The effect of chiropractic manipulation on salivary cortisol levels.
The stress response in humans is a healthy response and is necessary for life. The effects of chiropractic manipulation (CM), if any, on stress are ill-defined. Cortisol has been used as an accurate measure of the stress response system in humans. Salivary cortisol is a noninvasive technique to accurately quantify biologically active cortisol. To determine whether basal salivary cortisol levels can be properly detected and whether CM has any direct effect on basal salivary cortisol levels in humans. Subjects were adult male students attending a chiropractic college. Salivary samples were collected for 5 weeks. During Week 1, samples were collected by the students at home upon waking. During Weeks 2 through 5, home samples were collected upon waking and were followed by an additional time course of samples collected in a laboratory setting before and after CM. Salivary cortisol was measured by enzyme-linked immunoassay. Chiropractic manipulative therapy did not significantly change basal salivary cortisol levels. The time course of acute changes to cortisol levels was independent of testing week and group. A decrease in salivary cortisol was detected over time on each trial testing day. Overall, cortisol levels significantly decreased from the time of the home samples until the pretreatment laboratory measurement (P <.05). Cortisol levels subsequently decreased from pretreatment to 15 minutes after treatment (P <.05). After treatment, there were progressive decreases in cortisol levels from the 15- and 30-minute time points to the 60-minute time point (P <.05). The results of this pilot study suggest that there is no effect of CM on salivary cortisol levels in asymptomatic subjects. As such, we conclude that neither the anticipation of CM nor the spinal manipulative procedure itself induces a state of stress or anxiety.


The possibility of latent centromeres and a proposed nomenclature system for total chromosome and whole arm translocations.
Translocations involving entire chromosomes or whole chromosome arms may not necessarily require deletion of a centromere. Conceivably, in the process of centromeric or telomeric fusion or of fusion of a centromere with a telomere, centromeric inactivation may occur, thus preserving both centromeres--one functional, the other latent--in the resultant translocation chromosome. If such latent centromeres exist and, in addition, are capable of being reactivated, it would explain how additional functional centromeres are acquired in the reverse process of chromosomal fission or fragmentation. A system of nomenclature is proposed for identifying the origin and nature of these chromosomal rearrangements.


Part and Parcel: A Qualitative Interview Study Examining the Experience of Client Rudeness by Mental Health Workers.
Considerable research has demonstrated that workplace rudeness can have a variety of negative consequences. However, although research has examined the impact of patient aggression, no research has examined patient or client rudeness towards those who work in mental health roles. The present study investigated the nature of client rudeness, how mental health workers respond and the coping strategies used. Eighteen participants from a range of mental health roles and experience levels participated in semi-structured interviews based on their experience of client rudeness. Thematic analysis revealed that participants experienced a variety of client behaviours they classified as rude, the majority of which were verbal. Reasons for rudeness included the client's personal history, mood, and mental health, and as such rudeness was conceptualised as simply a part of the job. Client rudeness was found to have both negative and positive outcomes on a range of areas including work and client relationships. Participants identified supervisors and colleagues as key sources of support for coping with rudeness. These findings suggest that rudeness is "part and parcel" of a mental health practitioner's role. Supervisor support and further training are recommended to help practitioners deal with rudeness in practice.


An experimental design based quantitative structure-activity relationship study on beta-adrenergic blocking agents using PLS.
Quantitative structure-activity relationships for some beta-adrenergic blocking agents of phenoxyaminopropanol type are established with the PLS method. The basic model is based on a carefully selected training set using experimental design techniques.


Effects of 3 sequestering agents on milk aflatoxin M1 concentration and the performance and immune status of dairy cows fed diets artificially contaminated with aflatoxin B1.
This study examined whether adding 3 mycotoxin-sequestering agents to diets contaminated with aflatoxin B1 (AFB1) would reduce milk aflatoxin M1 (AFM1) concentration, and improve the performance and alter immune status of dairy cows. Fifteen lactating dairy cows were used in an experiment with an incomplete crossover design including four 28-d periods. Treatments included a control diet (C), a toxin diet (T; 1,725µg of AFB1/head per day; 75µg/kg), and diets containing the toxin and 20g/head per day of a proprietary mixture of Saccharomyces cerevisiae fermentation product containing a low (SEQ1) or high (SEQ2) dose of a chlorophyll-based additive, or a low dose of the chlorophyll-based additive and sodium bentonite clay (SEQ3). Sequestering agents were top-dressed on the total mixed ration (TMR) daily in each period, and AFB1 was dosed orally in gelatin capsules before the TMR was fed on d 21 to 25. Milk was sampled twice daily on d 20 to 28 and plasma was sampled on d 20 and 25. Sequestering agents did not affect milk AFM1 concentration during the toxin-dosing period. However, after AFB1 was withdrawn, the sequestering agents reduced the time required (24 vs. 48h) to reduce the milk AFM1 concentration below the Food and Drug Administration action level of 0.5µg/kg. Feeding T instead of C tended to reduce milk and fat-corrected milk yields, but feeding SEQ1 prevented these effects. Red blood cell count and hemoglobin concentration were reduced by feeding T instead of C, but not by feeding SEQ1, SEQ2, or SEQ3. The mean fluorescence intensity of antibody staining for 2 leukocyte adhesion molecules, L-selectin (CD62L) and β-integrin (CD18), tended to be greatest when SEQ1 and SEQ3 were fed. Plasma acid-soluble protein concentration was decreased by feeding SEQ1, SEQ2, and SEQ3 instead of T. Sequestering agents had no effect on milk AFM1 concentration, but they reduced the time required to reduce milk AFM1 concentration to a safe level after withdrawal of AFB1 from the diet. Only SEQ1 prevented the adverse effects of AFB1 on milk and fat-corrected milk yields.


A combined planning approach for improved functional and esthetic outcome of bimaxillary rotation advancement for treatment of obstructive sleep apnea using 3D biomechanical modeling.
In recent years, bimaxillary rotation advancement (BRA) has become the method of choice for surgical treatment of obstructive sleep apnea (OSA). As dislocation of the jaw bones affects both, airways and facial contours, surgeons are facing the challenge of finding an optimal jaw position that allows for the reestablishment of normal airway ventilation and esthetic surgical outcome. Owing to the complexity of the facial anatomy and its mechanical behavior, individual planning of surgical OSA treatment under consideration of functional and esthetic aspects presents a challenge that surgeons typically approach in a non-quantitative manner using subjective evaluation and clinical experience. This paper describes a framework for individual planning of OSA treatment using bimaxillary rotation advancement, which relies on computational modeling of hard and soft tissue mechanics. The described framework for simulation of functional and esthetic post-surgery outcome was used in 10 OSA patients. Comparison of the simulation results with post-surgery data reveals that biomechanical simulation provides a reliable estimate for post-surgery facial tissue behavior and antero-posterior airway extension, but fails to accurately describe a surprisingly large lateral stretch of the velopharyngeal region. This discrepancy is traced back to anisotropic effects of pharyngeal muscles. Possible approaches to improving the accuracy of model predictions and defining sharp criteria for optimizing combined OSA planning are discussed.


The shortage of doctorally prepared nursing faculty: a dire situation.
The decline in the number of doctorally prepared nursing faculty is a major problem contributing to the overall shortage of nursing personnel. This article evaluates the impact of faculty age and retirement timelines on the future availability of doctorally prepared nursing faculty. Age and retirement data were summarized from surveys of faculty conducted by the American Association of Colleges of Nursing. Additional data about characteristics of faculty and doctoral degree recipients were obtained from other national sources. Linear regression was used to determine average change in age and retirement year. Results showed steadily increasing faculty age, a shortening of time to likely retirement, and a loss of younger faculty. In addition to current initiatives aimed at increased financial support for doctoral study, nurse educators must rapidly arrive at short- and long-term solutions. Solutions may require examination of some of the sacrosanct traditions of nursing education.


Neural network-based adaptive synchronization for second-order nonlinear multiagent systems with unknown disturbance.
This paper handles the distributed adaptive synchronization problem for a class of unknown second-order nonlinear multiagent systems subject to external disturbance. It is supposed to be an unknown one for the underlying external disorder. First, the neural network-based disturbance observer is developed to deal with the impact induced by the strange disturbance. Then, a new distributed adaptive synchronization criterion is put forward based on the approximation capability of the neural networks. Next, we propose the necessary and sufficient condition on the directed graph to ensure the synchronization error of all followers can be reduced small enough. Then, the distributed adaptive synchronization criterion is further explored because it is difficult to obtain the relative velocity measurements of the agents. The distributed adaptive synchronization criterion without the velocity measurement feedback is also designed to fulfill the current investigation. Finally, the simulation example is performed to verify the correctness and effectiveness of the proposed theoretical results.


[Mild brain injuries: definition, classifications and prognosis].
Brain injuries may be graded into mild, moderate and severe depending on clinical and radiological criterions. Mild brain injuries (MBI) are usually defined by an initial unconsciousness limited to 30 minutes, a Glasgow score between 13 and 15, the absence of intra-cranial lesion on the CT scan, a post-traumatic amnesia period between one and 24 hours depending on the authors. The consequences of a MBI may be simple but the injured often suffer from a transitory post-concussive syndrome. Traumatic stress states are a well known pathology and consist in a psychological reaction against the trauma. The acute traumatic stress may or may not run its course to a chronic post-traumatic stress disorder, formerly called post-traumatic neurosis.


Do pregnant women prefer timing of elective cesarean section prior to versus after 39 weeks of gestation? Secondary analyses from a randomized controlled trial.
To evaluate women's preferences for timing of elective cesarean section (ECS) scheduled prior to versus after 39 completed weeks. Secondary analyses from a randomized controlled open-label trial were conducted at seven Danish tertiary hospitals from March 2009 to June 2011 with inclusion of singleton pregnant women with a healthy fetus. The women were allocated by a computerized telephone system to ECS scheduled at 38(+3) weeks or 39(+3) weeks of gestation. Dissatisfaction with timing of ECS and preferred timing of the procedure in a proposed future ECS delivery were evaluated. Data analyses were done by intention-to-treat, using logistic regression. A total of 1196 women (94%) completed an online questionnaire at follow-up eight weeks postpartum. In the 38 weeks group, 61 (10%) women 601 were dissatisfied with the timing of their ECS, whereas in the 39 weeks group 157 (26%) of 595 were dissatisfied (adjOR 3.18, 95% CI 2.30; 4.40). The proportion of women who preferred the same timing in a future ECS were 272 (45%) in the 38 weeks group compared to 232 (39%) in the 39(+3) weeks group (adjOR 0.75, 95% CI 0.60; 0.95). The women in this trial preferred ECS scheduled prior to 39 weeks of gestation.


The effect of personal, familial, and environmental characteristics on acne vulgaris: a prospective, multicenter, case controlled study.
There are only a few studies about epidemiological features of acne vulgaris in the literature. The aim of this study was to analyze demographic, clinical, familial and environmental characteristics of acne, the role of diet and aggravating factors and association of these factors with acne severity. Patients with a diagnosis of mild-moderate to severe acne were consecutively interviewed at the participating centers during the study period. A total of 3826 patients and 759 control patients were involved in this study. Mild acne was the most common type of acne, and most of the lesions were localized on face followed by the trunk. The severity of acne was worse in patients who had a positive family history of acne. The most common triggering factor was psychological stress. We found a positive correlation with chocolate, bread, green tea, milk, white sugar, ripe banana, ice cream, apple, orange, and red meat consumption. As we compare the acne severity according to geographical features we detected mild- moderate acne was more common in Mediterranean region and severe acne was more common in East Anatolian region. Family history positivity was more common in Aegean region and least common in Central Anatolian region. There was statistically significant relationship as we compare acne severity and dietary factors such as chocolate, dairy products such as milk, sunflower seed consumption within the geographical regions. This study presents the demographic and clinical characteristics of acne patients in Asian and the European parts of Turkey. We believe that this study will provide a useful overview of acne in Turkey.


Analysis of presurgery time as a prognostic factor in traumatic acute subdural hematoma.
Head trauma is the most commonly seen trauma mechanism which has the highest mortality rate in traffic accident. More than 1000 cases are registered every year in our institution. The mechanical forces applied to the head can create simple wound, skull fracture, and intracranial bleeding. Many factors affect the outcome. Mortality rate of acute traumatic subdural hematoma (ASDH) can reach 40-90%. Despite the principle of "golden hour" for ASDH patients, there is niehter no evidence to support it nor any surgeon management to duplicate. The purpose of this study was to analyze the presurgery time, i.e., the time elapsed from the accident to the definitive treatment, as a prognostic factor that might influence the mortality rate of traumatic acute subdural hematoma. Consecutive patients who underwent surgical intervention for traumatic ASDH between April 2009 and April 2011 were enrolled in the study. Their data were collected and classified into variables. Statistical measure using multivariate logistic regression was applied to search any relationship between presurgery time and patients' outcome. The study enrolled 93 patients, mostly male (75.3%). There were 6 cases of mild head injury, 28 of moderate and 58 of severe injury. Time passed between accident and operation, in overall, was 19.6 hours, with a range between 4-54 hours. Many factors affect the outcome of ASDH. Rapid transport to hospital with neurosurgery facility was associated with better outcomes. Being retrospective, this study has its own limitation. Future studies should recruit a larger number of patients.


[Effect of preoperative radiation on the success rate in the transplantation of human kidney cancer into thymus-aplastic nude mice].
The authors investigated the influence of a preoperative irradiation on the rate of successful implantations and the growth behavior of human hypernephromas implanted into nude mice. No successful implantation was observed in hypernephromas preirradiated with a dose of 2000 rd, which was also confirmed by histologic examinations. The rate of successful implantation of 17 non-preirradiated hypernephromas (10/17) is below that of the total group, and the rate of successful implantation in serial passage (6/17 = 35%) is markedly inferior. The clinical observation that the incidence of local recurrences is reduced by a preoperative irradiation is explained by our experimental findings.


A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging.
Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.


Intravitreal bevacizumab for the management of choroidal neovascularization in pseudoxanthoma elasticum.
To determine the results of intravitreal bevacizumab injections for the management of choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE)-associated angioid streaks. A consecutive series of patients with PXE and CNV were managed with intravitreal bevacizumab injection (1.25 mg per 0.05 cc). The main outcome measures were visual acuity and greatest lesion height as measured by optical coherence tomography (OCT). Nine eyes of nine consecutive patients received intravitreal bevacizumab (1.25 mg/0.05 mL) injections. The mean follow-up time was 6 months, during which eyes received an average of 1.8 injections. The baseline visual acuity was a mean of 20/368 and improved to 20/289 at the last visit (P = 0.056). Visual acuity either improved or stabilized in all 9 eyes (100%). Serial OCT measurements in 8 eyes showed a mean of 353 microm at baseline, which decreased to 201 mum at the last visit (P = 0.012). No complications were noted. These short-term results support the use of intravitreal bevacizumab for the management of CNV in patients with PXE. Continued experience with intravitreal bevacizumab in this population will help establish its longer-term efficacy and better define the potential need for serial injections to maintain these results.


Connecting Ca2+ and lysosomes to Parkinson disease.
The neurodegenerative movement disorder Parkinson disease (PD) is prevalent in the aged population. However, the underlying mechanisms that trigger disease are unclear. Increasing work implicates both impaired Ca2+ signalling and lysosomal dysfunction in neuronal demise. Here I aim to connect these distinct processes by exploring the evidence that lysosomal Ca2+ signalling is disrupted in PD. In particular, I highlight defects in lysosomal Ca2+ content and signalling through NAADP-regulated two-pore channels in patient fibroblasts harbouring mutations in the PD-linked genes, GBA1 and LRRK2. As an emerging contributor to PD pathogenesis, the lysosomal Ca2+ signalling apparatus could represent a novel therapeutic target.


Theoretical model of visible radiation from rare gas flashlamps.
A simple theoretical model of visible light emission from xenon flashlamps is presented. The continuum light emission is calculated from the rate of electron-ion recombination in the xenon plasma, which is treated as a greybody in thermal equilibrium. The effect of radiation reabsorption is calculated in terms of the temperature-dependent greybody emissivity. The model predictions of radiated power and energy are compared to measured data. Reasonable agreement is obtained over a wide range of parameters of practical interest. Thus the model provides a useful analytical tool for first-order engineering design of xenon flash-lamp illumination systems.


Organization of synaptic transmission in the mammalian solitary complex, studied in vitro.
1. Synaptic transmission and neuronal morphology were studied in the nucleus tractus solitarius and in the dorsal vagal motor nucleus (solitary complex), in coronal brain-stem slices of rat or cat, superfused in vitro. 2. Electrical stimulation of afferent fibres of the solitary tract evoked two different types of post-synaptic response recorded intracellularly in different solitary complex neurones. Labelling with horseradish peroxidase showed that these two sorts of orthodromically evoked responses were correlated with different post-synaptic neuronal morphologies. 3. The majority of recorded neurones (n = 93) showed a prolonged reduction in excitability following the initial solitary-tract-evoked excitatory post-synaptic potential (e.p.s.p.). A smaller number of neurones (n = 53) showed a prolonged increase in excitability following solitary tract stimulation. In no case did the solitary tract stimulation induce a burst of action potentials at high frequency. 4. The time-to-peak and the half-width of the initial solitary-tract-evoked e.p.s.p. were shorter in neurones with prolonged increased excitability than in those with prolonged reduced excitability. In neurones with prolonged reduced excitability, this e.p.s.p. was followed by a hyperpolarization lasting 60-100 ms. The latency of this inhibitory post-synaptic potential (i.p.s.p.) was 3-5 ms longer than that of the initial e.p.s.p. and its reversal potential was 10 mV more negative than the reversal potential of the response measured following application of gamma-aminobutyric acid or glycine. In neurones with prolonged increased excitability, at a membrane potential of -40 to -50 mV, the initial solitary tract e.p.s.p. was followed by a prolonged depolarization lasting 100-400 ms. 5. Background synaptic activity was high in neurones with prolonged increased excitability, consisting of unitary e.p.s.p.s with an amplitude of more than 0.8 mV. This activity was increased for a period of 300-800 ms following solitary tract stimulation. Spontaneous excitatory potentials of more than 0.5 mV were not seen in neurones with prolonged reduced excitability. In these neurones, after intracellular injection of choride ions, reversed unitary i.p.s.p.s formed a background activity which was increased following stimulation of the solitary tract. 6. Neurones with prolonged reduced excitability were found in the medial, ventral and ventrolateral part of the nucleus tractus solitarius and in the dorsal vagal motor nucleus where they were identified by their antidromic response to stimulation ventral and lateral to the tractus solitarius.(ABSTRACT TRUNCATED AT 400 WORDS)


Meiotic maturation of incompetent prepubertal sheep oocytes is induced by paracrine factor(s) released by gonadotropin-stimulated oocyte-cumulus cell complexes and involves mitogen-activated protein kinase activation.
In this study, sheep oocyte-cumulus cell complexes (OCC) derived from medium (M) antral follicles (M-OCC) were in vitro matured alone or in coculture with OCC derived from small (S) antral follicles (S-OCC) to investigate the contribution of cumulus cells (CC) and oocytes to the process of oocyte meiotic maturation and cumulus expansion (CE). Experiments were conducted with or without gonadotropins (FSH/LH). Regardless of culture conditions, about 12% of S-oocytes reached the metaphase II stage, and S-CC showed a low degree of CE. In contrast, both maturational processes were significantly stimulated by gonadotropins in M-OCC. However, about 48% of S-oocytes progressed to metaphase II, and S-CC expanded after coculture with gonadotropin-stimulated M-OCC and M-CC but not with mural granulosa cells. Both maturational processes were inhibited when S-OCC were cocultured with M-denuded oocytes, or when S-denuded oocytes were cocultured with M-CC. The capacity of these paracrine factor(s) to activate the MAPK pathway in somatic and germ cells of S-complexes was investigated. It was found that MAPK kinase/MAPK phosphorylation levels in M-OCC but not in S-OCC were significantly increased by gonadotropins, first in CC and later in the oocytes. Kinase phosphorylations were activated only in S-oocytes cocultured with M-OCC or M-CC. These results demonstrate that soluble factors specifically produced by M-CC are capable to induce meiotic maturation and CE in S-complexes by acting via CC. These factors can induce MAPK activation only in S-oocytes, whose meiotic arrest could be due to the inability of surrounding CC to respond to gonadotropin stimulation.


Dendritic cell vaccination plus low-dose doxorubicin for the treatment of spontaneous canine hemangiosarcoma.
Angiosarcoma is a deadly neoplasm of the vascular endothelium. Metastatic disease is often present at diagnosis, and 5-year survival is only 10-35%. Although there exist no immunocompetent mouse models of angiosarcoma with which to study immune-based approaches to therapy, angiosarcoma is a major killer of companion dogs, responsible for up to 2% of all canine deaths in some susceptible breeds or an estimated 120,000 per year in the US. The canine disease (HSA) often presents in the spleen as acute hemoabdomen secondary to splenic rupture. Even if life-saving splenectomy is performed, median overall survival (OS) is only 48 days, and 1-year survival is negligible. Here we report the analysis of a pilot phase I open-label trial of chemo-immunotherapy performed on consecutively presenting splenectomized canines with histologically verified HSA. Subjects received an abbreviated course of low-dose doxorubicin plus alpha interferon and an autologous dendritic cell-therapy reported to enhance durable CD8+ memory. Disease was monitored monthly by abdominal ultrasound, chest X-ray, and echocardiogram. Median OS in the per protocol population was 109 days including one of five animals that died cancer-free at 16 months after documented resolution of relapsed disease. These results indicate that therapeutic administration of chemo-immunotherapy is both feasible and safe, substantiating the rationale for additional veterinary and human clinical studies.


High-throughput transcriptome sequencing reveals the protective role of adenosine receptor-related genes in paraquat-exposed Caenorhabditis elegans.
This study sought to identify the genes associated with adenosine's protective action against paraquat (PQ)-induced oxidative stress via the adenosine receptor (ADOR-1) in Caenorhabditis elegans (C. elegans). The C. elegans was divided into 3 groups-2 groups exposed to PQ, one in presence, and one in absence of adenosine-and a control group that was not treated. Each group's total RNA was extracted and sequenced. When the transcriptomes of these groups were analyzed, several genes were found to be differently expressed. These differentially expressed genes were significantly enriched in adenosine-response biological processes and pathways, including gene ontology terms related to neuropeptide and kyoto encyclopedia of genes and genomes pathways associated to cAMP pathway regulator activity. Quantitative reverse-transcription PCR confirmed that G-protein-coupled receptors signaling pathway involving dop-1, egl-30, unc-13, kin-1, and goa-1 genes may play crucial roles in modulating adenosine's protective action. Interestingly, there are no significant variations in the expression of the ador-1 gene across the 3 treatments, thereby indicating that adenosine receptor exerts a consistent and stable influence on its related pathways irrespective of the presence or absence of PQ. Furthermore, the wild-type group with ador-1 gene has higher survival rate than that of the ador-1-/RNA interference group while treated with PQ in the presence of adenosine. Conclusively, our study uncovered a number of novel PQ-response genes and adenosine receptor-related genes in C. elegans, which may function as major regulators of PQ-induced oxidative stress and indicate the possible protective effects of adenosine.


Frequency of isolation and phenotypic antimicrobial resistance of fecal Salmonella enterica recovered from dairy cattle in Canada.
Salmonellosis is one of the leading causes of gastrointestinal infections in humans. In Canada, it is estimated that approximately 87,500 cases of salmonellosis occur every year in humans, resulting in 17 deaths. In the United States, it is estimated that 26,500 hospitalizations and 420 deaths occur every year. In dairy cattle, infections caused by nontyphoidal Salmonella enterica can cause mild to severe disease, including enteritis, pneumonia, and septicemia. Our study objectives were to determine the proportion of fecal samples positive for Salmonella in dairy cattle in Canada and determine the resistance pattern of these isolates. We used data collected through the Canadian Dairy Network for Antimicrobial Stewardship and Resistance (CaDNetASR). Pooled fecal samples from pre-weaned calves, post-weaned heifers, lactating cows, and manure storage were cultured for Salmonella, and the isolates were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined using the minimum inhibitory concentration test, and resistance interpretation was made according to the Clinical and Laboratory Standards Institute. A 2-level, multivariable logistic regression model was built to determine the probability of recovering Salmonella from a sample while accounting for province, year, and sample source. The proportion of farms with at least one positive sample were 12% (17/140), 19% (28/144), and 17% (24/144) for the sampling years 2019, 2020, and 2021, respectively. Out of the 113 Salmonella isolates, 23 different serovars were identified. The occurrence of Salmonella appeared to be clustered by farms and provinces. The most common serovars identified were Infantis (14%) and Typhimurium (14%). Overall, 21% (24/113) of the Salmonella isolates were resistant to at least one antimicrobial. Resistance to tetracycline was commonly observed (17%); however, very limited resistance to category I antimicrobials (categorization according to Health Canada that includes third-generation cephalosporins, fluoroquinolones, polymyxins, and carbapenems) was observed, with one isolate resistant to amoxicillin/clavulanic acid. The proportion of Salmonella isolates resistant to 2 and 3 antimicrobial classes was 3.5% and 8.8%, respectively. Our study provided valuable information on the proportion of fecal samples positive for Salmonella, the serovars identified, and associated resistance patterns across CaDNetASR herds, at regional and national levels.


A novel method for identifying SNP disease association based on maximal information coefficient.
To improve single-nucleotide polymorphism (SNP) association studies, we developed a method referred to as maximal information coefficient (MIC)-based SNP searching (MICSNPs) by employing a novel statistical approach known as the MIC to identify SNP disease associations. MIC values varied with minor allele frequencies of SNPs and the odds ratios for disease. We used a Monte Carlo-based permutation test to eliminate the effects of fluctuating MIC values and included a sliding-window-based binary search whose time-cost was 0.58% that of a sequential search to save time. The experiments examining both simulation and actual data demonstrated that our method is computationally and statistically feasible after reducing the resampling count to 4 times the number of markers and applying a sliding-window-based binary search to the method. We found that our method outperforms existing approaches.


Evidence for the progressive nature of neoplastic transformation in vitro.
The temporal acquisition of in vitro phenotypes associated with neoplasia were examined after exposure of Syrian hamster embryo cells to a chemical carcinogen. Quantitative assays measuring morphological changes, enhanced fibrinolytic activity, and anchorage independent growth were used to detect the development of transformed cells within a population of normal hamster embryo cells. Morphological transformation and enhanced fibrinolytic activity were early changes observed after treatment with benzo[alpha]-pyrene, whereas the ability to grow in semisolid agar was delayed 32-75 population doublings after carcinogen exposure. This delay was not due to selection of a small number of cells that were present early after treatment but at a level below detection, because a large percentage of the cells isolated at early passage (10(3)-fold above the level of detection) developed the potential for anchorage independent growth at later passages. This development of the anchorage independent growth phenotype was induced by the carcinogen treatment, because spontaneous transformation was rare. These observation suggest that multiple cellular changes are required for the acquisition of the capacity for anchorage independent growth and that neoplastic transformation in vitro is a progressive process through qualitatively different stages. Thus, an analogy can be drawn to the progressive nature of in vivo carcinogenesis. These results strongly justify the study of oncogenesis in cell culture as a model for neoplastic transformation in vivo.


Atomistic description of the folding of a dimeric protein.
Equilibrium molecular dynamics simulations are increasingly being used to describe the folding of individual proteins and protein domains at an atomic level of detail. Isolated protein domains, however, are rarely observed in vivo, where multidomain proteins and multimeric assemblies are far more common. It is clear that the folding of such proteins is often inextricably coupled with the process of dimerization; indeed, many protein monomers and protein domains are not stable in isolation, and fold to their native structures only when stabilized by interactions with other members of a protein complex. Here, we use equilibrium molecular dynamics simulations with an aggregate simulation length of 4 ms to elucidate key aspects of the folding mechanism, and of the associated free-energy surface, of the Top7-CFr dimer, a 114-amino-acid protein homodimer with a mixed α/β structure. In these simulations, we observed a number of folding and unfolding events. Each folding event was characterized by the assembly of two unfolded Top7-CFr monomers to form a stable, folded dimer. We found that the isolated monomer is unstable but that, early in the folding pathway, nascent native structure is stabilized by contacts between the two monomer subunits. These contacts are in some cases native, as in an induced-folding model, and in other cases non-native, as in a fly-casting mechanism. Occasionally, folding by conformational selection, in which both subunits form independently before dimerization, was also observed. Folding then proceeds through the sequential addition of strands to the protein β sheet. Although the long-time-scale relaxation of the folding process can be well described by a single exponential, these simulations reveal the presence of a number of kinetic traps, characterized by structures in which individual strands are added in an incorrect order.


Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects.
The authors' goal was to use structured clinical interviews to characterize the type and frequency of mental illness in adults with fetal alcohol syndrome or fetal alcohol effects. Twenty-five subjects who met criteria for fetal alcohol syndrome or fetal alcohol effects, who were older than 18 years old, and who had an IQ of greater than 70 were interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders and the Structured Clinical Interview for DSM-III-R Personality Disorders. Eighteen of the 25 subjects had received psychiatric treatment. The most common axis I disorders were alcohol or drug dependence (15 subjects), depression (11 subjects), and psychotic disorders (10 subjects). The most common axis II disorders were avoidant (six subjects), antisocial (four subjects), and dependent (three subjects) personality disorders. This study suggests that adults with fetal alcohol syndrome or fetal alcohol effects suffer from substantial mental illness.


[Clinico-immunological study of 16 cases of benzoate intolerance in children].
The authors report a sery of 16 cases of intolerance to the benzoates in children. Sixteen children (9 boys and 7 girls) were directed to the Hospital of Tarbes from June 1995 to July 1995, for recurring urticaria (7/16) combined with asthma (1/16), atopic eczema (2/16), dermorespiratory syndrome (2/16) and asthma (1/16). All were subject to an immunological examination comprising alimentation inquiry, prick test, IgE determination, RAST, oral provocation test to benzoates, which establishes the diagnosis, whose confirmation is certified by the benefit of the food eviction. To conclusion, the authors underline several points: the presumable underestimation of the intolerance, the often mentioned atopic familial context, the observed pathology (urticaria, asthma, eczema), the importance of the provocation test. Finally, besides food such as grey shrimps, sodas and antibiotic syrups, one finds benzoates in the antiallergic syrups initially prescribed as a preventive measure.


The association of placental pathology and neurodevelopmental outcomes in patients with neonatal encephalopathy.
Studies conflict on how acute versus chronic placental pathology impacts outcomes after neonatal encephalopathy from presumed hypoxic-ischemic encephalopathy (HIE). We examine how outcomes after presumed HIE vary by placental pathology categories. We performed retrospective chart review for neonates with presumed HIE, regardless of severity, focusing on 50 triads for whom placental specimens were available for re-review. Placentas were categorized as having only acute, any chronic, or no lesions. Primary outcomes included in-hospital morbidity/mortality and long-term neurodevelopmental symptoms. Secondary outcomes assessed neonatal MRI and EEG. Demographics did not differ between groups. Forty-seven neonates were treated with therapeutic hypothermia. Placental acuity category was not associated with primary or secondary outcomes, but clinical and/or histopathological chorioamnionitis was associated with abnormal EEG background and post-neonatal epilepsy (16.7%, n = 3 with chorioamnionitis versus 0%, n = 0 without chorioamnionitis, p = 0.04). When grouped by acute, chronic, or absent placental lesions, we observed no association with in-hospital, neurodevelopmental, MRI, or EEG outcomes. When reanalyzed by the presence of chorioamnionitis, we found that chorioamnionitis appeared to be associated with a higher risk of EEG alterations and post-neonatal epilepsy. Despite our limited sample size, our results emphasize the critical role of placental examination for neuroprognostication in presumed HIE. Neonatal encephalopathy presumed to result from impaired fetal cerebral oxygenation or blood flow is called hypoxic ischemic encephalopathy (HIE). Prior studies link placental pathology to various outcomes after HIE but disagree on the impact of acute versus chronic pathology. Our study determines that neurodevelopmental outcomes, in-hospital outcomes, injury on MRI, and EEG findings in patients with HIE are not differentially associated with acute versus chronic placental pathology. Chorioamnionitis is associated with an increased risk of abnormal EEG patterns and post-neonatal epilepsy. Histopathologic chorioamnionitis without clinical symptoms is common in HIE, emphasizing the crucial role of placental pathology for neuroprognostication.


Clonal analysis of liver-derived T cells of patients with primary biliary cirrhosis.
Lymphocyte infiltration in liver tissue is one important histological finding in primary biliary cirrhosis (PBC). So far, functional analyses of lymphocytes in PBC have focused on circulating lymphocytes, whereas lymphocytes at the involved site, the liver, have not been examined functionally. We have established interleukin 2 (IL-2)-dependent T lymphocyte lines (TLL) and clones (TLC) from liver biopsies of 14 patients with PBC. Phenotypic analysis using the monoclonal antibodies MT910 (CD2), MT811 (CD8), and MT151 (CD4) revealed that in nine of 14 TLL cytotoxic-suppressor T cells predominated (CD8+:52-84%; CD4+:14-48%), whereas in five of 14 TLL a preponderance of the CD4+ subpopulation was found (CD4+:56-73%; CD8+:28-45%). From 10 patients 137 TLC were generated which phenotypically correlated to the TLLs. We have tested the cytotoxic potential of seven TLL and 43 TLC in LDCC (lectin-dependent cell-mediated cytotoxicity), NK (natural killing) and ADCC (antibody-dependent cell-mediated cytotoxicity) assays. All TLL and all but one CD8+ TLC tested showed high activity in the LDCC assay, reflecting the cytolytic activity of cytotoxic T cells (CTL). CD4+ clones with LDCC activity were rarely found. NK activity and K cell activity could only be found in two clones. For the first time TLC and TLL from liver tissue of PBC patients could be generated. The high cytotoxic activity displayed by T cells derived from the liver indicates an important role for this immunological mechanism in the tissue damaging process.


ULTRASTRUCTURE OF EARLY EMBRYONIC SHELL FORMATION IN THE OPISTHOBRANCH GASTROPOD AEOLIDIA PAPILLOSA.
Early shell formation was examined in embryos of the opisthobranch gastropod Aeolidia papillosa. Secretion of the first organic shell material occurs prior to closure of the shell gland lumen, contrary to reports for other molluscan embryos. This difference suggests that in externally shelled gastropods and bivalves initiation of shell secretion may be coincident with narrowing of the shell gland pore rather than with closure of the lumen. The shell growth region was examined ultrastructurally. As no shell material is seen in the shell gland lumen, the shell gland seems not to be actively involved in shell secretion. Initial shell material is secreted only by cells surrounding the shell gland pore. Shell material seems to be added, not in a gap between cells as previously described, but over the apical surface of cells at the growing edge. The growing edge of the shell and the growing edge cells are covered by cytoplasmic extensions arising from the neighboring cells distal to the shell gland. No infoldings of the growing edge cell membranes are seen. The first organic shell material is 20 nm thick, consists of two electron dense layers separated by an electron lucent layer, and is secreted at least 33 hours (5°C) before shell mineralization, as detected by polarizing microscopy.


Split-face study to evaluate efficacy of global cryomodulation for reduction of pain and inflammation after nonablative fractional resurfacing.
Cryomodulation, or the delivery of controlled cooling to downregulate inflammatory processes in the skin, has been proposed to mitigate acute side effects following various dermatologic treatments. A new controlled cooling device has been developed to deliver cryomodulation for a range of different indications. In this clinical study, we evaluate the device for the reduction of pain, erythema, and edema following nonablative fractional resurfacing (NAFR). A single-blind, prospective, randomized, split-face study was conducted to assess the efficacy of the controlled dermal cooling device for the reduction of pain, edema, and erythema following nonablative fractional resurfacing with the dual 1550 nm erbium-doped fiber and 1927 nm thulium fiber laser. Subjects were randomized to receive a 10-min controlled cooling treatment to either the left or right side of the face immediately following full face NAFR. Pain ratings were recorded immediately postlaser treatment and immediately postcryomodulation treatment. At follow-up, subjects were surveyed for reduction of side effects and treatment satisfaction. Blinded review of photographs by two physicians was conducted to assess efficacy. The average pain score for subjects immediately post-NAFR was 5.15. Following cryomodulation, the average pain score on the treatment side was reduced by 69%, to an average of 1.6. The untreated side of the face was reduced by 19%, to an average of 4.2. Overall, 90% of subjects endorsed reduced discomfort. At follow-up, 70% of subjects reported a noticeable improvement in edema and 50% reported a noticeable improvement in erythema between the treatment and control sides. The average subject satisfaction score for the cryomodulation treatment was 4.2. All subjects (100%) indicated that they would elect to undergo the cryomodulation treatment again. Both blinded physician reviewers were successful in identifying the cryomodulation-treated side of the face in 70% of subjects' posttreatment photographs. The results of this split-face study support the efficacy of a global cryomodulation device for the reduction of pain, edema, and erythema following NAFR treatment. Cryomodulation was delivered in a simple 10 min procedure and yielded high patient satisfaction.


Influence of CpG island methylation status in O6-methylguanine-DNA methyltransferase expression of oral cancer cell lines.
It is known that the O6-methylguanine-DNA methyltransferase (MGMT) gene is susceptible to epigenetic regulation associated with an altered frequency of CpG methylation. To investigate whether epigenetic regulation of the MGMT gene might lead to significant reductions in the expression levels of cancer cells, we sought evidence of a link between the methylation status of the MGMT promoter and the expression levels of seven human oral cancer cell lines. We found two frequently methylated regions: the 5' region extending from nt 690 to nt 893 in the promoter, and the more 3' region extending from nt 1060 to nt 1151 in the untranslated first exon. The 3' region was hypermethylated independently of MGMT expression levels in all cell lines. By contrast, in the three MGMT-downregulated cell lines (SAS, Hep2, HO-1-u-1), the levels of MGMT expression were inversely related to the density of 5' region of the methylated CpGs in the MGMT promoter. Our results implied that the transcriptional inactivation of MGMT might require methylation of the 5' region, but not that of the 3' region in oral cancer cell lines. We further explored the role of methylation in MGMT expression by treating cells with 5-Aza-2'-deoxycytidine (5Aza-dC). 5Aza-dC treatment led to the partial or complete cytosine demethylation of two frequently methylated MGMT regions in all cell lines. 5Aza-dC succeeded in upregulating of the MGMT mRNA levels in only 2 of 7 cell lines (HSC3 and HO-1-u-1), and in fact reduced MGMT mRNA in the other 5 cell lines. Furthermore, 5Aza-dC had an inhibitory effect on MGMT protein levels in all cell lines. Our results suggest that MGMT levels may not revert after 5Aza-dC treatment. Based on our findings, the regulation of MGMT expression appears to be more complex than previously thought, although it is at least partially influenced by CpG methylation. Accordingly, care should be taken interpreting the link between MGMT methylation and expression.


Is the expansion of the pine processionary moth, due to global warming, impacting the endangered Spanish moon moth through an induced change in food quality?
Recent climate change is known to affect the distribution of a number of insect species, resulting in a modification of their range boundaries. In newly colonized areas, novel interactions become apparent between expanding and endemic species sharing the same host. The pine processionary moth is a highly damaging pine defoliator, extending its range northwards and upwards in response to winter warming. Its expansion in the Alps has resulted in an invasion into the range of the Spanish moon moth, a red listed species developing on Scots pine. Pine processionary moth larvae develop during winter, preceding those of the moon moth, which hatch in late spring. Using pine trees planted in a clonal design, we experimentally tested the effect of previous winter defoliation by pine processionary moth larvae upon the survival and development of moon moth larvae. Feeding on foliage of heavily defoliated trees (>50%) resulted in a significant increase in the development time of moon moth larvae and a decrease in relative growth rate compared to feeding on foliage of undefoliated trees. Dry weight of pupae also decreased when larvae were fed with foliage of defoliated trees, and might, therefore, affect imago performances. However, lower defoliation degrees did not result in significant differences in larval performances compared to the control. Because a high degree of defoliation by pine processionary moth is to be expected during the colonization phase, its arrival in subalpine pine stands might affect the populations of the endangered moon moth.


The safety, tolerability and effectiveness of generic antiretroviral drug regimens for HIV-infected patients in south India.
We investigated the safety, tolerability and effectiveness of locally produced generic highly active antiretroviral therapy (HAART) regimens with a chart review conducted at YRG CARE, a tertiary HIV referral centre in India. A total of 333 patients had been on Indian-manufactured generic HAART for at least 3 months. In this cohort, generic HAART was safe, well tolerated and effective at increasing CD4 T-lymphocyte counts in patients with advanced HIV, comparable to the experience with proprietary HAART.


Noninvasive biomarkers as surrogate predictors of clinical and endoscopic remission after infliximab induction in patients with refractory ulcerative colitis.
Treatment of refractory ulcerative colitis (UC) is a clinical challenge, and after biological therapy, monitoring clinical and endoscopic responses is fundamental. We aimed to investigate and compare the predictive power of different noninvasive parameters for clinical remission and mucosal healing after infliximab induction therapy in refractory UC patients. Serum and fecal biomarkers, including hemoglobin, white blood cells, erythrocyte sedimentation rate, C-reactive protein (CRP), and fecal calprotectin (FC), and colonoscopy were assessed in 44 patients with refractory UC before and after (week 12) infliximab induction. Clinical and endoscopic responses were measured by clinical Mayo score and endoscopic Mayo subscore, respectively. After infliximab induction, 54.5% and 65.9% had clinical remission and mucosal healing, respectively. Post-induction CRP and FC were significantly lower in clinical responders versus nonresponders (P = 0.01 and 0.001, respectively) and in patients with mucosal healing than without (P < 0.001). Among all the parameters tested, FC had the best predictive value of clinical remission [Area under the curve (AUC = 0.826)] and mucosal healing (AUC = 0.949). Post-induction FC had 87.5% sensitivity and 89% specificity (cut-off <100 μg/g) for predicting clinical remission and 89.7% sensitivity and 93.3% specificity (cut-off <58 μg/g) for predicting mucosal healing. Post-infliximab induction FC can be used as a surrogate marker for predicting clinical remission and mucosal healing in refractory UC patients.


Punishment sensitivity and the persistence of anorexia nervosa: High punishment sensitivity is related to a less favorable course of anorexia nervosa.
Cross-sectional research provides robust evidence that individuals with anorexia nervosa (AN) report higher punishment sensitivity (PS) than individuals without an eating disorder (ED). High PS might interfere with treatment motivation and the ability to learn from experience. The current study took a longitudinal approach to test predictions that follow from the proposed relevance of PS as a factor in the persistence of AN symptoms. More specifically we tested (1) if higher PS at the start of treatment was related to less improvement in ED symptoms after one year, and (2) if a decrease in ED symptoms was associated with a concurrent decrease in PS. Participants were 69 adolescents with a diagnosis of AN at the start of treatment of whom 62 participated again one year later. ED symptom severity and PS were assessed at both time points. Findings showed that (1) higher PS at the start of treatment was related to less improvement in ED symptoms, and (2) an improvement in ED symptoms was related to a decrease in PS. These findings are consistent with the proposed relevance of PS in the persistence of AN and suggest that it might be beneficial to address high PS in treatment. Consistent with the view that punishment sensitivity (PS) is related to the persistence of anorexia nervosa, high PS at the start of treatment was related to less improvement in eating disorder symptoms in patients with anorexia nervosa. Furthermore, an improvement in eating disorder symptoms was associated with a concurrent decrease in PS, suggesting that PS can be subject to change and may be a relevant target for treatment.


Tolerance to low temperatures of domestic and sylvatic Trichinella spp. in rat muscle tissue.
The present study was designed to investigate the tolerance to low temperatures of 9 Trichinella isolates in rat muscle tissue. Nine groups of 24 rats were infected with encapsulated Trichinella spiralis, Trichinella nativa, Trichinella britovi, Trichinella murrelli, Trichinella T6, Trichinella nelsoni, and 3 nonencapsulated Trichinella pseudospiralis strains. Six rats from each of the groups were necropsied at 5, 10, 20, and 40 wk postinfection (wpi). Muscle tissues containing Trichinella larvae were exposed to temperatures of -18, -5, and 5 C for 1 or 4 wk, and afterward the reproductive capacity index (RCI) in mice was determined for the 9 individual Trichinella isolates. Only T. nativa muscle larvae were infective after freezing at a temperature of -18 C. At 5 wpi all encapsulated isolates, except for the tropical species T. nelsoni, remained infective after exposure to a temperature of -5 C for both 1 and 4 wk, whereas nonencapsulated T. pseudospiralis survived only 1 wk of exposure. All Trichinella spp. remained infective after exposure to a temperature of 5 C. Muscle larvae for all investigated species remained infective as long as they persisted in live rats during the experiment. Analysis of variance showed a significant effect of age on the temperature tolerance of encapsulated T. spiralis and nonencapsulated T. pseudospiralis. In addition, significant interaction between age of muscle larvae and length of exposure was found. In general Trichinella muscle larvae of medium age (10 and 20 wpi) tolerated freezing better than early and late stages of infection (5 and 40 wpi). This is the first study to demonstrate such a relationship between age of infection and temperature tolerance of Trichinella spp. muscle larvae.


Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice.
Increased expression of Interleukin (IL)-33 has been detected in intestinal samples of patients with ulcerative colitis, a condition associated with increased risk for colon cancer, but its role in the development of colorectal cancer has yet to be fully examined. Here, we investigated the role of epithelial expressed IL-33 during development of intestinal tumors. IL-33 expression was detected in epithelial cells in colorectal cancer specimens and in the Apc Min/+ mice. To better understand the role of epithelial-derived IL-33 in the intestinal tumorigenesis, we generated transgenic mice expressing IL-33 in intestinal epithelial cells (V33 mice). V33 Apc Min/+ mice, resulting from the cross of V33 with Apc Min/+ mice, had increased intestinal tumor burden compared with littermate Apc Min/+ mice. Consistently, Apc Min/+ mice deficient for IL-33 receptor (ST2), had reduced polyp burden. Mechanistically, overexpression of IL-33 promoted expansion of ST2+ regulatory T cells, increased Th2 cytokine milieu, and induced alternatively activated macrophages in the gut. IL-33 promoted marked changes in the expression of antimicrobial peptides, and antibiotic treatment of V33 Apc Min/+ mice abrogated the tumor promoting-effects of IL-33 in the colon. In conclusion, elevated IL-33 signaling increases tumor development in the Apc Min/+ mice.


Synthesis and Evaluation of the First Fluorescent Antagonists of the Human P2Y2 Receptor Based on AR-C118925.
The human P2Y2 receptor ( hP2Y2R) is a G-protein-coupled receptor that shows promise as a therapeutic target for many important conditions, including for antimetastatic cancer and more recently for idiopathic pulmonary fibrosis. As such, there is a need for new hP2Y2R antagonists and molecular probes to study this receptor. Herein, we report the development of a new series of non-nucleotide hP2Y2R antagonists, based on the known, non-nucleotide hP2Y2R antagonist AR-C118925 (1), leading to the discovery of a series of fluorescent ligands containing different linkers and fluorophores. One of these conjugates, 98, displayed micromolar affinity for hP2Y2R (p Kd = 6.32 ± 0.10, n = 17) in a bioluminescence-energy-transfer (BRET) assay. Confocal microscopy with this ligand revealed displaceable membrane labeling of astrocytoma cells expressing untagged hP2Y2R. These properties make 98 one of the first tools for studying hP2Y2R distribution and organization.


Application of Artificial Neural Network and Support Vector Machines in Predicting Metabolizable Energy in Compound Feeds for Pigs.
In the nutrition literature, there are several reports on the use of artificial neural network (ANN) and multiple linear regression (MLR) approaches for predicting feed composition and nutritive value, while the use of support vector machines (SVM) method as a new alternative approach to MLR and ANN models is still not fully investigated. The MLR, ANN, and SVM models were developed to predict metabolizable energy (ME) content of compound feeds for pigs based on the German energy evaluation system from analyzed contents of crude protein (CP), ether extract (EE), crude fiber (CF), and starch. A total of 290 datasets from standardized digestibility studies with compound feeds was provided from several institutions and published papers, and ME was calculated thereon. Accuracy and precision of developed models were evaluated, given their produced prediction values. The results revealed that the developed ANN [R2 = 0.95; root mean square error (RMSE) = 0.19 MJ/kg of dry matter] and SVM (R2 = 0.95; RMSE = 0.21 MJ/kg of dry matter) models produced better prediction values in estimating ME in compound feed than those produced by conventional MLR (R2 = 0.89; RMSE = 0.27 MJ/kg of dry matter). The developed ANN and SVM models produced better prediction values in estimating ME in compound feed than those produced by conventional MLR; however, there were not obvious differences between performance of ANN and SVM models. Thus, SVM model may also be considered as a promising tool for modeling the relationship between chemical composition and ME of compound feeds for pigs. To provide the readers and nutritionist with the easy and rapid tool, an Excel® calculator, namely, SVM_ME_pig, was created to predict the metabolizable energy values in compound feeds for pigs using developed support vector machine model.


[Heart size and left ventricular function in coronary artery disease. II. Heart volume, coronary morphology and laevocardiogram (author's transl)].
We have investigated the possible relationship between the radiogically determined cardiac volume and the coronary angiogram and laevocardiogram. There was no relationship between cardiac size and coronary angiogram. Independently from the number of coronary vessels involved, we found normal sized hearts in patients without ECG-evidence of myocardial infarction, and enlarged hearts in patients with ECG-evidence of myocardial infarction. There was a significant, though loose relationship between the cardiac volume and the endsystolic and enddiastolic volumes (r=0.73 and 0.55 respectively) and the ejection fraction (r=0.69) as determined by laevocardiography. The critical value of the cardiac size, about which one encounters an increased number of abnormal volume parameters, was the upper boundary of 1-SD. Using this value we found a specifity of 81% and a sensitivity of 74% for the heart volume as a predictor of a pathological ejection fraction. On the other hand, using the upper boundary of 2-SD as a critical value, there was a sensitivity of only 58%, but a specificity of 92%. Only 11% of the patients with a cardiac size in the lower range of normal or below had an ejection fraction below 50%. Therefore the radiologically determined heart size is a simple, in daily practive acceptable method to assess and follow up left ventricular function in coronary patients.


[Variability of radiation-induced adaptive response in old age individuals and their correction by Peptide bioregulator -Livagen].
Effect of aging on adaptive response of cellular systems to low (stimulated) dozes of gamma-rays (0, 2 and 0, 5 Gy) and to disturbing dozes of radiation (1 and 2 Gy) has been investigated. PHA-stimulated cells were from 72-86 year-old individuals; control - 30-40 year-old individuals. The potentialities of induction of adaptive response in cells exposed to previously irradiated by stimulating dozes of gamma-rays with subsequent damaging effect of copper chloride (10(-3)M) has been investigated. The correcting activity of the peptide bioregulator Livagen was tested. The investigation showed that cells from aged individuals maintained radiation adaptive feature. Preliminary exposure to radiation caused stimulation of adaptive response in copper-treated cells. Corrective activity of Livagen was observed.


Purely epithelioid malignant peripheral nerve sheath tumor of the vulva.
Primary malignant peripheral nerve sheath tumors(MPNST) of the vulva are extremely rare and most of them are composed of a spindle cell component. A few cases of MPNST containing partially or purely epithelioid cells have been reported. Purely epithelioid MPNST differ from the ordinary epithelioid MPNST due to the absence of a spindle cell component. We present the first case of purely epithelioid MPNST arising in the vulva reviewing in the world literature without definite evidence of von Recklinghausen's disease or nerve involvement. The patient was a 63-year-old woman with a palpable vulvar mass, 6 x 4 x 1.5 cm in dimension, was not encapsulated but well-demarcated, ovoid and rubbery and showed pale yellow, homogeneous, fish-flesh appearance with focal cystic changes on cut surface. The histologic features consisted of solely epithelioid cells which were arranged in tight clusters or cords with solid growing pattern and focally scattered rosette-like structures. According to the immunohistochemical results, most of tumor cells were strongly positive for neuron specific enolase, and some of them were weakly positive for S-100 protein and vimentin. We considered that purely epithelioid MPNST would represent a certain degree of differentiation toward nerve or neuronal cells rather than Schwann cells.


The quality of deans' letters from medical schools.
Residency training directors have noted considerable variability in the quality of deans' letters sent by medical schools on behalf of graduating students. A total of 212 deans' letters from 103 U.S. medical schools received by a large psychiatric residency program were rated by two of the authors. Of these, 26.9 percent were judged excellent, 49.5 percent average, and 23.6 percent poor. Excellent letters were characterized by detailed personal and academic comments; verbatim statements for each clinical clerkship; tactful , yet explicit, remarks about problems; and internal consistency. Poor letters were generally short regardless of content, offered global impressions about clerkship performance by fusing remarks from several different clerkships without identifying sources, or omitted important information that was quickly evident to the discriminating interviewer. Recommendations are offered for authors and readers of deans' letters and to medical students.


Pharmacological treatments of tardive dyskinesia in the 1980s.
The studies of tardive dyskinesia treatment published in the 1980s were generally superior to earlier work in terms of methods (more double-blind trials using standardized rating scales), but relatively small sample sizes and short durations of studies were still the main deficiencies. The results continue to suggest an absence of an overall satisfactory treatment. Individual patients seem to respond to different drugs such as noradrenergic antagonists and GABAergic agents. Withdrawal of neuroleptics and antiparkinsonian agents is a useful strategy. Future work should concentrate on defining clinicopharmacological subtypes of tardive dyskinesia.


Hereditary generalized amyloidosis with polyneuropathy. Clinicopathological study of 65 Japanese patients.
A clinicopathological study was made on 65 patients from a small area of Nagano Prefecture, Japan, with hereditary generalized amyloidosis with polyneuropathy to clarify the clinical variety of the disease. Forty-five patients from Ogawa village showed similar clinical features. The age of onset ranged widely from 16 to 62 years. The main neurological manifestations were polyneuropathy starting in the legs and autonomic dysfunction. Lower cranial nerves were also affected in the advanced stages. Severe cardiac and renal involvement was uncommon. All these clinical features are consistent with type I familial amyloid polyneuropathy (FAP). The remaining 20 patients from five unrelated kinships showed unique clinical pictures. Two families from Ogawa village had type I FAP, but 4 out of the 5 affected patients showed marked nephropathy with heavy proteinuria from an early stage. Of the three other families, one, with 10 patients, was notable for the involvement of the central nervous system. Most of the patients showed cerebellar ataxia and pyramidal tract signs in addition to a sensorimotor and autonomic peripheral neuropathy. Another family had 2 siblings who had severe amyloid heart disease from the onset and developed polyneuropathy with autonomic features at an advanced stage. In the third family, onset occurred in the sixth decade in all 3 patients and the course was mild in 2, although the clinical features were those of typical type I FAP. Immunohistochemical study revealed that the amyloid fibril proteins in the patients with all four unusual clinical phenotypes were related to plasma prealbumin. The most common form of hereditary generalized amyloidosis in Japan is type I FAP, but the disease shows considerable variety in the age of onset and involves more systemic organs than previously recognized. The newly recognized clinical forms of hereditary generalized amyloidosis with severe amyloid heart disease or central nervous dysfunction indicate clinical heterogeneity of hereditary amyloidosis with polyneuropathy.


Is ethanol-induced damage of the gastric mucosa a hyperosmotic effect? Comparative studies on the effects of ethanol, some other hyperosmotic solutions and acetylsalicylic acid on rat gastric mucosa.
The involvement of hyperosmolarity in ethanol-induced gastric mucosal damage was studied by comparing the effects of ethanol on the rat gastric mucosa and those caused by hyperosmotic glucose and choline chloride solutions, and by an almost isosmotic solution of acetylsalicylic acid. Upon intragastric instillation, all test solutions, namely 3M and 5M ethanol (3330 and 5590 mosmol/kg resp.), 3M glucose (3890 mosmol/kg), 1.5 M choline chloride (2840 mosmol/kg) and 20 mM acetylsalicylic acid, also containing 100 mM HCl and 50 mM NaCl, produced macroscopic and microscopic lesions of the gastric mucosa. The haemorrhages induced by ethanol and acetylsalicylic acid solutions were more evenly distributed, whereas most lesions produced by the glucose and choline chloride solutions were located at the rumeno-fundic junction. There were no qualitative differences between the microscopic lesions caused by the various instillates, however. All the test solutions broke the gastric mucosal barrier and increased histamine release and pepsinogen output, but in the rats treated with acetylsalicylic acid these effects were less pronounced. Ethanol, glucose and choline chloride solutions increased gastric mucosal flow and fluid output from the stomach, whereas acetylsalicylic acid had no effect on these. The similarity between the ethanol-induced changes and those caused by hyperosmotic solutions of glucose and choline chloride leads to the suggestion that ethanol may cause damage in the gastric mucosa at least in part, via hyperosmolarity.


Expression of immune responsive genes in cell lines from two different Anopheline species.
Malaria infection results in increased expression of immune responsive genes, including those encoding antimicrobial peptides such as Gambicin (Gam1) and Cecropin A (Cec1). Understanding how these genes are regulated will provide insights how the mosquito immune system is activated by Plasmodium. We previously have shown that Cec1 was primarily regulated by the Imd-Relish (REL2) pathway in the Anopheles gambiae Sua1B cell line. We show here that expression of Defensin A (Def1) and Gam1 was reduced after RNA interference against components of the Imd-REL2 pathway in An. gambiae cell lines. Interestingly, promoter reporters of these antimicrobial peptides were expressed at very low level in the cell line MSQ43 from Anopheles stephensi. Surprisingly, over-expression of either NF-kappaB transcription factor REL1 or REL2 alone is sufficient to induce the expression of Cec1, Gam1 and Def1. These results suggest that expression of these antimicrobial peptides (AMP) in vivo may be regulated by both the Toll and Imd pathways. We also show here for the first time that Tep4, a gene encoding a thioester containing protein, is regulated by REL2. Taken together, these results suggest that there are significant overlaps of genes regulated by the Toll-Rel1 and Imd-Rel2 pathways. Further, the different expression patterns in two different Anopheline cell lines provide a platform to identify other key positive and negative regulators of the antimicrobial peptide genes.


Interaction of engineered nanomaterials with hydrophobic organic pollutants.
As nanomaterials become an increasing part of everyday consumer products, it is imperative to monitor their potential release during production, use and disposal, and to assess their impact on the health of humans and the ecosystem. This necessitates research to better understand how the properties of engineered nanomaterials (ENMs) lead to their accumulation and redistribution in the environment, and to assess whether they could become novel pollutants or if they can affect the mobility and bioavailability of other toxins. This study focuses on understanding the influence of nanostructured-TiO2 and the interaction of multi-walled carbon nanotubes with organic pollutants in water. We studied the adsorption and water phase dispersion of model pollutants with relatively small water solubility (i.e., two- and three-ring polyaromatic hydrocarbons and insecticides) with respect to ENMs. The sorption of pollutants was measured based on water phase analysis, and by separating suspended particles from the water phase and analyzing dried samples using integrated thermal-chromatographic-mass spectroscopic (TGA/GC/MS) techniques. Solid phase analysis using a combination of TGA/GC/MS is a novel technique that can provide real-time quantitative analysis and which helps to understand the interaction of hydrophobic organic pollutants and ENMs. The adsorption of these contaminants to nanomaterials increased the concentration of the contaminants in the aqueous phase as compared to the 'real' partitioning due to the octanol-water partitioning. The study showed that ENMs can significantly influence the adsorption and dispersion of hydrophobic/low water soluble contaminants. The type of ENM, the exposure to light, and the water pH have a significant influence on the partitioning of pollutants.


Protective effects of icariin on neurons injured by cerebral ischemia/reperfusion.
It is very important to search for novel anti-ischemia/reperfusion neuroprotective drugs for prevention or treatment of cerebrovascular diseases. Icariin, the major active component of traditional Chinese herb Yinyanghuo, may have a beneficial role for neurons in cerebral ischemia/reperfusion caused by accident. However, it was not clear yet. In this study, we observed the protective effects of icariin on neurons injured by ischemia/reperfusion in vitro and in vivo and investigated its protective mechanism. Cerebral cortical neurons of Wistar rats in primary culture were studied during the different periods of oxygen-glucose deprivation and reperfusion with oxygen and glucose. Cell viability was determined by methyl thiazoleterazolium (MTT) assay. The activity of lactate dehydrogenase (LDH) leaked from neurons, cell apoptosis and the concentration of intracellular free calcium were measured respectively. On the other hand, the mice model of transient cerebral ischemia/reperfusion was made by bilateral occlusion of common carotid arteries and ischemic hypotension/reperfusion. The mice were divided into several groups at random: sham operated group, model group and icariin preventive treatment group. The changes of mice behavioral, activities of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were measured, respectively. Treatment with icariin (final concentration 0.25, 0.5, and 1 mg/L) during ischemia/reperfusion-mimetic incubation in vitro concentration-dependently attenuated neuronal damage with characteristics of increasing injured neuronal absorbance of MTT, decreasing LDH release, decreasing cell apoptosis, and blunting elevation of intracellular calcium concentration. And in vivo the learning and memory abilities significantly decreased, activities of SOD were diminished and MDA level increased obviously in model group, compared with that in sham operated group. But pre-treatment of model mice with icariin (10, 30 and 100 mg/kg, i.g.) significantly blunted the decrease of mice learning, memory ability and SOD activity, and markedly decreased MDA level. Icariin has protective effects on cerebral ischemia/reperfusion injured neurons. And decreasing cell apoptosis, preventing intracellular calcium concentration elevation and enhancing anti-oxidant capacity may contribute to its protective effects.


Use of a biodegradable, oversized stent in a child with tracheomalacia secondary to vascular external compression.
We describe the implantation of an absorbable, custom-made stent of polydioxanone to treat tracheomalacia in a 5-month-old patient with extrinsic compression by a double aortic arch. The use of an absorbable, oversized stent treated the tracheal collapse caused by vascular compression, avoided removal procedures, and allowed the infant's growth. The use of an oversized stent prevented stent migration and gave minimal problems of granulation.


A GWAS SNP for Schizophrenia Is Linked to the Internal MIR137 Promoter and Supports Differential Allele-Specific Expression.
Single nucleotide polymorphisms (SNPs) within the MIR137 gene locus have been shown to confer risk for schizophrenia through genome-wide association studies (GWAS). The expression levels of microRNA-137 (miR-137) and its validated gene targets have also been shown to be disrupted in several neuropsychiatric conditions, including schizophrenia. Regulation of miR-137 expression is thus imperative for normal neuronal functioning. We previously characterized an internal promoter domain within the MIR137 gene that contained a variable number tandem repeat (VNTR) polymorphism and could alter the in vitro levels of miR-137 in a stimulus-induced and allele-specific manner. We now demonstrate that haplotype tagging-SNP analysis linked the rs1625579 GWAS SNP for schizophrenia to this internal MIR137 promoter through a proxy SNP rs2660304 located at this domain. We postulated that the rs2660304 promoter SNP may act as predisposing factor for schizophrenia through altering the levels of miR-137 expression in a genotype-dependent manner. Reporter gene analysis of the internal MIR137 promoter containing the common VNTR variant demonstrated genotype-dependent differences in promoter activity with respect to rs2660304. In line with previous reports, the major allele of the rs2660304 proxy SNP, which has previously been linked with schizophrenia risk through genetic association, resulted in downregulation of reporter gene expression in a tissue culture model. The genetic influence of the rs2660304 proxy SNP on the transcriptional activity of the internal MIR137 promoter, and thus the levels of miR-137 expression, therefore offers a distinct regulatory mechanism to explain the functional significance of the rs1625579 GWAS SNP for schizophrenia risk.


Inversion of Lake Bathymetry through Integrating Multi-Temporal Landsat and ICESat Imagery.
Lake bathymetry provides valuable information for lake basin planning and treatment, lake watershed erosion and siltation management, water resource planning, and environmental protection. Lake bathymetry has been surveyed with sounding techniques, including single-beam and multi-beam sonar sounding, and unmanned ship sounding. Although these techniques have high accuracy, most of them require long survey cycles and entail a high degree of difficulty. On the contrary, optical remote sensing inversion methods are easy to implement, but tend to provide less accurate bathymetry measures, especially when applied to turbid waters. The present study, therefore, aims to improve the accuracy of bathymetry measurements through integrating Landsat Thematic Mapper imagery, the Ice, Cloud, and Land Elevation Satellite's Geoscience Laser Altimeter System (ICESat/GLAS) data, and water level data measured at hydrological stations. First, the boundaries of a lake at multiple dates were derived using water extraction, initial boundary extraction, and Landsat Thematic Mapper/Enhanced Thematic Mapper (TM/ETM+) strip removal processing techniques. Second, ICESat/GLAS data were introduced to obtain additional topographic information of a lake. The striped topography of a lake's area was then obtained through eliminating and correcting erroneous points and interpolating the values of unknown points. Third, the entire bathymetry of the lake was obtained through interpolating water level values of lake boundary points in various dates. Experiments show that accurate bathymetry (±1 m) can be successfully derived.


Constructing inferences during narrative text comprehension.
The authors describe a constructionist theory that accounts for the knowledge-based inferences that are constructed when readers comprehend narrative text. Readers potentially generate a rich variety of inferences when they construct a referential situation model of what the text is about. The proposed constructionist theory specifies that some, but not all, of this information is constructed under most conditions of comprehension. The distinctive assumptions of the constructionist theory embrace a principle of search (or effort) after meaning. According to this principle, readers attempt to construct a meaning representation that addresses the reader's goals, that is coherent at both local and global levels, and that explains why actions, events, and states are mentioned in the text. This study reviews empirical evidence that addresses this theory and contrasts it with alternative theoretical frameworks.


Protocol for an experimental study design to evaluate computer-enabled intervention to prevent and manage metabolic syndrome.
The rising prevalence of overweight and obesity has a direct correlation with increasing prevalence of hypertension, dyslipidaemia, type 2 diabetes, metabolic syndrome (MetS) and cardiovascular diseases. Most of the previous studies have been cross-sectional in nature and have looked at the prevalence of metabolic syndrome. Despite the clinical and public health importance of this phenomenon, not enough work has been carried out so far to study and remedy this situation. The objectives of the proposed study is to develop an innovative user-centred informatics platform that will facilitate delivery of a multifactorial intervention after taking into account user sociodemographics, health behaviour, prior disease state and knowledge attitudes and practices. The objective of the proposed study is to develop an innovative user-centred informatics platform that will facilitate delivery of a multifactorial intervention after taking into account users' sociodemographics, health behaviour, prior disease state and knowledge, attitudes and behaviour. A randomised two-group repeated-measures clinical trial design will be used, on 750 subjects from urban, rural and slum areas, in an Indian setting. The study participants will be randomly assigned to either the intervention (computer-based MetS Program, CBMP) or control (printed educational material, PEM) group. Both the groups will undergo screening, learning and evaluation assessments at the time of the visit and at follow-up visits 30, 60 and 90 days after the first visit. The outcomes expected in the intervention group include improvement in Mets-related knowledge, adherence to self-care practices, better quality of life and increased satisfaction with medical care. The study has been approved by the Institutional Review Board of Asian Institute of Public Health (IRB#621). The proposed study will also help us assess the usefulness and challenges of technology to disseminate health education among diverse users. Findings will be disseminated through peer-reviewed publications and national and international conference presentations to various stakeholders and local community health leaders. The ClinicalTrials.gov Identifier is NCT01713465.


"Biqi" Bayberry Extract Promotes Skeletal Muscle Fiber Type Remodeling by Increasing Fast Myofiber Formation via the Akt/FoxO1 Pathway in Mice.
Bayberry is known to be a rich source of natural flavonoids and has been reported to have various health-promoting abilities. However, its function on regulating skeletal muscle fiber type remains unclear. This study examined whether bayberry extract affects skeletal muscle fiber type by promoting fast myofiber formation, as well as the potential molecular mechanism. After eight weeks, the "Biqi" bayberry extract (BBE) groups mice displayed markedly enhanced grip strength and improved metabolic rate compared to the control group mice. BBE also significantly increased myofibers size, LDH activity, MyHC-IIb (fast-twitch mRNA) expression, and the percentage of fast-twitch myofibers, while decreasing SDH activity, MyHC-I (slow-twitch mRNA) expression, and slow-twitch myofibers percentage in the skeletal muscle of the mice. The effect of BBE on regulating skeletal muscle fiber type remodeling is likely attributed to its activation of the Akt-FoxO1 pathway. Our findings indicated that BBE can effectively regulate the expression and proportion of fast-twitch fibers, making it a potential therapy for improving glucose homeostasis of skeletal muscle.


Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A meta-analysis.
Neoadjuvant chemotherapy before radical gastrectomy is preferred for locally advanced gastric cancer. To avoid the problematic use of pTNM for patients after neoadjuvant chemotherapy, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer TNM staging system (8th edition) added ypTNM for the first time. But patients achieving pathological complete response were not covered by the new ypTNM staging system. To investigate whether pathological complete response is associated with better outcome in gastric cancer, as was reported in rectal, breast and bladder cancer. We systematically searched the databases of PubMed, EMBASE, Web of Science and Cochrane Collaboration's Central register of controlled trials from January 1988 to April 2015 for publications which reported outcomes of patients with and without pathological complete response (pCR) (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or gastroesophageal junction (GEJ) treated with radical surgery is associated with better survival. The primary outcome was overall survival (OS). The secondary outcome was disease-free survival (DFS). Both were measured with a relative risk (RR). A meta-analysis was performed using the fixed effects model. Forest plots and the Q test was used to evaluate overall heterogeneity for OS and DFS. A total of seven trials, 1143 patients were included and analyzed after neoadjuvant chemotherapy and radical surgery with no other preoperative treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence interval [CI], 0.25-0.98; p = 0.04), 0.34 (95% CI, 0.21-0.55; p<0.0001) and 0.44 (95% CI, 0.30-0.63; p<0.0001) for one-year-OS, three-year-OS and five-year-OS, respectively. The summary RR for three-year-DFS was 0.43 (95% CI, 0.25-0.72; p = 0.002). Patients with resectable gastric or GEJ cancer who achieved pCR after neoadjuvant chemotherapy can gain a better outcome than patients without pCR.


Inhibitory action of synthetic proteinase inhibitors and substrates on the chemotaxis of rat polymorphonuclear leukocytes in vitro.
The effect of synthetic proteinase inhibitors (PIs) and proteinase substrates on chemotaxis of rat polymorphonuclear leukocytes (PMNs) was studied by using Boyden's method in vitro. Serine-PIs had a potent inhibitory activity on PMN chemotaxis. The relative potencies of the inhibitory action of PIs on the PMN chemotaxis in vitro were TPCK greater than inhibitor B greater than or equal to TLCK greater than EACA hexyl ester greater than FR 45009. The experiments using serine-proteinase substrates suggest an important role of chymotrypsin-like proteinase of PMNs in the process of PMN chemotaxis. Leupeptin had no direct effect on PMN chemotaxis in vitro, but significantly suppressed the zymosan-mediated generation of a chemoattractant for PMNs in rat serum. Other PIs had no effect on the generation of PMN chemoattractant. These results suggest that the PIs except leupeptin suppress PMN infiltration in vivo as a result of a direct action on PMNs, while leupeptin indirectly suppresses PMN infiltration in vivo through the inhibition of the generation of a chemoattractant for PMNs.


Gene expression analysis in SV-40 immortalized human corneal epithelial cells cultured with an air-liquid interface.
To compare the global gene expression profile of stratified epithelia generated in vitro using simian virus 40 (SV40) immortalized human corneal epithelial cells with the previously reported gene expression of normal human corneal epithelia. Immortalized cells expanded in submerged culture were grown in an air-liquid interface of liquid permeable collagen-coated filters to foster stratification and differentiation. Stratified epithelia displaying resistances exceeding 300 Ω·cm2 were dissolved in an RNA purification lysis buffer. Purified RNA was used to globally determine gene expression levels using high-density single-channel oligonucleotide microarrays. Raw hybridization readings were converted into relative gene expression levels using Robust Multi-array Average (RMA) algorithm. Expression levels for selected genes were validated by real-time RT-qPCR. The biologic significance of the gene expression profiles was interpreted with the help of several microarray software analysis tools and ad hoc thematical analysis. The stratified cell culture to native epithelial comparison identified over- and under-expression in 22% and 14% of the probed genes, respectively. The larger expression decreases occurred in genes intimately associated with both the stratified epithelial lineage at large such as keratin 14 and the corneal phenotype, such as keratin 12, connexin 43, aldehyde dehydrogenases (ALDHs), and paired box gene 6 (PAX6) and its whole downstream transcriptome. Overexpression related to genes associated with cell cycling stimulation. The results indicate that the stratified corneal epithelial cell model generated using SV40 immortalized cells may be useful only in certain research applications. Extrapolations of studies with these cells to actual tissue cells should be done with a great deal of caution.


Free radical scavenging activity of vanillin and o-vanillin using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical.
Vanillin, a plant derived natural product, used as food flavoring agent and its positional isomer o-vanillin, have been tested for their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical using high performance liquid chromatography (HPLC). Trolox, a water-soluble analogue of vitamin E and a well-known antioxidant was used as a reference compound. The DPPH radical was monitored at 517 nm and its retention time was 8.6 min. From the decrease in optical density of DPPH radical in the presence of the test compounds, it was observed that o-vanillin was a more effective scavenger than vanillin. At equimolar concentrations (1 mM), vanillin and o-vanillin exhibited 22.9% and 66.4% DPPH radical scavenging activity, respectively. The kinetics of the reaction of vanillin and o-vanillin with DPPH radical was studied using stopped flow spectrophotometry and their rate constants were estimated to be 1.7 +/- 0.1 M(-1)s(-1) and 10.1 +/- 0.8 M(-1)s(-1), respectively. In comparison, the rate constant for the reaction of trolox with DPPH was estimated to be 360.2 +/- 10.1 M(-1)s(-1). These scavenging reactions involve electron/H-atom transfer from antioxidant to DPPH. To confirm this, one electron reduction potentials of these compounds were estimated using cyclic voltammetry which showed that o-vanillin was more easily oxidized than vanillin. The reduction potential for o-vanillin was about 1.5 times that of trolox. These results demonstrate that o-vanillin is a more potent antioxidant than vanillin.


PVN activation is suppressed by repeated hypoglycemia but not antecedent corticosterone in the rat.
The mechanism(s) underlying hypoglycemia-associated autonomic failure (HAAF) are unknown. To test the hypothesis that the activation of brain regions involved in the counterregulatory response to hypoglycemia is blunted with HAAF, rats were studied in a 2-day protocol. Neuroendocrine responses and brain activation (c-Fos immunoreactivity) were measured during day 2 insulin-induced hypoglycemia (0.5 U insulin x 100 g body x wt(-1) x h(-1) iv for 2 h) after day 1 hypoglycemia (Hypo-Hypo) or vehicle. Hypo-Hypo animals demonstrated HAAF with blunted epinephrine, glucagon, and corticosterone (Cort) responses and decreased activation of the medial hypothalamus [the paraventricular (PVN), dorsomedial (DMH), and arcuate (Arc) nuclei]. To evaluate whether increases in day 1 Cort were responsible for the decreased hypothalamic activation, Cort was infused intracerebroventricularly (72 microg) on day 1 and the response to day 2 hypoglycemia was measured. Intracerebroventricular Cort infusion failed to alter the neuroendocrine response to day 2 hypoglycemia, despite elevating both central nervous system and peripheral Cort levels. However, day 1 Cort blunted responses in two of the same hypothalamic regions as Hypo-Hypo (the DMH and Arc) but not in the PVN. These results suggest that decreased activation of the PVN may be important in the development of HAAF and that antecedent exposure to elevated levels of Cort is not always sufficient to produce HAAF.


Harmful drinking and experiences of alcohol-related violence in Australian male construction industry apprentices.
This study sought to understand the prevalence of harmful alcohol use in a sample of Australian male construction industry apprentices and also examine alcohol-related violence. Although previous Australian research indicated that 45% of construction industry apprentices had Alcohol Use Disorders Identification Test scores indicative of harmful drinking, the current study identified that 66% of construction industry apprentices were drinking at harmful levels. It also identified positive correlations between harmful drinking behavior and alcohol-related violence (and precursors of violence such as verbal abuse). The article notes the role of masculine identity in alcohol consumption, particularly as it relates to the male-dominated construction industry. The article concludes by making recommendations for implementation of preventative education campaigns in apprentices' workplaces (or in training colleges), as it provides opportune settings to focus on high-risk groups, which are otherwise often difficult to access.


Analysis of the three-dimensional anatomical variance of the distal radius using 3D shape models.
Various medical fields rely on detailed anatomical knowledge of the distal radius. Current studies are limited to two-dimensional analysis and biased by varying measurement locations. The aims were to 1) generate 3D shape models of the distal radius and investigate variations in the 3D shape, 2) generate and assess morphometrics in standardized cut planes, and 3) test the model's classification accuracy. The local radiographic database was screened for CT-scans of intact radii. 1) The data sets were segmented and 3D surface models generated. Statistical 3D shape models were computed (overall, gender and side separate) and the 3D shape variation assessed by evaluating the number of modes. 2) Anatomical landmarks were assigned and used to define three standardized cross-sectional cut planes perpendicular to the main axis. Cut planes were generated for the mean shape models and each individual radius. For each cut plane, the following morphometric parameters were calculated and compared: maximum width and depth, perimeter and area. 3) The overall shape model was utilized to evaluate the predictive value (leave one out cross validation) for gender and side identification within the study population. Eighty-six radii (45 left, 44% female, 40 ± 18 years) were included. 1) Overall, side and gender specific statistical 3D models were successfully generated. The first mode explained 37% of the overall variance. Left radii had a higher shape variance (number of modes: 20 female / 23 male) compared to right radii (number of modes: 6 female / 6 male). 2) Standardized cut planes could be defined using anatomical landmarks. All morphometric parameters decreased from distal to proximal. Male radii were larger than female radii with no significant side difference. 3) The overall shape model had a combined median classification probability for side and gender of 80%. Statistical 3D shape models of the distal radius can be generated using clinical CT-data sets. These models can be used to assess overall bone variance, define and analyze standardized cut-planes, and identify the gender of an unknown sample. These data highlight the potential of shape models to assess the 3D anatomy and anatomical variance of human bones.


Comparison of cardiorespiratory fitness versus leisure time physical activity as predictors of coronary events in men aged < or = 65 years and > 65 years.
Both high peak oxygen consumption (VO(2)) and high levels of leisure time physical activity (LTPA) are associated with a reduced risk of cardiovascular morbidity and mortality. We examined the contributions of LTPA and peak VO(2) to the risk of coronary events (CEs) in healthy younger (< or = 65 years, n = 522) and older (>65 years, n = 167) men from the Baltimore Longitudinal Study of Aging. LTPA derived from self reports of time spent in 97 activities were converted into METs-minutes/24 hours and grouped into high (> or = 6 METs), moderate- (4 to 5.9 METs), and low-intensity LTPA (<4 METs). Cardiorespiratory fitness was determined by measuring peak VO(2) during a maximal treadmill exercise test. Over a mean follow-up of 13.4 +/- 6.3 years, CEs occurred in 63 men. After accounting for coronary risk factors, proportional-hazards analyses showed a relative CE risk of 0.53 (p <0.0001) for a SD increase in peak VO(2) in younger men and 0.61 (p = 0.024) in older men, whereas total LTPA was unrelated to coronary risk in either age group. When the 3 LTPA intensity levels were substituted for total LTPA in the model, peak VO(2) remained the only predictor of events in younger men, whereas high-intensity LTPA (RR = 0.39 for tertile 3 vs tertiles 1 and 2, p = 0.016) and peak VO(2) (RR = 0.61/SD increase, p = 0.024) were of similar importance in older men. Thus, in healthy younger men, higher cardiorespiratory fitness but not LTPA predicts a reduced risk of coronary heart disease, independent of conventional risk factors. For older men, high-intensity LTPA and fitness appear to be of similar importance in reducing coronary risk.


Hyperglycemia-induced oxidative stress in diabetic complications.
Reactive oxygen species are increased by hyperglycemia. Hyperglycemia, which occurs during diabetes (both type 1 and type 2) and, to a lesser extent, during insulin resistance, causes oxidative stress. Free fatty acids, which may be elevated during inadequate glycemic control, may also be contributory. In this review, we will discuss the role of oxidative stress in diabetic complications. Oxidative stress may be important in diabetes, not just because of its role in the development of complications, but because persistent hyperglycemia, secondary to insulin resistance, may induce oxidative stress and contribute to beta cell destruction in type 2 diabetes. The focus of this review will be on the role of oxidative stress in the etiology of diabetic complications.