Long-Term Body Weight Maintenance among StrongWomen-Healthy Hearts Program Participants.
Background. The repeated loss and regain of body weight, referred to as weight cycling, may be associated with negative health complications. Given today's obesity epidemic and related interventions to address obesity, it is increasingly important to understand contexts and factors associated with weight loss maintenance. This study examined BMI among individuals who had previously participated in a 12-week, evidence-based, nationally disseminated nutrition and physical activity program designed for overweight and obese middle-aged and older women. Methods. Data were collected using follow-up surveys. Complete height and weight data were available for baseline, 12-week program completion (post-program) and follow-up (approximately 3 years later) for 154 women (response rate = 27.5%; BMI characteristics did not differ between responders and nonresponders). Results. Mean BMI decreased significantly from baseline to post-program (-0.5, P < 0.001) and post-program to follow-up (-0.7, P < 0.001). Seventy-five percent of survey respondents maintained or decreased BMI post-program to follow-up. Self-efficacy and social support for healthy eating behaviors (but not physical activity) were associated with BMI maintenance or additional weight loss. Conclusions. These findings support the durability of weight loss following participation in a relatively short-term intervention.


Role of guanine nucleotide regulatory protein in polyphosphoinositide degradation and activation of phagocytic leukocytes by chemoattractants.
Leukocyte activation by chemoattractants provides an important model to study the biochemical mechanisms of stimulus-response coupling in these cells. Well-defined chemotactic factors induce readily quantifiable responses in phagocytic leukocytes. These include directed migration and the production and release of toxic substances including oxygen radicals and lysosomal enzymes. The development of radiolabeled synthetic oligopeptides with potent chemotactic activity allowed the demonstration of chemoattractant receptors on polymorphonuclear leukocytes (PMNs) as well as macrophages. In membrane preparations from these cells, these receptors exist in high- and low-affinity states which are regulated by guanosine di- and triphosphates. This suggested that chemoattractant receptors interact with guanine nucleotide regulatory proteins (N or G proteins). Although chemoattractants elicit a rapid but transient increase in intracellular cAMP levels, they neither stimulate nor inhibit membrane-bound adenylate cyclase, suggesting a novel role for N proteins in certain receptor-transduction mechanisms. Stimulation of phagocytes by chemoattractants is also associated with a rapid increase in cytosolic Ca2+ concentrations ([ Ca2+]i) which appears to result from the production of inositol 1,4,5-triphosphate (IP3) as a consequence of the diesteric cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2). Treatment of phagocytes with pertussis toxin (PT), which ADP-ribosylates and thereby inactivates certain N proteins, abolishes the cells' responsiveness to chemoattractants. More direct evidence for a role of a PT-sensitive N protein in leukocyte activation was provided by the demonstration that chemoattractants stimulate the hydrolysis of PIP2 in PMN membranes only in the presence of GTP. This receptor-mediated hydrolysis of PIP2 is not observed in plasma membranes prepared from PT-treated PMNs. Therefore, these studies suggest that occupancy of chemoattractant receptors activates a PT-sensitive N protein. The activated N protein shifts the Ca2+ requirement for phospholipase C activity from supraphysiological levels to ambient cytosolic Ca2+ concentrations. Cleavage of PIP2 results in the formation of the second messenger molecules, IP3 and 1,2-diacylglycerol, which can initiate cellular activation. These messengers also seem to activate responses which feed back to attenuate receptor stimulation of phospholipase.


Metastatic Intimal Sarcoma of the Pulmonary Artery Sensitive to Carboplatin-Vinorelbine Chemotherapy: Case Report and Literature Review.
Pulmonary artery intimal sarcoma (PAIS) is a very rare tumour with a very poor prognosis. In advanced stages, chemotherapy and radiotherapy are poorly efficient, and no standard chemotherapy guideline is currently available. Here, we report on a 37-year-old woman with PAIS initially treated with surgical resection who developed metastatic relapse refractory to anthracycline-based chemotherapy, then trabectedin, then pazopanib. The patient was then given carboplatin-vinorelbine chemotherapy. The treatment was well tolerated, and, rapidly, a CT scan showed an objective response that lasted 8 months despite the 4th therapeutic line. We review the literature and show that our case is the second one that provides evidence of the efficacy of platinum-vinorelbine regimens in this aggressive tumour.


Analysis of sea use landscape pattern based on GIS: a case study in Huludao, China.
This study aims to analyse sea use landscape patterns on a regional scale based on methods of landscape ecology integrated with sea use spatial characteristics. Several landscape-level analysis indices, such as the dominance index, complex index, intensivity index, diversity index and sea congruency index, were established using Geographic Information System (GIS) and applied in Huludao, China. The results indicated that sea use landscape analysis indices, which were created based on the characteristics of sea use spatial patterns using GIS, are suitable to quantitatively describe the landscape patterns of sea use. They are operable tools for the landscape analysis of sea use. The sea use landscape in Huludao was dominated by fishing use with a landscape dominance index of 0.724. The sea use landscape is a complex mosaic with high diversity and plenty of fishing areas, as shown by the landscape complex index of 27.21 and the landscape diversity index of 1.25. Most sea use patches correspond to the marine functional zonation plan and the sea use congruency index is 0.89 in the fishing zone and 0.92 in the transportation zone.


Modeling Pediatric Body Mass Index and Neighborhood Environment at Different Spatial Scales.
In public health research, it has been well established that geographic location plays an important role in influencing health outcomes. In recent years, there has been an increased emphasis on the impact of neighborhood or contextual factors as potential risk factors for childhood obesity. Some neighborhood factors relevant to childhood obesity include access to food sources, access to recreational facilities, neighborhood safety, and socioeconomic status (SES) variables. It is common for neighborhood or area-level variables to be available at multiple spatial scales (SS) or geographic units, such as the census block group and census tract, and selection of the spatial scale for area-level variables can be considered as a model selection problem. In this paper, we model the variation in body mass index (BMI) in a study of pediatric patients of the Virginia Commonwealth University (VCU) Medical Center, while considering the selection of spatial scale for a set of neighborhood-level variables available at multiple spatial scales using four recently proposed spatial scale selection algorithms: SS forward stepwise regression, SS incremental forward stagewise regression, SS least angle regression (LARS), and SS lasso. For pediatric BMI, we found evidence of significant positive associations with visit age and black race at the individual level, percent Hispanic white at the census block group level, percent Hispanic black at the census tract level, and percent vacant housing at the census tract level. We also found significant negative associations with population density at the census tract level, median household income at the census tract level, percent renter at the census tract level, and exercise equipment expenditures at the census block group level. The SS algorithms selected covariates at different spatial scales, producing better goodness-of-fit in comparison to traditional models, where all area-level covariates were modeled at the same scale. These findings underscore the importance of considering spatial scale when performing model selection.


Mosaic modularity: an updated perspective and research agenda for the evolution of vascular cambial growth.
Secondary growth from a vascular cambium, present today only in seed plants and isoetalean lycophytes, has a 400-million-yr evolutionary history that involves considerably broader taxonomic diversity, most of it hidden in the fossil record. Approaching vascular cambial growth as a complex developmental process, we review data from living plants and fossils that reveal diverse modes of secondary growth. These are consistent with a modular nature of secondary growth, when considered as a tracheophyte-wide structural feature. This modular perspective identifies putative constituent developmental modules of cambial growth, for which we review developmental anatomy and regulation. Based on these data, we propose a hypothesis that explains the sources of diversity of secondary growth, considered across the entire tracheophyte clade, and opens up new avenues for exploring the origin of secondary growth. In this hypothesis, various modes of secondary growth reflect a mosaic pattern of expression of different developmental-regulatory modules among different lineages. We outline an approach that queries three information systems (living seed plants, living seed-free plants, and fossils) and integrates data on developmental regulation, anatomy, gene evolution and phylogeny to test the mosaic modularity hypothesis and its implications, and to inform efforts aimed at understanding the evolution of secondary growth.


Interstitial lung abnormalities in patients with early rheumatoid arthritis: A pilot study evaluating prevalence and progression.
Pulmonary disease is a leading cause of morbidity and mortality in rheumatoid arthritis (RA). In this study, we investigated the prevalence and progression of interstitial lung abnormalities (ILA) in a prospective cohort study of 18 subjects with early RA. Eighteen adults diagnosed with anti-citrullinated protein-antibody-positive RA within the prior year underwent baseline high-resolution computed tomography (HRCT), symptom assessment, and pulmonary function and laboratory testing. The follow-up HRCT and clinical assessment were completed after 1 year. Seven of the 18 patients (39%) had baseline HRCT abnormalities including septal thickening, honeycombing, ground glass opacities, and/or traction bronchiectasis. At follow-up, 6 out of the 7 subjects (86%) with ILAs at baseline exhibited progression, while 10 out of 11 (91%) without ILAs at baseline remained stable. A higher Clinical Chronic Obstructive Pulmonary Disease Questionnaire score was associated with both the presence and progression of HRCT abnormalities (10 vs 2, p=0.045; 10 vs 2, p=0.009, respectively). C-reactive protein (CRP) trended higher in patients with radiologic abnormalities (3.5 mg/L vs 1.1 mg/L, p=0.08) and was significantly higher in those with progression (3.5 mg/L vs 1 mg/L, p=0.024). Smoking, pulmonary function, and autoantibodies were not associated with HRCT abnormalities. ILAs are prevalent in patients with early RA. If identified at baseline, radiographic progression of ILAs after 1 year is likely, while those without ILAs at baseline are unlikely to develop new ILAs. In addition, early respiratory symptoms and higher CRP levels may correlate with the presence and progression of underlying ILAs.


Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain.
The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene × Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid release upon exposure to stress. Both endophenotypes are regulated by the neuropeptide corticotropin-releasing factor (CRF) or hormone, which is expressed by the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, and the central amygdala (CeA). Therefore, we hypothesized that altered regulation of the expression of CRF in these areas represents a major neurobiological mechanism underlying the interaction of early life stress and 5-HTT gene variation. The programming of gene transcription by Gene × Environment interactions has been proposed to involve epigenetic mechanisms such as DNA methylation. In this study, we report that early life stress and 5-HTT genotype interact to affect DNA methylation of the Crf gene promoter in the CeA of adult male rats. Furthermore, we found that DNA methylation of a specific site in the Crf promoter significantly correlated with CRF mRNA levels in the CeA. Moreover, CeA CRF mRNA levels correlated with stress coping behavior in a learned helplessness paradigm. Together, our findings warrant further investigation of the link of Crf promoter methylation and CRF expression in the CeA with behavioral changes that are relevant for psychopathology.


Generation and characterization of Tmeff2 mutant mice.
TMEFF2 is a single-transmembrane protein containing one EGF-like and two follistatin-like domains. Some studies implicated TMEFF2 as a tumor suppressor for prostate and other cancers, whereas others reported TMEFF2 functioning as a growth factor for neurons and other cells. To gain insights into the apparently conflicting roles of TMEFF2, we generated a null allele of Tmeff2 gene by replacing its first coding exon with human placental alkaline phosphatase cDNA (Tmeff2(PLAP)). Tmeff2(PLAP/PLAP) homozygous mutant mice are born normal, but show growth retardation and die around weaning age. Tmeff2 is widely expressed in the nervous system, and the Tmeff2(PLAP) knock-in allele enables the visualization of neuronal innervations of skin and internal organs with a simple alkaline phosphatase staining. Tmeff2 is also highly expressed in prostate gland and white adipose tissues (WAT). However, with the exception of reduced WAT mass, extensive anatomical and molecular analyses failed to detect any structural or molecular abnormalities in the brain, the spinal cord, the enteric nervous system, or the prostate in the Tmeff2 mutants. No tumors were found in Tmeff2-mutant mice. The Tmeff2(PLAP/PLAP) knock-in mouse is an useful tool for studying the in vivo biological functions of TMEFF2.


Light promotion of hypocotyl gravitropism of a starch-deficient tobacco mutant correlates with plastid enlargement and sedimentation.
Dark-grown hypocotyls of a starch-deficient mutant (NS458) of tobacco (Nicotiana sylvestris) lack amyloplasts and plastid sedimentation, and have severely reduced gravitropism. However, gravitropism improved dramatically when NS458 seedlings were grown in the light. To determine the extent of this improvement and whether mutant hypocotyls contain sedimented amyloplasts, gravitropic sensitivity (induction time and intermittent stimulation) and plastid size and position in the endodermis were measured in seedlings grown for 8 d in the light. Light-grown NS458 hypocotyls were gravitropic but were less sensitive than the wild type (WT). Starch occupied 10% of the volume of NS458 plastids grown in both the light and the dark, whereas WT plastids were essentially filled with starch in both treatments. Light increased plastid size twice as much in the mutant as in the WT. Plastids in light-grown NS458 were sedimented, presumably because of their larger size and greater total starch content. The induction by light of plastid sedimentation in NS458 provides new evidence for the role of plastid mass and sedimentation in stem gravitropic sensing. Because the mutant is not as sensitive as the WT, NS458 plastids may not have sufficient mass to provide full gravitropic sensitivity.


[Non rheumatic pulmonary hemorrhage: case series description].
Pulmonary hemorrhage (PH) is characterized by diffuse hemorrhage from the pulmonary microvasculature. Its main features are dyspnea, hemoptysis, diffuse bilateral alveolar infiltrate and sudden fall in hemoglobin. Because the conditioning causes can be both: rheumatic and non-rheumatic, early recognition of the precipitating causes aids in orienting specific therapy. To identify the clinical and paraclinical features of non-rheumatic PH and determine the associated mortality. The charts of all patients diagnosed with HP in this institution between 1987 and 1997 were reviewed. OPERATIVE DESCRIPTIONS (DEFINITION): HP was confirmed by bronchoscopy, pulmonary biopsy, necropsy or at least three of the following criteria: a.--Sudden dyspnea, b.--Hemoptysis, c.--Hb decrease of 1 g/dL or more, d.--Recent alveolar infiltrate in the chest X-ray. Descriptive statistics. Nine cases of non rheumatic PH were identified. Median age of patients was 34 years. Six cases corresponded to men, chemotherapy was associated in three patients. The duration from diagnosis of the underlying disease to HP was one to 73 months. All the patients presented dyspnea, crepitant ates tachycardia, decrease in Hb (median 2 g/dL), hypoxemia a mean of 53.4 mmHg. A diffuse interstitial pattern was evident in X rays of six cases; bronchoscopy was performed in three. Seven patients died, six because of massive pulmonary hemorrhage as the direct cause of death and one because of ARDS. PH occurs in hematological diseases accompanied by severe thrombocytopenia and progressive pulmonary infections. Because its associated with high mortality, early detection and treatment are of utmost importance.


Decreased consumption of common weaning foods is associated with poor linear growth among HIV-exposed infants participating in the Kigali antiretroviral and breastfeeding assessment for the elimination of HIV (Kabeho) study.
The World Health Organization recommends that complementary foods that are adequate, safe, and appropriate be introduced to infants at age 6 months. Using an innovative modeling technique, we examine patterns of nutrient intake in HIV-exposed and uninfected (HEU) infants and establish their relationship with growth. Single-day dietary recalls and anthropometrics were collected every two to 3 months from 543 infants living in Kigali, Rwanda, and attending clinics for the prevention of mother-to-child HIV transmission. A common weaning food index (CWFI) was calculated in grams and nutrient density for infants to reflect the extent to which the infants consumed the weaning foods typical of this population at ages 6 to 10, 11 to 15, and 16 to 20 months. Regressions among the CWFI, length-for-age z-scores (LAZ), and weight-for-length z-scores (WLZ) were conducted to estimate the relationship between the dietary patterns and growth. Mean absolute intake of zinc and calcium from complementary foods was insufficient. Increasing CWFI was related to increasing cow milk consumption. The density CWFI showed a decrease in the density of iron and folate as infants consume more of the weaning foods typical of this population. Density CWFI, breastfeeding, and caloric intake act on early LAZ and WLZ and interact with one another. Among breastfed infants, those who consume little of the common weaning foods and have a high caloric intake develop deficits in LAZ and have an elevated WLZ. A diet that is more dominated by the typical weaning foods of this population may support a healthy growth pattern.


Photoinduced Charge Transfer and Recombination Dynamics in Star Nonfullerene Organic Solar Cells.
Nonfullerene acceptors (NFAs) are regarded as star candidates for efficient organic solar cells with power conversion efficiency (PCE) over 18%. In contrast to the rapid development of NFA materials, however, the underlying excited-state dynamics which fundamentally govern the device performance remains unclear. In this Perspective, we discuss recent advances and provide our insights on photoinduced charge transfer and combination dynamics in NFA-based organic solar cells (OSCs), including the biphasic hole-transfer process and its correlation with morphology, the role of driving force and Marcus normal region behavior on interfacial hole-transfer properties, and charge recombination energy loss by NFA triplet formation. We also discuss our understanding of how to control the charge-transfer and recombination processes by phase morphology and molecular design to improve OSC performance. Finally, we suggest a few research directions, including the interfacial charge transfer and separation mechanism, the origin of low fill factor, and complex excited-state dynamics in multicomponent OSCs.


Parthenogenesis is rare in the reproduction of a sexual field population of the isogamous brown alga Scytosiphon (Scytosiphonaceae, Ectocarpales).
Parthenogenetic development of unfused gametes is commonly observed in laboratory cultures among various brown algal taxa. There is, however, little information on the contribution of parthenogenesis to the reproduction of field populations. In this study, we investigated whether parthenogenesis is present in a sexual population of the isogamous brown alga Scytosiphon with a 1:1 sex ratio. In culture, both female and male gametes showed higher mortality and slower development compared to zygotes. More than 90% of surviving partheno-germlings formed parthenosporophytes irrespective of the culture conditions tested. Therefore, if parthenogenesis occurs in the field, most unfused gametes are expected to form parthenosporophytes. Contrary to this expectation, parthenosporophytes were rare in the field population. We collected 126 sporophytic thalli and isolated and cultured a unilocular sporangium from each of them. We confirmed that cultures of 120 unilocular sporangia produced both female and male gametophytes by the observation of zygotes or amplification of PCR-based sex markers indicating that these sporangia originated from zygotic sporophytes. Only females were detected in cultures from two sporangia and only males from four sporangia suggesting that these sporangia originated from parthenosporophytes. In the Scytosiphon population, although parthenogenesis is observable in culture, our results demonstrate that the contribution of parthenogenesis to reproduction is small (≤4.8%) compared to sexual reproduction. Unfused gametes may not survive to form mature parthenosporophytes in significant numbers in the field partly due to their higher mortality and slower development compared from zygotes.


[Toxocariasis in a 5-year-old boy--manifesting as bronchial asthma and behavioral disorder].
We report on a five year old boy who was admitted to hospital because of obstructive airway disease; initially, findings were interpreted to indicate bronchial asthma. In addition, the patient presented with a behavioural abnormality of aggressiveness and hyperactivity. Laboratory examinations showed an elevated IgE level and eosinophilia, chest x-ray revealed infiltrations in both lungs. After excluding a spectrum of chronic lung disorders by relevant investigations, serological testing for parasitosis revealed massively elevated toxocara IgG antibodies. The diagnosis of a "covert form" of toxocarosis was established and an antihelminthic therapy with albendazole was initiated. Chronic respiratory symptoms in childhood can also indicate the presence of a parasitic infestation.


Initial response and cellular protection through the Keap1/Nrf2 system during the exposure of primary mouse hepatocytes to 1,2-naphthoquinone.
Quinones are reactive chemical species that cause cellular damage by modifying protein thiols and/or catalyzing the reduction of oxygen to reactive oxygen species, thereby promoting oxidative stress. Transcription factor Nrf2 plays a crucial role in cellular defense against electrophilic modification and oxidative stress. In studies using 1,2-naphthoquinone (1,2-NQ) as a model quinone, we found that Keap1, the negative regulator of Nrf2, was readily arylated at its reactive thiols by 1,2-NQ. Exposure of primary mouse hepatocytes to 1,2-NQ resulted in the activation of Nrf2 and the upregulation of some of Nrf2's downstream genes. This interaction was further investigated in hepatocytes from Nrf2 knockout mice in which the proteins responsible for the metabolism and excretion of 1,2-NQ are minimally expressed. The chemical modification of cellular proteins by 1,2-NQ was enhanced by Nrf2 deletion, resulting in increased toxicity. However, deletion of the negative regulatory protein, Keap1, drastically reduced the covalent binding by 1,2-NQ and its cellular toxicity. Experiments with chemicals that inhibit the biotransformation and extracellular excretion of 1,2-NQ suggest that 1,2-NQ undergoes detoxification and excretion into the extracellular space predominantly by two-electron reduction and subsequent glucuronidation by NAD(P)H:quinone oxidoreductase 1 and uridine 5'-diphosphate-glucuronosyltransferases, followed by multidrug resistance-associated protein-dependent excretion. These findings suggest that the Keap1/Nrf2 system is essential for the prevention of cell damage resulting from exposure to 1,2-NQ.


[Digital fluorograph with automatic exposition].
Discussed in the paper is a system of automatic exposition choice in a digital fluorograph designed by the "Gelpik" company, Moscow. The perspective equipment variation is as follows: intensifying screen + optic system + charge-communication device-matrix.


Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men.
There is growing interest in understanding how diet affects the intestinal microbiota, including its possible associations with systemic diseases such as metabolic syndrome. Here we report a comprehensive and deep microbiota analysis of 14 obese males consuming fully controlled diets supplemented with resistant starch (RS) or non-starch polysaccharides (NSPs) and a weight-loss (WL) diet. We analyzed the composition, diversity and dynamics of the fecal microbiota on each dietary regime by phylogenetic microarray and quantitative PCR (qPCR) analysis. In addition, we analyzed fecal short chain fatty acids (SCFAs) as a proxy of colonic fermentation, and indices of insulin sensitivity from blood samples. The diet explained around 10% of the total variance in microbiota composition, which was substantially less than the inter-individual variance. Yet, each of the study diets induced clear and distinct changes in the microbiota. Multiple Ruminococcaceae phylotypes increased on the RS diet, whereas mostly Lachnospiraceae phylotypes increased on the NSP diet. Bifidobacteria decreased significantly on the WL diet. The RS diet decreased the diversity of the microbiota significantly. The total 16S ribosomal RNA gene signal estimated by qPCR correlated positively with the three major SCFAs, while the amount of propionate specifically correlated with the Bacteroidetes. The dietary responsiveness of the individual's microbiota varied substantially and associated inversely with its diversity, suggesting that individuals can be stratified into responders and non-responders based on the features of their intestinal microbiota.


Genetic Diversity and Population Structure of African Sorghum (Sorghum bicolor L. Moench) Accessions Assessed through Single Nucleotide Polymorphisms Markers.
Assessing the genetic diversity and population structure of cultivated sorghum is important for heterotic grouping, breeding population development, marker-assisted cultivar development, and release. The objectives of the present study were to assess the genetic diversity and deduce the population structure of 200 sorghum accessions using diversity arrays technology (DArT)-derived single nucleotide polymorphism (SNP) markers. The expected heterozygosity values ranged from 0.10 to 0.50 with an average of 0.32, while the average observed heterozygosity (0.15) was relatively low, which is a typical value for autogamous crops species like sorghum. Moderate polymorphic information content (PIC) values were identified with a mean of 0.26, which indicates the informativeness of the chosen SNP markers. The population structure and cluster analyses revealed four main clusters with a high level of genetic diversity among the accessions studied. The variation within populations (41.5%) was significantly higher than that among populations (30.8%) and between samples within the structure (27.7%). The study identified distantly related sorghum accessions such as SAMSORG 48, KAURA RED GLUME; Gadam, AS 152; CSRO1, ICNSL2014-062; and YALAI, KAFI MORI. The accessions exhibited wide genetic diversity that will be useful in developing new gene pools and novel genotypes for West Africa sorghum breeding programs.


Enzyme-linked immunosorbent assay for measurement of antibody against cytomegalovirus and rubella virus in a single serum dilution.
Enzyme-linked immunosorbent assays (ELISA) were developed for quantifying cytomegalovirus (CMV) and rubella antibodies using a single serum dilution (1/800) in conjunction with a standard curve. A near linear relation was found between the logarithms of absorbance values of sera at a dilution of 1/800 and the titres as determined by an end point dilution ELISA. The reproducibility of the single dilution ELISA was good; the within-test coefficients of variation averaged 7.5% for CMV antibody and 12.4% for rubella antibody. A close correlation was found between ELISA and complement-fixing (CF) antibody titres to CMV and between ELISA and haemagglutination-inhibition (HI) antibody titres to rubella virus. The titres in ELISA were 200 to 1000 times higher than in CF for CMV and 50 to 100 times higher than in HI for rubella virus.


1H NMR studies of porcine uteroferrin. Magnetic interactions and active site structure.
Pink (reduced) uteroferrin exhibits well resolved paramagnetic NMR spectra with resonances ranging from 90 ppm downfield to 70 ppm upfield. The intensities of these signals depend on the degree of reduction and correlate well with the intensity of the EPR signals with gave = 1.74. Analyses of chemical shifts and the temperature dependence of the paramagnetically shifted resonances indicate that the Fe(III)-Fe(II) cluster in the reduced protein exhibits weak antiferromagnetic exchange coupling (-J approximately equal to 10 cm-1), in agreement with the estimate derived from the temperature dependence of the EPR signal intensity. Purple (oxidized) uteroferrin, on the other hand, exhibits no discernible paramagnetically shifted resonances, reflecting either strong antiferromagnetic coupling or an unfavorable electron spin-lattice relaxation time. Evans susceptibility comparisons between pink and purple uteroferrin show that the Fe(III)-Fe(III) cluster in the oxidized protein is more strongly coupled (-J greater than 40 cm-1). This value concurs with low temperature magnetic susceptibility measurements on both the porcine and splenic purple acid phosphatases. The isotropically shifted protons of tyrosine coordinated to the cluster are assigned by comparison with synthetic complexes. Tyrosine, earlier implicated as a ligand by resonance Raman spectroscopy, appears to coordinate only to the ferric site in pink uteroferrin. This is consistent with the relatively invariant extinction coefficients of uteroferrin in its oxidized and reduced forms and the ease of reduction of the nonchromophoric iron compared to its chromophoric partner. Other possible ligands to the cluster include histidine, suggested by the presence of downfield-shifted solvent-exchangeable resonances with appropriate isotropic shifts.


Micronutrient Deficiencies in Systemic Sclerosis: A Scoping Review.
The primary aim is to identify the micronutrient deficiencies commonly reported in SSc. The exploratory aim is to evaluate associations between micronutrient deficiencies and SSc clinical manifestations. We conducted a scoping review of all published reports on SSc and nutrition in PubMed from its inception to August 2020. Clinical trials, observational studies, meta-analyses, and case series (with ≥20 cases) containing data on nutritional deficiency and SSc were included. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for reporting our findings. Two reviewers (ADN and ERV) studied the titles and abstracts of all search results with pre-specified inclusion and exclusion criteria. Among 790 retrieved publications, 35 full-length articles and 3 abstracts met the inclusion/exclusion criteria. Included studies took place across multiple geographic locations and included patients with both diffuse and limited cutaneous SSc. Vitamin D deficiency was the most commonly reported deficiency described in SSc, followed by vitamin B12, vitamin B9, selenium, zinc, and iron. In addition, some small studies found deficiencies in vitamins B1, B6, C, E, and A. While some studies reported associations between specific micronutrient deficiencies and SSc disease features (eg, interstitial lung disease was commonly associated with vitamin D deficiency and elevated homocysteine [Hcy]), the evidence to support these associations was not robust. Micronutrient deficiencies are common in SSc and are associated with specific SSc features. Routine screening for micronutrient deficiencies may lead to early detection of malnutrition. Future studies are needed to understand how interventions to replete micronutrient deficiencies affect patient outcomes in SSc.


Language mapping in multilingual patients: electrocorticography and cortical stimulation during naming.
Multilingual patients pose a unique challenge when planning epilepsy surgery near language cortex because the cortical representations of each language may be distinct. These distinctions may not be evident with routine electrocortical stimulation mapping (ESM). Electrocorticography (ECoG) has recently been used to detect task-related spectral perturbations associated with functional brain activation. We hypothesized that using broadband high gamma augmentation (HGA, 60-150 Hz) as an index of cortical activation, ECoG would complement ESM in discriminating the cortical representations of first (L1) and second (L2) languages. We studied four adult patients for whom English was a second language, in whom subdural electrodes (a total of 358) were implanted to guide epilepsy surgery. Patients underwent ECoG recordings and ESM while performing the same visual object naming task in L1 and L2. In three of four patients, ECoG found sites activated during naming in one language but not the other. These language-specific sites were not identified using ESM. In addition, ECoG HGA was observed at more sites during L2 versus L1 naming in two patients, suggesting that L2 processing required additional cortical resources compared to L1 processing in these individuals. Post-operative language deficits were identified in three patients (one in L2 only). These deficits were predicted by ECoG spectral mapping but not by ESM. These results suggest that pre-surgical mapping should include evaluation of all utilized languages to avoid post-operative functional deficits. Finally, this study suggests that ECoG spectral mapping may potentially complement the results of ESM of language.


Firing properties of single muscle vasoconstrictor neurons in the sympathoexcitation associated with congestive heart failure.
Congestive heart failure (CHF) in humans is associated with a marked sympathoexcitation, including an augmented muscle sympathetic nerve activity (MSNA) in intraneural multiunit recordings. In the present study, single-unit recording was used to evaluate whether the firing properties of individual muscle vasoconstrictor neurons can reveal underlying mechanisms for this increase in MSNA. Eight patients with CHF (NYHA class II to IV; left ventricular ejection fraction, 29+/-5%, mean+/-SEM) were studied. In standard multiunit recordings, MSNA burst incidence (bursts/100 heartbeats) ranged from 65% to 100% (88+/-5%). Using selective tungsten microelectrodes, we made recordings from 16 single muscle vasoconstrictor axons. Mean unit firing probability (ie, the percentage of cardiac intervals in which a single axon fired) was 54.5+/-5.2% (range, 21 to 89%), and mean firing frequency was 0.98+/-0.22 Hz (0.14 to 3.86 Hz), both of which were higher than seen previously in healthy subjects (P<0.001). Although single neurons occasionally generated multiple spikes per sympathetic burst, such multiple firing was rare and was not different from that seen in healthy subjects. An increased firing frequency of individual vasoconstrictor neurons is one mechanism for the increased number of multiunit MSNA bursts at rest in CHF. The neurons discharge in more diastoles than in healthy subjects (ie, firing probability is increased), but the likelihood of discharging >1 impulse per sympathetic burst is not increased. Despite the intense multiunit activity at rest, the firing characteristics of individual vasoconstrictor axons indicate a remaining capacity for transient increases of MSNA in CHF.


Female and younger subjects have lower adherence in PrEP trials: a meta-analysis with implications for the uptake of PrEP service to prevent HIV.
To estimate the medicine-taking compliance (MTC) level, explore its facilitators and barriers, and quantify the association between MTC level and pre-exposure prophylaxis (PrEP) protective efficacy in individuals at risk of acquiring HIV being administered oral PrEP. Meta-analysis. We searched PubMed, Cochrane and Embase databases for published randomized controlled trials (RCTs) pertaining to MTC of oral PrEP for HIV prevention up to 16 January 2017. The pooled proportion of MTC and risk ratio (RR) of HIV incidences between intervention group and control group were estimated. We identified 10 eligible studies with 24 193 participants. The overall pooled MTC for oral HIV PrEP was 59.9% (95% CI 43.1% to 74.6%). Subgroup analyses revealed that the MTC level of participants aged <30 years was lower than those equal or older than 30 years (34.9% vs 69.6%, p<0.001); those studies that enrolled only women as participants had lower MTC than those only recruiting either only men or both men and women (31.3% vs 71.7% and 31.3% vs 71.0%, all p<0.01). Additionally, the HIV infection risk increased as the MTC level declines, with the incidence RRs being 0.28 (95% CI 0.19 to 0.41), 0.42 (95% CI 0.29 to 0.62) and 0.75 (95% CI 0.45 to 1.25) in the good (≥80%), moderate (60%~80%) and poor (<60%) MTC subgroups, respectively (linear trend test p<0.01). According to the pooled proportion, the MTC of oral HIV PrEP is almost moderate, and its proportion in women and younger participants was relatively low. The protective efficacy of oral PrEP for HIV prevention increased with MTC level. These findings indicated that it is necessary to identify measures to enhance MTC of oral PrEP in future clinical usage, especially in women and younger participants with high HIV infection risk.


Impact on Kidney Function and Medium-Term Outcomes of Transcatheter Aortic Valve Replacement in Patients With Chronic Kidney Disease.
Transcatheter aortic valve replacement (TAVR) is now widely approved for the treatment of aortic stenosis, regardless of the patients' surgical risk. However, the outcomes of TAVR and their determinants in patients with chronic kidney disease (CKD) beyond 1 year of follow-up are unknown. We aimed to assess the medium-term outcomes of TAVR in CKD, develop a risk score to estimate the 2-year mortality in patients with CKD, and evaluate the changes in kidney function at discharge after TAVR. Adults who underwent TAVR were retrospectively identified. The CKD stage was determined using the Chronic Kidney Disease Epidemiology 2021 creatinine formula. Improved kidney function was defined as post-TAVR creatinine ≤50% of pre-TAVR creatinine or decrease in creatinine of ≥0.3 mg/100 ml compared with pre-TAVR creatinine. Overall, 1,523 patients (median age 82 years; 59% men; 735 with CKD stage II or less, 661 with CKD III, 83 with CKD IV, and 44 with CKD V [of whom 40 were on dialysis]) were included. The all-cause mortality was higher in CKD stages IV and V on the multivariable analysis (p <0.001) at median follow-up of 2.9 (interquartile range 2.0 to 4.2) years. Moderate or severe tricuspid regurgitation, anemia, right ventricular systolic pressure >40 mm Hg and CKD stages IV and V were independent predictors of 2-year mortality and were used to develop a risk score. At hospital discharge, persisting acute kidney injury after TAVR occurred in 88 of 1,466 patients (6%), whereas improved kidney function occurred in 170 of 1,466 patients (12%). In conclusion, CKD stage was an independent determinant of mortality beyond 2 years after TAVR. Kidney function was more likely to improve than worsen at the time of hospital discharge after TAVR.


The nestin-expressing and non-expressing neurons in rat basal forebrain display different electrophysiological properties and project to hippocampus.
Nestin-immunoreactive (nestin-ir) neurons have been identified in the medial septal/diagonal band complex (MS/DBB) of adult rat and human, but the significance of nestin expression in functional neurons is not clear. This study investigated electrophysiological properties and neurochemical phenotypes of nestin-expressing (nestin+) neurons using whole-cell recording combined with single-cell RT-PCR to explore the significance of nestin expression in functional MS/DBB neurons. The retrograde labelling and immunofluorescence were used to investigate the nestin+ neuron related circuit in the septo-hippocampal pathway. The results of single-cell RT-PCR showed that 87.5% (35/40) of nestin+ cells expressed choline acetyltransferase mRNA (ChAT+), only 44.3% (35/79) of ChAT+ cells expressed nestin mRNA. Furthermore, none of the nestin+ cells expressed glutamic acid decarboxylases 67 (GAD(67)) or vesicular glutamate transporters (VGLUT) mRNA. All of the recorded nestin+ cells were excitable and demonstrated slow-firing properties, which were distinctive from those of GAD(67) or VGLUT mRNA-positive neurons. These results show that the MS/DBB cholinergic neurons could be divided into nestin-expressing cholinergic neurons (NEChs) and nestin non-expressing cholinergic neurons (NNChs). Interestingly, NEChs had higher excitability and received stronger spontaneous excitatory synaptic inputs than NNChs. Retrograde labelling combined with choline acetyltransferase and nestin immunofluorescence showed that both of the NEChs and NNChs projected to hippocampus. These results suggest that there are two parallel cholinergic septo-hippocampal pathways that may have different functions. The significance of nestin expressing in functional neurons has been discussed.


Knowledge and attitudes of a group of South African mine workers towards noise induced hearing loss and the use of hearing protective devices.
The study aimed to explore the knowledge and attitudes of a group of mine workers regarding noise induced hearing loss and the use of hearing protective devices. These aims were investigated via a questionnaire administered in a group setting to 55 underground mine workers. The main finding that emerged from the study was that respondents were poorly informed regarding the fact that noise was a health hazard. Furthermore, the knowledge that respondents did possess, appeared to have been derived from the personal experience of working in noisy environments for many years, rather than from educational input. Contrary to expectations, respondents did not view deafness as a status symbol but rather as a negative attribute. Consequently, they were motivated to protect themselves from hearing impairment and to be educated about hearing and the effects of noise. The mine workers complained about discomfort when wearing hearing protective devices as well as feelings of insecurity due to inhibition of communication and the inability to hear warning signals. For these reasons, noise protection was mainly worn in situations perceived as noisy by workers themselves. These results are discussed in terms of their implications for the clinical practice of audiology; hearing conservation in the mining industry; further research; and the training and education of speech-language pathologists and audiologists.


[Speciation analysis of arsenic in traditional Chinese medicines by hydride generation-atomic fluorescence spectrometry with ion exchange resin separation].
A method for the determination of arsenic species (arsenide, arsenate) in traditional Chinese medicines using hydride generation atomic fluorescence spectrometry (HG-AFS) with ion exchange resin separation has been studied. The ion exchange resin was used to separate the arsenide and arsenate, and the separation conditions were investigated. The experimental conditions that influence the fluorescence intensity and the reduction of arsenic(V) were investigated and optimized, and the influence of foreign ions and its elimination were studied. The proposed method was applied to the determination of arsenic species in water leachate of traditional Chinese medicines. A detection limit of 89.1 ng x mL(-1) and a recovery range of 91.1%-109.3% were obtained.


Next-generation sequencing as an advanced supplementary tool for the diagnosis of pathogens in lower respiratory tract infections: An observational trial in Xi'an, China.
The application of next-generation sequencing (NGS) in routine clinical analysis is still limited. The significance of NGS in the identification of pathogens of lower respiratory tract infection should be assessed as part of routine clinical bacterial examinations and chest imaging results. In the present study, the alveolar lavage fluid samples of 30 patients (25 males and 5 females, aged 19-92 years old, with a median age of 62) were examined by routine bacterial culture and NGS, and the results of pathogen detection and identification were compared. Chest imaging showed consolidation in all 30 patients (100%), and pleural effusion in 13 of the 30 patients (43.33%). The routine bacterial culture of the lavage solution was only positive in 14 of the 30 patients (46.6%), and negative in 16 patients (53.33%). However, the positive rate of NGS test results of the lavage fluid was 100%. A total of 12 cases (40%) were completely consistent with the routine bacterial culture test, with 56 other pathogens of mixed infection detected, accounting for the short comings of the routine bacterial examination. Although NGS cannot distinguish between live and dead bacteria, it is still a useful detection technology for accurate diagnosis of clinical infectious diseases. It is worthy of adaptation in the clinic for more effective clinical management and treatment of the lower respiratory airway infection in addition to the routine bacterial culture testing.


Incorporation of an Intermediate Polyelectrolyte Layer for Improved Interfacial Polymerization on PAI Hollow Fiber Membranes.
In a single-step spinning process, we create a thin-walled, robust hollow fiber support made of Torlon® polyamide-imide featuring an intermediate polyethyleneimine (PEI) lumen layer to facilitate the integration and covalent attachment of a dense selective layer. Subsequently, interfacial polymerization of m-phenylenediamine and trimesoyl chloride forms a dense selective polyamide (PA) layer on the inside of the hollow fiber. The resulting thin-film composite hollow fiber membranes show high NaCl rejections of around 96% with a pure water permeability of 1.2 LMH/bar. The high success rate of fabricating the thin-film composite hollow fiber membrane proves our hypothesis of a supporting effect of the intermediate PEI layer on separation layer formation. This work marks a step towards the development of a robust method for the large-scale manufacturing of thin-film composite hollow fiber membranes for reverse osmosis and nanofiltration.


End-to-end ureteral anastomosis and double-pigtail ureteral stent placement for treatment of iatrogenic ureteral trauma in two dogs.
A 6-month-old spayed female Soft-Coated Wheaten Terrier and 8-month-old spayed female Shih Tzu were referred because of complications related to inadvertent ureteral ligation and transection during recent ovariohysterectomy. The Soft-Coated Wheaten Terrier had a 2-day history of stranguria and polyuria that began after ovariohysterectomy. Initial examination findings were unremarkable with the exception of high rectal temperature. The Shih Tzu had a 10-day history of pyrexia, vomiting, diarrhea, and stranguria that began after ovariohysterectomy. On examination, the dog had signs of depression; clinicopathologic tests revealed hypoalbuminemia, neutrophilia, lymphocytosis, and monocytosis. Abdominal ultrasonography was performed for both dogs, revealing severe unilateral pyelectasia and hydroureter (proximal portion). Both dogs underwent exploratory celiotomy; ureteral ligation and transection was confirmed. Ventral cystotomy was performed to allow retrograde placement of a double-pigtail ureteral stent into the affected ureter and renal pelvis. End-to-end ureteral anastomosis was performed over the stent with the aid of an operating microscope. Stent position was confirmed via fluoroscopy, and incisions were closed routinely. Dogs continued to have intermittent signs of stranguria until stent removal via cystoscopy 6 or 7 weeks after surgery. Ultrasonographic examination of the urogenital tract was performed 2 or 4 months after surgery, revealing resolution of pyelectasia and hydroureter. The surgical technique used provided a viable option for preserving renal function in dogs with focal, iatrogenic ureteral trauma. Use of a ureteral stent facilitated ureteral anastomosis and minimized postoperative complications.


[Treatment outcome study of the stuttering therapy summer camp 2000 for children and adolescents].
Therapists are generally confronted with the question, to what extent results of randomised clinical trials with their emphasis on internal validity are relevant for practitioners and their unselected patients. Often results from clinical trials are neglected in clinical practice and the "normal" practice remains unstudied. In this study a therapeutic approach for stuttering has been studied under practice conditions, but with a maximum of methodological validity. Beyond the concrete study it is also discussed whether the chosen procedure can be a model for practice studies. Patients from age 9 to 19 participated in a stuttering therapy summer-camp for children and adolescents by the Austria-Self-Aid-Initiative Stuttering. Participants were supposed to learn a more open handling of their stuttering and acquire basics for a fluent speech. The therapy concept includes elements of a fluency shaping and a stuttering modification therapy. The evaluation followed a panel design with two assessments before, one assessment after therapy and one follow-up and three types of measurement: 1. three videotaped speech situations, 2. four questionnaires for the participants and their parents, and 3. Goal Attainment Scalings (GAS). The stuttering frequency shows a reduction from 22.2 to 9.5 % (effect size 1.29). Follow-up results, GAS and all questionnaires also indicate clear improvements. Altogether, the Therapeutic Stuttering Summer-camp was able to reach its aims.


Assessment of simulated clinical skills and distance students: can we do it better?
Australian universities have traditionally been able to supplement clinical education, for undergraduate nursing courses, delivered on placement with weekly clinical teaching in the simulated environment. The Objective Structured Clinical Assessment (OSCA) tool has been used in this simulated environment to assess clinical skills. Recently, however, online delivery of undergraduate nursing courses has become more common. The move from an internal mode of teaching to an online external mode is seen worldwide and poses challenges to staff and students as well as changing the teaching and learning culture of institutions (Philip and Wozniak, 2009). This cultural shift and the resulting diminishing timeframe for students to acquire and practice simulated clinical skills imply that it may become necessary to rethink assessment forms such as the OSCA assessment. This study examines whether or not the OSCA tool developed by Bujack et al. (1991a) is the best tool to be used in this new context, where online teaching is supplemented by very short, annual, intensive periods of study. Skills acquisition theories dictate that time is required to produce an ideal skills acquisition environment (Quinn, 2000) but the time constraints placed on students in such intensive periods of study could influence skills acquisition. This cross-sectional qualitative study used semi-structured interviews and focus groups to collect data. 65% of the nursing faculty participated in the study. The teaching of the Bachelor of Nursing (BN) occurred on two campuses and staff from both areas participated. This group of nurse academics was employed across the range of academic levels (from lecturer to professor) at the University. Data analysis followed a generic thematic analysis framework. Findings in this study show that there are a variety of attitudes and underpinning beliefs amongst staff in relation to the OSCAs. Doubts were raised in regard to the suitability of the use of the OSCA tool in this setting. It also became apparent during this study that the OSCA tool possibly serves purposes other than an assessment tool.


Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature.
Human neuroblastoma remains enigmatic because it often shows spontaneous regression and aggressive growth. The prognosis of advanced stage of sporadic neuroblastomas is still poor. Here, we investigated whether genomic and molecular signatures could categorize new therapeutic risk groups in primary neuroblastomas. We conducted microarray-based comparative genomic hybridization (array-CGH) with a DNA chip carrying 2464 BAC clones to examine genomic aberrations of 236 neuroblastomas and used in-house cDNA microarrays for gene-expression profiling. Array-CGH demonstrated three major genomic groups of chromosomal aberrations: silent (GGS), partial gains and/or losses (GGP) and whole gains and/or losses (GGW), which well corresponded with the patterns of chromosome 17 abnormalities. They were further classified into subgroups with different outcomes. In 112 sporadic neuroblastomas, MYCN amplification was frequent in GGS (22%) and GGP (53%) and caused serious outcomes in patients. Sporadic tumors with a single copy of MYCN showed the 5-year cumulative survival rates of 89% in GGS, 53% in GGP and 85% in GGW. Molecular signatures also segregated patients into the favorable and unfavorable prognosis groups (P=0.001). Both univariate and multivariate analyses revealed that genomic and molecular signatures were mutually independent, powerful prognostic indicators. Thus, combined genomic and molecular signatures may categorize novel risk groups and confer new clues for allowing tailored or even individualized medicine to patients with neuroblastoma.


Three-dimensional porous biodegradable polymeric scaffolds fabricated with biodegradable hydrogel porogens.
We have developed a new fabrication technique to create three-dimensional (3D) porous poly(epsilon-caprolactone fumarate) (PCLF) scaffolds using hydrogel microparticle porogens, as an alternative to overcome certain limitations of traditional scaffold fabrication techniques such as a salt leaching method. Both natural hydrogel, gelatin, and synthetic hydrogel, poly(ethylene glycol) sebacic acid diacrylate, were used as porogens to fabricate 3D porous PCLF scaffolds. Hydrogel microparticles were prepared by a single emulsion technique with the particle size in the range of 100-500 microm after equilibrium in water. The pore size distribution, porosity, pore interconnectivity, and spatial pore heterogeneity of the 3D PCLF scaffolds were assessed using micro-computed tomography and imaging analysis. Scaffolds fabricated with the hydrogel porogens had higher porosity and pore interconnectivity as well as more homogeneous spatial pore distribution, compared to the scaffolds made from the salt leaching process. Compressive moduli of the scaffolds were also measured and showed that lower porosity yielded greater modulus of the scaffolds. Overall, the new fabrication technology using hydrogel porogens may be beneficial for certain tissue engineering applications.


Enhancing the Sensitivity of Photoelectrochemical DNA Biosensing Using Plasmonic DNA Barcodes and Differential Signal Readout.
Photoelectrochemical biosensors hold great promise for sensitive bioanalysis; however, similar to their electrochemical analogues, they are highly affected by the variable backgrounds caused by biological matrices. We developed a new PEC biosensing strategy that uses differential signal generation, combining signals from two separate but correlated binding events on the biosensor, for improving the limit-of-detection, sensitivity, and specificity of PEC DNA biosensors in biological samples. In this assay, the binding of unlabeled target DNA is followed by the capture of a signal amplification barcode featuring a plasmonic nanoparticle. The interaction of the plasmonic barcode with the semiconductive building blocks of the biosensor results in significant signal amplification, and together with differential signal processing enhances the limit of detection and sensitivity of the assay by up to 15- and three-fold, respectively, compared to the previously-used PEC assays with a single binding event, demonstrating a limit of detection of 3 fM.


Full characterization of anisotropic diffuse light.
We demonstrate a method for fully characterizing diffuse transport of light in a statistically anisotropic opaque material. Our technique provides a simple means of determining all parameters governing anisotropic diffusion. Anisotropy in the diffusion constant, the mean free path, and the extrapolation length are, for the first time, determined independently. These results show that the anisotropic diffusion model is effective for modeling transport in anisotropic samples, providing that the light is allowed to travel several times the transport mean free path from the source.


Functional analysis of grafts from living donors. Implications for the treatment of older recipients.
Living-related liver transplantation (LRLT) has established efficacy in children. In a larger recipient, LRLT requires the use of a small graft because of limits on the donor hepatectomy. The minimum graft weight required for successful transplantation has not been well established, although a characteristic pattern of graft dysfunction has been observed in our patients who receive small grafts. The authors present a clinicopathologic study of small liver grafts obtained from living donors. Clinical and histologic data were reviewed for 25 patients receiving LRLT. In five older recipients (small group), the graft represented 50% or less of expected liver weight, whereas in 20 others (large group), the graft represented at least 60% of expected liver weight. A retrospective analysis of graft function was conducted by analyzing clinical parameters and histology. In the small group, 2 of 5 grafts (40%) were lost due to poor function, leading to one patient death (20% mortality), whereas in the large group, 2 of 20 grafts (10%) were lost due to arterial thrombosis without patient mortality. Early ischemic damage related to transplant was comparable with aspartate aminotransferase 203 +/- 23 (small group) and 290 +/- 120 (large group) at 24 hours (p = not significant). Early function was significantly decreased in the small group, with prothrombin time 18.2 +/- 2.2 seconds versus 14.8 +/- 1.6 seconds (large group) on day 3 (p = 0.034). All small group patients developed cholestasis with significantly increased total bilirubin levels at day 7 (16 +/- 5.2 mg% vs. 3.7 +/- 2.7 mg%; p = 0.021) and day 14 (12.0 +/- 7.4 vs. 1.8 +/- 0.7; p = 0.021) compared with the large group. Protocol biopsies in the small group revealed a diffuse ischemic pattern with cellular ballooning on day 7, which progressed to cholestasis in subsequent biopsies. Large group biopsies showed minimal ischemic changes. Three small group patients recovered with normal liver function by 12 weeks. Clinical recovery after a small-for-size transplant is characterized by significant functional impairment associated with paradoxical histologic changes typical of ischemia. These changes apparently are due to graft injury, which can only be the result of small graft size. These findings have significant implications for the extension of LRLT to adults.


Normal volunteer studies with modified 99Tcm tin colloid.
99Tcm tin colloid, modified by the addition of various amounts of the surfactant Pluronic F68 was evaluated as a new liver imaging agent in normal adult male volunteers. The relative amounts taken up in the liver and spleen were measured by two quantitative methods with a view to establishing the most useful technique. The changes in biodistribution resulting from mechanical shaking during preparation of the colloids and in vitro ageing of the preparations were assessed. The pharmacokinetics of uptake into liver and spleen of the various formulations tested were independent of Pluronic F68 content. However, at low levels of Pluronic F68 the liver:spleen ratio decreased as the colloid preparation was aged before use. At high levels of Pluronic F68 there was increased background activity. An optimum formulation was identified combining low background activity with a stable pattern of biodistribution independent of preparation age.


[Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China].
Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus (2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces (autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months-17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted >3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 10%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate (19%, 4/21), procalcitonin (4%,1/28), liver enzyme (22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions: In this case series, 2019-nCoV infection in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis of 2019-nCoV infection. After general treatment, the short-term prognosis is good.


Caries detection and diagnosis: novel technologies.
Recent years have seen an increase in research activity surrounding diagnostic methods, particularly in the assessment of early caries lesions. The drive for this has come from two disparate directions. The first is from the dentifrice industry who are keen to develop techniques that would permit caries clinical trials (CCTs) to be reduced in duration and subject numbers to permit the investigation of novel new anti-caries actives. The second is from clinicians who, armed with the therapies to remineralise early lesions are now seeking methods to reliably detect such demineralised areas and implement true preventative dentistry. This review examines novel technologies and the research supporting their use. Techniques based on visual, optical, radiographic and some emerging technologies are discussed. Each have their benefits although systems based on the auto-fluorescence (such as QLF) of teeth and electrical resistance (such as ECM) seem to offer the most hope for achieving reliable, accurate detection of the earliest stages of enamel demineralisation.


Elevated hepatic mitochondrial and peroxisomal oxidative capacities in fed and starved adult obese (ob/ob) mice.
Hepatic mitochondrial and peroxisomal oxidative capacities were studied in young (4-5 weeks old) and adult (6-9 months old) lean and obese ob/ob mice that were fed or starved for 24 or 48 h. The adult obese mice showed elevated capacity for mitochondrial oxidation (ng-atoms of O consumed/min per mg of protein) of lipid and non-lipid substrates, with the exception of pyruvate + malate, and elevated activities of citrate synthase and total carnitine palmitoyltransferase. Oxidative rates and enzyme activities were not affected by starvation of lean or obese mice, and both males and females responded similarly. Peroxisomal palmitoyl-CoA oxidation (nmol/min per mg of peroxisomal protein) was also increased in livers of adult obese mice and did not change with starvation. In young mice, hepatic mitochondrial and peroxisomal oxidative capacities in lean and obese mice were comparable. The increased mitochondrial and peroxisomal oxidative capacities appear to develop with maturation in obese ob/ob mice.


Thiocapsa litoralis sp. nov., a new purple sulfur bacterium from microbial mats from the White Sea.
A new phototrophic purple sulfur bacterium, isolated from benthic microbial mats from the White Sea littoral zone, is described. Individual cells were spherical, non-motile and lacked gas vesicles. In pure cultures cells appeared in regular platelet-like arrangements of four, eight or sixteen cells. Cell division occurred inside a common envelope, surrounded by a thick capsule. Internal photosynthetic membranes were of the vesicular type. The colour of cell suspensions was pink to rose-red. Bacteriochlorophyll a and carotenoids of the spirilloxanthin series were found as photosynthetic pigments. Under anoxic conditions in the light, photolithoautotrophic growth occurred with sulfide, thiosulfate, sulfite and elemental sulfur as electron donors. Sulfur globules were stored as an intermediary oxidation product and were visible microscopically inside the cells. In the presence of sulfide and bicarbonate, photomixotrophic growth occurred with a number of organic substrates. Sulfate could serve as sole assimilatory source of sulfur. Chemolithoautotrophic growth in the dark was possible with sulfide and thiosulfate as electron donors. Optimum growth occurred in the presence of 1% NaCl, at pH 6.5 and at 30 degrees C. The DNA base composition of the type strain, BM5T, was 64.0 mol% G+C. According to 16S rDNA sequence information and DNA-DNA hybridization, the new isolate clearly belongs to the genus Thiocapsa, but is sufficiently different from other recognized Thiocapsa species to be described as a new species of this genus for which the name Thiocapsa litoralis sp. nov. is proposed. The type strain is BM5T (= ATCC 700894).


The role of diskography after negative postmyelography CT scans: retrospective review.
Review of our records for a 2-year period (1985-1986) yielded 15 patients in whom unequivocally normal myelograms and postmetrizamide CT scans had been obtained before diskography. In none of these patients was the diskogram or postdiskography CT scan positive for either central, posterolateral, or extreme lateral disk herniation. It was our experience that, with the new-generation, improved-resolution CT scanners with multiplanar reconstruction capabilities, diskography added no additional information, did not influence the surgeon's decision to operate, and was not a painless or innocuous procedure. When an entirely negative, technically flawless postcontrast CT scan is obtained in a patient with back pain, diskography should not be performed, as it offers no further information.


TIMI 11B. Enoxaparin versus unfractionated heparin for unstable angina or non-Q-wave myocardial infarction: a double-blind, placebo-controlled, parallel-group, multicenter trial. Rationale, study design, and methods. Thrombolysis in Myocardial Infarction (TIMI) 11B Trial Investigators.
Continuous intravenous (i.v.) heparin administered in the acute period after unstable coronary artery disease reduces the likelihood and severity of subsequent ischemic events. However, reactivation of the thrombotic process may occur when heparin therapy is withdrawn. Low-molecular-weight heparin provides more reliable anticoagulation and less need for patient monitoring and dosage adjustment than standard unfractionated heparin (UFH) and therefore is well suited for long-term anticoagulation on an outpatient basis. TIMI 11B is a randomized, double-blind, placebo-controlled clinical trial designed to compare the strategy of combined short-term and long-term administration of the low-molecular-weight heparin enoxaparin for unstable angina/non-Q-wave myocardial infarction versus the standard strategy of UFH administration only during the acute phase. Patients are randomized to receive either enoxaparin (30 mg i.v. bolus followed by subcutaneous (s.c.) injections of 1.0 mg/kg every 12 hours) or UFH (70 U/kg bolus followed by an infusion of 15 U/kg per hour, titrated to an activated partial thromboplastin time of 1.5 to 2.5 times control). Infusion of i.v. UFH or placebo continues for a minimum of 72 hours. S.c. weight-adjusted enoxaparin or placebo continues until hospital discharge or day 8, whichever comes first, at which time the long-term phase of the study begins. Patients randomized to receive enoxaparin in the acute phase receive fixed-dose s.c. enoxaparin (60 mg every 12 hours for patients > or =65 kg, 40 mg every 12 hours for patients <65 kg). Patients randomized to receive UFH in the acute phase receive s.c. placebo injections during the chronic phase. The primary efficacy endpoint is the sum, through day 43, of the occurrence of death, nonfatal myocardial infarction not present at enrollment, or severe recurrent ischemia requiring urgent revascularization. The primary safety endpoint is the occurrence of either major bleeding or other serious adverse events.


Linking outcomes analysis to critical clinical pathways.
Expert decision-support soft-ware systems, when integrated with outcomes analyses, provide the opportunity to develop behavioral healthcare delivery systems in which providers are equipped to act decisively in a socially responsible manner. Key benefits of such systems include: enhancing the consistency and quality of clinical decision making across providers with varying professional backgrounds; providing a mechanism to ensure the rapid dissemination and implementation of new clinical research findings; performing severity-adjusted profiling of providers and programs based on the outcomes their services produce; and linking the prospective focus of clinical pathways with the retrospective rigor of outcomes analysis to accelerate advances in behavioral health. Integrating expert systems with outcomes analyses has the potential to rectify the historical failure by the behavioral healthcare professions to systematically link patient assessment data and their analysis to actual clinical decision making. Such systems will help make behavioral healthcare practice more accountable, thereby strengthening the argument for psychiatric patients to gain parity in healthcare benefits.


Accessory pulsatile organs: evolutionary innovations in insects.
In addition to the dorsal vessel ("heart"), insects have accessory pulsatile organs ("auxiliary hearts") that supply body appendages with hemolymph. They are indispensable in the open circulatory system for hemolymph exchange in antennae, long mouthparts, legs, wings, and abdominal appendages. This review deals with the great diversity in the functional morphology and the evolution of these accessory pulsatile organs. In primitive insects, hemolymph is supplied to antennae and cerci by arteries connected to the dorsal vessel. In higher insects, however, these arteries were decoupled and associated with autonomous pumps that entered their body plan as evolutionary innovations. To ensure hemolymph supply to legs, wings, and some other appendages, completely new accessory pulsatile organs evolved. The muscular components of these pulsatile organs and their elastic antagonists were recruited from various organ systems and assembled to new functional units. In general, it seems that the evolution of accessory pulsatile organs has been determined by developmental and spatial constraints imposed by other organ systems rather than by changes in circulatory demands.


The effects of a high calcium dairy food on bone health in pre-pubertal children in New Zealand.
Childhood and adolescence is the period of most rapid skeletal growth in an individual's lifetime. A greater peak bone mass achieved in the first 2-3 decades of life, may protect against the risk of osteoporotic fracture in later life. The aim of this randomized, controlled study was to assess in pre-pubertal boys and girls (aged 8-10 years) the effect of 18 months of a calcium enriched, cocoa flavoured product on bone density, bone growth and bone size in New Zealand children. One hundred and fifty four pre-pubertal boys and girls (aged 8-10 years) were randomized to receive a high calcium dairy drink or a control drink reconstituted with water for 18 months. They were assessed at baseline and then every 6 months for the first 18 months, while they were having the supplement; they were then followed up 12 months after supplementation had finished. Bone mineral density and bone mineral content were assessed at the total body, hip and spine. Indicators of bone size (vertebral width and height) were also measured at the spine. Anthropometric data was collected, medical history questionnaires were administered (including the Tanner or pubertal stage questionnaire), dietary calcium intake was assessed with a calcium food frequency questionnaire and calcium supplement compliance was determined. There was no significant difference between the 2 groups for bone mineral density or bone mineral content at any time point. There was no difference in vertebral height or width at any stage of the study, indicating no additional influence on bone size at the lumbar vertebrae. There were no significant differences between height, weight, lean mass or fat mass at any time point. Both groups had higher habitual calcium intakes than recommended for this age group going into the study and throughout the study. In this 2(1/2) year study (18 months supplementation, 1 year follow-up) we did not observe a difference in bone mineral density in pre-pubertal children. This was probably due to their high habitual dietary calcium intake whereby minimal addition of calcium to the diet reached the threshold level where no further benefit was seen. There were no significant differences between the two groups in body composition. Growth and the mean height and weight remained between the 50th and 75th percentile for their age. We have shown calcium supplementation in children with high habitual dietary calcium intake appears not to have additional effects on bone mass. Calcium supplementation needs to be targeted in those children with low habitual dietary calcium intake.


Occupancy of alpha 1-adrenergic receptors and contraction of rat vas deferens.
The interaction of agonists and antagonists with alpha 1-adrenergic receptors in rat vas deferens was examined using radioligand binding assays and contractility measurements. 125I-Labeled BE 2254 (125IBE) was found to bind rapidly and reversibly to a single class of high-affinity binding sites in homogenates of rat vas deferens. The k1 for association was 3.8 X 10(7) 1/mole-sec, the k-1 for dissociation was 2.3 X 10(-3) sec-1, and the KD was 105 pM. The order of potency for antagonists inhibiting 125IBE binding was prazosin greater than indoramin greater than phentolamine greater than yohimbine. Norepinephrine, phenylephrine, and other alpha-adrenergic agonists produced dose-dependent contractions of whole vas deferens in vitro. This contractile response was competitively inhibited by alpha-adrenergic blocking drugs with the same potency order observed for inhibition of specific 125IBE binding. Comparison of pA2 values for alpha 1- and alpha 2-selective antagonists competitively inhibiting contractile responses to norepinephrine, epinephrine, or phenylephrine suggested that these drugs caused their contractile effects solely through alpha 1-adrenergic receptors, and that there were no alpha 2-adrenergic receptors mediating contraction in this tissue. The pA2 values for antagonist inhibition of alpha-adrenergic receptor-mediated contractile responses were highly correlated (r = 0.995) with the KD values for antagonist inhibition of 125IBE binding in this tissue. The EC50 values for partial agonists were also highly correlated with the KD values for inhibition of 125IBE binding in vas deferens. However, the EC50 values of full agonists in causing contraction were in general 10- to 100-fold lower than the KD values for inhibiting 125IBE binding, possibly representing a substantial "spare receptor" population in this tissue. The results suggest that rat vas deferens contains a homogeneous population of alpha 1-adrenergic receptors mediating the contractile response to norepinephrine, that these receptors can be directly labeled with 125IBE, and that there may be a nonlinear relationship between agonist occupancy of alpha 1-adrenergic receptors and the functional response of this tissue.


The Colorado Collaborative for Nursing Research: Providing Trended Nurse-Sensitive Patient Outcome Data Across Entities.
Nurse leaders lack timely access to trended electronic health record (EHR) data to drive decision making. Robust nurse-sensitive patient outcome data are difficult to locate in EHRs and largely absent across entities. The Colorado Collaborative for Nursing Research is currently testing a federated data system to get nurse leaders the information they need, when they need it.


Staphylococcal superantigen-like protein 10 enhances the amyloidogenic biofilm formation in Staphylococcus aureus.
Staphylococcus aureus is a highly infectious pathogen that represents a significant burden on the current healthcare system. Bacterial attachment to medical implants and host tissue, and the establishment of a mature biofilm, play an important role in chronic diseases such as endocarditis, osteomyelitis and wound infections. These biofilms decrease bacterial susceptibility to antibiotics and immune defences, making the infections challenging to treatment. S. aureus produces numerous exotoxins that contribute to the pathogenesis of the bacteria. In this study, we have identified a novel function of staphylococcal superantigen-like protein 10 (SSL10) in enhancing the formation of staphylococcal biofilms. Biofilm biomass is significantly increased when SSL10 is added exogenously to bacterial cultures, whereas SSL2 and SSL12 are found to be less active. Exogenously added SSL10 mask the surface charge of the bacterial cells and lowers their zeta potential, leading to the aggregation of the cells. Moreover, the biofilm formation by SSL10 is governed by amyloid aggregation, as evident from spectroscopic and microscopic studies. These findings thereby give the first overview of the SSL-mediated amyloid-based biofilm formation and further drive the future research in identifying potential molecules for developing new antibacterial therapies against Staphylococcus aureus.


Alcohol drinking, smoking, and cutaneous melanoma risk: Mendelian randomization analysis.
To investigate the causal relationship between poor lifestyle habits, such as smoking and drinking, and cutaneous malignant melanoma. In the present study, alcohol consumption and smoking were used as exposure factors, and single nucleotide polymorphisms closely associated with alcohol consumption and smoking were used as instrumental variables, while cutaneous melanoma was set as an outcome variable. Two-sample Mendelian randomization analyses were run between alcohol consumption and melanoma and smoking and melanoma to investigate their causal associations, respectively. We found a positive and statistically significant causal effect of alcohol intake on the risk of cutaneous malignant melanoma (OR: 2.23; 95%CI: 1.11-4.47; p=0.02). The present study showed no significant causal relationship between cigarettes per day and cutaneous melanoma (OR: 0.85; 95%CI: 0.54-1.35; p=0.50) or smoking initiation and cutaneous melanoma (OR: 1.02; 95%CI: 0.74-1.39; p=0.88). This study provides Mendelian randomization evidence supporting alcohol consumption as a risk factor for cutaneous malignant melanoma. And the causal relationship between smoking and cutaneous malignant melanoma still needs to be further investigated.


Pericyte-based human tissue engineered vascular grafts.
The success of small-diameter tissue engineered vascular grafts (TEVGs) greatly relies on an appropriate cell source and an efficient cellular delivery and carrier system. Pericytes have recently been shown to express mesenchymal stem cell features. Their relative availability and multipotentiality make them a promising candidate for TEVG applications. The objective of this study was to incorporate pericytes into a biodegradable scaffold rapidly, densely and efficiently, and to assess the efficacy of the pericyte-seeded scaffold in vivo. Bi-layered elastomeric poly(ester-urethane)urea scaffolds (length = 10 mm; inner diameter = 1.3 mm) were bulk seeded with 3 x 10(6) pericytes using a customized rotational vacuum seeding device in less than 2 min (seeding efficiency > 90%). The seeded scaffolds were cultured in spinner flasks for 2 days and then implanted into Lewis rats as aortic interposition grafts for 8 weeks. Results showed pericytes populated the porous layer of the scaffolds evenly and maintained their original phenotype after the dynamic culture. After implantation, pericyte-seeded TEVGs showed a significant higher patency rate than the unseeded control: 100% versus 38% (p < 0.05). Patent pericyte-seeded TEVGs revealed extensive tissue remodeling with collagen and elastin present. The remodeled tissue consisted of multiple layers of alpha-smooth muscle actin- and calponin-positive cells, and a von Willebrand factor-positive monolayer in the lumen. These results demonstrate the feasibility of a pericyte-based TEVG and suggest that the pericytes play a role in maintaining patency of the TEVG as an arterial conduit.


Choroidal pigmentation - a differential diagnosis.
Using only a few tests, it was possible to differentially diagnose a benign choroidal nevus with overlying medullation. Having revealed a flat retina with no apparent mass in the area, the ultrasound B-scan initially ruled out a choroidal malignant melanoma, choroidal hemangioma, metastatic tumor and a rhegmatogenous retinal detachment. Binocular indirect ophthalmoscopy and application of the Goldmann 3-mirror gonioscopy lens revealed that the lesion was not a retinal detachment. Due to the location of the lesion, disciform macular degeneration was also ruled out. Fluorescein angiography was the final test which aided in the definitive differential diagnosis, since it was characteristic of a choroidal nevus. Even though not all possible choroidal nevi need such an extensive work-up, occasionally specialized test can aid in the differential diagnosis of benign from potentially malignant lesions.


Estimates of Caffeine Use Disorder, Caffeine Withdrawal, Harm and Help-seeking in New Zealand: A cross-sectional survey.
Caffeine Use Disorder (CUD) is not yet formally recognized in the DSM-5, but emerging evidence suggests CUD could impact up to one in five people. The primary aim of this study was to estimate levels of caffeine consumption and its associations with CUD and withdrawal, taking socio-demographic characteristics (age, gender, ethnicity, income) into account. Secondary aims were to measure caffeine-related harm and treatment preferences. We administered an online cross-sectional survey via Facebook to a convenience sample of 2379 adults in New Zealand. Caffeine consumption was assessed across six products: coffee, tea, energy drinks, cola, alcohol mixed with caffeine, and other products (e.g., caffeine pills, sports supplements). 20% of participants met proposed criteria for CUD, with 30% meeting DSM-5 criteria for caffeine withdrawal. Moderate (200-400 mg per day) and high consumption (>400 mg per day) was associated with a three-fold increase in the odds of CUD and a two-fold increase in the odds of withdrawal. Women and current smokers were at higher risk of CUD and withdrawal even at moderate consumption levels. Nearly 85% of respondents experienced at least one caffeine-related harm in the past 12-months. The number of harms increased with level of caffeine consumption. Nearly 50% indicated a self-help treatment for caffeine reduction would be of interest. High rates of CUD and caffeine withdrawal amongst moderate caffeine users, women and smokers suggests caffeine consumption guidelines may need refinement. Caffeine-related harm that is not clinically meaningful may still be of concern to individuals and warrants further investigation.


Long-term survival after surgical resection for recurrent nasopharyngeal cancer after radiotherapy failure.
Results are reported of transpalatal, transcervical, and transmaxillary resection in 15 patients with recurrent nasopharyngeal cancer after failure of primary radiotherapy. Seven patients treated for cure have been followed up for more than 3 years (mean, 55 months; range, 40 to 82 months), with three (43%) remaining free of disease. Two patients are living with local disease (59 and 40 months postoperatively), while two have died of their local and regional recurrence (40 and 17 months postoperatively). Two additional patients underwent nasopharyngectomy for palliation. One of these patients died of uncontrolled disease 12 months postoperatively; the other remains alive with disease 70 months after resection. Six patients have been followed up for less than 3 years (mean, 22.3 months; range, 16 to 32 months). Of this group, one (17%) is without evidence of disease, four are living with local disease (13, 16, 17, and 27 months postoperatively), and one has died of disease (13 months postoperatively). Recurrence (10 of 13 patients) has occurred an average of 8 months after surgery (range, 4 to 17 months). Complications include transient marginal mandibular nerve weakness (one), permanent cranial nerve paralysis (two), nasopharyngitis and/or osteomyelitis of the cervical vertebrae or base of skull requiring intravenous antibiotics (two), aspiration pneumonia (two), prolonged nasogastric tube feeding (two), and intraoperative thyroid storm (one). No cerbrospinal fluid leaks or perioperative deaths occurred. The long-term cure rate and disease-free interval of transpalatal nasopharyngectomy lead us to believe that this technique is probably only slightly better than reirradiation in the appropriately selected patient.


Cell wall metabolism and hexose allocation contribute to biomass accumulation in high yielding extreme segregants of a Saccharum interspecific F2 population.
Sugarcane is an emerging dual-purpose biofuel crop for energy and sugar production, owing to its rapid growth rate, high sucrose storage in the stems, and high lignocellulosic yield. It has the highest biomass production reaching 1.9 billion tonnes in 2014 worldwide. To improve sugarcane biomass accumulation, we developed an interspecific cross between Saccharum officinarum 'LA Purple' and Saccharum robustum 'MOL5829'. Selected F1 individuals were self-pollinated to generate a transgressive F2 population with a wide range of biomass yield. Leaf and stem internodes of fourteen high biomass and eight low biomass F2 extreme segregants were used for RNA-seq to decipher the molecular mechanism of rapid plant growth and dry weight accumulation. Gene Ontology terms involved in cell wall metabolism and carbohydrate catabolism were enriched among 3274 differentially expressed genes between high and low biomass groups. Up-regulation of cellulose metabolism, pectin degradation and lignin biosynthesis genes were observed in the high biomass group, in conjunction with higher transcript levels of callose metabolic genes and the cell wall loosening enzyme expansin. Furthermore, UDP-glucose biosynthesis and sucrose conversion genes were differentially expressed between the two groups. A positive correlation between stem glucose, but not sucrose, levels and dry weight was detected. We thus postulated that the high biomass sugarcane plants rapidly convert sucrose to UDP-glucose, which is the building block of cell wall polymers and callose, in order to maintain the rapid plant growth. The gene interaction of cell wall metabolism, hexose allocation and cell division contributes to biomass yield.


Effects of dietary calorie restriction or exercise on the PI3K and Ras signaling pathways in the skin of mice.
Weight control by exercise and dietary calorie restriction (DCR) has been associated with reduced cancer risk, but the underlying mechanisms are not well understood. This study was designed to compare the effects of weight loss by increasing physical activity or decreasing calorie intake on tumor promoter-induced Ras-MAPK and PI3K-Akt pathways. SENCAR mice were randomly assigned to one of the following five groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AL+Exe), exercise but pair-fed at the amount as controls (PF+Exe), 20% DCR, and 20% DCR plus exercise (DCR+Exe). After 10 weeks, body weight and body fat significantly decreased in the groups of DCR, DCR+Exe, and PF+Exe when compared with the controls. AL+Exe did not induce weight loss due to, at least in part, increased food intake. Plasma IGF-1 levels reduced significantly in DCR and DCR+Exe but not PF+Exe. The protein H-Ras and activated Ras-GTP significantly decreased in TPA-induced skin tissues of DCR-fed mice but not exercised mice. PI3K protein, phosphoserine Akt, and p42/p44-MAPK were reduced, however, in both DCR and PF+Exe groups. Immunohistochemistry demonstrated that the significantly reduced H-Ras occurred in subcutaneous fat cells, while the reduced PI3K and PCNA took place only in the epidermis. Plasma leptin decreased in PF+Exe, DCR, and DCR+Exe, while the caspase-3 activity increased in DCR+Exe only. Genomic microarray analysis further indicated that the expression of 34 genes relevant to PI3K and 31 genes to the MAPK pathway were significantly regulated by either DCR or PF+Exe treatments. The reduced PI3K in PF+Exe mice was partially reversed by IGF-1 treatment. The overall results of this study demonstrated that DCR abrogated both Ras and PI3K signaling, which might inhibit TPA-induced proliferation and anti-apoptosis. Selective inhibition of PI3K by PF+Exe but not AL+Exe seems more attributable to the magnitude of the caloric deficit and/or body fat loss than diet versus exercise comparison.


Surgical treatment before assisted reproductive technologies.
Advances in technology have transformed surgery from a major approach into an art of science capable of treating many diseases and conditions in a less risky way. This advance let physicians perform surgery commonly in their practice. Today, surgery in reproductive medicine has become so customary that evidence has not been questioned commonly. Therefore, this review will help reproductive endocrinologists to read the most recent evidence for surgery to improve in vitro fertilization outcome. This will also help them to inform their patients with the most recent evidence.


Tourette syndrome, pimozide, and school phobia: the neuroleptic separation anxiety syndrome.
The development of school phobia has been reported in some patients with Tourette syndrome treated with haloperidol. The author reports on a patient who developed school phobia on each of three trials with pimozide, a neuroleptic chemically similar to haloperidol, and proposes the term "neuroleptic separation anxiety syndrome." The syndrome is clinically indistinguishable from DSM-III criteria for school phobia (separation anxiety disorder). Tricyclic antidepressants may have a therapeutic or prophylactic effect. It is not known whether this neuroleptic side effect occurs in patients other than those with Tourette syndrome.


Protein scaffold-based molecular probes for cancer molecular imaging.
Protein scaffold molecules are powerful reagents for targeting various cell signal receptors, enzymes, cytokines and other cancer-related molecules. They belong to the peptide and small protein platform with distinct properties. For the purpose of development of new generation molecular probes, various protein scaffold molecules have been labeled with imaging moieties and evaluated both in vitro and in vivo. Among the evaluated probes Affibody molecules and analogs, cystine knot peptides, and nanobodies have shown especially good characteristics as protein scaffold platforms for development of in vivo molecular probes. Quantitative data obtained from positron emission tomography, single photon emission computed tomography/CT, and optical imaging together with biodistribution studies have shown high tumor uptakes and high tumor-to-blood ratios for these probes. High tumor contrast imaging has been obtained within 1 h after injection. The success of those molecular probes demonstrates the adequacy of protein scaffold strategy as a general approach in molecular probe development.


Exploration of 3,4-unsubstituted coumarins as thioredoxin reductase 1 inhibitors for cancer therapy.
Coumarin and its derivatives have emerged as promising candidates in drug discovery. While the activity of coumarins as anticancer agents with different biological targets has been thoroughly investigated, reports on the potential of coumarins in the inhibition of thioredoxin reductase (TrxR) are still scarce. We focus on the design and synthesis of 3,4-unsubstituted coumarin analogues with systematic incorporation of substituents at the fifth to eighth positions of coumarin, which allowed definitive structure-activity relationship analysis to be conducted. In the obtained library, the substitution at the sixth position of the coumarin core with an aromatic or a cyclopropyl group turned out to be more activity enhancing. A bulky aromatic substituent with a large CF3 group encourages ligand alignment in a manner that enables covalent bond formation with the catalytic TrxR1 residue, according to the docking results. Our observations indicate that the activity of a series of coumarin analogues towards thioredoxin reductase 1 (TrxR1) is dependent on the nature (size and electronic effect) and the position of the substituent and more importantly - the accessibility of the Michael acceptor functionality. Several compounds (with at least 90% inhibition of the rat TrxR1 enzyme at 200 μM concentration) were further examined in in vitro cell-based assays to assess the cytotoxic effects on various cancer cell lines. The analogue 6-(4-(trifluoromethyl)phenyl)-2H-chromen-2-one was selected as the lead compound for further optimization. The results presented herein pave the way for the development of the next generation of coumarin-based TrxR1 inhibitors, where modification of the Michael acceptor moiety and incorporation of different aryl substituents at the sixth position of the coumarin core are planned.