Nano-confinement of block copolymers in high accuracy topographical guiding patterns: modelling the emergence of defectivity due to incommensurability.
Extreme ultraviolet interference lithography (EUV-IL) is used to manufacture topographical guiding patterns to direct the self-assembly of block copolymers. High-accuracy silicon oxide-like patterns with trenches ranging from 68 nm to 117 nm width are fabricated by exposing a hydrogen silsesquioxane (HSQ) resist layer using EUV-IL. We investigate how the accuracy, the low line width roughness and the low line edge roughness of the resulting patterns allow achieving DSA line/space patterns of a PS-b-PMMA (polystyrene-block-poly methyl methacrylate) block copolymer of 11 nm half-pitch with low defectivity. We conduct an in-depth study of the dependence of the DSA pattern morphology on the trench width and on how the neutral brush covers the guiding pattern. We identify the relation between trench width and the emergence of defects with nanometer precision. Based on these studies, we develop a model that extends available free energy models, which allows us to predict the patterning process window.


Molecular linkage mapping and phylogeny of the chalcone synthase multigene family in soybean.
Chalcone synthase (CHS), the key enzyme in the flavonoid biosynthesis pathway, is encoded by a multigene family, CHS1-CHS8 and dCHS1 in soybean. A tandem repeat of CHS1, CHS3 and CHS4, and dCHS1 that is believed to be located in the vicinity comprises the I locus that suppresses coloration of the seed coat. This study was conducted to determine the location of all CHS members by using PCR-based DNA markers. Primers were constructed based on varietal differences in either the nucleotide sequence of the 5'-upstream region or the first intron of two cultivars, Misuzudaizu, with a yellow seed coat (II), and Moshidou Gong 503, with a brown seed coat (ii). One hundred and fifty recombinant inbred lines that originated from a cross between these two cultivars were used for linkage mapping together with 360 markers. Linkage mapping confirmed that CHS1, CHS3, CHS4, dCHS1, and the I locus are located at the same position in molecular linkage group (MLG) A2. CHS5 was mapped at a distance of 0.3 cM from the gene cluster. CHS2 and CHS6 were located in the middle region of MLGs A1 and K, respectively, while CHS7 and CHS8 were found at the distal end of MLGs D1a and B1, respectively. Phylogenetic analysis indicated that CHS1, CHS3, CHS4, and CHS5 are closely related, suggesting that gene duplication may have occurred repeatedly to form the I locus. In addition, CHS7 and CHS8 located at the distal end and CHS2, CHS6, and CHS members around the I locus located around the middle of the MLG are also related. Ancient tetraploidization and repeated duplication may be responsible for the evolution of the complex genetic loci of the CHS multigene family in soybean.


DNA transposons mediate duplications via transposition-independent and -dependent mechanisms in metazoans.
Despite long being considered as "junk", transposable elements (TEs) are now accepted as catalysts of evolution. One example is Mutator-like elements (MULEs, one type of terminal inverted repeat DNA TEs, or TIR TEs) capturing sequences as Pack-MULEs in plants. However, their origination mechanism remains perplexing, and whether TIR TEs mediate duplication in animals is almost unexplored. Here we identify 370 Pack-TIRs in 100 animal reference genomes and one Pack-TIR (Ssk-FB4) family in fly populations. We find that single-copy Pack-TIRs are mostly generated via transposition-independent gap filling, and multicopy Pack-TIRs are likely generated by transposition after replication fork switching. We show that a proportion of Pack-TIRs are transcribed and often form chimeras with hosts. We also find that Ssk-FB4s represent a young protein family, as supported by proteomics and signatures of positive selection. Thus, TIR TEs catalyze new gene structures and new genes in animals via both transposition-independent and -dependent mechanisms.


Surgical anesthesia in turkeys with thialbarbital sodium.
Thialbarbital sodium was found to be a reliable and economical general anesthetic for domesticated turkeys. Despite shortness of action of the initial dose, surgical anesthesia was maintained longer than 2 hours by intermittent infusion via a brachial vein cannula. The drug was reconstituted just before use (66 mg/ml) with sterile 1% saline solution. Rapid smooth induction was produced with an initial dosage of 30 mg/kg for hens and 26.5 mg/kg for toms, when administered within a 30- to 60-second interval. Supplemental infusion of the drug in increments of 0.25 to 1.5 ml was used to sustain the desired level of deep narcosis. The occurrence of respiratory failure was considerably less for thialbarbital than with pentobarbital sodium. Recovery was rapid and smooth.


Differentiation of arginine vasopressin antagonistic effects by selective V2 versus dual V2/V1a receptor blockade in a preclinical heart failure model.
Arginine vasopressin (AVP) is increased in patients with heart failure (HF). Its actions are linked to free water reabsorption (V2-) and arteriolar vasoconstriction (V1a receptor). AVP can exacerbate the cardiorenal syndrome with excess fluid retention and afterload increase. Tolvaptan (TOL; selective V2 antagonist) and Conivaptan (CON; dual V1a/V2 antagonist) are two AVP antagonists that counteract the action of AVP with distinct profiles. We investigated the therapeutic effects of CON and TOL in an acute HF model. Mongrel dogs were paced continuously at 220 beats/min. After 14 days, the animals underwent acute testing. Dogs were instrumented to measure cardiac output, blood pressure, pulmonary artery pressure, and left ventricular dP/dtmax. Additionally, during the acute experiments, vasopressin was infused intravenously (4 mU/kg/min) to achieve constant and controlled pathophysiological levels of AVP. Subsequently, animals received either CON or TOL (n = 6; 0.1-mg/kg bolus). There were no significant differences in effect on mean arterial pressure, dP/dtmax, central venous pressure, and urine output between CON and TOL. In contrast, cardiac output increased by 0.15 l/min after CON and decreased by 0.6 l/min after TOL (P < 0.01). Accordingly, the total peripheral resistance increased after TOL by 250 dyn*s/cm and decreased after CON by 125 dyn*s/cm (P < 0.01). In conclusion, it was demonstrated that in an acute HF model, CON lowered, whereas TOL increased afterload. The results suggest that dual V1a/V2 blockade in the acute HF setting could be beneficial compared with selective V2 blockade. Chronic experiments are needed to determine whether this finding can translate into a sustained clinical advantage.


A study of the factors that influence consumer attitudes toward beef products using the conjoint market analysis tool.
This study utilizes an analysis technique commonly used in marketing, the conjoint analysis method, to examine the relative utilities of a set of beef steak characteristics considered by a national sample of 1,432 US consumers, as well as additional localized samples representing undergraduate students at a business college and in an animal science department. The analyses indicate that among all respondents, region of origin is by far the most important characteristic; this is followed by animal breed, traceability, animal feed, and beef quality. Alternatively, the cost of cut, farm ownership, the use (or nonuse) of growth promoters, and whether the product is guaranteed tender were the least important factors. Results for animal science undergraduates are similar to the aggregate results, except that these students emphasized beef quality at the expense of traceability and the nonuse of growth promoters. Business students also emphasized region of origin but then emphasized traceability and cost. The ideal steak for the national sample is from a locally produced, choice Angus fed a mixture of grain and grass that is traceable to the farm of origin. If the product was not produced locally, respondents indicated that their preferred production states are, in order from most to least preferred, Iowa, Texas, Nebraska, and Kansas.


[Building bridges: interdisciplinarity in practice. PopTrans Study: a study with transvestites and transsexual women in Salvador, Bahia State, Brazil].
Trans persons, including transvestites and transsexual women, show disproportionately high HIV/AIDS rates when compared to the rest of the population. However, few quantitative/qualitative studies have addressed trans persons in Brazil. Thus, a team of researchers from different fields is developing an interdisciplinary research project with the objective of shedding light on living conditions and ways of life among transvestites and transsexual women, while investigating determinant factors for HIV infection, syphilis, and hepatitis B and C. The article is intended to describe the experience with the implementation and development of an ethno-epidemiological study in Salvador, Bahia State, Brazil. Mapping the population began with a formative survey that was crucial for orienting the epidemiological survey. The production of ethno-epidemiological data posed a daily challenge for the researchers, triggering a series of reflections on the limits of our concepts and categories for translating the diversity of study participants' practices and experiences.


Prevalence of atherosclerosis risk factors in Egyptian patients with acute coronary syndrome: final data of the nationwide cross-sectional 'CardioRisk' project.
Little are known about the prevalence of atherosclerosis risk factors in Egyptian patients with acute coronary syndromes (ACS). Describe the prevalence of these risk factors with focus on gender-specific data and patients with premature presentation. From November 2015 to August 2018, data were collected from 3224 patients with ACS in 30 coronary care centers covering 11 governorates across Egypt, with focus premature ACS. The vast majority were males (74%) and the most prevalent age group was (56-65 years) representing 37% of whole study population. Among female patients, 92% were post-menopausal. The prevalence of premature ACS was 51%. Forty five percent of total males and 69.6% of total females with ACS had premature presentation (P<0.001). Abdominal obesity was the most prevalent risk factor (66%). Nearly half of the entire study patients were current smokers (48%). We showed a high prevalence of documented dyslipidemia (48%) as well. Early invasive management strategy was employed in 65% of patients with no significant gender disparity noticed. Vascular access for coronary angiography was most commonly femoral (80% of time). Emergent percutaneous coronary intervention (PCI) was attempted in 53% of patients. Thrombolytic therapy (using Streptokinase) was used in 24% of included participants. Among Egyptian patients with ACS, premature presentation is common with greater male preponderance. Abdominal obesity is the most prevalent risk factor followed by hypertension. Most traditional risk factors (apart from smoking) were more prevalent in women than men.


Novel Bartonella Species in Insectivorous Bats, Northern China.
Bartonella species are emerging human pathogens. Bats are known to carry diverse Bartonella species, some of which are capable of infecting humans. However, as the second largest mammalian group by a number of species, the role of bats as the reservoirs of Bartonella species is not fully explored, in term of their species diversity and worldwide distribution. China, especially Northern China, harbors a number of endemic insectivorous bat species; however, to our knowledge, there are not yet studies about Bartonella in bats in China. The aim of the study was to investigate the prevalence and genetic diversity of Bartonella species in bats in Northern China. Bartonella species were detected by PCR amplification of gltA gene in 25.2% (27/107) bats in Mengyin County, Shandong Province of China, including 1/3 Rhinolophus ferrumequinum, 2/10 Rhinolophus pusillus, 9/16 Myotis fimbriatus, 1/5 Myotis ricketti, 14/58 Myotis pequinius. Phylogenetic analysis showed that Bartonella species detected in bats in this study clustered into ten groups, and some might be novel Bartonella species. An association between Bartonella species and bat species was demonstrated and co-infection with different Bartonella species in a single bat was also observed. Our findings expanded our knowledge on the genetic diversity of Bartonella in bats, and shed light on the ecology of bat-borne Bartonella species.


Does the respiratory system limit exercise in mild chronic obstructive pulmonary disease?
It is not known if abnormal dynamic respiratory mechanics actually limit exercise in patients with mild chronic obstructive pulmonary disease (COPD). We reasoned that failure to increase peak ventilation and Vt in response to dead space (DS) loading during exercise would indicate true ventilatory limitation to exercise in mild COPD. To compare the effects of DS loading during exercise on ventilation, breathing pattern, operating lung volumes, and dyspnea intensity in subjects with mild symptomatic COPD and age- and sex-matched healthy control subjects. Twenty subjects with Global Initiative for Chronic Obstructive Lung Disease stage I COPD and 20 healthy subjects completed two symptom-limited incremental cycle exercise tests, in randomized order: unloaded control and added DS of 0.6 L. Peak oxygen uptake and ventilation were significantly lower in COPD than in health by 36% and 41%, respectively. With added DS compared with control, both groups had small decreases in peak work rate and no significant increase in peak ventilation. In health, peak Vt and end-inspiratory lung volume increased significantly with DS. In contrast, the COPD group failed to increase peak end-inspiratory lung volume and had a significantly smaller increase in peak Vt during DS. At 60 W, a 50% smaller increase in Vt (P < 0.001) in response to added DS in COPD compared with health was associated with a greater increase in dyspnea intensity (P = 0.0005). These results show that the respiratory system reached or approached its physiologic limit in mild COPD at a lower peak work rate and ventilation than in healthy participants. Clinical trial registered with www.clinicaltrials.gov (NCT 00975403).


Divergent short- and long-term effects of acute stress in object recognition memory are mediated by endogenous opioid system activation.
Acute stress induces short-term object recognition memory impairment and elicits endogenous opioid system activation. The aim of this study was thus to evaluate whether opiate system activation mediates the acute stress-induced object recognition memory changes. Adult male Wistar rats were trained in an object recognition task designed to test both short- and long-term memory. Subjects were randomly assigned to receive an intraperitoneal injection of saline, 1 mg/kg naltrexone or 3 mg/kg naltrexone, four and a half hours before the sample trial. Five minutes after the injection, half the subjects were submitted to movement restraint during four hours while the other half remained in their home cages. Non-stressed subjects receiving saline (control) performed adequately during the short-term memory test, while stressed subjects receiving saline displayed impaired performance. Naltrexone prevented such deleterious effect, in spite of the fact that it had no intrinsic effect on short-term object recognition memory. Stressed subjects receiving saline and non-stressed subjects receiving naltrexone performed adequately during the long-term memory test; however, control subjects as well as stressed subjects receiving a high dose of naltrexone performed poorly. Control subjects' dissociated performance during both memory tests suggests that the short-term memory test induced a retroactive interference effect mediated through light opioid system activation; such effect was prevented either by low dose naltrexone administration or by strongly activating the opioid system through acute stress. Both short-term memory retrieval impairment and long-term memory improvement observed in stressed subjects may have been mediated through strong opioid system activation, since they were prevented by high dose naltrexone administration. Therefore, the activation of the opioid system plays a dual modulating role in object recognition memory.


Appendicitis in Children in a Large Italian COVID-19 Pandemic Area.
Introduction: The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed the routine activities of pediatric surgical centers, and it determined the reduction of admissions in the pediatric emergency departments (PED). We reviewed the records of patients affected by acute appendicitis (AA) during the COVID-19 pandemic period in a large Italian COVID-19 pandemic area. Methods: Data regarding demographics, age, macroscopic and microscopic findings, and time between symptom onset and PED admission of patients affected by confirmed AA in the period between March and April 2020 were considered. The data were compared with those obtained during the same period of 2019, 2018, and 2017 in the included centers. Data were quoted as median (range) or absolute number. Non-parametric statistical tests were used to compare groups. A p ≤ 0.05 was regarded as significant. Since only anonymous data have been used and the data storage meets current data protection regulations, ethical committee approval was not required for this study. Results: Eighty-six patients underwent surgical appendectomy for AA between February 20th, 2020 and April 20th, 2020; 32.5% were complicated appendicitis and 67.5% were uncomplicated. Fifty-three patients were males and 33 were females. Patients' age ranged from 3 to 17 years and the median age was 10 years. The median time between the onset of symptoms and the admission in PED was 1.85 days. The average time between the symptom onset and PED admission was 1.8 days. Conclusions: Although fear from the COVID-19 pandemic determined a delayed diagnosis of serious pediatric diseases, the increasing prevalence and severity of AA were not demonstrated in the most COVID-19-affected areas of Italy.


A health insurance claims analysis on the effect of female sex on long-term outcomes after peripheral endovascular interventions for symptomatic peripheral arterial occlusive disease.
Several reports have addressed sex disparities in peripheral arterial occlusive disease (PAOD) treatment with inconclusive or even conflicting results. However, most previous studies have neither been sufficiently stratified nor used matching or weighting methods to address severe confounding. In the present study, we aimed to determine the disparities between sexes after percutaneous endovascular revascularization (ER) for symptomatic PAOD. Health insurance claims data from the second-largest insurance fund in Germany, BARMER, were used. A large cohort of patients who had undergone index percutaneous ER of symptomatic PAOD from January 1, 2010 to December 31, 2018 were included in the present study. The study cohort was stratified by the presence of intermittent claudication, ischemic rest pain, and wound healing disorders. Propensity score matching was used to adjust for confounding through differences in age, treated vessel region, comorbidities, and pharmacologic treatment. Sex-related differences regarding cardiovascular event-free survival, amputation-free survival, and overall survival within 5 years of surgery were determined using Kaplan-Meier time-to-event curves, log-rank test, and Cox regression analysis. In the present study, 50,051 patients (47.2% women) were identified and used to compose a matched cohort of 35,232 patients. Among all strata, female patients exhibited lower mortality (hazard ratio [HR], 0.69-0.90), fewer amputations or death (HR, 0.70-0.89), and fewer cardiovascular events or death (HR, 0.78-0.91). The association between female sex and improved long-term outcomes was most pronounced for the patients with intermittent claudication. In the present propensity score-matched analysis of health insurance claims, we observed superior cardiovascular event-free survival, amputation-free survival, and overall survival during 5 years of follow-up after percutaneous ER in women with symptomatic PAOD. Future studies should address sex disparities in the open surgical treatment of PAOD to illuminate whether the conflicting data from previous reports might have resulted from insufficient stratification of the studies.


Intraspecific phylogenetics: support for dental transmission of human immunodeficiency virus.
A new method to estimate within-species gene genealogies was used to establish linkages among individuals associated with the Florida dental human immunodeficiency virus transmission case. Phylogenetic relationships were estimated from 103 nucleotide sequences from the V3 region of the env gene representing the Florida dentist, eight of his seropositive patients, and many local controls. The cladogram estimation procedure supports linkages among individuals within the previously described dental clade, whereas local controls and other patients form independent networks or are outliers in the main network, indicating more distant evolutionary relationships. A nested statistical analysis also indicates significant cohesion of the dental clade group.


Spatial resolution and radiation dose of a 64-MDCT scanner compared with published CT urography protocols.
The objective of our study was to compare the spatial resolution and effective dose from 64-MDCT with several published CT urography protocols. A phantom containing 1-, 2-, or 4-mm cylindric channels to simulate ureters with 0.25- to 3-mm plugs to simulate ureteral filling defects or ureteral diverticula was imaged using eight helical CT urography protocols. Computed radiography (CR) was also performed. Coronal maximum-intensity-projection images were created and, with the CR image, were evaluated independently by two genitourinary radiologists. Spatial resolution was evaluated by scoring each abnormality as present, visible; or as absent, not visible. Effective dose estimates for 11 CT urography protocols, including the radiographs obtained in the CT urography protocol, were calculated using published Monte Carlo organ dose coefficients. All ureteral abnormalities detected on CR were detected on the highest-spatial-resolution reconstruction using the evaluated 64-MDCT system. The smallest filling defect identified by both was 0.25 mm. Three 0.25-mm filling defects were not detected using the evaluated 16-MDCT system. The 4-MDCT system protocols showed the poorest performance. The range of effective doses for the evaluated CT urography protocols was 20.1-66.3 mSv. The number of phases, anatomic coverage per phase, and scanning parameters all contributed to this variation in dose. The evaluated 64-MDCT system showed detection accuracy identical to that of CR. Limiting anatomic coverage for specific phases and combining phases can reduce dose for multiphase protocols by up to a factor of 2 relative to early (circa 2000) 4-MDCT.


Neural coordination of excitation of ferret trachealis muscle.
The distribution of junction potentials and synaptic potentials to muscle cells and ganglion cells in the ferret trachealis muscle-nerve plexus preparation was studied with local electrical stimulation of branches of the laryngeal nerve or the interganglionic nerve trunk. Stimulations evoked excitatory junction potentials in muscle cells and fast excitatory postsynaptic potentials in ganglion (AH) cells located throughout the preparation, regardless of the location of the stimulating electrode. Evoked excitatory junction potentials were nearly simultaneous in widely separated muscle cells, suggesting that excitation of different muscle cells is coordinated. The apparent conduction velocity to muscle cells after a local nerve stimulation was 0.1-0.2 m/s. Dissemination of input to ganglion cells and muscle cells was dependent on the integrity of the interganglionic nerve trunk. There was evidence based on analysis of conduction velocities that coupling of electrical activity in different AH ganglion cells and muscle cells was related to the following: 1) an interlacing arrangement of myelinated preganglionic neurons that enter the plexus from multiple branches of the laryngeal nerve, and 2) interlacing neural circuits characterized by synapses between neurons whose cell bodies lie in different ganglia.


Use of pre-operative imaging for symptomatic uterine myomas during pregnancy: a case report and a systematic literature review.
Uterine fibroids (UFs) occur in 10% of pregnancies and may lead to severe maternal-fetal complications, mainly depending on UFs characteristics and the distance to the uterine cavity (UC). When symptomatic, UFs are managed medically. Nevertheless, in about 2% of cases, surgery becomes necessary. Entry into the UC should be avoided during myomectomy. Consequentially, pre-operative assessment of this risk could be beneficial. Ultrasonography (US) represents the gold standard for UFs assessment; however, scarce evidence has been produced to assess the role of magnetic resonance imaging (MRI). The aim of the present study was to summarize current evidence about the pre-operative use of imaging techniques for UFs during pregnancy. A systematic research of the literature was conducted in Scopus, PubMed/MEDLINE, ScienceDirect and the Cochrane Library, including case reports and case series. A case report was also discussed. We collected data regarding patients, imaging assessment, UFs characteristics, surgical information, timing and modality of delivery. According to our search strategy, 66 articles were selected and 210 patients were included. US assessment was reported in 36 (17%) cases. MRI was reported in 10 (4.7%) cases. Only in one case, MRI was used to measure the distance between UFs and UC. US allows an adequate pre-operative evaluation of anterior, submucosal or pedunculated symptomatic UFs in pregnancy. However, compared to US, MRI may provide a more accurate evaluation of multiple, large, intramural or posterior UFs and could measure the distance between UFs and UC more accurately.


Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model.
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder characterized by progressive motor and cognitive dysfunction. Caused by an expanded polyglutamine tract in ataxin 1 (ATXN1), SCA1 pathogenesis involves a multifactorial process that likely begins with misfolding of ATXN1, which has functional consequences on its interactions, leading to transcriptional dysregulation. Because lithium has been shown to exert neuroprotective effects in a variety of conditions, possibly by affecting gene expression, we tested the efficacy of lithium treatment in a knock-in mouse model of SCA1 (Sca1(154Q/2Q) mice) that replicates many features of the human disease. Sca1(154Q/2Q) mice and their wild-type littermates were fed either regular chow or chow that contained 0.2% lithium carbonate. Dietary lithium carbonate supplementation resulted in improvement of motor coordination, learning, and memory in Sca1(154Q/2Q) mice. Importantly, motor improvement was seen when treatment was initiated both presymptomatically and after symptom onset. Neuropathologically, lithium treatment attenuated the reduction of dendritic branching in mutant hippocampal pyramidal neurons. We also report that lithium treatment restored the levels of isoprenylcysteine carboxyl methyltransferase (Icmt; alternatively, Pccmt), down-regulation of which is an early marker of mutant ATXN1 toxicity. The effect of lithium on a marker altered early in the course of SCA1 pathogenesis, coupled with its positive effect on multiple behavioral measures and hippocampal neuropathology in an authentic disease model, make it an excellent candidate treatment for human SCA1 patients.


Positive Oct -3/4 and D2-40 Immunohistochemical Expression in Germ Cells and Suspected Histology Pattern of Intratubular Germ Cell Neoplasia in Boys with Cryptorchidism Vanish after the Age of 2 Years.
Introduction Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers may fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen in boys younger than the age of 2 years, where most orchiopexies are performed. The aim of the study was to evaluate the diagnostic challenge to differentiate between a histological pattern of ITGCN and a histological pattern with some atypical germ cells and all positive cancer immunohistochemical markers, but no increased risk of malignancy. Materials and Methods Histology sections from 373 testicular biopsies from 289 boys aged 1 month to 2 years operated for cryptorchidism were incubated with primary antibodies including anti-placental-like-alkaline phosphatase, antiOct-3/4, anti-C-kit, anti-D2-40, and in case of repeat biopsy with anti-stem cell factor (SCF) receptor. Results The prevalence of Oct-3/4 and D2-40-positive staining of germ cells in testicular biopsies were in age groups less than 6 months, 100% and 50%; 6-12 months, 60% and 17%; and 1-2 years, 12% and 4%. A 1 year, 1-month-old boy with Prader-Willi syndrome treated with growth hormone had ITGCN in both cryptorchid testes. In another three bilateral nonsyndromic cases, 8 months, 8 months and 1-year-old, a histological pattern in accordance with ITGCN was found. These three boys had a repeat biopsy from both testes performed at the age of 3 years, 4 months, 3.5 years, and 3 years, 10months, respectively. In all cases, the Oct-3/4 and D2-40 positive germ cells turned negative and the histological pattern normalized completely. The primary biopsies had SCF negative germ cells. Conclusion This study is valuable in identifying the age-related change in Oct-3/4 or D2-40 immunopositive germ cells in seminiferous tubules. An ITGCN-like histological pattern in nonsyndromic cryptorchidism will vanish after the age of 3 years. Even when immunohistochemistry is applied, prepubertal ITGCN is so rarely demonstrated in cryptorchid testes, that it is not plausible that ITGCN generally originates during fetal development in cryptorchidism.


[DNA metabolism in the process of the maturation of male sex cells. I. Amplification of ribosomal genes in the spermatogenesis of rats].
It has been shown that amplification of ribosomal genes takes place in prophase I of rat spermatogenesis. At the pachytene I step, a 2-fold excess of rDNA was found. Amplification of ribosomal genes starts in the premeiotic interphase on the chromosomal DNA. At the initial stage of rDNA amplification, a rDNA-RNA hybrid was detected. Our results allow the suggestion to be made that RNA plays the role of a primer in synthesis of the excess rDNA. It is possible that AT-rich prenucleolar DNA is involved in amplification of rDNA.


A comparative study of coastal and clinical isolates of Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium having a versatile metabolic potential and great ecological and clinical significance. The geographical distribution of P. aeruginosahas revealed the existence of an unbiased genetic arrangement in terrestrial isolates. In contrast, there are very few reports about P. aeruginosa strains from marine environments. The present work was aimed at studying the distribution of P. aeruginosa in coastal waters along the Indian Peninsula and understanding the environmental influence on genotypic, metabolic and phenotypic characteristics by comparing marine and clinical isolates. Of the 785 marine isolates obtained on selective media, only 32 (~4.1%) were identified as P. aeruginosa, based on their fatty acid methyl ester profiles. A low Euclidian distance value (< 2.5) obtained from chemotaxonomic analysis suggested that all the environmental (coastal and marine) isolates originated from a single species. While UPGMA analyses of AP-PCR and phenotypic profiles separated the environmental and clinical isolates, fatty acid biotyping showed overlapping between most clinical and environmental isolates. Our study revealed the genetic diversity among different environmental isolates of P. aeruginosa. While biogeographical separation was not evident based solely on phenotypic and metabolic typing, genomic and metatranscriptomic studies are more likely to show differences between these isolates. Thus, newer and more insightful methods are required to understand the ecological distribution of this complex group of bacteria.


Suppression of salivary melatonin secretion under 100-Hz flickering and non-flickering blue light.
Bright light at night is known to suppress melatonin secretion. Novel photoreceptors named intrinsically photosensitive retinal ganglion cells (ipRGCs) are mainly responsible for projecting dark/bright information to the suprachiasmatic nucleus and thus regulating the circadian system. However, it has been shown that the amplitude of the electroretinogram of ipRGCs is considerably lower under flickering light at 100 Hz than at 1-5 Hz, suggesting that flickering light may also affect the circadian system. Therefore, in this study, we evaluated light-induced melatonin suppression under flickering and non-flickering light. Twelve male participants between the ages of 20 and 23 years (mean ± S.D. = 21.6 ± 1.5 years) were exposed to three light conditions (dim, 100-Hz flickering, and non-flickering blue light) from 1:00 A.M. to 2:30 A.M., and saliva samples were obtained just before 1:00 A.M. and at 1:15, 1:30, 2:00, and 2:30 A.M. A repeated measures t test with Bonferroni correction showed that at 1:15 A.M., melatonin concentrations were significantly lower following exposure to non-flickering light compared with dim light, whereas there was no significant difference between the dim and 100-Hz flickering light conditions. By contrast, after 1:30 A.M., the mean melatonin concentrations were significantly lower under both 100-Hz flickering and non-flickering light than under dim light. Although melatonin suppression rate tended to be lower under 100-Hz flickering light than under non-flickering light at the initial 15 min of the light exposure, the present study suggests that 100-Hz flickering light may have the same impact on melatonin secretion as non-flickering light.


THE EFFECT OF EXPOSURE PERIOD AND TEMPERATURE ON THE PHOTOSENSORY PROCESS IN CIONA.
1. Experiments are presented which show that the latent period in the photosensory response of Ciona is inversely proportional to the duration of the exposure period to light. From this it is found that the velocity of the chemical reaction which determines the latent period is directly proportional to the concentration of photochemical products formed during the exposure period. This is interpreted as showing that the two processes form a coupled photochemical reaction, of which the secondary reaction proceeds only in the presence of products from the primary reaction. This coupling may be a catalysis or a direct chemical relation. 2. Further experiments show that the relation between temperature and the latent period is accurately described by the Arrhenius equation in which micro = 16,200. The precise numerical value of micro tentatively identifies the latent period process as an oxidation reaction which is catalyzed by iron. 3. The photocatalytic properties of certain iron compounds are used as a model for the coupled photochemical reaction suggested for the photosensory mechanism of Ciona and Mya.


Aripiprazole in the acute treatment of male patients with schizophrenia: effectiveness, acceptability, and risks in the inner-city hospital setting.
Aripiprazole, a novel atypical antipsychotic that acts as a partial agonist at the dopamine D(2) receptors, has been reported to be effective in the treatment of chronic schizophrenia. However, the risks and benefits of using aripiprazole in the acute hospital setting to treat severe psychotic disorders are unclear. This naturalistic study assessed the effectiveness of aripiprazole monotherapy in a group of actively psychotic male patients (n = 10) with schizophrenia who were admitted to an inner-city acute psychiatric unit. Most patients (n = 7) responded to aripiprazole treatment, which was well tolerated and significantly ameliorated psychotic symptoms after 2-3 weeks. Patients who responded to it could be safely discharged on aripiprazole monotherapy. Side effects observed were mostly mild and transient, and included extrapyramidal symptoms (n = 1) and neutropenia (n = 1). Aripiprazole also remarkably attenuated dyskinetic movements in 1 patient with severe tardive dyskinesia, thereby suggesting that it may be useful in the treatment of other disorders that are also associated with dopamine dysfunction. Results showed that aripiprazole can be safely and effectively employed in the hospital setting to treat severely psychotic patients with schizophrenia, but further studies are required to establish the full range of adverse reactions and therapeutic indications associated with its use.


Contemporary utilization of digoxin in patients with atrial fibrillation. Clinical Quality Improvement Network Investigators.
To define the contemporary practice patterns of digoxin utilization for the management of patients with atrial fibrillation (AF). A retrospective medical records audit of 2490 patients with documented AF, from 12 Canadian hospitals and six outpatient clinics, during fiscal year 1993-1994, was conducted. There were 1158 women and 1332 men, with a mean age of 72 years; 956 patients were < 70 years of age and 1534 were > or = 70 years old. The majority of patients had nonvalvular AF (75% of those with a documented etiology). Paroxysmal AF (PAF) was documented in 800 patients, 936 had chronic AF, and 754 had new-onset AF. While the prescribing patterns were heterogeneous, the predominant strategy pursued in all subgroups appeared to be that of achieving rate control. Digoxin was the most commonly prescribed medication (79%) and was prescribed for the majority of patients in all subgroups, including patients with PAF (74%) and patients with a history of chronic AF who were currently in sinus rhythm (83%). Only 10% of the patients with PAF who were prescribed digoxin had congestive heart failure. Similarly, less than 25% of the patients with chronic AF who were prescribed digoxin after conversion to sinus rhythm had evidence of heart failure. In the absence of clinical trial evidence supporting either a strategy of antiarrhythmic therapy or rate control with anticoagulation, the appropriateness of the observed prescribing practices cannot be judged. However, digoxin is not the best rate-controlling agent for all patients and may be overused in certain subgroups of patients, such as those with PAF and those successfully converted to sinus rhythm.


Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway.
Migration toward pathology is the first critical step in stem cell engagement during regeneration. Neural stem cells (NSCs) migrate through the parenchyma along nonstereotypical routes in a precise directed manner across great distances to injury sites in the CNS, where they might engage niches harboring local transiently expressed reparative signals. The molecular mechanisms for NSC mobilization have not been identified. Because NSCs seem to home similarly to pathologic sites derived from disparate etiologies, we hypothesized that the inflammatory response itself, a characteristic common to all, guides the behavior of potentially reparative cells. As proof of concept, we show that human NSCs migrate in vivo (including from the contralateral hemisphere) toward an infarcted area (a representative CNS injury), where local astrocytes and endothelium up-regulate the inflammatory chemoattractant stromal cell-derived factor 1alpha (SDF-1alpha). NSCs express CXC chemokine receptor 4 (CXCR4), the cognate receptor for SDF-1alpha. Exposure of SDF-1alpha to quiescent NSCs enhances proliferation, promotes chain migration and transmigration, and activates intracellular molecular pathways mediating engagement. CXCR4 blockade abrogates their pathology-directed chain migration, a developmentally relevant mode of tangential migration that, if recapitulated, could explain homing along nonstereotypical paths. Our data implicate SDF-1alpha/CXCR4, representative of the inflammatory milieu characterizing many pathologies, as a pathway that activates NSC molecular programs during injury and suggest that inflammation may be viewed not simply as playing an adverse role but also as providing stimuli that recruit cells with a regenerative homeostasis-promoting capacity. CXCR4 expression within germinal zones suggests that NSC homing after injury and migration during development may invoke similar mechanisms.


MSL: Facilitating automatic and physical analysis of published scientific literature in PDF format.
Published scientific literature contains millions of figures, including information about the results obtained from different scientific experiments e.g. PCR-ELISA data, microarray analysis, gel electrophoresis, mass spectrometry data, DNA/RNA sequencing, diagnostic imaging (CT/MRI and ultrasound scans), and medicinal imaging like electroencephalography (EEG), magnetoencephalography (MEG), echocardiography (ECG), positron-emission tomography (PET) images. The importance of biomedical figures has been widely recognized in scientific and medicine communities, as they play a vital role in providing major original data, experimental and computational results in concise form. One major challenge for implementing a system for scientific literature analysis is extracting and analyzing text and figures from published PDF files by physical and logical document analysis. Here we present a product line architecture based bioinformatics tool 'Mining Scientific Literature (MSL)', which supports the extraction of text and images by interpreting all kinds of published PDF files using advanced data mining and image processing techniques. It provides modules for the marginalization of extracted text based on different coordinates and keywords, visualization of extracted figures and extraction of embedded text from all kinds of biological and biomedical figures using applied Optimal Character Recognition (OCR). Moreover, for further analysis and usage, it generates the system's output in different formats including text, PDF, XML and images files. Hence, MSL is an easy to install and use analysis tool to interpret published scientific literature in PDF format.


Evidence for an intermediate conformational state of LacY.
LacY mutant Cys154 → Gly exhibits a periplasmic-closed crystal structure identical to the WT, but is periplasmic-open in the membrane. The mutant hardly catalyzes transport, but binds galactosides from either side of the membrane with the same affinity and is resistant to site-directed proteolysis relative to the pseudo-WT. Site-directed alkylation was also applied to 11 single-Cys mutants in Cys154 → Gly LacY in right-side-out membrane vesicles or after solubilization and purification in dodecyl-β-D-maltopyranoside (DDM). Unlike the pseudo-WT, Cys replacements on the periplasmic side of the Cys154 → Gly mutant label rapidly in the membrane without sugar, but labeling decreases markedly after the mutant proteins are purified. Thus, Cys154 → Gly LacY likely favors a higher-energy intermediate periplasmic-open conformation in situ, but collapses to a lower-energy periplasmic-closed conformation in DDM after purification. Notably, branched-chain or neopentyl glycol maltoside detergents stabilize Cys154 → Gly LacY in the membrane-embedded form.


The Mcf1 toxin induces apoptosis via the mitochondrial pathway and apoptosis is attenuated by mutation of the BH3-like domain.
Photorhabdus are Gram-negative, nematode-vectored bacteria that produce toxins to kill their insect hosts. The expression of one of these, Makes caterpillars floppy 1 (Mcf1), is sufficient to allow Escherichia coli to survive within, and kill, caterpillars which are otherwise able to clear E. coli infection. Mcf1 treated caterpillars show rapid loss of body turgor (the 'floppy' phenotype) and death is associated with massive apoptosis of both the midgut epithelium and insect phagocytes. Mammalian tissue culture cells treated with Mcf1 also display key features of apoptosis including zeiosis, apoptotic nuclear morphology, DNA laddering, activation of the effector caspase-3 and PARP cleavage. As Mcf1 carries a single BH3-like domain, here we investigate the hypothesis that this toxin promotes apoptosis via the mitochondrial pathway by mimicking a BH3 domain-only protein. Consistent with this hypothesis, a double mutant within the BH3-like domain causes a dramatic decline in apoptosis. Mcf1 also alters mitochondrial membrane potential and triggers the release of cytochrome c. Cells overexpressing Bcl-x(L), an anti-apoptotic Bcl-2 family member, are resistant to Mcf1-mediated apoptosis, as are cells deficient in Bax. In addition, translocation of Bax to the mitochondrion is observed in response to Mcf1 treatment. Together, these results show that Mcf1 mediates apoptosis via the mitochondrial pathway, and are consistent with the hypothesis that the BH3-like domain in Mcf1 is a functional requirement for the pro-apoptotic activity of Mcf1.


[Discriminant function analysis in the assessment of laboratory values in children with food allergy in acute viral hepatitis B].
The purpose of this investigation was to define the impact of food allergy (FA) in children on the time of normalization of a complex of the indices of a blood biochemical test for bilirubin and enzymes in acute viral hepatitis B (VHB). Discriminant function analysis through the mathematical expression of the combined influence of variables in a complex of the values of a blood biochemical test for bilirubin and enzymes in children with FA who had experienced a mild icteric form of VHB showed the absence of their normalization throughout one-year follow-up after hospital discharge. Among the examinees, there were twenty-five 3-14-year-old children with FA who had experienced a mild icteric form of VHB. About half of them were girls (44%). Blood biochemical tests for bilirubin and enzymes were carried out in both the acute stage of the disease and in convalescence at least 5 times 1, 3, 6, 9, and 12 months after their hospital discharge. The similar laboratory tests (blood biochemical tests for bilirubin and enzymes, marker spectrum to hepatitis virus) were performed in 20 healthy children (a control group).


Next-Generation Allergic Rhinitis Care in Singapore: 2019 ARIA Care Pathways.
Allergic rhinitis (AR) is prevalent in Singapore, with a significant disease burden. Afflicting up to 13% of the population, AR impairs quality of life, leads to reduced work productivity and is an independent risk factor for asthma. In the last 2 decades, local studies have identified patient and physician behaviours leading to suboptimal control of the disease. Yet, there is an overall lack of attention to address this important health issue. Allergic Rhinitis and its Impact on Asthma (ARIA) is a European organisation aimed at implementing evidence-based management for AR worldwide. Recent focus in Europe has been directed towards empowering patients for self-management, exploring the complementary role of mobile health, and establishing healthcare system-based integrated care pathways. Consolidation of these ongoing efforts has led to the release of the 2019 ARIA care pathways. This review summarises the ARIA update with particular emphasis on the current status of adult AR in Singapore. In addition, we identify unmet needs and future opportunities for research and clinical care of AR in the local context.


Binding mode prediction of cytochrome p450 and thymidine kinase protein-ligand complexes by consideration of water and rescoring in automated docking.
The popular docking programs AutoDock, FlexX, and GOLD were used to predict binding modes of ligands in crystallographic complexes including X-ray water molecules or computationally predicted water molecules. Isoenzymes of two different enzyme systems were used, namely cytochromes P450 (n = 19) and thymidine kinases (n = 19) and three different "water" scenarios: i.e., docking (i) into water-free active sites, (ii) into active sites containing crystallographic water molecules, and (iii) into active sites containing water molecules predicted by a novel approach based on the program GRID. Docking accuracies were determined in terms of the root-mean-square deviation (RMSD) accuracy and, newly defined, in terms of the ligand catalytic site prediction (CSP) accuracy. Consideration of both X-ray and predicted water molecules and the subsequent pooling and rescoring of all solutions (generated by all three docking programs) with the SCORE scoring function significantly improved the quality of prediction of the binding modes both in terms of RMSD and CSP accuracy.


A modified sclerosing needle for the sclerotherapy of upper gastrointestinal bleeding.
A modified instrument that permits simultaneous endoscopic irrigation and sclerotherapy of a bleeding site in the gastrointestinal tract under direct visualisation is presented. To date, the system has been used in 12 patients. Five cases of grade III esophageal varices have been treated and in three cases of acute bleeding, definitive arrest of the bleeding was achieved. In seven cases of acute upper gastrointestinal hemorrhage presenting with gastric ulcer (n = 2 Forrest-Ia and n = 2 Forrest-Ib) and duodenal ulcer (n = 3 Forrest-Ib) bleeding was successfully stopped. The system is easy to handle, reliable in clinical practice, can be employed anywhere and the instrument is inexpensive.


Nursing home administrator self-assessed preparedness.
Nursing home administrators (NHAs) are in key positions to improve nursing home quality. NHAs require state-level licensure, which involves passing a national NHA licensure examination and fulfilling state-level licensure requirements that vary widely across states. With multiple pathways to NHA licensure, little is known about NHAs' preparation and training to meet the complex demands of this position. The aim of this study was to explore NHAs' self-assessed person-job fit based on NHAs' self-rated preparedness and the importance of the activities that supported their preparation. A descriptive cross-sectional design was used to collect data from NHAs (N = 175) randomly recruited from nursing homes in five states, with a mailed self-administered questionnaire. Data analysis included descriptive statistics, correlations, and t tests/ANOVA. Thirty percent of respondents reported they were well prepared, overall, for their first NHA position. The findings suggest NHA preferences for more formalized ways to develop their entry-level competencies, with lower preference for On-the-job training, Previous job experience, and Self-study and higher preference for Administrator-in-training, Bachelor's degree programs, and Mentoring. There is an urgent need for NHAs who are well prepared to effectively address our nation's mandates for nursing home quality improvement. With multiple pathways to NHA licensure, this exploratory study provides initial insights about NHAs' self-assessed preparation and training. The findings suggest that NHAs prefer more formalized ways to prepare for the NHA position. Research is needed to identify specific teaching/learning practices and on-the-job training that maximize the NHAs' preparation to meet their job demands.


Hepatocyte growth factor in cerebrospinal fluid differentiates community-acquired or nosocomial septic meningitis from other causes of pleocytosis.
Due to anatomical restrictions, the inflammatory response to intracerebral bacterial infections exposes swollen brain tissues to pressure and ischemia, resulting in life-threatening damage. Rapid diagnosis and immediate empirical antibiotic therapy is highly important. However, diagnosing meningitis in patients after neurosurgery is complicated, due to brain tissue damage and changes in cerebrospinal fluid (CSF) caused by surgery. Hepatocyte growth factor (HGF) is a local, acute-phase protein with healing properties. Previous studies on community-acquired septic meningitis reported high levels of intrathecally produced HGF. The present study focused on nosocomial meningitis in assessing the levels of HGF in the CSF. HGF concentrations (ELISA) and HGF binding to receptors; c-Met receptor and heparan sulfate proteoglycan were determined in CSF samples (surface plasmon resonance). CSF samples from patients with community-acquired or nosocomial meningitis (217 samples from 135 patients) were compared to those from controls without signs of cerebral nervous system involvement (N = 36) and patients with Alzheimer's disease (N = 20). Compared to samples from patients that had undergone neurosurgery and had other infectious diseases, CSF samples from patients with nosocomial meningitis had significantly higher HGF concentrations (p < 0.001) and binding affinity to c-Met (p < 0.001) and HSPG (p = 0.043) receptors. The sensitivity and specificity to identify nosocomial septic meningitis were 69.7 and 93.4%, respectively. The HGF concentration and binding affinity to HGF receptors were significantly higher in CSF from patients with community-acquired septic meningitis compared to patients with aseptic (viral and subacute) meningitis as well as controls (p < 0.001). The sensitivity and specificity to identify community-acquired septic meningitis were 95.4 and 95.7%, respectively. In febrile nosocomial infections that occurred post neurosurgery, HGF assessment could substantially improve the differentiation of meningitis from other infections and therefore might be a tool for rapid diagnosis, limiting injuries and guiding antibiotic therapy.


Impact of Dietary Isoflavone Supplementation on the Fecal Microbiota and Its Metabolites in Postmenopausal Women.
Isoflavones are metabolized by components of the gut microbiota and can also modulate their composition and/or activity. This study aimed to analyze the modifications of the fecal microbial populations and their metabolites in menopausal women under dietary treatment with soy isoflavones for one month. Based on the level of urinary equol, the women had been stratified previously as equol-producers (n = 3) or as equol non-producers (n = 5). The composition of the fecal microbiota was assessed by high-throughput sequencing of 16S rRNA gene amplicons and the changes in fatty acid excretion in feces were analyzed by gas chromatography. A greater proportion of sequence reads of the genus Slackia was detected after isoflavone supplementation. Sequences of members of the family Lachnospiraceae and the genus Pseudoflavonifractor were significantly increased in samples from equol-producing women. Multivariable analysis showed that, after isoflavone treatment, the fecal microbial communities of equol producers were more like each other. Isoflavone supplementation increased the production of caproic acid, suggesting differential microbial activity, leading to a high fecal excretion of this compound. However, differences between equol producers and non-producers were not scored. These results may contribute to characterizing the modulating effect of isoflavones on the gut microbiota, which could lead to unravelling of their beneficial health effects.


Role of novel biomarkers of inflammation in patients with stable coronary heart disease.
Atherosclerosis is a dynamic chronic inflammatory process, and some inflammatory biomarkers have roles in this process. The levels of C-reactive protein (CRP) in patients with chronic stable coronary heart disease (CHD) have not been investigated well, and the levels of macrophage colony-stimulating factor (M-CSF) and interleukin-3 (IL-3) in patients with chronic stable CHD and the effects of these cytokines on atherogenesis are not known. To determine whether new inflammatory biomarkers have roles in atherosclerosis, the authors measured the levels of CRP, M-CSF, and IL-3 in patients with chronic stable CHD and in healthy controls. They measured plasma CRP concentrations by using a highly sensitive CRP reagent with immunonephelometric method, and plasma M-CSF and IL-3 concentrations with the help of a commercial enzyme-linked immunoassay test in 31 patients with chronic stable CHD documented by coronary angiography and in 22 age-matched healthy control subjects documented by coronary angiography. Mean plasma CRP, M-CSF, and IL-3 concentrations in patients with chronic stable CHD were significantly higher than those in controls (8.2 vs 4.6 mg/L, 195.3 vs 28.9 pg/mL, 173 vs 118 ng/mL, respectively, ppi.05). CRP, M-CSF, and IL-3 were all increased in patients with chronic stable CHD relative to controls. These findings suggest that these are new inflammatory biomarkers that may have important roles in the development of atherosclerotic lesions.


[Physiopathology of the cerebral arterial circulation. Application to cerebro arterial surgery].
Autoregulation of cerebral arterial circulation corresponds to a hemodynamic reserve enabling normal cerebral blood flow to be assured when arterial blood pressure drops. However, the capacity of this autoregulatory system is exceeded when pressure drops below 60 +/- 10 mmHg, at which time metabolic disturbances appear followed by the arrest of electric activity and the death or neurons. These ischemic phenomena involve more or less extended regions: cerebral or choroidal arterioles or arteries, or even those of the entire brain. They can occur in series as, for example, the embolism of a cerebral arteriole or artery in a brain already globally hypoperfused downstream from a carotid occlusion or narrow stenosis. The association of these phenomena accounts for the different clinicopathologic cerebrovascular accidents. These disturbances of cerebral blood flow can be explored clinically by isotopic techniques. A cerebral perfusion blood pressure drop can be suspected, when nonhemispheric symptoms appear, on the basis of ophthalmodynamometry, oculoplethysmography or changes in intracranial arterial velocity (transcranial Doppler examination) during the Diamox (Acetazolamide) test. After release of carotid clamping or correction of a "hemodynamically significant" stenosis, increased cerebral blood flow can be observed, with sometimes a "cerebral hyperperfusion" syndrome similar to that of hypertensive events which exceed the capacities of cerebral arterial autoregulation.


T-cell responses to dengue virus in humans.
Dengue virus (DENV) is a leading cause of morbidity and mortality in most tropical and subtropical areas of the world. Dengue virus infection induces specific CD4+CD8- and CD8+CD4- T cells in humans. In primary infection, T-cell responses to DENV are serotype cross-reactive, but the highest response is to the serotype that caused the infection. The epitopes recognized by DENV-specific T cells are located in most of the structural and non-structural proteins, but NS3 is the protein that is most dominantly recognized. In patients with dengue hemorrhagic fever (DHF) caused by secondary DENV infection, T cells are highly activated in vivo. These highly activated T cells are DENV-specific and oligoclonal. Multiple kinds of lymphokines are produced by the activated T cells, and it has been hypothesized that these lymphokines are responsible for induction of plasma leakage, one of the most characteristic features of DHF. Thus, T-cells play important roles in the pathogenesis of DHF and in the recovery from DENV infection.


Clinical and bone density outcomes of tumor-induced osteomalacia after treatment.
To report the outcomes of tumor-induced osteomalacia after treatment, particularly related to recovery of bone mass. We review the clinical course of a 61-year-old man extremely debilitated from multiple fractures and neuromuscular weakness due to tumor-induced osteomalacia and report the changes in biochemical markers and bone density after removal of the causative neoplasm. At the time of diagnosis, the patient's serum phosphorus and 1,25 dihydroxyvitamin D levels were depressed, and his fibroblast growth factor-23 level was markedly elevated. These values normalized 2 days after surgery and remained within their respective reference ranges 4 and 12 months after resection of a mesenchymal tumor. Lumbar bone density values (T-scores) were 0.445 g/cm2 (-5.9) preoperatively, 0.939 g/cm2 (-1.4) 4 months after surgery, and 1.152 g/cm2 (0.7) 12 months after surgery. Left femoral neck values at the same time points were 0.525 g/cm2 (-3.0), 1.035 g/cm2 (-0.8), and 1.184 g/cm2 (1.9). Ultra-distal radius values at the same time points were 0.128 g/cm2 (-7.0), 0.191 g/cm2 (-5.9), and 0.259 g/cm2 (-4.8). In addition, he recovered neuromuscular function and was able to leave his wheelchair. Tumor-induced osteomalacia can be an extremely debilitating disease. With successful localization, identification, and resection of the neoplasm, bone mass and physical function can recover.


Career Development Anxiety and Mental Health Regulation of University Music Teachers.
Mental health essentially refers to a state of mind. It means that an individual can keep a good or normal state in behavior. It is not only related to the overall development of the individual body and mind but also affects the construction of university teachers. This paper mainly studies the career development anxiety of music teachers in colleges and universities in China, analyzes its causes, and puts forward corresponding countermeasures and suggestions to alleviate the pressure and promote the physical and mental harmony of music teachers and the common growth of a good social atmosphere. The purpose is to help music teachers in colleges and universities better manage their mental health. This paper collects the data of occupational stress and mental health of 164 music teachers in many colleges and universities through the method of a questionnaire survey and processes the data with the analysis formula of sample variance and standard deviation. The analysis shows that a considerable number of the respondents have career development anxiety.


Identification of a translation initiation factor 3 (eIF3) core complex, conserved in yeast and mammals, that interacts with eIF5.
Only five of the nine subunits of human eukaryotic translation initiation factor 3 (eIF3) have recognizable homologs encoded in the Saccharomyces cerevisiae genome, and only two of these (Prt1p and Tif34p) were identified previously as subunits of yeast eIF3. We purified a polyhistidine-tagged form of Prt1p (His-Prt1p) by Ni2+ affinity and gel filtration chromatography and obtained a complex of approximately 600 kDa composed of six polypeptides whose copurification was completely dependent on the polyhistidine tag on His-Prt1p. All five polypeptides associated with His-Prt1p were identified by mass spectrometry, and four were found to be the other putative homologs of human eIF3 subunits encoded in S. cerevisiae: YBR079c/Tif32p, Nip1p, Tif34p, and YDR429c/Tif35p. The fifth Prt1p-associated protein was eIF5, an initiation factor not previously known to interact with eIF3. The purified complex could rescue Met-tRNAiMet binding to 40S ribosomes in defective extracts from a prt1 mutant or extracts from which Nip1p had been depleted, indicating that it possesses a known biochemical activity of eIF3. These findings suggest that Tif32p, Nip1p, Prt1p, Tif34p, and Tif35p comprise an eIF3 core complex, conserved between yeast and mammals, that stably interacts with eIF5. Nip1p bound to eIF5 in yeast two-hybrid and in vitro protein binding assays. Interestingly, Sui1p also interacts with Nip1p, and both eIF5 and Sui1p have been implicated in accurate recognition of the AUG start codon. Thus, eIF5 and Sui1p may be recruited to the 40S ribosomes through physical interactions with the Nip1p subunit of eIF3.


[Neuroimaging and neuroscience of emotional processes].
In neurosciences, there is increasing interest in studying affective, emotional and social processes in humans and animals. What are the conceptual framework identified for these studies and the technical approaches undertaken? What information has already emerged from these studies? Which results have already been obtained and what are the researchers' goals? Can these neuroimaging analyses provide novel insights to improve our understanding of psychiatric disorders? These are some of the questions addressed in this concise overview of our knowledge in this domain.


Transfusion protocol for implantation and explantation of cardiac devices in an academic medical center.
Few reports in the literature describe the transfusion support needed for implantation and explantation of cardiac assist devices. Because such devices are frequently used at this institution, we have established a protocol to support these patients. We reviewed blood bank records to document the usage of blood components in all patients on cardiac assist devices from 1989 to 2005 (n = 215). The data were separated into components given at the time of implantation and explantation of the device. Implantation data on 214 patients showed the mean use as follows: red blood cells (RBC), 5.7 U; platelets (PLT), 2.4 U; fresh frozen plasma (FFP), 7.5 U; and cryoprecipitate, 0 U. Explantation data on 134 patients showed a mean use as follows: RBC, 7.7 U; PLT, 2.4 U; FFP, 9.9 U; and cryoprecipitate, 3.7 U. Our protocol for the preparation of blood components for implantation and explantation of a cardiac device is, implantation: RBC, 4 U; PLT, 1 U; FFP, 6 U; explantation: RBC, 8 U; PLT, 2 U; FFP, 8 U. Our data do not support the need for preparation of cryoprecipitate before implantation or explantation.


Attitudes of Oncology Nurses Towards Care of Dying Patients and the Principles of Dying with Dignity and Their Views on Good Death.
This study investigated oncology nurses' attitudes toward caring for dying patients, their principles of dying with dignity, and their views on good death. This descriptive study included 257 oncology nurses working at two university hospitals, an educational research hospital and a state hospital in Turkey. Data were collected using the descriptive characteristics information form, the Frommelt Attitudes toward Care of the Dying scale, the Assessment Scale of Attitudes toward the Principles of Dying with Dignity, and the Good Death Scale. The nurses obtained mean scores of 99.53 ± 7.76 on the Frommelt Attitudes toward Care of the Dying scale, 26.84 ± 12.45 on the Assessment Scale of Attitudes toward the Principles of Dying with Dignity, and 57.23 ± 7.48 on the Good Death Scale. The nurses' personal and professional characteristics influenced their attitudes toward caring for dying patients, the principles of dying with dignity, and their views on good death.


Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen.
The direct-instillation nasal allergen challenge (NAC) and the environmental exposure chamber (EEC) are 2 methods of conducting controlled allergen provocations. The clinical and biological comparability of these methods has not been thoroughly investigated. We sought to compare clinical and immunologic responses to cat allergen in NAC versus EEC. Twenty-four participants were randomized to receive either NAC followed by a 2-day challenge in an EEC or a 2-day challenge in an EEC followed by NAC. Challenges were separated by 28-day washout periods. We measured total nasal symptom scores, peak nasal inspiratory flow, nasal (0-8 hours) and serum cytokines, serum antibodies, peripheral blood antigen-specific T lymphocytes, and gene expression in nasal scrapings. The primary outcome was the total nasal symptom score area under the curve for the first 3 hours after allergen exposure in NAC or after initiation of exposure in EEC. Both challenges increased IL-5 and IL-13 in nasal fluids and serum and resulted in altered nasal cell expression of gene modules related to mucosal biology and transcriptional regulation. Changes in gene modules, more so than cytokine measurements, showed significant associations with total nasal symptom score and peak nasal inspiratory flow. Overall, EEC exposure generated larger responses and more early terminations compared with NAC. Although the 2 challenges did not correlate in symptom magnitude or temporality, striking correlations were observed in cytokine levels. Although clinical outcomes of NAC and EEC were temporally different and nonequivalent in magnitude, immunologic responses were similar. Selection of a particular allergen challenge method should depend on considerations of study objectives and cost.


Serum bile acids as a prognostic biomarker in biliary atresia following Kasai portoenterostomy.
In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group. Participants with biliary atresia from the Childhood Liver Disease Research Network were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6-month post-KP clinic visit ( n = 137). Bile acids were measured from the stored serum samples and used to divide participants into ≤40 μmol/L ( n = 43) or >40 μmol/L ( n = 94) groups. At 2 years of age, the ≤40 μmol/L compared with >40 μmol/L group had significantly lower total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bile acids, and spleen size, as well as significantly higher albumin and platelet counts. Furthermore, during 734 person-years of follow-up, those in the ≤40 μmol/L group were significantly less likely to develop splenomegaly, ascites, gastrointestinal bleeding, or clinically evident portal hypertension. The ≤40 μmol/L group had a 10-year cumulative incidence of liver transplant/death of 8.5% (95% CI: 1.1%-26.1%), compared with 42.9% (95% CI: 28.6%-56.4%) for the >40 μmol/L group ( p = 0.001). Serum bile acid levels may be a useful prognostic biomarker for infants achieving normalized bilirubin levels after KP.


Neuro-Behcet's Disease, a Diagnostic Challenge.
Neuro-Behcet's disease (NBD) is a rare neurological manifestation of the systemic small vessel vasculitis called Behcet's disease. It can present in various ways with predilection for the brain stem, thalamo- hypothalamic regions, cerebellum and basal ganglia. In this case, we describe a case of young stroke that was later attributed to NBD.


Perceptions of European ME/CFS Experts Concerning Knowledge and Understanding of ME/CFS among Primary Care Physicians in Europe: A Report from the European ME/CFS Research Network (EUROMENE).
Background and Objectives: We have conducted a survey of academic and clinical experts who are participants in the European ME/CFS Research Network (EUROMENE) to elicit perceptions of general practitioner (GP) knowledge and understanding of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and suggestions as to how this could be improved. Materials and Methods: A questionnaire was sent to all national representatives and members of the EUROMENE Core Group and Management Committee. Survey responses were collated and then summarized based on the numbers and percentages of respondents selecting each response option, while weighted average responses were calculated for questions with numerical value response options. Free text responses were analysed using thematic analysis. Results: Overall there were 23 responses to the survey from participants across 19 different European countries, with a 95% country-level response rate. Serious concerns were expressed about GPs' knowledge and understanding of ME/CFS, and, it was felt, about 60% of patients with ME/CFS went undiagnosed as a result. The vast majority of GPs were perceived to lack confidence in either diagnosing or managing the condition. Disbelief, and misleading illness attributions, were perceived to be widespread, and the unavailability of specialist centres to which GPs could refer patients and seek advice and support was frequently commented upon. There was widespread support for more training on ME/CFS at both undergraduate and postgraduate levels. Conclusion: The results of this survey are consistent with the existing scientific literature. ME/CFS experts report that lack of knowledge and understanding of ME/CFS among GPs is a major cause of missed and delayed diagnoses, which renders problematic attempts to determine the incidence and prevalence of the disease, and to measure its economic impact. It also contributes to the burden of disease through mismanagement in its early stages.


Health and eating behavior differs between lean/normal and overweight/obese low-income women living in food-insecure environments.
To explore differences and similarities in environmental, personal, and behavioral factors influencing eating behavior among low-income women of varying weight status. Focus groups (n = 16) were used to collect qualitative data. Quantitative data collected included demographic, lifestyle, and anthropometric (heights and weights). Community centers, libraries, and homeless shelters in low-income neighborhoods. Of the 83 participants, 58% were African-American, 28% were white, and the remainder were American Indian, Hispanic, or mixed race. A total of 35% of participants were lean/normal (body mass index <25 kg/m(2)) and 65% were overweight/obese (body mass index >25 kg/m(2)). Focus group methodology was used to collect data on 83 participants. Social Cognitive Theory (SCT) provided the theoretical basis. Transcripts were analyzed using the open-coding method and comments between lean/normal and overweight/obese women were systematically compared. Focus group themes were food environment, aberrant eating behavior, health values, and beliefs. Differences in personal and behavioral factors were apparent between overweight/obese and lean/normal women, with the former group frequently discussing emotional eating, overeating, and stashing food, and the latter group communicating greater nutrition knowledge and describing regular physical activity. Both groups similarly expressed experiences with food insecurity and lived in low-income environments. For low-income women, personal and behavioral factors may modify the influence of their obesogenic food environment. Further research within the context of SCT should examine differences between lean/normal and overweight/obese women living in the same environment.


Does a prenatal diagnosis affect mortality and morbidity for neonatal arterial switch operation.
The effect of prenatal diagnosis on prognosis in patients with transposition of the great arteries is not clear. In this study, we compared the outcomes after arterial switch operation. Outcome of 112 patients who had arterial switch operation in the neonatal period were analysed. The patients were divided into two groups: those who had prenatal diagnosis (Group 1; n = 34) and those who did not (Group 2; n = 78). The patients were also classified based on their diagnosis: simple transposition, transposition with ventricular septal defect and/or aortic arch hypoplasia, and Taussig-Bing anomaly. In Group 1, the C-section delivery rate was higher (82% vs. 44%; p = 0.004), and it was observed that patients in Group 1 were more often intubated upon admission to the neonatal ICU (38% vs. 9%; p = 0.005). No differences were found between the two groups in terms of operation time, cardiopulmonary bypass time, post-operative invasive respiratory support duration, or extracorporeal membrane oxygenation support. It was observed that those who had Taussig-Bing anomaly had a higher mortality. Timely treatment have a positive effect on neonatal mortality and morbidity. That's why all families with prenatal diagnosis of critical CHD should be recommended to have the delivery in a tertiary care hospital. Although it could not be demonstrated in this study, prenatal diagnosis has a potential to improve surgical results especially in countries or cities, which does not have enough resources for transfer and surgical units. Further efforts are needed to improve prenatal screening programmes.


Coexistence of myasthenia gravis and seropositive juvenile chronic arthritis.
The development of myasthenia gravis (MG) in a patient with juvenile chronic arthritis (JCA) is a rare occurrence. This report concerns a patient with seropositive JCA who developed MG during her second pregnancy.


Therapeutic Targeting of Cancer Metabolism with Triosephosphate Isomerase.
The increase in glycolytic flux in cancer, known as aerobic glycolysis, is one of the most important hallmarks of cancer. Therefore, glycolytic enzymes have importance in understanding the molecular mechanism of cancer progression. Triosephosphate isomerase (TPI) is one of the key glycolytic enzymes. Furthermore, it takes a part in gluconeogenesis, pentose phosphate pathway and fatty acid biosynthesis. To date, it has been shown altered levels of TPI in various cancer types, especially in metastatic phenotype. According to other studies, TPI might be considered as a potential therapeutic target and a cancer-related biomarker in different types of cancer. However, its function in tumor formation and development has not been fully understood. Here, we reviewed the relationship between TPI and cancer for the first time.


Sports medicine applications of platelet rich plasma.
Platelet rich plasma (PRP) is a powerful new biologic tool in sports medicine. PRP is a fraction of autologous whole blood containing and increased number of platelets and a wide variety of cytokines such as platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor beta-1 (TGF-B1), fibroblast growth factor (FGF), Insulin-like growth factor-1 (IGF-1) among many others. Worldwide interest in this biologic technology has recently risen sharply. Basic science and preclinical data support the use of PRP for a variety of sports related injuries and disorders. The published, peer reviewed, human data on PRP is limited. Although the scientific evaluation of clinical efficacy is in the early stages, elite and recreational athletes already use PRP in the treatment of sports related injuries. Many questions remain to be answered regarding the use of PRP including optimal formulation, including of leukocytes, dosage and rehabilitation protocols. In this review, a classification for platelet rich plasma is proposed and the in-vitro, preclinical and human investigations of PRP applications in sports medicine will be reviewed as well as a discussion of rehabilitation after a PRP procedure. The regulation of PRP by the World Anti-Doping Agency will also be discussed. PRP is a promising technology in sports medicine; however, it will require more vigorous study in order to better understand how to apply it most effectively.


Antigen-presenting cells in the induction of contact hypersensitivity in mice: evidence that Langerhans cells are sufficient but not required.
One explanation for the fact that certain genetically defined strains of mice prove to be resistant to effects of low dose ultraviolet B radiation on the induction of contact hypersensitivity is that ultraviolet B resistant mice possess a second pathway for antigen presentation through the skin--a pathway that is independent of epidermal Langerhans cells and beyond the reach of the damaging effects of ultraviolet B light. As a corollary, ultraviolet-B susceptible mice would be expected to be deficient in this pathway. Several experimental strategies were employed to determine whether Langerhans cells are required for the induction of contact hypersensitivity by epicutaneously applied hapten. The results reveal that tape-stripped skin supports the induction of contact hypersensitivity, whereas surgical excision of hapten-painted skin within 1 h of application fails to permit the development of contact hypersensitivity. Because the former selectively eliminates epidermal Langerhans cells while the latter deletes both Langerhans cells and dermal antigen-presenting cells, we conclude that either Langerhans cells or dermal cells are sufficient to provide antigen presentation in the induction of contact hypersensitivity. When large amounts of hapten are painted epicutaneously, or when hapten is injected subcutaneously or painted on sub-dermal tissues, contact hypersensitivity also results, indicating that induction of contact hypersensitivity does not require that antigen processing and presentation be provided by cutaneous cells. Reasons are presented for concluding that under physiologic circumstances induction of contact hypersensitivity by epicutaneous hapten application relies primarily upon the antigen-presenting capabilities of epidermal (Langerhans cells) and dermal cells.


Nonenzymatic Posttranslational Modifications and Peptide Cleavages Observed in Peptide Epimers.
Posttranslational modifications (PTMs) play vital roles in cellular homeostasis and are implicated in various pathological conditions. This work uses two ion mobility spectrometry-mass spectrometry (IMS-MS) modalities, drift-tube IMS (DT-IMS) and trapped IMS (TIMS), to characterize three important nonenzymatic PTMs that induce no mass loss: l/d isomerization, aspartate/isoaspartate isomerization, and cis/trans proline isomerization. These PTMs are assessed in a single peptide system, the recently discovered pleurin peptides, Plrn2, from Aplysia californica. We determine that the DT-IMS-MS/MS can capture and locate asparagine deamidation into aspartate and its subsequent isomerization to isoaspartate, a key biomarker for age-related diseases. Additionally, nonenzymatic peptide cleavage via in-source fragmentation is evaluated for differences in the intensities and patterns of fragment peaks between these PTMs. Peptide fragments resulting from in-source fragmentation, preceded by peptide denaturation by liquid chromatography (LC) mobile phase, exhibited cis/trans proline isomerization. Finally, the effects of differing the fragmentation voltage at the source and solution-based denaturation conditions on in-source fragmentation profiles are evaluated, confirming that LC denaturation and in-source fragmentation profoundly impact N-terminal peptide bond cleavages of Plrn2 and the structures of their fragment ions. With that, LC-IMS-MS/MS coupled with in-source fragmentation could be a robust method to identify three important posttranslational modifications: l/d isomerization, Asn-deamidation leading to Asp/IsoAsp isomerization, and cis/trans proline isomerization.


Lost in Translation: Piloting a Novel Framework to Assess the Challenges in Translating Scientific Uncertainty From Empirical Findings to WHO Policy Statements.
Calls for evidence-informed public health policy, with implicit promises of greater program effectiveness, have intensified recently. The methods to produce such policies are not self-evident, requiring a conciliation of values and norms between policy-makers and evidence producers. In particular, the translation of uncertainty from empirical research findings, particularly issues of statistical variability and generalizability, is a persistent challenge because of the incremental nature of research and the iterative cycle of advancing knowledge and implementation. This paper aims to assess how the concept of uncertainty is considered and acknowledged in World Health Organization (WHO) policy recommendations and guidelines. We selected four WHO policy statements published between 2008-2013 regarding maternal and child nutrient supplementation, infant feeding, heat action plans, and malaria control to represent topics with a spectrum of available evidence bases. Each of these four statements was analyzed using a novel framework to assess the treatment of statistical variability and generalizability. WHO currently provides substantial guidance on addressing statistical variability through GRADE (Grading of Recommendations Assessment, Development, and Evaluation) ratings for precision and consistency in their guideline documents. Accordingly, our analysis showed that policy-informing questions were addressed by systematic reviews and representations of statistical variability (eg, with numeric confidence intervals). In contrast, the presentation of contextual or "background" evidence regarding etiology or disease burden showed little consideration for this variability. Moreover, generalizability or "indirectness" was uniformly neglected, with little explicit consideration of study settings or subgroups. In this paper, we found that non-uniform treatment of statistical variability and generalizability factors that may contribute to uncertainty regarding recommendations were neglected, including the state of evidence informing background questions (prevalence, mechanisms, or burden or distributions of health problems) and little assessment of generalizability, alternate interventions, and additional outcomes not captured by systematic review. These other factors often form a basis for providing policy recommendations, particularly in the absence of a strong evidence base for intervention effects. Consequently, they should also be subject to stringent and systematic evaluation criteria. We suggest that more effort is needed to systematically acknowledge (1) when evidence is missing, conflicting, or equivocal, (2) what normative considerations were also employed, and (3) how additional evidence may be accrued.


Daptomycin dose-effect relationship against resistant gram-positive organisms.
Daptomycin exhibits in vitro bactericidal activity against clinically significant gram-positive bacteria. We employed pharmacodynamic modeling to determine a once-daily dosing regimen of daptomycin that correlates to pharmacodynamic endpoints for different resistant gram-positive clinical strains. An in vitro pharmacodynamic model with an initial inoculum of 6 log(10) CFU/ml was used to simulate daptomycin regimens ranging in dose from 0 to 9 mg/kg of body weight/day, with corresponding exposures reflecting free-daptomycin concentrations in serum. Bacterial density was profiled over 48 h for two methicillin-resistant Staphylococcus aureus (MRSA-67 and -R515), two glycopeptide intermediate-resistant S. aureus (GISA-992 and -147398), and two vancomycin-resistant Enterococcus faecium (VREF-12366 and -SF12047) strains. A sigmoid dose-response model was used to estimate the effective dose required to achieve 50% (ED(50)) and 80% (ED(80)) bacterial density reduction at 48 h. Daptomycin MICs for study isolates ranged from 0.125 to 4 micro g/ml. Model fitting resulted in an r(2) of >0.80 for all tested isolates. Control growths at 48 h ranged from 7.3 to 8.5 log(10) CFU/ml. Sigmoid relationships were not superimposable between categorical resistant species: ED(50) and ED(80) values were 1.9 and 3.1, 4.2 and 5.6, and 5.4 and 6.8 mg/kg for MRSA, GISA, and VREF isolates, respectively. Doses required to achieve ED(50) and ED(80) values correlated with MIC differences between tested organisms. Corresponding area under the concentration-time curve from 0 to 24 h/MIC exposure ratios demonstrated a wide range of ED(80) values among the tested isolates. Doses ranging between 3 and 7 mg/kg produced significant bactericidal activity (ED(80)) against these multidrug-resistant S. aureus and E. faecium isolates.


Spatial Ecology of the American Crocodile in a Tropical Pacific Island in Central America.
Conservation of large predators has long been a challenge for biologists due to the limited information we have about their ecology, generally low numbers in the wild, large home ranges and the continuous expansion of human settlements. The American crocodile (Crocodylus acutus) is a typical apex predator, that has suffered from all of these characteristic problems, especially the latter one. Humans have had a major impact on the recovery of this species throughout its range, even though most of the countries it inhabits have banned hunting. The last decade has made it clear that in order to implement sound conservation and management programs, we must increase our understanding of crocodile spatial ecology. However, in only two countries where American crocodiles have telemetry studies even been published. Herein we have characterized the spatial ecology of C. acutus on Coiba Island, Panama, by radio-tracking (VHF transmitters) 24 individuals between 2010 and 2013, to determine movement patterns, home range, and habitat use. We have then compared our findings with those of previous studies to develop the most comprehensive assessment of American crocodile spatial ecology to date. Females showed a higher average movement distance (AMD) than males; similarly, adults showed a higher AMD than sub-adults and juveniles. However, males exhibited larger home ranges than females, and concomitantly sub-adults had larger home ranges than juveniles, hatchlings, and adults. There was an obvious relationship between seasonal precipitation and AMD, with increased AMD in the dry and "low-wet" seasons, and reduced AMD during the "true" wet season. We found disaggregate distributions according to age groups throughout the 9 habitat types in the study area; adults and hatchlings inhabited fewer habitat types than juveniles and sub-adults. These sex- and age-group discrepancies in movement and habitat choice are likely due to the influences of reproductive biology and Coiba's precipitation cycle. Juveniles also showed distinct movement patterns and home ranges; however, with sexual maturation and development, these behaviors became more characteristic of adults and sub-adults. Ours is one of a very small number of studies that will allow future management and conservation planning to be based on the comprehensive integration of the spatial ecology of a Neotropical crocodylian apex predator.


A Pediatric Decannulation Protocol: Outcomes of a 10-Year Experience.
(1) Describe an institutional protocol that focuses on the essential steps for decannulation of pediatric patients with long-term tracheostomies. (2) Discuss the preliminary observations of the safety of this protocol in regard to decannulation failures and successes in a selected patient population. Case series with chart review. A tertiary pediatric hospital. Subjects were pediatric patients with chronic tracheostomies undergoing decannulation. Ages ranged from 1 to 17 years old. Indications for initial tracheostomy included chronic lung disease, airway obstruction, and trauma. Subjects underwent decannulation attempt following a specific protocol. The protocol consisted of operative laryngoscopy and bronchoscopy. If the airway was deemed adequate for decannulation at that time, the tracheotomy tube was removed, and the child was monitored overnight; the patient was considered for discharge the following day if no complications arose. No routine capping, downsizing, or polysomnography was performed. Thirty-five patients fit the criteria and were decannulated within 24 hours of endoscopy. Successful decannulation served as the primary outcome. Of the 35 decannulated patients, 54% (n = 19) were discharged the day following decannulation and another 37% (n = 13) on postdecannulation day 2. There were no acute failures or readmissions. Average inpatient stay for those decannulated was 1.8 days. This study describes the preliminary observations of a decannulation protocol in a small subset of patients. The protocol resulted in no acute failures and offers a conservative approach to resource utilization, making it unique when compared with other published protocols.


Implementing value-based healthcare using a digital health exchange platform to improve pregnancy and childbirth outcomes in urban and rural Kenya.
Maternal and neonatal mortality rates in many low- and middle-income countries (LMICs) are still far above the targets of the United Nations Sustainable Development Goal 3. Value-based healthcare (VBHC) has the potential to outperform traditional supply-driven approaches in changing this dismal situation, and significantly improve maternal, neonatal and child health (MNCH) outcomes. We developed a theory of change and used a cohort-based implementation approach to create short and long learning cycles along which different components of the VBHC framework were introduced and evaluated in Kenya. At the core of the approach was a value-based care bundle for maternity care, with predefined cost and quality of care using WHO guidelines and adjusted to the risk profile of the pregnancy. The care bundle was implemented using a digital exchange platform that connects pregnant women, clinics and payers. The platform manages financial transactions, enables bi-directional communication with pregnant women via SMS, collects data from clinics and shares enriched information via dashboards with payers and clinics. While the evaluation of health outcomes is ongoing, first results show improved adherence to evidence-based care pathways at a predictable cost per enrolled person. This community case study shows that implementation of the VBHC framework in an LMIC setting is possible for MNCH. The incremental, cohort-based approach enabled iterative learning processes. This can support the restructuring of health systems in low resource settings from an output-driven model to a value based financing-driven model.


Absolute frequency list of the ν3-band transitions of methane at a relative uncertainty level of 10(-11).
We determine the absolute frequencies of 56 rotation-vibration transitions of the ν(3) band of CH(4) from 88.2 to 90.5 THz with a typical uncertainty of 2 kHz corresponding to a relative uncertainty of 2.2 × 10(-11) over an average time of a few hundred seconds. Saturated absorption lines are observed using a difference-frequency-generation source and a cavity-enhanced absorption cell, and the transition frequencies are measured with a fiber-laser-based optical frequency comb referenced to a rubidium atomic clock linked to the international atomic time. The determined value of the P(7) F(2)((2)) line is consistent with the International Committee for Weights and Measures recommendation within the uncertainty.


Evaluating the Quality of Experience Performance Metric for UAV-Based Networks.
In this work, we consider a UAV-assisted cell in a single user scenario. We consider the Quality of Experience (QoE) performance metric calculating it as a function of the packet loss ratio. In order to acquire this metric, a radio-channel emulation system was developed and tested under different conditions. The system consists of two independent blocks, separately emulating connections between the User Equipment (UE) and unmanned aerial vehicle (UAV) and between the UAV and Base station (BS). In order to estimate scenario usage constraints, an analytical model was developed. The results show that, in the described scenario, cell coverage can be enhanced with minimal impact on QoE.


Genome-Wide Association Studies of Seven Root Traits in Soybean (Glycine max L.) Landraces.
Soybean [Glycine max (L.) Merr.], an important oilseed crop, is a low-cost source of protein and oil. In Southeast Asia and Africa, soybeans are widely cultivated for use as traditional food and feed and industrial purposes. Given the ongoing changes in global climate, developing crops that are resistant to climatic extremes and produce viable yields under predicted climatic conditions will be essential in the coming decades. To develop such crops, it will be necessary to gain a thorough understanding of the genetic basis of agronomic and plant root traits. As plant roots generally lie beneath the soil surface, detailed observations and phenotyping throughout plant development present several challenges, and thus the associated traits have tended to be ignored in genomics studies. In this study, we phenotyped 357 soybean landraces at the early vegetative (V2) growth stages and used a 180 K single-nucleotide polymorphism (SNP) soybean array in a genome-wide association study (GWAS) conducted to determine the phenotypic relationships among root traits, elucidate the genetic bases, and identify significant SNPs associated with root trait-controlling genomic regions/loci. A total of 112 significant SNP loci/regions were detected for seven root traits, and we identified 55 putative candidate genes considered to be the most promising. Our findings in this study indicate that a combined approach based on SNP array and GWAS analyses can be applied to unravel the genetic basis of complex root traits in soybean, and may provide an alternative high-resolution marker strategy to traditional bi-parental mapping. In addition, the identified SNPs, candidate genes, and diverse variations in the root traits of soybean landraces will serve as a valuable basis for further application in genetic studies and the breeding of climate-resilient soybeans characterized by improved root traits.


Increased bcl-2/bax ratio in B-cell chronic lymphocytic leukemia is associated with a progressive pattern of disease.
In order to evaluate clinical implications of altered expression of bcl-2 and bax proteins in B-cell chronic lymphocytic leukemia (CLL) we studied 27 patients with this disease. Cytofluorometric levels of bcl-2 did not reflect the status of disease. In contrast bax expression was lower in progressive than in non-progressive disease, therefore leading to a higher bcl-2/bax ratio in patients of the former group. If confirmed in longitudinal studies, quantitative cytofluorometric evaluation of bcl-2 and bax protein might help to identify patients with progressive disease who could possibly benefit from early therapy.