Complete Genome Sequence of a Wild-Type Measles Virus Isolated during a 2016 Winter Outbreak in a Refugee Settlement in Calais, France.
Measles outbreaks are regularly reported in European countries despite efforts to improve vaccination coverage. In January 2016, an outbreak occurred in a refugee settlement in Calais, France. We report here the complete genome sequence of a wild-type measles virus isolated from a health care worker (MVi/Calais. FRA/01.16) infected during this outbreak.


Effect of acute perinatal asphyxia on development of the lung and brain in the rat.
Fetal rats were exposed to asphyxia by compression of the umbilical vessels, and the animals were studied shortly after delivery, close to term (21st fetal day). Following asphyxia on the 20th fetal day, the lungs appeared immature. The surface active phospholipids, disaturated lecithin and phosphatidylglycerol, as well as the elastic tissue around the alveoli were lower than in the control littermates. However, lung maturity was little affected following asphyxia on the 17th-18th fetal day. As studied in the brain, hemorrhages in the periventricular area, sometimes intraventricular hemorrhages, were evident (asphyxia on the 17-18 and 20th fetal days). In addition, cells in cerebral cortex were altered following asphyxia of 17 - to 18-day-old fetuses. The present animal model clarifies the mechanism of increased incidence of respiratory distress syndrome following acute asphyxia and may prove to be useful in studies of pathogenesis of periventricular hemorrhages.


Impact of Respiratory Compromise in Inpatient Interventional Radiology Procedures with Moderate Sedation in the United States.
Background Despite increased use of moderate sedation in interventional radiology (IR), patient reactions to moderate sedation are difficult to predict. The rate, risk factors, and burden of respiratory compromise in patients who undergo IR procedures with moderate sedation in the United States are poorly understood. Purpose To identify risk factors and quantify the clinical and economic burden of respiratory compromise in inpatient IR procedures in the United States. Materials and Methods Primary inpatient IR procedures with moderate sedation conducted from October 1, 2012, to September 30, 2015, were analyzed by using a retrospective claims database. Exclusions included age younger than 18 years, use of anesthesia, pre-existing cardiac or respiratory arrest, and respiratory failure. Respiratory compromise was defined as use of naloxone or flumazenil, nonmechanical or cardiopulmonary resuscitation, or endotracheal intubation on the day of the IR procedure. Propensity score matching was performed to risk adjust patients for cost and outcomes analysis, including hospital and intensive care unit (ICU) length of stay, invasive mechanical ventilation, and death before hospital discharge. Results This study analyzed 525 151 patients (mean age, 60 years ± 17 [standard deviation]; 278 576 women). Respiratory compromise occurred in 1.0% (5235 of 525 151) of patients, predicted by long-term opioid therapy or active substance abuse (odds ratio [OR], 2.7; P < .001), age 65 years or older (OR, 1.4; P < .001), and sleep apnea (OR, 1.3; P < .001). Risk-adjusted patients with respiratory compromise compared with patients without respiratory compromise had $6904 higher costs (P < .001), 1.1-day longer hospital length of stay (P < .001), and higher rates of ICU admission (69.7% [3125 of 5235] vs 25.5% [1333 of 5235], respectively; P < .001), invasive mechanical ventilation (33.6% [1758 of 5235] vs 1.6% [85 of 5235], respectively; P < .001), and death (27.1% [1421 of 5235] vs 3.2% [166 of 5235], respectively; P < .001). Conclusion In the United States, respiratory compromise in interventional radiology procedures with moderate sedation contributes to worse clinical outcomes and higher costs. Respiratory compromise risk factors including long-term opioid therapy or active substance abuse, age 65 years or older, and sleep apnea should be preassessed and used to help guide intraprocedural monitoring to prevent respiratory compromise, improve patient outcomes, and reduce costs. © RSNA, 2019 See also the editorial by Rosen and Walz in this issue. Online supplemental material is available for this article.


Sex-related patterns in the electroencephalogram and their relevance in machine learning classifiers.
Deep learning is increasingly being proposed for detecting neurological and psychiatric diseases from electroencephalogram (EEG) data but the method is prone to inadvertently incorporate biases from training data and exploit illegitimate patterns. The recent demonstration that deep learning can detect the sex from EEG implies potential sex-related biases in deep learning-based disease detectors for the many diseases with unequal prevalence between males and females. In this work, we present the male- and female-typical patterns used by a convolutional neural network that detects the sex from clinical EEG (81% accuracy in a separate test set with 142 patients). We considered neural sources, anatomical differences, and non-neural artifacts as sources of differences in the EEG curves. Using EEGs from 1140 patients, we found electrocardiac artifacts to be leaking into the supposedly brain activity-based classifiers. Nevertheless, the sex remained detectable after rejecting heart-related and other artifacts. In the cleaned data, EEG topographies were critical to detect the sex, but waveforms and frequencies were not. None of the traditional frequency bands was particularly important for sex detection. We were able to determine the sex even from EEGs with shuffled time points and therewith completely destroyed waveforms. Researchers should consider neural and non-neural sources as potential origins of sex differences in their data, they should maintain best practices of artifact rejection, even when datasets are large, and they should test their classifiers for sex biases.


Simulation of reversible molecular mechanical logic gates and circuits.
Landauer's principle places a fundamental lower limit on the work required to perform a logically irreversible operation. Logically reversible gates provide a way to avoid these work costs and also simplify the task of making the computation as a whole thermodynamically reversible. The inherent reversibility of mechanical logic gates would make them good candidates for the design of practical logically reversible computing systems if not for the relatively large size and mass of such systems. In this paper we outline the design and simulation of reversible molecular mechanical logic gates that come close to the limits of thermodynamic reversibility even under the effects of thermal noise, and outline associated circuit components from which arbitrary combinatorial reversible circuits can be constructed and simulated. We demonstrate that isolated components can be operated in a thermodynamically reversible manner, and explore the complexities of combining components to implement more complex computations. Finally, we demonstrate a method to construct arbitrarily large reversible combinatorial circuits using multiple external controls and signal boosters with a working half-adder circuit.


2-[(E)-(2,4-Dihy-droxy-benzyl-idene)aza-nium-yl]-3-phenyl-propano-ate.
The title compound, C(16)H(15)NO(4), exists as a zwitterion in the solid state, with the carb-oxy-lic acid group being deprotonated and the imine N atom being protonated. The mol-ecule adopts an E configuration about the C=N double bond. The dihedral angle between the benzene rings is 46.34 (4)°. An intra-molecular N-H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, adjacent mol-ecules are connected by inter-molecular O-H⋯O and C-H⋯O hydrogen bonds, forming supra-molecular ribbons along the a axis.


[The history of discovery of bulbourethral glands].
The article outlines the chronology of the discovery of the bulbourethral glands. Their first image appeared in 1600 in a collection of anatomical tables by Italian anatomist Hieronymus Fabricius of Acquapendente. In the scientific literature, they were first mentioned in one of the editions of "Journal des scavans" in 1684 as discovered by the French surgeon Jean Mry. The first detailed description of the structure, topography and function of these glands was presented in the work of English physician and anatomist William Cowper in 1699.


Dietary L-carnitine increases plasma insulin-like growth factor-I concentration in chicks fed a diet with adequate dietary protein level.
1. The effect of L-carnitine supplemented into experimental diets with varying dietary protein concentrations (50, 200 and 400 g/kg) on body weight gain and plasma insulin-like growth factor-I (IGF-I) concentration in chicks was examined. 2. Dietary L-carnitine supplementation provided 0, 200, 500 and 1000 mg/kg. Chicks were given the diet ad libitum for 10 d. 3. When L-carnitine was provided as 500 or 1000 mg/kg, body weight gain was significantly improved in birds receiving the 200 and 400 g protein/kg diets. 4. There was an interaction between dietary L-carnitine and protein content on plasma IGF-I concentration. L-carnitine supplementation had little influence on plasma IGF-I concentrations in birds receiving the low protein (50 g/kg) diet. When dietary L-carnitine concentrations were increased from 0 to 1000 mg/kg in the adequate protein (200 g/kg) diet, plasma IGF-I concentrations were also increased. However, when dietary L-carnitine content was more than 500 mg/kg in the 400 g/kg protein group, plasma IGF-I concentration decreased with increasing dietary L-carnitine content. 5. Body weight change correlated significantly with the alteration in plasma IGF-I concentrations in chicks given diets with adequate dietary protein. 6. In conclusion, the improvement in body weight gain caused by dietary L-carnitine supplementation was achieved when chicks were given their dietary protein requirement, which may be partially explained by an increase in plasma IGF-I concentration.


[Comparative biochemical and ultrastructural study of the hepatic response induced in the rat by 2 hypolipemic agents: clofibrate and itanoxone].
A comparative biochemical and ultrastructural investigation o hepatic response induced in rats by clofibrate and itanoxone, a new hypolipemic agent, was performed. Normocholesterolemic Sprague-Dawley male rats were distributed into homogeneous groups and orally treated on 10 successive days either by the vehicle alone (1%--carboxymethylcellulose), or by clofibrate (300 mg/kg/day) or by itanoxone (100 and 300 mg/kg/day). On the eleventh day, a last dose was applied after about 16 hours fasting, one hour before sacrificing the animals. Biochemical parameters (total serum cholesterol, hepatic catalase activity) and morphological ones (liver weight, ultrastructural analysis of the hepatic cell with especially cytochemical evaluation and counting of peroxisomes) were studied. The treatment with clofibrate gave the following results: fall in total serum cholesterol (-25%), increase in liver weight (+89%) and hepatic catalase activity (+69%), high proliferation of hepatic peroxisomes (+246%). These data are in agreement with literature. The following observations were noted with itanoxone: a decrease in total serum cholesterol proportional to the dose applied and of higher intensity as compared to clofibrate (-36,5% at 100 mg/kg; -54% at 300 mg/kg), a moderate increase in liver weight (+25% at 100 mg/kg; +41% at 300 mg/kg) and hepatic peroxisomes (+12% at 100 mg/kg; +85% at 300 mg/kg), no effect on hepatic catalase activity. The moderate feature of the hepatic response induced by itanoxone in spite of a marked hypocholesterolemic activity was discussed: first in connection with the hypothesis about a relation between the proliferation of hepatic peroxisomes induced by many hypolipemic agents and the advent of tumors in rats, then, in connection with the association sometimes assumed between the increased number of hepatic peroxisomes and the effect on lipids of several hypolipemic substances related or not to clofibrate.


The Brief Peer Conflict Scale: Psychometric Properties Among a Sample of Incarcerated Male Juvenile Offenders.
Aggression can be considered a multidimensional construct that influences various forms of antisocial behavior, including juvenile delinquency and conduct problems. The aim of the present study was to assess the psychometric properties of the Brief Peer Conflict Scale-20 item version (PCS-20) among a Portuguese forensic sample (N = 192) of incarcerated male juvenile offenders ( M = 16.62 years; SD = 1.52 years; age range = 13-18 years). The PCS-20 demonstrated good psychometric properties in terms of its four-factor structure, internal consistency, convergent validity, and discriminant validity that generally justify its use among incarcerated male youth. The findings provide additional support for the extension of the PCS-20 across different cultures, ethnic groups, and samples.


Phosphoproteome analysis of synoviocytes from patients with rheumatoid arthritis.
To explore disease-associated molecules in rheumatoid arthritis (RA), we comprehensively analyzed phosphoproteins purified from RA synoviocytes. Synoviocytes were obtained from three patients with RA and three patients with osteoarthritis (OA). Profiles of phosphoproteins purified from the synoviocytes were compared by two-dimensional differential gel electrophoresis (2D-DIGE) between the RA and OA groups. Protein spots with significantly different phosphorylation levels were identified by mass spectrometry. Recombinant protein of annexin A4 (ANXA4), one of the identified phosphoproteins, was transfected into synoviocytes from an OA patient to mimic RA synoviocytes and humoral factor secretion was compared between rANXA4-transfected and non-transfected synoviocytes under a tumor necrosis factor-α (TNFα)-stimulated condition. In 2D-DIGE, 318 phosphoprotein spots were detected, of which 94 spots showed significantly different intensities between the two groups (P < 0.05). Among the 94 spots, 22 spots showed two-fold or higher intensity and one spot showed less than 1/2-fold intensity in the RA group compared to the OA group. From the 22 spots, 11 phosphoproteins were identified, which included kinases, carrier and chaperone proteins, cytoskeletal proteins, proteases and calcium-binding proteins. One of the identified calcium-binding proteins was ANXA4, an exocytosis-regulating protein. The transfected rANXA4 was found to be phosphorylated intracellularly, and secretion of chemokine (C-X-C motif) ligand 1 and interleukin-8 induced by TNFα stimulation was significantly suppressed by the transfection (P < 0.01). The phosphoprotein profile of RA synoviocytes was different from that of OA synoviocytes. This difference would reflect the different pathophysiologies of the diseases. ANXA4 may be one of therapeutic targets in RA.


Late embryonic and early posthatch growth of heart and lung in White Leghorn lines of chickens.
Growth and development of heart and lungs were measured from day 15 of incubation to 25 days after hatch in lines of chickens that had undergone long-term selection for high (HAS) or low (LAS) antibody titers to sheep erythrocytes. A correlated response to this selection was heavier 28-day body weights for LAS than HAS chickens. In this experiment body weights were heavier in line LAS than HAS from 15 days of incubation to 5 days after hatch and again at 25 days after hatch. Absorption of residual yolk was greater in HAS than LAS chicks. Although there were no differences between lines for absolute heart weights, lungs were heavier in line LAS than HAS at all ages except 20 days after hatch. Relative to body weight, both heart and lung weights declined with age, however, the pattern of decline differed. For this criterium, hearts were larger in line HAS than LAS to 5 days after hatch with no difference thereafter; for lungs lines were similar until 5 days after hatch after which they were larger in LAS than HAS chicks. In all but one case (HAS at hatch) the left:right relationship for lung weights exhibited fluctuating asymmetry with the left minus right character difference having a normal distribution and mean zero. The degree of fluctuating asymmetry, however, varied with age.


Some basics for operating and analyzing data using the thickness shear mode resonator.
The promises of obtaining meaningful measurements on physical systems loading the quartz crystal microbalance are extremely bright. The two aspects of this process, namely the gathering of faithful data and reductions of these data by way of modelling, need careful consideration to avoid some very common missteps which could frustrate this effort. The experimental techniques are emphasized here but a brief introduction to the basic methodologies of modelling is also given.


Critical appraisal of clinical practice guidelines for adult cancer patients with febrile neutropenia.
To critically appraise published international clinical practice guidelines (CPGs) for management of febrile neutropenia in adult patients with cancer and to determine opportunities for improved development and reporting. A literature search identified CPGs for adult cancer patients with febrile neutropenia. Four independent assessors evaluated each included CPG according to the Appraisal of Guidelines for Research and Evaluation II instrument. Standardized scores were calculated for each guideline and polled collectively. Reliability of assessment was determined using a two-way random model intraclass correlation coefficients. Eight CPGs were independently evaluated by four assessors. Collectively, the highest scoring domain was editorial independence (83.3), followed by clarity of presentation (55.4), scope and purpose (53.4), stakeholder involvement (53.1), rigour of development (52.7) and applicability (47.8). Overall assessments ranged from 28.6 to 96.4 of 100 possible points. Three (37.5%) guidelines were recommended for use without alterations, two (25%) guidelines were recommended with alterations, and three (37.5%) guidelines were not recommended for implementation into practice. Reliability varied between guidelines with intraclass correlation coefficients ranging from 0.41 to 0.82. Clinical practice guidelines for febrile neutropenia in adult patients with cancer were moderately rated with a 37.5% of guidelines being recommended for use in practice. Guideline developers should focus on improving CPG applicability and rigour in the development and reporting processes. Critical appraisal of guidelines should become a standard practice prior to implementation into clinical settings.


Academy of Breastfeeding Medicine Clinical Protocol #21: Breastfeeding in the Setting of Substance Use and Substance Use Disorder (Revised 2023).
Background: The Academy of Breastfeeding Medicine (ABM) revised the 2015 version of the substance use disorder (SUD) clinical protocol to review the evidence and provide updated literature-based recommendations related to breastfeeding in the setting of substance use and SUD treatments. Key Information: Decisions around breastfeeding are an important aspect of care during the peripartum period, and there are specific benefits and risks for substance-exposed mother-infant dyads. Recommendations: This protocol provides breastfeeding recommendations in the setting of nonprescribed opioid, stimulant, sedative-hypnotic, alcohol, nicotine, and cannabis use, and SUD treatments. Additionally, we offer guidance on the utility of toxicology testing in breastfeeding recommendations. Individual programs and institutions should establish consistent breastfeeding approaches that mitigate bias, facilitate consistency, and empower mothers with SUD. For specific breastfeeding recommendations, given the complexity of breastfeeding in mothers with SUD, individualized care plans should be created in partnership with the patient and multidisciplinary team with appropriate clinical support and follow-up. In general, breastfeeding is recommended among mothers who stop nonprescribed substance use by the time of delivery, and they should continue to receive ongoing postpartum care, such as lactation support and SUD treatment. Overall, enhancing breastfeeding education regarding substance use in pregnancy and lactation is essential to allow for patient-centered guidance.


Renin angiotensin system blockage associates with insertion/deletion polymorphism of angiotensin-converting enzyme in patients with hypertensive emergency.
Hypertensive crisis (HC) stands out as a form of acute elevation of blood pressure (BP). It can manifest itself as hypertensive emergency (HE) or hypertensive urgency (HU), which is usually accompanied with levels of diastolic BP ≥120 mmHg. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism may influence manifestations of HC. Thus, this study evaluated the influence of ACE I/D polymorphism in individuals with HC. A total of 187 patients admitted with HC (HU [n=69] and HE [n=118]) and 75 normotensive individuals were included in the study. Peripheral blood was drawn for a biochemical and genetic analysis of the ACE I/D polymorphism by Polymerase Chain Reaction. HC group showed higher systolic BP, body mass index (BMI), glycemia, creatinine, and lower high-density lipoprotein (HDL) cholesterol compared with normotensive individuals. The use of renin-angiotensin system (RAS) blockers was more frequent in the HU group than in the HE group (p=0.020). The II genotype was more predominant in normotensive and HU individuals than among HE individuals (18.7%, 11.6%, and 2.5%, respectively; p=0.004). Higher BMI and glycemia were associated with HC in the logistic regression model. ACE II genotype (odds ratio [OR] 0.14; 95% confidence interval [CI] 0.04-0.51) and HDL cholesterol were protective for the development of HE. ACE II genotype was present in the HU group, compared with the HE group (OR 0.18; 95% CI 0.04-0.88). This study shows an association between the low prevalence of ACE I/D polymorphism II genotype and a greater occurrence of HE in Brazilian individuals. The lower blockage of RAS, which was detected in the HE group, may interact with the low frequency of II genotype, conferring an increased risk for HE.


Protective effects of components of the Chinese herb grassleaf sweetflag rhizome on PC12 cells incubated with amyloid-beta42.
The major ingredients of grassleaf sweetflag rhizome are β-asarone and eugenol, which can cross the blood-brain barrier and protect neurons. This study aimed to observe the neuroprotective effects and mechanisms of β-asarone and eugenol, components of the Chinese herb grassleaf sweetflag rhizome, on PC12 cells. First, PC12 cells were cultured with different concentrations (between 1 × 10(-10) M and 1 × 10(-5) M) of β-asarone and eugenol. Survival rates of PC12 cells were not significantly affected. Second, PC12 cells incubated with amyloid-beta42, which reduced cell survival, were cultured under the same conditions (1 × 10(-6) M β-asarone and eugenol). The survival rates of PC12 cells significantly increased, while expression levels of the mRNAs for the pro-apoptotic protein Bax decreased, and those for the anti-apoptotic protein Bcl mRNA increased. In addition, the combination of β-asarone with eugenol achieved better results than either component alone. Our experimental findings indicate that both β-asarone and eugenol protect PC12 cells through inhibiting apoptosis, and that the combination of the two is better than either alone.


Internet Healthcare Policy Analysis, Evaluation, and Improvement Path: Multidimensional Perspectives.
Internet healthcare is a crucial component of the healthcare industry's digital transformation and plays a vital role in achieving China's Healthy China strategy and promoting universal health. To ensure the development of internet healthcare is guided by scientifically sound policies, this study analyzes and assesses current policy texts, aiming to identify potential issues and inadequacies. By examining 134 national-level policy documents, utilizing multiple research methods, including policy bibliometrics, content analysis, and the PMC Index Model, the study investigates policy characteristics, distribution of policy instruments, and evaluation outcomes related to internet healthcare. The study findings reveal that internet healthcare policies place emphasis on enhancing service quality, driving technological innovation, and promoting management standardization. Although policy instruments align with the current stage of internet healthcare development in China, they are plagued by imbalances in implementation. While policies are generally well-formulated, there are discernible discrepancies among them, necessitating the reinforcement and refinement of certain provisions. Hence, it is imperative to strategically optimize the amalgamation and implementation of policy instruments while concurrently endeavoring to achieve a dynamic equilibrium in policy combinations. Furthermore, policymakers should diligently refine the policy content pertaining to its nature and effectiveness in order to fully maximize policy utility.


Investigation of Mycobacterium avium complex (MAC) in Australian commercial milk using qPCR.
This technical research communication describes the first study to use quantitative polymerase chain reaction (qPCR) to investigate the presence of Mycobacterium avium complex (MAC) in Australian pasteurised milk. MAC is the most common NTM responsible for human illnesses and includes M. avium subspecies paratuberculosis (MAP). MAC is a causative agent of lymphadenitis in children, with contaminated food and water considered as a likely source. As such the presence of MAC in milk would have public health significance. MAP has been linked to Crohn's disease and is also the causative agent of Johne's disease in cattle. Previous studies have detected MAP in pasteurised milk from Brazil, India, Czech Republic, USA, Argentina, UK, Iran, Ireland and the United Kingdom. This study investigated a total of 180 commercially available Australian pasteurised milk samples which were tested for MAC DNA in triplicate using PCR. All samples were negative for MAC DNA. An additional 14 milk samples were tested, incubated for 3 weeks at 37 °C to potentially increase the concentration of any viable MAC that may be present and then retested. All samples were again negative for MAC DNA. This could be due to concentrations below the limit of detection, limited sample size or could be reflective of the Australian biosecurity control protocols and surveillance of Johne's disease in ruminant animals.


Serum time course of two brain-specific proteins, alpha(1) brain globulin and neuron-specific enolase, in tick-born encephalitis and Lyme disease.
Time courses of the serum concentrations of two brain-specific proteins (BSP), alpha(1) brain globulin (alpha(1)BG, an astroglial marker) and neuron-specific enolase (NSE), were studied in patients with severe tick-born encephalitis (TBE) and Lyme disease (LD; neuroborreliosis). The concentrations were determined on the second day of the acute phase and then on the 7th, 12th, 18th, and 23rd days. Apparent rate constants for the elimination of the BSP from blood (k(e)) were calculated with the non-linear regression. In patients with TBE, the highest serum concentrations of alpha(1)BG and NSE, observed on the second day, were followed by their monotonic decrease to the normal levels reached by the 23rd day. The mean k(e) values for alpha(1)BG and NSE were found to be significantly different (0.086+/-0.003 vs. 0.057+/-0.006 day(-1), respectively; p<0.05). Higher serum levels of both BSP were observed in the more severe clinical cases and in the cases with unfavorable outcomes. Similar profiles were also observed for the serum alpha(1)BG and NSE in LD. These results suggest that, in the patients examined, the blood-brain barrier was partially impaired; the quantitative parameters of the serum BSP time courses can be indicative of the extents of the neuronal and/or glial lesions.


[Uveitis associated with thyroïditis in HTLV-1 carriers].
The oncovirus HTLV-1 is aetiologically associated with uveitis and autoimmune thyroiditis in endemic areas. The association of uveitis with autoimmune thyroiditis in HTLV-1 carriers is less common moreover in non-endemic area. We report two original cases of simultaneous uveitis and autoimmune thyroiditis in HTLV-1 carriers, without other disease due to HTLV-1. The visual outcome was favorable in both cases. A significant correlation exists between hyperthyroidism, uveitis and HTLV-1, but still needs to be confirmed. The autoimmune or immune mediated mecanism of HTLV-1 may be involved in the uveitis and the thyroidits.


Uncertainty Quantification and Sensitivity Analysis of Partial Charges on Macroscopic Solvent Properties in Molecular Dynamics Simulations with a Machine Learning Model.
The molecular dynamics (MD) simulation technique is among the most broadly used computational methods to investigate atomistic phenomena in a variety of chemical and biological systems. One of the most common (and most uncertain) parametrization steps in MD simulations of soft materials is the assignment of partial charges to atoms. Here, we apply uncertainty quantification and sensitivity analysis calculations to assess the uncertainty associated with partial charge assignment in the context of MD simulations of an organic solvent. Our results indicate that the effect of partial charge variance on bulk properties, such as solubility parameters, diffusivity, dipole moment, and density, measured from MD simulations is significant; however, measured properties are observed to be less sensitive to partial charges of less accessible (or buried) atoms. Diffusivity, for example, exhibits a global sensitivity of up to 22 × 10-5 cm2/s per electron charge on some acetonitrile atoms. We then demonstrate that machine learning techniques, such as Gaussian process regression (GPR), can be effective and rapid tools for uncertainty quantification of MD simulations. We show that the formulation and application of an efficient GPR surrogate model for the prediction of responses effectively reduces the computational time of additional sample points from hours to milliseconds. This study provides a much-needed context for the effect that partial charge uncertainty has on MD-derived material properties to illustrate the benefit of considering partial charges as distributions rather than point-values. To aid in this treatment, this work then demonstrates methods for rapid characterization of resulting sensitivity in MD simulations.


Antigestogens: the holy grail of contraception.
Progesterone is essential for the establishment and maintenance of pregnancy. The discovery of antagonists of progesterone offered the possibility of developing new methods of fertility regulation. It was very quickly demonstrated that antigestogens would induce bleeding in early pregnancy, and mifepristone in combination with a prostaglandin is used as a method of abortion in several countries. Mifepristone will also inhibit ovulation, prevent implantation and induce menstrual bleeding at the time of expected menses. However, the development of these contraceptive uses of antigestogens has been inhibited by political and ethical controversy surrounding abortion. Surely the time has come to dissociate the ongoing debate about the ethics of abortion from the method so that the full therapeutic potential of this class of drugs can be exploited fully.


[Procedures and technical aptitude of primary care physicians: which practice?].
There is little knowledge of the practices of private physicians in Switzerland. However, this knowledge is a prerequisite for definition of the learning objectives in post-graduate and continuous education. To ascertain the procedural skills of family physicians and general internists and compare them with variables such as education and the location of practice. Questionnaire containing 68 procedural skills sent to all family physicians and general internists in the Cantons of Valais (VS) and Geneva (GE). 142/204 questionnaires (69%) were analyzed. A mean of 28.7 skills are practiced by the physicians. The internists use fewer procedures than the generalists. There is no difference between generalists practising in VS and GE, nor between location of the practice (urban or rural). The internists in GE and/or those practising in urban settings use fewer procedures than those practising in VS and in rural locations. Internists practising in rural setting use the same number of procedures than the generalists. Fifteen procedures are used by > or = 75% of physicians, 6 of these concern X-ray procedures. 60% of the procedures are used more frequently by the generalists, in particular surgical, ENT and gynecological procedures. There is no difference between generalists and internists as far emergency procedures or procedures in the cardiological and pneumological domain are concerned. The number of procedures depends nor only on the speciality of the private physician (generalist or general internist), but also and mainly on the location of the practice, the density of physicians and emergency practice. These findings can be used in defining the learning objectives of the primary care curriculum.


Dynamic MRI follow-up of radiation encephalopathy in the temporal lobe following nasopharyngeal carcinoma radiotherapy.
The natural course of radiation encephalopathy following nasopharyngeal carcinoma (NPC) radiotherapy remains poorly understood. The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and evolution of radiation encephalopathy. A series of 162 follow-up MRI examinations from 68 NPC patients with radiation encephalopathy in the temporal lobes were analyzed retrospectively. Each component of radiation encephalopathy was defined as follows: i) contrast enhanced lesions were enhanced lesions on contrast enhanced T1-weighted images (T1WI); ii) white matter lesions were lesions of homogeneous hyperintensity on T2-weighted images (T2WI) and hypointensity on T1WI; iii) cysts were round or oval well-defined lesions of hyperintensity on T2WI; iv) hemosiderin deposition were nodular or annular hypointense lesions with lower hypointense than normal white matter on both T1WI and T2WI; v) gray matter lesions were defined as disruption or erosion of hyperintensity in the cortex on T2WI. Contrast enhanced lesions, white matter lesions, gray matter lesions, cysts and hemosiderin deposition were detected in 105 (100.0%), 98 (93.3%), 94 (89.5%), 2 (1.7%) and 2 (1.7%) cases of the 105 initial diagnosed temporal lobe lesions. Contrast enhanced lesions were the most commonly observed, followed by white matter lesions, gray matter lesions, temporal lobe atrophy, cysts and hemosiderin deposition. In addition, 12 new lesions were identified during the follow-up, 4 of which presented as solid enhanced nodular lesions. Importantly, in 11 of the 117 (9.4%) affected temporal lobes, solid enhanced nodular lesions were observed to be the only initial abnormalities to occur. For those enhanced nodular lesions measuring <0.8 cm, no necrosis could be detected. On the contrary, all the contrast enhanced lesions measuring >2.0 cm exhibited a necrotic core. To the best of our knowledge, the present study revealed for the first time solid enhanced nodular lesions as the earliest MRI abnormalities of radiation encephalopathy following NPC radiotherapy.


Pharmacological characterization and binding modes of novel racemic and optically active phenylalanine-based antagonists of AMPA receptors.
In order to map out molecular determinants for the competitive blockade of AMPA receptor subtypes, a series of racemic aryl-substituted phenylalanines was synthesized and pharmacologically characterized in vitro at native rat ionotropic glutamate receptors. Most of the compounds showed micromolar affinity and preference for AMPA receptors. Individual stereoisomers of selected compounds were further evaluated at recombinant homomeric rat GluA2 and GluA3 receptors. The most potent compound, (-)-2-amino-3-(6-chloro-2',5'-dihydroxy-5-nitro-[1,1'-biphenyl]-3-yl)propanoic acid, the expected R-isomer showing Ki of 1.71 μM at the GluA2 subtype, was found to competitively antagonize GluA2(Q)i receptors in TEVC electrophysiological experiments (Kb = 2.13 μM). Molecular docking experiments allowed us to compare two alternative antagonist binding modes for the synthesized phenylalanines at the GluA2 binding core, showing the direction for further structural modifications.


SunSafe in the Middle School Years: a community-wide intervention to change early-adolescent sun protection.
Rising rates of skin cancer associated with early-life sun exposure make it important to improve adolescent sun-protection practices. Our study objective was to determine if a multicomponent community-wide intervention could alter the decline in sun protection that begins in early adolescence. A randomized, controlled trial was conducted in 10 communities to assess the impact of the SunSafe in the Middle School Years program. The intervention sought to (1) educate and activate adults and peers to role model and actively promote sun-protection practices and (2) create a pro-sun protection community environment. It targeted school personnel, athletic coaches, lifeguards, and clinicians and enlisted teens as peer advocates. Annual observations of cross-sectional samples of teens at community beach/pool sites were used to assess the impact of 1 and 2 years of intervention exposure compared to grade-matched controls. The outcome was percent of body surface protected by sunscreen, clothing, or shade. Observers determined the sun protection level of 1927 adolescents entering 6th to 8th grades. After 2 years of intervention exposure, adolescents at the beach/pool in intervention communities were significantly better protected than those in control communities. Over 2 years, the percent of body surface area protected declined by 23% in the control arm but only 8% in intervention arm. After intervention, the average percent of body surface protected at intervention sites (66.1%) was significantly greater than control sites (56.8%). Teens in intervention communities reported sun-protection advice from more adult sources, were more likely to use sunscreen, and applied it more thoroughly than control-site teens. Our multicomponent model addressing adolescent sun protection shows the power of engaging teens and adults from across the community as role models and educators. This new ecological approach shows promise in changing adolescent sun protection behaviors and reducing skin cancer risks.


The dynamic focus of nursing: a challenge to nursing administration.
Nursing administrators are challenged to establish a climate that facilitates the use of appropriate frameworks to guide nursing. The author presents an extension of a self-care practice model demonstrating that the focus of nursing strategies changes as the patient's health state changes. Practical application of the proposed model is included.


[The development and transplantation of LCD module-based interface for medical diagnosis instrument].
Based on LCD Module and Visual C++ development environment, this paper proposes a new method which can quickly develop the human-machine interface .We define a LCD module programming interface by designing Serial Communication Class(SCS). On this basis,we achieve the transplantation on an Embedded ARM Platform to fulfil the requirements of Medical Diagnostic Instruments (MDI). Experimental results show that this method has advantages of short development cycle and high level transplantation which has broad application prospects in the field of Medical Diagnosis Instrument.


Clinical and Hemodynamic Associations and Prognostic Implications of Ventilatory Efficiency in Patients With Preserved Left Ventricular Systolic Function.
Ventilatory efficiency (minute ventilation required to eliminate carbon dioxide, VE/VCO2) during exercise potently predicts outcomes in advanced heart failure with reduced ejection fraction, but its prognostic significance for at-risk individuals with preserved left ventricular systolic function is unclear. We aimed to characterize mechanistic determinants and prognostic implications of VE/VCO2 in a single-center dyspneic referral cohort (MGH-ExS [Massachusetts General Hospital Exercise Study]) and in a large sample of community-dwelling participants in the FHS (Framingham Heart Study). Maximum incremental cardiopulmonary exercise tests were performed. VE/VCO2 was assessed as the slope pre- and post-ventilatory anaerobic threshold (VE/VCO2pre-VATslope, VE/VCO2post-VATslope), the slope throughout exercise (VE/VCO2overall-slope), and as the lowest 30-second value (VE/VCO2nadir). In the MGH-ExS (N=493, age 56±15 years, 61% women, left ventricular ejection fraction 64±8%), higher VE/VCO2nadir was associated with lower peak exercise cardiac output and steeper increases in exercise pulmonary capillary wedge pressure (both P<0.0001). VE/VCO2nadir (hazard ratio, 1.34 per 1-SD unit [95% CI, 1.10-1.62] P=0.003) was associated with future cardiovascular hospitalization/death and outperformed classical VE/VCO2 measures used in heart failure with reduced ejection fraction (VE/VCO2overall-slope). In FHS (N=1936, age 54±9 years, 53% women), VE/VCO2 measures taken in low-to-moderate intensity exercise (including VE/VCO2pre-VATslope, VE/VCO2nadir) were directly associated with cardiovascular risk factor burden (smoking, Framingham cardiovascular disease risk score, and lower fitness; all P<0.001). Impaired ventilatory efficiency is associated with cardiovascular risk in the community and with adverse hemodynamic profiles and future hospitalizations/death in a referral population, highlighting the prognostic importance of easily acquired submaximum exercise ventilatory gas exchange measurements in broad populations with preserved left ventricular systolic function.


Nursing care for the relinquishing mother.
Unmarried adolescents with unplanned pregnancies face, along with the usual physiologic and psychologic changes, parental force and/or peer pressure to leave home and live elsewhere and a decision about the relinquishment of the infant. An important figure during the parental and immediate postpartum periods is the nurse. Nursing care required by relinquishing mothers is outlined and recommendations are given.


Boron monoxide dimer as a building block for boroxine based buckyballs and related cages: a theoretical study.
B3LYP/DZP level calculations are used to predict B2O2 cage oligomers, which are constructed from polyhedra by locating their B-B bonds at edge midpoints and three oxygen atoms at each degree 3 vertex. The stability of such cage oligomers depends highly on the B2nOn (n = 3, 4, 5) cavities corresponding to the polyhedral faces. All such polyhedral oligomers are found to have larger cohesive energies (Ec's) than corresponding planar structures, except for the smallest (B2O2)6 tetrahedron with extremely high strain arising from the four B6O3 cavities forming the tetrahedron faces. Promising (B2O2)n cages with the highest cohesive energies include pentagonal dodecahedral (B2O2)30 (c-B30) with B10O5 cavities, truncated octahedral (B2O2)36 (t-B36-2) with B8O4 cavities, and truncated icosahedral (B2O2)90 (t-B90) with B10O5 cavities. However, smaller (B2O2)n oligomers are also expected to exhibit cage structures having B8O4 or even B6O3 cavities because of their large Ec(s).


[A case of transverse colon cancer mimicking urachal cancer].
A 55-year-old man was admitted to our hospital because of abdominal distension. Computed tomography revealed an abscess in the anterior abdominal wall and invasion of the large intestine. Biopsy of the large intestine revealed adenocarcinoma. Immunohistochemically, the antigen expression profile of the tumor was positive for cytokeratin 7, cytokeratin 903 (34βE12), and cytokeratin 20. We diagnosed the tumor as urachal cancer and performed surgery. Examination of the resected specimen showed that the tumor was located in the transverse colon. Finally, the patient was diagnosed as having transverse colon cancer with urachal abscess.


Dislocation mobility in a quantum crystal: the case of solid 4He.
We investigate the structure and mobility of dislocations in hcp 4He crystals. In addition to fully characterizing the five elastic constants of this system, we obtain direct insight into dislocation core structures on the basal plane, which demonstrates a tendency toward dissociation into partial dislocations. Moreover, our results suggest that intrinsic lattice resistance is an essential factor in the mobility of these dislocations. This insight sheds new light on the possible correlation between dislocation mobility and the observed macroscopic behavior of crystalline 4He.


Binary analysis and optimization-based normalization of gene expression data.
Most approaches to gene expression analysis use real-valued expression data, produced by high-throughput screening technologies, such as microarrays. Often, some measure of similarity must be computed in order to extract meaningful information from the observed data. The choice of this similarity measure frequently has a profound effect on the results of the analysis, yet no standards exist to guide the researcher. To address this issue, we propose to analyse gene expression data entirely in the binary domain. The natural measure of similarity becomes the Hamming distance and reflects the notion of similarity used by biologists. We also develop a novel data-dependent optimization-based method, based on Genetic Algorithms (GAs), for normalizing gene expression data. This is a necessary step before quantizing gene expression data into the binary domain and generally, for comparing data between different arrays. We then present an algorithm for binarizing gene expression data and illustrate the use of the above methods on two different sets of data. Using Multidimensional Scaling, we show that a reasonable degree of separation between different tumor types in each data set can be achieved by working solely in the binary domain. The binary approach offers several advantages, such as noise resilience and computational efficiency, making it a viable approach to extracting meaningful biological information from gene expression data.


Depression as a Risk Factor of Organic Diseases:An International Integrative Review.
This integrative review offers a systematic synthesis of the international literature regarding the role of depression as a risk factor in physical illnesses and the mechanisms of this connection. Special attention is paid to those modifiable factors. Published studies of depression and physical illness and disease(N = 24) from five countries that were indexed in PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), APA PsycNET, Scopus, Dialnet, and CUIDEN were examined. Results suggest that depression is a significant risk factor for the development of physical illnesses and diseases. More commonly studied were the connections between depression and cardiovascular disease, metabolic syndrome, biochemical alterations, diabetes, dementia, cognitive impairment, Alzheimer's disease, somatization and chronic pain, asthma, arthritis, and hyperlipidemia. Less frequently studied conditions connected to depression were cancer, infections, allergies, autoimmune disease, gastric ulcer, rhinitis, thyroiditis, bronchitis, migraines, fractures, and osteoporosis. Mechanisms connecting depression to physical illness appear to involve alterations in the hypothalamic-pituitary axis, unhealthy lifestyle, chronic or acute stressors including posttraumatic stress, an increase in C-reactive protein (CRP) in men, taking antidepressant medication, and social and emotional loneliness. A good patient-provider relationship can help to promote decreased acute or chronic stressors, increased family and social support, decreased loneliness, modification of unhealthy lifestyles such as smoking, obesity, physical inactivity, alcohol, control of CRP, and antidepressant medication. Nurses are well placed to help prevent physical diseases through detection and referral of patients who are depressed or undiagnosed and not receiving adequate mental health treatment.


One-Step Conversion of Methyl Ketones to Acyl Chlorides.
Treatment of aromatic and heteroaromatic methyl ketones with sulfur monochloride and catalytic amounts of pyridine in refluxing chlorobenzene leads to the formation of acyl chlorides. Both electron-rich and electron-poor aryl methyl ketones can be used as starting materials. The resulting C1-byproduct depends on the precise reaction conditions chosen.


Post-Stroke Seizures Is Associated with Low Alberta Stroke Program Early CT Score.
Ischemic stroke is a leading cause of new-onset seizures. Cortical ischemia and large ischemic lesion size are among the most consistently reported risk factors for post-stroke seizures. Alberta Stroke Program Early CT Score (ASPECTS) is a simple and reliable tool for quantifying the extent of cerebral ischemia and may function as a screening tool for patients with high risk of seizure development. We investigated the association of post-stroke seizures with the extent of ischemia assessed by ASPECTS and with cortical involvement identified on non-contrast CT (NCCT). This cohort study was based on a prospectively maintained clinical database of acute ischemic stroke patients who were given intravenous tissue plasminogen activator treatment. We included patients with anterior circulation stroke admitted between January 2008 and October 2014. Patients with pre-stroke seizures were excluded. Clinical data and seizure follow-up data were collected. NCCT scans acquired both on stroke admission and at 24 h were analyzed. Logistic regression and cox regression were performed in statistical analysis. A total of 348 patients (median age 73 years, interquartile range [IQR] 63-80, 55% male) were included. During follow-up (median duration 559 days, IQR 107.5-1188.5 days), 22 (6.3%) patients developed post-stroke seizures. Median time from stroke to seizure onset was 138 days (IQR 10-342 days). In univariate logistic regression, both ASPECTS on admission (OR 0.69 per 1-point increase; 95% CI 0.55-0.86; p = 0.001) and at 24 h (OR 0.80 per 1-point increase; 95% CI 0.70-0.92; p = 0.002) were significantly associated with post-stroke seizures. Cortical involvement at 24 h also correlated with seizure occurrence (OR 3.01; 95% CI 1.08-8.34; p = 0.03). Cox regression confirmed the higher risk of developing seizures at any time point in patients with lower ASPECTS value and cortical ischemia. Of note, ASPECTS was the only independent predictor for post-stroke seizures in multivariate logistic regression. The extent of ischemia assessed by ASPECTS and cortical involvement identified on NCCT were associated with the development of post-stroke seizures.


Structural and Lattice-Dynamical Properties of Tb2O3 under Compression: A Comparative Study with Rare Earth and Related Sesquioxides.
We report a joint experimental and theoretical investigation of the high pressure structural and vibrational properties of terbium sesquioxide (Tb2O3). Powder X-ray diffraction and Raman scattering measurements show that cubic Ia3̅ (C-type) Tb2O3 undergoes two phase transitions up to 25 GPa. We observe a first irreversible reconstructive transition to the monoclinic C2/m (B-type) phase at ∼7 GPa and a subsequent reversible displacive transition from the monoclinic to the trigonal P3̅m1 (A-type) phase at ∼12 GPa. Thus, Tb2O3 is found to follow the well-known C → B → A phase transition sequence found in other cubic rare earth sesquioxides with cations of larger atomic mass than Tb. Our ab initio theoretical calculations predict phase transition pressures and bulk moduli for the three phases in rather good agreement with experimental results. Moreover, Raman-active modes of the three phases have been monitored as a function of pressure, while lattice-dynamics calculations have allowed us to confirm the assignment of the experimental phonon modes in the C- and A-type phases as well as to make a tentative assignment of the symmetry of most vibrational modes in the B-type phase. Finally, we extract the bulk moduli and the Raman-active mode frequencies together with their pressure coefficients for the three phases of Tb2O3. These results are thoroughly compared and discussed in relation to those reported for rare earth and other related sesquioxides as well as with new calculations for selected sesquioxides. It is concluded that the evolution of the volume and bulk modulus of all the three phases of these technologically relevant compounds exhibit a nearly linear trend with respect to the third power of the ionic radii of the cations and that the values of the bulk moduli for the three phases depend on the filling of the f orbitals.


Decreasing Inappropriate Use of Mobile Devices in Urban High School Classrooms: Comparing an Antecedent Intervention With and Without the Good Behavior Game.
As the capabilities of portable technology continue to advance and become more accessible, educators express concern about the impact of the inappropriate use of mobile devices on academic engagement and learning. An alternating treatments design was used to compare the effectiveness of an antecedent (Clear Box) intervention and an interdependent group contingency (Clear Box + Good Behavior Game [GBG]) intervention to typical classroom management techniques (Control) in increasing the academic engagement and decreasing mobile device use of high school students during instruction. The results indicate an increase in academic engagement and a decrease in the inappropriate presence of mobile devices in both classrooms with the implementation of the Clear Box + GBG, as compared with the Clear Box and Control conditions. In addition, teacher and student social validity data suggested that teachers and students viewed the Clear Box + GBG intervention favorably. Discussion focuses on contributions to the current literature, implications for practice, and suggestions for future areas of research.


A Study on Regional GDP Forecasting Analysis Based on Radial Basis Function Neural Network with Genetic Algorithm (RBFNN-GA) for Shandong Economy.
Gross domestic product (GDP) is an important indicator for determining a country's or region's economic status and development level, and it is closely linked to inflation, unemployment, and economic growth rates. These basic indicators can comprehensively and effectively reflect a country's or region's future economic development. The center of radial basis function neural network and smoothing factor to take a uniform distribution of the random radial basis function artificial neural network will be the focus of this study. This stochastic learning method is a useful addition to the existing methods for determining the center and smoothing factors of radial basis function neural networks, and it can also help the network more efficiently train. GDP forecasting is aided by the genetic algorithm radial basis neural network, which allows the government to make timely and effective macrocontrol plans based on the forecast trend of GDP in the region. This study uses the genetic algorithm radial basis, neural network model, to make judgments on the relationships contained in this sequence and compare and analyze the prediction effect and generalization ability of the model to verify the applicability of the genetic algorithm radial basis, neural network model, based on the modeling of historical data, which may contain linear and nonlinear relationships by itself, so this study uses the genetic algorithm radial basis, neural network model, to make, compare, and analyze judgments on the relationships contained in this sequence.


Places: A 10 Million Image Database for Scene Recognition.
The rise of multi-million-item dataset initiatives has enabled data-hungry machine learning algorithms to reach near-human semantic classification performance at tasks such as visual object and scene recognition. Here we describe the Places Database, a repository of 10 million scene photographs, labeled with scene semantic categories, comprising a large and diverse list of the types of environments encountered in the world. Using the state-of-the-art Convolutional Neural Networks (CNNs), we provide scene classification CNNs (Places-CNNs) as baselines, that significantly outperform the previous approaches. Visualization of the CNNs trained on Places shows that object detectors emerge as an intermediate representation of scene classification. With its high-coverage and high-diversity of exemplars, the Places Database along with the Places-CNNs offer a novel resource to guide future progress on scene recognition problems.


[Cesarean section on demand--an equivalent alternative to spontaneous delivery?].
Due to advances in perioperative management, surgical techniques as well as anaesthesia, caesarean section has become a very safe intervention for mother and child. In certain high-risk situations, an early delivery by caesarean section can prevent serous morbidity and mortality of the fetus and newborn. It has been postulated that a planned caesarean section is a true alternative to vaginal birth, and in the absence of a specific medical reason the woman's demand may be an indication for the operation. A critical review of studies based on large regional perinatal datasets shows that the risk for minor as well as serious complications in the mother and the newborn is increased after planned caesarean section. Serious consequences for subsequent pregnancies like uterine rupture or placenta praevia, which may be associated with accreta or abruptio of the placenta, are of major concern. On the other hand, trauma to the pelvic floor with urinary or anal incontinence is more frequent after vaginal birth. The balance of these risks including the very rare cases of severe intrapartal asphyxia, which might be prevented by a planned caesarean section, must be carefully evaluated together with the patient on an individual basis. These risks must be carefully balanced and the final decision about the type of delivery requires a detailed informed consent.critical review of studies based on large regional perinatal datasets shows that the risk for minor as well as serious complications in the mother and the newborn is increased after planned caesarean section. Serious consequences for subsequent pregnancies like uterine rupture or placenta praevia, which may be associated with accreta or abruptio of the placenta, are of major concern. On the other hand, trauma to the pelvic floor with urinary or anal incontinence is more frequent after vaginal birth. The balance of these risks including the very rare cases of severe intrapartal asphyxia, which might be prevented by a planned caesarean section, must be carefully evaluated together with the patient on an individual basis. These risks must be carefully balanced and the final decision about the type of delivery requires a detailed informed consent.


Competing Principles for Allocating Health Care Resources.
We clarify options for conceptualizing equity, or what we refer to as justice, in resource allocation. We do this by systematically differentiating, expounding, and then illustrating eight different substantive principles of justice. In doing this, we compare different meanings that can be attributed to "need" and "the capacity to benefit" (CTB). Our comparison is sharpened by two analytical tools. First, quantification helps to clarify the divergent consequences of allocations commended by competing principles. Second, a diagrammatic approach developed by economists Culyer and Wagstaff offers a visual and conceptual aid. Of the eight principles we illustrate, only two treat as relevant both a person's initial health state and a person's CTB per resource unit expended: (1) allocate resources so as to most closely equalize final health states and (2) allocate resources so as to equally restore health states to population norms. These allocative principles ought to be preferred to the alternatives if one deems relevant both a person's initial health state and a person's CTB per resource unit expended. Finally, we examine some possibilities for conceptualizing benefits as relative to how badly off someone is, extending Parfit's thought on Prioritarianism (a prioritizing of the worst off). Questions arise as to how much intervention effects accruing to the worse off count for more and how this changes with improving health. We explicate some recent efforts to answer these questions, including in Dutch and British government circles. These efforts can be viewed as efforts to operationalize need as an allocative principle. Each effort seeks to maximize in the aggregate quanta of effect that are differentially valued in favor of the worst off. In this respect, each effort constitutes one type of Prioritarianism, which Parfit failed to differentiate from other types.


[Assessment of the amount of palladium-silver alloy used for cast posts and veneer crowns].
Average amounts of palladium-silver alloy were assessed in a sample of 966 veneer crowns and 667 casted posts. The mean weight values of the samples under study were compared in relation to particular types of anterior teeth. The specimens cast in Auropal SE were weight by the precise balance, Tehtnica, type 6215. Results were analyzed by weight according to the type of the sample under study, and classified according to age, and to the anterior teeth of the upper and lower jaws. On an average, the heaviest posts and veneer crowns were measured on upper canines, whereas the lighest were those on lower incisors. A cast post was found to be by about 40% heavier than a veneer crown on the same tooth.


Hepatic FGF21: Its Emerging Role in Inter-Organ Crosstalk and Cancers.
Fibroblast growth factor (FGF) 21 is one of the FGF members with special endocrine properties. In the last twenty years, it has attracted intense research and development for its physiological functions that respond to dietary manipulation, pharmacological benefits of improving the macronutrient metabolism, and clinical values as a biomarker of various human diseases. Generally, FGF21 can be produced by major metabolic organs, but only the subgroup from the liver shows canonical endocrine properties, which emphasizes the special value of delineating the unique secretory and functional characteristics of hepatic FGF21. There has been a growth in literature to address the extra-hepatic activities of FGF21, and many striking findings have therefore been published. Yet, they are fragmented and scattered, and controversies are raised from divergent findings. For this reason, there is a need for a systematic and critical evaluation of current research in this aspect. In this review, we focus on the current knowledge about the molecular biology of endocrine FGF21, especially present details on the regulation of circulating levels of FGF21. We also emphasize its emerging roles in inter-organ crosstalk and cancer development.


Perkinsus olseni detected in Vietnamese aquacultured reef clams Tridacna crocea imported to the USA, following a mortality event.
Morbidity and mortality were observed in a group of 30 reef clams Tridacna crocea that were imported to Florida, USA, from a Vietnamese culture facility and held in research facility aquaria. Clinical signs included an incompletely extended mantle, slow mantle responses to stimuli, and sloughing of byssal tissue beginning 2 to 5 d prior to death. Necropsy findings included emaciation, visceral mass edema, and rare multifocal 1 mm off-white to light-tan gill nodules. Histopathology revealed marked inflammation and necrosis within the visceral mass and gills, with interstitial edema and atrophy of glandular, gonadal, and muscular tissues. Inflamed tissues contained large numbers of 10 to 15 microm extracellular round organisms consistent with Perkinsus sp. trophozoites. The organisms often formed clusters of 1 to 4 cells and were surrounded by a 1 to 3 microm rim of eosinophilic material variably forming a radiating corona pattern and by 3 to 4 host hemocytes with dense round nuclei. Polymerase chain reaction assays indicated the presence of Perkinsus sp. DNA in these animals, and species-specific assays indicated the presence of P. olseni, and possibly other Perkinsus spp., but not P. marinus. Identification of Perkinsus spp. other than P. marinus in T. crocea imported from Vietnam confirms that importation of untested and unquarantined ornamental reef clams has possibly allowed incursion of P. olseni into the USA.


In Vivo Visualization of Mobile mRNA Particles in Plants Using BglG.
Cells have developed mechanisms for cytoplasmic RNA transport and localization that participate in the regulation and subcellular localization of protein synthesis. In addition, plants can exchange RNA molecules between cells through plasmodesmata and to distant tissues in the phloem. These mechanisms are hijacked by RNA viruses to establish their replication complexes and to disseminate their genomes throughout the plant organism with the help of virus-encoded movement proteins (MP). Live imaging of RNA molecules is a fundamental approach to understand the regulation and molecular basis of these processes. The most widely used experimental systems for the in vivo visualization of genetically encoded RNA molecules are based on fluorescently tagged RNA binding proteins that bind to specific motifs inserted into the RNA, thus allowing the tracking of the specific RNA molecule by fluorescent microscopy. Recently, we developed the use of the E. coli RNA binding protein BglG for the imaging of RNAs tagged with BglG-binding sites in planta. We describe here the detailed method by which we use this in vivo RNA tagging system for the real-time imaging of Tobacco mosaic virus (TMV) MP mRNA.


Quantitative Analysis of Flavonoids in Fruiting Bodies of Sanghuangporus Using Ultra-High-Performance Liquid Chromatography Coupled with Triple Quadrupole Mass Spectrometry.
A rapid, precise, and dependable method for quantifying flavonoids in the fruiting bodies of Sanghuangporus was established using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS). Separation was achieved using a ZORBAX Eclipse Plus C18 column (1.8 μm, 3.0 mm × 100 mm) with a 15 min gradient of a mobile phase consisting of 0.01% aqueous formic acid and 2 mm/L ammonium formate (mobile phase A), and 0.01% formic acid and 2 mm/L ammonium formate in methanol (mobile phase B). A mass spectrometry analysis was performed using the multiple reaction monitoring (MRM) mode with an electrospray ion source. This method enabled the simultaneous detection of 10 flavonoids (sakuranetin, quercitrin, myricitrin, kaempferol, luteolin, rutin, hyperoside, kaempferol-3-O-rutinoside, catechin, and catechin gallate) in the fruiting bodies of Sanghuangporus. Additionally, we applied this method to analyze the flavonoid content in fruiting bodies of various Sanghuangporus species. The results revealed substantial variations in flavonoid content, up to a 100-fold difference, among different species, with myricitrin, hyperoside, and rutin identified as the most abundant flavonoids. This protocol serves as a valuable tool for quantifying flavonoid compounds in different Sanghuangporus species or under diverse cultivation conditions, particularly for identifying species with high levels of specific flavonoid compounds.


Effects of growth hormone on nuclear maturation of ovine oocytes and subsequent embryo development.
The objective of this study was to determine the effect of the presence of recombinant ovine growth hormone either alone or together with follicle stimulating hormone (FSH) during ovine oocyte in vitro maturation (IVM) on nuclear maturation and subsequent embryo development. Moreover, the effect of growth hormine (GH) on embryo development whether influenced by the presence of foetal bovine serum (FBS) was assessed. The abattoir-derived oocytes were randomly divided into four treatment groups and cultured in maturation medium supplemented with: (i) 0.05 IU/ml FSH; (ii) 300 ng/ml roGH; (iii) FSH + roGH; and (iv) no FSH and GH (control). The percentages of germinal vesicle-stage oocytes in GH-treated group after 8 h of culture was significantly higher than the FSH and FSH + GH groups and lower than control (22.4%, 8.7%, 9.1%, and 32% respectively). The percentage of MII-stage oocytes was significantly increased in the presence of GH after 16 and 24 h of culture compared to the control (44.7% and 83.1% vs 32.6% and 73.6% respectively). There was no significant synergism between GH and FSH in terms of nuclear maturation. The blastocyst rates in serum-supplemented groups were enhanced by the presence of FSH and GH compared to the control (35.4% and 31.3 vs 11.4% respectively). Compared with either GH or FSH alone, the subsequent embryo development (blastocyst rate), however, was negatively influenced by co-presence of both hormones (22.8%). In contrast, the corresponding values were not affected in the absence of serum. In conclusion, GH had positive effect on nuclear maturation of sheep oocytes. Moreover, the pattern of the effect of GH on embryo development was influenced by the presence of FBS during IVM.


Experimental Cortical Spreading Depression Induces NMDA Receptor Dependent Potassium Currents in Microglia.
Cortical spreading depression (CSD) is a propagating event of neuronal depolarization, which is considered as the cellular correlate of the migraine aura. It is characterized by a change in the intrinsic optical signal and by a negative DC potential shift. Microglia are the resident macrophages of the CNS and act as sensors for pathological changes. In the present study, we analyzed whether microglial cells might sense CSD by recording membrane currents from microglia in acutely isolated cortical mouse brain slices during an experimentally induced CSD. Coincident with the change in the intrinsic optical signal and the negative DC potential shift we recorded an increase in potassium conductance predominantly mediated by K(+) inward rectifier (Kir)2.1, which was blocked by the NMDA receptor antagonist D-AP5. Application of NMDA and an increase in extracellular K(+) mimics the CSD-induced Kir activation. Application of D-AP5, but not the purinergic receptor antagonist RB2, blocks the NMDA-induced Kir activation. The K(+) channel blocker Ba(2+) blocks both the CSD- and the NMDA-triggered increase in Kir channel activity. In addition, we could confirm previous findings that microglia in the adult brain do not express functional NMDA receptors by recording from microglia cultured from adult brain. From these observations we conclude that CSD activates neuronal NMDA receptors, which lead to an increase in extracellular [K(+)] resulting in the activation of Kir channel activity in microglia. Cortical spreading depression (CSD) is a wave of neuronal depolarization spreading through the cortex and is associated with the aura of migraine. Here we show that microglial cells, which are viewed as pathologic sensors of the brain, can sense this wave. The increase in the extracellular potassium concentration associated with that wave leads to the activation of an inward rectifying potassium conductance in microglia. The involvement of neuronal NMDA receptors is crucial because NMDA mimics that response and microglia do not express functional NMDA receptors. Although it is now evident that CSD leads to a signal in microglia, the consequences of this microglial activation during CSD needs to be explored.


An innovative brioche enriched in protein and energy improves the nutritional status of malnourished nursing home residents compared to oral nutritional supplement and usual breakfast: FARINE+ project.
To compare the effects of a 12-week nutritional intervention, in which an innovative protein-and-energy-enriched brioche, an oral nutritional supplement or a usual breakfast were eaten, on food intake and nutritional status in nursing home residents. Three-armed, multicentre, controlled trial. Eight nursing homes in Burgundy, France. Sixty-eight malnourished participants aged between 70 and 99 years old. Participants were randomly assigned to one of three groups according to the breakfast provided: brioche group, one portion of 65 g brioche enriched in protein and energy (12.8 g and 180 kcal) added to usual breakfast; supplement group, 200-ml of a ready-to-use, energy-dense liquid (14 g protein and 200 kcal) added to usual breakfast or control group, a usual breakfast only. Total energy intakes were assessed for three days at different periods of the study (day 0, day 30 and day 90); blood parameters, nutritional status (mini nutritional assessment, weight) and functional capacities (grip strength and activity level) were measured at the beginning and at the end of the nutritional intervention study (day 0 and day 90). The participants of the brioche group had higher total energy intakes at day 30 (p value 0.004) and at day 90 (p value 0.018) compared with the supplement group and the control group. At the end of the interventional study, 72% of the participants in the brioche group had reached the recommended minimum level of protein of 0.8 g/kg/day, compared with 53% in the supplement group and 36% in the control group (p value 0.036). In addition, between day 0 and day 90 in the brioche group, blood levels of vitamins B9, B2, D (all p value <0.001), B6 (p value 0.026) and B12 (p value 0.036) had increased and plasma homocysteine had decreased (p value 0.024). The protein-and-energy-enriched brioche effectively increased energy and protein intakes and improved the nutritional status of elderly people living in nursing homes. It could be a good alternative to oral liquid nutritional supplements to counteract protein-energy-malnutrition.


Three-dimensional structure of aspartate aminotransferase from Escherichia coli at 2.8 A resolution.
The crystal structure of aspartate aminotransferase of Escherichia coli was determined by X-ray structure analysis at 2.8 A resolution. The structure was solved by the molecular replacement method and refined to an R-factor of 0.27, and it was found that the overall structure of AspAT of E. coli is similar to that of those of higher animals.


[The affinity between Le family of Tong Ren Tang and acu-moxibustion as viewed from Mian xue tang zhen jiu ji cheng (Mian Xuetang's Synthetic Work of Acu-moxibustion)].
This compilation process of Mian xue tang zhen jiu ji cheng(Mian Xuetang's Synthetic Work of Acu-moxibustion)was quite mysterious, the book's advent coincidentally met with several major historical events which made its value of decoding its historical functions far beyond its academic value. The editor of this book is Le Xianyang, the founder of Tong Ren Tang. While compiling this book, he also made a replica of Ming-Dynasty's Zhengtong bronze statue. More than 200 years later, Le Jingyu, the 12th generation of the Le family revised Ming Tang Tuinherited from his ancestors and engraved Ming Tang Tuon the stone for its standardization. This great achievement of Le family was no less than the recasting of the Tiansheng bronze statue and the reengraving Tong ren shu xue zhen jiu tu jing(Illustrated Manual of Acupuncture Points of the Bronze Figure) by support of state power for building the Beijing Imperial Hospital in the eighth year of the Zhengtong reign (1443).


Evaluation of Wound Healing Property of the Ethanolic Extract of Glycyrrhiza Glabra on Vero Cell Lines Using In Vitro Scratch Assay Test.
The successful restoration of damaged tissue requires a complicated, dynamic process called wound healing, which is supported by a wide range of cellular activities. Natural materials generated from medicinal plants have been identified, and their therapeutic potential evaluation has resulted in the development of novel, affordable medicines that can be used to treat a variety of illnesses, including chronic wounds, with limited side effects. This study aimed to assess the wound-healing property of Glycyrrhiza Glabra (Athimathuram) plant extracts by using an in vitro scratch assay test, as well as to evaluate their cellular toxicity. Using the Soxhlet device, ethanolic extraction of the plant material was done, and the cytotoxicity of the extract on the Vero cell line was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. One of the most often utilized mammalian in vitro cell lines in research was Vero cells. To assess the wound healing properties of G. glabra plant extract, an in vitro scratch assay was used, and their potential mechanisms of action were examined. Even at higher concentrations, the MTT assay showed that G. Glabra plant extracts had no cytotoxic effects on the cells. In vitro scratch assay showed that the healing process of the cell line was increased by 23.33% when compared with the controlled cell lines. Our research demonstrated that G. glabra has in vitro wound healing capabilities. As a result, G. glabra can be suggested as a possible source of compounds that treat wounds.


Functional electrical stimulation and lower extremity bracing for ambulation exercise of the spinal cord injured individual: a medically prescribed system.
The purpose of this study was to determine whether commercially available electrical muscle stimulators could provide functional ambulation exercise for the spinal cord injured individual. Commercially available electrical muscle stimulators were used for functional electrical stimulation and interfaced with reciprocating gait orthoses so that a new system has been developed. Advantages of the system include commercially available subsystems and subsystems for applications such as gait training. The system involves six electrical stimulation units worn on a belt; controlled by remote switches; and interfacing to electrodes placed over the quadriceps femoris, hamstring, and gluteal muscle groups of each leg. Four electrical stimulation units (for quadriceps femoris muscle stimulation) function primarily for stand-up and sit-down activities. Two other units (for stimulation of the hip extensor muscles) function primarily for ambulation. The system is described for use with a C7-level quadriplegic individual. The patient successfully performed over 20 repetitions of stand-up and sit down exercises with the system. An average walking distance of about 0.8 km was routinely traversed at velocities ranging from 1.2 to 2.0 km per hour. It was concluded that muscle fatigue, rather than battery power, was the functionally limiting factor for the quadriplegic patient. A recommendation is that application of the system for walking exercise should be preceded by a physical conditioning program of functional electrical stimulation. Specific medical criteria should be satisfied prior to formally prescribing the system for an individual. Finally, the steps involved in the writing of the walking system prescription are outlined.


Dielectric screening effect of electronic polarization and intramolecular hydrogen bonding.
Recent site-resolved hydrogen exchange measurements have uncovered significant discrepancies between simulations and experimental data during protein folding, including the excessive intramolecular hydrogen bonds in simulations. This finding indicates a possibility that intramolecular charge-charge interactions have not included sufficient dielectric screening effect of the electronic polarization. Scaling down peptide atomic charges according to the optical dielectric constant is tested in this study. As a result, the number of intramolecular hydrogen bonds is lower than using unscaled atomic charges while reaching the same levels of helical contents or β-hairpin backbone hydrogen bonds, because van der Waals interactions contribute substantially to peptide folding in water. Reducing intramolecular charge-charge interactions and hydrogen bonding increases conformational search efficiency. In particular, it reduces the equilibrium helical content in simulations using AMBER force field and the energy barrier in folding simulations using CHARMM force field.


Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections.
Hippocampal area CA1 provides the major cortical output of the hippocampus, but only its projections to the subiculum and lateral septal nucleus are well characterized. The present study reexamines these extrinsic projections by using anterograde and retrograde tracing techniques. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in the septal one-third of CA1 label axons and terminals in subicular, postsubicular, retrosplenial, perirhinal, and entorhinal cortices, lateral septal nucleus, and diagonal band of Broca. The septal CA1 injections also label terminal fields in contralateral CA1, and in contralateral subicular, postsubicular, perirhinal, and entorhinal cortices. Injections into the splenial one-third of CA1 label axons and terminals in subiculum, postsubiculum, ventral area infraradiata, and lateral septal nucleus, but they do not label axons and terminals on the contralateral side of the brain. Injections in the temporal one-third of CA1 label axons and terminals in subicular, parasubicular, entorhinal, and infraradiata cortices, anterior olfactory nucleus, olfactory bulb, lateral septal nucleus, nucleus accumbens, amygdala, and hypothalamus. The temporal CA1 injections label no axons on the contralateral side of the brain. These data demonstrate that CA1 has more widespread projections than previously appreciated, and they provide the first clear evidence that CA1 projects to the contralateral cortex and to the ipsilateral olfactory bulb, amygdala, and hypothalamus. The results also demonstrate a heterogeneity in the efferent projections originating in different septotemporal levels of CA1.


Accuracy of stress myocardial perfusion imaging to diagnose coronary artery disease in end stage liver disease patients.
Patients with end-stage liver disease (ESLD) who also have underlying coronary artery disease (CAD) may be at increased risk for undergoing hemodynamically challenging orthotopic liver transplantation. Noninvasive single-photon emission computed tomographic (SPECT) imaging is often used to determine whether a patient with ESLD has unsuspected CAD. The objective of this study was to determine the accuracy of SPECT imaging for detection of CAD in patients with ESLD. Patients with ESLD who underwent coronary angiography and SPECT imaging before orthotopic liver transplantation were analyzed retrospectively. The predictive accuracy of clinical risk factors was calculated and compared to the results of SPECT imaging. There were 473 SPECT imaging studies. Adenosine SPECT imaging had a sensitivity of 62%, specificity of 82%, positive predictive value of 30%, and negative predictive value of 95% for diagnosing severe CAD. Regadenoson SPECT imaging had a sensitivity of 35%, specificity of 88%, positive predictive value of 23%, and negative predictive value of 93% for diagnosing severe CAD. The accuracy of a standard risk factor analysis showed no statistical difference in predicting CAD compared with adenosine (sensitivity McNemar's p = 0.48, specificity McNemar's p = 1.00) or regadenoson (sensitivity McNemar's p = 0.77, specificity McNemar's p = 1.00) SPECT studies. In conclusion, the 2 pharmaceutical agents had low sensitivity but high specificity for diagnosing CAD. However, because the sensitivity of the test is low, the chances of missing patients with ESLD with CAD is high, making SPECT imaging an inaccurate screening test. A standard risk factor analysis as a predictor for CAD in patients with ESLD is less expensive, has no radiation exposure, and is as accurate as SPECT imaging.


Multispiral computed tomographic angiography of renal arteries of live potential renal donors: a review of 118 cases.
Review of the angiographic data of 118 live kidney donors was performed to assess the renal vessel anatomy; compare the findings with the perioperative findings using multislice spiral (MS) computed tomographic angiography (CTA) with the use of 50 mL of intravenous contrast; determine the sensitivity of this technique in the workup of live potential renal donors; and finally to discuss and compare the results of the present study with the reported results using single-slice spiral (SS) CTA, magnetic resonance angiography (MRA), and conventional angiography (CA). Retrospective analysis of the angiographic data of 118 of prospective live kidney donors was performed. All donors underwent renal angiography on MSCTA scanning using 50 mL of intravenous contrast with 1.25-mm slice thickness followed by maximum intensity projection and virtual rendering techniques postprocessing algorithms. Analysis was made on imaging and intraoperatively for the number of renal arteries as well as their bifurcation pattern, location, vessel caliber, length, and venous anatomy, and these were then compared with each other. MSCTA showed clear delineation of the main renal arteries in all the donors with detailed vessel morphology. The study also revealed a 100% sensitivity in the detection of accessory renal vessels, which had an overall incidence of 26.67%, with the most common distribution in the perihilar region. The present study showed a 100% sensitivity and specificity in the visualization and detection of main and accessory renal vessels with the use of only 50 mL of intravenous contrast with similar results seen with CA which has so far been considered the "gold standard." The results on MSCTA were also better than those with the use of SSCTA and MRA in the workup of liver renal donors, with the above technique also proving to be more cost effective. The overall incidence of supernumerary vessels was the same as reported in the literature; however, a higher incidence of single aberrant vessels was seen on the right side, contrary to what has been suggested so far and was attributable to improved detection of accessory vessels less then 2 mm in diameter.


Neuroscience Symposium and Workshop on SAAPCON-2016, Nepal.
Physiological Society of Nepal, with support from the South Asian Association of Physiologists (SAAP), organized the 5th Biennial Conference of the South Asian Association of Physiologists in conjunction with the 2nd Annual Conference of Physiological Society of Nepal. The purpose of this conference is to bring the scientists, researchers, and students from the South Asian countries in one platform to share and discuss the recent advances and achievements in the field of physiology. Since physiology is the backbone of medical science which deals with the functions of the human body, the theme of the conference was given as "Redefining health in nature." Giving the emphasis on this theme, the conference was organized on November 10-14, 2016, in Kathmandu University, Dhulikhel, Nepal. A total of 300 participants from 15 countries including the South Asian Association of Regional Cooperation (SAARC) and Non-SAARC countries participated in the conference. The scientific program of main conference, which ran for 2 days, was divided into 7 symposia - neuroscience, cardiopulmonary physiology, cellular and integrative physiology, health and lifestyle, role of physiology and medical education, endocrine and reproductive physiology, and high altitude and respiratory physiology - to highlight the latest progresses made in the field of physiology around the globe. Neuroscience symposium held on the second day consisted of 7 advance lectures and 3 young scientist presentations and poster session. Post-conference workshop on system neuroscience was held in BP Koirala Institute of Health Sciences, Dharan, Nepal.


Activation antigen expression on peripheral blood neutrophils following rat small bowel transplantation. NKR-P1 is a novel antigen preferentially expressed during allograft rejection.
This study used flow cytometric analyses to monitor activation antigen expression (MHC class II; interleukin-2 receptor, p55IL-2R and 3.2.3/NKR-P1 antigen) on peripheral blood neutrophils following rat small bowel transplantation. The rat 3.2.3 antigen is a member of the NKR-P1 family of natural killer (NK) cell-associated molecules, which are expressed at high levels on NK cells and lymphokine-activated killer cells, and low levels on at least one T cell subset. Peripheral blood neutrophils in normal animals express very low or undetectable levels of NKR-P1. Detectable levels of NKR-P1 were induced as early as day 1 following small bowel transplantation in all allografted animals, whereas expression was only rarely detected in isografted animals. In addition, NKR-P1 density was significantly higher in allografted animals and was maintained as rejection developed. MHC class II and p55IL-2R expression was also induced following transplantation. The mechanisms of induction and functional relevance of NKR-P1 expression on neutrophils remain to be defined. However, the concomitant increased expression of MHC class II and p55IL-2R suggest NKR-P1 to be a neutrophil activation marker and implicate a potential role for NKR-P1+ neutrophils in small bowel allograft rejection. This hypothesis is further supported by the loss of detectable peripheral blood neutrophils only with developing rejection. Flow cytometric analysis of neutrophil activation antigen expression may be useful for monitoring human small bowel transplant recipients.


Coronary artery fistula diagnosed by transthoracic Doppler echocardiography.
A 47-year-old Malay woman complained of an episode of shortness of breath after a shower. There was no previous complaint of shortness of breath or chest pain. Physical examination revealed a wide pulse pressure. Blood pressure was 160/66 mmHg, and heart rate was 77/minute and regular. What was initially thought to be a loud pansystolic murmur was heard over the precordium. Electrocardiography showed left ventricular hypertrophy with a volume overload pattern. Transthoracic Doppler echocardiography revealed a right coronary artery-right ventricular fistula, arising from the right coronary artery and draining into the right ventricular cavity.


Effects of X-radiation on the retina of the albino rabbit as viewed with the transmission electron microscope.
The eyes of albino rabbits were exposed in vivo to 7,000 rad of X-radiation. The retinae were dissected and examined with a transmission electron microscope 24 and 72 h following irradiation. Damage after 24 h was minimal, but after 72 h it was very pronounced. In both cases the damage was restricted to the photoreceptors.


Novel variant in the TP63 gene associated to ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome.
Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome is a disorder resulting from anomalous embryonic development of ectodermal tissues. There is evidence that AEC syndrome is caused by mutations in the TP63 gene, which encodes the p63 protein. This is an important regulatory protein involved in epidermal proliferation and differentiation. Genome sequencing was performed in DNA from peripheral blood leukocytes of a newborn with AEC syndrome and her parents. Variants were searched in all coding exons and intron-exon boundaries of the TP63 gene. A heterozygous missense variant (NM_003722.4:c.1063G>C (p.Asp355His) was found in the newborn patient. No variants were found in either of the parents. We identified a previously unreported variant in TP63 gene which seems to be involved in the somatic malformations found in the AEC syndrome. The absence of this variant in both parents suggests that the variant appeared de novo.


Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment.
Expression of CA IX is normally restricted to the mucosa of alimentary tract, but on the other hand, it takes place in a high percentage of human cancers derived from tissues which are normally CA IX-negative. It is a transmembrane protein with two extracellular domains: carbonic anhydrase (CA) with a high catalytic activity and a proteoglycan-like segment (PG), mediating cell-cell adhesion. Both CA and PG domains interact with the microenvironment and they could play a role in tumorigenesis, but their roles are poorly understood. The present work characterizes some newly recognized properties of the PG. One of them is a prevalently negative charge, caused by a high proportion of dicarboxylic amino acids. This is reflected by easy dissociation of complexes formed by PG either with monoclonal antibody M75 or with the cell surface receptor already at slightly acidic pH. This property might facilitate separation of cells from the primary tumor. Released cells may subsequently attach elsewhere in the organism and eventually start metastatic growth. Another aim of the present study was to identify human tumor cell lines which are expressing the presumed CA IX receptor molecule. The same cell lines were also tested for the presence of CA IX protein; we found that expression of CA IX and of the receptor is independent of each other. In addition, we examined the species specificity of CA IX receptors. The PG domain, which contains the epitope of mAb M75 -PGEEDLP- overlapping with the binding site for putative receptor is relatively conserved in evolution: human and rat CA IX cross-react with M75 antibody on western blots. Consistently with this, human and rat cells can attach to purified human CA IX protein. On the other hand, murine CA IX contains an entirely different equivalent of PG sequence and it does not react with M75 antibody or attach to human CA IX protein. This is suggestive of the co-evolution of CA IX protein together with its receptor.


The ratio of ubiqiunon redox forms in the liver mitochondria under toxic hepatitis induced on the background of alimentary protein deficiency.
The level of the total ubiqiunon and redox forms CoQ in the rat liver mitochondria under the conditions of alimentary protein deficiency and toxic hepatitis, induced on the background protein deficiency has been investigated. Research has been carried out on 36 white non-linear rats, divided into 4 groups: 1 – rats, maintained on the complete semisynthetic ration; 2 – rats, fed low-protein ration; 3 – rats with acute acetaminophen-induced hepatitis, maintained on complete ration; 4 – rats with acetaminophen-induced hepatitis, maintained under the conditions of protein deficiency. The content of total and oxidized ubiqiunon was determined spectrophotometrically at λ=275 nm (molar extinction coefficient 12.25 Mm-1×sm-1). Reduced ubiqiunon content was determined by the difference between total and oxidized ubiqiunon content. The amount of tyrosine in the liver was measured in deproteinised by 6% sulfosalicylic acid extracts of liver tissue on an automated amino acid analyzer. The decrease of the total ubiqiunon content in liver mitochondria by 35% on the background of 2-fold decrease of oxidized ubiqiunon and preservation of reduced ubiqiunon amount has been estimated under the conditions of low-protein diet. Simultaneously the 5-fold decrease of liver content of tyrosine – the ubiqiunon precursor – has been observed. It has been shown, that under the conditions of acetaminophen-induced hepatitis the content of total ubiqiunon and its redox forms in the liver mitochondria of rats fed complete diet didn't change significantly comparing to control. A decrease of total ubiqiunon by 60% on the background of acute (18-fold) decrease of reduced ubiqiunon in liver mitochondria of rats with hepatitis, fed low-protein diet, has been observed. Established changes of the content of redox ubiquinone forms (a key component of the oxidative phosphorylation system in the liver mitochondria) can be considered as one of the mechanisms of malfunction of energy biotransformation system under the conditions of toxic liver injury in animals with protein deficiency.


[Structural and functional studies on proteins as potential drug discovery targets].
Structural biology teaches us about the fundamental nature of biological molecules. Drug design is the most immediate medical application of structural biology. Therefore our studies have been focused on structural and functional studies of human disease-related proteins and proteins essential for the growth and development of pathogenic organisms. The present paper describes 1) structural biological studies of human autocrine motility factor, 2) structural biological studies of human ribonuclease L, and 3) structural biological studies of Plasmodium falciparum S-adenosyl- L-homocysteine hydrolase.


Integration of exercise response and allometric scaling in endotherms.
The relationship between heart beat frequency and the rate of oxygen consumption for different species of birds and mammals is influenced by body size, the type of exercise being undertaken and its intensity. Here a model is presented combining allometric scaling and exercise-induced variations in oxygen consumption and blood flow, when birds and mammals undergo their primary mode of locomotion. Novel relationships, common to the regulatory systems of all endotherms, are found to relate the rate of oxygen consumption, heart-rate, body and heart mass in 24 species of endotherms spanning 5 orders of body mass. We show that these relationships can be derived from linearity between heart-rate and the arteriovenous oxygen difference, present in data from exercise-attuned humans. We find that the metabolic rate of endotherms undergoing their primary mode of locomotion across a range of exercise intensities is quadratically related to heart-rate and that body mass is inferior to heart mass as a predictive scaling variable. The model facilitates graphical comparisons between species, and enables metabolic costs to be extrapolated from heart-rate data whenever direct measurements of oxygen consumption prove prohibitively challenging.