because the efferent limb of the immunological reflex are within the anterior chamber has been demonstrated to be intact, it was suggested that the unique properties of the anterior chamber may depend upon the forced intravascular presentation of antigen and consequent aberrant central processing.


Trend analysis for national surveys: Application to all variables from the Canadian Health Measures Survey cycle 1 to 4.
Trend analysis summarizes patterns over time in the data to show the direction of change and can be used to investigate uncertainties in different time points and associations with other factors. However, this approach is not widely applied to national surveys and only selected outcomes are investigated. This study demonstrates a research framework to conduct trend analysis for all variables in a national survey, the Canadian Health Measures Survey (CHMS). The CHMS cycle 1 to 4 was implemented between 2007 and 2015. The characteristics of all variables were screened and associated to the weight variables. Missing values were identified and cleaned according to the User Guide. The characteristics of all variables were extracted and used to guide data cleaning. Trend analysis examined the statistical significance of candidate predictors: the cycles, age, sex, education, household income and body mass index (BMI). R (v3.2) and RStudio (v0.98.113) were used to develop the framework. There were 26557 variables in 79 data files from four cycles. There were 1055 variables significantly associated with the CHMS cycles and 2154 associated with the BMI after controlling for other predictors. The trend of blood pressure was similar to those published. Trend analysis for all variables in the CHMS is feasible and is a systematic approach to understand the data. Because of trend analysis, we have detected data errors and identified several environmental biomarkers with extreme rates of change across cycles. The impact of these biomarkers has not been well studied by Statistics Canada or others. This framework can be extended to other surveys, especially the Canadian Community Health Survey.


Changes of serum hemolytic activity and the number of reticulocytes in canine Babesia gibsoni-infection.
When the serum hemolytic activity in Babesia gibsoni-infected dogs was determined with self red blood cells from the infected animals, the decrease in the activity is paralleled with the increase in the number of reticulocytes. The activity determined with red blood cells from phenylhydrazine-induced anemia also decreased parallel with the increase in the number of reticulocytes. These results suggest that the rapid decrease in the serum hemolytic activity after reaching the peak is due to the increase in reticulocytes, which are probably unsusceptible to the hemolytic factor(s).


The descriptive epidemiology and trends in incidence of nonocular malignant melanoma in Bombay and India.
Nonocular malignant melanoma is a rare but lethal disease increasing in incidence and mortality in western countries with improved survival if diagnosed and treated early. This study reports its epidemiology from cancer registry data in six different parts of India; its anatomic distribution and trends in Bombay from 1964 to 1984. Age-adjusted incidence in Bombay patients shows no increase from 1964 to 1984 unlike in white caucasians. Males exceed females in patients 45 years or older unlike whites, but are equalled or exceeded by females in those less than 45 years. The sole of foot and internal mucous membranes are its major anatomic sites in Indians as in negroid blacks. This cancer in Indians resembles that in blacks and nonwhites in affecting less pigmented epithelia and skin. Susceptible melanosomes and ultraviolet light exposure may both be involved in its aetiopathogenesis.


NANDA-I, NOC, and NIC linkages to SARS-CoV-2 (COVID-19): Part 3. Family response.
To provide guidance to nurses caring for families with COVID-19, we developed linkages using interoperable standardized nursing terminologies: NANDA International (NANDA-I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC). In addition, we wanted to identify gaps in the terminologies and potential new nursing diagnoses, outcomes, and interventions for future development related to nurse roles in family care during a pandemic. Using a consensus process, seven nurse experts created the linkages focused on families during the COVID-19 pandemic using the following steps: (1) creating an initial list of potential nursing diagnoses, (2) selecting and categorizing outcomes that aligned with all components of each nursing diagnosis selected, and (3) identifying relevant nursing interventions. We identified a total of seven NANDA-I nursing diagnoses as the basis for the linkage work. These are distributed in three NANDA-I Domains and based in the psychosocial dimension of the Nursing Care in Response to Pandemics model. Eighty-nine different NOC outcomes were identified to guide care based on the nursing diagnoses, and 54 different NIC interventions were suggested as possible interventions. Fifteen new proposed concepts were identified for future development across the three classifications. The linkages of nursing diagnoses, outcomes, and interventions provide a guide to enhance nursing practice and care documentation that could quantify the impact of nursing care to patient outcomes for families at risk for or infected by COVID-19. NANDA-I, NOC, and NIC linkages identified in this paper provide resources to support clinical decisions and guide critical thinking for nurses encountering care needs of families with COVID-19. Documentation of these linkages provides data that can create new knowledge to enhance the care of families impacted by COVID-19.


Diet restriction retards the age-related loss of beta-adrenergic receptors and adenylate cyclase activity in rat lung.
In the rat, dietary restriction prolongs life span and retards a variety of physiological processes that change with age. Beta-adrenergic responsiveness declines with age. We assessed beta-adrenergic receptor density and adenylate cyclase activity in lungs of 6-, 18-, 24-, and 27-month-old rats fed ad libitum or restricted to 60% of the ad libitum food after 6 weeks of age. Beta-adrenergic receptor density declined in the ad libitum group (M +/- SE, 417 +/- 30, 349 +/- 23, 297 +/- 19, 260 +/- 30 fmol/mg protein, p less than .01). In the diet-restricted group, beta-adrenergic receptor density declined between 6 and 18 months (493 +/- 35, 370 +/- 28, p less than .05) but remained unchanged from 18 to 27 months (370 +/- 28, 333 +/- 19, 360 +/- 16). Isoproterenol-stimulated adenylate cyclase activity declined with age in the ad libitum group (53.4 +/- 7.5, 46.8 +/- 8.8, 38 +/- 3.9, 27.8 +/- 3.3 p mol cAMP/mg protein, p less than .05) but not in diet-restricted group (45.1 +/- 8.9, 44 +/- 7.9, 41.8 +/- 2.4, 47.3 +/- 5.1). Changes in forskolin-stimulated adenylate cyclase activity with age were not affected by diet restriction. These data suggest that diet restriction retards some of the age-related changes in the beta-adrenergic pathway.


A comparison of isolation procedures for salmonellas from polluted water using two forms of Rappaport's medium.
The efficiency of Rappaport's broth ( RB10 ) and Rappaport's broth containing novobiocin ( NRB10 ) were compared for the isolation of salmonellas from polluted water, both as direct enrichment media and after pre-enrichment in buffered peptone water. Ninety samples were examined and 41 were found to contain salmonellas by at least one of the procedures used. Direct inoculation of the sample into RB10 resulted in the recovery of salmonellas from only 29.3% of the samples found to be positive. The use of NRB10 as a direct enrichment medium increased the percentage recovery to 78.0% of the total positive samples. Pre-enrichment in buffered peptone water allowed the recovery of salmonellas from a total of 41 samples whereas direct enrichment recovered them from only 32. No significant difference was demonstrated in the efficiencies of RB10 and NRB10 in recovering salmonellas after pre-enrichment in buffered peptone water. Three selective agars were used: no significant difference in their ability to recover salmonellae was demonstrated.


[Hormonal regulation mechanisms during puerperium].
The regulation of the hypothalamic-hypophyseal-ovarian axis during puerperium is reviewed. The lactotrophic hormone prolactin is necessary for the growth of the milk producing system, initiation and maintenance of lactation. Inappropriate responsiveness of the hypothalamic-hypophyseal-ovarian system causes independent of the actual prolactin serum values postpartum amenorrhea during early puerperium. However, the duration of amenorrhea depends on the duration of breast-feeding. The prolactin peaks induced by suckling interfere with the reappearance of normal cyclic ovarian regulation.


Potential impacts from simulated vessel noise and sonar on commercially important invertebrates.
Human usage of coastal water bodies continues to increase and many invertebrates face a broad suite of anthropogenic stressors (e.g., warming, pollution, acidification, fishing pressure). Underwater sound is a stressor that continues to increase in coastal areas, but the potential impact on invertebrates is not well understood. In addition to masking natural sound cues which may be important for behavioral interactions, there is a small but increasing body of scientific literature indicating sublethal physiological stress may occur in invertebrates exposed to high levels of underwater sound, particularly low frequency sounds such as vessel traffic, construction noise, and some types of sonar. Juvenile and sub-adult blue crabs (Callinectes sapidus) and American lobsters (Homarus americanus) were exposed to simulated low-frequency vessel noise (a signal was low-pass filtered below 1 kHz to ensure low-frequency content only) and mid-frequency sonar (a 1-s 1.67 kHz continuous wave pulse followed by a 2.5 to 4.0 kHz 1-s linear frequency modulated chirp) and behavioral response (the animal's activity level) was quantified during and after exposure using EthoVision XT™ from overhead video recordings. Source noise was quantified by particle acceleration and pressure. Physiological response to the insults (stress and recovery) were also quantified by measuring changes in hemolymph heat shock protein (HSP27) and glucose over 7 days post-exposure. In general, physiological indicators returned to baseline levels within approximately 48 h, and no observable difference in mortality between treatment and control animals was detected. However, there was a consistent amplified hemolymph glucose signal present 7 days after exposure for those animals exposed to mid-frequency sound and there were changes to C. sapidus competitive behavior within 24 h of exposure to sound. These results stress the importance of considering the impacts of underwater sound among the suite of stressors facing marine and estuarine invertebrates, and in the discussion of management actions such as protected areas, impact assessments, and marine spatial planning efforts.


Brain energy metabolism spurns fatty acids as fuel due to their inherent mitotoxicity and potential capacity to unleash neurodegeneration.
The brain uses long-chain fatty acids (LCFAs) to a negligible extent as fuel for the mitochondrial energy generation, in contrast to other tissues that also demand high energy. Besides this generally accepted view, some studies using cultured neural cells or whole brain indicate a moderately active mitochondrial β-oxidation. Here, we corroborate the conclusion that brain mitochondria are unable to oxidize fatty acids. In contrast, the combustion of liver-derived ketone bodies by neural cells is long-known. Furthermore, new insights indicate the use of odd-numbered medium-chain fatty acids as valuable source for maintaining the level of intermediates of the citric acid cycle in brain mitochondria. Non-esterified LCFAs or their activated forms exert a large variety of harmful side-effects on mitochondria, such as enhancing the mitochondrial ROS generation in distinct steps of the β-oxidation and therefore potentially increasing oxidative stress. Hence, the question arises: Why do in brain energy metabolism mitochondria selectively spurn LCFAs as energy source? The most likely answer are the relatively higher content of peroxidation-sensitive polyunsaturated fatty acids and the low antioxidative defense in brain tissue. There are two remarkable peroxisomal defects, one relating to α-oxidation of phytanic acid and the other to uptake of very long-chain fatty acids (VLCFAs) which lead to pathologically high tissue levels of such fatty acids. Both, the accumulation of phytanic acid and that of VLCFAs give an enlightening insight into harmful activities of fatty acids on neural cells, which possibly explain why evolution has prevented brain mitochondria from the equipment with significant β-oxidation enzymatic capacity.


Association of Streptococcus gallolyticus strains of high and low virulence with the intestinal tract of pigeons.
We investigated the ability of a high virulence (STR 357) and a low virulence (STR 598) strain of Streptococcus gallolyticus to attach to the intestinal tract of pigeons. For that purpose, first of all, two groups of six pigeons were anesthetized and ligatures were placed at the beginning of duodenum, jejunum, ileum, and colon. The obtained intestinal loops of the birds of the first and second group were injected with S. gallolyticus strains STR 357 and STR 598, respectively. At 15, 30, and 60 min postinoculation, two pigeons of each group were euthanatized and the various intestinal loops were sampled for histologic, immunohistochemical, and electron microscopic examination. Both the high and low virulence strains were able to adhere to the intestinal mucosa. Indeed, all samples dearly showed numerous coccal-shaped bacteria that stained positively with S. gallolyticus antiserum and were lining up against the intestinal epithelium. Likewise, on electron microscopic examination, cocci were seen in the mucus covering the intestinal epithelium. Second, the association of S. gallyticus strains of differing virulence with the intestinal tissue was determined quantitatively. Experiments were performed as described above. The number of S. gallolyticus bacteria that adhered to the intestinal epithelium was determined by plating out 10-fold serial dilutions of the segments. No significant differences in the number of adhered bacteria were found between the strains of high and low virulence.


Targeting MCF-7 Cell Line by Listeriolysin O Pore Forming Toxin Fusion with AHNP Targeted Peptide.
Tumor-targeting peptides are attracting subjects in cancer therapy. These peptides, which are widely studied, deliver therapeutic agents to the specific sites of tumors. In this study, we produced a new form of recombinant listeriolysin O (LLO) with genetically fused Anti-HER2/neu peptide (AHNP) sequence adding to its C-terminal end. The aim of the study was to engineer this pore-forming toxin to make it much more specific to tumor cells. Two forms of the toxin (with and without peptide) were subcloned into a bacterial expression plasmid. Subcloning was performed using a polymerase chain reaction (PCR) product as a megaprimer in a quick-change PCR to introduce the whole insert gene into the expression plasmid. After expression of two recombinant forms of LLO in BL21 DE3 cells, purification was performed using Ni-NTA affinity column. MDA-MB-231 and MCF-7 cell lines (as negative and positive controls, respectively) were treated with both LLO toxins to evaluate their cytotoxicity and specificity. The IC50 of LLO on MDA-MB-231 and MCF-7 cells was 21 and 5 ng/ml, respectively. In addition, IC50 for the fusion AHNP-LLO toxin was 140 and 60 ng/ml, respectively. It was found that the cytotoxicity of the new engineered AHNP-LLO toxin has decreased by about 9x compared to the wild-type toxin and the specificity of the AHNP-LLO toxin has been also reduced. Results show that the C-terminal of the LLO should not be modified and it seems that N-terminal of the toxin should be preferred for engineering and adding peptide modules.


Cyclic hematopoiesis associated with feline leukemia virus infection in two cats.
Cyclic oscillations in the numbers of blood elements were detected in 2 cats with FeLV infection. Periodic neutropenia, followed by a return to normal neutrophil numbers, was detected in both cats. The mean cycle duration was 11.8 days, with a range of 8 to 14 days. Just before the return of normal neutrophil numbers, monocytosis developed. In 1 cat, cyclic variations in the number of reticulocytes and platelets also were detected. Bone marrow aspirates obtained during periods of neutropenia had a predominance of progranulocytes in the myeloid cell line. myeloid hyperplasia, with numerous segmented neutrophils, was seen in bone marrow aspirates obtained during periods of normal neutrophil numbers. Oral administration of prednisolone resulted in cessation of the cyclic oscillations of blood elements in 1 cat. Cyclic hematopoiesis appeared to be another non-neoplastic manifestation of FeLV infection.


Efficacy of Fluorescence Technology vs Conventional Oral Examination for the Early Detection of Oral Pre-Malignant Lesions. A Clinical Comparative Study.
Oral cancer is one of the most common malignancies that affect human beings across the world and early detection of oral cancer is believed to reduce the morbidity significantly. Fluorescence diagnosis is emerging as a promising method in the differentiation of cancerous lesions and thus helping in the determination of resolution for the surgical resection of affected area of malignancy very accurately. The aim of this study was to evaluate the usefulness of an autofluorescence hand held device (OralID) to detect oral premalignant lesions. 98 potentially high-risk oral cancer patients were divided into two groups (n=49/group). Both the groups were first examined by conventional oral examination under white light and oral findings were noted. Subjects under group B were further examined under fluorescence light through hand held device, i.e. OralID. After the examinations, a surgical biopsy sample was taken from the suspected lesions under local anaesthesia from both the groups to confirm the diagnosis through histopathological analysis. The positive potential malignant lesions (PMLs) observed in Group A when compared with biopsy reporting was 89.47% true positive while in Group B was 95.24%. The sensitivity reported of Group A was 89.47% and Group B was 97.56%. We observed 8.09% more sensitivity and 11.36% more specificity when we incorporate adjunctive the fluorescence examination using OralID. Results from this study suggests that OralID is a true adjunct to conventional oral examination in detecting early potential malignant changes in subjects visiting for regular dental check-up.


Null Alleles and FIS × FST Correlations.
Three published papers in this journal have considered the proposition that, under a Wahlund effect caused by population mixture, a positive correlation is expected between single-locus values of FIS for a sample from the mixture and FST between the populations contributing to the mixture. Two of the papers assumed unbiased samples to estimate FST but did not consider possible effects of null alleles; the other paper focused on effects of nulls but used biased samples that also included Wahlund effects to estimate FST. The result is an information gap regarding scenarios that include null alleles but have unbiased estimates of FST. Simulations were used to fill this information gap, with the following results: 1) converting ~10% of alleles to nulls substantially reduced apparent heterozygosity and substantially increased FIS, with few exceptions; 2) adding null alleles also increased FST at most loci, although the effect was much more modest; 3) null alleles generally degraded correlations between FIS and FST, but the relationship remained relatively strong for FST ≥ 0.06; and 4) null alleles had only a small effect on correlations between r2, a measure of linkage disequilibrium between pairs of loci, and the product of FST values for those loci. These results argue for some caution in interpreting FIS × FST correlations under conditions where null alleles might be common and suggest that two-locus analyses might provide more robust assessments of Wahlund effects.


[Clinical evaluation of cefoxitin in surgery].
Cefoxitin (CFX) was administered to 13 patients who were admitted to the surgical ward of the hospital. The results of the study as follows; Disc susceptibility tests of the 11 strains isolated from the patients to antibiotic were performed and 10 strains showed good susceptibility to CFX. The clinical response was good in all 4 patients with surgical infections. It is noted that 1 patient with mixed infection caused by E. coli, Clostridium sp. and Bacteroides sp. showed good response to CFX. Out of 9 patients treated with CFX for prophylaxis of postoperative infections, 8 patients responded effectively to CFX, and clinical efficacy rate was 88.9%. No side effects were noted due to CFX. It is considered from these results of the study that CFX is a highly effective and safe drug for treatment of infections and for the prevention of postoperative infections in surgery.


Gut microbiota and IBD: causation or correlation?
A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host-microbial relationships relevant to human disease and amenable to therapeutic interventions.


[Minimally invasive injection therapy in lumbar syndromes].
Minimally invasive injection therapy is an effective approach for the treatment of sciatica with less complications. This therapy is a sufficient option in cases without absolute indications for operation.The paper describes in detail the different injection techniques like spinal nerve analgesia, epidural dorsal/perineural injections, vertebral joint infiltrations, and radiculographies.


Changes in enteric neurone phenotype and intestinal functions in a transgenic mouse model of enteric glia disruption.
The influence of enteric glia on the regulation of intestinal functions is unknown. Our aim was to determine the phenotype of enteric neurones in a model of glia alterations and the putative changes in intestinal motility and permeability. Transgenic mice expressing haemagglutinin (HA) in glia were used. Glia disruption was induced by injection of activated HA specific CD8+ T cells. Control mice consisted of non-transgenic littermates injected with activated HA specific CD8+ T cells. Immunohistochemical staining for choline acetyltransferase (ChAT), substance P (SP), vasoactive intestinal peptide (VIP), and nitric oxide synthase (NOS) was performed on jejunal submucosal plexus (SMP) and myenteric plexus (MP). Neurally induced jejunal muscle activity was characterised in vitro. Gastrointestinal transit and paracellular permeability were measured using fluorescein isothiocyanate-dextran markers. CD3 positive T cells infiltrates were observed in the MP of transgenic mice. In the SMP, the proportions of VIP and SP positive neurones decreased in transgenic mice compared with control mice. ChAT remained unchanged. In the MP, the proportions of ChAT and NOS positive neurones increased and decreased, respectively, in transgenic mice. In contrast, VIP and SP remained unchanged. Neurally mediated jejunal relaxation was lower in transgenic mice than in controls. This relaxation was reduced by NG-nitro-L-arginine methyl ester in control mice but not in transgenic mice. Gastrointestinal transit was delayed and intestinal permeability increased in transgenic mice compared with control mice. Glia disruption induces changes in the neurochemical coding of enteric neurones, which may partly be responsible for dysfunctions in intestinal motility and permeability.


Influenza and respiratory syncytial viruses: Efficacy of different diagnostic assays.
To determine the efficacy of cell culture, immunoflourescence Assay (IFA) and real time polymerase chain reaction (rRT-PCR) in relation to diagnosis of influenza and Respiratory Syncytial Virus (RSV). Total 2781 specimens of throat swabs and nasopharyngeal aspirates were obtained from patients suspected of respiratory viruses' infections from January 2009 to December 2011 at Universiti Kebangsaan Malaysia Medical Centre(UKMMC). The specimens were processed by cell culture and immunoflurescence assay (IFA) and (rRT-PCR). Thirty three (1.19%) specimens were positive for influenza virus A and 42 (1.51%) were positive for RSV by cell culture and IFA. On the other hand, rRT-PCR was able to identify 189 of 505 (37.43%) specimens in which 65 were influenza A virus and 124 were RSV. Sensitivity of rRT-PCR was 100% for both influenza A virus and RSV and specificity was 88% and 77% for influenza A virus and RSV, respectively. rRT-PCR diagnosed respiratory viruses in shorter time with a high level of sensitivity in comparison to conventional assays - cell culture and IFA. These advantages help in managing patients by saving cost and hospitalization stay.


A time series evaluation of the treatment of histrionic personality disorder with cognitive analytic therapy.
The central aim of this study was to assess the effectiveness of cognitive analytic therapy (CAT) with a patient presenting with Histrionic Personality Disorder (HPD). The methodology employed an A/B single case time-series experimental design, with additionally 6 months of continuous follow-up in the experimental measures. Five HPD experimental variables were collected on a daily basis, creating 357 days of continual data for analysis, across various phases of assessment baseline (A), treatment (B) and follow-up. The therapy contract was 24 sessions of CAT, with 4 additional follow-up sessions, spread over the 6-month's post-therapy period. Three out of the five HPD experimental variables (focus on physical appearance, emptiness and child inside) displayed statistically significant phase of treatment effects. Graphing of such data indicated that a 'sudden deterioration' occurred at the point of termination, with eventual recovery and maintenance of the progress made during the intervention. A battery of validated clinical measures were also completed at assessment, termination and final follow-up sessions; analysis of the general measures illustrated clinically significant change, indexing personality integration and reductions to depression. The study is discussed in terms of methodological and clinical limitations, the central importance of process issues and effective termination in HPD, plus the potential utility of CAT in the treatment of HPD presentations.


Metabolic responses to ammonium acetate infusion in exercising horses.
The relationship between elevated plasma ammonia (NH3) levels, fatigue development and muscle metabolism were examined in horses during a submaximal fatigue test. Eight Quarter Horse mares were intravenously infused prior to exercise with either sodium acetate (control) or ammonium acetate (AMINF), and exercised to fatigue on an 11% grade treadmill, carrying 27 kg of lead. Time to fatigue was not different (P greater than 0.05) between groups. Intramuscular NH3 and lactate increased (P less than 0.001) during exercise; however, the treatment did not (P greater than 0.05) affect either. A treatment by exercise interaction (P less than 0.01) occurred for plasma NH3. The reciprocal relationship between changes in plasma and intramuscular alanine (ala) and glutamate (glu) indicated activation of the glucose-alanine cycle. Plasma glutamine (gln) increased (P less than 0.001) during exercise; however intramuscular gln was not (P greater than 0.05) altered. The excretion of urea-N was depressed as a result of exercise while the orotic acid/creatinine ratio did not (P greater than 0.05) change. The amino acids and urinary metabolites were not (P greater than 0.05) affected by treatment. These results did not show any metabolic evidence for a role of increased plasma NH3 levels in fatigue development. However this study did provide insight into other aspects of nitrogen metabolism during exercise in the horse.


Cytomegalovirus infection rate among heart transplant patients in relation to anti-thymocyte immunoglobulin induction therapy. Copenhagen Heart Transplant Group.
During a 2-year period, 49 patients underwent heart transplantation at Rigshospitalet, Copenhagen. Nine (18%) were females and the mean age for all patients was 44 years (range 14-56 years). Immunosuppressive therapy included cyclosporin, azathioprine and steroids in all patients. 43 patients received in addition short-term (approx. 4 days) induction treatment with antithymocyte immunoglobulin (ATG). 17 patients received ATG Fresenius, 2.5 mg/kg/day or ATGAM, 12.5 mg/kg/day, whereas the remaining 26 patients received ATG Merieux, 2.5 mg/kg/day. Prophylactic antimicrobial chemotherapy included ceftriaxone, acyclovir (1 g daily), nystatin, and pyrimethamine in toxoplasmosis mismatch patients. Serological assays for cytomegalovirus (CMV), Epstein-Barr virus, varicella-zoster virus, herpes simplex virus, legionella and toxoplasmosis as well as CMV and bacterial culturing were carried out before transplantation, at regular intervals and when clinically indicated. Five patients developed septicaemia. Nine had pulmonary bacterial infections, including 2 cases of legionella pneumonia. Two had Clostridium difficile diarrhoea. Three patients had Pneumocystis carinii pneumonitis. 24 patients (49%) had evidence of CMV infection/reactivation. Seven out of 10 CMV mismatch (pos donor/neg recipient) patients and 3 out of 12 CMV match (pos donor/pos recipient) patients developed clinical CMV disease. The rate of CMV infection/reactivation was significantly higher among patients who had CMV-positive donors (p < 0.01) and among patients receiving ATG Merieux induction treatment (p < 0.0001). Logistic regression analysis showed that both positive CMV donor status and ATG Merieux induction treatment were significant independent predictors of CMV infection. Six patients (12%) died. Two out of 4 infection related deaths could be ascribed to CMV disease.


Reduced encephalopathy in pigs with ischemia-induced acute hepatic failure treated with a bioartificial liver containing alginate-entrapped hepatocytes.
To analyze the effects of an extracorporeal bioartificial liver containing alginate bead-entrapped hepatocytes on pigs with ischemia-induced acute hepatic failure. Prospective animal study. University and INSERM laboratory. Fifteen Large White/Pietrin female pigs weighing 20-30 kg. Acute hepatic failure was induced by end-to-side portocaval shunt and ligature of the whole porta hepatitis. The bioartificial liver was in a thermostabilized column, containing a fluidized bed of alginate beads that embedded porcine hepatocytes, connected to a plasmapheresis system. Intracranial pressure; survival; ammonia, total bilirubin, aminotransferases, alkaline phosphatase, and lactate concentrations; and clotting factors were studied. The groups were pigs with acute hepatic failure (group 1, n = 4), pigs with acute hepatic failure treated with bioartificial liver containing empty beads (group 2, n = 4), or porcine hepatocytes (group 3, n = 5). In group 1, survival of pigs averaged 10.9 +/- 1.0 hrs; intracranial pressure reached 32.3 +/- 3.8 mm Hg and was associated with coma and cerebral edema. After connection to the bioartificial liver, the survival of acute hepatic failure pigs was 12.1 +/- 1.4 hrs in group 2 and 14.8 +/- 2.5 hrs in group 3. In group 3, intracranial pressure and bilirubin concentrations were reduced significantly compared with both group 1 and group 2. Neither signs of encephalopathy nor cerebral edema was observed in any animal of group 3. In all animals, plasma ammonium, aminotransferases, alkaline phosphatase, and lactate concentrations increased and clotting factors decreased with no significant differences between the three groups. Autopsy revealed a total necrosis of the liver, which was histologically confirmed. The ischemia-induced model of acute hepatic failure in pigs is reproducible and provides measurable clinical and biological features. A bioartificial liver containing alginate bead-entrapped hepatocytes improves the signs of encephalopathy in pigs with ischemia-induced acute hepatic failure, suggesting that the bioartificial liver can clear out toxic compounds that are released from necrotic livers.


Towards a multilingual version of terminologia anatomica.
Terminologia Anatomica (TA) is the new standard in anatomical terminology. This terminology is available only in Latin and English and its worldwide adoption is subdued to the addition of terms from others languages. On the other hand Nomina Anatomica (NA), the previous standard, has been widely translated. Aim of this work was to append foreign terms to TA by using similarity matching algorithm between its Latin terms and those from NA. A semi-automatic matching of Latin terms from TA with those of NA was performed using a string-to-string distance algorithm and manual assessment. We used a French - Latin version of NA together with TA and we suggested French terms for TA. Coverage was evaluated by the number of exact and approximate matches. A target of 80% was set due to the superior number of terms in TA compared to NA. Relevance was estimated by manually comparing the meanings of the English and French terms related to the same Latin term. The question was whether they refer to the same anatomical structure. Exact or approximate matches were found for 5,982 terms (76.5%) of TA. Our results outlined that more than 75% of the terms from TA came from NA, most of them were left unchanged and all were used with the same meaning. This method produces relevant results, reaching our 80% target. The method is based only on Latin terms and can be used for other languages and for others terminologies including Latin terms.


Controlling mixed-protein adsorption layers on colloidal alumina particles by tailoring carboxyl and hydroxyl surface group densities.
We show that different ratios of bovine serum albumin (BSA) and lysozyme (LSZ) can be achieved in a mixed protein adsorption layer by tailoring the amounts of carboxyl (-COOH) and aluminum hydroxyl (AlOH) groups on colloidal alumina particles (d50 ≈ 180 nm). The particles are surface-functionalized with -COOH groups, and the resultant surface chemistry, including the remaining AlOH groups, is characterized and quantified using elemental analysis, ζ potential measurements, acid-base titration, IR spectroscopy, electron microscopy, nitrogen adsorption, and dynamic light scattering. BSA and LSZ are subsequently added to the particle suspensions, and protein adsorption is monitored by in situ ζ potential measurements while being quantified by UV spectroscopy and gel electrophoresis. A comparison of single-component and sequential protein adsorption reveals that BSA and LSZ have specific adsorption sites: BSA adsorbs primarily via AlOH groups, whereas LSZ adsorbs only via -COOH groups (1-2 -COOH groups on the particle surface is enough to bind one LSZ molecule). Tailoring such groups on the particle surface allows control of the composition of a mixed BSA and LSZ adsorption layer. The results provide further insight into how particle surface chemistry affects the composition of protein adsorption layers on colloidal particles and is valuable for the design of such particles for biotechnological and biomedical applications.


[Mask physiotherapy for prevention of pulmonary complications after heart surgery. A controlled study].
The objective of this prospective, consecutive, randomized, controlled study was to investigate the effects of mask physiotherapy on postoperative complications after heart surgery. Sixty-six low-risk male patients undergoing coronary artery by-pass graft surgery were evaluated. The patients were treated with routine chest physiotherapy alone or supplied with either positive expiratory pressure (PEP), or inspiratory resistance-positive expiratory pressure (IR-PEP). Postoperative pulmonary complications were assessed by forced vital capacity (FVC), arterial oxygen tension (PaO2), and chest X-ray examination. There was an almost equal decrease and subsequent rise in spirometric and blood gas values in all three groups, but patients treated with the PEP mask had a borderline significantly higher increase in PaO2 from day three to day six compared with patients treated with no mask. There was an almost equal frequency of atelectasis in the three treatment groups. It is concluded that no significant differences in outcome were found between the three groups.