Total Synthesis of Amphirionin-4.
The first total synthesis of amphirionin-4 has been achieved using a combination of cross-coupling strategies to access the polyene side chain and a chlorohydrin-based approach to construct the tetrahydrofuranol core. The remote C9-stereocenter was introduced through a Nozaki-Hiyama-Kishi coupling that proceeded with remote stereoinduction.


Factors associated with the use of rapid antigen diagnostic tests in children presenting with acute pharyngitis among French general practitioners.
In this investigation, we wanted: (i) to describe the attitudes and declared practices of a representative sample of French general practitioners (GPs) regarding rapid antigen diagnostic tests (RADTs) for acute pharyngitis and (ii) to identify the GPs' characteristics associated with the use of an RADT in the last paediatric patient with pharyngitis. We performed a cross-sectional survey conducted in 2012 among a representative sample of 1,126 self-employed GPs in France. 60.1 % of GPs declared that they used an RADT in their last patient aged between 3 and 16 years presenting with acute pharyngitis; 29.6 % of these tests were positive. Among the GPs who did not use an RADT, 50.2 % prescribed an antibiotic, compared to 30.5 % of prescriptions among GPs who performed an RADT, whatever its result. In a multivariate analysis, GPs' age between 45 and 54 years and having attended Continuing Medical Education (CME) sessions on infectious diseases in the past year were significantly associated with an increased use of an RADT in the last patient with pharyngitis, whereas a low volume of activity, occasionally practising alternative medicine, receiving pharmaceutical representatives at the practice and declaring a consultation duration <15 min were factors associated with a decreased use of RADTs. The use of RADTs by GPs must be promoted; our findings could help define interventions to improve practice.


Effect of high-temperature inside-outside spray on survival of campylobacter jejuni attached to prechill chicken carcasses.
Prechill chicken carcasses, inoculated with Campylobacter jejuni, were sprayed in an inside-outside birdwasher at 20, 55, or 60 C, with or without 50 ppm chlorine, in a poultry processing pilot plant. Carcasses were sprayed for 12 s at 80 pounds per square inch (psi). Next, carcasses were placed in a chiller filled with 50 ppm chlorinated ice water at 4 C for 50 min. Most probable numbers of C. jejuni were determined based on chicken carcass wash water before and after the spray treatment. The skin color of chicken carcasses was measured. The results of this study showed that the 55 and 60 C water spray treatments significantly reduced C. jejuni by more than 0.78 log cfu/carcass compared with the 20 C water spray treatment. However, all of the 50 ppm chlorine spray treatments at three different temperatures were not significantly different. The skin color of chicken carcasses did not change significantly after the spray treatments at temperatures less than 60 C. The chilling process with 50 ppm chlorinated ice water at 4 C further reduced more C. jejuni (approximately 1 log cfu/carcass) among the water spray treatments but did not result in greater reduction of C. jejuni among the chlorine spray treatments.


A management information system to study space diets.
A management information system (MIS), including a database management system (DBMS) and a decision support system (DSS), was developed to dynamically analyze the variable nutritional content of foods grown and prepared in an Advanced Life Support System (ALSS) such as required for long-duration space missions. The DBMS was designed around the known nutritional content of a list of candidate crops and their prepared foods. The DSS was designed to determine the composition of the daily crew diet based on crop and nutritional information stored in the DBMS. Each of the selected food items was assumed to be harvested from a yet-to-be designed ALSS biomass production subsystem and further prepared in accompanying food preparation subsystems. The developed DBMS allows for the analysis of the nutrient composition of a sample 20-day diet for future Advanced Life Support missions and is able to determine the required quantities of food needed to satisfy the crew's daily consumption. In addition, based on published crop growth rates, the DBMS was able to calculate the required size of the biomass production area needed to satisfy the daily food requirements for the crew. Results from this study can be used to help design future ALSS for which the integration of various subsystems (e.g., biomass production, food preparation and consumption, and waste processing) is paramount for the success of the mission.


A minimally invasive method for clinical trans-diaphragmatic pressure measurement in anaesthetized dogs.
To measure trans-diaphragmatic pressures, as an indication of diaphragmatic contractility, in anaesthetized dogs breathing normally, or during inspiratory obstruction (Mueller's manoeuvre) in order to assess if the method is practicable for use in clinical circumstances. Pilot study. Twenty eight client-owned dogs, ASA I or II, 1-10 years old, 5-30 kg bodyweight, which required anaesthesia for surgery, and were to be positioned in lateral recumbency. Following a standardized regimen of premedication and anaesthetic induction, anaesthesia was stabilized and maintained with isoflurane. Two commercially available balloon catheters were introduced orally, and advanced, one into the stomach and one into the mid-third of the oesophagus. Oesophageal and gastric pressures were measured from these catheters, and trans-diaphragmatic pressure (Pdi ) calculated and recorded continuously. At three separate time points during anaesthesia, for one breath, inspiration was obstructed (Mueller's manoeuvre) and Pdi was measured. Placement of the catheters in the stomach was not easy, and failed in three cases. In five dogs, their size resulted in failure of correct placement of catheters. Good traces of all three pressures reflecting respiratory cycles were obtained from 20 dogs. During normal spontaneous breathing (mean ± SD [range]) Pdi was 5 ± 2.1 (3-10) mmHg. During Mueller's manoeuvre, Pdi was 14.6 ± 4.5 (9-21) mmHg. Abnormal waveforms were seen included cardiac oscillations (five dogs), inadequate intra-gastric pressure tracing (one dog), deflections with a double peak (one dog), and multiple artifacts when there was increased heart rate and tachypnoea (two dogs in response to surgery). Measurement of trans-diaphragmatic pressure with balloon catheters was practicable in suitably sized dogs anaesthetized for clinical purposes and might be a useful tool in the assessment of diaphragmatic function. A range of catheters are required if the technique is to work in all dogs.


Dopamine D1 and D3 Receptors Modulate Heroin-Induced Cognitive Impairment through Opponent Actions in Mice.
Chronic abuse of heroin leads to long-lasting and complicated cognitive impairment. Dopamine receptors are critically involved in the impulsive drug-driven behavior and the altered attention, processing speed, and mental flexibility that are associated with higher relapse rates. However, the effects of the different dopamine receptors and their possible involvement in heroin-induced cognitive impairment remain unclear. The 5-choice serial reaction time task was used to investigate the profiles of heroin-induced cognitive impairment in mice. The expression levels of dopamine D1- and D2-like receptors in the prefrontal cortex, nucleus accumbens, and caudate-putamen were determined. The effects of dopamine receptors on heroin-induced impulsivity in the 5-choice serial reaction time task were examined by agonist/antagonist treatment on D1 or D3 receptor mutant mice. Systemic heroin administration influences several variables in the 5-choice serial reaction time task, most notably premature responses, a measure of motor impulsivity. These behavioral impairments are associated with increased D1 receptor and decreased D3 receptor mRNA and protein levels in 3 observed brain areas. The heroin-evoked increase in premature responses is mimicked by a D1 agonist and prevented by a D1 antagonist or genetic ablation of the D1 receptor gene. In contrast, a D3 agonist decreases both basal and heroin-evoked premature responses, while genetic ablation of the D3 receptor gene results in increased basal and heroin-evoked premature responses. Heroin-induced impulsive behavior in the 5-choice serial reaction time task is oppositely modulated by D1 and D3 receptor activation. The D1 receptors in the cortical-mesolimbic region play an indispensable role in modulating such behaviors.


Pre-term delivery and periodontal disease: a case-control study from Croatia.
The aim of this report was to assess the strength and influence of periodontitis as a possible risk factor for pre-term birth (PTB) in a cohort of 81 primiparous Croatian mothers aged 18-39 years. PTB cases (n = 17; mean age 25 +/- 2.9 years; age range 20-33 years) were defined as spontaneous delivery after less than 37 completed weeks of gestation that were followed by spontaneous labour or spontaneous rupture of membranes. Controls (full-time births) were normal births at or after 37 weeks of gestation (n = 64; mean age 25 +/- 2.9 years; age range 19-39 years). Information on known risk factors and obstetric factors included the current pregnancy history, maternal age at delivery, pre-natal care, nutritional status, tobacco use, alcohol use, genitourinary infections, vaginosis, gestational age, and birth weight. Full-mouth periodontal examination was performed on all mothers within 2 days of delivery. PTB cases had significantly worse periodontal status than controls (p = 0.008). Multivariate logistic regression model, after controlling for other risk factors, demonstrated that periodontal disease is a significant independent risk factor for PTB, with an adjusted odds ratio of 8.13 for the PTB group (95% confidence interval 2.73-45.9). Periodontal disease represents a strong, independent, and clinically significant risk factor for PTB in the studied cohort. There are strong indicators that periodontal therapy should form a part of preventive prenatal care in Croatia.


Organization of the superior olivary complex in the guinea pig. I. Cytoarchitecture, cytochrome oxidase histochemistry, and dendritic morphology.
The superior olivary complex is a prominent component of the auditory system. It consists of the lateral and medial superior olivary nuclei and a large number of smaller cell groups known as the periolivary nuclei, which are sources of both ascending and descending projections. The goal of this study was to establish criteria for identifying the periolivary nuclei in the guinea pig. Use of Nissl stains, the Golgi impregnation technique, and cytochrome oxidase histochemistry allowed us to distinguish eleven periolivary nuclei on the basis of differences in the types of cells they contain, in the distribution of cell types, and in the cytochrome oxidase staining characteristics of both the cells and the neuropil. The nuclei, named according to their position with respect to the lateral and medial superior olivary nuclei, can be divided into four groups: (1) a lateral group comprising the lateral nucleus of the trapezoid body and the anterolateral and posteroventral periolivary nuclei, (2) a dorsal group comprising the dorsal and dorsolateral periolivary nuclei, (3) a ventral group comprising the ventral nucleus of the trapezoid body and the anteroventral, ventromedial and rostral periolivary nuclei, and (4) a medial group comprising the medial nucleus of the trapezoid body and the superior paraolivary nucleus. Cytological distinctions among the periolivary nuclei are consistent with other evidence that they serve different functions and highlight the need for detailed study of their connections, immunocytochemistry and physiological response properties.


Stat testing and DRGs: a strategy for cost containment.
To reduce costs in the laboratory we must determine when stat testing is appropriate and establish a monitoring system. Here, as a means of reviewing the use of such tests and as an aid in decision making, is a break down of the probability of stat testing based on Diagnosis-related Group categories.


Care Provision and Prescribing Practices of Physicians Treating Children and Adolescents With ADHD.
Care provision and prescribing practices of physicians treating children with attention-deficit hyperactivity disorder (ADHD) were compared. A retrospective cohort study was conducted with the 1995-2010 General Electric Centricity Electronic Medical Record database. The sample included children (≤18 years) with newly diagnosed ADHD (ICD-9-CM code 314.XX) who received a prescription for a stimulant or atomoxetine. Identification of comorbid psychiatric disorders, duration from initial ADHD diagnosis to treatment, prescription of other psychotropic medications, and follow-up care during the ten months after the ADHD treatment initiation were compared across provider type (primary care physicians [PCPs], child psychiatrists, and physicians with an unknown specialty). The associations between provider type and practice variations were further determined by multivariate logistic regression accounting for patient demographic characteristics, region, insurance type, and prior mental health care utilizations. Of the 66,719 children identified, 75.8% were diagnosed by PCPs, 2.6% by child psychiatrists, and 21.6% by physicians whose specialty was unknown. Child psychiatrists were less likely than PCPs to initiate ADHD medication immediately after the diagnosis. However, once the ADHD treatment was initiated, they were more likely to prescribe psychotropic polytherapy even after analyses accounted for the comorbid psychiatric disorders identified. Only one-third of ADHD cases identified by both PCPs and child psychiatrists have met the HEDIS quality measure for ADHD medication-related follow-up visits. Differences were found by physician type in care of children with ADHD. Additional studies are needed to understand clinical consequences of these differences and the implications for care coordination across provider specialties.


[Relationships between social factors and suicidal attempts of adolescent girls].
This study presents a comparative analysis of family and school situation among adolescent girls, who attempted a suicide and those who did not. The control group was represented by normative sample of school girls of Lithuania. The results indicate that most of the attempters live in incomplete families, with step-father, step-sisters and step-brothers. The results showed that there were more conflicts within families of the attempters than within the other groups of the study. The girls, who completed a suicide attempt more often reported about arguing with their parents. They also appeared to brake the law more frequently and also they experienced abuse more often than girls in the control group. The attempters more frequently reported about financial difficulties of their families. Those girls also reported more problems at school such as truancy. The attempters also evaluated their academic achievements much lower than girls in the control group.


The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions.
There is considerable unexplained variability in alfentanil pharmacokinetics, particularly systemic clearance. Alfentanil is extensively metabolized in vivo, and thus systemic clearance depends on hepatic biotransformation. Cytochrome P450 3A4 was previously shown to be the predominant P450 isoform responsible for human liver microsomal alfentanil metabolism in vitro. This investigation tested the hypothesis that P450 3A4 is responsible for human alfentanil metabolism and clearance in vivo. Nine healthy male volunteers who provided institutionally approved written informed consent were studied in a three-way randomized crossover design. Each subject received alfentanil (20 micrograms/kg given intravenously) 30 min after midazolam (1 mg injected intravenously) on three occasions: control; high P450 3A4 activity (rifampin induction); and low P450 3A4 activity (selective inhibition by troleandomycin). Midazolam is a validated selective in vivo probe for P450 3A4 activity. Venous blood was sampled for 24 h and plasma concentrations of midazolam and alfentanil and their primary metabolites 1'-hydroxymidazolam and noralfentanil were measured by gas chromatography-mass spectrometry. Pharmacokinetic parameters were determined by two-stage analysis using both noncompartmental and three-compartment models. Plasma alfentanil concentration-time profiles depended significantly on P450 3A4 activity. Alfentanil noncompartmental clearance was 5.3 +/- 2.3, 14.6 +/- 3.8, and 1.1 +/- 0.5 ml.kg-1.min-1, and elimination half-life was 58 +/- 13, 35 +/- 7, and 630 +/- 374 min, respectively, in participants with normal (controls), high (rifampin), and low (troleandomycin) P450 3A4 activity (means +/- SD; P < 0.05 compared with controls). Multicompartmental modeling suggested a time-dependent inhibition-resynthesis model for troleandomycin effects on P450 3A4 activity, characterized as k10(t) = k10[1-phi e-alpha(t-tzero)], where k10(t) is the apparent time-dependent rate constant, k10 is the uninhibited rate constant, phi is the fraction of P450 3A4 inhibited, and alpha is the apparent P450 3A4 reactivation rate. Alfentanil clearance was calculated as V1 k10 for controls and men receiving rifampin, and as V1.average k10(t) for men receiving troleandomycin. This clearance was 4.9 +/- 2.1, 13.2 +/- 3.6, and 1.5 +/- 0.8 ml.kg-1.min-1, respectively, in controls and in men receiving rifampin or troleandomycin. There was a significant correlation (r = 0.97, P < 0.001) between alfentanil systemic clearance and P450 3A4 activity. Modulation of P450 3A4 activity by rifampin and troleandomycin significantly altered alfentanil clearance and disposition. These results strongly suggest that P450 3A4 is the major isoform of P450 responsible for clinical alfentanil metabolism and clearance. This observation, combined with the known population variability in P450 3A4 activity, provides a mechanistic explanation for the interindividual variability in alfentanil disposition. Furthermore, known susceptibility of human P450 3A4 activity to induction and inhibition provides a conceptual framework for understanding and predicting clinical alfentanil drug interactions. Finally, human liver microsomal alfentanil metabolism in vitro is confirmed as an excellent model for human alfentanil metabolism in vivo.


In vivo phosphorylation of myelin basic proteins in developing mouse brain: evidence that phosphorylation is an early event in myelin formation.
Myelin basic proteins (MBPs) can be detected in 5-day mouse brain, even though there is very little myelin present. In addition to the 4 MBP components (with molecular weights of 14, 17, 18.5 and 21.5 kilodaltons), that are commonly observed, other larger MBP-related polypeptides are also present. We have investigated the possibility of MBP phosphorylation at early stages of development in order to establish the point at which this modification occurs in the assembly of myelin. In vivo isotope studies show that in the 5-day mouse brain 14-, 17-, 18.5- and 21.5- kilodalton MBPs are phosphorylated and that they may be present in an immature form of myelin. Larger MBP-related proteins with a molecular weight of 35 and 42 kilodaltons are also phosphorylated but appear to be present mostly in nonmyelin structures or compartments.


Renin and ACTH responses to hypercapnia and hypoxia after chronic carotid chemodenervation.
We studied the effect of chronic carotid body denervation on renin (plasma renin activity, PRA), adrenocorticotropin (ACTH), blood pressure, and hematocrit responses to acute normocapnic (arterial CO2 partial pressure, PaCO2, 35 Torr) and hypercapnic (PaCO2, 65 Torr) hypoxia (arterial O2 partial pressure, PaO2, 31 Torr) in five anesthetized, artificially ventilated dogs. Animals were studied at least 3 days before and again at least 10 days after carotid body denervation (bilateral carotid sinus nerve resection). Increases in PRA during hypercapnic normoxia [21.8 +/- 6.4 ng angiotensin I (ANG I) X ml-1 X 3 h-1] and normocapnic hypoxia (13.3 +/- 4.2 ng ANG I X ml-1 X 3 h-1) were not attenuated by carotid body denervation. Increases in ACTH during normocapnic hypoxia (117 +/- 34 pg/ml) were attenuated but not eliminated by carotid body denervation; the increase in ACTH during hypercapnic hypoxia (295 +/- 93 pg/ml) was not attenuated by carotid body denervation. Both the blood pressure and hematocrit responses to normocapnic and hypercapnic hypoxia were attenuated by carotid body denervation. We concluded that 1) the renin response to hypercapnia and hypoxia is not a carotid chemoreflex, 2) the ACTH response to hypoxia is partially a carotid chemoreflex, and 3) blood pressure and hematocrit responses to hypoxia are primarily carotid chemoreflexes.


Factors influencing medical practitioner participation in population carrier screening for cystic fibrosis.
Cystic fibrosis (CF) carrier screening should be offered to people planning a pregnancy or in early pregnancy, according to current recommendations. However, research indicates rates of offering CF carrier screening are low. Health professionals (HPs) play an important role in offering population carrier screening. To determine the opinions, knowledge and practice patterns of HPs with regard to the routine offering of population carrier screening for CF. Five key informant interviews informed the development of an online questionnaire which was distributed to a select group of HPs involved in prenatal care in Victoria, Australia. Of the participants who completed the questionnaire (n = 87), 35.6% reported offering CF carrier screening to all patients attending for preconception or early pregnancy consultations. High referrers of CF carrier screening were more likely to be female, work in the private sector, in metropolitan areas and specialise as an obstetrician. High referrers demonstrated a greater level of knowledge of CF and carrier screening than low referrers (t = -3.779, P < 0.001). Low referrers perceived more barriers to offering carrier screening than high referrers (t = 2.125, P = 0.037). Low referrers were more likely to perceive lack of community awareness and HP knowledge as a barrier to offering CF carrier screening, compared to high referrers, who were more likely to perceive time constraints as a barrier. To promote routine offering of population CF carrier screening, resources are needed to improve knowledge and provide clinical support thereby reducing perceived barriers.


Electrical Membrane Properties and Circadian Rhythm in Extensor Cells of the Laminar Pulvini of Phaseolus coccineus L.
Circadian changes of three parameters of electrical properties in extensor cells of the laminar pulvini of Phaseolus coccineus L. have been recorded by standard microelectrode techniques. In the low turgor state of the cells, the resting potential and the CN(-) (1 millimolar NaCN) induced depolarizations are large, while the K(+)-induced voltage changes are small, and vice versa in the high turgor state. These results demonstrate that during a circadian cycle the low turgor state of the extensor cells is correlated with the active state of an electrogenic pump. This correlation can be explained by electroosmosis.


Test-Time Adaptation for Optical Flow Estimation Using Motion Vectors.
Due to the prohibitive cost as well as technical challenges in annotating ground-truth optical flow for large-scale realistic video datasets, the existing deep learning models for optical flow estimation mostly rely on synthetic data for training, which in turn may lead to significant performance degradation under test-data distribution shift in real-world environments. In this work, we propose the methodology to tackle this important problem. We design a self-supervised learning task for adjusting the optical flow estimation model at test time. We exploit the fact that most videos are stored in compressed formats, from which compact information on motion, in the form of motion vectors and residuals, can be made readily available. We formulate the self-supervised task as motion vector prediction, and link this task to optical flow estimation. To the best of our knowledge, our Test-Time Adaption guided with Motion Vectors (TTA-MV), is the first work to perform such adaptation for optical flow. The experimental results demonstrate that TTA-MV can improve the generalization capability of various well-known deep learning methods for optical flow estimation, such as FlowNet, PWCNet, and RAFT.


Nuclear expression of CXCR4 in tumor cells of non-small cell lung cancer is correlated with lymph node metastasis.
The stromal-derived factor 1alpha (CXCL12)/chemokine receptor CXCR4 system plays an important role in the metastatic process of a variety of cancers, with CXCR4 frequently expressed by tumor cells homing to CXCL12-rich compartments. The current study evaluated a possible association of CXCR4 expression with lymph node metastasis in primary non-small cell lung cancer. CXCR4 expression levels were evaluated using immunohistology in 46 non-small cell lung cancer specimens of patients without or with lymph node involvement (N0 = 24, N1/N2/N3 = 22). Evaluation of immunostaining was performed semiquantitatively by visual assessment. Statistical analyses with multiple testing adjustments for confirmatory comparisons were performed to assess relevant parameters associated with lymph node metastases. In all samples of non-small cell lung cancer, tumor cells stained positively for cytoplasmic CXCR4. The intensity of the CXCR4 staining varied considerably between specimens: 2 (4%) tumors demonstrated weak cytoplasmic CXCR4, 22 (48%) intermediate, and 22 (48%) strong staining. Membranous staining was absent; however, nuclear staining of CXCR4 was observed in 5 non-small cell lung cancer samples. Statistical analyses of the association between presence of lymph node metastases and CXCR4 expression levels revealed that cytoplasmic CXCR4 expression was not associated with the presence of lymph node metastases. However, nuclear CXCR4 was significantly correlated with increasing lymph node stage (P = .008), linear-to-linear association. The association between aberrant expression of CXCR4 in the nucleus of non-small cell lung cancer and metastasis to lymph nodes points toward a potential tumor metastasis promoting function of nuclear CXCR4.


Aqueous-based route toward noble metal nanocrystals: morphology-controlled synthesis and their applications.
Noble metal nanocrystals with controlled morphologies play important role in many fields, such as catalysis and SERS, etc. To date, solution-based methods developed to synthesize nanocrystals mainly exploit organic reagents as solvents including polyol, oleic acid/oleylamine, toluene, diphenyl ether and so on. In organic solvent systems, expensive organometallic precursors and toxic organic solvents are often used, bringing about substantial environmental issues. In this article, based on our recent endeavors, we will summarize facile, general aqueous methods to synthesize monodisperse, uniform, single and binary noble metal nanostructures and their applications in liquid fuel cells. We believe this review article will be useful to those devoted to the catalysis and nanocrystal fields.


The prevalence of undiagnosed thyroid disease in patients with symptomatic vocal fold paresis.
Vocal fold paresis has a multifactorial etiology and is idiopathic in many individuals. The incidence of thyroid-related neuropathy in the larynx has not been previously described. The purpose of this study was to evaluate the prevalence of previously undiagnosed thyroid disease in patients with laryngeal neuropathy and to compare this prevalence with that in a cohort of patients with a neurotologic neuropathy. Case series with chart review; tertiary care, otolaryngology practice. Charts of 308 consecutive patients with dysphonia and vocal fold paresis and 333 consecutive patients with sensorineural hearing loss, who presented for evaluation during a 3-year period, were reviewed. One hundred forty-six of 308 (47.4%) patients with vocal fold paresis were diagnosed with concurrent thyroid disease, whereas 55 of 333 (16.5%) patients with sensorineural hearing loss were diagnosed with concurrent thyroid disease (P<0.001, Pearson chi-square = 92.896; degrees of freedom = 5). Thyroid diagnoses among those with vocal fold paresis included benign growths (29.9%), thyroiditis (7.8%), hyperthyroidism (4.5%), hypothyroidism (3.6%), and thyroid malignancy (1.6%). Thyroid abnormalities are more prevalent in patients with dysphonia and vocal fold paresis than in patients with symptomatic sensorineural hearing loss, suggesting a greater association between previously undiagnosed thyroid abnormalities and laryngeal neuropathy than that between neurotologic neuropathy and thyroid disease.


Influence of non-alcoholic fatty liver disease on autonomic changes evaluated by the time domain, frequency domain, and symbolic dynamics of heart rate variability.
Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular atherosclerosis independent of classical risk factors. This study investigated the influence of NAFLD on autonomic changes, which is currently unknown. Subjects without an overt history of cardiovascular disease were enrolled during health checkups. The subjects diagnosed for NAFLD using ultrasonography underwent 5-min heart rate variability (HRV) measurements that was analyzed using the following indices: (1) the time domain with the standard deviation of N-N (SDNN) intervals and root mean square of successive differences between adjacent N-N intervals (rMSSD); (2) the frequency domain with low frequency (LF) and high frequency (HF) components; and (3) symbolic dynamics analysis. Routine blood biochemistry data and serum leptin levels were analyzed. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured. Of the 497 subjects (mean age, 46.2 years), 176 (35.4%) had NAFLD. The HRV indices (Ln SDNN, Ln rMSSD, Ln LF, and Ln HF) were significantly decreased in the NAFLD group (3.51 vs 3.62 ms, 3.06 vs 3.22 ms, 5.26 vs 5.49 ms(2), 4.49 vs 5.21 ms(2), respectively, all P<0.05). Ln SDNN was significantly lower in the NAFLD group after adjustment for age, sex, hypertension, dyslipidemia, metabolic syndrome, body mass index, smoking, estimated glomerular filtration rate, HOMA-IR, and leptin (P<0.05). In the symbolic dynamic analysis, 0 V percentage was significantly higher in the NAFLD group (33.8% vs 28.7%, P = 0.001) and significantly correlated with linear HRV indices (Ln SDNN, Ln rMSSD, and Ln HF). NAFLD is associated with decreased Ln SDNN and increased 0 V percentage. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). Further risk stratification of autonomic dysfunction with falls or cardiovascular diseases by these HRV parameters is required in patients with NAFLD.


Non-absorbable suture granuloma mimicking a retroperitoneal metastatic implant in a patient with sigmoid neoplasm.
The development of a foreign body granuloma from non-absorbable suture is a relatively uncommon condition, exceptional in the retroperitoneum of patients operated on for colorectal surgery. We report the case of a patient with a history of sigmoid neoplasm showing a retroperitoneal nodule on CT and high activity on PET, mimicking a tumor implant. Pathology found a foreign body granuloma. Foreign body granuloma from suture is a condition that may look identical to tumor relapse or metastatic disease on CT and PET scans, thus requiring pathology confirmation.


Reduction in acute coronary syndromes during coronavirus disease 2019 global pandemic: data from the Marche region of Italy.
During the novel severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019) pandemic, a worldwide reduction in total acute coronary syndrome (ACS) has been reported. In early 2020, Italy became the most affected country and national lockdown was declared early on in March. We described trends in ACS from all the Marche coronary catheterization laboratories (CCL) during the global pandemic. Retrospective study of all consecutive patients admitted to the four regional CCL. The coronavirus disease 2019 period (20 February 2020 to 15 April 2020) was compared with the interyear control period (1 January 2020 to 19 February 2020) and to the intrayear control period (20 February 2019 to 15 April 2019). All patients with an initial diagnosis of ACS were included in the analysis, and further stratified into ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI)/unstable angina. A total of 1239 patients were enrolled. Daily incidence of ACS was 6.1, 6.3 and 4.5 for the interyear control period, the intrayear control period and the case period, respectively. There was no difference in overall STEMI daily incidence while NSTEMI/unstable angina fell from 3.6 and 3.3-1.8 during the case period (P = 0.01). Incidence rate ratios were significantly lower when the case period was compared with the intrayear control period (incidence rate ratios: 0.49, 95% confidence interval 0.41-0.59, P = 0.001) and the interyear control period (incidence rate ratios: 0.67, 95% confidence interval 0.50-0.90, P = 0.008). During the global pandemic there was a significant reduction in total ACS and NSTEMI in the Marche region. Unlike previous reports, there was no difference in overall access to CCL for STEMI during the same period.


Neutral and color-selective beam splitting assemblies with polarization-independent intensities.
Arrangements consisting of at least three beam splitting surfaces are described that give rise to at least four different beams, of which at least two have polarization-independent spectral intensities. They can act over a wide spectral region and can be designed to be either achromatic or color selective. The performance of an experimentally produced device is described.


Irreducible fracture dislocation of the knee.
A unique case of an irreducible fracture dislocation of the knee is reported. A review of the literature revealed no previously reported cases of fracture dislocation of the distal femur not amenable to closed reduction.


Practicality in using diphenyl cyclo propenone for alopecia areata.
Diphenyl cyclo propenone (DPCP) is used as a topical immunomodulator in alopecia areata. It is a potent allergen. The process of procuring, dilution and application limits its wider use. This short communication aims to make the DPCP application easy to use.


[Health behavior and its rational in the perception of employees in medium-size and large companies].
The paper presents beliefs of employees working in Polish medium-size and large enterprises concerning the most essential aspects of healthy lifestyles and reasons for undertaking particular activities. In the study, carried out in 2002, questionnaire-based interviews were taken in a group of 1134 employees of 250 Polish enterprises employing 100 or more workers. The following forms of taking care of one's own health were perceived by the respondents as the best ones: healthy nutrition (68%); physical activity and fitness (46%); adequate rest and relaxation (45%); coping with stress (35%); and regular health checkups (34%). There are various reasons why respondents undertake particular activities. Among them willingness to take care of their own good health (79%); maintaining fitness (72%); and enhancing work ability (67%) were most frequently reported. Ill health and illness were less often mentioned (57% and 43%, respectively). Taking care of health is rather motivated by the will to avoid the dependence on negatively perceived health care institutions than by fear of discomfort due to ill health or occurrence of an illness. Health enhancing activities are more often undertaken by better educated, wealthier and younger people, while in case of illness, the opposite groups become more active. Social differences in motivation for healthy behaviors stress the need to apply various methods in health promotion programs to be able to influence target social groups.


Evaluation of the Relationship Between Bioactive Components in Seaweeds and Advanced Glycation End-Products Inhibitory Activities Using Principal Component Analysis.
This study comprehensively presents the relationship between the bioactive substance of 70% (v/v) aqueous ethanol extract of 38 species of seaweeds (SWEs), and anti-glycation activities. The contents of bioactive substance of SWEs, such as total phenolic, total flavonoid and condensed tannins, were determined through a colorimetric analysis. Among the tested species, Ecklonia bicyclis, Ishige foliacea, and Cladophora urightiana var. minor had the highest amount of total phenolic (255.75 mg GAE/g DW), total condensed tannins (63.36 mg CE/g DW), and total flavonoid content (85.26 mg CE/g DW), respectively. Anti-glycation properties of SWEs were evaluated through advanced glycation end-products (AGEs) formation, AGEs-collagen cross-link formation, and AGEs-collagen cross-link breaking assay. Brown algae species exhibited a more prominent inhibitory activity on AGEs formation and AGEs-collagen cross-links, and the breaking of AGEs-collagen cross-links compared to that exhibited by aminoguanidine and ALT-711 (positive controls). Using principal component analysis, we confirmed that the AGEs formation inhibitory property and AGEs-collagen cross-links breaking activity were closely correlated with total phenolic and the condensed tannin contents contained in SWEs. Therefore, the bioactive substances such as phenolics and condensed tannins in seaweeds can be used as predictive indices in selecting compounds for the development of a therapeutic agent that prevents diabetic complications related to the AGEs. In addition, our results suggest that brown algae species, which contains more bioactive substances than green and red algae species, can be utilized as a promising natural resource for the prevention and alleviation of AGEs-related diabetic complications as AGE inhibitor and cross-links breaker.


Cardiovascular responses elicited by the "binge" administration of methamphetamine.
Methamphetamine (METH) abuse is often characterized by a repeated pattern of frequent drug administrations (binge) followed by a period of abstinence. The effect of this pattern of METH use on cardiovascular function has not been characterized. Radiotelemetry was used to record the cardiovascular responses elicited during three successive METH binges (3 mg/kg, b.i.d. for 4 days) in conscious rats. Each binge was followed by a 10-day METH-free period. The effects of METH administration on vascular reactivity, Bezold-Jarisch reflex function, and cardiac morphology were also evaluated. The pressor responses elicited by the first three doses of METH in the second and third binges were significantly larger than those elicited by the corresponding doses in the first binge. The heart rate (HR) responses elicited by METH were similar within and among the three binges. Ten days after the last binge, the depressor responses elicited by the i.v. injection of sodium nitroprusside, isoproterenol, and acetylcholine were significantly smaller than those elicited before each binge. The arterial pressure and HR responses elicited by phenylephrine were unchanged. Bezold-Jarisch reflex function evoked by i.v. serotonin (10 microg/kg) was significantly altered. The hearts from treated rats showed focal inflammatory infiltrates with abundant monocytes and occasional necrotic foci. These results indicate that this binge pattern of METH administration can significantly alter cardiovascular function and cardiovascular reflex function and produce serious cardiac pathology.


Synthetic approaches to the microtubule stabilizing agent (-)-laulimalide.
In the past few years, the microtubule stabilizing agent (-)-laulimalide has attracted considerable attention, as it could constitute a potential treatment for cancer. Several total syntheses of (-)-laulimalide have now been reported. This review summarizes available biological data and synthetic approaches to (-)-laulimalide, reported prior to July 2002.


A review on antifungal activity and mode of action of essential oils and their delivery as nano-sized oil droplets in food system.
An escalated demand of minimally processed food and increased negative perception for synthetic preservative has led to a lookout for a natural preservative. Essential oils (EOs) are volatile and aromatic secondary metabolites of plants that have been tapped mainly for its flavour and fragrances and various biological properties such as antimicrobial and antioxidant. The constituents and antifungal potential of EOs have been reported widely in the present scientific literature. Moreover, the current scientific research dealing with the mode of action of EOs on fungal spores and mycelial cells are very scarce, unlike bacteria. The antimicrobial efficacy of EO in real food system may alter due to interaction with food matrix components. Besides, minimum alteration in sensory qualities while retaining its maximum activity is the most sought-after criteria for food preservation with EOs. If the oil is applied in excess to have better antimicrobial activity, it may end up having an unacceptable organoleptic impact on the food. Appropriate edible delivery systems of EOs as an emulsion is a probable approach to retain the maximum efficacy of EOs in the food system. Nano-emulsification of EO could increase its bioactivity due to increased bioavailability in the food matrix. The basis of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of EOs, and to recognize the application of EO as nano-sized oil droplets in the food system.


Moiré fringe multiplication with a nonsymmetrical doubly blazed reference grating.
A fine reference grating and coarse specimen grating in series are illuminated so that two dominant diffraction sequences take symmetrical paths in the intergrating space. In this optimum configuration, observation is on or near the axis of symmetry. Moiré sensitivity is that of the reference grating and independent of the specimen grating. The contour map described by moiré fringes depicts in-plane displacements uniquely, being insensitive to thickness and taper of gap between gratings. Moiré fringes are nearly perfect two-beam interference fringes of superb contrast. Existing gratings blazed for single-order dominance can be used under conditions that produce the required double-order dominance. In experimental evaluations, coarse gratings of 200 rulings/cm were mated with various reference gratings up to 12,000 rulings/cm for fringe multiplications by factors up to 60.


Stroke and age-brain barrier: how many bricks in the wall?
Although older people contribute more and more to the increasing social burden of stroke, they are often excluded from potentially effective treatments in clinical practice. With the aim to separate myth from reality, we have examined the barriers preventing such therapies (with reference to atrial fibrillation, thrombolysis, carotid stenosis and patent foramen ovale) in the elderly. We conclude that elevated age alone should not be considered an exclusion criterion and both stroke physicians and researchers should make efforts to greatly improve management of these patients.


Strategies of Mesenchymal Invasion of Patient-derived Brain Tumors: Microenvironmental Adaptation.
The high mortality in glioblastoma multiforme (GBM) patients is primarily caused by extensive infiltration into adjacent tissue and subsequent rapid recurrence. There are no clear therapeutic strategies that target the infiltrative subpopulation of GBM mass. Using mesenchymal mode of invasion, the GBM is known to widely infiltrate by interacting with various unique components within brain microenvironment such as hyaluronic acid (HA)-rich matrix and white matter tracts. However, it is unclear how these GBM microenvironments influence the strategies of mesenchymal invasion. We hypothesize that GBM has different strategies to facilitate such invasion through adaptation to their local microenvironment. Using our in vitro biomimetic microenvironment platform for three-dimensional GBM tumorspheres (TSs), we found that the strategies of GBM invasion were predominantly regulated by the HA-rich ECM microenvironment, showing marked phenotypic changes in the presence of HA, which were mainly mediated by HA synthase (HAS). Interestingly, after inhibition of the HAS gene, GBM switched their invasion strategies to a focal adhesion (FA)-mediated invasion. These results demonstrate that the microenvironmental adaptation allowed a flexible invasion strategy for GBM. Using our model, we suggest a new inhibitory pathway for targeting infiltrative GBM and propose an importance of multi-target therapy for GBM, which underwent microenvironmental adaptation.


Diagnostic value of fasting capillary glucose, fructosamine and glycosylated haemoglobin in detecting diabetes and other glucose tolerance abnormalities compared to oral glucose tolerance test.
New diagnostic criteria for diabetes mellitus recommend lowering of the fasting plasma glucose to 7.0 mmol/l. In contrast to recommendations of the American Diabetes Association (ADA), WHO recommends using the oral glucose tolerance test (OGTT) in clinical practice. In this study. based on OGTT results and WHO 1998 criteria, we determined if measuring fasting capillary glycaemia (FCG) along with fructosamine and/or glycosylated haemoglobin allows the detection of glucose tolerance abnormalities better than FCG alone. OGTT was performed in 538 patients. Serum fructosamine was determined in 480 of the patients, and glycosylated haemoglobin in 234 of the patients. According to WHO 1998 criteria, the patients were divided into groups due to glucose tolerance abnormalities. Fructosamine correlated stronger with 2-h post-load glucose concentrations than with FCG. HbAlc correlated stronger with FCG than with 2-h post-load glucose. Combined use of fructosamine and FCG predicted 2-h post-load glucose better than combined use of FCG and HbA1c. Receiver operating characteristic curve analyses showed that FCG was the best criterion in discriminating diabetes. Combined use of FCG and fructosamine slightly improved the ability to discriminate glucose tolerance abnormalities from normal glucose tolerance. FCG is the most effective predictor of 2-h post-load glucose and the best criterion for discriminating diabetes and other glucose tolerance abnormalities from normal glucose tolerance. Fructosamine is a potentially useful post-load glycaemia index. OGTT is irreplaceable in identification of patients with high post-load glycaemia.


Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development.
Various types of collagen have been identified as potential ligands for the two mammalian discoidin domain receptor tyrosine kinases, DDR1 and DDR2. Here, we used a recombinant fusion protein between the extracellular domain of DDR1 and alkaline phosphatase to detect specific receptor binding sites during mouse development. Major sites of DDR1-binding activity, indicative of ligand expression, were found in skeletal bones, the skin, and the urogenital tract. Ligand expression in the uterus during implantation and in the mammary gland during pregnancy colocalized with the expression of the DDR1 receptor. The generation of DDR1-null mice by gene targeting yielded homozygous mutant animals that were viable but smaller in size than control littermates. The majority of mutant females were unable to bear offspring due to a lack of proper blastocyst implantation into the uterine wall. When implantation did occur, the mutant females were unable to lactate. Histological analysis showed that the alveolar epithelium failed to secrete milk proteins into the lumen of the mammary gland. The lactational defect appears to be caused by hyperproliferation and abnormal branching of mammary ducts. These results suggest that DDR1 is a key mediator of the stromal-epithelial interaction during ductal morphogenesis in the mammary gland.


Treadmill Running and Rutin Reverse High Fat Diet Induced Cognitive Impairment in Diet Induced Obese Mice.
To determine the effects of treadmill exercise training and rutin intervention independently and in combination on key molecules involved in Alzheimer's disease (AD) pathology and cognitive function in diet induced obese (DIO) mice. C57BL/6J mice were randomized into 5 groups: chow group, high fat diet group (HFD), HFD plus rutin intervention group (HR), HFD combined with treadmill running group (HE), HFD combined with treadmill running and rutin group (HRE). At the end of the intervention, Morris water maze test was conducted to assess hippocampal dependent, long term spatial learning and memory retention. Hippocampus and cortex were dissected and the protein expression of key molecules including insulin-degrading enzyme (IDE), Beta-secretase (BACE1), signal transducer and activator of transcription 3 (STAT3), cAMP-response element binding protein (CREB), post-synaptic density protein 95 (PSD-95) and synaptophysin were measured via western blotting. Exercise and rutin enhances HFD induced cognitive deficits in DIO mice. In the hippocampus, although HFD has no effect on IDE, BACE1, phosphorylation (p)-STAT3 and p-CREB, HR and HE group have elevated protein expression of IDE; meanwhile, p-CREB was elevated in the HE and HRE group. In the cortex, HFD led to induction in BACE1 and reduction in p-STAT3 and PSD95. Rutin or exercise reversed BACE1, p-STAT3 and PSD95 to normal levels. Treadmill running and rutin could improve HFD induced cognitive impairment, and p-STAT3, p-CREB, BACE1, IDE, and PSD95 are potential mediators involved in the protective effects of rutin or exercise against HFD induced cognitive dysfunction.


Swelling behaviour and glass transition in genipin-crosslinked chitosan systems.
High-solid chitosan matrices were prepared to investigate the effect of their swelling on structural relaxation and glass transition. Degree of crosslinking in genipin-crosslinked chitosan networks was measured with a ninhydrin assay and a suitable crosslinker concentration was determined for gels used in swelling and thermomechanical analysis. Fourier transform infrared spectroscopy and wide angle X-ray diffraction examined the intermolecular interactions, crystallinity and amorphicity of the biopolymer networks. Swelling characteristics following immersion in water included approximate equilibrium values of the average molecular weight between crosslinks and network mesh size, e.g. 902 g mol-1 and 110 nm for the preparation with an initial solids content of 60% (w/w) after 80 min of swelling, which were quantified with the modified Flory-Rehner theory. Thermal glass transition temperature was observed in the condensed crosslinked networks (≥ 70% w/w total solids) during differential scanning calorimetry experiments. Time-temperature superposition of rheological measurements, obtained with dynamic oscillation in-shear, generated a master curve describing the viscoelastic behaviour of the system, moving through the rubbery, glass transition region and glassy state. Combined analysis using the modified Arrhenius and William-Landel-Ferry theories determined mechanical glass transition temperatures in the range of -68 to -8 °C for the crosslinked biopolymer at intermediate-solid concentrations (40 to 60% w/w solids). An understanding of the effect of swelling on molecular network characteristics was achieved, which is crucial for greater control in the design of systems for the targeted delivery of bioactive compounds.


Survey of waste comminglers' VOC exposures.
Twelve U.S. universities performing hazardous waste solvent commingling operations were surveyed for waste handler exposures to 45 U.S. Environmental Protection Agency (EPA)-designated volatile organic compounds (VOCs). Personal exposures (n = 33) and area concentrations (n = 30) were determined using gas chromatography/ mass spectrometry (GC/MS) analysis of passively collected samples. Air monitoring data were used to determine the veracity of laboratory-generated reports of waste container contents. Participants completed a questionnaire concerning the use of personal protective equipment, ventilation, and other appropriate safety equipment for their specific commingling operation. Follow-up telephone interviews were conducted to elucidate safeguards in place. Results showed that personal exposures exceeded area concentrations in 70% of operations. For the contaminant concentrations reported, 17% of personal samples exceeded Occupational Safety & Health Administration (OSHA) time-weighted average or ceiling limit values. Methylene chloride was a frequently seen airborne contaminant not listed on drum inventory sheets. When airborne constituents were compared with container content tags, 44% of the chemicals detected in air were omitted from the waste tags. This study concluded that the most frequently necessary safeguard is respiratory protection, preferably a supplied-air-type. The use of local exhaust ventilation systems rather than dilution or natural systems and facility operation in a totally explosion-safe manner are also recommended.


Impact of COVID-19 on cancer management in military hospitals of Saudi Arabia.
To evaluate the impact of COVID-19 on cancer management in Saudi Arabia's military hospitals. This multi-centric, retrospective study compared cancer patients diagnosed from February-July 2019 and 2020, focusing on the time duration for acceptance and time for oncologic treatment initiation. Eligibility and referral status were recorded. Clinical data of COVID-19-positive cancer patients were collected and evaluated their outcomes and survival. Data of 1574 cancer patients (mean age, 57.1 years) were collected. Mean time for acceptance was 7.3 days in 2019 and 8 days in 2020, with no statistically significant difference. Mean time for oncology treatment initiation was 38.4 days in 2019 and 44.3 days in 2020, with no statistically significant difference. The number of new cancer patients decreased in 2020 but increased in peripheral hospitals. It decreased in Riyadh and Jeddah hospitals. Concerning referral status, a statistically significant modification was recorded only in Riyadh and Tabuk hospitals. No significant changes observed in time duration for acceptance of new patients and oncology treatment initiation from 2019-2020. A total of 76 COVID-19-positive cancer patients recorded; 72% were symptomatic, 73.6% recovered, 22.3% died due to COVID-19 complications, and 8% died due to cancer; cancer progressed in 7 patients. COVID-19 did not affect oncology service in Saudi Arabia's military hospitals. New cancer cases reduced during the pandemic. Cancer patients are at increased risk for COVID-19 complications, including death.


The Relationship between Bilirubin Levels and Patients with Lupus Nephritis.
Bilirubin acts as an antioxidant. In this study, we assessed the relationship between the bilirubin level and lupus nephritis (LN). We included 50 newly diagnosed LN patients and 74 healthy individuals. Patients with LN were divided into three groups according to pathological classification. According to the activity index (AI), 42 LN patients were divided into two additional groups: AI < 4 and AI ≥ 4. We evaluated the changes in the bilirubin levels in 4 LN patients after glucocorticoid treatment. The bilirubin levels in the LN patients were significantly lower than those in the controls. The bilirubin levels in the patients with active LN were lower than those in the patients with non-active LN. The levels of bilirubin in the AI ≥ 4 group were lower than those in AI < 4 group. Moreover, bilirubin was negatively correlated with the 24-hour urine protein, but it was positively correlated with the glomerular filtration rate. The glucocorticoid treatment reduced the 24-hour urine protein level, and it increased the bilirubin level. The serum bilirubin level in the LN patients was decreased significantly, and this was related to the disease activity.


Injectable hydrogels for ophthalmic applications.
The demand for effective eye therapies is driving the development of injectable hydrogels as new medical devices for controlled delivery and filling purposes. This article introduces the properties of injectable hydrogels and summarizes their versatile application in the treatment of ophthalmic diseases, including age-related macular degeneration, cataracts, diabetic retinopathy, glaucoma, and intraocular cancers. A number of injectable hydrogels are approved by FDA as surgery sealants, tissue adhesives, and are now being investigated as a vitreous humor substitute. Research on hydrogels for drug, factor, nanoparticle, and stem cell delivery is still under pre-clinical investigation or in clinical trials. Although substantial progress has been achieved using injectable hydrogels, some challenging issues must still be overcome before they can be effectively used in medical practice.


[Testicular microlithiasis influences seminal profile and testicular blood flow in infertile men].
To investigate the testicular blood flow in patients with testicular microlithiasis (TM) and its correlation with the seminal profile in infertile men. We selected 88 infertile men and examined them by testicular color Doppler and routine seminal tests. Testicular microlithiasis was found in 19 (19.3%) of the patients, classic testicular microlithiasis (CTM) in 7 (8.0%), and limited testicular microlithiasis (LTM) in 10 (11.3%). No significant differences were observed in the age of onset, bilateral testicular volume, resistance index (RI) of bilateral testicular arteries, semen amount and the rate of teratospermia. The bilateral testicular peak systolic velocity (PSV), sperm count and sperm motility were significantly lower in the CTM than in the LTM group (P < 0.05), but showed no statistically significant difference between the LTM and the non-calcification group. TM may be one of the causes of poor sperm function in infertile men.


Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population: role of serine protease inhibitor Kazal 1type and alcohol.
To test the hypothesis that calcium sensing receptor (CASR) polymorphisms are associated with chronic pancreatitis (CP), and to determine whether serine protease inhibitor Kazal 1type (SPINK1) N34S or alcohol are necessary co-factors in its etiology. Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms (SNPs) in exon 7 (A986S, R990G, and Q1011E). The CASR exon 7 R990G polymorphism was significantly associated with CP (OR, 2.01; 95% CI, 1.12-3.59; P = 0.015). The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption (OR, 3.12; 95% CI, 1.14-9.13; P = 0.018). There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.


Separation and Some Properties of Large and Small Amyloplasts throughout Development in Barley Endosperm.
A method is described whereby amyloplasts from immature barley (Hordeum distichum L.) endosperm could be separated into two populations of large and small amyloplasts at all stages of development. The small amyloplasts had more amylopectin than the large at early stages, but by 60 days after anthesis, the large had the greater proportion of amylopectin. Starch synthetase activity was associated with both types of amyloplast. The nucleotide specificity of the starch synthetase associated with each population varied independently throughout development. At 25 days after anthesis, the large amyloplasts were more susceptible than the small to alpha-amylolysis; however, at 38 and 60 days, the small amyloplasts became more susceptible.


Acetylome with structural mapping reveals the significance of lysine acetylation in Thermus thermophilus.
Lysine acetylation in proteins has recently been globally identified in bacteria and eukaryotes. Even though acetylproteins are known to be involved in various cellular processes, its physiological significance has not yet been resolved. Using a proteomics approach in combination with immunoprecipitation, we identified 197 lysine acetylation sites and 4 N-terminal acetylation sites from 128 proteins in Thermus thermophilus HB8, an extremely thermophilic eubacterium. Our analyses revealed that identified acetylproteins are well conserved across all three domains of life and are mainly involved in central metabolism and translation. To characterize the functional significance further, we successfully mapped 172 acetylation sites on their 59 authentic and 54 homologous protein structures. Although the percentage of acetylation on ordered structures was higher than that of the disordered structure, no tendency of acetylation in T. thermophilus was detected in secondary structures. However, the acetylated lysine was situated near the negatively charged glutamic acid residues. In tertiary structure analyses, 58 sites of 103 acetylations mapped on 59 authentic structures of T. thermophilus were located within a considerable distance that can disrupt electrostatic interactions and hydrogen bonding networks on protein surfaces, demonstrating the physiological significance of the acetylation that can directly alter the protein structure. In addition, we found 16 acetylation sites related to Schiff base formation, ligand binding, and protein-RNA and protein-protein interactions that involve the potential function of the proteins. The structural mapping of acetylation sites provides new molecular insight into the role of lysine acetylation in the proteins.


Comparing different preparation methods to study human fibrin fibers and platelets using TEM.
For the study of cellular ultrastructure, the sample needs to be stabilized by fixation, with the ultimate aim to preserve the native tissue organization and to protect the tissue against later stages of preparation. Chemical and freezing fixation are most used, and chemical fixation employs agents that permeate tissues and cells by diffusion and covalently bind with their major biochemical constituents to fix them. Most widely used chemical fixatives are aldehydes, e.g., formaldehyde and glutaraldehyde, which are noncoagulating, crosslinking agents. Cryofixation methods for ultrastructural studies are also popular, and high-pressure freezing immobilizes all cell constituents and arrests biological activity by removing the thermal energy from the system. In the current research, we used platelet-rich plasma (PRP) to study expansive fibrin fibers and platelet ultrastructure to compare the two fixation techniques. We also used thrombin and calcium chloride as a clotting agent to determine the technique most suitable for the formation of extensive fibrin networks. Chemically fixated fibrin fibers were more compact and condensed and also showed a banding pattern on longitudinal sections. High-pressure frozen samples were more dispersed while platelets fixated showed better preserved cellular membranes and organelle structure. PRP coagulated by addition of CaCl(2) showed blood platelets that are noticeably more activated compared with PRP; however, with thrombin, a sharp ultrastructure was seen. We conclude that PRP mixed with thrombin, and freeze substituted, is the most suitable method for the study of extensive fibrin fibers as well as platelets.


Comparing prevalence of HIV-related behaviors among female injecting drug users (IDU) whose regular sexual partner was or was not IDU in Sichuan and Yunnan Provinces, China.
Injecting drug users made up a high percentage of HIV cases in China; partners of IDU are hence, at very high risk of HIV transmission. The goal of this study is to compare characteristics and prevalence of injecting drug use and sex-related risk behaviors among female IDU who were or were not having a regular sex partner (RSP) with concordant IDU status. Data were obtained from all female IDU respondents (n=1414) surveyed in the behavioral surveillance surveys as conducted during 2003 through 2006 in Sichuan and Yunnan, China. The findings from this research reveal that about half of the female IDU respondents belonged to the concordant group (50.4%). As compared to members of the discordant group, such concordant respondents were significantly more likely to have practiced different types of studied syringe sharing behaviors (adjusted odds ratios AOR=1.34-2.23, p<0.05), to have served as female sex workers in the last month (AOR=1.24, p<0.05), or to have used some particular types of HIV-related prevention services (AOR=1.36-1.60, p<0.05) but were less likely to be always using new needles for drug injection in the last month (AOR=0.54, p<0.05) or to have used a condom in the last episode of sex with their RSP (AOR=0.64, p<0.01). The findings suggest that concordant IDU status is very common among RSP of IDU. The risk for HIV transmission between concordant RSP seems to be very high and the prevention services seem unable to alleviate the risk. Specific programs targeting concordant IDU couples are greatly warranted.


The use of composite acellular allodermis-ultrathin autograft on joint area in major burn patients--one year follow-up.
Scar contracture is a major long-term sequelae of meshed split-thickness skin grafts in the case of full-thickness burn injuries, and especially in joint areas. Severe contracture around joints may lead to loss of mobility. The thickness of the dermis in the autograft plays a major role in the functional and cosmetic outcomes of the third degree burn. How to replace lost dermis is a major problem in skin restoration following severe burns. The human allograft skin (AlloDerm) is an acellular dermal matrix with normal collagen bundling organization and intact basement membrane complex. We present 12 cases of clinical application of a composite grafting technique in which the allogeneic skin (AlloDerm) provided source of dermis, and an ultrathin autograft (0.004-0.006 inch in thickness) provided epidermis. In these patients, The composite grafts were applied to full-thickness burn wounds over various articular skin surfaces. The average skin graft take rate was 91.5%. These ultrathin autografts allow the donor sites to heal faster. The mean time of donor site reepithelization was 6 days. All patients had a nearly normal range of joint motion (average 95% of normal) after one year's follow up. Wound assessment over time has shown supple skin that has been resistant to trauma and infection. The cosmetic results were judged to be fair to good by surgeons and patients after one year's follow up.


Predominant Determinants of Delayed Tuberculosis Sputum Conversion in Indonesia.
Sputum conversion in the first 2 months of tuberculosis (TB) treatment is closely related to successful treatment and a decrease in the likelihood of relapse. In 2015, there were 76% high TB burden countries with low rate of TB successful treatment. This study aims to evaluate the correlation between delayed sputum conversion and several determinants including social determinants, smoking, malnutrition, and type II diabetes mellitus (DM). A case-control approach was used to study the potential determinants. A case sample group consisted of smear-positive TB patients with delayed sputum conversion (31 patients) at community health centers in Bandar Lampung, Indonesia. Meanwhile, a control sample group consisted of smear-positive TB patients with sputum conversion (62 patients). Primary data consisted of social determinants and smoking, were collected through in-depth interviews. Meanwhile, secondary data consisted of malnutrition, DM, and sputum conversion were obtained from the medical record. Data were analyzed using Chi-square and multivariate logistic regression. Low education (odds ratio [OR]: 5.313; 95% (confidence interval [CI]: 1.711-16.503), low social class (OR: 4.993; 95% CI: 1.430-17.430), smoking (OR: 7.457; 95% CI: 1.757-31.640), and DM (OR: 7.168; 95% CI: 1.746-29.431) influenced delayed sputum conversion. TB control programs in high TB burden countries with low rate of TB successful treatment, should be integrate TB treatment education, smoking cessation programs and follow-up treatments for TB patients with DM to improve the probability of sputum conversion and successful treatment.


Functional Optical Zone and Centration Following SMILE and LASIK: A Prospective, Randomized, Contralateral Eye Study.
To compare centration and functional optical zone (FOZ) after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (LASIK). In this prospective, randomized, single-masked, paired-eyed, clinical trial, 70 patients received SMILE in one eye and LASIK in the other eye for myopia and myopic astigmatism. FOZ was calculated using custom software on 3-month postoperative refractive power maps (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany). Programmed treatment area was defined as the total area of the programmed OZ plus the transition zone. Centration was evaluated by the linear distance between FOZ centroid and the pupil center and the corneal apex. The average preoperative spherical equivalent (-5.38 ± 1.65 vs -5.45 ± 1.61 diopters [D]), postoperative spherical equivalent (0.05 ± 0.39 vs 0.06 ± 0.39 D), uncorrected distance visual acuity (0.01 ± 0.13 vs 0.00 ± 0.08 logMAR), and corrected distance visual acuity (-0.07 ± 0.10 vs -0.07 ± 0.10 logMAR) were comparable in SMILE- and LASIK-treated eyes of the 60 patients with complete datasets (P > .419). Postoperative increase in spherical aberration was lower in SMILE than in LASIK (0.08 ± 0.16 vs 0.17 ± 0.18 µm, P = .002). The FOZ area was significantly larger in SMILE than in LASIK (30.25 ± 3.60 vs 29.21 ± 3.72 mm2), despite the smaller programmed OZ diameter (6.48 ± 0.08 vs 6.52 ± 0.11 mm) and smaller programmed treatment area (33.87 ± 0.81 vs 46.30 ± 2.61 mm2, P < .037). Pupil centration (0.43 ± 0.21 vs 0.41 ± 0.22 mm) and apex centration (0.48 ± 0.24 vs 0.48 ± 0.22 mm) were comparable between SMILE and LASIK (P > .694). SMILE created a larger FOZ than LASIK, despite the smaller programmed OZ. This may be due to a difference in the biomechanical response between the two procedures. Visual outcome and centration were comparable between SMILE and LASIK. [J Refract Surg. 2019;35(4):230-237.].


[Statistical analysis of the fabrication of fixed and removable partial dentures (in 2002)].
A statistical survey based on laboratory records was performed on the number of fixed partial dentures and removable partial dentures fabricated at the dental hospital of Tokyo Medical and Dental University from April 1 to September 30, 2002. A comparison was also performed with a previous survey that had been carried out in 1997 to detect any change and possible alternations in the near future. From the findings of this statistical survey, the conclusions were as follows: 1. A total of 2,656 fixed and removable partial dentures were fabricated during the six-month period in 2002. 2. The 3-unit fixed partial denture was most common (64.0%), and the number of fixed partial dentures decreased as the number of units increased. 3. For a single missing tooth, a fixed partial denture was more popular (80.8%) than a removable partial denture. 4. For two missing teeth, there was little difference between the number of fixed and removable partial dentures. In the anterior region, fixed partial denture was more common, while in contrast, in the posterior region, removable partial denture was more common.


The Influence of Radiological Severity and Symptom Duration of Osteoarthritis on Postoperative Outcome After Total Hip Arthroplasty: A Prospective Cohort Study.
We aimed to investigate the influence of preoperative radiological severity and symptom duration of hip osteoarthritis (OA) on the postoperative functional outcome, quality of life, as well as abductor muscle strength after total hip arthroplasty (THA). In this prospective cohort study, we studied 250 patients. Preoperatively, we evaluated the function with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and quality of life with euroqol-5D (EQ-5D). At 1 year after THA, the same scores and also hip abductor muscle strength were measured in 222 patients. We divided the cohort twice, first according to the radiological OA severity [Kellgren-Lawrence classification (KL)] and then according to the OA symptom duration. We investigated whether the preoperative KL class and symptom duration influenced the 1-year WOMAC (primary outcome measure) or EQ-5D and abductor muscle strength (secondary outcome measures). The crude results showed that KL class and symptom duration had no influence (P = .90 and P = .20, respectively) on the 1-year WOMAC. Younger age, male gender, and lower body mass index were associated with a better function. Regarding 1-year EQ-5D, the crude results showed that body mass index and KL class had no influence (P = .83 and P = .39, respectively). The adjusted results showed that only age and gender influenced the postoperative EQ-5D. No influence of the tested factors was found on the 1-year abductor muscle strength. Preoperative radiological OA severity and symptom duration had no influence on the outcome of THA and should probably not affect the decision about timing the operative intervention.


Molecular Identification of Nocardia seriolae and Comparative Analysis of Spleen Transcriptomes of Hybrid Snakehead (Channa maculata Female × Channa argus Male) With Nocardiosis Disease.
Hybrid snakehead (Channa maculata female × Channa argus male) is a new freshwater aquaculture fish species in southern China. During intensive aquaculture, hybrid snakeheads are often infected by Nocardia seriolae. In this study, hybrid snakehead infected suspiciously by N. seriolae in an artificial breeding pond were examined. Diseased hybrid snakeheads swam slowly without food intake, and the clinical symptoms included skin wound, anal swelling and ascites, and white granulomatous in liver, spleen, and kidney of fish. Through bacterial isolation, 16S rDNA sequencing, fluorescence in situ hybridization (FISH) and artificial infection experiment, the pathogen was identified as N. seriolae. Furthermore, the spleen samples from diseased and healthy male hybrid snakeheads in the same pond were used for RNA-Seq analysis. A total of 3,512 unique transcripts (unigenes) were identified as differentially expressed genes (DEGs), and 1,886 of them were up-regulated in diseased fish. The expression patterns of 20 DEGs were verified by quantitative polymerase chain reaction (qPCR). Several immune-related pathways and many immune-related genes were identified. qPCR results showed that the expression patterns of immune-related genes in the liver and kidney of diseased fish were comparable to that in the spleen. This study provides deep-sequencing data of hybrid snakehead spleen and will help understand the immune response of hybrid snakehead to N. seriolae. It is also helpful for the biomarker screening of fish-borne Nocardia spp. and the breeding of nocardiosis-resistant fish species.


The MMN amplitude increases in hypnosis: a case study.
The neural mechanisms associated with hypnosis were investigated in a single highly hypnotizable subject by measuring the mismatch negativity (MMN) component of auditory ERP, reflecting the preattentive discrimination of change in stimulus flow, in normal baseline state and under hypnosis. It has been proposed that the frontal inhibition associated with hypnosis can be measured as a decrease in MMN. ERPs were elicited using the passive oddball paradigm with standard and deviant sine tone stimuli of 500 and 553Hz, respectively. The measurement was repeated in five separate sessions. In hypnosis the MMN was significantly larger compared to baseline. The results indicate that hypnosis can give rise to altered information processing in the brain even at a relatively early, i.e. preattentive level and that the larger MMN measured under hypnosis does not support frontal inhibition theory.


Characterization of surface ligands on functionalized magnetic nanoparticles using laser desorption/ionization mass spectrometry (LDI-MS).
Functionalized magnetic nanoparticles (MNPs) have been characterized by laser desorption/ionization mass spectrometry (LDI-MS). Quantitative information about surface ligand composition and structure for monolayer and mixed monolayer protected Fe3O4 and FePt NPs can be obtained rapidly with very little sample consumption.


Symbolic computations of nonlinear observability.
Observability is a very useful concept for determining whether the dynamics of complicated systems can be correctly reconstructed from a single (univariate or multivariate) time series. When the governing equations of dynamical systems are high-dimensional and/or rational, analytical computations of observability coefficients produce large polynomial functions with a number of terms that become exponentially large with the dimension and the nature of the system. In order to overcome this difficulty, we introduce here a symbolic observability coefficient based on a symbolic computation of the determinant of the observability matrix. The computation of such coefficients is straightforward and can be easily analytically carried out, as demonstrated in this paper for a five-dimensional rational system.


Salinity effects on photosynthesis in isolated mesophyll cells of cowpea leaves.
Mesophyll cells from leaves of cowpea (Vigna unquiculata [L.] Walp.) plants grown under saline conditions were isolated and used for the determination of photosynthetic CO(2) fixation. Maximal CO(2) fixation rate was obtained when the osmotic potential of both cell isolation and CO(2) fixation assay media were close to leaf osmotic potential, yielding a zero turgor pressure. Hypotonic and hypertonic media decreased the rate of photosynthesis regardless of the salinity level during plant growth. No decrease in photosynthesis was obtained for NaCl concentrations up to 87 moles per cubic meter in the plant growing media and only a 30% decrease was found at 130 moles per cubic meter when the osmotic potential of cell isolation and CO(2) fixation media were optimal. The inhibition was reversible when stress was relieved. At 173 moles per cubic meter NaCl, photosynthesis was severely and irreversibly inhibited. This inhibition was attributed to toxic effects caused by high Cl(-) and Na(+) accumulation in the leaves. Uptake of sorbitol by intact cells was insignificant, and therefore not associated with cell volume changes. The light response curve of cells from low salinity grown plants was similar to the controls. Cells from plants grown at 173 moles per cubic meter NaCl were light saturated at a lower radiant flux density than were cells from lower salinity levels.


Dietary Flavonoids Alleviate Inflammation and Vascular Endothelial Barrier Dysfunction Induced by Advanced Glycation End Products In Vitro.
The aim of this study was to compare the protective effects of three dietary flavonoids (apigenin-7-O-glucoside (A7G), isorhamnetin-3-O-rutinoside (I3R), and cyanidin-3-O-glucoside (C3G)) on advanced glycation end products (AGEs)-induced inflammation and vascular endothelial dysfunction. Furthermore, the potential mechanisms of varied effects of those three dietary flavonoids were analyzed by molecular docking analysis. Results showed that C3G (40 μM) achieved the best inhibition on inflammatory cytokines (TNF-α, IL-1β, and IL-6) in AGEs-induced RAW264.7 cells, followed by I3R, and A7G was the weakest. The molecular docking results also showed that C3G exhibited the closest binding with the receptor for AGE. However, I3R (40 μM) demonstrated the best effect in improving endothelial dysfunction in AGEs-induced EA.hy926 cells, followed by C3G, and A7G was the weakest, as evidenced by the molecular docking results of flavonoids with profilin-1. This work may provide knowledge and helpful suggestions regarding the benefits of dietary flavonoids in diabetic vascular complications.


Screening of antinociceptive components in Corydalis yanhusuo W.T. Wang by comprehensive two-dimensional liquid chromatography/tandem mass spectrometry.
Formalin-induced pain models were used in rats to evaluate the antinociceptive effect of the total alkaloids of Corydalis yanhusuo (TAC). The results indicated that formalin-evoked spontaneous nociceptive responses (licking behavior) could be inhibited significantly by giving (intragingival) TAC at a single dose of 150 mg/kg. Subsequently, an online comprehensive two-dimensional biochromatography method with a silica-bonded human serum albumin (HSA) column in the first dimension and a monolithic ODS column in the second was developed. The absorbed bioactive components were screened by comparing and contrasting the components detected in the plasma and striatum with those in TAC. More than 100 compounds were separated and detected in the TAC, among which 13 compounds were identified. About 40 compounds (seven compounds identified) were absorbed into the plasma with appropriate concentrations and about 20 compounds (four compounds identified) passed through the blood-brain barrier into the striatum. Of interest, four compounds (protopine, glaucine, tetrahydropalmatine, and corydaline) which were reported to possess profound antinociceptive effects exhibited high concentrations in the striatum. This may result from their synergistic effects in regulating the formalin-induced nociception. The results indicated that the comprehensive two-dimensional biochromatography method developed is capable of screening the bioactive components in Corydalis yanhusuo and providing valuable information for understanding the mechanisms by which Corydalis yanhusuo alleviates nociception.


Application of a novel antioxidative assay in beer analysis and brewing process monitoring.
A novel antioxidative assay based on direct current polarography has been developed. Quantification of antioxidative (AO) activity has been based on a decrease of hydrogen peroxide anodic current in the presence of antioxidants. An efficient experimental procedure, without any special pretreatment of analyzed samples, has been applied. Antioxidative activity of different kinds of commercial beers (dark, blond, and alcohol-free), some small-scale made special beers with medicinal herbs and mushroom extracts, extracts themselves, as well as individual phenolic components present in beer has been measured. In addition, changes of AO activity during the full-scale industrial process of beer production have been monitored. A strong correlation between results obtained and total phenolics content has been observed. The assay can be recommended for application in brewing industry, either to survey a process with the aim to optimize relevant technological factors or to analyze quality of final product.


Urgent intracranial carotid artery decompression after penetrating head injury.
We describe a case of intracranial carotid artery occlusion due to penetrating craniofacial injury by high velocity foreign body that was relieved by decompressive surgery. A 46-year-old man presented with a penetrating wound to his face. A piece of an electric angular grinder disc became lodged in the anterior skull base. Computed tomography revealed that the disc had penetrated the unilateral paraclinoid and suprasellar areas without flow of the intracranial carotid artery on the lesion side. The cavernous sinus was also compromised. Removal of the anterior clinoid process reopened the carotid blood flow, and the injection of glue into the cavernous sinus restored complete hemostasis during extraction of the fragment from the face. Digital subtraction angiography revealed complete recanalization of the carotid artery without any evidence of dissection. Accurate diagnosis regarding the extent of the compromised structures and urgent decompressive surgery with adequate hemostasis minimized the severity of penetrating damage in our patient.


TNF-α (-308G>A) and TNF-R1 (36A>G) single nucleotide polymorphisms are strong risk factors for odontogenic keratocystic tumor development.
Polymorphisms in genes encoding tumor necrosis factor-α (TNF-α) and its receptor TNF-R1 have been shown to affect one person's susceptibility to develop certain neoplastic diseases. The aim of the present association study was to investigate whether single nucleotide polymorphisms (SNPs) in TNF-α (-308G>A) and TNF-R1 (36A>G) genes modulate the susceptibility for keratocystic odontogenic tumors (KCOTs) development in Serbian patients. Genotyping was performed in 60 KCOT patients and 125 healthy individuals, using polymerase chain reaction/restriction fragment length polymorphism analysis. A significant difference in genotype and allele frequencies was found between patients and controls for both SNPs (P < 0.05). Carriers of the TNF-α A variant had an eightfold increase of KCOT risk (OR = 8.12, 95% CI = 3.98-16.56, P < 0.0001), while carriers of the TNF-R1 G variant had approximately a fourfold increase of KCOT risk (OR=3.65, CI: 1.60-8.40, P = 0.001). Our findings suggest that the two polymorphisms are strong risk factors for KCOT development in Serbian population.


CD36 expression and lipid metabolism following an oral glucose challenge in South Asians.
To investigate lipid metabolism and the relationship with monocyte expression of the fatty acid translocase CD36 in South Asians. An observational study of South Asians whom as an ethnic group have - a higher risk of developing diabetes. The susceptibility to diabetes is coupled with an earlier and more rapid progression of micro-, and macro-vascular complications. Twenty-nine healthy South Asian participants [mean age 34.6 (8.9) years, 76.2% male, mean body-mass index 25.0 (5.2) kg/m(2)] were recruited from an urban residential area of central Birmingham (United Kingdom). The main outcomes measured were post prandial (30 min) and post absorptive (120 min) changes from fasting (0 min) in circulating lipoproteins, lipds and hormones, and monocyte expression of CD36 post injection of a 75 g oral glucose challenge. The inducements of variations of monocyte CD36 expression were analysed. Our results showed evident changes in monocyte CD36 expression following the glucose challenge (P < 0.001). Non-esterified fatty acids (NEFA) levels decreased progressively during the challenge (P < 0.001), in contrast to increased cholesterol (but not triglyceride) concentrations within very low density lipoprotein (VLDL) and low density lipoprotein subfractions (P < 0.01). Levels of, glucose, serum triglycerides and high density lipoprotein cholesterol remained largely unchanged. Variations of monocyte CD36 were negatively (r = -0.47, P = 0.04) associated to fat from the diet and positively to carbohydrate from the diet (r = 0.65, P < 0.001). These data suggest that the initiation of VLDL genesis follows the consumption of glucose within this population, inferring that the sequestration of NEFA from these particles happens due to the increased availability of CD36 receptors. While these are preliminary results, it would appear that lifestyle exposures have a role in moderating the expression of CD36.


Mechanisms for modification of bromobenzene hepatotoxicity by coadministered toluene and chlorobenzene.
Hepatotoxicity of bromobenzene (2 mmole/kg) in combination with toluene or chlorobenzene (4 mmole/kg each) were studied in vivo on the basis of GPT elevation and histological examinations. Both toluene and chlorobenzene suppressed bromobenzene hepatotoxicity 24 hr after the treatment, and chlorobenzene dramatically potentiated the toxicity at 48 hr. The glutathione level became lower at 12 hr and recovered at 24 hr when bromobenzene was given alone. The recovery delayed until 48 hr when chlorobenzene was coadministered. In experiments in vitro with microsomes from phenobarbital-pretreated rats, both toluene and chlorobenzene at 0.6 mM inhibited p-bromophenol formation noncompetitively but had no effect on o-isomer formation. Multiple factors may determine overall hepatotoxicity in combined exposure; bromobenzene hepatotoxicity will be suppressed in the early phase owing to metabolic inhibition of 3,4-epoxidation, but potentiated later because of delayed recovery in the glutathione level. A time-saving yet reliable assay system with an ECD-gas chromatograph was developed for bromobenzene metabolism study.


So much for the city: Urban-rural song variation in a widespread Asiatic songbird.
Song plays a fundamental role in intraspecific communication in songbirds. The temporal and structural components of songs can vary in different habitats. These include urban habitats where anthropogenic sounds and alteration of habitat structure can significantly affect songbird vocal behavior. Urban-rural variations in song complexity, song length and syllable rate are not fully understood. In this study, using the oriental magpie-robin (Copsychus saularis) as a model, we investigated urban-rural variation in song complexity, song length, syllable rate, syllable length and inter-syllable interval. Comparing urban and rural songs from 7 countries across its natural Asiatic range (Bangladesh, India, Malaysia, Nepal, Singapore, Sri Lanka and Thailand), we found no significant differences in oriental magpie-robin song complexity. However, we found significant differences in temporal song variables between urban and rural sites. Longer songs and inter-syllable intervals in addition to slower syllable rates within urban sites contributed the most to this variance. This indicates that the urban environment may have driven production of longer and slower songs to maximize efficient transmission of important song information in urban habitats.


Bayesian inference for finite mixtures of univariate and multivariate skew-normal and skew-t distributions.
Skew-normal and skew-t distributions have proved to be useful for capturing skewness and kurtosis in data directly without transformation. Recently, finite mixtures of such distributions have been considered as a more general tool for handling heterogeneous data involving asymmetric behaviors across subpopulations. We consider such mixture models for both univariate as well as multivariate data. This allows robust modeling of high-dimensional multimodal and asymmetric data generated by popular biotechnological platforms such as flow cytometry. We develop Bayesian inference based on data augmentation and Markov chain Monte Carlo (MCMC) sampling. In addition to the latent allocations, data augmentation is based on a stochastic representation of the skew-normal distribution in terms of a random-effects model with truncated normal random effects. For finite mixtures of skew normals, this leads to a Gibbs sampling scheme that draws from standard densities only. This MCMC scheme is extended to mixtures of skew-t distributions based on representing the skew-t distribution as a scale mixture of skew normals. As an important application of our new method, we demonstrate how it provides a new computational framework for automated analysis of high-dimensional flow cytometric data. Using multivariate skew-normal and skew-t mixture models, we could model non-Gaussian cell populations rigorously and directly without transformation or projection to lower dimensions.


Nondiscrimination on the basis of handicap--Office of the Secretary, HHS. Interim final rule.
The interim final rule modifies existing regulations to meet the exigent needs that can arise when a handicapped infant is discriminatorily denied food or other medical care. Three current regulatory provisions are modified to allow timely reporting of violations, expeditious investigation, and immediate enforcement action when necessary to protect a handicapped infant whose life is endangered by discrimination in a program or activity receiving federal financial assistance. Recipients that provide health care to infants will be required to post a conspicuous notice in locations that provide such care. The notice will describe the protections under federal law against discrimination toward the handicapped, and will provide a contact point in the Department of HHS for reporting violations immediately by telephone.


Evaluating the Reliability and Reproducibility of the AO and Lauge-Hansen Classification Systems for Ankle Injuries.
Ankle injuries are responsible for more than 5 million emergency department visits each year. The AO and Lauge-Hansen classification systems are widely used in the clinical diagnosis of ankle injuries. This study aimed to analyze the intraobserver reliability and interobserver reproducibility of the AO and Lauge-Hansen classification systems. In addition, the authors explored the differences among physicians' classification responses and evaluated the clinical value for diagnosis. Fifty-six patients with an ankle injury with complete clinical and radiologic data were enrolled. The definition of injury type, the index score typing methods, and the specific study criteria were explained in detail. Five observers, who were orthopedic surgeons, determined the classifications according to both the AO and Lauge-Hansen systems. The classification was repeated 1 month later. Cronbach's alpha and Cohen's kappa test were used to determine interobserver reliability and intraobserver reproducibility. The physicians conducted 560 classifications (56 cases × 5 physicians × 2 times per patient). Average inter- and intraobserver kappa values for the AO system were 0.708 and 0.608, respectively. Average inter- and intraobserver kappa values for the Lauge-Hansen system were 0.402 and 0.398, respectively. Cronbach's alpha coefficient was 96.7% for the AO system and 76.0% for the Lauge-Hansen system. The Lauge-Hansen classification system is a comprehensive yet cumbersome system. Comparatively, the AO classification system is easier to understand. This study shows that the AO classification system has more reliability and reproducibility, and thus has more value in clinical practice, than the Lauge-Hansen classification system.


Insight in the relationship between the structure and property of methimazole monolayers on a silver surface: electrochemical and Raman study.
Methimazole (MMI) monolayers on the silver surface were studied by electrochemical impedance spectroscopy (EIS), electrochemical polarization measurement, and surface-enhanced Raman scattering (SERS) spectroscopy. The EIS mechanism of the silver surface with MMI monolayers was fitted with the mode of LR(QR)(QR), and the electrochemical polarization experimental results showed a high inhibitive efficiency around 82.6%. SERS results indicated that the MMI molecule with a tilted orientation anchored at the silver surface via S(6), N(2), and N(5) atoms, resulting in a strong interaction between the MMI molecule and the surface. In situ electrochemical SERS observation suggested that the molecule experienced a transition state of the adsorption because of the electrochemical hydrogen evolution reaction occurred about -0.1 V vs SCE.


Lifetime economic burden of prostate cancer.
Prostate cancer (PCa) is the most common cancer affecting men in the United States. The initial treatment and subsequent monitoring of PCa patients places a large burden on U.S. health care systems. The objectives of this study were to estimate the total and disease-related per-patient lifetime costs using a phase-based model of cancer care for PCa patients enrolled in Medicare. A model was developed to estimate life-time costs for patients diagnosed with PCa. Patients ≥ 65 years old and diagnosed with PCa between calendar years 1991-2002 were selected from the SEER database. Using SEER, we estimated survival times for PCa patients from diagnosis until death. The period of time patients contributed to treatment phases was determined using an algorithm designed to model the natural history of PCa. Costs were obtained from the US SEER-Medicare database and estimated during specific phases of care. Cost estimates were then combined with survival data to yield total and PCa-related life-time costs. Overall, the model estimated life-time costs of $110,520 (95% CI 110,324-110,739) per patient. PCa-related costs made up approximately 31% of total costs ($34,432). Prostate cancer places a significant burden on U.S. health-care systems with average life-time PCa-related costs in excess of $30,000.


The thin-fat phenotype and global metabolic disease risk.
There has been a great deal of interest in the thin-fat phenotype evident in Asian Indians and its risk associations in the epidemic of noncommunicable chronic disease associated with it. The cause of this phenotype is probably related to lifestyle and environment; however, genotypic and epigenetic modifications in utero also have been considered. The thin-fat phenotype occurs when fat is added to an already thin frame. This may occur with rural-urban migration, when positive energy balance occurs in a migrating population who were predominantly thin and physically active to begin with. The role of the pre-existing skeletal muscle mass and its interaction with newly deposited fat must be considered. The thin-fat phenotype may be programmed during fetal growth, but the evidence for this phenomenon is still not completely clear. Finally, although there is increased chronic disease morbidity at lower BMI and younger age in south Asian populations, BMI-related mortality does not appear to follow this trend. At present, the weight of evidence appears to link the thin-fat phenotype to an environmental and lifestyle phenomenon occurring in previously thin people. This is particularly relevant in India, given the pace of transition over the last two decades.