Metabolic pathways in tropical dicotyledonous albuminous seeds: Coffea arabica as a case study.
* The genomic era facilitates the understanding of how transcriptional networks are interconnected to program seed development and filling. However, to date, little information is available regarding dicot seeds with a transient perisperm and a persistent, copious endosperm. Coffea arabica is the subject of increasing genomic research and is a model for nonorthodox albuminous dicot seeds of tropical origin. * The aim of this study was to reconstruct the metabolic pathways involved in the biosynthesis of the main coffee seed storage compounds, namely cell wall polysaccharides, triacylglycerols, sucrose, and chlorogenic acids. For this purpose, we integrated transcriptomic and metabolite analyses, combining real-time RT-PCR performed on 137 selected genes (of which 79 were uncharacterized in Coffea) and metabolite profiling. * Our map-drawing approach derived from model plants enabled us to propose a rationale for the peculiar traits of the coffee endosperm, such as its unusual fatty acid composition, remarkable accumulation of chlorogenic acid and cell wall polysaccharides. * Comparison with the developmental features of exalbuminous seeds described in the literature revealed that the two seed types share important regulatory mechanisms for reserve biosynthesis, independent of the origin and ploidy level of the storage tissue.


Flux of transcript patterns during soybean seed development.
To understand gene expression networks leading to functional properties of the soybean seed, we have undertaken a detailed examination of soybean seed development during the stages of major accumulation of oils, proteins, and starches, as well as the desiccating and mature stages, using microarrays consisting of up to 27,000 soybean cDNAs. A subset of these genes on a highly-repetitive 70-mer oligonucleotide microarray was also used to support the results. It was discovered that genes related to cell growth and maintenance processes, as well as energy processes like photosynthesis, decreased in expression levels as the cotyledons approached the mature, dry stage. Genes involved with some storage proteins had their highest expression levels at the stage of highest fresh weight. However, genes encoding many transcription factors and DNA binding proteins showed higher expression levels in the desiccating and dry seeds than in most of the green stages. Data on 27,000 cDNAs have been obtained over five stages of soybean development, including the stages of major accumulation of agronomically-important products, using two different types of microarrays. Of particular interest are the genes found to peak in expression at the desiccating and dry seed stages, such as those annotated as transcription factors, which may indicate the preparation of pathways that will be needed later in the early stages of imbibition and germination.


A Multi-institutional Study Evaluating Pediatric Burn Injuries During the COVID-19 Pandemic.
During the COVID-19 pandemic, children were out of school due to Stay-at-Home Orders. The objective of this study was to investigate how the COVID-19 pandemic may have impacted the incidence of burn injuries in children. Eight Level I Pediatric Trauma Centers participated in a retrospective study evaluating children <18 years old with traumatic injuries defined by the National Trauma Data Bank. Patients with burn injuries were identified by ICD-10 codes. Historical controls from March to September 2019 ("Control" cohort) were compared to patients injured after the start of the COVID-19 pandemic from March to September 2020 ("COVID" cohort). A total of 12,549 pediatric trauma patients were included, of which 916 patients had burn injuries. Burn injuries increased after the start of the pandemic (COVID 522/6711 [7.8%] vs Control 394/5838 [6.7%], P = .03). There were no significant differences in age, race, insurance status, burn severity, injury severity score, intent or location of injury, and occurrence on a weekday or weekend between cohorts. There was an increase in flame burns (COVID 140/522 [26.8%] vs Control 75/394 [19.0%], P = .01) and a decrease in contact burns (COVID 118/522 [22.6%] vs Control 112/394 [28.4%], P = .05). More patients were transferred from an outside institution (COVID 315/522 patients [60.3%] vs Control 208/394 patients [52.8%], P = .02), and intensive care unit length of stay increased (COVID median 3.5 days [interquartile range 2.0-11.0] vs Control median 3.0 days [interquartile range 1.0-4.0], P = .05). Pediatric burn injuries increased after the start of the COVID-19 pandemic despite Stay-at-Home Orders intended to optimize health and increase public safety.


Family communication matters: the impact of telling relatives about unclassified variants and uninformative DNA-test results.
Unclassified variant and uninformative BRCA1/2 results are not only relevant for probands to whom results are disclosed but also for untested relatives. Previous studies have seldom included relatives and have not explained how their lives were influenced by these results. We explored the family communication timeline of genetic counseling: (1) genetic counselors communicate the relatives' cancer risk, (2) probands perceive this risk and (3) communicate this to relatives; (4) relatives perceive this information, and (5) experience an impact on their lives. We conducted a retrospective descriptive study in 13 probands with an unclassified variant and 5 with an uninformative result, and in, respectively, 27 and 12 of their untested female relatives from moderate cancer risk families. In questionnaires, probands described their perception of the DNA-test result (i.e., recollections and interpretations of cancer risks and heredity likelihood). Relatives described the communication process, their perception, and impact (i.e., medical decisions, distress, quality of life, and life changes). Bootstrap analysis was used to analyze mediation effects. The relatives' own perception strongly predicted breast self-examination, breast/ovarian surveillance or surgery, levels of distress and quality of life, and amount of reported life changes. The extent to which the proband had communicated the DNA-test result in an understandable, direct, reassuring way, predicted the relatives' perception. The actual communicated relatives' cancer risks or the proband's perception did not predict relatives' perception and impact measures. Family characteristics influenced the communication process but not the relatives' perception and outcomes. Relatives seem to make poorly informed decisions on the basis of their own perception, which was unrelated to the information that probands had communicated on the basis of the actual communicated result. Therefore, genetic counselors may guide probands in the communication process and may directly inform relatives, if possible.


[The pharmacokinetic process: is the drug getting to its site of action? Drug absorption].
The pharmacokinetic process is concerned with the absorption, distribution, and elimination (by metabolism and excretion) of drugs. It is evident that drug molecules have to pass many structural and metabolic barriers. The concentration of a drug at its site of action must have the blood concentration as one of its determinants. Only the free form of the drug is susceptible of management by the body Drug bioavailability and the factors that may affect it are influencing the choice of an optimal route of drug administration and the pharmaceutical form as well as bioequivalence between different preparations. There are three kinds of factors that may affect drug bioavailability: drug-related, patient-related and environmental-related factors. A reduction of the speed of absorption is leading to diminished pharmacological after single oral doses of the drug but it is not affecting the steady-state concentration of the drug or drug effects. On the contrary Tmax is not affected by those factors that are reducing the amount of available drug in the body through drug absorption impairment. However, they may cause therapeutic failure due to low steady-state concentration of the drug during long-term treatment.


Inhibition of p53 Mutant Peptide Aggregation In Vitro by Cationic Osmolyte Acetylcholine Chloride.
Mutations of tumor suppressor protein p53 are present in almost about 50% of all cancers. It has been reported that the p53 mutations cause aggregation and subsequent loss of p53 function, leading to cancer progression. Here in this study we focus on the inhibitory effects of cationic osmolyte molecules acetylcholine chloride, and choline on an aggregation prone 10 amino acid p53 mutant peptide WRPILTIITL, and the corresponding wildtype peptide RRPILTIITL in vitro. The characterization tools used for this study include Thioflavin- T (ThT) induced fluorescence, transmission electron microscopy (TEM), congo red binding, turbidity, dynamic light scattering (DLS), and cell viability assays. The results show that acetylcholine chloride in micromolar concentrations significantly inhibit p53 mutant peptide aggregation in vitro, and could be promising candidate for p53 mutant/ misfolded protein aggregation inhibition.


Fertility Preservation for Transgender Individuals: A Review.
Transgender individuals represent a small, albeit growing, patient population that is encountered more frequently in clinical care due to improved insurance coverage and increasing awareness. Gender-affirming treatments, including both gender-affirming hormone therapy and gender-affirming surgery, pose significant risks to fertility potential and outcomes, ranging from potentially impaired fertility rates to full elimination of reproductive potential depending on the type of treatment pursued. However, there are relatively limited data specific to fertility preservation for transgender individuals. Current approaches to treatment are extrapolated from options for fertility preservation after oncologic diagnoses. In this review, we aim to summarize current clinical approaches, fertility preservation options, and patient experiences in fertility preservation for transgender individuals. Several forms of fertility preservation options are available depending on the pubertal status of a transgender individual. Despite the multiple options for fertility preservation, major barriers exist to patient care and there are reports of mixed patient experiences. Further awareness of this clinical situation and understanding of these processes will allow for comprehensive and specialized care for transgender individuals who may otherwise miss opportunities for adequate counseling or treatment options regarding fertility preservation.


History matters more when explaining genetic diversity within the context of the core-periphery hypothesis.
The core-periphery hypothesis (CPH) predicts that populations located at the periphery of a species' range should have lower levels of genetic variation than those at the centre of the range. However, most of the research on the CPH focuses on geographic distance and not on ecological distance, or uses categorical definitions of core and periphery to explain the distribution of genetic diversity. We use current climate data and historical climate data from the last glacial maxima to develop quantitative estimates of contemporary and historical ecological suitability using ecological niche models. We analysed genetic diversity using 12 polymorphic microsatellites to estimate changes in heterozygosity, allelic richness and population differentiation in 31 populations of the wood frog (Lithobates sylvaticus) spanning the species' entire eastern clade (33(o) to 45(o) latitude) from Alabama, USA, to Nova Scotia, Canada. Our data support predictions based on the CPH. Populations showed significant differences in genetic diversity across the range, with lower levels of genetic variation at the geographic range edge and in areas with lower levels of historical and contemporary ecological suitability. However, history and geography (not current ecological suitability) best explain the patterns. This study highlights the importance of examining more than just geography when assessing the CPH, and the importance of historical ecological suitability in the maintenance of genetic diversity and population differentiation.


Q fever.
Q fever is a zoonosis with a worldwide distribution with the exception of New Zealand. The disease is caused by Coxiella burnetii, a strictly intracellular, gram-negative bacterium. Many species of mammals, birds, and ticks are reservoirs of C. burnetii in nature. C. burnetii infection is most often latent in animals, with persistent shedding of bacteria into the environment. However, in females intermittent high-level shedding occurs at the time of parturition, with millions of bacteria being released per gram of placenta. Humans are usually infected by contaminated aerosols from domestic animals, particularly after contact with parturient females and their birth products. Although often asymptomatic, Q fever may manifest in humans as an acute disease (mainly as a self-limited febrile illness, pneumonia, or hepatitis) or as a chronic disease (mainly endocarditis), especially in patients with previous valvulopathy and to a lesser extent in immunocompromised hosts and in pregnant women. Specific diagnosis of Q fever remains based upon serology. Immunoglobulin M (IgM) and IgG antiphase II antibodies are detected 2 to 3 weeks after infection with C. burnetii, whereas the presence of IgG antiphase I C. burnetii antibodies at titers of >/=1:800 by microimmunofluorescence is indicative of chronic Q fever. The tetracyclines are still considered the mainstay of antibiotic therapy of acute Q fever, whereas antibiotic combinations administered over prolonged periods are necessary to prevent relapses in Q fever endocarditis patients. Although the protective role of Q fever vaccination with whole-cell extracts has been established, the population which should be primarily vaccinated remains to be clearly identified. Vaccination should probably be considered in the population at high risk for Q fever endocarditis.


[Salic law and punishment by castration].
Lex Salica was made at the end of the 5th century and it governed the Salian Franks. In those times, there were other so-called leges barbarorum, which together formed (as well as Lex Salica) important source of early feudal law in Western Europe. Lex Salica included common law of the Salian Franks which was adopted by the government and therefore had the effect of the law. Most provisions included punishment by whipping, and there were two cases of punishment by castration, although, the alternative to this punishment was a hefty fine that a slave could never pay. Punishment by castration in Lex Salica was intended only for male slaves (while it was strictly forbidden to punish free people in this way) in two cases: - A slave "had sexual relations" (presumably involuntary) with another master's female slave, if such act caused the death of said female slave. - A slave committed burglary (breaking and entering). The existing legal texts do not provide a clue as to who performed the castration of these slaves.


PSA testing for men at average risk of prostate cancer.
Prostate-specific antigen (PSA) testing of men at normal risk of prostate cancer is one of the most contested issues in cancer screening. There is no formal screening program, but testing is common - arguably a practice that ran ahead of the evidence. Public and professional communication about PSA screening has been highly varied and potentially confusing for practitioners and patients alike. There has been much research and policy activity relating to PSA testing in recent years. Landmark randomised controlled trials have been reported; authorities - including the 2013 Prostate Cancer World Congress, the Prostate Cancer Foundation of Australia, Cancer Council Australia, and the National Health and Medical Research Council - have made or endorsed public statements and/or issued clinical practice guidelines; and the US Preventive Services Task Force is revising its recommendations. But disagreement continues. The contention is partly over what the new evidence means. It is also a result of different valuing and prioritisation of outcomes that are hard to compare: prostate cancer deaths prevented (a small and disputed number); prevention of metastatic disease (somewhat more common); and side-effects of treatment such as incontinence, impotence and bowel trouble (more common again). A sizeable proportion of men diagnosed through PSA testing (somewhere between 20% and 50%) would never have had prostate cancer symptoms sufficient to prompt investigation; many of these men are older, with competing comorbidities. It is a complex picture. Below are four viewpoints from expert participants in the evolving debate, commissioned for this cancer screening themed issue of Public Health Research & Practice. We asked the authors to respond to the challenge of PSA testing of asymptomatic, normal-risk men. They raise important considerations: uncertainty, harms, the trustworthiness and interpretation of the evidence, cost (e.g. of using multiparametric magnetic resonance imaging to triage patients with elevated PSA), a likely bias towards intervention (particularly for cancer), and the potential to limit harm by treating more conservatively (although this may not occur consistently). They provide important insights, and disagree on some issues, but generally concur that men should decide for themselves whether to be tested. It seems reasonable to support men's autonomy to make their own decisions based on their own values. However, the support men might require to decide is likely to be considerable, and this needs to be taken seriously in policy making.


Evolution of the insulin receptor family and receptor isoform expression in vertebrates.
The molecular phylogeny of the vertebrate insulin receptor (IR) family was reconstructed under maximum likelihood (ML) to establish homologous relationships among its members. A sister group relationship between the orphan insulin-related receptor (IRR) and the insulin-like growth factor 1 receptor (IGF1R) to the exclusion of the IR obtained maximal bootstrap support. Although both IR and IGF1R were identified in all vertebrates, IRR could not be found in any teleost fish. The ancestral character states at each position of the receptor molecule were inferred for IR, IRR + IGF1R, and all 3 paralogous groups based on the recovered phylogeny using ML in order to determine those residues that could be important for the specific function of IR. For 18 residues, ancestral character state of IR was significantly distinct (probability >0.95) with respect to the corresponding inferred ancestral character states both of IRR + IGF1R and of all 3 vertebrate paralogs. Most of these IR distinct (shared derived) residues were located on the extracellular portion of the receptor (because this portion is larger and the rate of generation of IR shared derived sites is uniform along the receptor), suggesting that functional diversification during the evolutionary history of the family was largely generated modifying ligand affinity rather than signal transduction at the tyrosine kinase domain. In addition, 2 residues at positions 436 and 1095 of the human IR sequence were identified as radical cluster-specific sites in IRR + IGF1R. Both Ir and Irr have an extra exon (namely exon 11) with respect to Igf1r. We used the molecular phylogeny to infer the evolution of this additional exon. The Irr exon 11 can be traced back to amphibians, whereas we show that presence and alternative splicing of Ir exon 11 seems to be restricted exclusively to mammals. The highly divergent sequence of both exons and the reconstructed phylogeny of the vertebrate IR family strongly indicate that both exons were acquired independently by each paralog.


Genetic relationships and population structure of the endangered Steamboat buckwheat, Eriogonum ovalifolium var. williamsiae (Polygonaceae).
Eriogonum ovalifolium var. williamsiae (Steamboat buckwheat) is a narrow endemic subshrub, known from a single locality in Washoe County, Nevada. We examined genetic structure of the only known population by analyzing patterns of allozyme variation. Our results suggest that Steamboat buckwheat has high genetic variability, with levels of variation similar to that typical of a widespread species rather than a narrow endemic. Genotype frequencies suggest that mating is random. We detected no genetic subdivision of the population. Several clones spanning up to 67 cm were found, but we do not know if such clones are common. We used allozyme data to assess the genetic similarity of var. williamsiae to five other varieties of E. ovalifolium. All six varieties are very similar allozymically with var. williamsiae being the most similar to the widespread var. ovalifolium. Although var. williamsiae and var. ovalifolium are morphologically distinct, their genetic similarity warrants further study to determine whether or not they should be treated as separate taxa. Evidence of male sterility in var. williamsiae plus other data leads us to hypothesize that this taxon might be either a hybrid or undergoing cytoplasmic introgression. Information gathered from this study, in concert with ongoing work on the breeding system of Steamboat buckwheat, should be helpful in forming management strategies for this plant.


Hand infections seen in the industrial clinic.
Following a few basic principles will help the industrial physician in managing hand infections. They are: (1) recognizing the infection early; (2) drainage and/or debridement; (3) identifying the organism; and (4) antibiotics. Following the course of a wound is extremely important. The infected wound that does not respond to surgery and antibiotics may need to be re-explored and cultured again. The wound that heals well without antibiotics or on the wrong antibiotic may be left alone. That is, antibiotics can be withheld or stopped.


Betweenness-Based Method to Identify Critical Transmission Sectors for Supply Chain Environmental Pressure Mitigation.
To develop industry-specific policies for mitigating environmental pressures, previous studies primarily focus on identifying sectors that directly generate large amounts of environmental pressures (a.k.a. production-based method) or indirectly drive large amounts of environmental pressures through supply chains (e.g., consumption-based method). In addition to those sectors as important environmental pressure producers or drivers, there exist sectors that are also important to environmental pressure mitigation as transmission centers. Economy-wide environmental pressure mitigation might be achieved by improving production efficiency of these key transmission sectors, that is, using less upstream inputs to produce unitary output. We develop a betweenness-based method to measure the importance of transmission sectors, borrowing the betweenness concept from network analysis. We quantify the betweenness of sectors by examining supply chain paths extracted from structural path analysis that pass through a particular sector. We take China as an example and find that those critical transmission sectors identified by betweenness-based method are not always identifiable by existing methods. This indicates that betweenness-based method can provide additional insights that cannot be obtained with existing methods on the roles individual sectors play in generating economy-wide environmental pressures. Betweenness-based method proposed here can therefore complement existing methods for guiding sector-level environmental pressure mitigation strategies.


A pediatric food allergy support group can improve parent and physician communication: results of a parent survey.
Rationale. We sought to evaluate the impact of having an allergist at a food allergy support group (FASG) on the relationship between parents and their child's allergist. Methods. Ninety-eight online surveys were sent to parents who attend a FASG affiliated with our institution. Responses were analyzed looking for reasons for attending the support group and comfort with having an allergist present at the meetings. The main objective of this study was to evaluate the impact of having an allergist at the food allergy support group on the relationship between parents and their child's allergist. Results. The FASG decreased anxiety about food allergies for 77.7% of those who responded. Most (71.4%) felt the FASG improved their child's quality of life. Greater than 90% felt comfortable having an allergist at the support group meeting, and 64.3% felt that talking to an allergist at the FASG made it easier to speak with their child's allergist. Conclusions. FASG meetings appear to be a good way for families of children with food allergies to learn more about food allergies, improve quality of life, and increase comfort in communicating with a child's allergist.


National and State Level Opioid-Restricting Legislation in Total Joint Arthroplasty: A Systematic Review.
The opioid epidemic is a health crisis in the United States. Within orthopedic surgery, opioid misuse and incautious prescription remains a concern. In the last several years, there has been a growing interest and public effort toward reducing opioid use in total joint arthroplasty (TJA) in response to the opioid epidemic in the United States. We aim to review opioid-limiting practices, policies, and legislations that are implemented at the state level and nationally that are relevant to TJA, as well as evaluate studies that measure the efficacy of these policies in the management of patients undergoing TJA. Two independent reviewers conducted a systematic review of national and state level opioid-limiting policies implemented in the United States and their effects on opioid prescription, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). We identified 3 national bills and 9 policies set forth by national organizations that imposed limits on opioid prescription. Opioid-reducing legislation was also identified in 24 states, with the majority specifying a 7-day limit on initial opioid prescription for acute pain management. Six research studies evaluating the impact of opioid-restricting policies on postoperative opioid prescription for TJA patients were found. Three studies assessed legislation at the state level while the others were institution-based guidelines. Overall, these studies demonstrated a significant decrease in mean morphine milligram equivalents of initial opioid prescription after implementing the policies. Recent opioid-restricting legislation is effective in decreasing postoperative opioid prescriptions following TJA.


Intra-abdominal hypertension--an experimental study of early effects on intra-abdominal metabolism.
The main aim of this experimental study was to investigate the early effects of intra-abdominal hypertension (IAH) on intra-abdominal metabolism and intestinal mucosal blood flow to evaluate whether metabolites can serve as markers for organ dysfunction during IAH. A swine model was used, and the animals were anesthetized and ventilated. Fifteen animals were subjected to IAH of 30 mm Hg for 4 hr by carbon dioxide insufflation. Seven animals served as controls. Hemodynamic data, arterial blood samples, and urine output were analyzed. Intraluminal laser Doppler flowmetry measured intestinal mucosal blood flow. Glucose, glycerol, lactate, and pyruvate concentrations and lactate-to-pyruvate (l/p) ratio were measured intraperitoneally and intramurally in the small intestine and rectum using microdialysis. IAH lowered the abdominal perfusion pressure by 12-18 mm Hg, reduced the intestinal mucosal blood flow by 45-63%, and decreased urine output by 50-80%. In the intervention group, glycerol concentrations increased at all locations, pyruvate concentrations decreased, and the l/p ratio increased intraperitoneally and intramurally in the small intestine. Control animals remained metabolically stable. Glucose and lactate concentrations were only slightly affected or unchanged in both the groups. IAH reduces intestinal blood flow and urinary output and causes early metabolic changes, indicating a discrete shift toward anaerobic metabolism. Intraperitoneal microdialysis may be useful in the early detection of impaired organ dysfunction with metabolic consequences in IAH and abdominal compartment syndrome.


Poly-vinyl-alcohol (PVA) coating of cochlear implant electrode arrays: an in-vivo biosafety study.
The tissue response and biosafety of poly-vinyl-alcohol (PVA) has been investigated to explore its potential use as an agent to straighten pre-curved cochlear implant electrode arrays for surgical insertion. Test arrays were implanted either subcutaneously or into the cochlea of guinea pigs for 3 months. The arrays were uncoated (Treatment 1) or coated with low molecular weight (MW) PVA (Treatment 2), high MW PVA (Treatment 3) or a 50:50 mixture of low and high MW PVA (Treatment 4). After explantation the tissues were examined histologically. In both study groups, Treatment 2 dissolved completely and induced the least tissue reaction, while Treatments 3 and 4 not only dissolved incompletely, but also induced more fibrous tissue growth. Treatment 4 coated arrays induced severe insertion trauma in all the cochleas, most likely due to the thickness of the coat and the resulting rigidity of the array. Spiral ganglion cell density (SGCD) in the basal turn of the scala tympani was reduced for both Treatments 2 and 4. While the reduction in SGCD in the Treatment 4 group is likely to be a result of the insertion trauma caused and the subsequent loss of peripheral dendrites, it is unknown what caused the reduction of SGCD in the Treatment 2 group. Prior to the specific use of PVA as electrode array coating material, the ideal composition and its biosafety needs to be reassessed.


Circumferential Stabilization of the Thoracolumbar Junction Via Posterior-Only Approach for the Management of Burst Fractures.
The management of thoracolumbar burst fractures often includes combined anterior/posterior approaches with prolonged operative time and complications. The transpedicular approach offers a posterior only approach with circumferential reconstruction and decompression. We aim to present the experience of a single center in the management of thoracolumbar burst fractures using a posterior-only approach for circumferential stabilization and report on this technique's effectiveness in restoring the alignment of the thoracolumbar junction. A case review of the medical records of patients admitted to the adult neurosurgery service (from January 2011 through June 2014) with traumatic non-pathological thoracolumbar burst fractures and subsequently treated with a transpedicular corpectomy (including the placement of an expandable cage) was performed, retrospectively. A total of 20 patients underwent a posterior transpedicular corpectomy consisting of anterior column reconstruction using an expandable cage with supplementary posterior fixation within 72 hours of injury. The average pre-operative canal compromise was 69%. The average pre-operative kyphotic angle was 21.6°. The average post-operative kyphotic angle was 5.15°, with an average correction of 16.45°. There were 11 patients with pre-operative neurological compromises, of which patients, 8 experienced variable degrees of recovery. The average operating time was 410.5 minutes (range, 240-550 min). The average blood loss was 880 mL (range, 650-1500). Three patients experienced complications during surgery; 1 patient died. The transpedicular approach for circumferential reconstruction and stabilization provides an alternative technique for the management of thoracolumbar fractures, having an acceptable risk and the associated lower morbidity of a posterioronly approach.


Potential bacterial core species associated with digital dermatitis in cattle herds identified by molecular profiling of interdigital skin samples.
Although treponemes are consistently identified in tissue from bovine digital dermatitis (DD) lesions, the definitive etiology of this debilitating polymicrobial disease is still unresolved. To study the microbiomes of 27 DD-infected and 10 healthy interdigital skin samples, we used a combination of different molecular methods. Deep sequencing of the 16S rRNA gene variable regions V1-V2 showed that Treponema, Mycoplasma, Fusobacterium and Porphyromonas were the genera best differentiating the DD samples from the controls. Additional deep sequencing analysis of the most abundant genus, Treponema, targeting another variable region of the 16S rRNA gene, V3-V4, identified 15 different phylotypes, among which Treponema phagedenis-like and Treponema refringens-like species were the most abundant. Although the presence of Treponema spp., Fusobacterium necrophorum and Porphyromonas levii was confirmed by fluorescence in situ hybridization (FISH), the results for Mycoplasma spp. were inconclusive. Extensive treponemal epidermal infiltration, constituting more than 90% of the total bacterial population, was observed in 24 of the 27 DD samples. F. necrophorum and P. levii were superficially located in the epidermal lesions and were present in only a subset of samples. RT-qPCR analysis showed that treponemes were also actively expressing a panel of virulence factors at the site of infection. Our results further support the hypothesis that species belonging to the genus Treponema are major pathogens of DD and also provide sufficient clues to motivate additional research into the role of M. fermentans, F. necrophorum and P. levii in the etiology of DD.


New perspectives on analysing data from biological collections based on social network analytics.
Biological collections have been historically regarded as fundamental sources of scientific information on biodiversity. They are commonly associated with a variety of biases, which must be characterized and mitigated before data can be consumed. In this work, we are motivated by taxonomic and collector biases, which can be understood as the effect of particular recording preferences of key collectors on shaping the overall taxonomic composition of biological collections they contribute to. In this context, we propose two network models as the first steps towards a network-based conceptual framework for understanding the formation of biological collections as a result of the composition of collectors' interests and activities. Building upon the defined network models, we present a case study in which we use our models to explore the community of collectors and the taxonomic composition of the University of Brasília herbarium. We describe topological features of the networks and point out some of the most relevant collectors in the biological collection as well as their taxonomic groups of interest. We also investigate their collaborative behaviour while recording specimens. Finally, we discuss future perspectives for incorporating temporal and geographical dimensions to the models. Moreover, we indicate some possible investigation directions that could benefit from our approach based on social network analytics to model and analyse biological collections.


Effect of replacing ground corn and soybean meal with licuri cake on the performance, digestibility, nitrogen metabolism and ingestive behavior in lactating dairy cows.
Licuri (Syagrus coronate) cake is a biodiesel by-product used in ruminant feed as a beneficial energy source for supplementation in managed pastures. The objective was to evaluate the performance, digestibility, nitrogen balance, blood metabolites, ingestive behavior and diet profitability of eight crossbred Holstein (3/4)×Gyr (5/8) multiparous cows (480±25 kg BW and 100 days milking) grazing and supplemented with licuri cake partially replacing ground corn and soybean meal in concentrate (0, 200, 400 and 600 g/kg in dry matter (DM)), distributed in an experimental duplicated 4×4 Latin square design. Licuri cake partially replacing ground corn and soybean meal increased (P<0.01) the intake and digestibility of ether extract and decreased the non-fiber carbohydrates; however, there were no influences on the intakes of DM, CP, NDF and total digestible nutrients (TDN). The digestibilities of DM, CP and NDF were not influenced by licuri cake addition. There was a decrease trend on TDN digestibility (P=0.08). Licuri cake replacing ground corn and soybean meal in concentrate did not affect the intake; fecal, urinary and mammary excretions; N balance; and triglycerides concentrations. However, the blood urea nitrogen (P=0.04) concentration decreased with the licuri cakes inclusion in cow supplementation. There was an increasing trend for serum creatinine (P=0.07). Licuri cake inclusion did not affect body condition score, production, yield, protein, lactose, total solids and solid non-fat contents of milk and Minas frescal cheese. There was a linear decrease in average daily weight gain (g/day). The milk fat concentration and cheese fat production (P<0.1) presented a linear increase with partial replacement of ground corn and soybean meal with licuri cakes. The addition of licuri cake did not alter the time spent feeding, ruminating or idling. There was an increasing trend in NDF feeding efficiency (P=0.09). The replacing of ground corn and soybean meal with licuri cake up to 600 g/kg decreased the concentrate cost by US$0.45/cow per day. Licuri cake replacing corn and soybeans (400 g/kg) in concentrate promoted a profit of US$0.07/animal per day. Licuri cake is indicated to concentrate the supplementation of dairy cows with average productions of 10 kg/day at levels up to 400 g/kg in the concentrate supplement because it provides an additional profit of US$0.07/animal per day and increased milk and Minas frescal cheese fat without negative effects on productive parameters.


Sleep quality perception in the chronic fatigue syndrome: correlations with sleep efficiency, affective symptoms and intensity of fatigue.
One of the core symptoms of the chronic fatigue syndrome (CFS) is unrefreshing sleep and a subjective sensation of poor sleep quality. Whether this perception can be expressed, in a standardized questionnaire as the Pittsburgh Sleep Quality Index (PSQI), has to our knowledge never been documented in CFS. Furthermore, correlations of subjective fatigue, PSQI, affective symptoms and objective parameters such as sleep efficiency are poorly described in the literature. Using a cross-sectional paradigm, we studied subjective measures like PSQI, Fatigue Severity Scale scores and intensity of affective symptoms rated by the Hamilton Depression and Anxiety scales as well as objective sleep quality parameters measured by polysomnography of 28 'pure' (no primary sleep and no psychiatric disorders) CFS patients compared to age- and gender-matched healthy controls. The PSQI showed significantly poorer subjective sleep quality in CFS patients than in healthy controls. In contrast, objective sleep quality parameters, like the Sleep Efficiency Index (SEI) or the amount of slow-wave sleep did not differ significantly. Subjective sleep quality showed a correlation trend with severity of fatigue and was not correlated with the intensity of affective symptoms in CFS. Our findings indicate that a sleep quality misperception exists in CFS or that potential nocturnal neurophysiological disturbances involved in the nonrecovering sensation in CFS are not expressed by sleep variables such as the SEI or sleep stage distributions and proportions.


A virtual reality system to analyze neural activity and behavior in adult zebrafish.
Virtual realities are powerful tools to analyze and manipulate interactions between animals and their environment and to enable measurements of neuronal activity during behavior. In many species, however, optical access to the brain and/or the behavioral repertoire are limited. We developed a high-resolution virtual reality for head-restrained adult zebrafish, which exhibit cognitive behaviors not shown by larvae. We noninvasively measured activity throughout the dorsal telencephalon by multiphoton calcium imaging. Fish in the virtual reality showed regular swimming patterns and were attracted to animations of conspecifics. Manipulations of visuo-motor feedback revealed neurons that responded selectively to the mismatch between the expected and the actual visual consequences of motor output. Such error signals were prominent in multiple telencephalic areas, consistent with models of predictive processing. A virtual reality system for adult zebrafish therefore provides opportunities to analyze neuronal processing mechanisms underlying higher brain functions including decision making, associative learning, and social interactions.


Synthesis and application of dipeptides; current status and perspectives.
The functions and applications of L-alpha-dipeptides (dipeptides) have been poorly studied compared with proteins or amino acids. Only a few dipeptides, such as aspartame (L-aspartyl-L-phenylalanine methyl ester) and L-alanyl-L-glutamine (Ala-Gln), are commercially used. This can be attributed to the lack of an efficient process for dipeptide production though various chemical or chemoenzymatic method have been reported. Recently, however, novel methods have arisen for dipeptide synthesis including a nonribosomal peptide-synthetase-based method and an L-amino acid alpha-ligase-based method, both of which enable dipeptides to be produced through fermentative processes. Since it has been revealed that some dipeptides have unique physiological functions, the progress in production methods will undoubtedly accelerate the applications of dipeptides in many fields. In this review, the functions and applications of dipeptides, mainly in commercial use, and methods for dipeptide production including already proven processes as well as newly developed ones are summarized. As aspartame and Ala-Gln are produced using different industrial processes, the manufacturing processes of these two dipeptides are compared to clarify the characteristics of each procedure.


Integrated 18F-fluorodeoxyglucose positron emission tomography and computerized tomography in endodermal sinus tumor.
Application of an in-line positron emission tomography and computerized tomography (PET-CT) in endodermal sinus tumor (EST) is described in this study. CASE 1: A young female with massive ascites postovarian mass resection had elevated alpha-fetoprotein (AFP) serum levels. Following a positive PET-CT study with increased (18)F-fluorodeoxyglucose (FDG) uptake, a CT-guided core biopsy of a peritoneal mass was performed. EST was diagnosed histologically. The patient was disease free after chemotherapy. Follow-up PET-CT was negative in keeping with no viable tumor tissue. CASE 2: A large pelvic mass diagnosed histologically as primarily EST was removed in a teenage patient with elevated AFP levels. PET-CT showed diffuse abdominal spread of FDG uptake, suggesting extensive peritoneal seeding. The patient was disease free after chemotherapy. Follow-up PET-CT was negative. EST is an FDG-avid tumor. PET-CT delineated the prechemotherapy tumor extent adequately ruled out the presence of residual tumor after a successful treatment.


Long-term study of disodium cromoglycate in treatment of severe extrinsic or intrinsic bronchial asthma in adults. Brompton Hospital-Medical Research Council collaborative trial.
The results are reported here of a long-term double-blind controlled clinical trial of disodium cromoglycate (D.S.C.G.) and isoprenaline, D.S.C.G. alone, isoprenaline alone, and a placebo given as a powder for inhalation in the treatment of severe bronchial asthma.At the end of one year 16 out of 20 patients on D.S.C.G.-isoprenaline remained on the allocated capsules, compared with 10 out of 15 on D.S.C.G., 5 out of 20 on isoprenaline, and 3 out of 19 taking the placebo. The differences between each of the D.S.C.G.-isoprenaline and D.S.C.G. regimens compared with the isoprenaline and placebo regimens were statistically significant. After eight weeks on four capsules a day the patients in each group were allocated at random so that half continued on full dosage and half on a reducing regimen. At the end of the year there was no significant difference in the failure rate between patients allocated the full dosage and the patients on the reducing dosage. The capsules were well tolerated and toxicity to D.S.C.G. was not observed.


First anal intercourse and condom use among men who have sex with men in Switzerland.
The aim of this study was to analyze the circumstances of first anal intercourse (FAI) among men who have sex with men (MSM) and to identify factors associated with condom use at this event. We conducted a cross-sectional survey among a convenience sample of MSM living in Switzerland (N = 2,200). Anonymous questionnaires were distributed using Swiss gay communication channels (newspapers, associations, websites) and gay bathhouses. We gathered data on age at FAI, age of the partner, degree of familiarity with him, place of first meeting, and sociodemographic indicators. We did not ask whether FAI was insertive, receptive, or both. Data were stratified by birth year classes (birth cohorts). The median age at FAI fell from 24.5 years among men born before 1965 to 20.0 years among those born between 1975 and 1984 (p < .001). In each birth cohort, between 20 and 30% reported a partner 10 years older or more. Of eight variables examined in multivariate analysis, two were positively associated with condom use: age of participants at FAI and low degree of familiarity between partners. Conversely, large age discrepancy between partners was negatively associated with condom use. In conclusion, our data showed that early initiation of anal intercourse and large age discrepancy were associated with risk taking: a pattern of initiation that may facilitate HIV transmission from older to younger cohorts of MSM. Since age at FAI is on the decrease, there is an urgent need to heighten awareness of prevention actions regarding sexual debut of MSM.


Cardiovascular effects of medications for the treatment of attention-deficit hyperactivity disorder: what is known and how should it influence prescribing in children?
The effective medications currently marketed for attention-deficit hyperactivity disorder (ADHD) have central and peripheral catecholaminergic effects that have been shown to result in statistically significant increases in heart rate and blood pressure. The impact of these medications on serious cardiovascular events in healthy children is unknown, but serious cardiovascular events related to ADHD medications are considered rare. However, children with cardiac pathology may be at greater risk given that increased sympathetic tone has been reported as a causal factor in generating ventricular arrhythmias in adults with coronary artery disease, and physical exercise has been consistently reported as a trigger for increased risk of sudden cardiac death in athletes with underlying cardiovascular disease. ADHD has high co-morbidity with anxiety and depression. These conditions in adults have been reported to have their own cardiovascular risks that may be compounded by interactions resulting from combined pharmacotherapeutic treatments; this interaction has not been evaluated in children. High rates of ADHD reported in subjects with cardiac pathology, as well as in patients with genetic disorders associated with cardiovascular pathology, also suggest that the prevalence of cardiac pathology in ADHD subjects may be greater than that in the general population. Currently, the US FDA and Health Canada require warnings on prescription labeling information for ADHD medications, suggesting that these medications should not generally be used in children or adults with 'known' serious cardiac pathology. Family history, medical history, and physical examination have very low sensitivity for identifying serious cardiac pathology, but this can be markedly enhanced in many instances with the use of electrocardiography, which has high specificity and sensitivity. Identifying and managing underlying cardiovascular pathology may not eliminate the risk of serious cardiovascular events but may increase the safety of using medication frequently required for effective management of ADHD. When the very common and serious consequences from untreated ADHD are also considered in the assessment of risks and benefits, even in the presence of cardiac pathology, it seems that the prescribing of ADHD medications in children should remain unchanged.


Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells.
The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their function is unknown. We have determined that these fingers mediate homodimerization and binding of MLL to Cyp33, a nuclear cyclophilin. These two proteins interact in vitro and in vivo in mammalian cells and colocalize at specific nuclear subdomains. Overexpression of the Cyp33 protein in leukemia cells results in altered expression of HOX genes that are targets for regulation by MLL. These alterations are suppressed by cyclosporine and are not observed in cell lines that express a mutant MLL protein without PHD fingers. These results suggest that binding of Cyp33 to MLL modulates its effects on the expression of target genes.


Compositional and structural engineering of DNA multilayer films.
We report the layer-by-layer (LbL) preparation of multilayered thin films that consist solely of DNA. The properties of the films were varied by assembling the layers from different oligonucleotide building blocks, which are composed of repeating homopolymeric units of nucleotides [adenosine (A), cytosine (C), guanine (G), and thymidine (T)] or "random" sequences. Films assembled from oligonucleotides with a single complementary unit did not show continual layer buildup. To form a repeating multilayer system, it was necessary for single-stranded DNA to be available for subsequent layers to hybridize. By using oligonucleotides with multiple nucleotide units, multilayer films were successfully assembled. We demonstrate that the thickness and swellability of the films can be controlled by the extent of hydrogen bonding (the G/C content of the oligonucleotide) and orientation of the oligomers. We have examined the stability and swellability of the films in solutions of varying salt concentration as well as in a denaturing urea solution. Stable, hollow DNA capsules were also formed by preparing the films on sacrificial colloidal templates, followed by removal of the core. The assembly of propagating structures through DNA hybridization paves the way for the engineering of DNA films with tailored composition, structure, and permeability, making them likely to find application in drug/gene delivery and biomolecular sensing.


Shock-wave compression and x-ray studies of titanium dioxide.
The Hugoniot of the rutile phase of titanium dioxide has been determined to 1.25 megabars, and data show the existence of a phase change at about 0.33 megabar. The volume decrease associated with this transformation appears to be quite large (approximately 21 percent). Rutile, when recovered from shockloading in excess of the transformation pressure, is found to be irreversibly transformed to the orthorhombic lead dioxide structure (a distortion of the fluorite structure) with parameters a, 4.529; b, 5.464; and c, 4.905 angstroms and a calculated density of 4.374 grams per cubic centimeter. The new phase reverts to rutile at temperatures above 450 degrees C. It is suggested that the new phase may be another diagnostic indicator of meteorite impact on the earth's surface.


Probing the epigenetic regulation of HIF-1α transcription in developing tissue.
HIF-1 is the master regulator of cellular hypoxia response; the oxygen sensitive HIF-1α subunit transactivates its own expression in hypoxia via a hypoxia response element (HRE) in the promoter of the HIF-1α gene. This transactivation loop significantly contributes to the build up of HIF-1α at the onset of hypoxia, with the binding of HIF-1 to the HIF-1α promoter being dependent on the epigenetic status of a CpG dinucleotide in the upstream HRE. Given the central role played by HIF-1 in tissue development, we sought to probe the epigenetic status of the HIF-1α HRE and that of its downstream target EPO in embryonic tissue. Our data shows that the CpG dinucleotide in HIF-1α HRE is unmethylated in several embryonic tissue samples, suggesting that transactivation of HIF-1α plays a significant role in HIF-1 mediated hypoxia response during development.


An in-depth investigation of molecular interaction in zeaxanthin/corn silk glycan complexes and its positive role in hypoglycemic activity.
Glycans in corn silk could interact with co-existing small molecules during its absorption, digestion, and biological process. In order to understand the exact mechanism of action of zeaxanthin, it is critical to investigate the biomolecular interactions, which were necessary to form a glycan-small molecule complex and yet produce the bioactive effect. So far, the in-depth study of these natural interactions has not been fully elucidated. Here, we probed that the molecular interaction between zeaxanthin (ZEA) and glycans from corn silk (CSGs) was driven by enthalpy. More importantly, it was the first time found that CSGs can bind to lipid-soluble ZEA could be binded with CSGs. It was the first report on the thermostability of insulin structure and natural glycans. This study should facilitate our understanding of the interaction between lipid soluble molecules and glycans, and provide a more comprehensive understanding of the nutrient base in food.


Analysis of chlorinated insecticides and congeners.
A review on the state-of-the-art for analysis of chlorinated insecticides and their congeners is presented. Tables are included that show comparisons among gas chromatographic systems, high speed liquid chromatographic systems and sample preparation methods as well as an overview on sample cleanup.


[The formation of a small intestine-large intestine anastomosis: the end to the side method].
The longitudinal ileotransversostomy forming method according to which the ileum is divided at an angle of 45 degrees to the mesentery edge, forming a single layer anastomosis end to the side at an angle of 45 degrees in isoperistaltic mode, was elaborated. Clinico-experimental investigations were conducted on 45 mongrel dogs. Method was applied in 6 patients with malignant tumor of caecum and colon ascendens.


Psychiatric severity and mortality in substance abusers: a 15-year follow-up of drug users.
Previous research has shown that most transitions into abstinence happens in the stages of the drug career quickly after the first treatment episode. Mortality is somewhat reduced for patients who become abstinent, but remains high for patients who remain addicted. However, even among substance abusers who become abstinent, mortality is often higher than in the general population. A consecutive sample of drug users admitted for detoxification was followed for 15 years. Face-to-face interviews were conducted at 5-year follow-up. At 15-year follow-up, 24% were dead. Cox proportional hazard regression was conducted to predict mortality for continuous variables, and Gehan's Wilcoxon test was used to predict mortality for dichotomous variables. Psychiatric status at 5-year follow-up was predictive of 15-year mortality, whereas abstinence was not. Subjects who later died had higher scores on the Symptom Checklist 90 [SCL-90] Global Severity Index, lower meaningfulness on the Sense of Coherence scale, and lower Global Assessment of Functioning [GAF] scores at 5-year follow-up. By contrast, there were no associations between baseline drug use and antisocial personality disorder diagnoses and mortality. Psychiatric treatment, including psychotherapy, may be more life-saving for substance abusers than drug-abuse services.


Will an unsupervised self-testing strategy for HIV work in health care workers of South Africa? A cross sectional pilot feasibility study.
In South Africa, stigma, discrimination, social visibility and fear of loss of confidentiality impede health facility-based HIV testing. With 50% of adults having ever tested for HIV in their lifetime, private, alternative testing options are urgently needed. Non-invasive, oral self-tests offer a potential for a confidential, unsupervised HIV self-testing option, but global data are limited. A pilot cross-sectional study was conducted from January to June 2012 in health care workers based at the University of Cape Town, South Africa. An innovative, unsupervised, self-testing strategy was evaluated for feasibility; defined as completion of self-testing process (i.e., self test conduct, interpretation and linkage). An oral point-of-care HIV test, an Internet and paper-based self-test HIV applications, and mobile phones were synergized to create an unsupervised strategy. Self-tests were additionally confirmed with rapid tests on site and laboratory tests. Of 270 health care workers (18 years and above, of unknown HIV status approached), 251 consented for participation. Overall, about 91% participants rated a positive experience with the strategy. Of 251 participants, 126 evaluated the Internet and 125 the paper-based application successfully; completion rate of 99.2%. All sero-positives were linked to treatment (completion rate:100% (95% CI, 66.0-100). About half of sero-negatives were offered counselling on mobile phones; completion rate: 44.6% (95% CI, 38.0-51.0). A majority of participants (78.1%) were females, aged 18-24 years (61.4%). Nine participants were found sero-positive after confirmatory tests (prevalence 3.6% 95% CI, 1.8-6.9). Six of nine positive self-tests were accurately interpreted; sensitivity: 66.7% (95% CI, 30.9-91.0); specificity:100% (95% CI, 98.1-100). Our unsupervised self-testing strategy was feasible to operationalize in health care workers in South Africa. Linkages were successfully operationalized with mobile phones in all sero-positives and about half of the sero-negatives sought post-test counselling. Controlled trials and implementation research studies are needed before a scale-up is considered.


Solvent-surface interactions control the phase structure in laser-generated iron-gold core-shell nanoparticles.
This work highlights a strategy for the one-step synthesis of FeAu nanoparticles by the pulsed laser ablation of alloy targets in the presence of different solvents. This method allows particle generation without the use of additional chemicals; hence, solvent-metal interactions could be studied without cross effects from organic surface ligands. A detailed analysis of generated particles via transmission electron microscopy in combination with EDX elemental mapping could conclusively verify that the nature of the used solvent governs the internal phase structure of the formed nanoparticles. In the presence of acetone or methyl methacrylate, a gold shell covering a non-oxidized iron core was formed, whereas in aqueous media, an Au core with an Fe3O4 shell was generated. This core-shell morphology was the predominant species found in >90% of the examined nanoparticles. These findings indicate that fundamental chemical interactions between the nanoparticle surface and the solvent significantly contribute to phase segregation and elemental distribution in FeAu nanoparticles. A consecutive analysis of resulting Fe@Au core-shell nanoparticles revealed outstanding oxidation resistance and fair magnetic and optical properties. In particular, the combination of these features with high stability magnetism and plasmonics may create new opportunities for this hybrid material in imaging applications.


Interventions for primary vesicoureteric reflux.
Vesicoureteric reflux (VUR) results in urine passing, in a retrograde manner, up the ureter. Urinary tract infections (UTIs) have been considered the main cause of permanent renal parenchymal damage in children with reflux. Management of these children has been directed at preventing infection by antibiotic prophylaxis and/or surgical correction of reflux. Controversy remains as to the optimum strategies. To evaluate the benefits and harms of different treatment options for primary VUR. Randomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings. Date of last search: June 2006 Any treatment of VUR including surgery, antibiotic prophylaxis of any duration, non-invasive techniques and any combination of therapies. Two authors independently searched the literature, determined study eligibility, assessed quality, extracted and entered data. For dichotomous outcomes, results were expressed as relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. Eleven studies (1148 children) were identified. Seven compared correction of VUR (by surgery or endoscope) plus antibiotics for 1-24 months with antibiotics alone, two compared antibiotics with no treatment and two compared different materials for endoscopic correction of VUR. Risk of UTI by 2, 5 and 10 years was not significantly different between surgical and medical groups (2 years RR 1.07, 95% CI 0.32 to 2.09; 5 years RR 0.99, 95% CI 0.79 to 1.26; 10 years RR 1.06, 95% CI 0.78 to 1.44). Combined treatment resulted in a 50% reduction in febrile UTI by 10 years (RR 0.54, 95% CI 0.55 to 0.92) but no concomitant reduction in risk of new or progressive renal damage by 10 years (RR 1.03, 95% CI 0.53 to 2.00). In two small studies no significant differences in risk for UTI (RR 0.75, 95% CI 0.15 to 3.84) or renal damage (RR 1.70, 95% CI 0.36 to 8.07) were found between antibiotic prophylaxis and no treatment. It is uncertain whether the treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine reimplantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.


Growth stage signal transduction and the requirements for srfA induction in development of competence.
srfA is an operon needed for the development of genetic competence in Bacillus subtilis. This operon is normally expressed at a low level during growth, and its transcription increases sharply just before the transition to stationary phase. The genetic requirements for the full expression of srfA were previously examined in several laboratories and shown to include spo0A, spo0H, spo0K, comQ, and comA. In the present study these results were confirmed with an isogenic set of strains. We have also shown that comP is needed for srfA expression but that other regulatory genes required for competence (degU, sin, and abrB) are not needed for the expression of srfA. We have used the expression of srfA under control of the regulatable Pspac promoter to study the kinetics of competence development and to determine whether the genes ordinarily required for expression of srfA are needed for any additional roles during the development of competence. When expression of srfA was driven from Pspac, competence was expressed constitutively throughout growth. Furthermore, when srfA was expressed from Pspac, the spo0K, comQ, comP, and comA determinants were no longer required for the expression of competence. We conclude therefore that the multiple signals which trigger the initiation of competence development in relation to growth stage are ordinarily received prior to the increase in srfA expression. We propose that these signals are mediated by the products of spo0K, comQ, comP, and comA, resulting in the phosphorylation of ComA by ComP. This in turn would enable ComA to function as a positive transcription factor for srfA, leading to the elaboration of the srfA product(s) and the consequent initiation of competence. We also propose that this is the major, and possibly the only, role for the spo0K, comQ, comP, and comA products during competence development.


Sigmoid perforation in patients with chronic constipation.
From 1976 to 1982, seven cases of free perforation of the sigmoid colon were treated at the Soroka University Hospital. None of the patients suffered any known underlying disease of the affected bowel such as malignancy, diverticulosis, stercoral ulcer, colitis, or trauma. The only feature common to all seven patients was a long history of chronic constipation. All patients were treated surgically with no mortality and with minimal morbidity. We believe that severe untreated chronic constipation may, on rare occasions, cause free perforation of the sigmoid colon.


Recent trends in cyclist fatalities in Australia.
The study examines trends in bicycling fatalities reported to the Australian police between 1991 and 2013. Trends were estimated using Poisson regression modelling. Overall, cycling fatalities decreased by 1.9% annually between 1991 and 2013. However, while deaths following multivehicle crashes decreased at a rate of 2.9% per annum (95% CI -4.0% to -1.8%), deaths from single vehicle crashes increased by 5.8% per annum (95% CI 4.1% to 7.5%). Over the study period, the average age of cyclists who died in single vehicle crashes (45.3 years, 95% CI 41.5 to 49.1) was significantly higher than cyclists who died in multivehicle crashes (36.2 years, 95% CI 34.7 to 37.7). The average age of deceased cyclists increased significantly for both types of crashes. The observed increase in single vehicle crashes need to be closely monitored in Australia and internationally. In-depth studies are needed to investigate the circumstances of fatal single bicycle crashes in order to develop appropriate countermeasures.


Eyelid Retraction in Isolated Unilateral Congenital Blepharoptosis.
Isolated unilateral congenital ptosis is encountered relatively infrequently in clinical practice. It typically consists of a unilateral droopy eyelid, weak levator palpebrae superioris muscle function, lid lag, and an absent upper lid crease with no other abnormalities on examination. We present a four-and-a-half-year-old girl with isolated and mild unilateral congenital ptosis who unexpectedly demonstrated a static upper eyelid on downgaze in conjunction with a well-formed upper lid skin crease. We attribute this uncommon sign in congenital ptosis to stiffness and presumed fibrosis of the levator muscle. Examining the function of the eyelids in all directions of gaze is important in patients with abnormalities of lid position, since additional useful information can be gleaned about the status of the levator muscle including, aberrant regeneration or fibrosis.


Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A.
Adipose triglyceride lipase (ATGL) is required for efficient mobilization of triglyceride (TG) stores in adipose tissue and non-adipose tissues. Therefore, ATGL strongly determines the availability of fatty acids for metabolic reactions. ATGL activity is regulated by a complex network of lipolytic and anti-lipolytic hormones. These signals control enzyme expression and the interaction of ATGL with the regulatory proteins CGI-58 and G0S2. Up to date, it was unknown whether ATGL activity is also controlled by lipid intermediates generated during lipolysis. Here we show that ATGL activity is inhibited by long-chain acyl-CoAs in a non-competitive manner, similar as previously shown for hormone-sensitive lipase (HSL), the rate-limiting enzyme for diglyceride breakdown in adipose tissue. ATGL activity is only marginally inhibited by medium-chain acyl-CoAs, diglycerides, monoglycerides, and free fatty acids. Immunoprecipitation assays revealed that acyl-CoAs do not disrupt the protein-protein interaction of ATGL and its co-activator CGI-58. Furthermore, inhibition of ATGL is independent of the presence of CGI-58 and occurs directly at the N-terminal patatin-like phospholipase domain of the enzyme. In conclusion, our results suggest that inhibition of the major lipolytic enzymes ATGL and HSL by long-chain acyl-CoAs could represent an effective feedback mechanism controlling lipolysis and protecting cells from lipotoxic concentrations of fatty acids and fatty acid-derived lipid metabolites.


Reengineering respiratory support following extubation: avoidance of critical care unit costs.
We prospectively investigated alternative clinical practice strategies for critically ill trauma patients following extubation to evaluate the cost-effectiveness of these maneuvers. The primary change was elimination of the routine use of postextubation supplemental oxygen, with concurrent utilization of noninvasive positive pressure ventilatory support (NPPV) to manage occurrences of postextubation hypoxemia. Prospective, consecutive accrual of patients undergoing extubation. Trauma ICU in a university hospital. All patients received mechanical ventilation using pressure support ventilation (PSV) with continuous positive airway pressure (CPAP) as the primary mode. The patients were extubated to room air following a 20-min preextubation trial of 5 cm H(2)O CPAP at FIO(2) of 0.21, and demonstrating a spontaneous respiratory rate </= 38 breaths/min, pH >/= 7.30, PaCO(2) </= 50 mm Hg, and PaO(2) >/= 50 mm Hg. The subgroup of patients who became hypoxemic (pulse oximetric saturation < 88%) within 24 h of extubation were treated with NPPV for up to 48 h duration. Patients who failed NPPV were reintubated. Four hundred fifty-one (84%) patients were successfully extubated to room air. Seventy-two patients (13%) became hypoxemic within 24 h, and NPPV was administered. Fifty-two patients (72% of those who were hypoxemic) responded to NPPV, while 20 patients failed to respond to therapy, were reintubated, and received mechanical ventilation for a mean of 4 days. Thirteen additional patients (2%) were reintubated for reasons other than hypoxemia. The overall reintubation rate for the group (n = 536) was 6.2%; for the postextubation hypoxemic group who failed NPPV, the reintubation rate was 3.7%. The elimination of routine supplemental oxygen via nasal cannula following extubation resulted in a potential direct cost avoidance of $50,006.88 for 451 patient days. Moreover, the 52 patients who were spared reintubation and mechanical ventilation provided an additional potential cost avoidance of $19,740.24 in unused ventilator days per patient. Eliminating the routine use of supplemental oxygen and employing NPPV as a method to prevent reintubation can facilitate a more aggressive, cost-effective strategy for the management of the trauma ICU patient who has been extubated.


Visceral Varicella-Zoster Virus Infection in An Immunocompromised Patient: Uncommon Endoscopic Differential Diagnosis.
Varicella-Zoster virus (VZV) infection is well-known for its dermatological appearances, such as chickenpox and shingles. In addition to its dermal disease, we report a case of visceral dissemination of VZV in immunocompromised patients. A 38-year-old male Caucasian with a history of bone marrow transplantation due to diffuse large B-cell-lymphoma presented himself with severe abdominal pain. Immediate endoscopy revealed numerous gastric and duodenal ulcerations, while histological and molecular evaluation on tissue biopsies and blood samples confirmed VZV infection. Positive serological findings and history of chickenpox during childhood supported visceral VZV dissemination due to reactivation of VZV. The patient received Aciclovir treatment and fully recovered. This case illustrates that visceral dissemination of VZV may lead to acute abdominal pain due to severe mucosal ulcerations even in the absence of dermatological manifestations. Early endoscopic evaluation may therefore be crucial and the only means to immediately guide differential diagnosis, especially in immunocompromised patients. Characteristic histomorphological findings from mucosal ulcerations should lead to the immediate initiation of antiviral therapy and specific molecular evaluation in order to avoid detrimental spread of visceral VZV infection.


The COOH terminus of aminoglycoside phosphotransferase (3')-IIIa is critical for antibiotic recognition and resistance.
The aminoglycoside phosphotransferases (APHs) are widely distributed among pathogenic bacteria and are employed to covalently modify, and thereby detoxify, the clinically relevant aminoglycoside antibiotics. The crystal structure for one of these aminoglycoside kinases, APH(3')-IIIa, has been determined in complex with ADP and analysis of the electrostatic surface potential indicates that there is a large anionic depression present adjacent to the terminal phosphate group of the nucleotide. This region also includes a conserved COOH-terminal alpha-helix that contains the COOH-terminal residue Phe(264). We report here mutagenesis and computer modeling studies aimed at examining the mode of aminoglycoside binding to APH(3')-IIIa. Specifically, seven site mutants were studied, five from the COOH-terminal helix (Asp(261), Glu(262), and Phe(264)), and two additional residues that line the wall of the anionic depression (Tyr(55) and Arg(211)). Using a molecular modeling approach, six ternary complexes of APH(3')-IIIa.ATP with the antibiotics, kanamycin, amikacin, butirosin, and ribostamycin were independently constructed and these agree well with the mutagenesis data. The results obtained show that the COOH-terminal carboxylate of Phe(264) is critical for proper function of the enzyme. Furthermore, these studies demonstrate that there exists multiple binding modes for the aminoglycosides, which provides a molecular basis for the broad substrate- and regiospecificity observed for this enzyme.


Plasmid Vectors for Xylella fastidiosa Utilizing a Toxin-Antitoxin System for Stability in the Absence of Antibiotic Selection.
The phytopathogen Xylella fastidiosa causes disease in a variety of important crop and landscape plants. Functional genetic studies have led to a broader understanding of virulence mechanisms used by this pathogen in the grapevine host. Plasmid shuttle vectors are important tools in studies of bacterial genetics but there are only a limited number of plasmid vectors available that replicate in X. fastidiosa, and even fewer that are retained without antibiotic selection. Two plasmids are described here that show stable replication in X. fastidiosa and are effective for gene complementation both in vitro and in planta. Plasmid maintenance is facilitated by incorporation of the PemI/PemK plasmid addiction system, consisting of PemK, an endoribonuclease toxin, and its cognate antitoxin, PemI. Vector pXf20pemIK utilizes a native X. fastidiosa replication origin as well as a high-copy-number pUC origin for propagation in Escherichia coli cloning strains. Broad-host-range vector pBBR5pemIK is a medium- to low-copy-number plasmid based on the pBBR1 backbone. Both plasmids are maintained for extended periods of time in the absence of antibiotic selection, as well as up to 14 weeks in grapevine, without affecting bacterial fitness. These plasmids present an alternative to traditional complementation and expression vectors which rely on antibiotic selection for plasmid retention.


A district-based audit of the causes and circumstances of maternal deaths in South Kalimantan, Indonesia.
A district-based audit of maternal and perinatal mortality began during 1994 in three provinces of South Kalimantan, Indonesia. Both medical and non-medical factors were documented and an effort was made to progress from merely assessing substandard care to recommending improvements in access to care and the quality of care. Extensive discussions of cases of maternal death were held during regular meetings with providers, policy-makers and community members. The sources of information included verbal autopsies with family members and medical records. Between 1995 and 1999 the audit reviewed 130 maternal deaths. The leading causes of death were haemorrhage (41%) and hypertensive diseases (32%). Delays in decision-making and poor quality of care in health facilities were seen as contributory factors in 77% and 60% of the deaths, respectively. Economic constraints were believed to have contributed to 37% of the deaths. The distance between a patient's home and a health provider or facility did not appear to have a significant influence, nor did transport problems. The audit led to changes in the quality of obstetric care in the district. Its success was particularly attributable to the process of accountability of both health providers and policy-makers and to improved working relationships between health providers at different levels and between providers and the community. With a view to the continuation and further expansion of the audit it may be necessary to reconsider the role of the provincial team, the need of health providers for confidentiality, the added benefit of facility-based audits, the need to incorporate scientific evidence into the review process, and the possible consideration of severe complications as well as deaths. It may also be necessary to recognize that village midwives are not solely responsible for maternal deaths.


Improvement of paracellular transport in the Caco-2 drug screening model using protein-engineered substrates.
The Caco-2 assay has achieved wide popularity among pharmaceutical companies in the past two decades as an in vitro method for estimation of in vivo oral bioavailability of pharmaceutical compounds during preclinical characterization. Despite its popularity, this assay suffers from a severe underprediction of the transport of drugs which are absorbed paracellularly, that is, which pass through the cell-cell tight junctions of the absorptive cells of the small intestine. Here, we propose that simply replacing the collagen I matrix employed in the standard Caco-2 assay with an engineered matrix, we can control cell morphology and hence regulate the cell-cell junctions that dictate paracellular transport. Specifically, we use a biomimetic engineered extracellular matrix (eECM) that contains modular protein domains derived from two ECM proteins found in the small intestine, fibronectin and elastin. This eECM allows us to independently tune the density of cell-adhesive RGD ligands presented to Caco-2 cells as well as the mechanical stiffness of the eECM. We observe that lower amounts of RGD ligand presentation as well as decreased matrix stiffness results in Caco-2 morphologies that more closely resemble primary small intestinal epithelial cells than Caco-2 cells cultured on collagen. Additionally, these matrices result in Caco-2 monolayers with decreased recruitment of actin to the apical junctional complex and increased expression of claudin-2, a tight junction protein associated with higher paracellular permeability that is highly expressed throughout the small intestine. Consistent with these morphological differences, drugs known to be paracellularly transported in vivo exhibited significantly improved transport rates in this modified Caco-2 model. As expected, permeability of transcellularly transported drugs remained unaffected. Thus, we have demonstrated a method of improving the physiological accuracy of the Caco-2 assay that could be readily adopted by pharmaceutical companies without major changes to their current testing protocols.


Using 3D differential forms to characterize a pigmented lesion in vivo.
After the formulation of ABCD rules, many new feature extraction methods are emerging to describe the asymmetry, border irregularity, color variation and diameter of malignant melanoma. In this paper, a new research direction orthogonal to ABCD rules that characterizes 3D local disruption of skin surfaces to realize automatic recognition of melanoma is described. This paper examines 3D differential forms of skin surfaces to characterize the local geometrical properties of melanoma. Firstly, 3D data of skin surfaces are obtained using a photometric stereo device. Then differential forms of lesion surfaces are determined to describe the geometrical texture patterns involved. Using only these geometrical features, a simple least-squared error-based linear classifier can be constructed to realize the classification of malignant melanomas and benign lesions. As with the 3D data of 35 melanoma and 66 benign lesion samples collected from local pigmented lesion clinics, the optimal sensitivity and specificity of the constructed linear classifier are 71.4% and 86.4%, respectively. The total area enclosed by the corresponding receiver operating characteristics curve is 0.823. This study indicates that differential forms obtained from 3D data are very promising in characterizing melanoma. Combining these features with other skin features such as border irregularity and color variation might further improve the accuracy and reliability of the automatic diagnosis of melanoma.


Shift work of nursing professionals and blood pressure, burnout and common mental disorders.
To analyze the influence of shift work on blood pressure, the presence of burnout and common mental disorders in nursing professionals. A cross-sectional study. Burnout was assessed by the Maslach Burnout Inventory, and Common Mental Disorders by the Self-Reporting Questionnaire. Casual blood pressure measurement and Ambulatory Blood Pressure Monitoring (ABPM) were performed. 231 professionals participated. The majority (59.7%) worked in shifts, and this condition was associated (p≤0.05) with: higher weekly workload; doing the night shift; shorter training and work time at the institution; alcoholism; leisure activity; and alteration in ambulatory blood pressure monitoring of the sleep period. The professionals with common mental disorders and who worked in shifts had lower casual diastolic pressure levels (p = 0.039) and higher hypertension prevalence (p = 0.045). The presence of emotional exhaustion was associated with normal waking blood pressure and depersonalization with altered sleep blood pressure. Shift work was associated with a higher prevalence of work-related negative factors, inadequate habits and lifestyles, and change in sleep blood pressure.


Outcomes and disease activity measures for assessing treatments in the idiopathic inflammatory myopathies.
The assessment and treatment of patients with idiopathic inflammatory myopathy has taken a major step forward over the past few years. Through the efforts of multi-disciplinary international groups of experts interested in the management of patients with myositis, initiatives have led to the development of a core set of outcome measures critical to their assessment. Similarly, the lack of consensus on several issues of clinical trial design has been addressed resulting in the development of a definition of clinical improvement for adult and juvenile patients with inflammatory myopathy using the core set outcomes. The final step in the puzzle of well-designed therapeutic trials in myositis is the determination of consensus guidelines to conduct such trials in adult and pediatric populations of myositis patients.


Is aorto-arteritis a manifestation of primary antiphospholipid antibody syndrome?
A 23 year old female presented with dyspnea on exertion and absent pulses in the left upper limb. She had prior history of two first trimester abortions and pre-eclampsia with premature delivery. A Doppler examination had revealed left subclavian and axillary artery thrombosis for which she had been given warfarin six months previously. She was admitted and investigated. Patient had low positive aCL IgG antibody, positive antibeta2gp1 antibody, negative lupus anticoagulant and negative ANA. Patient had cardiomegaly and her echocardiography showed severe aortic regurgitation, moderate mitral regurgitation and moderate pulmonary artery hypertension with poor ejection fraction with normal aortic root. A diagnosis of primary antiphospholipid antibody syndrome with valvular involvement with dilated cardiomyopathy was entertained. A CT angiogram of the aorta revealed narrowing and irregularity of the aorta and its multiple branches suggestive of type III Takayasu's arteritis. Temporal relationship suggests development of aorto-arteritis secondary to APS but simultaneous presence of both these disorders in this patient cannot be ruled out.


After initial invigoration by heading, young pear trees show reduction in axis vigour and increased propensity to flower.
Fast establishment of the canopy in young trees, followed by reduced vegetative vigour and precocity are desirable traits in fruit production. Severe heading (cutting back the primary axis of the tree after the first year of growth) to induce branching is a nursery practice to increase early fruit yield. Our aim was to provide a systematic study of the responses of young pear trees to severe heading. We used an experimental system with two scion genotypes and three rootstocks to create trees with contrasting branching habits and vigour. The trees' trunks were headed and a single bud was allowed to outgrow in the following season. Architectural analysis was used to quantify the development of regenerated trees. In the first year after heading, the growth of the primary axes and, depending on the scion genotype, the sylleptic branching of regenerating trees, were invigorated. In the second year, the percentage of budbreak was also increased, but the shoot growth was greatly reduced. Axis propensity to flower in spring of the third year of growth was increased. The new insights into the effects of heading on tree aging and flowering will be used for guiding the best approaches to managing young pear trees.


Group and Phase Velocities for Rayleigh Waves of Period Greater than 380 Seconds.
Recent theoretical and experimental investigations of the periods of free spheroidal oscillation of the earth have shown good agreement. These data are used to determine group and phase velocities for Rayleigh waves of period greater than 380 seconds. The velocities so obtained are compared with those determined from analysis of progressive waves. It is concluded that group and phase velocities determined by either of the two methods are in agreement.


Primary Health Care in Brazil and the Mais Médicos (More Doctors) Program: an analysis of production indicators.
This study analyzes the number of medical appointments and referrals performed in primary health care in Brazil focusing on the Mais Médicos Program (More Doctors Program). It is a cross-sectional study on the work of physicians included, or not, to the Mais Médicos Program in 2014. Based on validation protocols, a unified database was created from two health information system databases - SIAB and ESUS. Absolute indicators were defined: the total of medical appointments per month; medical referrals and community health education activities. In addition, other indicators were considered, such as weekly rates and productivity of appointments, in line with the profile of Brazilian municipalities. The mean of all appointments was 285 per month corresponding to an average of 14.4 appointments/day. In the poorest municipalities, the figures for the Mais Médicos Program physicians were higher than national rates. The educational activities provided by primary care teams that included a Mais Médicos Program professional were higher in Brazilian capital cities. The Mais Médicos Program achieved one of its main goals, which was to increase health access for vulnerable populations and to contribute towards the consolidation of primary health care in Brazil.


[Collaboration of the involved psychosocial systems in the management of children and adolescents with psychiatric disorders].
Described and discussed here are the concrete need for professional help for children and juveniles with psychological problems as well as support systems and their institutions. The necessity of cooperation between systems and institutions is explained, and the obstacles to and problems involved in such cooperation are outlined. The attitudes toward cooperation held by professionals and the expectations and views of those in need of help are compared.


Allofrancisella inopinata gen. nov., sp. nov. and Allofrancisella frigidaquae sp. nov., isolated from water-cooling systems, and transfer of Francisella guangzhouensis Qu et al. 2013 to the new genus as Allofrancisella guangzhouensis comb. nov.
Five bacterial strains (SYSU YG23T, SYSU 10HL1970T, 10HP82-10, 10HL1938, 10HP457) isolated from water reservoirs of cooling systems were characterized using a polyphasic taxonomic approach. The isolates were Gram-stain-negative, strictly aerobic and non-motile. Growth was enhanced in the presence of l-cysteine. The major fatty acids (>5 %) for the five strains were C10 : 0, C16 : 0, C16 : 0 3-OH, C18 : 0 3-OH and C18 : 1ω9c. Ubiquinone-8 was detected as the respiratory quinone while the polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, three unidentified phospholipids, two unidentified aminophospholipids and three unidentified glycolipids. The strains shared 16S rRNA gene sequence similarities of 99.0-99.2 % with Francisella guangzhouensis 08HL01032T but less than 95.2 % with other members of the family Francisellaceae. The phylogenetic dendrogram based on 16S rRNA gene sequences showed that these strains form a separate cluster along with Francisella guangzhouensis. This cluster was also confirmed from multilocus-sequence typing based on sequences of the mdhA, rpoB and sdhA genes. Matrix-assisted laser desorption ionization time-of-flight MS analyses of the strains along with closely and distantly related Francisella strains also showed a distinct cluster for these strains. Based on the findings from the polyphasic taxonomy studies, the strains were considered to represent two novel species of a new genus for which the names Allofrancisella inopinata gen. nov., sp. nov. (type strain SYSU YG23T=KCTC 42968T=DSM 101834T) and Allofrancisella frigidaquae sp. nov. (type strain SYSU 10HL1970T=KCTC 42969T=DSM 101835T) are proposed. In addition, Francisella guangzhouensisQu et al. 2013 is proposed to be transferred to this new genus as Allofrancisella guangzhouensis comb. nov.


Enhanced detection of bacteremia with a new BACTEC resin blood culture medium.
In this multicenter study, 621 sets of blood culture specimens were drawn from 280 patients who were suspected of being septic and who were receiving antimicrobial therapy. Equal volumes of each specimen were inoculated into BACTEC 6B and 16B media. The 16B medium contained adsorbent and cationic resins for neutralizing the effects of the drugs. Of the 621 sets drawn, there were 72 positive cultures in 16B and 52 positive cultures in 6B. In 23 cases the organism was detected only in the 16B medium, and in 3 cases the organism was detected in 6B only. The remaining 49 positives were detected in both culture bottles. In 13 of these 49 cultures, detection in 16B was made between 1 and 5 days earlier than in 6B, whereas 3 of 49 specimens were detected 1 day earlier in 6B; the remaining 33 cultures became positive at approximately the same time in both media. There were a total of 43 patients with positive cultures in this study. Of these patients, 28 had sepsis detected in both the 16B and 6B media. The 6B medium alone detected an additional three cases of sepsis, and the 16B resin medium alone identified 12 additional cases. Supplementary culturing of samples from patients receiving antimicrobial therapy significantly increased the number of positive cultures and positive patients, as well as significantly shortening the time to positivity in these cultures.


Leveraging both individual-level genetic data and GWAS summary statistics increases polygenic prediction.
The accuracy of polygenic risk scores (PRSs) to predict complex diseases increases with the training sample size. PRSs are generally derived based on summary statistics from large meta-analyses of multiple genome-wide association studies (GWASs). However, it is now common for researchers to have access to large individual-level data as well, such as the UK Biobank data. To the best of our knowledge, it has not yet been explored how best to combine both types of data (summary statistics and individual-level data) to optimize polygenic prediction. The most widely used approach to combine data is the meta-analysis of GWAS summary statistics (meta-GWAS), but we show that it does not always provide the most accurate PRS. Through simulations and using 12 real case-control and quantitative traits from both iPSYCH and UK Biobank along with external GWAS summary statistics, we compare meta-GWAS with two alternative data-combining approaches, stacked clumping and thresholding (SCT) and meta-PRS. We find that, when large individual-level data are available, the linear combination of PRSs (meta-PRS) is both a simple alternative to meta-GWAS and often more accurate.


A multi-level similarity measure for the retrieval of the common CT imaging signs of lung diseases.
The common CT imaging signs of lung diseases (CISLs) which frequently appear in lung CT images are widely used in the diagnosis of lung diseases. Computer-aided diagnosis (CAD) based on the CISLs can improve radiologists' performance in the diagnosis of lung diseases. Since similarity measure is important for CAD, we propose a multi-level method to measure the similarity between the CISLs. The CISLs are characterized in the low-level visual scale, mid-level attribute scale, and high-level semantic scale, for a rich representation. The similarity at multiple levels is calculated and combined in a weighted sum form as the final similarity. The proposed multi-level similarity method is capable of computing the level-specific similarity and optimal cross-level complementary similarity. The effectiveness of the proposed similarity measure method is evaluated on a dataset of 511 lung CT images from clinical patients for CISLs retrieval. It can achieve about 80% precision and take only 3.6 ms for the retrieval process. The extensive comparative evaluations on the same datasets are conducted to validate the advantages on retrieval performance of our multi-level similarity measure over the single-level measure and the two-level similarity methods. The proposed method can have wide applications in radiology and decision support. Graphical abstract.


Developmental changes and day-night expression of the gonadotropin-inhibitory hormone system in the European sea bass: Effects of rearing temperature.
The role of rearing temperature on fish development, sex differentiation and puberty has been largely addressed, but the impact of water temperature on the ontogeny of the main neuroendocrine systems controlling reproduction has received little attention. Gonadotropin-inhibitory hormone (GnIH) has been shown to act on gonadotropin-releasing hormone (GnRH) neurons and on the pituitary to inhibit gonadotropin release and synthesis in vertebrates, including sea bass, Dicentrarchus labrax. In the present study we investigated the effects of rearing temperature during the thermosensitive period (5-60days post-fertilization, dpf) on the expression of the GnIH gene (gnih) and its receptor (gnihr). Animals were maintained under two different conditions, low temperature (LT, 15°C) or high temperature (HT, 21°C), throughout the thermosensitive period and sampled from 5 to 360dpf at mid-light (ML) and mid-dark (MD). Our results showed significant effects of temperature on gnih and gnihr expression during the thermosensitive period, with higher transcript levels under LT condition. Some differences were also evident after the completion of the sex differentiation process. Moreover, we revealed daily variations in the developmental expression of gnih and gnihr, with higher diurnal mRNA levels at early stages (until 25dpf), and a shift to higher nocturnal expression levels at 300-360dpf, which corresponded with the beginning of the winter (reproductive season). To the best of our knowledge, this work represents the first study reporting the effects of rearing temperature on the transcription of gnih system genes, as well as its daily variations during the development of a fish species.


Morphometric measurements of the anterior skull base for endoscopic transoral and transnasal approaches.
The objective of this study is to determine the bony limits of the transnasal and transoral approaches to the anterior skull base. The data we present are meant to assist surgeons in preoperative planning for lesions of the sella, clivus, foramen magnum, and odontoid. Using precise measurements undertaken on 41 high-resolution computed tomography scans from patients at the University of Pennsylvania without any history of sinus or sellar pathology, we sought to define the bony limits of transoral and transnasal approaches. Direct measurements and calculated angles were used to assess the dimensions of the anterior skull base. Using our measurements, a transnasal approach can reach an average of 22.5 mm below the plane of the hard palate to the body of C2, and a transoral route can reach 38 mm above the basion along the length of the clivus. Analysis of variance demonstrated no significant differences when subjects were grouped based on race or gender. The measurements outlined within this article help to define the relative dimensions necessary for adapted transoral and transnasal skull base surgeries.