Evaluation of the Cavitron Spirometric Computer for accuracy in clinical screening spirometry.
Ten healthy male cardiopulmonary technicians, 10 aircrew members, and 10 patients performed a series of pulmonary function studies to compare the Cavitron Spirometric Computer to the conventional water-sealed Collins 13.5-/spirometer. A total of 50 studies were performed on the spirometers individually and then with the spirometers linked in-line. The Cavitron FVC averaged 6% less, the FEV1--7% less, and the FEF 25-75%--11.6% less than comparable measurements from the Collins spirometer. Since these difference are within the suggested guidelines for screening studies, the Cavitron Spirometric Computer is acceptable for use in clinical screening spirometry.


The morphologic and functional features of LAD myocardial bridging at multi-detector computed tomography coronary angiography: correlation with coronary artery disease.
The aim of this study was to retrospectively evaluate the morphologic and functional features of myocardial bridging (MB) and to investigate the impact of morphologic features on presence of atherosclerosis with multi-detector computed tomography (MDCT) coronary angiography. The study population consisted of 191 consecutive patients. Besides coronary lesions, morphologic features of the MB (depth, length and the distance of the tunneled artery from the left coronary ostium) were analyzed. MDCT detected MB on left anterior descending artery in 41 patients (21.5%). The prevalence of atherosclerotic plaques proximal to the MB of LAD was 49% (20/41). There was a statistically significant correlation between percentage of systolic compression and depth of the tunneled segment (r=0.538, p<0.01). There was no relation between distance of the tunneled segment from the ostium and degree of systolic compression. No significant correlation was found between percentage of systolic compression and length of the tunneled segment (r=0.058, p=0.721). Morphologic features of MB were not related to the presence of CAD in proximal segments. MDCT coronary angiography depicts the morphologic and functional features of the MB in detail. The depth of MB segment was correlated with systolic compression of MB. There was no relationship between distance of the tunneled segment from the ostium and systolic compression.


Influence of quinidine on ATP-linked calcium binding by heart mitochondria and microsomes.
The action of quinidine on heart microsomal and mitochondrial calcium binding in the presence of MgATP was studied under different experimental conditions and compared with other antiarrhythmic agents such as procaine amide and lidocaine. Quinidine stimulated microsomal calcium binding but depressed mitochondrial calcium binding. Although procaine amide stimulated microsomal calcium binding, it did not affect mitochondrial calcium binding. On the other hand, lidocaine depressed calcium binding by mitochondria without affecting calcium binding by the microsomal fraction. The stimulation of microsomal calcium binding by quinidine was not apparent at high concentrations of Mg2+, low concentrations of ATP, or low concentrations of Ca2+. The depressant action of quinidine on mitochondrial calcium binding was not observed at low concentrations of Mg2+ or ATP but was more pronounced at low concentrations of Ca2+. These results suggest that the action of quinidine on mitochondria may play a major role in eliciting cardiodepressant effect.


Study of the diradicaloid character in a prototypical pancake-bonded dimer: the stacked tetracyanoethylene (TCNE) anion dimer and the neutral K(2)TCNE(2) complex.
The π-bonded tetracyanoethylene anion dimer (TCNE2(2-)) and the neutral K2TCNE2 system have been investigated to obtain new insights into the unique features of two-electron multicenter (2e-mc) π-pancake bonding. The inter-radical interaction leads to a significant diradicaloid character described by two singly occupied molecular orbitals (SOMOs) of the monomers. A highly correlated approach, the multireference averaged quadratic coupled-cluster (MR-AQCC) method, has been used to achieve a balanced description of the different types of electron correlation that occur in this system. The analysis of the interaction energies for the two systems in the singlet and the lowest triplet states and of the unpaired electron densities demonstrate the importance of diradical π bonding in addition to the conventional van der Waals interactions that occur in intermolecular interactions. In this analysis, the separation of the repulsive Coulomb interaction energies from the remaining terms turned out to be a crucial prerequisite to achieve consistent results. Our calculations also confirm that the driving force behind the energetic stability of the pancake bonds predominantly derives from the overlap of the SOMO-SOMO bonding interaction.


MicroRNA and HER2-overexpressing cancer.
The discovery of microRNAs (miRNAs) has opened up new avenues for studying cancer at the molecular level, featuring a post-genomic era of biomedical research. These non-coding regulatory RNA molecules of ~22 nucleotides have emerged as important cancer biomarkers, effectors, and targets. In this review, we focus on the dysregulated biogenesis and function of miRNAs in cancers with an overexpression of the proto-oncogene HER2. Many of the studies reviewed here were carried out in breast cancer, where HER2 overexpression has been extensively studied and HER2-targeted therapy practiced for more than a decade. MiRNA signatures that can be used to classify tumors with different HER2 status have been reported but little consensus can be established among various studies, emphasizing the needs for additional well-controlled profiling approaches and meta-analyses in large and well-balanced patient cohorts. We further discuss three aspects of microRNA dysregulation in or contribution to HER2-associated malignancies or therapies: (a) miRNAs that are up- or down-regulated by HER2 and mediate the downstream signaling of HER2; (b) miRNAs that suppress the expression of HER2 or a factor in HER2 receptor complexes, such as HER3; and (c) miRNAs that affect responses to anti-HER2 therapies. The regulatory mechanisms are elaborated using mainly examples of miR- 205, miR-125, and miR-21. Understanding the regulation and function of miRNAs in HER2-overexpressing tumors shall shed new light on the pathogenic mechanisms of microRNAs and the HER2 proto-oncogene in cancer, as well as on individualized or combinatorial anti-HER2 therapies.


HIV knowledge and sexual risk behavior among street adolescents in rehabilitation centres in Kinshasa; DRC: gender differences.
Street children, common in Africa, are increasingly vulnerable to alcohol and drugs of abuse and lack access to both healthcare and knowledge about HIV and AIDS. Hence, this study assessed the level of knowledge about sexually transmitted infections (STIs), including HIV, among street adolescents in the Democratic Republic of the Congo (DRC). A random sampling of 200 street children (10-25 years of age) were selected from 17 rehabilitation centres in Kinshasa, and a structured questionnaire was administered to all participants in their respective centres. High knowledge, knowledge or awareness of condom was defined when a participant gave more than 67% of correct responses. Chi square analysis was used to test differences between sexes. The knowledge level of respondents was high. 54.3% of males and 45.7% of girls have heard about HIV), and few participants cited unprotected sex as mode of transmission (42.9% for males and 57.1% for females). A high number of children reported a previous sexual experience. Satisfying a natural bodily need was the main reason for having sex. However, the use of condoms is still low in both genders (26.2 versus 59.3%, p<0.01). Neither gender reported a reason why they are not using a condom. This study highlights the high knowledge about HIV, which contrasts with low condom use and high past sexual experiences with the high number of sexual partners and sexual contacts. Policies targeting these findings are warranted to reverse such trends.


[Adaptive stabilization of myocardium under the influence of electroacupuncture and cardiac protection].
Adaptation of animals to short-term stress is known to result in the development of the adaptive structure stabilization phenomenon. At the level of the heart, the phenomenon appears as increased resistance to elevated catecholamine and calcium levels, reperfusion paradox. This study attempted to reproduce the phenomenon without applying any stress, but using a course of transauricular electric acupuncture. The isolated hearts of rats undergoing a course of the acupuncture were ascertained to show a clear-cut high resistance to the reperfusion paradox. After coronary ligation, the extent of necrosis in the animals having the acupuncture was significantly lower, as in those adapted to stress. The assumption that the phenomenon forming the basis for cardioprotective effects develops with electric acupuncture is discussed in the paper.


Synthetic Ingenols Maximize Protein Kinase C-Induced HIV-1 Latency Reversal.
Antiretroviral therapy (ART) does not cure HIV-1 infection due to the persistence of proviruses in long-lived resting T cells. Strategies targeting these latently infected cells will be necessary to eradicate HIV-1 in infected individuals. Protein kinase C (PKC) activation is an effective mechanism to reactivate latent proviruses and allows for recognition and clearance of infected cells by the immune system. Several ingenol compounds, naturally occurring PKC agonists, have been described to have potent latency reversal activity. We sought to optimize this activity by synthesizing a library of novel ingenols via esterification of the C-3 hydroxyl group of the ingenol core, which itself is inactive for latency reversal. Newly synthesized ingenol derivatives were evaluated for latency reversal activity, cellular activation, and cytotoxicity alongside commercially available ingenols (ingenol-3,20-dibenzoate, ingenol 3-hexanoate, and ingenol-3-angelate) in HIV latency cell lines and resting CD4+ T cells from aviremic participants. Among the synthetic ingenols that we produced, we identified several compounds that demonstrate high efficacy and represent promising leads as latency reversal agents for HIV-1 eradication.


Membrane potential can influence the rate of membrane photomodification.
Though cellular photomodification has been shown to change cellular resting membrane potential, an effect of membrane potential on the rate of photomodification has never been reported. Here we demonstrate that the rate of photomodification of potassium channels in frog atrial cells is voltage dependent. The rate of potassium channel photomodification using negatively charged Rose Bengal as the photosensitizer is about 2.5 times greater at the resting membrane potential of -70 mV compared to +40 mV. Similar results are obtained using the positively charged photosensitizer methylene blue. On the other hand, the rate of photomodified increase of leak current in the same cells does not significantly change in this voltage range with Rose Bengal as photosensitizer, but demonstrates a voltage dependence like that of potassium current when methylene blue is the photosensitizer. These observations cannot be explained based on voltage-dependent partitioning of the sensitizer, as similar effects on potassium current were obtained using either a positively charged or negatively charged sensitizer.


Assessment of person-to-person transmission of hantavirus pulmonary syndrome in a Chilean hospital setting.
Person-to-person transmission of Andes hantavirus among healthcare workers was reported in Argentina for the first time in 1996. To determine whether such transmission of the virus occurred during a 1997 outbreak of hantavirus pulmonary syndrome (HPS) in southern Chile due to Andes virus, we conducted a serological and epidemiological study in the Coyhaique Regional Hospital, where the majority of HPS patients were admitted. Workers in every department of the hospital were evaluated for immunoglobulin G (IgG) and IgM hantavirus antibodies using the enzyme-linked immunosorbent assay (ELISA). A standardized questionnaire was used to determine the type and extent of exposure to HPS patients, as well as other potential risk factors and previous febrile respiratory illnesses requiring hospitalization. Less than half (44%) reported always using gloves when touching patients or their secretions; respiratory protection was not used. Of the 319 participants (87.9% of those eligible), 12 (3.7%) had IgG antibodies. This finding is consistent with the antibody prevalence in the community in which the participants lived. Of the 12 positive healthcare workers, six reported contact with HPS patients. A similar exposure was found in those who tested negative [6/140 (4%) compared to 6/179 (3%), P = 0.66]. There was no significant difference in the types of hospital activities performed or the number of hospitalizations for febrile respiratory illnesses between antibody-positive and antibody-negative individuals. These data suggest that there was no person-to-person transmission among healthcare workers during a recent outbreak of HPS in Southern Chile in 1997, despite the inconsistent use of any precautions against transmission.


Mass Spectrometric Studies of Apolipoprotein Proteoforms and Their Role in Lipid Metabolism and Type 2 Diabetes.
Apolipoproteins function as structural components of lipoprotein particles, cofactors for enzymes, and ligands for cell-surface receptors. Most of the apoliporoteins exhibit proteoforms, arising from single nucleotide polymorphisms (SNPs) and post-translational modifications such as glycosylation, oxidation, and sequence truncations. Reviewed here are recent studies correlating apolipoproteins proteoforms with the specific clinical measures of lipid metabolism and cardiometabolic risk. Targeted mass spectrometric immunoassays toward apolipoproteins A-I, A-II, and C-III were applied on large cross-sectional and longitudinal clinical cohorts. Several correlations were observed, including greater apolipoprotein A-I and A-II oxidation in patients with diabetes and cardiovascular disease, and a divergent apoC-III proteoforms association with plasma triglycerides, indicating significant differences in the metabolism of the individual apoC-III proteoforms. These are the first studies of their kind, correlating specific proteoforms with clinical measures in order to determine their utility as potential clinical biomarkers for disease diagnosis, risk stratification, and therapy decisions. Such studies provide the impetus for the further development and clinical translation of MS-based protein tests.


Parametric evolution for a deformed cavity.
We consider a classically chaotic system that is described by a Hamiltonian H(Q,P;x), where (Q,P) describes a particle moving inside a cavity, and x controls a deformation of the boundary. The quantum eigenstates of the system are /n(x)>. We describe how the parametric kernel P(n/m)=/<n(x)/m(x(0))>/(2), also known as the local density of states, evolves as a function of deltax=x-x(0). We illuminate the nonunitary nature of this parametric evolution, the emergence of nonperturbative features, the final nonuniversal saturation, and the limitations of random-wave considerations. The parametric evolution is demonstrated numerically for two distinct representative deformation processes.


Steady-state solutions to PBPK models and their applications to risk assessment I: Route-to-route extrapolation of volatile chemicals.
Although analysis of in vivo pharmacokinetic data necessitates use of time-dependent physiologically-based pharmacokinetic (PBPK) models, risk assessment applications are often driven primarily by steady-state and/or integrated (e.g., AUC) dosimetry. To that end, we present an analysis of steady-state solutions to a PBPK model for a generic volatile chemical metabolized in the liver. We derive an equivalent model that is much simpler and contains many fewer parameters than the full PBPK model. The state of the system can be specified by two state variables-the rate of metabolism and the rate of clearance by exhalation. For a given oral dose rate or inhalation exposure concentration, the system state only depends on the blood-air partition coefficient, metabolic constants, and the rates of blood flow to the liver and of alveolar ventilation. At exposures where metabolism is close to linear, only the effective first-order metabolic rate is needed. Furthermore, in this case, the relationship between cumulative exposure and average internal dose (e.g., AUCs) remains the same for time-varying exposures. We apply our analysis to oral-inhalation route extrapolation, showing that for any dose metric, route equivalence only depends on the parameters that determine the system state. Even if the appropriate dose metric is unknown, bounds can be placed on the route-to-route equivalence with very limited data. We illustrate this analysis by showing that it reproduces exactly the PBPK-model-based route-to-route extrapolation in EPA's 2000 risk assessment for vinyl chloride. Overall, we find that in many cases, steady-state solutions exactly reproduce or closely approximate the solutions using the full PBPK model, while being substantially more transparent. Subsequent work will examine the utility of steady-state solutions for analyzing cross-species extrapolation and intraspecies variability.


Psychotropic drugs and the risk of fall injuries, hospitalisations and mortality among older adults.
To investigate whether psychotropics are associated with an increased risk of fall injuries, hospitalizations, and mortality in a large general population of older adults. We performed a nationwide matched (age, sex, and case event day) case-control study between 1 January and 31 December 2011 based on several Swedish registers (n = 1,288,875 persons aged ≥65 years). We used multivariate conditional logistic regression adjusted for education, number of inpatient days, Charlson co-morbidity index, dementia and number of other drugs. Antidepressants were the psychotropic most strongly related to fall injuries (ORadjusted : 1.42; 95% CI: 1.38-1.45) and antipsychotics to hospitalizations (ORadjusted : 1.22; 95% CI: 1.19-1.24) and death (ORadjusted : 2.10; 95% CI: 2.02-2.17). Number of psychotropics was associated with increased the risk of fall injuries, (4 psychotropics vs 0: ORadjusted : 1.53; 95% CI: 1.39-1.68), hospitalization (4 psychotropics vs 0: ORadjusted : 1.27; 95% CI: 1.22-1.33) and death (4 psychotropics vs 0: ORadjusted : 2.50; 95% CI: 2.33-2.69) in a dose-response manner. Among persons with dementia (n = 58,984), a dose-response relationship was found between number of psychotropics and mortality risk (4 psychotropics vs 0: ORadjusted : 1.99; 95% CI: 1.76-2.25). Our findings support a cautious prescribing of multiple psychotropic drugs to older patients. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons, Ltd.


Initial European clinical experience with pulsatile extracorporeal membrane oxygenation.
Extracorporeal membrane oxygenation (ECMO) for post-cardiotomy heart failure in neonates and infants still carries high mortality and morbidity rates. In this study we present the first European clinical experience with the Medos DeltaStream DP1, a new pulsatile flow pump, in neonates and infants. The DP1 is an extracorporeal rotary blood pump. The pump features a diagonal flow impeller, and can be used for both continuous and pulsatile output. Special characteristics include its small priming volume of approximately 30 ml and a high pumping capacity. A temperature sensor and speed sensors are integrated into the pump. The pump has a delivery rate of up to 8 liters/min and a speed range of 100 to 10,000 rpm. Two patients being assisted with the pulsatile pump system were successfully weaned after 36 and 53 hours, respectively. Based on our limited experience with 2 patients, we believe that pulsatile DP1 device is a reasonable alternative to current conventional non-pulsatile systems.


Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types.
Deregulation of the β-catenin signaling has long been associated with cancer. Intracellular components of this pathway, including axin, APC, and β-catenin, are frequently mutated in a range of human tumors, but the contribution of specific extracellular ligands that promote cancer development through this signaling axis remains unclear. We conducted a reporter-based screen in a panel of human tumors to identify secreted factors that stimulate β-catenin signaling. Through this screen and further molecular characterization, we found that R-spondin (RSPO) proteins collaborate with Wnt proteins to activate β-catenin. RSPO family members were expressed in several human tumors representing multiple malignancies, including ovarian, pancreatic, colon, breast, and lung cancer. We generated specific monoclonal antibody antagonists of RSPO family members and found that anti-RSPO treatment markedly inhibited tumor growth in human patient-derived tumor xenograft models, either as single agents or in combination with chemotherapy. Furthermore, blocking RSPO signaling reduced the tumorigenicity of cancer cells based on serial transplantation studies. Moreover, gene-expression analyses revealed that anti-RSPO treatment in responsive tumors strongly inhibited β-catenin target genes known to be associated with cancer and normal stem cells. Collectively, our results suggest that the RSPO family is an important stimulator of β-catenin activity in many human tumors and highlight a new effective approach for therapeutically modulating this fundamental signaling axis.


A Simple Plasma Retinol Isotope Ratio Method for Estimating β-Carotene Relative Bioefficacy in Humans: Validation with the Use of Model-Based Compartmental Analysis.
Background: Provitamin A carotenoids are an important source of dietary vitamin A for many populations. Thus, accurate and simple methods for estimating carotenoid bioefficacy are needed to evaluate the vitamin A value of test solutions and plant sources. β-Carotene bioefficacy is often estimated from the ratio of the areas under plasma isotope response curves after subjects ingest labeled β-carotene and a labeled retinyl acetate reference dose [isotope reference method (IRM)], but to our knowledge, the method has not yet been evaluated for accuracy.Objectives: Our objectives were to develop and test a physiologically based compartmental model that includes both absorptive and postabsorptive β-carotene bioconversion and to use the model to evaluate the accuracy of the IRM and a simple plasma retinol isotope ratio [(RIR), labeled β-carotene-derived retinol/labeled reference-dose-derived retinol in one plasma sample] for estimating relative bioefficacy.Methods: We used model-based compartmental analysis (Simulation, Analysis and Modeling software) to develop and apply a model that provided known values for β-carotene bioefficacy. Theoretical data for 10 subjects were generated by the model and used to determine bioefficacy by RIR and IRM; predictions were compared with known values. We also applied RIR and IRM to previously published data.Results: Plasma RIR accurately predicted β-carotene relative bioefficacy at 14 d or later. IRM also accurately predicted bioefficacy by 14 d, except that, when there was substantial postabsorptive bioconversion, IRM underestimated bioefficacy. Based on our model, 1-d predictions of relative bioefficacy include absorptive plus a portion of early postabsorptive conversion.Conclusion: The plasma RIR is a simple tracer method that accurately predicts β-carotene relative bioefficacy based on analysis of one blood sample obtained at ≥14 d after co-ingestion of labeled β-carotene and retinyl acetate. The method also provides information about the contributions of absorptive and postabsorptive conversion to total bioefficacy if an additional sample is taken at 1 d.


[Psychopathology of the late period of closed military craniocerebral injuries (non-psychotic forms)].
The author analyzes nonpsychotic disturbances at the late period of a combat closed craniocerebral injury (CCCI) in 97 veterans of the Great Patriotic War. Considerable differences were found in the incidence and structure of the organic decrease in mental activity, the psychoorganic syndrome as well as emotional-volitional and affective disorders, which depended on the clinical variant of the time-course at the late period of a CCCI. The author identified the following clinical variants: protracted decompensation of long-term sequels of a CCCI; cerebrovascular disease associated with residual manifestations of a CCCI; and a predominantly cerebrovascular disease in individuals with a history of a CCCI.


Spirochaetes and other bacterial species associated with bovine digital dermatitis.
The 16S rRNA genes from spirochaetes associated with digital dermatitis of British cattle were amplified by polymerase chain reaction from digital dermatitis lesion biopsies using one universal and one treponeme-specific primer. Two treponemal sequences were identified both of which shared a high degree of homology with the oral pathogen Treponema denticola (98%). Two further 16S rRNA gene sequences were obtained and shared similarity to Bacteroides levii (99%) and Mycoplasma hyopharyngis (98%). Polymerase chain reaction with T. denticola-specific primers amplified a potential virulence gene from digital dermatitis lesions which shared a high degree of homology to the 46-kDa haemolysin gene of T. denticola. The significance of the presence of organisms in digital dermatitis lesions of the bovine foot which are closely related to oral pathogens is discussed.


Whole-Genome Multi-omic Study of Survival in Patients with Glioblastoma Multiforme.
Glioblastoma multiforme (GBM) has been recognized as the most lethal type of malignant brain tumor. Despite efforts of the medical and research community, patients' survival remains extremely low. Multi-omic profiles (including DNA sequence, methylation and gene expression) provide rich information about the tumor. These profiles are likely to reveal processes that may be predictive of patient survival. However, the integration of multi-omic profiles, which are high dimensional and heterogeneous in nature, poses great challenges. The goal of this work was to develop models for prediction of survival of GBM patients that can integrate clinical information and multi-omic profiles, using multi-layered Bayesian regressions. We apply the methodology to data from GBM patients from The Cancer Genome Atlas (TCGA, n = 501) to evaluate whether integrating multi-omic profiles (SNP-genotypes, methylation, copy number variants and gene expression) with clinical information (demographics as well as treatments) leads to an improved ability to predict patient survival. The proposed Bayesian models were used to estimate the proportion of variance explained by clinical covariates and omics and to evaluate prediction accuracy in cross validation (using the area under the Receiver Operating Characteristic curve, AUC). Among clinical and demographic covariates, age (AUC = 0.664) and the use of temozolomide (AUC = 0.606) were the most predictive of survival. Among omics, methylation (AUC = 0.623) and gene expression (AUC = 0.593) were more predictive than either SNP (AUC = 0.539) or CNV (AUC = 0.547). While there was a clear association between age and methylation, the integration of age, the use of temozolomide, and either gene expression or methylation led to a substantial increase in AUC in cross-validaton (AUC = 0.718). Finally, among the genes whose methylation was higher in aging brains, we observed a higher enrichment of these genes being also differentially methylated in cancer.


Effects of a Collaborative Intervention Process on Parent Empowerment and Child Performance: A Randomized Controlled Trial.
To examine the effects of a four-step collaborative intervention process on parent and child outcomes and describe parents' and therapists' experiences. Eighteen children with physical disabilities, their mothers, and 16 physical therapists participated. Therapists randomized to the experimental group were instructed in the collaborative intervention process. All family-therapist dyads participated in six weekly sessions. Outcomes included the adapted Family Empowerment Scale (FES) and Canadian Occupational Performance Measure (COPM). A questionnaire was completed by parents and therapists to rate and describe their experiences. Mean scores on the FES (p <.05) and COPM (p <.001) increased after intervention but there were no group differences (p >.05). Effect size for change in child performance (.73) and parent satisfaction (1.08) on the COPM favored the experimental group. Parents in the experimental group were more confident in carrying out activities during daily routines (p =.01) and worked together with therapists to a greater extent (p =.01) than parents in the comparison group. Therapists in the experimental group perceived that they provided information/instruction (p <.01) and worked together with parents (p =.02) to a greater extent than therapists in the comparison group. Findings support the importance of shared goal setting for children's activities. Further research is recommended.


Integrating Diabetes Prevention Education Among Teenagers Involved in Summer Employment: Encouraging Environments for Health in Adolescence (ENHANCE).
Type 2 diabetes (T2D) in youth is a growing healthcare and public health concern. It is costly, and youth suffer from disabling and deadly comorbid conditions at a faster pace than adult onset. However, T2D is preventable. The population of obese youth at greatest risk for T2D is of minority race/ethnicity and socioeconomically disadvantaged background, which creates barriers to health promoting lifestyles. Despite being the first line of prevention efforts for T2D, efficacious behavioral lifestyle interventions are still lacking at the community level. During the summers of 2016 and 2017, a study integrated obesity and diabetes prevention health education into TeenWorks summer employment program at Indy Urban Acres in Indianapolis, Indiana. Results were analyzed using paired sample t-tests. Participants (N = 168) had a mean age of 15.8 ± 0.7 years, 61% female, 13% Hispanic, 80% Black. By the end of the intervention, physical activity (p = 0.000) and prevention knowledge (p = 0.000) were significantly higher. Dietary intake (p = 0.204), self-efficacy (p = 0.58), food insecurity (p = 0.058) and depression screening scores (p = 0.809) were not significantly different. In light of the continuing childhood obesity epidemic and increasing prevalence of prediabetes and T2D in youth, there is a pressing need to understand and reduce barriers to obesity and diabetes prevention in high-risk populations. This study demonstrated the feasibility of integrating obesity and T2D prevention health education into a teen summer employment program.


Take five - Type VII secretion systems of Mycobacteria.
Mycobacteria use type VII secretion (T7S) systems to secrete proteins across their complex cell envelope. Pathogenic mycobacteria, such as the notorious pathogen Mycobacterium tuberculosis, have up to five of these secretion systems, named ESX-1 to ESX-5. At least three of these secretion systems are essential for mycobacterial virulence and/or viability. Elucidating T7S is therefore essential to understand the success of M. tuberculosis and other pathogenic mycobacteria as pathogens, and could be instrumental to identify novel targets for drug- and vaccine-development. Recently, significant progress has been achieved in the identification of T7S substrates and a general secretion motif. In addition, a start has been made with unraveling the mechanism of secretion and the structural analysis of the different subunits. This review summarizes these recent findings, which are incorporated in a working model of this complex machinery. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.


APOE-ε4 and BIN1 increase risk of Alzheimer's disease pathology but not specifically of Lewy body pathology.
Lewy body (LB) pathology commonly occurs in individuals with Alzheimer's disease (AD) pathology. However, it remains unclear which genetic risk factors underlie AD pathology, LB pathology, or AD-LB co-pathology. Notably, whether APOE-ε4 affects risk of LB pathology independently from AD pathology is controversial. We adapted criteria from the literature to classify 4,985 subjects from the National Alzheimer's Coordinating Center (NACC) and the Rush University Medical Center as AD-LB co-pathology (AD+LB+), sole AD pathology (AD+LB-), sole LB pathology (AD-LB+), or no pathology (AD-LB-). We performed a meta-analysis of a genome-wide association study (GWAS) per subpopulation (NACC/Rush) for each disease phenotype compared to the control group (AD-LB-), and compared the AD+LB+ to AD+LB- groups. APOE-ε4 was significantly associated with risk of AD+LB- and AD+LB+ compared to AD-LB-. However, APOE-ε4 was not associated with risk of AD-LB+ compared to AD-LB- or risk of AD+LB+ compared to AD+LB-. Associations at the BIN1 locus exhibited qualitatively similar results. These results suggest that APOE-ε4 is a risk factor for AD pathology, but not for LB pathology when decoupled from AD pathology. The same holds for BIN1 risk variants. These findings, in the largest AD-LB neuropathology GWAS to date, distinguish the genetic risk factors for sole and dual AD-LB pathology phenotypes. Our GWAS meta-analysis summary statistics, derived from phenotypes based on postmortem pathologic evaluation, may provide more accurate disease-specific polygenic risk scores compared to GWAS based on clinical diagnoses, which are likely confounded by undetected dual pathology and clinical misdiagnoses of dementia type.


Reparative myocardial mechanisms in adult C57BL/6 and MRL mice following injury.
Previous studies have suggested that the heart may be capable of limited repair and regeneration in response to a focal injury, while other studies indicate that the mammalian heart has no regenerative capacity. To further explore this issue, we performed a series of superficial and transmural myocardial injuries in C57BL/6 and MRL/MpJ adult mice. At defined time intervals following the respective injury (days 3, 14, 30 and 60), we examined cardiac function using echocardiography, morphology, fluorescence-activated cell sorting for 5-bromo-2-deoxyuridine-positive cells and molecular signature using microarray analysis. We observed restoration of myocardial function in the superficial MRL cryoinjured heart and significantly less collagen deposition compared with the injured hearts of C57BL/6 mice. Following a severe transmural myocardial injury, the MRL mouse has increased survival and decreased ventricular remodeling compared with the C57BL/6 mouse but without evidence of complete regeneration. The cytoprotective program observed in the severely injured MRL heart is in part due to increased cellular proliferation, increased vasculogenesis, and decreased apoptosis that limits the extension of the injury. We conclude that MRL injured hearts have evidence of myocardial regeneration, in response to superficial injury, but the stabilized left ventricular function and improved survival observed in the MRL mouse following severe injury is not associated with complete myocardial regeneration.


Mixed care networks of community-dwelling older adults with physical health impairments in the Netherlands.
As part of long-term care reforms, home-care organisations in the Netherlands are required to strengthen the linkage between formal and informal caregivers of home-dwelling older adults. Information on the variety in mixed care networks may help home-care organisations to develop network type-dependent strategies to connect with informal caregivers. This study first explores how structural (size, composition) and functional features (contact and task overlap between formal and informal caregivers) contribute to different types of mixed care networks. Second, it examines to what degree these network types are associated with the care recipients' characteristics. Through home-care organisations in Amsterdam, the Netherlands, we selected 74 frail home-dwelling clients who were receiving care in 2011-2012 from both informal and formal caregivers. The care networks of these older adults were identified by listing all persons providing help with five different types of tasks. This resulted in care networks comprising an average of 9.7 caregivers, of whom 67% were formal caregivers. On average, there was contact between caregivers within 34% of the formal-informal dyads, and both caregivers carried out at least one similar type of task in 29% of these dyads. A principal component analysis of size, composition, contact and task overlap showed two distinct network dimensions from which four network types were constructed: a small mixed care network, a small formal network, a large mixed network and a large formal network. Bivariate analyses showed that the care recipients' activities of daily living level, memory problems, social network, perceived control of care and level of mastery differed significantly between these four types. The results imply that different network types require different actions from formal home-care organisations, such as mobilising the social network in small formal networks, decreasing task differentiation in large formal networks and assigning co-ordination tasks to specific dyads in large mixed care networks.


Presentation and perioperative management of arterioportal fistulas.
Arterioportal fistulas (APFs) are usually traumatic in origin and may result in portal hypertension and its complications. Over six years, six patients (aged 20 to 59 years) presented with APFs. Two APFs developed after percutaneous liver biopsy, but only one was complicated (hemobilia). Neither patient was treated operatively. Four APFs occurred two days to three years after gunshot wounds. Three patients presented with gastrointestinal tract hemorrhage. All patients had abdominal bruits. Two patients underwent primary repair. One patient underwent APF resection and replacement of the superior mesenteric artery with autogenous vein. Another patient underwent APF and bowel resection. Three patients survived. One patient died of liver failure. The development of an abdominal bruit in a patient with penetrating abdominal trauma suggests APF and should prompt angiography. Elective repair is recommended before complications of portal hypertension develop.


An Integrative Review of Approaches Used to Assess Course Interventions.
Objective. The objectives of this review are to describe the utility of approaches used for the assessment of course interventions in pharmacy education and to provide recommendations that may guide faculty members in their scholarship of teaching and learning (SoTL) efforts that encompass assessment of course interventions.Findings. Thirty-four articles that included educational interventions published between 2016 and 2020 in the American Journal of Pharmaceutical Education and Currents in Pharmacy Teaching and Learning were selected for analysis. Those articles used various approaches for the assessment of course interventions. In the order of decreasing frequency of use, those methods were surveys, student academic performance, student evaluations, mixed quantitative and qualitative methods, pre- and posttest, and learning analytics.Summary. The use of more than one assessment approach, ie, triangulation, and multiple student cohorts are advantageous. When multiple cohorts are used, it is beneficial to present the students' demographic information. Student academic performance should be part of an assessment of course interventions whenever relevant. Surveys about student perceptions and confidence may contribute to the assessment of course interventions. However, since the information collected is subjective and is usually unrelated to student learning, such an approach should be coupled with other assessment approaches that reflect student learning, such as academic performance and/or a pre- and a posttest. Depending on the research question, qualitative methods and learning analytics may also be a part of the assessment of course interventions.


Transformative community projects in East Germany's rural spaces: exploring more sustainable forms of learning, working, and living.
Increasingly people experience alienation in educational institutions, in work life, and fragmentation in their personal life. This study explores more self-determined, healthy, and sustainable forms of working, learning, and living through a dynamic process that began in 2020 with the purchase of an old homestead in Eastern Germany. Through the remodeling of the buildings and grounds, the first social and cultural references emerged. Along with practical uses, the farm project sees itself as a future workshop or think tank. The resulting consideration includes ideas of compulsory schooling woven into a self-designed format and the introduction of an unconditional basic income. These components could lead to thousands of such projects in rural and urban areas. Drawing from communitarianism, the belief is that an active civil society must take on social, economic, and educational responsibilities and offer children and young people improved conditions in which to grow up. Theory development on the individual components exists, such as entrepreneurship, transformation, community-building, basic income, or self-directed learning but not on the interaction of these variables in the overall context. We tentatively call this integrated design a transformative community project.


Nonoperative treatment in lumbar spondylolysis and spondylolisthesis: a systematic review.
Both spondylolysis and spondylolisthesis can be diagnosed across the life span of sports-participating individuals. Determining which treatments are effective for these conditions is imperative to the rehabilitation professional. A computer-assisted literature search was completed in MEDLINE, CINAHL, and EMBASE databases (1966-April 2012) utilizing keywords related to nonoperative treatment of spondylolysis and/or spondylolisthesis. Reference lists were also searched to find all relevant articles that fit our inclusion criteria: English language, human, lumbar pain with diagnosed spondylolysis and/or spondylolisthesis, inclusion of at least 1 nonoperative treatment method, and use of a comparative study design. Data were independently extracted from the selected studies by 2 authors and cross-referenced. Any disagreement on relevant data was discussed and resolved by a third author. Ten studies meeting the criteria were rated for quality using the GRADE scale. Four studies found surgical intervention more successful than nonoperative treatment for treating pain and functional limitation. One study found no difference between surgery and nonoperative treatment with regard to future low back pain. Improvement was found in bracing, bracing and exercises emphasizing lumbar extension, range of motion and strengthening exercises focusing on lumbar flexion, and strengthening specific abdominal and lumbar muscles. No consensus can be reached on the role of nonoperative versus surgical care because of limited investigation and heterogeneity of studies reported. Studies of nonoperative care options suffered from lack of blinding assessors and control groups and decreased patient compliance with exercise programs.


Dielectric properties of ocular tissues at 37 degrees C.
Values of the relative permittivity, dielectric loss and conductivity are given for various rabbit ocular tissues at frequencies in the range 10 MHz-10 GHz. The tissues measured were cornea, retina, choroid, iris, and the cortical and nuclear zones of the lens. The dielectric parameters were determined using the technique of multiple response time domain spectroscopy. For all tissues the water relaxation could be characterised by a Debye dispersion with a relaxation time longer than that of pure water, indicating that its dielectric behaviour was affected by the presence of the biological macromolecules.


How to be a graduate advisee.
Successful graduate training benefits from committed mentors and motivated students. Because scientific research involves investigating unexplored territory, however, each student's experience will necessarily be unique, making it rarely possible to conform to an idealized training sequence. To approach this inherently uncontrolled situation constructively, students are encouraged, first, to become aware of their own learning patterns and to apply this knowledge to selecting a thesis laboratory, and second, to cultivate an educational philosophy that helps them adapt to many circumstances.


SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation.
Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone that facilitates the maturation of a wide range of proteins, and it has been recognized as a crucial facilitator of oncogene addiction and cancer cell survival. Although HSP90 function is regulated by a variety of post-translational modifications, the physiological significance of methylation has not fully been elucidated. Here we demonstrate that HSP90AB1 is methylated by the histone methyltransferase SMYD2 and that it plays a critical role in human carcinogenesis. HSP90AB1 and SMYD2 can interact through the C-terminal region of HSP90AB1 and the SET domain of SMYD2. Both in vitro and in vivo methyltransferase assays revealed that SMYD2 could methylate HSP90AB1 and mass spectrometry analysis indicated lysines 531 and 574 of HSP90AB1 to be methylated. These methylation sites were shown to be important for the dimerization and chaperone complex formation of HSP90AB1. Furthermore, methylated HSP90AB1 accelerated the proliferation of cancer cells. Our study reveals a novel mechanism for human carcinogenesis via methylation of HSP90AB1 by SMYD2, and additional functional studies may assist in developing novel strategies for cancer therapy.


Role of ascorbic acid supplement in amelioration of anaemia in lead intoxication.
To assess anaemia and oxidative stress in rats that were injected lead and to evaluate the possible effects of ascorbic acid supplementation on these parameters. This randomised control trial study was conducted at the Army Medical College, Rawalpindi, Pakistan, from October 2007 to September 2008, and comprised Sprague Dawley rats. The rats were randomly divided into three groups. The rats in Group 1 were given weekly injections of sodium acetate, and rats of Group 2 and 3 were given weekly injections of lead acetate. Ascorbic acid was supplemented in the drinking water of rats of Group 3. At the end of six weeks, terminal sampling was done and blood obtained was used to assess the serum malondialdehyde levels and red cell parameters. Of the 105 rats, each group had 35(33.33%). The overall mean age was 105±15 days and the mean weight was 225±25gm. The mean malondialdehyde level was 3.2±0.39 µmol /L in Group 1, 7.8±0.48 in Group 2 and 3.8±0.34 in Group 3 (p<0.001). The mean haemoglobin level was 13.16±0.57 g/dL, 10.64±0.86 and 12.22±0.81, respectively (p<0.001). The red blood cells count was 7.63±0.33 106/µL in Group 1, 6.29±0.54 in Group 2 and 6.83±0.45 in Group 3 (p<0.001). Administration of ascorbic acid in drinking water significantly reduced the oxidative stress and anaemia caused by lead intoxication.


Influence of maternal testosterone on the strategies in the open field behaviour of rats.
The purpose of the present study was to characterize the influence of testosterone administered to pregnant females on offsprings postnatal behavioral strategies in the open field. The influence of maternal testosterone on behaviour of 23 day old male and female offsprings was studied in a 20-minute open field test. A total of 9 behavioural events were compared between a control (male n=12, female n=8) and a testosterone group (male n=9, female n=9). Dynamics and patterns of association of these behavioural events were analyzed. The testosterone group was prenatally exposed to testosterone (a single intramuscular injection of 2.5 mg testosteroni isobutyras on gestation day 14). Male offsprings exposed prenatally to testosterone displayed significantly high levels of ambulation (P<0.05), sniffing (P<0.01), sniffing the air (P<0.05), urination (P<0.05) and significantly lower level of vocalization (P<0.05) than control. Female offsprings exposed prenatally to testosterone displayed significantly higher level of sniffing the air (P<0.05) than control. Significant differences in the dynamics of habituation process were registered only in the group of male. They were from 5 to 10 min in ambulation (P<0.05), from 10 to 15 min in sniffing (P<0.05) and vocalization (P<0.05), from 10 to 15 min and from 15 to 20 min in sniffing the air (P<0.05) and from 0 to 5 min in defecation (P<0.05) and urination (P<0.01). Our results suggest that maternal testosterone may influence especially male postnatal open field strategies.


Depression as a contributing factor in cerebrovascular disease.
Stroke is a leading cause of morbidity and mortality in the United States. Physical and psychological impairment from stroke may negatively affect quality of life. From a psychological perspective, depression, which is common in stroke patients, may influence functional recovery and possibly mortality after a stroke. Although somewhat controversial, the risk of poststroke depression may be related to lesion location, specifically left anterior or left basal ganglia lesions. Because poststroke depression can affect recovery, treatment with antidepressants may be warranted. Emerging evidence suggests that nortriptyline and fluoxetine may be effective; paroxetine, sertraline, and other selective serotonin reuptake inhibitors have shown efficacy in treating a related phenomenon known as pathologic crying. The influence of depression on the risk of stroke has not been extensively studied; however, several epidemiologic studies raise the possibility that a relation exists. In one study of elderly individuals, higher depressive symptoms increased the risk of stroke. Many older individuals who have depression develop later in life have evidence of subtle cerebrovascular disease. Specifically, silent strokes that do not involve the sensory or motor parts of the brain are quite common in the elderly population. Vascular depression is depression that occurs in patients with cerebrovascular or ischemic changes in the brain. Preliminary evidence indicates that these vascular changes may be related to atherosclerosis, hypertension, or myocardial infarction. However, additional studies are needed to gain a better profile of these patients and to explore potential treatment modalities.


Genomic and expression analysis of canine calcitonin receptor-stimulating peptides and calcitonin/calcitonin gene-related peptide.
Calcitonin receptor-stimulating peptides (CRSPs) are new members of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family identified in pigs, dogs and other domestic animals, and CRSP-1 is an active ligand for the CT receptor (CT-R). We recently sequenced porcine CRSP genes (Crsps) and found similarity with the CT/CGRP gene (Ct/Cgrp) in sequence and genomic organization. In this study, we identified five Crsps, Crsp-1 to Crsp-5, in dogs. Crsp-1 has five exons with an exon-intron organization identical to that of porcine Crsp-1 or Crsp-2, while Crsp-2 and Crsp-3 have additional CT-2- and CT-3-coding exons like Ct/Cgrp. Crsp-2 was renamed as Ct-2/Crsp-2 because both CRSP-2 and CT-2 mRNAs were tissue-specifically expressed. Crsp-4 and Crsp-5 are presumably generated by retrotransposition. We postulate that Crsps were generated from the gene duplication of Ct/Cgrp, and gained their diversity during mammalian evolution. Among the canine CTs and CRSPs, CRSP-1, CT-1 and CT-2 are active ligands for the CT-R, but CRSP-2 and others are inactive. Canine CRSP-1 and CT-2 are expressed in the central and peripheral systems, while CT-1 is localized in the thyroid gland. These findings indicate that dogs can be used for an experimental model as analysing the physiological roles of the CT/CGRP/CRSP family.


Expression from a betageo gene trap in the Slain1 gene locus is predominantly associated with the developing nervous system.
Slain1 was originally identified as a novel stem cell-associated gene in transcriptional profiling experiments comparing mouse and human embryonic stem cells (ESCs) and their immediate differentiated progeny. In order to obtain further insight into the potential function of Slain1, we examined the expression of beta-galactosidase in a gene-trap mouse line in which a beta-geo reporter gene was inserted into the second intron of Slain1. In early stage embryos (E7.5), the Slain1-betageo fusion protein was expressed within the entire epiblast, but by E9.5 became restricted to the developing nervous system and gastrointestinal tract. In later stage embryos (E11.5 - E13.5), expression was predominantly within the developing nervous system. Lower level expression was also observed in the developing limb buds, in the condensing mesenchyme, along the apical epidermal ridge and, at later stages, within the digital zones. These observations suggest that Slain1 may play a role in the development of the nervous system, as well as in the morphogenesis of several embryonic structures.


Somatic mutations of the protein kinase gene family in human lung cancer.
Protein kinases are frequently mutated in human cancer and inhibitors of mutant protein kinases have proven to be effective anticancer drugs. We screened the coding sequences of 518 protein kinases (approximately 1.3 Mb of DNA per sample) for somatic mutations in 26 primary lung neoplasms and seven lung cancer cell lines. One hundred eighty-eight somatic mutations were detected in 141 genes. Of these, 35 were synonymous (silent) changes. This result indicates that most of the 188 mutations were "passenger" mutations that are not causally implicated in oncogenesis. However, an excess of approximately 40 nonsynonymous substitutions compared with that expected by chance (P = 0.07) suggests that some nonsynonymous mutations have been selected and are contributing to oncogenesis. There was considerable variation between individual lung cancers in the number of mutations observed and no mutations were found in lung carcinoids. The mutational spectra of most lung cancers were characterized by a high proportion of C:G > A:T transversions, compatible with the mutagenic effects of tobacco carcinogens. However, one neuroendocrine cancer cell line had a distinctive mutational spectrum reminiscent of UV-induced DNA damage. The results suggest that several mutated protein kinases may be contributing to lung cancer development, but that mutations in each one are infrequent.


Mutagenesis of FAD2 genes in peanut with CRISPR/Cas9 based gene editing.
Increasing the content of oleic acid in peanut seeds is one of the major goals in peanut breeding due to consumer and industry benefits, such as anti-oxidation and long shelf-life. Homeologous ahFAD2A and ahFAD2B genes encode fatty acid desaturases, which are the key enzymes for converting oleic acid to linoleic acid that oxidizes readily. To date, all high oleic acid peanut varieties result from natural mutations occurred in both genes. A method to induce mutations in the genes of other elite cultivars could speed introgression of this valuable trait. The gene-editing approach utilizing CRISPR/Cas9 technology was employed to induce de novo mutations in the ahFAD2 genes using peanut protoplasts and hairy root cultures as models. The hot spot of natural mutation in these genes was selected as the target region. Appropriate sgRNAs were designed and cloned into a CRISPR/Cas9 expression plasmid. As a result of CRISPR/Cas9 activity, three mutations were identified - G448A in ahFAD2A, and 441_442insA and G451T in ahFAD2B. The G448A and 441_442insA mutations are the same as those seen in existing high oleate varieties and the G451T is new mutation. Because natural mutations appear more often in the ahFAD2A gene than in the ahFAD2B gene in subspecies A. hypogaea var. hypogaea, the mutations induced in ahFAD2B by gene editing may be useful in developing high oleate lines with many genetic backgrounds after validation of oleic acid content in the transformed lines. The appearance of the G448A mutation in ahFAD2A is a further benefit for high oleic acid oil content. Overall, these results showed that mutations were, for the first time, induced by CRISPR-based gene editing approach in peanut. This research demonstrated the potential application of gene editing for mutagenesis in peanut and suggested that CRISPR/Cas9 technology may be useful in the peanut breeding programs.


Bayesian refinement of protein functional site matching.
Matching functional sites is a key problem for the understanding of protein function and evolution. The commonly used graph theoretic approach, and other related approaches, require adjustment of a matching distance threshold a priori according to the noise in atomic positions. This is difficult to pre-determine when matching sites related by varying evolutionary distances and crystallographic precision. Furthermore, sometimes the graph method is unable to identify alternative but important solutions in the neighbourhood of the distance based solution because of strict distance constraints. We consider the Bayesian approach to improve graph based solutions. In principle this approach applies to other methods with strict distance matching constraints. The Bayesian method can flexibly incorporate all types of prior information on specific binding sites (e.g. amino acid types) in contrast to combinatorial formulations. We present a new meta-algorithm for matching protein functional sites (active sites and ligand binding sites) based on an initial graph matching followed by refinement using a Markov chain Monte Carlo (MCMC) procedure. This procedure is an innovative extension to our recent work. The method accounts for the 3-dimensional structure of the site as well as the physico-chemical properties of the constituent amino acids. The MCMC procedure can lead to a significant increase in the number of significant matches compared to the graph method as measured independently by rigorously derived p-values. MCMC refinement step is able to significantly improve graph based matches. We apply the method to matching NAD(P)(H) binding sites within single Rossmann fold families, between different families in the same superfamily, and in different folds. Within families sites are often well conserved, but there are examples where significant shape based matches do not retain similar amino acid chemistry, indicating that even within families the same ligand may be bound using substantially different physico-chemistry. We also show that the procedure finds significant matches between binding sites for the same co-factor in different families and different folds.


Endovascular treatment of high-flow carotid cavernous fistulas by stent-assisted coil placement.
Endovascular techniques are the methods of choice for the treatment of patients with carotid cavernous fistulas. We report our experience using stent-assisted coil placement for treatment of patients with high-flow fistulas that are associated with severe laceration of the internal carotid artery. In a retrospective review of an internal endovascular therapy database covering the interval between October 2001 and October 2003, we identified a total of 5 patients presenting with 6 high-flow type A carotid cavernous fistulas (one had a bilateral fistula) that were associated with severe laceration of the internal carotid artery. All were treated first with stenting of the injured segment of the internal carotid artery followed by transarterial (3/6) and/or transvenous (4/6) obliteration of the fistula with detachable platinum coils. In 2 cases, a liquid adhesive was also used. In all instances, a compliant balloon was inflated within the stented arterial segment during coil deposition to avoid extension of coils into the parent artery. All 6 fistulas were obliterated, and each internal carotid artery was successfully reconstructed. Except for posttraumatic cranial nerve dysfunction in 1 patient, clinical outcome was very good. Follow-up angiograms in 3 of the 6 patients obtained at intervals between 3 and 6 months (mean, 4.5 months) revealed no fistula recurrence and no evidence of intimal hyperplasia within the stent. In this series of patients with high-flow carotid cavernous fistula associated with severe injury to the internal carotid artery, stent-assisted coil placement offered a safe and effective treatment. Stent-assisted coil placement may increase the ability to successfully treat fistulas with severe injury to the internal carotid artery with preservation of the parent artery.


Collaborative health care information system development through sharable infrastructure, services, and paradigms.
The Decision Systems Group has focused for several years on software architectures and software engineering approaches to support collaborative development for health care information systems. The goal is to be able to more readily develop complex applications that require integration of a variety of information resources. Our efforts are aimed at four primary capabilities: (1) a software environment, Arachne, for developing applications by incorporation of components created by disparate developers, developing component classes, for providing cross-platform graphical user interface support with remote rendering, and incorporating evolving software engineering standards; (2) a library of domain-specific components for medical applications; (3) a user interaction paradigm that provides a framework for applications that integrate both clinical data and other information resources for education and decision support; and (4) improved understanding of the collaborative process per se and the development of methodologies to support it.


Computer-aided Volumetry of Part-Solid Lung Cancers by Using CT: Solid Component Size Predicts Prognosis.
Purpose To investigate the relationship between the postoperative prognosis of patients with part-solid non-small cell lung cancer and the solid component size acquired by using three-dimensional (3D) volumetry software on multidetector computed tomographic (CT) images. Materials and Methods A retrospective study by using preoperative multidetector CT data with 0.5-mm section thickness, clinical records, and pathologic reports of 96 patients with primary subsolid non-small cell lung cancer (47 men and 49 women; mean age ± standard deviation, 66 years ± 8) were reviewed. Two radiologists measured the two-dimensional (2D) maximal solid size of each nodule on an axial image (hereafter, 2D MSSA), the 3D maximal solid size on multiplanar reconstructed images (hereafter, 3D MSSMPR), and the 3D solid volume of greater than 0 HU (hereafter, 3D SV0HU) within each nodule. The correlations between the postoperative recurrence and the effects of clinical and pathologic characteristics, 2D MSSA, 3D MSSMPR, and 3D SV0HU as prognostic imaging biomarkers were assessed by using a Cox proportional hazards model. Results For the prediction of postoperative recurrence, the area under the receiver operating characteristics curve was 0.796 (95% confidence interval: 0.692, 0.900) for 2D MSSA, 0.776 (95% confidence interval: 0.667, 0.886) for 3D MSSMPR, and 0.835 (95% confidence interval: 0.749, 0.922) for 3D SV0HU. The optimal cutoff value for 3D SV0HU for predicting tumor recurrence was 0.54 cm3, with a sensitivity of 0.933 (95% confidence interval: 0.679, 0.998) and a specificity of 0.716 (95% confidence interval: 0.605, 0.811) for the recurrence. Significant predictive factors for disease-free survival were 3D SV0HU greater than or equal to 0.54 cm3 (hazard ratio, 6.61; P = .001) and lymphatic and/or vascular invasion derived from histopathologic analysis (hazard ratio, 2.96; P = .040). Conclusion The measurement of 3D SV0HU predicted the postoperative prognosis of patients with part-solid lung cancer more accurately than did 2D MSSA and 3D MSSMPR. © RSNA, 2018.


Single dose trimethoprim-sulphamethoxazole treatment of symptomatic urinary infection.
Seventy-nine children with symptoms of urinary tract infections were randomly allocated to treatment with a single dose or a 7-day course of trimethoprim-sulphamethoxazole. Of the 42 patients (39 girls, 3 boys) who fulfilled the criteria for the trial, 23 were given a single-dose regimen and 19 of them a 7-day regimen. Both groups of patients had sterile urine cultures 2 days after starting treatment. Eight patients had underlying structural renal abnormalities (n = 3, single-dose regimen; n = 5, 7-day regimen). One patient in the single dose group had a recurrence of infection on day 7. These results show that single dose trimethoprim-sulphamethoxazole is as effective as the conventional 7-day course in children with symptomatic urinary tract infection. Further investigation of the renal tract is necessary regardless of the fact that the infection has been eradicated by single-dose treatment.


The rationale of surgical pulmonary vein isolation for treatment of atrial fibrillation.
With the development of less invasive surgical approaches and new ablation techniques, surgical treatment of atrial fibrillation has gained increasing interest over the past decade. Contrary to the complex Maze procedure, new less laborious approaches with pulmonary vein isolation as the main focus are within the reach of most cardiothoracic surgeons. However, although important new pathophysiological mechanisms have emerged in recent years due to extensive basic and clinical research, several uncertainties and hurdles concerning this treatment modality remain. This article reviews the rationale of surgical pulmonary vein isolation, based on these increased insights. Furthermore, important technical aspects including the possible advantages of an epicardial approach, the optimal left-sided lesion set and the need for transmurality are discussed in depth.


Effects of simulated acid rain on the pollen germination and pollen tube growth of apple (Malus sylvestris Miller cv. Golden).
The pollens of apple flowers have been treated with simulated acid rain solutions in range of pHs 2.9 to 5.0 in order to determine the threshold proportion values that lead the observed symptoms of detriments of acid rain. Compared to controls (pH 6.5), pollen germination decreased by 41.75% at pH 3.3 and pollen tube elongation decreased by 24.3% at pH 3.4. Acid rain threshold proportion value was around pH 3.3 and 3.4 for apple pollen germination and pollen tube elongation, respectively. Furthermore, pollen tube elongation was determined to be more sensitive to acid rain than pollen germination. The pH values below 3.1 resulted in complete destruction of pollen tubes. Pollen germination entirely stopped at around pH 3.0. Finally, it has been shown that the acid rain has a blocking effect on pollen germination and pollen tube elongation in apple. The conclusion is that not only pH value but also the quantity of acid rain is important factor in germination. The results were found statistically significant through the LSD test at levels of p < 0.05 and p < 0.01.


Increase in cell mass during the division cycle of Escherichia coli B/rA.
Increase in the mean cell mass of undivided cells was determined during the division cycle of Escherichia coli B/rA. Cell buoyant densities during the division cycle were determined after cells from an exponentially growing culture were separated by size. The buoyant densities of these cells were essentially independent of cell age, with a mean value of 1.094 g ml-1. Mean cell volume and buoyant density were also determined during synchronous growth in two different media, which provided doubling times of 40 and 25 min. Cell volume and mass increased linearly at both growth rates, as buoyant density did not vary significantly. The results are consistent with only one of the three major models of cell growth, linear growth, which specifies that the rate of increase in cell mass is constant throughout the division cycle.


Study of socio-demographic and health status of the people of Duwakot VDC, Bhaktapur district.
To know the population pattern, socio-economic status, socio cultural aspect and common prevailing disease of the Duwakot VDC of Bhaktapur district. This is a cross sectional descriptive study. Out of total 206 household, only 120 houses were purposively selected for the survey. A set of semi-structured questionnaire was administered to the representative member of the sample households. Report obtained from the household survey, ward no. 3 and 4 of Duwakot, the total population of 120 household was found to be 658 and out of that male population was 329 and female population was also 329. That means 50% of population was male and 50% of population was female. Family size refers to the total number of people in the family. The family size depends upon numerous factors like duration of marriage, education of the people. Family planning services will promote the democratic principle that individuals be free to make choices for themselves. It is clear from the table that the more number of males than female respondents knew the family planning methods. Family planning helps not only to attain birth control, proper spacing and limitation of birth but also reduce the population growth and improve over all maternal and child health status including socio economic status. Out of 43 children, BCG, DPT, polio was taken by all children whereas 38 (88.4%) children had taken measles vaccine due to the age less than 9 months and only 5 (11.6%) children were found taken hepatitis B vaccine. It may be due to new invention.


RN to BSN Students' Experiences With Asynchronous Audio-Video Discussion Responses.
Literature suggests use of audio-video (AV) technology enhances a sense of connectedness between students in online programs. In a previous quantitative study conducted by these authors, the use of AV discussion responses revealed that social presence was negatively impacted. This descriptive study explored RN to BSN students' experiences with AV discussion formats. Participants found value related to forming distinct impressions of others but expressed feelings of distress; they described issues with technology and time as barriers. Implications suggest that AV format is not supported for use in every discussion forum but may be of value if limited to select discussion forums.


Fate of urine nitrogen in three soils throughout a grazing season.
The fate of 15N-labeled cattle (Bos taurus) urine (52 g N m(-2)), applied to a 0.4-m2 surface area on three dates between May and October to three different pasture soils, was studied using 2-m2 lysimeters. Over a period of two years, the sward recovered most of the 15N, but the amount recovered decreased with application date (62% in spring to 17% in fall). However, N uptake by ryegrass (Lolium perenne L.) in Year 2 showed that some nitrogen came from the previous year's urine application. The largest leaching losses of urine N resulted from the late application date. These losses mainly occurred during the first winter despite the small amount of water drainage. Soil type largely determined 15N losses. The granitic Brunisol was the most freely draining and had the greatest leaching (up to 35% recovery of urinary N). In contrast, leaching in the silty loam Neoluvisol remained under 4% of 15N applied. The Calcosol appeared to be susceptible to all kinds of N losses with intermediate unaccounted-for N pool and leaching fractions and lesser utilization of urinary N by grass. Immobilization in soil organic matter, roots and litter, and stubble pools were not markedly influenced by the date of application or soil type. They amounted to 25 to 33, 2, and 2% of N applied as urine, respectively. In these climatic conditions with moderate drainage, leaching of water poor in quality for nitrate only occurred for late-season grazing or on the granitic Brunisol, which was very vulnerable to leaching.


The NHLBI Study on Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC): Design and Objectives.
The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. This multicenter observational cohort study will enroll at least 600 patients <21 years old who meet the Centers for Disease Control and Prevention case definition of MIS-C across multiple North American centers over 2 years. The study will collect detailed hospital and follow-up data for up to 5 years, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF) <45% during the acute illness. The primary outcomes are the worst LVEF and the highest coronary artery z-score of the left anterior descending or right coronary artery. Other outcomes include occurrence and course of non-cardiac organ dysfunction, inflammation, and major medical events. Independent adjudication of cases will classify participants as definite, possible, or not MIS-C. Analysis of the outcomes will include descriptive statistics and regression analysis with stratification by definite or possible MIS-C. The MUSIC study will provide phenotypic data to support basic and translational research studies. The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.


[Intensive therapy in complicated forms of purulent gestational pyelonephritis].
The experience with 65 cases of purulent gestational pyelonephritis (PGP) is reviewed. The efficacy of PGP intensive therapy depends on early surgical elimination of the source of bacteriemia and sepsis. Choice of the surgical technique should be based both on extension of destructive changes in the kidney and severity of the complications. In some cases it is necessary to perform nephrostomy with sanation of the pyonecrotic foci in the kidney, in the other--it is necessary to perform urgent nephrectomy. Three basic components of pre- and postoperative intensive care should be considered: antibacterial treatment, infusion-transfusion therapy and efferent detoxication. Etiotropic therapy is conducted with three antibiotics injected intravenously and intramuscularly to provide effective concentrations of the drugs in the blood, urine and affected organs. PGP medication is based on inhibitor-defended penicillines and cephalosporines of the third-forth generation. Combined use of these antibiotics is effective in 95% cases. If the condition is life-threatening, carbapenems, fluoroguinolones, aminoglycosides and metronidasol can be applied. Detoxication is provided by 24-h infusion of crystalloids, concentrated glucose solutions (10-20%) with insulin, transfusion of fresh frozen plasm, albumin, protein. Plasmapheresis accelerates recovery, diminished nephrectomy rate by 14% and obstetric complications 1.8 fold, enables physiological term of delivery (37-39 weeks) in significant reduction of postnatal complications. Lethal outcomes were absent.


Influence of microvascular mandibular bony reconstruction on the posterior airway space: A retrospective cohort study.
The posterior airway space (PAS) is a common site of passive obstructions with high morbidity. Surgical changes to the craniomandibular system may affect the PAS. Data regarding the effects of mandibular reconstruction using vascularized bone flaps on PAS are insufficient. This retrospective cohort study aimed to investigate changes in PAS after mandibular reconstruction. Pre- and post-reconstructive computed tomography scans of 40 patients undergoing segmental mandibulectomy and mandibular reconstruction with deep circumflex iliac artery or fibula flaps were analyzed. Absolute differences in PAS geometry and relative trends of PAS volume changes were compared within the study population and between subgroups formed according to the extent of resection, timing and type of reconstruction, and presence of pre-reconstructive radiotherapy. Irradiated patients were characterized by an increase in PAS volume after reconstruction. Absolute differences in total PAS volume after reconstruction were significantly different (p = 0.024) compared to non-irradiated patients. Reconstruction of central mandible segments resulted in decrease of the cross-sectional PAS areas. Absolute differences in middle cross-sectional PAS area after reconstruction were significantly different (p = 0.039) compared to non-central reconstructions. Patients who received radiotherapy were less likely to show a total PAS volume reduction after reconstruction (OR: 0.147; p = 0.007), with values adjusted for gender, age, body mass index, timing and type of reconstruction, and transplant length. Mandibular reconstruction causes changes in PAS geometry. Specifically, reconstructions of central mandibular segments can lead to a reduction in the cross-sectional areas of PAS, and mandibular reconstructions in irradiated sites may cause an increase in PAS volume.


Characterization of a Synechococcus sp. strain PCC 7002 mutant lacking Photosystem I. Protein assembly and energy distribution in the absence of the Photosystem I reaction center core complex.
A Synechococcus sp. strain PCC 7002 ΔpsaAB::cat mutant has been constructed by deletional interposon mutagenesis of the psaA and psaB genes through selection and segregation under low-light conditions. This strain can grow photoheterotrophically with glycerol as carbon source with a doubling time of 25 h at low light intensity (10 μE m(-2) s(-1)). No Photosystem I (PS I)-associated chlorophyll fluorescence emission peak was detected in the ΔpsaAB::cat mutant. The chlorophyll content of the ΔpsaAB::cat mutant was approximately 20% that of the wild-type strain on a per cell basis. In the absence of the PsaA and PsaB proteins, several other PS I proteins do not accumulate to normal levels. Assembly of the peripheral PS I proteins PsaC,PsaD, PsaE, and PsaL is dependent on the presence of the PsaA and PsaB heterodimer core. The precursor form of PsaF may be inserted into the thylakoid membrane but is not processed to its mature form in the absence of PsaA and PsaB. The absence of PS I reaction centers has no apparent effect on Photosystem II (PS II) assembly and activity. Although the mutant exhibited somewhat greater fluorescence emission from phycocyanin, most of the light energy absorbed by phycobilisomes was efficiently transferred to the PS II reaction centers in the absence of the PS I. No light state transition could be detected in the ΔpsaAB::cat strain; in the absence of PS I, cells remain in state 1. Development of this relatively light-tolerant strain lacking PS I provides an important new tool for the genetic manipulation of PS I and further demonstrates the utility of Synechococcus sp. PCC 7002 for structural and functional analyses of the PS I reaction center.


Synthesis and in vitro and in vivo evaluation of 18F-labeled positron emission tomography (PET) ligands for imaging the vesicular acetylcholine transporter.
A new class of vesicular acetylcholine transporter inhibitor that incorporates a carbonyl group into the benzovesamicol structure was synthesized, and analogues were evaluated in vitro. (+/-)-trans-2-Hydroxy-3-(4-(4-[(18)F]fluorobenzoyl)piperidino)tetralin (9e) has K(i) values of 2.70 nM for VAChT, 191 nM for sigma(1), and 251 nM for sigma(2). The racemic precursor (9d) was resolved via chiral HPLC, and (+/-)-[(18)F]9e, (-)-[(18)F]9e, and (+)-[(18)F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [(18)F]/F(-) and Kryptofix/K(2)CO(3) in DMSO with radiochemical yields of approximately 50-60% and specific activities of >2000 mCi/micromol. (-)-[(18)F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat striatum and a striatum/cerebellum ratio of 1.88 at 30 min postinjection (p.i.). MicroPET imaging of macaques demonstrated a 2.1 ratio of (-)-[(18)F]9e in putamen versus cerebellum at 2 h p.i. (-)-[(18)F]9e has potential to be a PET tracer for clinical imaging of the VAChT.


Regulation of expression of the paralogous Mlp family in Borrelia burgdorferi.
The Mlp (multicopy lipoproteins) family is one of many paralogous protein families in Borrelia burgdorferi. To examine the extent to which the 10 members of the Mlp family in B. burgdorferi strain 297 might be differentially regulated, antibodies specific for each of the Mlps were developed and used to analyze the protein expression profiles of individual Mlps when B. burgdorferi replicated under various cultivation conditions. All of the Mlps were upregulated coordinately when B. burgdorferi was cultivated at either elevated temperature, reduced culture pH, or increased spirochete cell density. Inasmuch as the expression of OspC is influenced by a novel RpoN-RpoS regulatory pathway, similar induction patterns for OspC and the Mlp paralogs prompted an assessment of whether the RpoN-RpoS pathway also was involved in Mlp expression. In contrast to wild-type B. burgdorferi, both RpoN- and RpoS-deficient mutants were unable to upregulate OspC or the Mlp paralogs when grown at lower pH (6.8), indicating that pH-mediated regulation of OspC and Mlp paralogs is dependent on the RpoN-RpoS pathway. However, when RpoN- or RpoS-deficient mutants were shifted from 23 degrees C to 37 degrees C or were cultivated to higher spirochete densities, some induction of the Mlps still occurred, whereas OspC expression was abolished. The combined findings suggest that the Mlp paralogs are coordinately regulated as a family and have an expression profile similar, but not identical, to that of OspC. Although Mlp expression as a family is influenced by the RpoN-RpoS regulatory pathway, there exists at least one additional layer of gene regulation, yet to be elucidated, contributing to Mlp expression in B. burgdorferi.


Effect of Nutritional Intervention on the Management of Radiotherapy and Chemotherapy for Nasopharyngeal Carcinoma.
To investigate the application of nutritional intervention in the management of radiotherapy and chemotherapy for nasopharyngeal carcinoma. There were 60 patients with nasopharyngeal carcinoma who were treated with chemoradiotherapy in our department from June 2020 to August 2022, including 30 subjects from the control group and 30 cases from the intervention group. (1) In 2002, the 3-week and 24-week NRS scores for radiotherapy and chemotherapy in the control group were higher than those in the intervention group (2.36 ± 0.85 and 1.86 ± 0.57, p = 0.014; 2.76 ± 0.77 and 2.43 ± 0.77, p = 0.023), and the difference was statistically significant (p < 0.05) (Table 2). (2) The weight of patients in the two groups after 3 wk and 24 wk of radiotherapy and chemotherapy were compared, and we found that the weights of the control group were lower than those of the intervention group (66.13 ± 5.53 and 69.03 ± 5.22, p = 0.037; 61.03 ± 5.83 and 64.93 ± 6.85, p = 0.044), and again, the difference was statistically significant (p < 0.05) (Table 3). At week 10 of chemoradiotherapy, the control group lost ≥10% of their weight in the intervention group, and severe malnutrition occurred. The control group lost ≥5% of their weight at 24 wk of chemoradiotherapy and developed malnutrition. (3) The quality of life (measured by the SF-36 scale score) after 24 wk between the two groups was compared, and the control group was lower than the intervention group in all aspects, and this difference was statistically significant (p < 0.05) (Table 4). Nutritional intervention is used in the whole management of radiotherapy and chemotherapy for nasopharyngeal carcinoma to improve patient nutritional status and quality of life.


Forecasting the 2017/2018 seasonal influenza epidemic in England using multiple dynamic transmission models: a case study.
Since the 2009 A/H1N1 pandemic, Public Health England have developed a suite of real-time statistical models utilising enhanced pandemic surveillance data to nowcast and forecast a future pandemic. Their ability to track seasonal influenza and predict heightened winter healthcare burden in the light of high activity in Australia in 2017 was untested. Four transmission models were used in forecasting the 2017/2018 seasonal influenza epidemic in England: a stratified primary care model using daily, region-specific, counts and virological swab positivity of influenza-like illness consultations in general practice (GP); a strain-specific (SS) model using weekly, national GP ILI and virological data; an intensive care model (ICU) using reports of ICU influenza admissions; and a synthesis model that included all data sources. For the first 12 weeks of 2018, each model was applied to the latest data to provide estimates of epidemic parameters and short-term influenza forecasts. The added value of pre-season population susceptibility data was explored. The combined results provided valuable nowcasts of the state of the epidemic. Short-term predictions of burden on primary and secondary health services were initially highly variable before reaching consensus beyond the observed peaks in activity between weeks 3-4 of 2018. Estimates for R0 were consistent over time for three of the four models until week 12 of 2018, and there was consistency in the estimation of R0 across the SPC and SS models, and in the ICU attack rates estimated by the ICU and the synthesis model. Estimation and predictions varied according to the assumed levels of pre-season immunity. This exercise successfully applied a range of pandemic models to seasonal influenza. Forecasting early in the season remains challenging but represents a crucially important activity to inform planning. Improved knowledge of pre-existing levels of immunity would be valuable.


Optical fiber refractometer based on cladding-mode Bragg grating.
We demonstrate an optical fiber refractometer based on a cladding-mode Bragg grating. It consists of a long-period grating (LPG) followed by a fiber Bragg grating (FBG). The LPG partially couples light from the core mode to a cladding mode, both of which are reflected by the FBG. Part of the cladding mode reflection is coupled back to the core mode through the original LPG and used for refractive index sensing. The core mode reflection is used to compensate for the temperature cross sensitivity of the refractometer. The sensors operate in the reflection mode and can be multiplexed on a fiber in wavelength domain.


The Saccharomyces cerevisiae SRK1 gene, a suppressor of bcy1 and ins1, may be involved in protein phosphatase function.
The Saccharomyces cerevisiae SRK1 gene, when expressed on a low-copy shuttle vector, partially suppresses the phenotype associated with elevated levels of cyclic AMP-dependent protein kinase activity and suppresses the temperature-sensitive cell cycle arrest of the ins1 mutant. SRK1 is located on chromosome IV, 3 centimorgans from gcn2. A mutant carrying a deletion mutation in srk1 is viable. SRK1 encodes a 140-kDa protein with homology to the dis3+ protein from Schizosaccharomyces pombe. The ability of SRK1 to alleviate partially the defects caused by high levels of cyclic AMP-dependent protein kinase and the similarity of its encoded protein to dis3+ suggest that SRK1 may have a role in protein phosphatase function.


The case for visual analytics of arsenic concentrations in foods.
Arsenic is a naturally occurring toxic metal and its presence in food could be a potential risk to the health of both humans and animals. Prolonged ingestion of arsenic contaminated water may result in manifestations of toxicity in all systems of the body. Visual Analytics is a multidisciplinary field that is defined as the science of analytical reasoning facilitated by interactive visual interfaces. The concentrations of arsenic vary in foods making it impractical and impossible to provide regulatory limit for each food. This review article presents a case for the use of visual analytics approaches to provide comparative assessment of arsenic in various foods. The topics covered include (i) metabolism of arsenic in the human body; (ii) arsenic concentrations in various foods; (ii) factors affecting arsenic uptake in plants; (ii) introduction to visual analytics; and (iv) benefits of visual analytics for comparative assessment of arsenic concentration in foods. Visual analytics can provide an information superstructure of arsenic in various foods to permit insightful comparative risk assessment of the diverse and continually expanding data on arsenic in food groups in the context of country of study or origin, year of study, method of analysis and arsenic species.


Limiting amino acids for growing Holstein steers limit-fed soybean hull-based diets.
Studies were conducted to determine limiting amino acids (AA) for cattle limit-fed soybean hull-based diets. Ruminally cannulated Holstein steers were maintained in metabolism crates, fed the same basal diet (73% soyhulls, 19% alfalfa, DM basis), and given the same intraruminal infusions (400 g/d acetate; to supply energy without increasing microbial protein supply). Treatments were infused abomasally. In Exp. 1, steers (200 kg) were provided 1) water, 2) 10 g/d of methionine (MET), or 3) a mixture of 10 essential AA (10AA). Nitrogen retention (13.7 g/d) was greatest (P < .05) for steers receiving 10AA. Steers receiving MET (7.9 g/d) had greater (P < .05) N retention than control steers (5.4 g/d). In Exp. 2, steers (200 kg) were provided 10AA or 10AA with L-Lys deleted from the mixture. Steers receiving 10AA tended (P < .09) to have greater N retention (19.0 g/d) than those receiving no lysine (16.3 g/d). In Exp. 3, steers (194 kg) were provided 10AA or 10AA with L-Thr deleted from the mixture. Nitrogen retention was not affected by removal of threonine. In Exp. 4, steers (152 kg) were provided 10AA or 10AA with L-His, L-Trp, L-Arg, L-Phe, or branched-chain AA (L-Leu, L-Ile, and L-Val) removed. Nitrogen retention was reduced (P < .05) by removal of either L-His or the branched-chain AA. For steers limit-fed soybean hull-based diets, methionine was first-limiting; histidine, at least one of the branched-chain AA, and possibly lysine were also limiting.


RNA misfolding and the action of chaperones.
RNA folds to a myriad of three-dimensional structures and performs an equally diverse set of functions. The ability of RNA to fold and function in vivo is all the more remarkable because, in vitro, RNA has been shown to have a strong propensity to adopt misfolded, non-functional conformations. A principal factor underlying the dominance of RNA misfolding is that local RNA structure can be quite stable even in the absence of enforcing global tertiary structure. This property allows non-native structure to persist, and it also allows native structure to form and stabilize non-native contacts or non-native topology. In recent years it has become clear that one of the central reasons for the apparent disconnect between the capabilities of RNA in vivo and its in vitro folding properties is the presence of RNA chaperones, which facilitate conformational transitions of RNA and therefore mitigate the deleterious effects of RNA misfolding. Over the past two decades, it has been demonstrated that several classes of non-specific RNA binding proteins possess profound RNA chaperone activity in vitro and when overexpressed in vivo, and at least some of these proteins appear to function as chaperones in vivo. More recently, it has been shown that certain DExD/H-box proteins function as general chaperones to facilitate folding of group I and group II introns. These proteins are RNA-dependent ATPases and have RNA helicase activity, and are proposed to function by using energy from ATP binding and hydrolysis to disrupt RNA structure and/or to displace proteins from RNA-protein complexes. This review outlines experimental studies that have led to our current understanding of the range of misfolded RNA structures, the physical origins of RNA misfolding, and the functions and mechanisms of putative RNA chaperone proteins.


Prevalence, correlates, and course of minor depression and major depression in the National Comorbidity Survey.
Data from the National Comorbidity Survey are used to study the lifetime prevalences, correlates, course and impairments associated with minor depression (mD), major depression 5-6 symptoms (MD 5-6), and major depression with seven or more symptoms (MD 7-9) in an effort to determine whether mD is on a continuum with MD. There is a monotonic increase in average number of episodes, average length of longest episode, impairment, comorbidity, and parental history of psychiatric disorders as we go from mD to Md 5-6 to MD 7-9. In most of these cases, though, the differences between mD and MD 5-6 are no longer than the differences between MD 5-6 and MD 7-9, arguing for continuity between mD and MD. Coupled with the finding from earlier studies that subclinical depression is a significant risk factor for major depression, these results argue that minor depression is a variant of depressive disorder that should be considered seriously both as a target for preventive intervention and for treatment. The paper closes with suggestions regarding the analysis of mD subtypes in future longitudinal studies.


Increasing the effectiveness of contraceptive usage in university students.
Prevention of pregnancy requires correct and consistent use of an effective method of contraception and knowledge alone is not sufficient to ensure such use, as many complex social and behavioral factors influence contraceptive behavior. Women are particularly likely to change their contraceptive method after a contraceptive 'shock'. In this study, the change in contraceptive behavior of a group of university students who presented for emergency contraception is studied. Each student participated in a single individualized educational session. A total of 465 women requested emergency contraception in a 3.5-year period at a large student health center. Of these, 24% had not previously used contraception, 50% had previously used condoms and 25% had taken the pill (COC). Of those who usually used condoms, 79% had had a condom accident and 21% had not used them at the last intercourse. Only 30% of COC users had had a problem with the pill and the remaining 70% were not taking it at the time of last intercourse, for social rather than medical reasons. Follow-up is available for 309 (66.5%). Paired-sample analysis of these women shows a decrease in the number using no contraception (22% to 8%), and an increase in the number using COCs (33% to 66%). These changes reached statistical significance (p < 0.0001). University students, despite their intelligence, exhibit a high degree of risk-taking behavior but become more effective contraceptive users after an interactive counselling session following a contraceptive scare.


An illuminated grid for macular testing.
The status of the macula should be included in the preoperative evaluation of patients about to undergo keratoplasty or cataract extraction. Frequently, corneal opacities or cataracts preclude visualization of macular details. In such cases, the Amsler grid is useful in assessing macular function. This study evaluated 15 patients with opaque media. In 13 patients, the opacity was too dense to allow the patient to see the Amsler grid. However, all 13 patients could see the illuminated version of the grid. Of the three abnormal responses detected by the use of the illuminated grid, two were caused by macular pathology and one by amblyopia.


Non-parametric combination analysis of multiple data types enables detection of novel regulatory mechanisms in T cells of multiple sclerosis patients.
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system with prominent neurodegenerative components. The triggering and progression of MS is associated with transcriptional and epigenetic alterations in several tissues, including peripheral blood. The combined influence of transcriptional and epigenetic changes associated with MS has not been assessed in the same individuals. Here we generated paired transcriptomic (RNA-seq) and DNA methylation (Illumina 450 K array) profiles of CD4+ and CD8+ T cells (CD4, CD8), using clinically accessible blood from healthy donors and MS patients in the initial relapsing-remitting and subsequent secondary-progressive stage. By integrating the output of a differential expression test with a permutation-based non-parametric combination methodology, we identified 149 differentially expressed (DE) genes in both CD4 and CD8 cells collected from MS patients. Moreover, by leveraging the methylation-dependent regulation of gene expression, we identified the gene SH3YL1, which displayed significant correlated expression and methylation changes in MS patients. Importantly, silencing of SH3YL1 in primary human CD4 cells demonstrated its influence on T cell activation. Collectively, our strategy based on paired sampling of several cell-types provides a novel approach to increase sensitivity for identifying shared mechanisms altered in CD4 and CD8 cells of relevance in MS in small sized clinical materials.