Rs9679162 genotype predicts prognosis of real-world advanced hepatocellular carcinoma treated by sorafenib.
Sorafenib and lenvatinib are tyrosine kinase inhibitors widely used in the targeted therapy to treat advanced hepatocellular carcinoma (aHCC). The GALNT14-rs9679162 genotype is a predictor of therapeutic outcome in multiple gastrointestinal cancers. To investigate the predictive role of the GALNT14-rs9679162 genotype in aHCC treated with sorafenib or lenvatinib. Totally 350 real-world patients with aHCC received sorafenib or lenvatinib were enrolled for GALNT14-rs9679162 genotyping and outcome analysis. Kaplan-Meier and Cox regression analysis were conducted to evaluate therapeutic outcomes. Cell-based assays were performed to determine the underlying mechanism. Kaplan-Meier and Cox regression analysis showed that the "GG" genotype was not associated with overall survival (OS) when all patients were included. However, it was associated with shorter OS in specific clinical subgroups, including anti-hepatitis C virus antibody-positive (n= 108; P= 0.005) and hepatitis B surface antigen-negative (n= 117; P= 0.002) patients. Intriguingly, hepatitis B virus X protein trans-suppressed the GALNT14 promoter, thereby reducing the elevated expression of GALNT14 in hepatoma cells, which partially contributed to the inability of the GALNT14-rs9679162 genotypes to predict the outcome of hepatitis B-related HCC. Finally, by analyzing the outcomes of 52 patients with aHCC treated with lenvatinib, patients with the "GG" genotype were associated with a favorable/shorter time-to-response (P= 0.013). The GALNT14-rs9679162 "GG" genotype predicted shorter OS in patients with HBsAg-negative aHCC treated with sorafenib, but predicted a favorable response in all patients with aHCC treated with lenvatinib.


Extracorporeal membrane oxygenation following lung transplantation: indications and survival.
Extracorporeal membrane oxygenation (ECMO) is employed to rescue patients with early graft dysfunction after lung transplantation (LTx). Rates of post-LTx ECMO and subsequent outcomes have been limited to single-center reports. UNOS registry was queried for LTx recipients from March 2015 to March 2016; 2,001 recipients were identified and stratified by need for post-LTx ECMO. Logistic regression was used to determine variables associated with post-LTx ECMO. Cox proportional hazards modeling identified factors associated with survival. Kaplan-Meier analysis with log-rank testing was employed for survival analysis. Of 2,001 recipients identified, 107 required post-LTx ECMO (5.1%). Recipients requiring ECMO were younger (56 vs 60 years, p = 0.007) and had higher body mass index (27.2 vs 25.8, p = 0.012). Recipients requiring post-LTx ECMO were more likely to have required mechanical ventilation before transplant (9.3% vs 4.9%, p = 0.049) and were more likely to have required pre-transplant ECMO (15% vs 3.7%, p < 0.001). On multivariable analysis, pre-transplant ECMO and increasing ischemic time were associated with post-LTx ECMO. Six-month survival for recipients requiring ECMO was 62.2%. On multivariable analysis, need for post-transplant dialysis was associated with mortality. Six-month survival for recipients requiring ECMO with and without dialysis was 25.8% and 86.7% (p < 0.001). In a nationally representative database, ischemic time and pre-transplant ECMO and/or ventilator requirement were associated with need for post-LTx ECMO. Need for post-transplant dialysis was associated with mortality in patients requiring post-LTx ECMO. These data may permit improved prediction of graft dysfunction. Strategies to minimize renal toxicity in the perioperative phase may lead to improved early survival post-LTx.


Regulation of Gene Expression in the Remobilization of Carbon Reserves in Rice Stems During Grain Filling.
Carbon reserves in rice straw (stem and sheath) before flowering contribute to a significant portion of grain filling. However, the molecular mechanism of carbon reserve remobilization from straw to grains remains unclear. In this study, super rice LYP9 and conventional rice 9311 showed different carbon reserve remobilization behaviors. The transcriptomic profiles of straws of LYP9 and 9311 were analyzed at three stages of grain filling. Among the differentially expressed genes (DGs), 5,733 genes were uniquely up- or down-regulated at 30 days after anthesis (DAA) between LYP9 and 9311 in comparison with 681 at 10 DAA and 495 at 20 DAA, suggesting that the gene expression profile of LYP9 was very different from that of 9311 at the late stage of grain filling. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) classification of DGs both showed that the carbohydrate catabolic pathway, plant hormone signal transduction and photosynthesis pathway were enriched in DGs, suggesting their roles in carbon reserve remobilization, which explains to a certain extent the difference in non-structural carbohydrate content, photosynthesis and ABA content between the two cultivars during grain filling. Further comparative analysis and confirmation by quantitative real-time PCR and enzyme assays suggest that genes involved in trehalose synthesis (trehalose-phosphate phosphatase and trehalose 6-phosphate synthase/phosphatase), starch degradation (β-amylase) and sucrose synthesis (sucrose-phosphate synthase and sucrose synthase) were important for carbon reserve remobilization, whereas ABA content was determined by the counteraction of NCED1 and ABA8ox1 genes. The higher expression level of all these genes and ABA content in 9311 resulted in better efficiency of carbon reserve remobilization in 9311 than in LYP9.


Minimally invasive thoracotomy for myocardial revascularisation. A study of 32 cases.
This study aimed to evaluate the advantages offered by a myocardial revascularisation technique proposed by Kolessov in 1967: minimally invasive thoracotomy for myocardial revascularisation. The aim was to assess its short and medium-term benefits. During the course of the 1980s, the problems linked to extracorporeal circulation (ECC) and the contraindications for traditional myocardial revascularisation led to a renewed popularity of "beating heart" revascularisation techniques. The largest and most extensive series of patients in the literature undergoing myocardial revascularisation during left mini-thoracotomy was reported by Calafiore et al. In this study we report the series treated by our centre which, albeit involving only 32 cases, obtained good results in the short and medium term. This surgical procedure can only be applied to patients presenting monovasal obstructive coronary disease affecting the anterior interventricular artery (IVA) which must not present small calibre, calcified walls or a lateralised or intramyocardial anatomic position. Invasive and non-invasive instrumental tests carried out to control the distal anastomoses of the left internal mammary artery (IMA) did not reveal angulations and/or stenosing tractions before the anastomosis of IMA to a significant extent also for treatment, when isolating IMA, able to obtain the longest possible length and the best mobility. No infection of surgical wounds was reported postoperatively, as sometimes occurs in median longitudinal sternotomy. The 2-year follow-up showed the resolution of angina in 100% of the patients studied, as well as a satisfactory and rapid renewal of social relations.


Synonymous sites for accessibility around microRNA binding sites in bacterial spot and speck disease resistance genes of tomato.
The major causes of mass tomato infections in both covered and open ground are agents of bacterial spot and bacterial speck diseases. MicroRNAs (miRNAs) are 16-21 nucleotides in length, non-coding RNAs that inhibit translation and trigger mRNA degradation. MiRNAs play a significant part in plant resistance to abiotic and biotic stresses by mediating gene regulation via post-transcriptional RNA silencing. In this study, we analyzed a collection of bacterial resistance genes of tomato and their binding sites for tomato miRNAs and Pseudomonas syringe pv. tomato miRNAs. Our study found that two genes, bacterial spot disease resistance gene (Bs4) and bacterial speck disease resistance gene (Prf), have a 7mer-m8 perfect seed match with miRNAs. Bs4 was targeted by one tomato miRNA (sly-miR9470-3p) and three Pseudomonas syringe pv. tomato miRNAs (PSTJ4_3p_27246, PSTJ4_3p_27246, and PSTJ4_3p_27246). Again, Prf gene was found to be targeted by two tomato miRNAs namely, sly-miR9469-5p and sly-miR9474-3p. The accessibility of the miRNA-target site and its flanking regions and the relationship between relative synonymous codon usage and tRNAs were compared. Strong access to miRNA targeting regions and decreased rate of translations suggested that miRNAs might be efficient in binding to their particular targets. We also found the existence of rare codons, which suggests that it could enhance miRNA targeting even more. The codon usage pattern analysis of the two genes revealed that both were AT-rich (Bs4 = 63.2%; Prf = 60.8%). We found a low codon usage bias in both genes, suggesting that selective restriction might regulate them. The silencing property of miRNAs would allow researchers to discover the involvement of plant miRNAs in pathogen invasion. However, the efficient validation of direct targets of miRNAs is an urgent need that might be highly beneficial in enhancing plant resistance to multiple pathogenic diseases.


Evolution of enlarged body size of coal tits Parus ater in geographic isolation from two larger competitors, the crested tit Parus cristatus and the willow tit Parus montanus, on six Scandinavian islands.
Here, we report that on six widely separated Scandinavian islands, the coal tit Parus ater has evolved morphologically in the direction of two absent competitors, the crested tit P. cristatus and the willow tit P. montanus, to the effect that it is up to 10% larger in linear dimensions than conspecifics on the adjacent Swedish mainland, where all three species coexist. The large size is genetically determined, as ascertained by clutch exchange experiments between island and mainland nests. We conclude that the increased size of P. ater in places where it is geographically isolated from its larger congeners is the result of evolutionary adaptation, due ultimately to relaxed interspecific competition. On the islands, P. ater has evolved into a medium-sized generalist, with selection pressures likely governed by the following causal relationships. When competitors are lacking, P. ater takes over the foraging space of the absentees. The enlarged food base allows higher population densities, which intensifies intraspecific interference competition. This, in turn, selects for increased body size. When P. ater coexists with its larger congeners, it occupies peripheral foraging sites in trees, which requires excellent manoeuvrability and energy-expensive locomotion modes. Reduction of body size increases locomotor capacity for mechanical and aerodynamic reasons and lowers energy consumption, so small size is favoured in sympatry. But in geographic isolation, P. ater exploits the tree periphery less and the inner tree regions more, and it also adopts the easier locomotion modes of the absent species. Therefore, selection for manoeuvrability and a small body size is relaxed. The new selection regime shifts the balance between opposing selection forces towards a larger body size. We were able to test 11 alternative hypotheses and available evidence conclusively eliminates them all. As a result, here, evolution could be predicted regarding both direction and amount of change.


Surgical cleft soft palate repair in a foal.
An Anglo-Arab foal with bilateral postprandial nasal discharge was diagnosed as having a full-length defect of the soft palate. Surgical repair was attempted using a combination of two surgical approaches. Initially a mandibular symphysiotomy approach was used. The posterior portion of the defect did not heal adequately, so a ventral laryngotomy, bisecting the body of the thyroid cartilage and extending to a pharyngotomy approach, was performed 5 months later. The foal has since matured fully despite a slight unilateral nasal discharge. This case report demonstrates that these two surgical approaches used simultaneously provide surgical access that is superior to either approach used individually.


Agenesis of the long head of the biceps brachii tendon: ignored variations of the anatomy and the next tendon to disappear?
Bilateral agenesis of the long head of the biceps brachial tendon (LHB) is a very rare variation of the anatomy. We report a case of an 18-year-old man with bilateral agenesis of the long head of the biceps brachii tendon. We present initial findings, radiographical examinations and the follow-up of an unusual entity. Diagnosis of agenesis of the LHB can be challenging especially in cases of traumatic shoulder pain. It is not a very known entity because of its rareness. However, it could be associated with other congenital anomalies. The absence of the LHB is easily ignored in the diagnostic process. Clinical examination should be a pitfall, radiological examination is helpful to confirm the suspicion of LHB absence. MRI is often the first choice, although ultrasonography is cheaper and much easier to access and it is an excellent tool to visualise this anatomic variation with empty or shallow intertubercular groove.


Tracking the COVID-19 crisis with high-resolution transaction data.
Payments systems generate vast amounts of naturally occurring transaction data rarely used for constructing official statistics. We consider billions of transactions from card data from a large bank, Banco Bilbao Vizcaya Argentaria, as an alternative source of information for measuring consumption. We show, via validation against official consumption measures, that transaction data complements national accounts and consumption surveys. We then analyse the impact of COVID-19 in Spain, and document: (i) strong consumption responses to business closures, but smaller effects for capacity restrictions; (ii) a steeper decline in spending in rich neighbourhoods; (iii) higher mobility for residents of lower-income neighbourhoods, correlating with increased disease incidence.


Follow-up of the term infant after hypoxic-ischemic encephalopathy.
While the number of survivors of term hypoxic-ischemic encephalopathy (HIE) is lower than the number of survivors of extreme prematurity, the proportion of neonates with long-term sequelae is higher. All neonates with Sarnat stages 2 (moderate) and 3 (severe) should be enrolled in follow-up programs. The present paper discusses the clinical and imaging diagnostic criteria for HIE, which are essential to decisions about follow-up. Prognostic indicators are also summarized. The recommendations for follow-up and intervention are based on the clinical condition of the baby at the time of discharge from intensive care, including an assessment of feeding, vision, hearing and whether seizures continue to be present. Early assessments (at four to eight months) focus on head growth, general health and motor neurodevelopment. Assessments at 12 to 24 months focus on cognitive skills and language development. Preschool assessments are also strongly recommended to provide for the identification of children requiring early education programs. Knowledge of long-term outcome and its secular changes enhance prognostication, and the evaluation of new preventive and therapeutic approaches.


Control of parental investment changes plastically over time with residual reproductive value.
Evolutionary conflict between parents and offspring over parental resource investment is a significant selective force on the traits of both parents and offspring. Empirical studies have shown that for some species, the amount of parental investment is controlled by the parents, whereas in other species, it is controlled by the offspring. The main difference between these two strategies is the residual reproductive value of the parents or opportunities for future reproduction. Therefore, this could explain the patterns of control of parental investment at the species level. However, the residual reproductive value of the parents will change during their lifetime; therefore, parental influence on the amount of investment can be expected to change plastically. Here, we investigated control of parental investment when parents were young and had a high residual reproductive value, compared to when they were old and had a low residual reproductive value using a cross-fostering experiment in the burying beetle Nicrophorus quadripunctatus. We found that parents exert greater control over parental investment when they are young, but parental control is weakened as the parents age. Our results demonstrate that control of parental investment is not fixed, but changes plastically during the parent's lifetime.


Filoviruses and the balance of innate, adaptive, and inflammatory responses.
The Filoviruses Marburg virus and Ebola virus are among the deadliest of human pathogens, causing fulminant hemorrhagic fevers typified by overmatched specific immune responses and profuse inflammatory responses. Keys to both vaccination and treatment may reside, first, in the understanding of immune dysfunctions that parallel Filoviral disease and, second, in devising ways to redirect and restore normal immune function as well as to mitigate inflammation. Here, we describe how Filoviral infections may subvert innate immune responses through perturbances of dendritic cells and neutrophils, with particular emphasis on the downstream effects on adaptive immunity and inflammation. We suggest that pivotal events may be subject to therapeutic intervention as Filoviruses encounter immune processes.


[Benefit of sediment reduction by biological measures in the watershed scale].
Based on the measured data and the model of plotted watershed hydrology, the benefit of sediment reduction by biological harnesses of soil and water conservation was studied in the watershed scale. The result indicated that the erosion modulus in Wangdonggou watershed, which were 1869 t.km-2, 1050 t.km-2, 383 t.km-2, and 504 t.km-2 in the periods of the sixth, seventh, eighth, and ninth five-year plans, respectively, were gradually reduced by comprehensive measures. Taken out the effect of rainfall, the sediment reduction by biological measures of soil and water conservation was increased by 24.1% and 22.4% in the periods of eighth and ninth five-year plans compared to that in the seventh five-year plan.


Coordinating associative and ecological accounts of learning in the garden snail Cornu aspersum.
Pavlovian conditioning of tentacle lowering in the snail, Cornu aspersum, as an instance of associative learning, has proven effective to show evidence of paradigmatic associative phenomena (e.g., blocking) explained by current models of conditioning. Nevertheless, the available literature questions the biological function of the conditioned response (i.e., tentacle lowering) in snails since no advantages in terms of food finding had been observed. Ecological accounts of learning claim that learning abilities contribute to the adaptation to the environmental demands, and there is experimental evidence supporting this in several species (e.g., grasshoppers, fish, or antlions). However, there is a lack of evidence in snails, which is surprising given that the conditioned response of tentacle lowering is a robust finding that fits in with several predictions of associative learning theory (e.g., blocking or conditioned inhibition). The goal of this manuscript was to test whether food detection is affected by prior experience with the food, distance, and conditioning. We found that prior experience with a food source is necessary for snails to locate the same food item; that the optimal distance to test for food detection is between 5 and 7cm and that snails seem to use different food searching strategies after conditioning depending on the stimuli that are present. The data provided constitute a small contribution to the vindication of a greater coordination between the fruitful research tool provided by the associative account of learning and the evolutionary vocation of the ecological approach of learning.


Internal fixation of distal tibiofibular syndesmotic injuries: a systematic review with meta-analysis.
No consensus had been reached about the optimal method for syndesmotic fixation. The present study analysed syndesmotic fixation based on the highest level of clinical evidence in order to obtain more reliable results. Medline, Embase and Cochrane database were searched through the OVID retrieval engine. Manual searching was undertaken afterward to identify additional studies. Only randomized controlled trials (RCT) and prospective comparative studies were selected for final inclusion. Study screening and data extraction were completed independently by two reviewers. All study characteristics were summarized into a table. The extracted data were used for data analysis. Twelve studies were finally included: six of them were RCTs, two were quasi-randomized studies and four were prospective comparative studies. Four comparisons with traditional metallic screw were identified in terms of bioabsorbable screws, tricortical fixation method, suture-button device as well as non-fixation choice in low syndesmotic injuries. Both absorbable screws and the tricortical fixation method showed almost no better results than traditional quadricortical metallic screw (p > 0.05). Additionally, existing studies could not illustrate their efficiency of reducing hardware removal rate. The suture button technique had significantly better functional score (p = 0.003), ankle motion (p = 0.02), time to full weightbearing (p < 0.0001) and much less complications (p = 0.0008) based on short and intermediate term follow-up data. Transfixation in low syndesmotic injuries showed poorer results than the non fixed group in all outcome measurements, but didn't reach a significant level (p > 0.05). The present evidence still couldn't find superior performance of the bioabsorbable screw and tricortical fixation method. Their true effects in decreasing second operation rate need further specific studies. Better results of the suture-button made it a promising technique, but it still needs long-term testing and cost-efficiency studies. The patients with low syndemotic injuries should be well assessed before fixation determination and the indication of screw placement in such conditions needs to be further defined.


Distinct regulation of osmoprotective genes in yeast and mammals. Aldose reductase osmotic response element is induced independent of p38 and stress-activated protein kinase/Jun N-terminal kinase in rabbit kidney cells.
In yeast glycerol-3-phosphate dehydrogenase 1 is essential for synthesis of the osmoprotectant glycerol and is osmotically regulated via the high osmolarity glycerol (HOG1) kinase pathway. Homologous protein kinases, p38, and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) are hyperosmotically activated in some mammalian cell lines and complement HOG1 in yeast. In the present study we asked whether p38 or SAPK/JNK signal synthesis of the osmoprotectant sorbitol in rabbit renal medullary cells (PAP-HT25), analogous to the glycerol system in yeast. Sorbitol synthesis is catalyzed by aldose reductase (AR). Hyperosmolality increases AR transcription through an osmotic response element (ORE) in the 5'-flanking region of the AR gene, resulting in elevated sorbitol. We tested if AR-ORE is targeted by p38 or SAPK/JNK pathways in PAP-HT25 cells. Hyperosmolality (adding 150 mM NaCl) strongly induces phosphorylation of p38 and of c-Jun, a specific target of SAPK/JNK. Transient lipofection of a dominant negative mutant of SAPK kinase, SEK1-AL, into PAP-HT25 cells specifically inhibits hyperosmotically induced c-Jun phosphorylation. Transient lipofection of a dominant negative p38 kinase mutant, MKK3-AL, into PAP-HT25 cells specifically suppresses hyperosmotic induction of p38 phosphorylation. We cotransfected either one of these mutants or their empty vector with an AR-ORE luciferase reporter construct and compared the hyperosmotically induced increase in luciferase activity with that in cells lipofected with only the AR-ORE luciferase construct. Hyperosmolality increased luciferase activity equally (5-7-fold) under all conditions. We conclude that hyperosmolality induces p38 and SAPK/JNK cascades in mammalian renal cells, analogous to inducing the HOG1 cascade in yeast. However, activation of p38 or SAPK/JNK pathways is not necessary for transcriptional regulation of AR through the ORE. This finding stands in contrast to the requirement for the HOG1 pathway for hyperosmotically induced activation of yeast GPD1.


Digestion stability as a criterion for protein allergenicity assessment.
Assessing the allergenic potential of transgenic proteins introduced into genetically engineered food remains a critical part of the overall safety assessment of these foods. Stability to digestion has been proposed as one of the steps in the decision tree approach to assess the allergenic potential of transgenic proteins. The validity of digestion stability as a criterion for protein allergenicity assessment, however, has encountered some criticism in recent years. This chapter gives an overview of the rationale behind the use of digestion stability as a criterion for protein allergenicity assessment and reviews the available data that may or may not support its use. The application of in vitro digestion assays for the assessment of allergenic potential of novel proteins and the factors that affect the assay results are also discussed. There is a need to establish standardized assay conditions so that direct comparison of results from different laboratories can be made. Consensus also needs to be reached on relating the measured digestibility to the allergenic potential of proteins.


Evaluation of phenotypic and genotypic approaches for the detection of class A and class B carbapenemases in Enterobacteriaceae.
The spread of carbapenemases in Enterobacteriaceae is among the most important issues in the antimicrobial resistance. The rapid and recent diffusion of class A and B carbapenemases determined the need of specific diagnostic tests able to detect with high sensitivity this type of resistance and to discriminate between the different enzymes. The aim of this study was to test two carbapenemase detection assays, the Rosco Synergic and the Hyplex polymerase chain reaction-enzyme-linked immunosorbent assays for screening carbapenemase-producing Enterobacteriaceae. The phenotypic and genotypic tests were evaluated among 108 clinical isolates, including Klebsiella pneumoniae carbapenemase (KPC) (n=50) and metallo-β-lactamase- (MBL) (n=20), and AmpC- (n=10) producing Enterobacteriaceae. The commercial phenotypic assay showed a high sensitivity performance detecting all KPC and MBL producers, including New Delhi MBL 1 (NDM-1) strains. In addition, the Rosco Synergic assay was able to distinguish specifically between the different mechanisms that confer resistance to carbapenems in Enterobacteriaceae. We also demonstrated that the genotypic test was able to detect all the class A and B carbapenemases showing high sensitivity (100%) and specificity (98%) in a fast and reliable time. Based on these results, both the commercial phenotypic and the genotypic assays could be helpful as confirmatory and discriminatory tests for the detection of class A and class B carbapenemases.


[Transient cerebral ischemia and long-term potentiation in the rat hippocampus].
Long-term potentiation (LTP) has been widely studied as a form of synaptic plasticity that represents a cellular mechanism of learning and memory. Among numerous processes and molecules that may be involved in LTP formation, a great many of them including neurotrophic and transcription factors have been described as those involved in neural death after ischemic insult. Nitric oxide (NO) is a molecule that is known to also exert double-edged effects on LTP formation. Here we will be describing recent advances with respect to the LTP mechanisms in the hippocampal synapses, a critical brain region for learning and memory function. In another context, we described our study elucidating the changes in hippocampal LTP as a functional response to transient cerebral ischemic insult, from the viewpoint of its relevance to NO production. As indices of NO production, nitrite and nitrate levels were determined by in vivo microdialysis. It was demonstrated that hippocampal LTP deficiency after transient cerebral ischemia was preceded by an increase in hippocampal NO production. Direct or indirect inhibition of an inducible NO synthase restored ischemia-induced LTP deficiency. These findings suggest that NO production, in part via inducible NO synthase, is responsible for LTP deficiency after transient cerebral ischemia in the rat hippocampus.


Early Childhood Vision Screening in Hawai'i Utilizing a Hand-Held Screener.
The goal of early childhood vision screening is to detect subnormal vision and amblyopic risk factors that threaten visual development so that treatment can be initiated early to yield the highest benefit. Hand-held, portable, instrument-based vision screening devices can be used in children as young as 6 months of age. We assessed the feasibility of hand-held photoscreeners to screen for vision disorders in pre-school children in Hawai'i. A total of 137 preschool children on O'ahu in the "Tutu and Me"/Partners in Development program were screened at 6 different locations using the Plusoptix S12 hand-held photoscreener. Once technical issues were resolved, screening was fast and well tolerated. Possible vision abnormalities were found in 11 of the 137 children (8%). Poor compliance for follow-up with formal vision examination limited our ability to confirm these abnormalities. We conclude that photoscreening has the potential to facilitate early childhood vision screening in Hawai'i. The optimal referral criteria for use in Hawai'i will need to be determined after considering the age of the screening population and the available medical resources in Hawai'i. Early detection of treatable eye disorders has far-reaching benefits for the visual development and long term health and well-being of children. A comprehensive early childhood vision screening program in Hawai'i utilizing automated hand-held photoscreeners may have public health value. Such a program should integrate referral to an eye care professional for confirmation and management of vision disorders of at-risk children found on screening.


Factors associated with canine resource guarding behaviour in the presence of people: A cross-sectional survey of dog owners.
Resource guarding (RG) involves the use of specific behaviour patterns to control access to an item of potential "value" to the dog. Of particular concern are patterns involving aggression, due to safety concerns, but other patterns of RG behaviour are prevalent and include avoidance (i.e., positioning of the head or body to maintain item control, or location change with the item) and rapid ingestion (i.e., rapid ingestion of a consumable item). Current research has not investigated the etiology of RG aggression in depth, nor have the additional patterns of resource guarding been considered. Dog owners (n=3068) were recruited through social media to answer questions regarding dog- and household-related factors, as well as their dog's current and past behaviour around resources in the presence of people. Participants were screened for their ability to identify different forms of resource guarding from video, and were removed from the study if they incorrectly identified any of the videos provided. This resulted in a final sample of 2207 participants representing information for 3589 dogs. Multiple multi-level logistic regression models were developed to determine the association between independent variables of interest and each pattern of resource guarding. Dogs with higher levels of impulsivity were more likely to display avoidance, rapid ingestion and aggressive RG (p<0.001), and dogs with higher levels of fearfulness were also more likely to display RG aggression (p<0.001). Neutered males (p<0.01) and mixed breeds (p<0.05) were more likely to be RG aggressive compared to dogs of other sexes, neuter statuses, and breeds. Teaching dogs to reliably "drop" items when requested was associated with a reduced likelihood of RG aggression (p<0.01) and avoidance (p<0.001). Furthermore, the addition of palatable bits of food during mealtime was associated with an increased likelihood of less severe RG behaviour (p<0.01), whereas removal of the food dish during mealtime was associated with an increased likelihood of expressing more severe or frequent RG behaviours (p<0.05). Relationships between the three types of RG patterns were varied, suggesting that RG behaviour patterns are flexible when humans are involved. The results highlight various factors that might predispose dogs to RG behaviour and potential methods for prevention of RG aggression, and can serve as a basis for future longitudinal RG research to establish causation.


The effects of H+, NH3OH+ and NH4+ on the thermal decomposition of bistetrazole N-oxide anion.
The bistetrazole N-oxide energetic ionic salt dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) has attracted great interest as it breaks through the limitations of the traditional nitro group, high detonation velocity and moderate impact sensitivity. Reports show that TKX-50 transforms into the 5,5'-bis(2-hydroxytetrazole) (BTO) precursor, which is further decomposed and partly converted to diamino 5,5'-bistetrazole-1,1'-diolate (ABTOX). Studying the effects of H+, NH3OH+ and NH4+ on the thermal decomposition mechanism of bistetrazole N-oxide anion would provide a more comprehensive understanding of the TKX-50 decomposition mechanism. Herein, TKX-50, BTO and ABTOX decomposition rates, on-line analysis of the gas products, as well as quantitative analysis, are presented. It was found that the presence of two H+ decreases the decomposition temperature, whereas NH3OH+ greatly increases the decomposition rate. In the presence of NH3OH+, the bistetrazole N-oxide anion completely decomposes without producing C2N2; however, NH4+ promotes the polymerization of C2N2 generated by the bistetrazole N-oxide anion, and the amount of NO produced is greater than that of N2O. Therefore, in the TKX-50 decomposition process, the bistetrazole N-oxide anion does not receive two H+ simultaneously and converts into BTO. Furthermore, the competition between cations and their decomposition products for the H+ affects the degree of decomposition, which is important in understanding the energy release mechanism.


Downregulated SOX9 mediated by miR-206 promoted cell apoptosis in Legg-Calvé-Perthes disease.
Legg-Calvé-Perthes disease (LCPD) commonly onsets in adolescents, and threatens their health. However, the potential mechanism underlying LCPD remains unclear. MicroRNA (miR)-206 and SRY-box 9 (SOX9) serve an important role in chondrocytes; however, their role in LCPD remains ambiguous. In the present study, whether miR-206 and SOX9 mediated cell apoptosis in dexamethasone (DEX)-induced LCPD was investigated. The chondrocytes of the LCPD and normal control group were isolated from clinical tissues. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression of miR-206 and SOX9 mRNA. Western blotting was used to measure the protein level of SOX9. A combination of Annexin V-fluorescein isothiocyanate flow cytometry was used to assess cell apoptosis. The association between miR-206 and SOX9 was detected using a luciferase reporter assay. miR-206 was overexpressed while SOX9 was downregulated in chondrocytes treated with DEX obtained from patients with LCPD. miR-206 targeted SOX9 to regulate its expression. Overexpression of miR-206 promoted cell apoptosis in TC28, while it was reversed by SOX9 overexpression. TC28 cells pretreated with DEX significantly promoted cell apoptosis, while cells transfected with miR-206 inhibitor significantly reversed the effect; however, downregulated SOX9 abolished the effects of miR-206 inhibitor. SOX9 mediated by miR-206 possibly contributed to the pathogenesis of LCPD. The results of the present study suggest that miR-206 and SOX9 function as important therapeutic targets for the future of clinical therapy.


Effects of vitamin E on growth performance, tissue α-tocopherol, and lipid peroxidation of starter White Pekin ducks.
Two experiments were conducted to evaluate the effects of vitamin E on growth performance, tissue α-tocopherol, and lipid peroxidation of White Pekin ducks from hatch to 21 d of age. The 6 supplemental vitamin E levels (0, 5, 10, 20, 40, and 100 mg DL-α-tocopheryl acetate/kg) and 4 supplemental vitamin E levels (0, 10, 20, and 100 mg DL-α-tocopheryl acetate/kg) were utilized in experiments 1 and 2, respectively. All treatments were replicated 8 times using 7 ducklings per pen in experiment 1 and 6 times using 8 birds per pen in experiment 2. All ducks were raised from hatch to 21 d of age. In both experiments, compared with ducks fed vitamin E-supplemented diets, the birds fed basal diets with no supplemental vitamin E had less weight gain and feed intake (P < 0.05) but these two criteria showed no linear or quadratic response to increasing supplemental vitamin E levels (P > 0.05). On the other hand, the plasma or liver α-tocopherol was dependent on supplemental vitamin E levels. The plasma or liver α-tocopherol increased linearly or quadratically as supplemental vitamin E increased gradually in both experiments (P < 0.05). In addition, supplementation of vitamin E in basal diets could reduce liver lipid peroxidation but the further reduction did not take place when supplemental vitamin E level was above 5 mg/kg in experiment 1 or 10 mg/kg in experiment 2 due to no linear or quadratic response to increasing supplemental levels of this vitamin (P > 0.05). Therefore, when including the vitamin E content of basal diets, the dietary total vitamin E should not be less than 10 mg/kg in order to keep optimal growth performance and antioxidant capacity of starter Pekin ducks from hatch to 21 days of age. Plasma or liver α-tocopherol were sensitive indicators for the status of this vitamin.


A finite element model of an idealized diarthrodial joint to investigate the effects of variation in the mechanical properties of the tissues.
The stiffness of articular cartilage increases dramatically with increasing rate of loading, and it has been hypothesized that increasing the stiffness of the subchondral bone may result in damaging stresses being generated in the articular cartilage. Despite the interdependence of these tissues in a joint, little is understood of the effect of such changes in one tissue on stresses generated in another. To investigate this, a parametric finite element model of an idealized joint was developed. The model incorporated layers representing articular cartilage, calcified cartilage, the subchondral bone plate and cancellous bone. Taguchi factorial design techniques, employing a two-level full-factorial and a four-level fractional factorial design, were used to vary the material properties and thicknesses of the layers over the wide range of values found in the literature. The effects on the maximum values of von Mises stress in each of the tissues are reported here. The stiffness of the cartilage was the main factor that determined the stress in the articular cartilage. This, and the thickness of the cartilage, also had the largest effect on the stresses in all the other tissues with the exception of the subchondral bone plate, in which stresses were dominated by its own stiffness. The stiffness of the underlying subchondral bone had no effect on the stresses generated in the cartilage. This study shows how stresses in the various tissues are affected by changes in their mechanical properties and thicknesses. It also demonstrates the benefits of a structured, systematic approach to investigating parameter variation in finite element models.


Evaporation of water from particles in the aerodynamic lens inlet: an experimental study.
The extremely high particle transmission efficiency of aerodynamic lens inlets resulted in their wide use in aerosol mass spectrometers. One of the consequences of transporting particles from high ambient pressure into the vacuum is that it is accompanied by a rapid drop in relative humidity (RH). Since many atmospheric particles exist in the form of hygroscopic water droplets, a drop in RH may result in a significant loss of water and even a change in phase. How much water is lost in these inlets is presently unknown. Since water loss can affect particle size, transmission efficiency, ionization probability, and mass spectrum, it is imperative to provide definitive experimental data that can serve to guide the field to a reasonable and uniform sampling approach. In this study, we present the results of a number of highly resolved measurements, conducted under well-defined conditions, of water evaporation from a range of particles, during their transport through an aerodynamic lens inlet. We conclude that the only sure way to avoid ambiguities during measurements of aerodynamic diameter in instruments that utilize low-pressure aerodynamic lens inlets is to dry the particles prior to sampling.


[Appendiceal "mucocele": apropos of 2 cases].
Two patients affected by appendiceal mucocele underwent emergency operation in our Department. Clinical findings and surgical management of the disease are discussed as well as controversy regarding the pathologic classification of the disease. The term "mucocele" is not referred to an exact histopathologic lesion: it describes the gross enlargement of the appendix, due to the accumulation of mucus in the dilated lumen. Currently such lesions are classified as nonneoplastic or as retention appendiceal cysts or as mucous-secreting tumours; the benign forms are cured by appendectomy, the malignant ones often require right colectomy for technical reasons. Pseudomyxoma peritonei significantly decreases survival of patients suffering from mucinous cystadenocarcinoma, but it does not affect survival in case of mucinous cystadenoma.


Coronary risk factors in a rural community.
A cross-sectional health examination survey was carried out among a random sample of 406 people of 30 years and above from a rural community to investigate the prevalence of coronary heart disease risk factors. Prevalence of smoking and tobacco use was 16%, alcohol intake 9.4 %, daily Salt intake (> or = 5 gram) 34.2%, daily saturated fat intake ( > or =10 % of daily energy intake) 47.0 % and physical inactivity 18.5 %. BMI was > or =25 Kg /m(2) in 18 percent and it was > or =30 Kg / m(2) in 3.2 percent population. Truncal obesity (WHR: men> 0.9; women > 0.8) was found 18.5 percent more in case of males (20.7). Abdominal obesity(men > or =102; women > or = 88)was found 15.7 percent more in case of males (20.6).18.5 percent population was found suffering from systolic hypertension> or =140 mm Hg )and 15 percent from diastolic hypertension(> or =90 mm Hg). Awareness of CHD risk factors was present in 30.0 percent population. Differences in prevalence of riskfactor in male and female were found statistically significant in case of smoking, alcohol consumption and abdominal obesity. The present study shows that prevalence of CHD risk factors increases significantly in men and women having BMI equal or more than 25 Kg /m(2) so this cutoff, should be used to determine obesity in Indian population.


[Clinical use of bedside cerebral microdialysis: a review].
To review the current data on clinical bedside use of cerebral microdialysis. Search through Medline database of articles in French and English (keywords: microdialysis, cerebral ischaemia, head trauma, subarachnoid haemorrhage, clinical study). All clinical articles published between 1995 and 2005, including original papers and some case reports. Microdialysis after occlusive stroke has shown elevated levels of glutamate and lactate. When space-occupying oedema develops, biochemistry abnormalities occur first, before ICP increases. Bedside microdialysis appears to be a sensitive and earlier indicator of space occupying oedema. Most Accurate markers to monitor ischaemia induced by vasospasm are glutamate and lactate/pyruvate ratio. These markers are earlier than clinical abnormalities or pressure measurements (sensibility 82%, specificity 89%). In the field of head trauma, the same compounds were utilised. The level of these compounds correlates with outcome in a different manner whether the area studied is close to a concussion or not. Most of biochemical events are linked to global cerebral ischaemia. We can observe some abnormalities limited to the pericontusional area, which are not detected by the global monitoring. Microdialysis appears a useful tool to investigate disease mechanisms but cannot be recommended for a widespread use after head trauma. Bedside cerebral microdialysis allows clinical decisions in the setting of subarachnoid haemorrhage and ischaemic stroke. It represents a valuable tool to investigate head trauma pathophysiology.


Lithium-Ion-Conducting Electrolytes: From an Ionic Liquid to the Polymer Membrane.
This work concerns the design, the synthesis, and the characterization of the N-butyl-N-ethylpiperidinium N,N-bis(trifluoromethane)sulfonimide (PP(24)TFSI) ionic liquid (IL). To impart Li-ion transport, a suitable amount of lithium N,N-bis-(trifluoromethane)sulfonimide (LiTFSI) is added to the IL. The Li-IL mixture displays ionic conductivity values on the order of 10(-4) S cm(-1) and an electrochemical stability window in the range of 1.8-4.5 V vs Li(+)/Li. The voltammetric analysis demonstrates that the cathodic decomposition gives rise to a passivating layer on the surface of the working electrode, which kinetically extends the stability of the Li/IL interface as confirmed by electrochemical impedance spectroscopy measurements. The LiTFSI-PP(24)TFSI mixture is incorporated in a poly(vinylidene fluoride-co-hexafluoropropylene) matrix to form various electrolyte membranes with different LiTFSI-PP(24)TFSI contents. The ionic conductivity of all the membranes resembles that of the LiTFSI-IL mixture, suggesting an ionic transport mechanism similar to that of the liquid component. NMR measurements demonstrate a reduction in the mobility of all ions following the addition of LiTFSI to the PP(24)TFSI IL and when incorporating the mixture into the membrane. Finally, an unexpected but potentially significant enhancement in Li transference number is observed in passing from the liquid to the membrane electrolyte system.


A Japanese case of tinea corporis caused by Arthroderma benhamiae.
We report a case of tinea corporis in Japan caused by Arthroderma benhamiae. A 53-year-old female scientist, who had been working on dermatophytes in a laboratory, noticed pruritic erythema on the outer corner of her left lower eyelid. She used a steroid ointment for three days, but the lesion continued to expand. When she visited our clinic, the erythema was 15 mm in diameter and clearly demarcated with a slightly depressed center. A scale from the periphery of the erythema was positive with direct KOH examination, and T mentagrophytes was isolated from the lesion. The erythema was successfully treated with topical application of butenafine hydrochloride. The isolate was mated with a (+) strain of the Americano-European race of A. benhamiae. Using the most sensitive molecular typing method, restriction exzyme analysis of the non-transcribed spacer region of the ribosomal DNA, the restriction profile of the isolate was the same as that of strains used in her laboratory but different from those of any Japanese isolates associated with pet animals. The results suggest that the patient became infected during her experiment.


Hot-Carrier Extraction in Nanowire-Nanoantenna Photovoltaic Devices.
Nanowires bring new possibilities to the field of hot-carrier photovoltaics by providing flexibility in combining materials for band engineering and using nanophotonic effects to control light absorption. Previously, an open-circuit voltage beyond the Shockley-Queisser limit was demonstrated in hot-carrier devices based on InAs-InP-InAs nanowire heterostructures. However, in these first experiments, the location of light absorption, and therefore the precise mechanism of hot-carrier extraction, was uncontrolled. In this Letter, we combine plasmonic nanoantennas with InAs-InP-InAs nanowire devices to enhance light absorption within a subwavelength region near an InP energy barrier that serves as an energy filter. From photon-energy- and irradiance-dependent photocurrent and photovoltage measurements, we find that photocurrent generation is dominated by internal photoemission of nonthermalized hot electrons when the photoexcited electron energy is above the barrier and by photothermionic emission when the energy is below the barrier. We estimate that an internal quantum efficiency up to 0.5-1.2% is achieved. Insights from this study provide guidelines to improve internal quantum efficiencies based on nanowire heterostructures.


Hemoplasma prevalence and hematological abnormalities associated with infection in three different cat populations from Southern Brazil.
Three hemoplasma species are recognized in domestic cats: Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum' and 'Candidatus Mycoplasma turicensis'. We report the prevalence and hematological abnormalities of hemoplasma infection in 369 domestic cats from three different populations (blood donors, hospitalized cats and shelter cats) from Southern Brazil. Complete blood counts were performed at the time of blood collection, and DNA was extracted and tested by conventional PCR for each hemoplasma species. A total of 79 samples (21.40%) were positive for at least one species. The most prevalent hemoplasma was 'Candidatus Mycoplasma haemominutum', with 50/369 (13.55%) positive cats, followed by 'Candidatus Mycoplasma turicensis', 10/369 (2.71%), and Mycoplasma haemofelis, 8/369 (2.16%). Mycoplasma haemofelis and 'Candidatus Mycoplasma haemominutum' coinfection was observed in 4/369 (1.08%), whereas 'Candidatus Mycoplasma haemominutum' and 'Candidatus Mycoplasma turicensis' in 5/369 (1.35%). Three cats (0.81%) were infected with all three hemoplasmas. There was no association between infection and the different populations. Anemia was associated with Mycoplasma haemofelis and 'Candidatus Mycoplasma haemominutum', but not with 'Candidatus Mycoplasma turicensis'. Male cats and cats with outdoor access were more likely to be infected. Although 'Candidatus Mycoplasma haemominutum' is believed to cause minimal or no hematological alterations, the infected cats studied herein were more likely to be anemic.


2-Hydroxyisophthalic acid: hydrogen-bonding patterns in the monohydrate and the tetraphenylphosphonium salt. An instance of dramatic acidity enhancement by symmetric, internally hydrogen-bonded anion stabilization.
The monohydrate of the title phenolic diacid (C8H6O5.H2O, 2-hydroxybenzene-1,3-dioic acid or 3-carboxysalicylic acid) adopts a planar conformation, with the phenol hydrogen internally hydrogen-bonded to the carbonyl of one highly ordered carboxyl, which, in turn, donates a hydrogen bond to the oxygen of water. The second carboxyl is disordered and hydrogen-bonded both to water and to the disordered carboxyl of a centrosymmetrically related neighbor in a static disorder arrangement extending over two full asymmetric units. The water accepts either one or two hydrogen bonds and donates a long bifurcated hydrogen bond shared equally by O atoms of the phenol and the disordered carboxyl. The hydrogen bonding includes no standard carboxyl pairing and is entirely two-dimensional. The resulting planar ribbons stack translationally at a distance of 3.413 (8) A, in an offset arrangement having non-translational interplanar distances of 0.821 (5) and 2.592 (6) A. This structure is compared with two previously reported for this compound. The title compound forms a monoanion, whose tetraphenylphosphonium salt is described (C32H25O5P, tetraphenylphosphonium 2,6-dicarboxyphenolate, tetraphenylphosphonium 2-oxidoisophthalic acid or tetraphenylphosphonium 3-carboxysalicylate). The phenol oxygen is the site of formal negative charge on the anion, which is stabilized in a planar arrangement by symmetrical hydrogen bonds from both ortho-carboxyl groups. The energetics of this arrangement, the phenol and carboxyl acidities, and factors affecting those acidities and providing anion stabilization are discussed.


Alpha 2-adrenoceptor-mediated antisecretory effect of hypoxia in conscious rats.
Gastric acid secretion is suppressed, resulting in a significant rise in gastric pH, when conscious rats are exposed to hypoxia (Yamaji et al., 1996). When adrenal medullectomized rats were exposed to moderate (10.5% O2) hypoxia for 3 h, gastric acid secretion was restored to nearly the level in normoxia by the adrenal medullectomy. In severe (7.6% O2) hypoxia, the operation also caused an increase in the level of gastric acid output, although the extent was lower than that under 10.5% O2 hypoxic conditions. Gastric pH was normalized by the operation even with 7.6% O2 hypoxia. Similar results were obtained when reserpine, which causes an adrenergic discharge, was administered. When an alpha 2-adrenoceptor blocking agent, yohimbine, was administered, the inhibitory effect of 10.5% and 7.6% O2 hypoxia on gastric acid secretion was almost completely removed. However, neither prazosin (an alpha 1-adrenoceptor blocker) nor propranolol (a beta-adrenoceptor blocker) showed any significant effects on gastric acid output in hypoxia. These results indicate that acute hypoxia stimulated the adrenergic response from the adrenal medulla, and that gastric acid secretion was consequently suppressed through alpha 2-adrenoceptor.


What is Phase in Cellular Clocks?
Four inter-related measures of phase are described to study the phase synchronization of cellular oscillators, and computation of these measures is described and illustrated on single cell fluorescence data from the model filamentous fungus, Neurospora crassa. One of these four measures is the phase shift ϕ in a sinusoid of the form x(t) = A(cos(ωt + ϕ), where t is time. The other measures arise by creating a replica of the periodic process x(t) called the Hilbert transform x̃(t), which is 90 degrees out of phase with the original process x(t). The second phase measure is the phase angle FH(t) between the replica x̃(t) and x(t), taking values between -π and π. At extreme values the Hilbert Phase is discontinuous, and a continuous form FC(t) of the Hilbert Phase is used, measuring time on the nonnegative real axis (t). The continuous Hilbert Phase FC(t) is used to define the phase MC(t1,t0) for an experiment beginning at time t0 and ending at time t1. In that phase differences at time t0 are often of ancillary interest, the Hilbert Phase FC(t0) is subtracted from FC(t1). This difference is divided by 2π to obtain the phase MC(t1,t0) in cycles. Both the Hilbert Phase FC(t) and the phase MC(t1,t0) are functions of time and useful in studying when oscillators phase-synchronize in time in signal processing and circadian rhythms in particular. The phase of cellular clocks is fundamentally different from circadian clocks at the macroscopic scale because there is an hourly cycle superimposed on the circadian cycle.


Assessment of in vitro platelet activation by Advia 120 platelet parameters.
The Advia 120 Hematology System provides new platelet parameters that have been proposed as useful markers of platelet activation. The aim of this study was to investigate platelet parameter variations after adenosine diphosphate (ADP) activation of platelet-rich plasma (PRP) in vitro, with particular interest in the mean platelet component (MPC), which was compared with two well-known degranulation antigens. Changes in platelet parameters that were induced by the activation of PRP with different concentrations of ADP were examined first. The time course of parameter values up to 60 minutes after maximal ADP activation and the relationships between the MPC and P-selectin and granulophysin expression as determined by flow cytometry were then investigated. After 10 minutes of ADP stimulation, the MPC presented a dose-dependent increase. At the maximal ADP concentration, the initial increase of the MPC was followed by a progressive decrease, leading the MPC to become significantly lower with respect to the baseline after 60 minutes of incubation. Significant variations in other parameters are also described. Finally, a negative correlation was found between the MPC change with respect to time 0 and both P-selectin and granulophysin expression. The present study suggests that platelet parameter variation, particular in the MPC, may be used to assess platelet activation in PRPs stimulated by ADP.


Bad Behavior: Improving Reproducibility in Behavior Testing.
Systems neuroscience research is increasingly possible through the use of integrated molecular and circuit-level analyses. These studies depend on the use of animal models and, in many cases, molecular and circuit-level analyses. Associated with genetic, pharmacologic, epigenetic, and other types of environmental manipulations. We illustrate typical pitfalls resulting from poor validation of behavior tests. We describe experimental designs and enumerate controls needed to improve reproducibility in investigating and reporting of behavioral phenotypes.


Insect fauna associated with sugarcane plantations in Sri Lanka.
A survey conducted over 13 years (1986-1999) in sugarcane plantations in Sri Lanka to identify insects associated with sugarcane recorded a total of 103 insect species comprising Coleoptera (31 spp.), Dictyoptera (2 spp.), Diptera (5 spp.), 12 Heteroptera (12 spp.), Homoptera (18 spp.), Hymenoptera (7 spp.), Isoptera (3 spp.), Lepidoptera (13 spp.), Orthoptera (9 spp.), and one species each of Thysanoptera, Nuroptera and Trichoptera. Among them were forty-six species of sugarcane pests. In addition, 27 species of natural enemies of sugarcane pests belonging to the orders Coleoptera, Diptera and Hymenoptera were identified Epiricania melanoleuca (Fletcher) introduced into Sri Lanka from Pakistan in 1991 for the control of the sugarcane planthopper was also recorded. Five new pest species previously not recorded from sugarcane in Sri Lanka have been identified.


Scaling of average power in sub-MW peak power Yb-doped tapered fiber picosecond pulse amplifiers.
Prospects for average power scaling of sub-MW output peak power picosecond fiber lasers by utilization of a Yb-doped tapered fiber at the final amplification stage were studied. In this paper, it was shown experimentally that a tapered fiber allows the achievement of an average power level of 150 W (limited by the available pump power) with a peak power of 0.74 MW for 22 ps pulses with no signs of transverse mode instability. Measurements of the mode content using the S2 technique showed a negligible level of high order modes (less than 0.3%) in the output radiation even for the maximum output power level. Our reliability tests predict no thermal issues during long-term operation (105 hours) of the developed tapered fiber laser up to kilowatt output average power levels.


Nitrate utilization and growth in biotin-deficient Aspergillus nidulans.
A marked increase in the cellular synthesis accompanied by a decrease in the total fatty acid content was observed when Aspergillus nidulans was grown on NH4NO3 as a sole nitrogen source, in the medium containing avidin. Because of the increased uptake of NH4(plus), the level of NH4(plus), was lowered in the medium; as a result there is early uptake and assimilation of nitrate by a biotin-deficient culture as compared with the normal culture of A. nidulans. At about 17mM concentration, NH4(plus) repressed the activity of nitrate reductase. The regulation of NO3(minus) uptake and its assimilation with respect to the growth of A. nidulans have been discussed.


Gyrodactylus konovalovi sp. n. (Gyrodactylidae: Monogenoidea) from Phoxinus lagowskii Dybowski.
A new species of the genus Gyrodactylus, G. konovalovi, from the fins, gills and skin of Phoxinus lagowskii Dybowski is described. The specimens were found for the first time in the Mongolian People's Republic by Ergens and Dulmaa (1967) and were erroneously determined as D. macronychus Malmberg, 1957.


An ensemble classification of exudates in color fundus images using an evolutionary algorithm based optimal features selection.
Atomic recognition of the Exudates (EXs), the major symbol of diabetic retinopathy is essential for automated retinal images analysis. In this article, we proposed a novel machine learning technique for early detection and classification of EXs in color fundus images. The major challenge observed in the classification technique is the selection of optimal features to reduce computational time and space complexity and to provide a high degree of classification accuracy. To address these challenges, this article proposed an evolutionary algorithm based solution for optimal feature selection, which accelerates the classification process and reduces computational complexity. Similarly, three well-known classifiers that is, Naïve Bayes classifier, Support Vector Machine, and Artificial Neural Network are used for the classification of EXs. Moreover, an ensemble-based classifier is used for the selection of best classifier on the basis of majority voting technique. Experiments are performed on three well-known benchmark datasets and a real dataset developed at local Hospital. It has been observed that the proposed technique achieved an accuracy of 98% in the detection and classification of EXs in color fundus images.


A review and update on melanocyte stimulating hormone therapy: afamelanotide.
Afamelanotide ([Nle4-D-Phe7]-alpha-MSH) is an analog of alpha-melanocyte stimulating hormone given as a subcutaneous injection. Afamelanotide is currently undergoing phase II and III trials in Europe and the US for skin diseases including vitiligo, erythropoietic protoporphyria, polymorphic light eruption and prevention of actinic keratoses in organ transplant recipients. Unregulated analogs and chemicals are being sold online ahead of formal approval. A number of counterfeit chemicals, 'Melanotans' are being sold for tanning purposes. Currently, afamelanotide is already on the market in Italy and Switzerland for patients with erythropoietic protoporphyria. This paper will review the current literature on this promising compound.


Sensing Nitrogen Mustard Gas Simulant at the ppb Scale via Selective Dual-Site Activation at Au/Mn3O4 Interfaces.
The efficient detection of chemical warfare agents (CWAs), putting at stake human life and global safety, is of paramount importance in the development of reliable sensing devices for safety applications. Herein, we present the fabrication of Mn3O4-based nanocomposites containing noble metal particles for the gas-phase detection of a simulant of vesicant nitrogen mustard, i.e., di(propylene glycol) monomethyl ether (DPGME). The target materials were fabricated by chemical vapor deposition of manganese oxide on Al2O3 substrates and subsequent functionalization with silver or gold via radio frequency sputtering. The obtained high purity composites, characterized by an intimate metal/oxide contact, yielded an outstanding efficiency in the detection of DPGME. In particular, sensing of the latter analyte with an ultralow detection limit of 0.6 ppb could be performed selectively with respect to other CWA simulants. In addition, the tuneability of selectivity patterns as a function of metal nanoparticle nature paves the way to the development of efficient and selective devices for practical end uses.


Refined potential model for atomistic simulations of ionic liquid [bmim][PF6].
Refined parameters of an atomistic interaction potential model for the room temperature ionic liquid 1-n-butyl,3-methylimidazolium hexafluorophosphate are presented. Classical molecular dynamics simulations have been carried out to validate this fully flexible all-atom model. It predicts the density of the liquid at different temperatures between 300 and 500 K within 1.4% of the experimental value. Intermolecular radial distribution functions and the spatial distribution functions obtained from the new model are in close agreement with ab initio simulations. The calculated diffusion coefficients of ions and the surface tension of the liquid agree well with experiment.


Predicting water sorption and volume swelling in dense polymer systems via computer simulation.
Atomistic model structures of amorphous polyamide 6 (PA-6) and of an adhesive system consisting of the diglycidyl ether of bisphenol A (DGEBA) as epoxy resin and isophorone diamine (IPD) as a curing agent are generated. For the adhesive, we use a new approach for the generation of the cross-linked polymer networks. It takes into account the chemical reaction kinetics of the curing reaction and, therefore, results in more realistic network structures. On the basis of the corresponding model structures, the equilibrium water content and the swelling ratio of amorphous PA-6 and of the DGEBA+IPD networks are calculated via computer simulation for different thermodynamic conditions. A hybrid method is used combining the molecular dynamics technique with an accelerated test particle insertion method. The results are in reasonable agreement with experiments and, in the case of the PA-6 system, with results obtained via other computer simulation methods.


Focal increase of cerebral blood flow during stereognostic testing in man.
An attempt was made to study the regional cerebral blood flow (rCBF) pattern during stereognostic discrimination in man. The rCBF was measured in 18 subjects who had no major neurological defects. The clearance from the hemisphere of xenon 133 injected (133Xe) into the carotid artery was measured with a 254-channel dynamic gamma camera. During stereognostic discrimination with hand, mouth, or foot, the rCBF increased focally in the corresponding contralateral sensory-motor region and increased focally in the premotor part of the frontal lobe. The increase in the sensory region was attributed to the work of neurons extracting spatial features from the received input, while the increase in the motor region was ascribed to the formulation of motor strategies and motor commands. The physiological significance of the increase in the frontal region was unclear, tentatively, it was suggested to reflect the intention, selective attention, and decision of the subject.


Peripheral oxygenation in term neonates.
The aim of this study was to analyse changes in peripheral oxygenation in healthy term neonates within the first week of life with near-infrared spectroscopy and venous occlusion. Oxygen delivery did not change with increasing age. Oxygen consumption and fractional oxygen extraction increased, whereas tissue oxygenation index decreased with increasing age.


Consistent second-order boundary implementations for convection-diffusion lattice Boltzmann method.
In this study, an alternative second-order boundary scheme is proposed under the framework of the convection-diffusion lattice Boltzmann (LB) method for both straight and curved geometries. With the proposed scheme, boundary implementations are developed for the Dirichlet, Neumann and linear Robin conditions in a consistent way. The Chapman-Enskog analysis and the Hermite polynomial expansion technique are first applied to derive the explicit expression for the general distribution function with second-order accuracy. Then, the macroscopic variables involved in the expression for the distribution function is determined by the prescribed macroscopic constraints and the known distribution functions after streaming [see the paragraph after Eq. (29) for the discussions of the "streaming step" in LB method]. After that, the unknown distribution functions are obtained from the derived macroscopic information at the boundary nodes. For straight boundaries, boundary nodes are directly placed at the physical boundary surface, and the present scheme is applied directly. When extending the present scheme to curved geometries, a local curvilinear coordinate system and first-order Taylor expansion are introduced to relate the macroscopic variables at the boundary nodes to the physical constraints at the curved boundary surface. In essence, the unknown distribution functions at the boundary node are derived from the known distribution functions at the same node in accordance with the macroscopic boundary conditions at the surface. Therefore, the advantages of the present boundary implementations are (i) the locality, i.e., no information from neighboring fluid nodes is required; (ii) the consistency, i.e., the physical boundary constraints are directly applied when determining the macroscopic variables at the boundary nodes, thus the three kinds of conditions are realized in a consistent way. It should be noted that the present focus is on two-dimensional cases, and theoretical derivations as well as the numerical validations are performed in the framework of the two-dimensional five-velocity lattice model.


[The emigration of the Freud family in 1938].
The knowledge we had of the fates of Freud and his family, of the Viennese Psychoanalytic Association and its publishing house, of the centre for treatment and the premises of the Bergasse in 1938 was still very fragmentary, despite the research accomplished by Régine Lockot, Karen Brecht, Volker Friedrich, Jones' biography, and the accounts made by Richard Sterba and Max Schur. Two years ago the Viennese lawyer Dr. Martin Binder made over more than thirty files containing the deeds concerning the requests for reparation made in the name of Dr. Harry Freud and his heirs to the archives of the Sigmund Freud Gesellschaft. These files also included the deeds made out by another Viennese lawyer, Dr. Alfred Indra, who had represented Sigmund Freud in 1938, and his heirs after that in 1945. These documents have enabled us to bridge the gaps in existing accounts and to present in a more systematic fashion, with corresponding figures and dates, a part of these horrific events.


Radiotherapeutic Outcomes for Localized Primary Rectal Mucosa-Associated Lymphoid Tissue Lymphoma: A Consecutive Case Series of Three Patients.
Gastrointestinal malignant lymphoma is uncommon and accounts for a small proportion of all gastrointestinal neoplasms. Primary rectal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) is a rare type of intestinal lymphoma. Here, we report about three patients (two females, one male) with localized rectal MALToma who were treated with external beam radiation therapy (EBRT). The median age of the patients was 59 years (range: 50-67 years). Chemotherapy or eradication therapy was not performed before EBRT. All patients received a radiation dose of 30 Gy in 15 fractions using X-ray photon beams. Pathological examination confirmed complete remission of rectal MALToma after EBRT in all patients. At approximately five years after EBRT, none of the patients showed any evidence of recurrence of rectal MALToma. The use of EBRT resulted in excellent disease control, and no severe radiation-induced toxicity was observed. These results suggest that EBRT is a useful treatment modality for primary rectal MALToma.


Selection of determinants of students' adherence to COVID-19 guidelines and translation into a brief intervention.
When reopening universities in times of COVID-19, students still have to adhere to COVID-19 behavioral guidelines. We explored what behavioral determinants (and underlying beliefs) related to the adherence to guidelines are both relevant and changeable, as input for future interventions. A cross-sectional online survey was conducted (Oct-Nov 2020), identifying behavioral determinants (and underlying beliefs) of university students' adherence to COVID-19-guidelines, including keeping 1.5 m distance, getting tested, and isolating (N = 255). Attitude, perceived norm, self-efficacy, and several beliefs (e.g., risk perception beliefs 'I am not afraid because I am young' [r = -0.33; p < .001]; attitudinal beliefs, e.g., 'I feel responsible for telling people to adhere to guidelines' [r = 0.37; p < .001]; self-efficacy beliefs, e.g., 'COVID-19-prevention guidelines are difficult to adhere to' [r = -0.30; p < .001]) were associated with intention to adhere to guidelines, and for those beliefs there was room for improvement, making them suitable as possible intervention targets. Students mostly adhere to COVID-19 guidelines, but there is room for improvement. Interventions need to enhance students' adherence behavior by targeting the most relevant determinants as identified in this study. Based on these findings, a small intervention was introduced targeting the determinants of students' adherence to guidelines.


Interferon, fluorescent antibody, and neutralizing antibody responses in sera of calves inoculated with bovine respiratory syncytial virus.
Interferon, fluorescent antibody, and neutralizing antibody responses were studied in sera of 9 calves inoculated with bovine respiratory syncytial virus, in relation to viral shedding and clinical signs of disease. The calves (5.5 to 6.5 weeks of age) were assigned to 3 groups. Group I was inoculated once with the virus, and groups II and III were challenge exposed at postinoculation day (PID) 15 or 37. Serum-neutralizing and indirect fluorescent antibody techniques were used to measure antibody responses. The plaque-inhibition technique, using vesicular stomatitis virus, was applied to measure serum interferon titers. The virus was recovered by inoculation of nasal secretions onto cell cultures. Fluorescent antibody was detected in all calves on PID 3, with maximum titers appearing approximately on PID 10. Low neutralizing antibody was detected in most animals on PID 3, and titers peaked approximately 4.5 weeks after inoculation and then decreased. Interferon titers were high in all calves during the early stage of infection, dropped to undetectable amounts by PID 6, and reappeared in low amounts at least 1 week later. All infected calves manifested clinical signs of disease by PID 4 to 9. Clinical signs of disease were not observed after challenge exposure at PID 15 or 37, and anamnestic responses were not detected. Virus was recovered after challenge exposure at PID 15, but not at PID 37.


The impact of obesity and exercise on cognitive aging.
Obesity is a major concern in the aging population and degrades health, motor functions and cognition in older adults. The effects of obesity are pervasive and challenging to health-care systems, making this a widespread and critically important public health dilemma. In this review, we examine the relationship between obesity, cognitive aging, and related dysfunctions. Potential neural mechanisms underlying such relationship are described. We propose that cost-effective exercises can be employed to cope with obesity and cognitive declines in older adults. Finally, we discuss implications and future research directions.


Targeted Transfection Using PEGylated Cationic Liposomes Directed Towards P-Selectin Increases siRNA Delivery into Activated Endothelial Cells.
: The progress in small-interfering RNA (siRNA) therapeutics depends on the development of suitable nanocarriers to perform specific and effective delivery to dysfunctional cells. In this paper, we questioned whether P-selectin, a cell adhesion molecule specifically expressed on the surface of activated endothelial cells (EC) could be employed as a target for nanotherapeutic intervention. To this purpose, we developed and characterized P-selectin targeted PEGylated cationic liposomes able to efficiently pack siRNA and to function as efficient vectors for siRNA delivery to tumour necrosis factor-α (TNF-α) activated EC. Targeted cationic liposomes were obtained by coupling a peptide with high affinity for P-selectin to a functionalized PEGylated phospholipid inserted in the liposomes' bilayer (Psel-lipo). As control, scrambled peptide coupled cationic liposomes (Scr-lipo) were used. The lipoplexes obtained by complexation of Psel-lipo with siRNA (Psel-lipo/siRNA) were taken up specifically and at a higher extent by TNF-α activated b.End3 endothelial cells as compared to non-targeted Scr-lipo/siRNA. The Psel-lipo/siRNA delivered with high efficiency siRNA into the cells. The lipoplexes were functional as demonstrated by the down-regulation of the selected gene (GAPDH). The results demonstrate an effective targeted delivery of siRNA into cultured activated endothelial cells using P-selectin directed PEGylated cationic liposomes, which subsequently knock-down the desired gene.


Ethics consultation: a dangerous, antidemocratic charlatanry?
Giles Scofield's argument indicates ethics consultants may need to better clarify what in fact they are and what they are not doing, claiming, and striving for. But we must not step back too far. We must neither engage in putting in envious professional claims for exclusive rights in the area of difficult and momentous decisions in healthcare nor get stuck in discussing normative ethics at the level of metaphysics, ontology, and dogmatics (as has happened in Germany for decades). We must not do so especially in view of the achievements of ethics consultation and the growing demand for it by all parties involved, conceded even by sceptics. Ethics consultation, according to Scofield, appears to be dangerous....Let us look more closely at the logic of the argument by discussing the presumed "antidemocratic" nature. The "new tyranny" of thoughts, and the "proper" role of bioethics consultation. Some considerations about the possibility of ethics expertise shall be left for the end.


Analysis of neutrophil-derived antimicrobial peptides in gingival crevicular fluid suggests importance of cathelicidin LL-37 in the innate immune response against periodontogenic bacteria.
During periodontitis, an innate immune response to bacterial challenge is primarily mediated by neutrophils. We compared neutrophilic content and the level of neutrophil-derived antimicrobial peptides in gingival crevicular fluid (GCF) in two clinical forms of severe periodontitis. GCF was collected from 14 patients with aggressive periodontitis, 17 patients with chronic periodontitis, and nine healthy subjects. Samples were analyzed for periodontopathogen load using real-time polymerase chain reactions. The amounts of myeloperoxidase and alpha-defensins (HNP1-3) were determined by enzyme-linked immunosorbent assay, and the level of cathelicidin (hCAP18/LL-37) was assayed by Western blot. Myeloperoxidase concentration was not correlated with levels of LL-37 and HNP1-3 in samples from patients, compared to controls. The amount of HNP1-3 was twofold and fourfold higher in patients with aggressive and chronic periodontitis, respectively. Those with chronic disease had significantly elevated amounts of mature LL-37. The increased concentration of both peptides in chronic periodontitis correlated with the load of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. The lack of a correlation between LL-37, HNP1-3, and myeloperoxidase content suggests that neutrophils are not the sole source of these bactericidal peptides in the GCF of patients with periodontitis; and that other cells contribute to their local production. The bacterial proteases of P. gingivalis, T. forsythia, and T. denticola might degrade hCAP18/LL-37, because the 11-kDa cathelicidin-derived fragment was present in GCF collected from pockets infected with these bacteria. Collectively, it appears that a local deficiency in LL-37 can be considered as a supporting factor in the pathogenesis of severe cases of periodontitis.


Comparing the performance of the EQ-5D-3L and the EQ-5D-5L in young Portuguese adults.
Some studies have reported a ceiling effect in EQ-5D-3L, especially in healthy and/or young individuals. Recently, two further levels have been included in its measurement model (EQ-5D-5L). The purposes of this study were (1) to assess the properties of the EQ-5D-5L in comparison with the standard EQ-5D-3L in a sample of young adults, (2) to foreground the importance of collecting qualitative data to confirm, validate or refine the EQ-5D questionnaire items and (3) to raise questions pertaining to the wording in these questionnaire items. The data used came from a sample of respondents aged 30 or under (n = 624). They completed both versions of the EQ-5D, which were compared in terms of feasibility, level of inconsistency and ceiling effect. Agreement between the instruments was assessed using correlation coefficients and Bland-Altman plots. Known-groups validity of the EQ-5D-5L was also assessed using non-parametric tests. The discriminative properties were compared using receiver operating characteristic curves. Finally, four interviews were conducted for retrospective reports to elicit respondents' understanding and perceptions of the format, instructions, items, and responses. Quantitative results show a ceiling effect reduction of 25.3 % and a high level agreement between both indices. Known-groups validity was confirmed for the EQ-5D-5L. Explorative interviews indicated ambiguity and low degree of certainty in regards to conceptualizing differences between levels moderate-slight across three dimensions. The EQ-5D-5L performed better than the EQ-5D-3L. However, the explorative interviews demonstrated several limitations in the EQ-5D questionnaire wording and high context-dependent answers point to lack of illnesses' experience amongst young adults.


[Electrostimulation anesthesia in comparison with enflurane-nitrous-oxide inhalation anesthesia during gynecologic operations. 2. Hormonal reactions in the pre-, intra- and postoperative course].
This study describes the secretion of cortisol, growth hormone, prolactin and catecholamines before, under, and following gynaecological surgery in electrostimulation anaesthesia combined with nitrous oxide (ESA). The hormonal stress reactions of ESA were compared to inhalation anaesthesia with enflurane-nitrous oxide ( EFL ). Twenty-two patients undergoing laparotomy were allocated evenly to one of these procedures. In both groups serum levels for cortisol, growth hormone, and prolactin increased during surgery. Growth hormone showed a considerably higher increase during ESA at the end of the operation, whereas prolactin was higher at all periods of surgery during EFL . Cortisol, however, was identical for both groups. Renal excretion rates of adrenaline and noradrenaline were not significantly different. During surgery more metanephrine and normetanephrine were excreted in the urine under ESA than under EFL . There is no advantage with ESA intra- or postoperatively as compared to other routine procedures of anaesthesia for abdominal gynaecological surgery with regard to the so-called stress hormones or sympathetic activity.


A Custom-Developed Emergency Department Provider Electronic Documentation System Reduces Operational Efficiency.
Electronic health record implementation can improve care, but may also adversely affect emergency department (ED) efficiency. We examine how a custom, ED provider, electronic documentation system (eDoc), which replaced paper documentation, affects operational performance. We analyzed retrospective operational data for 1-year periods before and after eDoc implementation in a single ED. We computed daily operational statistics, reflecting 60,870 pre- and 59,337 postimplementation patient encounters. The prespecified primary outcome was daily mean length of stay; secondary outcomes were daily mean length of stay for admitted and discharged patients and daily mean arrival time to disposition for admitted patients. We used a prespecified multiple regression model to identify differences in outcomes while controlling for prespecified confounding variables. The unadjusted change in length of stay was 8.4 minutes; unadjusted changes in secondary outcomes were length of stay for admitted patients 11.4 minutes, length of stay for discharged patients 1.8 minutes, and time to disposition 1.8 minutes. With a prespecified regression analysis to control for variations in operational characteristics, there were significant increases in length of stay (6.3 minutes [95% confidence interval 3.5 to 9.1 minutes]) and length of stay for discharged patients (5.1 minutes [95% confidence interval 1.9 to 8.3 minutes]). There was no statistically significant change in length of stay for admitted patients or time to disposition. In our single-center study, the isolated implementation of eDoc was associated with increases in overall and discharge length of stay. Our findings suggest that a custom-designed electronic provider documentation may negatively affect ED throughput. Strategies to mitigate these effects, such as reducing documentation requirements or adding clinical staff, scribes, or voice recognition, would be a valuable area of future research.


Standardization and validation of an alkaline phosphatase-linked immunoassay to quantify a plant-derived antibody directed against the hepatitis B virus surface antigen.
Immunopurification is one of the most effective chromatography steps to purify the hepatitis B surface antigen, which have successfully been used as an active pharmaceutical ingredient of hepatitis B vaccines. Plant-derived antibodies could be an appropriated ligand for such purposes because plants are the most cost-effective production systems and have the additional advantage that plant viruses cannot infect humans. In this work, a polyclonal antibody alkaline phosphatase-linked immunoassay was standardized and validated to quantify a plant-derived antibody directed against the HBsAg. The validation of an immunoassay to quantify plantibodies is a relatively complex task due to the complexity of the plant extract, the low level of expression of this molecule, and the potential interferences of endogenous peroxidases contributed by plants. These results allow estimating the plant-derived antibody concentration up to 3.81 ng/mL with high specificity, precision, and repeatability. The working range of the standard curve was between 3.81 and 60 ng/mL, and the intra- and inter-variation coefficients were between 10% and 20% in a production process's sample dependent way. This enzyme-linked immunosorbent assay is considered valuable to improve the design of the purification process and also to obtain a better estimation of the antibody expression level and process's recovery.


A population-based study of prognosis of ruptured cerebral aneurysm: mortality and recurrence of subarachnoid hemorrhage.
To determine the risk of recurrent subarachnoid hemorrhage (SAH), mortality, and relative survivorship following SAH caused by ruptured cerebral aneurysm (RCA). The 86 individuals with a first diagnosis of SAH caused by RCA in Iceland from 1958 through 1968 were followed a minimum of 24 years (range, 24 to 32.5 years) or until death to determine mortality and to identify those with recurrent SAH. Thirty-eight patients (44%) died within 30 days of the index event. Two additional (both comatose from onset of ictus) died in the following month. There were no deaths between 3 and 6 months after onset. Based upon the age/gender-specific person years of observation for the population of Iceland, the Standardized Mortality Ratio for the 44 surgically treated patients surviving 6 months was 1.3. Those neurologically normal or with only mild impairment at 6 months had no identified increase in mortality. Excess mortality that was limited to individuals with severe neurologic deficit at 6 months could be identified through the first 10 years after onset. Two 6-month survivors experienced recurrent SAH. Early mortality is high (47%) in patients with RCA. In patients operated on for RCA and surviving 6 months, recurrent SAH occurred in 5%. Survivorship among patients surgically treated and neurologically normal or with mild residual neurologic impairment at 6 months following presentation was similar to that expected in the general population. Survivorship among patients surgically treated who had severe residual neurologic impairment at 6 months was significantly reduced.


[Modulation of cortical excitability by transcranial direct current stimulation].
Modulation of cerebral excitability is thought to be one mechanism underlying the pharmacological treatment of neuropsychiatric diseases such as epilepsy, depression, and dystonia. Repetitive transcranial magnetic stimulation (rTMS) has been tested for several years as a nonpharmacological, noninvasive method of directly influencing patients' cortical functions. We present an overview of the more easily performed transcranial direct current stimulation (tDCS) with weak current, which produces distinctly more pronounced changes in excitability than rTMS. The basic underlying mechanism is a shift in the resting membrane potential towards either hyper- or depolarisation, depending on stimulation polarity. This in turn leads to changes in the excitability of cortical neurons. Anodic stimulation increases cortical excitability, while cathodic stimulation decreases it. These changes persist after the end of stimulation if the stimulation lasts long enough, i.e., at least several minutes. The duration of this aftereffect can be controlled through the duration and intensity of the stimulation. Transcranial direct current stimulation essentially allows a focal, selective, reversible, pain-free, and noninvasive induction of changes in cortical excitability, the therapeutic potential of which must be evaluated in clinical studies, once possible risk factors have been assessed.


Longitudinal assessment of bone mineral density in children and adolescents with inflammatory bowel disease.
Low bone mineral density (BMD) is recognized as a potential problem in children with inflammatory bowel disease (IBD). We aimed to describe the longitudinal development of BMD in a population of Swedish pediatric patients with IBD. A total of 144 patients with IBD (93 males; 83 with ulcerative colitis [UC], 45 with Crohn disease [CD]) were examined with dual-energy x-ray absorptiometry at baseline. At follow-up 2 years later, 126 of the initial 144 patients were reexamined. BMD values are expressed as z scores. Children with UC and CD had significantly lower mean BMD z scores for the lumbar spine (LS) at baseline and after 2 years. The reduction in BMD was equally pronounced in patients with UC and CD, and neither group improved their z score during the follow-up period. Furthermore, significantly lower mean BMD z scores for the LS were found at baseline in boys (-1.1 SD, ±2.7 SD, P < 0.001), but not in girls (-0.0 SD, ±3.0 SD). This finding remained unchanged at follow-up. Subanalyses of the different age groups at baseline showed the lowest BMD values in the group of patients ages 17 to 19 years in boys (mean z score for the LS 1.59 SD, ±3.1 SD) and in girls (mean z score for the LS -3.40 SD, ±3.1 SD); however, at follow-up, these patients had improved their BMD significantly (mean change z score for the LS 1.00 SD, 95% CI 0.40-1.60; 1.90 SD, 95% CI 0.60-3.20). In this longitudinal study, the entire group of pediatric patients with IBD showed permanent decreases in their BMD z scores for the LS; however, our data indicate that afflicted children have the potential to improve their BMD by the time they reach early adulthood.


Activatable QD-Based Near-Infrared Fluorescence Probe for Sensitive Detection and Imaging of DNA.
Accurate detection of DNA is essential for the precise diagnosis of diseases. Here we report an activatable near-infrared (NIR) fluorescence nanoprobe (QD-Al-GFLX) composed of NIR quantum dots (QDs) and Al(III)-gatifloxacin (Al-GFLX) complexes for the sensitive detection of double-stranded DNA (dsDNA) both in aqueous solution and in living cells. We demonstrated that the initial strong NIR fluorescence of QDs in QD-Al-GFLX was quenched by the Al-GFLX complex via a photoinduced electron transfer (PET) mechanism. Upon interaction with dsDNA, the high binding affinity between dsDNA and Al-GFLX complex could trigger QD-Al-GFLX dissociation, which could eliminate the PET process, resulting in significant enhancement of NIR fluorescence. QD-Al-GFLX was sensitive and specific to detect dsDNA in aqueous solution, with a detection limit of 6.83 ng/mL. The subsequent fluorescence imaging revealed that QD-Al-GFLX holds a high ability to enter into live cells, generating strong NIR fluorescence capable of reporting on dsDNA levels. This study highlighted the potential of using QD-Al-GFLX nanoprobe for the real-time detection and imaging of dsDNA in living cells.


Technical note: adipose tissue blood flow in miniature swine (Sus scrofa) using the 133xenon washout technique.
The purpose of this study was to examine the 133xenon washout technique as a viable method for measuring adipose tissue blood flow (ATBF) in swine. Using a total of 32 female Yucatan miniature swine (Sus scrofa), the partition coefficient for 133xenon in swine subcutaneous adipose tissue was determined and ATBF was measured at rest and under various physiological conditions. These conditions included feeding, anesthesia, epinephrine infusion, and acute exercise. The effects of epinephrine and acute exercise were examined in both sedentary and exercise-trained swine. The partition coefficient value for 133xenon in swine subcutaneous adipose tissue was 9.23+/-0.26 mL/g (mean +/- SD, n = 10). The average value for resting ATBF in swine was 3.98+/-2.72 mL/(100 g tissue-min) (n = 19). Feeding increased ATBF by approximately fivefold over fasting values, and isoflurane anesthesia significantly decreased ATBF compared to rest (1.64+/-1.12 vs 3.92+/-4.22 mL/[100 g x min], n = 10). A 30-min epinephrine infusion (1 microg/[kg BW x min]) significantly increased ATBF from a resting value of 3.13+/-2.61 to 10.35+/-5.31 mL/(100 g x min) (n = 12). Epinephrine infusion into exercise-trained swine increased ATBF to the same extent as when infused into sedentary swine. An acute, 20-min bout of exercise significantly increased ATBF in swine, and the sedentary swine showed a larger increase in ATBF than their exercise-trained littermates relative to rest: 7.83 vs 2.98 mL/(100 g x min). In conclusion, the 133xenon washout technique appears to be a viable method for measuring ATBF in swine; our findings are comparable to swine ATBF values reported using the microsphere method and are consistent with values reported in animal and human studies.


Vaccine-induced humoral response against SARS-CoV-2 dramatically declined but cellular immunity possibly remained at 6 months post BNT162b2 vaccination.
To evaluate vaccine-induced humoral and cell-mediated immunity at 6 months after completion of two doses of BNT162b2 vaccination, immunoglobulin G against SARS-CoV-2 spike protein (SP IgG), 50% neutralizing antibody (NT50), and spot-forming cell (SFC) counts were evaluated by interferon-γ releasing ELISpot assay of 98 healthy subjects (median age, 43 years). The geometric mean titers of SP IgG and NT50 decreased from 95.2 (95% confidence interval (CI) 79.8-113.4) to 5.7 (95% CI 4.9-6.7) and from 680.4 (588.0-787.2) to 130.4 (95% CI 104.2-163.1), respectively, at 3 weeks and 6 months after the vaccination. SP IgG titer was negatively correlated with age and alcohol consumption. Spot-forming cell counts at 6 months did not correlate with age, gender, and other parameters of the patients. SP IgG, NT50, and SFC titers were elevated in the breakthrough infected subjects. Although the levels of vaccine-induced antibodies dramatically declined at 6 months after vaccination, a certain degree of cellular immunity was observed irrespective of the age.


Improving Sleep Health Among Refugees: A Systematic Review.
Sleep disorders among refugees are common yet understudied. Interventions are difficult in resource-limited settings where most of these populations live. A systematic review of sleep disorders in refugee populations is warranted to identify prevalence, comorbidities, and the limitations of the current state of sleep health among refugees. Sleep disturbances, particularly insomnia and nightmares, occur with a higher prevalence among refugees. Diseases associated with insomnia in this population included fibromyalgia, posttraumatic stress disorder, depression, and anxiety. Risk factors include trauma, migration, lower socioeconomic status, lower educational level, and settlement in areas with a high influx of new residents or proximity to conflict. Only a few partially successful therapies were identified. This review identifies the high prevalence of the disturbed sleep in this population and its risk factors. It proposes ways of increasing awareness of it in this vulnerable population as a first step toward remediation.


The Staged Urethroplasty with Vascularised Scrotal Flap and Buccal Mucosa Graft after Failed Hypospadias Surgery: A Reliable Technique with a Novel Tool.
Background/Aims/Objectives: To report the outcome of staged urethroplasty with buccal mucosa and vascularised scrotal flap after failed hypospadias surgery. n = 35. destroyed urethral plate, deficient local skin, fistula and penile deviation. Five out of 35 patients also had a secondary proximal stricture. Stage 1: excision of scarred tissue and fistulae, correction of the penile deviation through dorsal plication and the ventral placement and quilting of buccal graft. Stage 2: tubularisation of the neourethral plate; in 20 patients with deficient penile skin a vascularised scrotal flap was developed and transferred on the tubularised urethra. In 5 patients, the proximal stricture was repaired during a separate operation by using buccal graft, the distal urethra was marsupialised. The repair of the distal urethra was performed later as described above. Thirty-three patients are recurrence-free without further interventions; successful reoperation was done in 2 cases. 1 graft necrosis; 1 coronary fistula; 1 scrotal flap necrosis and 1 case of hematoma. Complicated strictures after multiple failed hypospadias repair are well managed by using buccal graft. The vascularised scrotal flap is a very useful tool in case of deficient and scarred penile skin and could explain the low rate of fistula formation in our series.