[Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia].
Objective: To compare and analyze patient's general condition, changes in laboratory parameters, and the spectrum of UGT1A1 mutations in patients with inherited non-hemolytic unconjugated hyperbilirubinemia. Methods: A retrospective study was conducted at Nanjing Second Hospital from January 2015 to July 2018 and patients' demographic characteristics, liver function test, and UGT1A1 gene were analyzed. The categorical variable data were compared by χ (2) test. The normal distribution continuous variable data were compared by t-test and the non-normal distribution continuous variable data were compared using Mann-Whitney U test. Results: Of the 51 patients with inherited non-hemolytic unconjugated hyperbilirubinemia, 44 (86.3%) were Gilbert's syndrome (GS) and seven (13.7%) were Crigler-Najjar syndrome type II (CNS- II). The male to female ratio was 2.9:1 and the average age was 36.11 ± 13.17 years. Six variant types were detected: C. -40_-39insTA, C. -3279T > G, c.211G > A (p.G71R), c.686C > A (p.P229Q), c.1091C > T (p.P364L), c.1456T > G (P.Y486D). Among them, c.211G > A accounted for 58.82% (30/51), c.-40_-39insTA accounted for 27.5% (14/51), and c.1456T > G accounted for 25.5% (13/51). The total bilirubin(TB) and unconjugated bilirubin (UCB) in CNS-II patients were significantly higher than GS patients[155.91 (130 ~ 207) vs. 38.25(29 ~ 52.15) μmol/L, U = 0, P < 0.01; 144.13 (120.8 ~ 197) vs. 30.00 (21.7 ~ 46.75) μmol/L, U = 0.00, P < 0.01, respectively]. Exon mutations of c.1091C > T and c.1456T > G were statistically significant(P < 0.01).There were no differences in age, TB, UCB, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the c.211G > A homozygous variants and heterozygous variants (P > 0.05). Conclusion: The common pathogenic mutations of UGT1A1 gene were c.211G > A, c.-40_-39insTA, c.1456T > G. c.211G > A. The mutation has little effect on the level of total bilirubin, but c.1091C > T, c.1456T > G mutations has great influence on the level of total bilirubin.


Complementary Intradermal and Patch Testing for Increased Diagnostic Accuracy of Nickel Allergy in Non-Celiac Wheat Insensitivity.
D'Alcamo et al. astutely highlighted a potential immunologic association between nickel allergy, determined by positive epicutaneous patch testing, and the rise of non-celiac wheat sensitivity (NCWS) in the world of gluten-related diseases. Consecutive algorithms including both patch and intradermal testing could provide vital information to more accurately define the patient populations with NCWS, systemic nickel allergy syndrome, and nickel-associated allergic contact dermatitis.


Functional diversity response to hardwood forest management varies across taxa and spatial scales.
Contemporary forest management offers a trade-off between the potential positive effects of habitat heterogeneity on biodiversity, and the potential harm to mature forest communities caused by habitat loss and perforation of the forest canopy. While the response of taxonomic diversity to forest management has received a great deal of scrutiny, the response of functional diversity is largely unexplored. However, functional diversity may represent a more direct link between biodiversity and ecosystem function. To examine how forest management affects diversity at multiple spatial scales, we analyzed a long-term data set that captured changes in taxonomic and functional diversity of moths (Lepidoptera), longhorned beetles (Coleoptera: Cerambycidae), and breeding birds in response to contemporary silvicultural systems in oak-hickory hardwood forests. We used these data sets to address the following questions: how do even- and uneven-aged silvicultural systems affect taxonomic and functional diversity at the scale of managed landscapes compared to the individual harvested and unharvested forest patches that comprise the landscapes, and how do these silvicultural systems affect the functional similarity of assemblages at the scale of managed landscapes and patches? Due to increased heterogeneity within landscapes, we expected even-aged silviculture to increase and uneven-aged silviculture to decrease functional diversity at the landscape level regardless of impacts at the patch level. Functional diversity responses were taxon-specific with respect to the direction of change and time since harvest. Responses were also consistent across patch and landscape levels within each taxon. Moth assemblage species richness, functional richness, and functional divergence were negatively affected by harvesting, with stronger effects resulting from uneven-aged than even-aged management. Longhorned beetle assemblages exhibited a peak in species richness two years after harvesting, while functional diversity metrics did not differ between harvested and unharvested patches and managed landscapes. The species and functional richness of breeding bird assemblages increased in response to harvesting with more persistent effects in uneven- than in even-aged managed landscapes. For moth and bird assemblages, species turnover was driven by species with more extreme trait combinations. Our study highlights the variability of multi-taxon functional diversity in response to forest management across multiple spatial scales.


Role of radiomics in predicting lymph node metastasis in gastric cancer: a systematic review.
Gastric cancer (GC) is an aggressive and clinically heterogeneous tumor, and better risk stratification of lymph node metastasis (LNM) could lead to personalized treatments. The role of radiomics in the prediction of nodal involvement in GC has not yet been systematically assessed. This study aims to assess the role of radiomics in the prediction of LNM in GC. A PubMed/MEDLINE systematic review was conducted to assess the role of radiomics in LNM. The inclusion criteria were as follows: i. original articles, ii. articles on radiomics, and iii. articles on LNM prediction in GC. All articles were selected and analyzed by a multidisciplinary board of two radiation oncologists and one surgeon, under the supervision of one radiation oncologist, one surgeon, and one medical oncologist. A total of 171 studies were obtained using the search strategy mentioned on PubMed. After the complete selection process, a total of 20 papers were considered eligible for the analysis of the results. Radiomics methods were applied in GC to assess the LNM risk. The number of patients, imaging modalities, type of predictive models, number of radiomics features, TRIPOD classification, and performances of the models were reported. Radiomics seems to be a promising approach for evaluating the risk of LNM in GC. Further and larger studies are required to evaluate the clinical impact of the inclusion of radiomics in a comprehensive decision support system (DSS) for GC.


Fargesin improves lipid and glucose metabolism in 3T3-L1 adipocytes and high-fat diet-induced obese mice.
This study examined the effects of fargesin, a neolignan isolated from Magnolia plants, on obesity and insulin resistance and the possible mechanisms involved in these effects in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. Fargesin promoted the glucose uptake in 3T3-L1 adipocytes. In HFD-induced obese mice, fargesin decreased the body weight gain, white adipose tissue (WAT), and plasma triglyceride, non-esterified fatty acid and glucose levels, and improved the glucose tolerance. Fargesin increased glucose transporter 4 (GLUT4) protein expression and phosphorylation of Akt, AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC) in both 3T3-L1 adipocytes and WAT of HFD-induced obese mice. Fargesin also decreased the mRNA expression levels of fatty acid oxidation-related genes, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase-1 (CPT-1), uncoupling protein-2 (UCP-2) and leptin in WAT. Taken together, the present findings suggest that fargesin improves dyslipidemia and hyperglycemia by activating Akt and AMPK in WAT.


Heterogeneous treatment effects in stratified clinical trials with time-to-event endpoints.
When analyzing clinical trials with a stratified population, homogeneity of treatment effects is a common assumption in survival analysis. However, in the context of recent developments in clinical trial design, which aim to test multiple targeted therapies in corresponding subpopulations simultaneously, the assumption that there is no treatment-by-stratum interaction seems inappropriate. It becomes an issue if the expected sample size of the strata makes it unfeasible to analyze the trial arms individually. Alternatively, one might choose as primary aim to prove efficacy of the overall (targeted) treatment strategy. When testing for the overall treatment effect, a violation of the no-interaction assumption renders it necessary to deviate from standard methods that rely on this assumption. We investigate the performance of different methods for sample size calculation and data analysis under heterogeneous treatment effects. The commonly used sample size formula by Schoenfeld is compared to another formula by Lachin and Foulkes, and to an extension of Schoenfeld's formula allowing for stratification. Beyond the widely used (stratified) Cox model, we explore the lognormal shared frailty model, and a two-step analysis approach as potential alternatives that attempt to adjust for interstrata heterogeneity. We carry out a simulation study for a trial with three strata and violations of the no-interaction assumption. The extension of Schoenfeld's formula to heterogeneous strata effects provides the most reliable sample size with respect to desired versus actual power. The two-step analysis and frailty model prove to be more robust against loss of power caused by heterogeneous treatment effects than the stratified Cox model and should be preferred in such situations.


Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study.
Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles. To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced. Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity. Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.


Structural and Mechanistic Insights into Protein Translocation.
Many proteins are translocated across the endoplasmic reticulum (ER) membrane in eukaryotes or the plasma membrane in prokaryotes. These proteins use hydrophobic signal sequences or transmembrane (TM) segments to trigger their translocation through the protein-conducting Sec61/SecY channel. Substrates are first directed to the channel by cytosolic targeting factors, which use hydrophobic pockets to bind diverse signal and TM sequences. Subsequently, these hydrophobic sequences insert into the channel, docking into a groove on the outside of the lateral gate of the channel, where they also interact with lipids. Structural data and biochemical experiments have elucidated how channel partners, the ribosome in cotranslational translocation, and the eukaryotic ER chaperone BiP or the prokaryotic cytosolic SecA ATPase in posttranslational translocation move polypeptides unidirectionally across the membrane. Structures of auxiliary components of the bacterial translocon, YidC and SecD/F, provide additional insight. Taken together, these recent advances result in mechanistic models of protein translocation.


Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry.
Skeletal muscle terminal differentiation starts with the commitment of pluripotent mesodermal precursor cells to myoblasts. These cells have still the ability to proliferate or they can differentiate and fuse into multinucleated myotubes, which maturate further to form myofibers. Skeletal muscle terminal differentiation is orchestrated by the coordinated action of various transcription factors, in particular the members of the Muscle Regulatory Factors or MRFs (MyoD, Myogenin, Myf5, and MRF4), also called the myogenic bHLH transcription factors family. These factors cooperate with chromatin-remodeling complexes within elaborate transcriptional regulatory network to achieve skeletal myogenesis. In this, MyoD is considered the master myogenic transcription factor in triggering muscle terminal differentiation. This notion is strengthened by the ability of MyoD to convert non-muscle cells into skeletal muscle cells. Here we describe an approach used to identify MyoD protein partners in an exhaustive manner in order to elucidate the different factors involved in skeletal muscle terminal differentiation. The long-term aim is to understand the epigenetic mechanisms involved in the regulation of skeletal muscle genes, i.e., MyoD targets. MyoD partners are identified by using Tandem Affinity Purification (TAP-Tag) from a heterologous system coupled to mass spectrometry (MS) characterization, followed by validation of the role of relevant partners during skeletal muscle terminal differentiation. Aberrant forms of myogenic factors, or their aberrant regulation, are associated with a number of muscle disorders: congenital myasthenia, myotonic dystrophy, rhabdomyosarcoma and defects in muscle regeneration. As such, myogenic factors provide a pool of potential therapeutic targets in muscle disorders, both with regard to mechanisms that cause disease itself and regenerative mechanisms that can improve disease treatment. Thus, the detailed understanding of the intermolecular interactions and the genetic programs controlled by the myogenic factors is essential for the rational design of efficient therapies.


Dural Tears In Patients With Depressed Skull Fractures.
The presence of skull fracture in patients sustaining traumatic brain injury is an important risk factor for intracranial lesions. Assessment of integrity of dura in depressed skull fracture is of paramount importance because if dura is torn, lacerated brain matter may be present in the wound which needs proper debridement followed by water tight dural closure to prevent meningitis, cerebral abscess, and pseudomeningocoele formation. The objective of this study was to determine the frequency of dural tear in patients with depressed skull fractures. This cross-sectional study was conducted at Department of Neurosurgery Ayub Teaching Hospital Abbottabad. All the patients of either patients above 1 year of age with depressed skull fracture were included in this study in consecutive manner. Patients were operated for skull fractures and per-operatively dura in the region of depressed skull fracture was closely observed for any dural tear. The data were collected on a predesigned pro forma. A total of 83 patients were included in this study out of which 57 (68.7%) were males and 26 (31.3%) were females. The age of the patients ranged from 1-50 (mean 15.71±13.49 years). Most common site of depressed skull fracture was parietal 32 (38.6%), followed by Frontal in 24 (28.9%), 21(25.3%) in temporal region, 5(6.0%) were in occipital region and only 1 (1.2%) in posterior fossa. Dural tear was present in 28 (33.7%) patients and it was absent in 55 (66.3%) of patients. In depressed skull fractures, there are high chances of associated traumatic dural tears which should be vigilantly managed.


[Clinical value of determination of digoxin concentration in blood during treatment of cardiac insufficiency].
The concentration of digoxin in blood was determined by the radio-immunologic method in 41 patients with circulatory insufficiency and permanent form of auricular fibrillation who were treated with the drug. In 85.5% of cases the therapeutic digoxin concentrations did not exceed 2 ng/ml. The therapeutic concentrations ranged from 0.3 to 3.6 ng/ml, the toxic from 0.9 to 6 ng/ml. A relationship was established between the dose of digoxin and its concentration in the blood of patients with normal renal filtration. It is concluded that the blood digoxin concentrations alone, without the clinical data being taken into account, cannot be a reliable criterion in assessment of the level of saturation with cardiac glycosides. Study of the dynamics of blood digoxin concentration in each patient allows its determination to be used to assess the tolerance to the drug, choose the adequate maintenance dose and the time for its correction, and to confirm the clinical signs of digitalis intoxication if the concentration of digoxin is above 2.5 ng/ml.


Can't control yourself? Monitor those bad habits.
What strategies can people use to control unwanted habits? Past work has focused on controlling other kinds of automatic impulses, especially temptations. The nature of habit cuing calls for certain self-control strategies. Because the slow-to-change memory trace of habits is not amenable to change or reinterpretation, successful habit control involves inhibiting the unwanted response when activated in memory. In support, two episode-sampling diary studies demonstrated that bad habits, unlike responses to temptations, were controlled most effectively through spontaneous use of vigilant monitoring (thinking "don't do it," watching carefully for slipups). No other strategy was useful in controlling strong habits, despite that stimulus control was effective at inhibiting responses to temptations. A subsequent experiment showed that vigilant monitoring aids habit control, not by changing the strength of the habit memory trace but by heightening inhibitory, cognitive control processes. The implications of these findings for behavior change interventions are discussed.


Polymorphism of the human Ha-ras oncogene locus in chronic lymphocytic and chronic myelogenous leukemia.
DNA from white blood cells from healthy controls demonstrates a restriction fragment length polymorphism (RFLP) of the Ha-ras oncogene locus after cleavage with the restriction enzymes BamH I or MspI plus HpaII, representing frequent and rare alleles. We have studied the RFLP of 15 patients with B-cell chronic lymphocytic (CLL) and of 16 patients with chronic myelogenous leukemia (CML). As in healthy controls the RFLP in the leukemic cells indicates the occurrence of frequent and rare Ha-ras alleles. But rare alleles are not more frequent in the patients than in the healthy control group. The frequency of rare Ha-ras alleles also does not differ between chronic lymphocytic and chronic myelogenous leukemia. While rare alleles of this oncogene locus occur in CML and CLL as frequently as in healthy controls, they do not reflect an inherent increased risk for chronic leukemia in man.


Tea-based biochar-mediated changes in cation diffusion homeostasis in rice grown in heavy metal (loid) contaminated mining soil.
Foreseeable future scenarios highlight the urgency of applying eco-safe avoidance methods or tolerance to heavy metal(loid) (HM) stress in agricultural production areas of contamination. The analyses show that the Ni, Mn, As, and Cr concentrations detected in the soils of the paddy fields in the Black Sea region vary between 123.60 and 263.30; 687-1271; 8.90-14.50; 162.00-340.00 mg kg-1 proving high accumulation of Ni, Mn, As, Cr in rice. Overconsumption of rice farmed extensively on these soils might also lead to human HM-related health problems. Therefore, in the current study, the approach of using tea-based biochar (BC) proven to have one of the most significant potentials as a soil amendment to reduce HM transmission to in-vitro-grown rice plants was investigated in the soil medium naturally contaminated with HMs. The tea-BC was produced from readily available local black tea waste of a conventional fermentation process and applied in the in-vitro experiments. Among the tested doses examined, 1% tea-BC showed a more positive effect on rice plant growth and development characterized by a better relative growth rate (59.7 and 84 mg g-1 d-1 for root and shoot tissues), photosynthetic pigment intactness (62.48 μg mL-1), cellular membrane integrity (93%), and relative water (96%) than the other rates (0% BC, 3%BC, 5%BC). The mRNA expression data highlights the probability of a cation diffusion facilitator (CDF) (OsMTP11) in concert with catalase isozyme (CATa) and dehydration-responsive element binding protein (DREB1a) linking the HM detoxification, oxidative defense, and dehydration pathways with the help of tea-BC. At the optimum concentration (1%BC), this approach might reduce HM accumulation levels of crops planted in HM-contaminated farmlands.


Demographic and clinical risk factors for diagnosis of sleep disorders in ESRD patients.
Sleep disturbances in patients with end-stage renal disease (ESRD) are common and more prevalent than in the general population. This study aims to assess the demographic and clinical risk factors for the diagnosis of sleep disorders in ESRD patients. This study is a retrospective analysis of the United States Renal Data System (USRDS) to evaluate risk factors for the diagnosis of sleep disorders, including hypersomnolence, insomnia, restless leg syndrome (RLS), or obstructive or central sleep apnea (OSA/CSA). All ESRD subjects enrolled in the USRDS between 2004-2015 were eligible for inclusion. The risk factors analyzed were age, race, sex, ethnicity, access type, dialysis modality, and the Charlson Comorbidity Index (CCI). All statistical analysis was performed using SAS 9.4, and statistical significance was assessed using an alpha level of 0.05. Descriptive statistics on all variables overall and by each sleep diagnosis were determined. Increasing age, black race, other race, and Hispanic ethnicity were associated with decreased risk of each sleep diagnosis while CCI was associated with increased risk. Females were at increased risk of RLS and insomnia while males were at increased risk of OSA/CSA. Catheter and graft access decreased risk of RLS but increased risk of insomnia compared to AVF access. Catheter access increased risk of OSA/CSA compared to graft access. Hemodialysis increased risk of OSA/CSA compared to peritoneal dialysis. Some ESRD patients are at an increased risk for diagnosis of sleep disorders based on age, race, sex, comorbid health conditions, and dialysis modality.


One fish, two fish, red fish, blue fish: geography, ecology, sympatry, and male coloration in the lake Malawi cichlid genus labeotropheus (perciformes: cichlidae).
While sexual selection on male coloration has been important in haplochromine cichlid speciation, few studies to date have examined potential environmental influences on color pattern evolution. Data from multiple sources on male nuptial coloration of the Lake Malawi endemic genus Labeotropheus were used to examine the relationship between color patterns and the environments in which these patterns were found. Red- or carotenoid-pigmented males were concentrated in the northwestern portion of Lake Malawi and were also associated with increasing depth. Further, the presence or absence of L. fuelleborni influenced the coloration of L. trewavasae populations; when L. fuelleborni was present, L. trewavasae males were more likely to exhibit some degree of red coloration. While these results support the idea that sexual selection on male coloration is an important factor in the haplochromine speciation, they also underscore the importance of environmental influences on the evolution of color patterns.


Atherogenesis and autoimmune disease: the model of lupus.
Accelerated atherosclerosis is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Certain 'classic' risk factors are associated with atherosclerosis risk in SLE. However, these factors alone do not fully explain the excess risk observed. Atherosclerosis is increasingly recognized as a chronic inflammatory condition and in SLE, complement activation and immune complex formation may promote atheroma development. Similarly, autoantibody production, especially those in the anticardiolipin (ACLA) family are gaining increasing attention. The role of steroids may not be completely straightforward, low doses may have a beneficial anti-inflammatory role whereas higher doses may exacerbate metabolic factors. In contrast, antimalarials have a beneficial effect on lipids as well as anti-inflammatory and anti-platelet effects. The aetiology of atherosclerosis in SLE is therefore multifactorial. A better understanding of the interface of autoimmunity and atherogenesis in the context of SLE will benefit lupus patients and will also help us better understand the pathogenesis of atherosclerosis in general.


Tissue-specific Tregs in cancer metastasis: opportunities for precision immunotherapy.
Decades of advancements in immuno-oncology have enabled the development of current immunotherapies, which provide long-term treatment responses in certain metastatic cancer patients. However, cures remain infrequent, and most patients ultimately succumb to treatment-refractory metastatic disease. Recent insights suggest that tumors at certain organ sites exhibit distinctive response patterns to immunotherapy and can even reduce antitumor immunity within anatomically distant tumors, suggesting the activation of tissue-specific immune tolerogenic mechanisms in some cases of therapy resistance. Specialized immune cells known as regulatory T cells (Tregs) are present within all tissues in the body and coordinate the suppression of excessive immune activation to curb autoimmunity and maintain immune homeostasis. Despite the high volume of research on Tregs, the findings have failed to reconcile tissue-specific Treg functions in organs, such as tolerance, tissue repair, and regeneration, with their suppression of local and systemic tumor immunity in the context of immunotherapy resistance. To improve the understanding of how the tissue-specific functions of Tregs impact cancer immunotherapy, we review the specialized role of Tregs in clinically common and challenging organ sites of cancer metastasis, highlight research that describes Treg impacts on tissue-specific and systemic immune regulation in the context of immunotherapy, and summarize ongoing work reporting clinically feasible strategies that combine the specific targeting of Tregs with systemic cancer immunotherapy. Improved knowledge of Tregs in the framework of their tissue-specific biology and clinical sites of organ metastasis will enable more precise targeting of immunotherapy and have profound implications for treating patients with metastatic cancer.


[The treatment with biosynthetic growth hormone (GH) of familial short stature].
The effect of growth hormone (GH) treatment in non-GH deficient subjects has been amply studied over the past few years. Although the results of these studies are encouraging, there are still no definitive data since the findings are not comparable due to the different characteristics of the populations examined. In the present study the authors examined the following parameters: stature, height SDS, growth rate, bone age and final height prediction according to Tanner, pubertal stage, before and after treatment with biosynthetic GH at a dose of 1.4 IU/kg of bodyweight for 12 months. The population treated consisted of 10 subjects (5 males and 5 females) aged between 7.3 and 9.5 years old, all prepubertal, with "familial short stature", selected according to the following criteria: stature below the 3rd centile, normal growth rate, normal GH response to stimuli using clonidine and insulin, correlation with parental stature between 25th and 75th centile, bone age correlated to chronological age, absence of other pathologies. After 12 months height SDS moved from -2.75 +/- 0.26 to -2.23 +/- 0.25 (p < 0.5); the growth rate changed from 5.75 +/- 0.63 to 6.66 +/- 0.56 (p < 0.05). No abnormal acceleration of bone age as observed: it moved from 8.2 +/- 0.62 to 9.5 +/- 0.72; all subjects continued to be prepubertal. The expected final stature changed from 154 +/- 2.38 to 159 +/- 0.7 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


[Hospital infection prevention in an intensive care unit].
Aim of the study was to evaluate the efficacy of the hospital infection preventive procedures adopted in the intensive care unit (ICU) of the "S. Camillo-Forlanini" hospital in Rome. First the following prevention protocols were analysed: invasive procedures (intubation, CVC and urinary catheter), surveillance cultures, infection management and antimicrobial prophylaxis. Comparison with international guidelines was carried out and protocols enforcement by the personnel was verified. Secondly a one year longitudinal surveillance study was performed in order to monitor the following site-specific infection rates: pneumonia (PNE), blood stream infections (BSI), urinary tract infections (UTI), surgical site infections (SSI). According to CDC definitions all patients developing infection 48 hours or more after ward admission were included. Furthermore risk factors (i.e. age, sex, SAPS II), invasive procedures (i.e. endotracheal intubation, vascular and urinary catheterisation), microbiological isolates and their antibiotic susceptibility were screened. Overall 302 patients (191 men and 111 women) were admitted; age 55.1 +/- 20.7 years (mean), SAPS II 42.4 +/- 16.2 (mean) and average ward stay 12.5 +/- 21.7 days. Crude mortality was 15.9%. Results showed a total of 37 infection episodes (20 PNE , 7 BSI, 8 UTI and 2 SSI) in 33 patients (10.9%). Infection and mortality rates were among the lowest registered in other italian ICU's. Standardized infection rates associated to invasive procedures were: Ventilator-associated PNE rate (7.8/1000), central venous catheter-associated BSI rate (2.2/1000), urinary catheter-associated UTI rate (2.1/1000). The first (PNE) was higher than the NNIS mean rate, whwreas BSI and urinary catheter associated rates were minor than the mean rates reported by NNIS. Gram-negatives were 61.7%, gram-positives 27.6% and Candida spp. 10.6%. The results confirm the ICU successful preventive strategy.


[Preventive antifibrillatory treatment of sudden cardiac death in acute myocardial infarct].
The pathophysiological basis of sudden cardiac death due to ventricular arrhythmias in acute myocardial infarction has been extensively investigated in experimental as well as in some clinical studies. Numerous clinical studies have been performed with the aim to establish the feasibility of antifibrillatory prophylaxis of sudden cardiac death by pretreatment with antiarrhythmic drugs. Using class I-antiarrhythmic drugs the reported findings were contradictory. While the antiarrhythmic efficacy of Lidocaine and other, newer class I-antiarrhythmic drugs is well established, the antifibrillatory effects of these drugs in the early phase of acute myocardial infarction remain uncertain. In clinical studies with the endpoint of mortality in patients at risk, longterm administration of orally effective class I-antiarrhythmic drugs did not prove to be superior to placebo. However, beta-sympatholytic agents have been shown to reduce mortality in patients at risk in several large clinical studies. The basic mechanism seems to be primarily a reduction in sudden cardiac death which is caused predominantly by ventricular fibrillation. The antifibrillatory properties of beta-blockers was demonstrated as well by a reduction in the number of episodes of ventricular fibrillation. The recognition of patients at risk who profit most from chronic beta-blocker therapy remains the main problem when treatment of numerous low-risk patients is avoided. In the ISIS I-study with Atenolol intravenous administration of a beta-blocker in the early phase of acute myocardial infarction has been shown to be beneficial if hemodynamic monitoring, for example using flow-directed heart catherization is performed. In general this does not apply to the treatment with calciumantagonists, especially with Verapamil and Nifedipine. These drugs do not improve prognosis of acute myocardial ischemia, obviously because of hemodynamic side effects. The antifibrillatory efficacy of Verapamil-type calciumantagonists, shown in the experimental model, could not be demonstrated in the clinical setting. Nevertheless, further clinical studies performing longterm prophylactic treatment of patients at risk before the onset of myocardial ischemia seem to be worthwhile. Concerning class III-antiarrhythmic agents, clinical experience in the setting of acute myocardial infarction is limited; hence a final conclusion about their antifibrillatory efficacy under clinical conditions at present is impossible.


Esophageal Penetration of the Magnetic Sphincter Augmentation Device: History Repeats Itself.
An alternative approach to the treatment of gastroesophageal reflux disease (GERD) has recently been introduced in clinical practice, involving the implantation of a magnetic sphincter augmentation device (MSAD). This "magnetic ring" is implanted laparoscopically around the lower esophageal sphincter to improve its barrier function. The literature is still limited on the midterm results achieved in controlling reflux because the MSAD is a very new procedure. So far, only a few cases of the MSAD causing erosion of the esophagus have been reported. We report on two cases of progressive and severe dysphagia after the implantation of an MSAD elsewhere. In both cases, the symptoms were caused by the migration of the device into the esophagus. The devices were removed endoscopically in a single step in both cases, using the Olympus cutter. After 3 months, the first patient had a laparoscopic Nissen fundoplication without any complications and with a good final reflux control. The second only underwent removal of the device, using the same endoscopic approach and again without any complications. Judging from the literature, MSAD implantation may be an effective way to control GERD, but the method can carry major complications, such as migration of the device into the esophagus (as in the two cases reported here). Endoscopic removal of a device possibly penetrating inside the esophagus is feasible and safe, and may later be followed up with a laparoscopic antireflux procedure without any particular difficulty.


Using an aseptic technique to reduce the risk of infection.
It is essential that nurses recognise the consequences of patients acquiring a healthcare-associated infection (HCAI). This article outlines how handwashing continues to be the most important factor in reducing HCAI, but that the use of an aseptic technique will further cut the risk of infection. Because most aseptic techniques do not require a surgical aseptic technique, emphasis is placed on the use of an aseptic non-touch technique, which is required for many procedures in hospital and the community.


Characterization of an intronic enhancer that regulates myelin proteolipid protein (Plp) gene expression in oligodendrocytes.
The myelin proteolipid protein (Plp) gene is expressed in oligodendrocytes and encodes the most abundant protein (approximately 50%) present in mature myelin from the central nervous system (CNS). Plp gene activity is low to nonexistent early in development but sharply increases, concurrently with the active myelination period of CNS development. Work from our laboratory suggests that the temporal regulation of Plp gene expression in mice is mediated by a positive regulatory element located within Plp intron 1 DNA. We have termed this regulatory element/region ASE (for antisilencer/enhancer). The ASE is situated approximately 1 kb downstream of exon 1 DNA and encompasses nearly 100 bp. To understand the mechanisms by which the ASE augments Plp gene expression in oligodendrocytes, Plp-lacZ constructs were generated and transfected into a mouse oligodendroglial cell line (N20.1). Results presented here demonstrate that upstream regulatory elements in the Plp promoter/5'-flanking DNA are not required for ASE activity; the ASE worked perfectly well when the thymidine kinase (TK) promoter was substituted for the Plp promoter. However, the relative location of the ASE appears to be important. When placed upstream of 2.4 kb of Plp 5'-flanking DNA, or downstream of the lacZ expression cassette, the ASE was no longer effective. Thus, the ASE might have to be in the context of the intron in order to function. To begin to identify the crucial nucleotides within the ASE, orthologous sequences from rat, human, cow, and pig Plp genes were swapped for the mouse sequence. Results presented here demonstrate that the orthologous sequence from rat can substitute for the mouse ASE, unlike those from human, cow, or pig.


Generative Multi-Label Zero-Shot Learning.
Multi-label zero-shot learning strives to classify images into multiple unseen categories for which no data is available during training. The test samples can additionally contain seen categories in the generalized variant. Existing approaches rely on learning either shared or label-specific attention from the seen classes. Nevertheless, computing reliable attention maps for unseen classes during inference in a multi-label setting is still a challenge. In contrast, state-of-the-art single-label generative adversarial network (GAN) based approaches learn to directly synthesize the class-specific visual features from the corresponding class attribute embeddings. However, synthesizing multi-label features from GANs is still unexplored in the context of zero-shot setting. When multiple objects occur jointly in a single image, a critical question is how to effectively fuse multi-class information. In this work, we introduce different fusion approaches at the attribute-level, feature-level and cross-level (across attribute and feature-levels) for synthesizing multi-label features from their corresponding multi-label class embeddings. To the best of our knowledge, our work is the first to tackle the problem of multi-label feature synthesis in the (generalized) zero-shot setting. Our cross-level fusion-based generative approach outperforms the state-of-the-art on three zero-shot benchmarks: NUS-WIDE, Open Images and MS COCO. Furthermore, we show the generalization capabilities of our fusion approach in the zero-shot detection task on MS COCO, achieving favorable performance against existing methods.


[Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients in the coronavirus disease (COVID-19)].
On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.


Systemic cytomegalovirus infection during postoperative chemoradiotherapy for malignant astrocytoma: case report with immunohistochemistry and in situ hybridization.
We report a patient with a systemic cytomegalovirus (CMV) infection, which occurred during postoperative chemoradiotherapy for a malignant astrocytoma. To our knowledge, there is no report that is especially focused on the association with a CMV infection. Interstitial pneumonia and gastrointestinal bleeding, which developed suddenly during postoperative chemoradiotherapy, resulted in the patient's death. A histopathological examination of the postmortem specimens revealed numerous "owl's eye" cells containing intranuclear inclusion bodies, which were identified as CMV by immunohistochemical examination and in situ hybridization. The premortem diagnosis of CMV infection is usually difficult, because an anti-CMV titer can be nonspecifically elevated. With immunohistochemical examination and in situ hybridization, CMV in excretory or biopsy specimens can be identified and the diagnosis of CMV infection can be established. When serious pneumonia or massive gastrointestinal bleeding occurs during postoperative chemoradiotherapy, the differential diagnosis should include the possibility of CMV infection and we recommend an immunohistochemical examination and in situ hybridization for the detection of CMV.


Prognostic significance of absolute lymphocyte count and lymphocyte subsets in lymphomas.
Lymphocytopenia is a poor prognostic marker in initial staging of non- Hodgkin lymphomas (below 1.0 x 10(9)/l) and Hodgkin lymphoma (below 0.6 x 10(9)/l) and in relapsed diffuse large B cell lymphoma. Early lymphocyte recovery > or =0.5 x 10(9)/l after autologous and allogeneic stem cell transplantation is a significant predictor of tumor control and survival in lymphomas. Natural killer cells are involved in tumor cell killing and are the only subset of lymphocytes associated with disease outcome in initial staging and after autologous stem cell transplantation in lymphomas. The antitumor effect of various NK cell subsets should be defined.


Sexuality education for youth with chronic conditions.
Pediatric nursing has long neglected the important topic of sexuality, supporting the myth that children are asexual. How can we learn about this crucial topic? How can we incorporate sexuality education into our nursing care in a respectful and supportive manner? How can we honor the whole person, including the sexual self? This article addresses the need for sexuality education for children with chronic conditions and their families; describes a framework for education for the separate yet inter-relating aspects of sexuality; provides practical pointers for nurses to include sexuality education in their client care; and identifies sources of information for health care providers and families.


[Late sequelae after severe intracranial hemorrhage in 23 premature children. Parental perspectives].
Cerebral hemorrhage in very premature infants results in high mortality and increases the risk of handicap. The aim of the study was to evaluate: 1) the parental opinion of the child's motor function, 2) their opinion of the child's development compared to their expectations, and 3) how they experienced the information given by nurses and doctors at the time of the diagnosis. Parents of 23 of 24 premature infants answered a questionnaire. During the neonatal period all infants had suffered from a major cerebral hemorrhage. The children had reached an age between two and seven years. Half of the children had motor deficits (48%), and 22% of the children had severe motor problems. Future development and motor function were reliably estimated by the doctors during the neonatal period. Most of the parents (79%), however, estimated that their child's development was better than expected. The majority of the parents were satisfied with the information that had been given at the time of diagnosis, and they had received adequate support. Cerebral hemorrhage in premature infants is still a major problem. Our results, however, do not suggest major change of clinical practice.


Subwavelength plasmonic color printing protected for ambient use.
We demonstrate plasmonic color printing with subwavelength resolution using circular gap-plasmon resonators (GPRs) arranged in 340 nm period arrays of square unit cells and fabricated with single-step electron-beam lithography. We develop a printing procedure resulting in correct single-pixel color reproduction, high color uniformity of colored areas, and high reproduction fidelity. Furthermore, we demonstrate that, due to inherent stability of GPRs with respect to surfactants, the fabricated color print can be protected with a transparent dielectric overlay for ambient use without destroying its coloring. Using finite-element simulations, we uncover the physical mechanisms responsible for color printing with GPR arrays and suggest the appropriate design procedure minimizing the influence of the protection layer.


Interface Anchored Effect on Improving Working Stability of Deep Ultraviolet Light-Emitting Diode Using Graphene Oxide-Based Fluoropolymer Encapsulant.
The graphene oxide (GO)-based fluoropolymer is first proposed as an interface encapsulant to improve the light extraction efficiency and achieve the ultralong working stability of deep ultraviolet light-emitting diodes (DUV-LEDs), benefitting from its superior interface performance based on an anchored effect. For the GO-based fluoropolymer composite, the anchored structure is designed to effectively and tightly rivet the quartz lens on the DUV-LED chip by using the interface reaction between GO embedded in fluoropolymer and 3-aminopropyltriethoxy-silane grafted on the surfaces. Experimental results show that on the basis of the interface anchored effect, the air voids in the interface layer of DUV-LED are reduced by 84%, leading to an improvement of the light output power by 15% and a decrease of the junction temperature by 5%, by virtue of the sealing characteristics of the 0.10 wt % GO-based fluoropolymer. In addition, the steady working time is dramatically improved by 660% and it was attributed to the good interface anchored bonding of the 0.10 wt % GO-based fluoropolymer. This novel graphene oxide-based fluoropolymer is believed to provide a feasible and effective interface encapsulant to improve the performance of DUV-LEDs.


Mixed-stock analysis reveals the migrations of juvenile hawksbill turtles (Eretmochelys imbricata) in the Caribbean Sea.
Hawksbill turtles (Eretmochelys imbricata) migrate between nesting beaches and feeding habitats that are often associated with tropical reefs, but it is uncertain which nesting colonies supply which feeding habitats. To address this gap in hawksbill biology, we compile previously published and new mitochondrial DNA (mtDNA) haplotype data for 10 nesting colonies (N = 347) in the western Atlantic and compare these profiles to four feeding populations and four previously published feeding samples (N = 626). Nesting colonies differ significantly in mtDNA haplotype frequencies (Phi(ST) = 0.588, P < 0.001), corroborating earlier conclusions of nesting site fidelity and setting the stage for mixed-stock analysis. Feeding aggregations show lower but significant structure (Phi(ST) = 0.089, P < 0.001), indicating that foraging populations are not homogenous across the Caribbean Sea. Bayesian mixed-stock estimates of the origins of juveniles in foraging areas show a highly significant, but shallow, correlation with nesting population size (r = 0.378, P = 0.004), supporting the premise that larger rookeries contribute more juveniles to feeding areas. A significant correlation between the estimated contribution and geographical distance from nesting areas (r = -0.394, P = 0.003) demonstrates the influence of proximity on recruitment to feeding areas. The influence of oceanic currents is illustrated by pelagic stage juveniles stranded in Texas, which are assigned primarily (93%) to the upstream rookery in Yucatan. One juvenile had a haplotype previously identified only in the eastern Atlantic, invoking rare trans-oceanic migrations. The mixed-stock analysis demonstrates that harvests in feeding habitats will impact nesting colonies throughout the region, with the greatest detriment to nearby nesting populations.


Ulnar dimelia.
Three cases of ulnar dimelia, one in an adult, are described and reference is made to earlier reported cases. The etiology of the condition is discussed.


Update on the Diagnosis and Prognosis of Preeclampsia with the Aid of the sFlt-1/ PlGF Ratio in Singleton Pregnancies.
Preeclampsia (PE) is involved in a group of obstetrical conditions closely related by the presence of placental dysfunction (PD), which also includes intrauterine growth restriction and placental abruption. The timely and accurate recognition and management of PE are often challenging because diagnostic criteria are still based on nonspecific signs and symptoms and because common severity criteria correlate poorly with adverse maternal and fetal outcomes. The discovery of the role of angiogenesis-related factors - soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) - in the underlying pathophysiology of PD has marked an important step for improving its early diagnosis and prognosis assessment before gestational week 34. Nowadays, an sFlt-1/PlGF ratio cutoff level of ≤38 is widely accepted for ruling out PE in patients with suspicion of the disease, and its use is cost-effective. However, the evidence is more limited regarding the management and prognosis of women with an abnormally high sFlt-1/PlGF ratio. This review summarizes the current evidence of the clinical application of the sFlt-1/PlGF ratio for the diagnosis and prognosis assessment of PE and points out the next challenges for these biomarkers, including their role as target for the development and monitoring of new therapies.


Systemic Capillary Leak Syndrome Secondary to Coronavirus Disease 2019.
Systemic capillary leak syndrome is a rare disorder characterized by dysfunctional inflammatory response, endothelial dysfunction, and extravasation of fluid from the vascular space to the interstitial space leading to shock, hemoconcentration, hypoalbuminemia, and subsequent organ failure. The condition may be idiopathic or secondary to an underlying cause, which can include viral infections. Here we describe a patient with acute coronavirus disease 2019 (COVID-19) infection who presented with hemoconcentration, shock, and hypoalbuminemia. The patient subsequently developed rhabdomyolysis and compartment syndrome of all four extremities, requiring fasciotomies. This is the first reported case of systemic capillary leak syndrome associated with COVID-19 infection. This case adds to the evolving spectrum of inflammatory effects associated with this viral infection.


Prophylactic efficacy of a novel method against postendoscopic papillary balloon dilation pancreatitis.
This study aimed to investigate whether a novel method including prophylactic pancreatic stent (PS) placement prevents postendoscopic papillary balloon dilation pancreatitis. This study enrolled 200 consecutive patients with bile duct stones measuring up to 8 mm in diameter and retrospectively recruited 113 patients undergoing ordinary endoscopic papillary balloon dilation (EPBD) without PS placement from our previous study. In the novel method, EPBD and PS placement was attempted with a guidewire left in the main pancreatic duct for patients in whom stable guidewire placement in the main pancreatic duct was possible. EST was performed for patients in whom stable guidewire placement was impossible. The incidence rate of pancreatitis was compared between the novel method and ordinary EPBD, and risk factors for pancreatitis were analyzed. Of 194 patients undergoing the novel method, EPBD and EST were performed in 180 and 14 patients, respectively. Following EPBD, PS placement was successful in 177/180 (98.3%) of patients. Pancreatitis occurred in 7/194 (3.6%) of patients after the novel method and 9/113 (8.0%) of patients after ordinary EPBD. There was a trend toward lower incidence rate of pancreatitis in the novel method. Stent dislodgement by the first postoperative morning and no previous endoscopic nasobiliary drainage (ENBD) were identified as risk factors for pancreatitis after EPBD with PS placement. No previous ENBD was also identified as a risk factor for pancreatitis after ordinary EPBD. Our novel method is likely to be superior to ordinary EPBD in preventing pancreatitis. Previous ENBD may prevent post-EPBD pancreatitis regardless of PS placement.


Thermal and non-thermal methods to evaluate compatibility of granisetron hydrochloride with tablet excipients.
Compatibility of granisetron hydrochloride with selected excipients was assessed using Differential Scanning Calorimetry (DSC) as a thermal screening technique. Non-thermal methods like Fourier Transform Infrared spectroscopy and Thin Layer Chromatography were used as complementary techniques to adequately support and assist in interpretation of DSC results. Some drug-excipient interaction was observed with beta-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, mannitol, and magnesium stearate in DSC studies. However, further evaluation of these incompatible excipients with non-thermal methods showed that these excipients were compatible with granisetron hydrochloride. Non-thermal methods were, thus, of help in interpreting DSC results and excluding all relevant pharmaceutical incompatibilities.


Nonpainful remote electrical stimulation alleviates episodic migraine pain.
To evaluate the efficacy of remote nonpainful electrical upper arm skin stimulation in reducing migraine attack pain. This is a prospective, double-blinded, randomized, crossover, sham-controlled trial. Migraineurs applied skin electrodes to the upper arm soon after attack onset for 20 minutes, at various pulse widths, and refrained from medications for 2 hours. Patients were asked to use the device for up to 20 attacks. In 71 patients (299 treatments) with evaluable data, 50% pain reduction was obtained for 64% of participants based on best of 200-μs, 150-μs, and 100-μs pulse width stimuli per individual vs 26% for sham stimuli. Greater pain reduction was found for active stimulation vs placebo; for those starting at severe or moderate pain, reduction (1) to mild or no pain occurred in 58% (25/43) of participants (66/134 treatments) for the 200-μs stimulation protocol and 24% (4/17; 8/29 treatments) for placebo (p = 0.02), and (2) to no pain occurred in 30% (13/43) of participants (37/134 treatments) and 6% (1/17; 5/29 treatments), respectively (p = 0.004). Earlier application of the treatment, within 20 minutes of attack onset, yielded better results: 46.7% pain reduction as opposed to 24.9% reduction when started later (p = 0.02). Nonpainful remote skin stimulation can significantly reduce migraine pain, especially when applied early in an attack. This is presumably by activating descending inhibition pathways via the conditioned pain modulation effect. This treatment may be proposed as an attractive nonpharmacologic, easy to use, adverse event free, and inexpensive tool to reduce migraine pain. NCT02453399. This study provides Class III evidence that for patients with an acute migraine headache, remote nonpainful electrical stimulation on the upper arm skin reduces migraine pain.


The Decline of Arranged Marriage? Marital Change and Continuity in India.
This article evaluates whether arranged marriage declined in India from 1970 to 2012. Specifically, the authors examine trends in spouse choice, the length of time spouses knew each other prior to marriage, intercaste marriage, and consanguineous marriage at the national level, as well as by region, urban residence, and religion/caste. During this period, women were increasingly active in choosing their own husbands, spouses meeting on their wedding day decreased, intercaste marriage rose, and consanguineous marriage fell. However, many of these changes were modest in size and substantial majorities of recent marriages still show the hallmarks of arranged marriage. Further, instead of displacing parents, young women increasingly worked with parents to choose husbands collectively. Rather than unilateral movement towards Western marriage practices, as suggested by theories of family change and found in other Asian contexts, these trends point to a hybridization of customary Western and Indian practices.


The identification of culicine mosquitoes in the Shadegan wetland in southwestern Iran.
In order to study the culicine mosquito fauna (Diptera: Culicidae: Culicinae) of the Shadegan wetland in southern Khouzestan Province of Iran, sampling was carried out using hand catch, total catch, and New Jersy light traps, from October 2008 to March 2009. A total of 2664 culicine mosquitoes were captured. Three genera and five species were identified, including Culex pipiens L., Cx. tritaeniorhynchus Giles, Cx. sinaiticus Kirkpatrik, Cx. modestus Ficalbi, Ochlerotatus caspius Pallas and a Culiseta species. All of these species, reported for the first time, were from the Shadegan wetland and Khouzestan Province, and some are medically important.


Large depth differences between target and flankers can increase crowding: Evidence from a multi-depth plane display.
Crowding occurs when the presence of nearby features causes highly visible objects to become unrecognizable. Although crowding has implications for many everyday tasks and the tremendous amounts of research reflect its importance, surprisingly little is known about how depth affects crowding. Most available studies show that stereoscopic disparity reduces crowding, indicating that crowding may be relatively unimportant in three-dimensional environments. However, most previous studies tested only small stereoscopic differences in depth in which disparity, defocus blur, and accommodation are inconsistent with the real world. Using a novel multi-depth plane display, this study investigated how large (0.54-2.25 diopters), real differences in target-flanker depth, representative of those experienced between many objects in the real world, affect crowding. Our findings show that large differences in target-flanker depth increased crowding in the majority of observers, contrary to previous work showing reduced crowding in the presence of small depth differences. Furthermore, when the target was at fixation depth, crowding was generally more pronounced when the flankers were behind the target as opposed to in front of it. However, when the flankers were at fixation depth, crowding was generally more pronounced when the target was behind the flankers. These findings suggest that crowding from clutter outside the limits of binocular fusion can still have a significant impact on object recognition and visual perception in the peripheral field.


Conventional vs drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma.
Transarterial chemoembolization (TACE) is the current standard of therapy for patients with intermediate-stage hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE (cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drug-eluting beads (DEBs) have been imposed as novel drug-delivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEB-TACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.


Synthesis of (R)-1,3-butanediol by enantioselective oxidation using whole recombinant Escherichia coli cells expressing (S)-specific secondary alcohol dehydrogenase.
The synthesis of (R)-1,3-butanediol (BDO) from its racemate was studied using whole cells of recombinant Escherichia coli expressing an (S)-specific secondary alcohol dehydrogenase (CpSADH) from Candida parapsilosis by enantioselective oxidation. Under the optimized conditions, the yield of (R)-1,3-BDO reached 72.6 g/l, with a molar recovery yield of 48.4% from a racemate of 15% and an optical purity of 95% ee.


Role of phytobiotics in relieving the impacts of Aeromonas hydrophila infection on aquatic animals: A mini-review.
Aeromonas hydrophila is a ubiquitous bacterium with various hosts that causes mass mortality in farm-raised fish species and significant economic losses. The current antibiotic treatment is ineffective in controlling this bacterium infection in aquaculture species. Therefore, an evaluation of potential phytobiotics is needed to find an alternative antimicrobial agent to reduce the over-reliance on antibiotics in aquaculture and safeguard public and environmental health. Furthermore, the rise in antibiotic resistance cases among pathogenic bacteria indicates an urgent need for new fish and shellfish health management solutions. In this context, phytobiotics applications in aquaculture can be defined as any medicinal plant-based antimicrobial agent used in fish and shellfish health management. This review will focus on the impacts of Motile Aeromonas Septicemia (MAS) due to A. hydrophila in aquaculture, the potential of phytobiotics in enhancing the tolerance of aquaculture species against MAS and the combination of phytobiotics with other antimicrobial and therapeutic agents against MAS.


Outcome and 2-Year Survival Rate in Elderly Patients With Lateral Compression Fractures of the Pelvis.
Osteoporotic pelvic ring fractures are a rising problem for surgeons in industrialized countries. There is no evidence-based treatment strategy especially for lateral compression (LC) fractures involving the sacrum. The aim of this study was to evaluate and compare outcome and survival rate of nonoperative and operative treatment strategies for lateral compression fractures. In a retrospective study, 128 patients (aged ≥65 years) with an Orthopedic Trauma Association (OTA) types B2.1 and B3.3 fracture were included and analyzed regarding demographic and treatment data and adverse events. After a follow-up period of at least 2-year survival rate, quality of life and pain were evaluated using the EuroQol-5D and Short Form-12 questionnaires and the visual analog scale. Fifty patients (78.3 ± 7.6 years) obtained operative treatment and 77 patients (82.7 ± 7.9 years) obtained nonoperative treatment. One died within 24 hours after admission. High rates of complications occurred in both groups (operative group: 18% and nonoperative group: 8%). Eighteen percent (14 of the 77) of conservatively treated patients needed operative treatment after discharge due to worsening pain and mobilization. The 2-year follow-up showed a high overall mortality (30%), with a significant higher survival rate for operatively treated patients (2-year survival: operatively treated 82% vs conservative 61%). No difference was found in pain and quality of life. Elderly patients display a high rate and variety of complications and mortality in the aftermath of lateral compression fractures of the pelvis. Although a significantly higher 2-year survival rate for operatively treated patients was found, this study cannot give proof of superior position for operative treatment. Due to lacking data for alternative treatment algorithms especially for fracture-related immobilized patients, we recommended operative treatment with the aim to reduce complications related to prolonged bed rest and ensure early mobilization.


Yb@C2n (n = 40, 41, 42): new fullerene allotropes with unexplored electrochemical properties.
A series of(13)C-enriched monoytterbium endohedral metallofullerenes (EMFs)-Yb@C(2n) (n = 40, 41, 42)-was synthesized and isolated. Their cage structures were systematically determined for the first time using computational and experimental (13)C NMR studies. The results revealed that all isomers adopt cage structures conforming to the isolated pentagon rule. In detail, Yb@C(80) possesses the C(2v)(3) cage; Yb@C(82)(I, II, III) bear C(s)(6), C(2)(5), and C(2v)(9) cages, respectively; and Yb@C(84)(II, III, IV) have C(2)(13), C(1)(12), and C(2)(11) cage structures, respectively. This is the first report describing C(2)(13)-C(84) and C(1)(12)-C(84) cage structures. It is noteworthy that the cage structures found for mono-EMFs generally differ from either the corresponding empty fullerenes or the related EMFs encapsulating more than one metal atom, indicating that the metal atom inside the fullerene cage plays an important role in determining the EMF structure. On the basis of the fact that the structure of Yb@C(2)(13)-C(84) resembles that of Yb@C(2)(5)-C(82), a metal-templated growth process was proposed as a kinetic factor controlling EMF formation. Furthermore, previous electrochemical studies of divalent EMFs have failed to observe their oxidation potentials, which have raised the assumption that such species are large-bandgap molecules. This study revealed that all isomers of Yb@C(2n) (n = 40, 41, 42) display one or two reversible oxidation steps together with four reversible reduction processes in 1,2-dichlorobenzene, even at a low scan rate (20 mV/s), which enables estimation of their electrochemical bandgaps (DeltaE = (ox)E(1)-(red)E(1)). The results show a DeltaE value of 0.88-1.41 V for Yb@C(2n) (2n = 40, 41, 42), which is much larger than the values of trivalent mono-EMFs (DeltaE < 0.5 V), but generally smaller than those of metal nitride cluster EMFs (1.4 V < DeltaE < 2.1 V). Results further demonstrated that the DeltaE values correlate reasonably with their relative abundances.


Three-dimensional-printed upper limb prosthesis for a child with traumatic amputation of right wrist: A case report.
For traumatic upper limb amputees, the prohibitive cost of a custom-made prosthesis brings an insufferable financial burden for their families in developing countries. Three-dimensional (3D) printing allows for creating affordable, lightweight, customized, and well-fitting prosthesis, especially for the growing children. We presented a case of an 8-year-old boy, who suffered a traumatic right wrist amputation as result of a mincing machine accident. The patient was immediately sent to the emergency orthopedics department after the accident. He was diagnosed as severed mangled limb crash injury at the level of the right wrist with a Mangled Extremity Severity Score of 8. A wrist disarticulation was performed and a 3D-printed prosthetic hand was designed and manufactured for this child. A personalized prosthetic rehabilitation training was applied after the prosthesis installation at 6 months postoperatively. The function of the prosthesis was evaluated at 1-month and 3-month follow-up using the Children Amputee Prosthetics Projects (CAPP) score and the University Of New Brunswick Test Of Prosthetic Function for Unilateral Amputees (UNB test). The materials cost <20 dollars. The printing took <8 hours and the component assembling was completed within 20 minutes. During the 3-month follow-up, the child's parents were satisfied with the prosthesis and the UNB test showed the significantly improved function of the prosthesis. This novel 3D-printed upper limb prosthesis in a child with the traumatic wrist amputation might serve as a practical and affordable alternative for children in developing countries and those lacking access to health care providers. A personalized prosthetic rehabilitation needs to be undertaken and more clinical studies are warranted to validate the potential superiority of similar 3D-printed prostheses.


Factors affecting the use of peritoneal dialysis among the ESRD population in India: a single-center study.
Factors such as limited health-care budget allotment and poor accessibility of the majority of the population to hemodialysis (HD) facilities should favor the use of peritoneal dialysis (PD) in India. However, only 6% of end-stage renal disease patients undergoing dialysis in India are on PD. We undertook this prospective study to evaluate various factors that could contribute to this low rate of use of PD at a tertiary-care state-run hospital in Northern India. All the patients who entered our HD or PD program from August 2001 to December 2003 were interviewed using a preset questionnaire. The questionnaire recorded their basic disease and comorbidity, social and demographic characteristics, awareness of the various modalities of renal replacement therapy (RRT), and the reasons for choosing their present modality of therapy. Treating nephrologists were also interviewed with respect to the factors that, in their opinion, were responsible for the limited use of PD at our institute. In total, 342 patients on HD, 66 patients on PD, and 24 nephrologists were interviewed. The rate of PD use was 16.2%. Mean age of patients on HD and PD was 34.6 +/- 11.8 years and 62.9 +/- 10.3 years respectively (p < 0.0001). The incidence of diabetes mellitus and coronary artery disease in the HD and PD populations was 2.5% and 62.5%, and 9.1% and 46.7% respectively (p < 0.0001 for both). Only 30.4% of patients on HD were aware of PD as a modality of RRT and 83.6% of them found PD to be expensive, 65.4% had low enthusiasm toward a domiciliary therapy such as PD, and 61.5% were not recommended PD by their nephrologist. Only 5 (7.6%) patients were initiated on PD directly, the remaining 61 patients were shifted from HD after a mean duration on HD of 185.3 +/- 15.4 days: 67.1% were shifted due to poor tolerance of HD, 29.4% were advised to shift to PD because of comorbidity and vascular access problems, and only 3.3% took up PD because of the independent lifestyle it offered. None of the interviewed nephrologists routinely discussed PD in predialysis counseling. They found financial constraints (100%), lack of patient enthusiasm (100%), doubtful patient compliance (83.2%), and lack of an organized PD program (79.2%) to be the main factors limiting more widespread use of PD at our institute. Peritoneal dialysis is an underused modality of RRT at our institute. The patients who are taken up for PD at our institute are elderly and have a higher incidence of other comorbid conditions, such as diabetes mellitus and coronary artery disease. Also, most patients who switch to PD do so due to their unsuitability for HD rather than by their own choice. The factors contributing to this low rate of use of PD are ignorance of PD, increased cost of therapy, low enthusiasm toward domiciliary therapy, and lack of adequate infrastructure for PD at our institute. Effective predialysis counseling, reduction in the cost of the therapy, and development of an adequate infrastructure can increase the rate of use of PD.


Levetiracetam-induced eosinophilic pneumonia.
Levetiracetam is widely regarded as a benign antiepileptic drug, compared to older antiepileptic medication. We report a case of eosinophilic pneumonia due to levetiracetam use in a non-smoking woman aged 59 years with no previous respiratory history. Our patient presented with exertional breathlessness and marked desaturation on exertion. She displayed 'reverse bat-wing' infiltrates on her chest radiograph and peripheral eosinophilia on a complete blood count. Her symptoms, radiology and peripheral eosinophilia resolved completely with cessation of levetiracetam and a course of prednisolone. This is the first report of isolated eosinophilic pneumonia due to levetiracetam. Other reports of levetiracetam-induced eosinophilia describe drug rash, eosinophilia and systemic symptoms (DRESS syndrome). Detection of pulmonary drug reactions requires a careful drug history and high index of suspicion. Identifying and reporting a causative agent is crucially important, as cessation of the drug is essential for resolution of the syndrome.


The molecular biology of cytoplasmically inherited male sterility and prospects for its engineering.
Nucleocytoplasmic male sterilities are binary genetic systems driven by mitochondrial, maternally inherited genes that induce male sterility and a female phenotype and which are overcome by nuclear restorers of fertility. They contribute to the reproductive biology and evolution of natural populations and are valuable tools for the commercial production of hybrid seeds in crops. For species with no natural form of cytoplasmic male sterility, such sterility can in some cases be introduced from different, but related, species through sexual crosses or somatic hybridisation. Somatic hybridisation is the only technique currently available for manipulating plant mitochondrial genomes. Recent successes in plastid transformation have opened up entirely new perspectives for the engineering of cytoplasmic male sterilities in transplastomic plants.


Effects of standardized extract of Ferula gummosa root on glutamate-induced neurotoxicity.
Glutamate is one of the major excitatory neurotransmitters in the central nervous system. Increasing glutamate leads to neurodegenerative disease. Nowadays, plant medicine plays a role in the treatment of some disorders. In this research, we investigated the neuroprotective effect of Ferula gummosa root extract against glutamate-induced oxidative stress in the rat adrenal pheochromocytoma (PC12) and mouse neuroblastoma (N2a) cell lines. The cells were pretreated with extract for 2 h and then exposed to glutamate for 24 h. After 24 h the level of malondialdehyde (MDA), reactive oxygen species (ROS), and apoptotic cells were determined in both cell lines. Glutamate increased lipid peroxidation, ROS, and apoptotic cells in both cell lines. The extract significantly increased the cell viability and decreased the ROS generation under glutamate-induced oxidative stress in these cells. Also, the extract decreased the MDA level and apoptotic cells. The results showed that Ferula gummosa root may have a protective effect on glutamate-induced toxicity, suggesting that the extract protects neuronal cells from glutamate-induced oxidative stress..


Intracellular survival of Staphylococcus aureus: correlating production of catalase and superoxide dismutase with levels of inflammatory cytokines.
Superoxide dismutase (SOD) and catalase are anti-oxidant enzymes potentially used by the bacteria to neutralize macrophage microbicidal molecules such as hydrogen peroxide (H2O2). To investigate contribution of bacterial anti-oxidant enzymes in intracellular survival of Staphylococcus aureus (S. aureus) within macrophages. Murine peritoneal macrophages and S. aureus (CMC-524, ICH-629 and ICH-757). 10(6) colony forming units (CFU) of the 90 minutes (min) intracellularly viable S. aureus were administered (i.v.) per mouse through 0.1 ml saline. Anti-oxidant enzyme assay, phagocytic activity, H2O2 release, Zymography for catalase, serum tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) level were estimated. One-way Model I ANOVA and one tail Student's t-test were performed. Survival of S. aureus was least after 90 min of reincubation within macrophages. Maximum amount of bacterial anti-oxidant enzymes were released after 90 min of re-incubation. H2O2 released after 90 min of re-incubation with S. aureus was maximum. Higher activity of catalase and SOD by S. aureus occurred in response to the gradual production of H2O2. Serum IL-6 and TNF-alpha was also elevated 1h post infection. Bacterial catalase and SOD combat reactive oxygen species enabling S. aureus to persist within macrophages, inducing local inflammation, causing greater induction of serum TNF-alpha and IL-6.


Visual inhibitions of automobile driving.
Three patients in psychotherapy who were symptomatically unable to drive automobiles also gave histories of having been afflicted with oculomotor disorders in childhood. This calls attention to the previously undiscussed visual dimension of automobile driving, which is considered in general terms. The specific question of an inhibition of visual function resulting in avoidance of automobile driving is then raised, and a case illustration given in which the attachment of sexual and aggressive meanings to the act of looking was important in the formation of an automobile driving symptom. The particular impact of ocular deviation on early psychosexual development is explored, using the clinical material as a point of departure.


Incremental healthcare cost burden in patients with atrial flutter only.
Limited information is available on the costs related to atrial flutter only. This study provides a comprehensive estimate of the cost in patients with atrial flutter only versus matched patients without any atrial arrhythmia. Patients over 20 years of age with a minimum of one inpatient or two outpatient diagnosis codes for atrial flutter in 2005 and a minimum of 12 months of continuous enrollment pre- and post-index were identified using the MarketScan Commercial and Medicare databases. Atrial flutter patients were propensity matched to patients without atrial arrhythmias. Total costs for each patient for 12 months post-index were calculated. National cost was estimated using the projected prevalence of atrial flutter for 2010. A total of 1,042 patients with atrial flutter only were successfully matched with comparison patients. For atrial flutter patients compared to matched controls without atrial arrhythmias, total mean annual cost per patient was 81% higher ($23,008 vs. $12,717) and mean annual inpatient expenditure was 214% higher ($8,518 vs. $2,713). When applied to national atrial flutter prevalence data, total incremental cost burden was estimated to be $687.9 million per year more than patients without atrial arrhythmias, primarily due to cardiovascular specific expenditure ($377 million, 55% of total) with 58% ($218.5 million) of the increased inpatient expenditure due to cardiovascular specific admissions and $159 million (23%) for atrial flutter specific care. Sex-related differences were also present in atrial flutter only patients. Although atrial flutter-only patients are less prevalent than atrial fibrillation patients, the national incremental cost burden in atrial flutter is substantial on a per-patient level.


Prevalence of Triple-Negative Breast Cancer in India: Systematic Review and Meta-Analysis.
There is considerable variation in prevalence rates of triple-negative breast cancer (TNBC) reported by various studies from India. We performed a systematic review and literature-based meta-analysis of these studies. We searched databases of Medline, Scopus, EMBASE, and Web of Science for studies that reported on the prevalence of TNBC in India that were published between January 1, 1999, and December 31, 2015. We extracted relevant information from each study by using a standardized form. We pooled study-specific estimates by using random-effects meta-analysis to provide summary estimates. We explored sources of heterogeneity by using subgroup analyses and metaregression. Data were obtained from 17 studies that involved 7,237 patients with breast cancer. Overall combined prevalence of TNBC was 31% (95% CI, 27% to 35%). There was substantial heterogeneity across the studies (I2 of 91% [95% CI, 88% to 94%]; P < .001) that was not explained by available study level characteristics, including study location, definition of human epidermal growth factor receptor 2 or estrogen receptor, mean age of participants, proportion of patients with premenopausal cancer, grade 3 disease, or tumor size > 5 cm. Overall combined prevalence of hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer was 48% (95% CI, 42% to 54%) and 27% (95% CI, 24% to 31%), respectively. There was no evidence of publication bias. Prevalence of TNBC in India is considerably higher compared with that seen in Western populations. As many as as one in three women with breast cancer could have triple-negative disease. This finding has significant clinical relevance as it may contribute to poor outcomes in patients with breast cancer in India. Additional research is needed to understand the determinants of TNBC in India.


Reduced Field-of-View Diffusion-Weighted Imaging in Histological Characterization of Rectal Cancer: Impact of Different Region-of-Interest Positioning Protocols on Apparent Diffusion Coefficient Measurements.
To compare four region-of-interest (ROI) protocols for apparent diffusion coefficient (ADC) quantifications derived from reduced field-of-view diffusion-weighted imaging (rDWI) in histological characterization of rectal cancer. Forty-nine patients with rectal cancer underwent rDWI at 3.0 T. Two readers independently performed mean and minimum ADC measurements using four different ROI positioning protocols (whole tumor volume [WTV], single-slice [SS], three-slices observer-based sampling [TSOB] and three-slices predefined sampling [TSPD]). Inter-observer variation was evaluated. Mean and minimum ADC values obtained from each method were compared in terms of different histological factors of rectal cancer, and their diagnostic abilities were assessed by receiver operating characteristic curve (ROC) analysis. The corresponding times for ADC measurements were recorded and compared between ROI methods. The inter-observer agreement was excellent for ADC values obtained by two readers using the four ROI methods (ICC range, 0.906-0.994). Mean and minimum ADC values by WTV method were significantly higher and lower than other methods respectively for both readers (P < 0.05). The AUCs of mean ADC measurements for assessment of well-differentiated tumors, T2 stage tumors and N0 status (no lymph node metastasis) (0.936, 0.840 and 0.714) were greater by WTV method than those by SS method (0.782, 0.761 and 0.677). The WTV method required longer measurement time than other ROI methods (P < 0.001). ADC measurements based on rDWI were influenced by ROI positioning protocols. rDWI technique had diagnostic value for histological characterization of rectal cancer, using WTV method with overall best inter-observer reproducibility, but with the longest measurement time.


Catamenial hemoptysis. Diagnosis with MRI.
Thoracic endometriosis is a rare disorder. We report a case of a 26-year-old woman with a 4-year history of catamenial hemoptysis due to thoracic endometriosis which was diagnosed by MRI and treated successfully by means of video-assisted thoracoscopic wedge-resection of the solitary pulmonary lesion. Medical therapy with hormones was not necessary. There is no evidence of recurrence 10 months after the operation. This case demonstrates that MRI of the chest may be considered for the diagnostic work-up of patients with catamenial hemoptysis. It also shows that wedge-resection of pulmonary endometriosis foci by means of video-assisted thoracoscopy-an approach that has not been described in the literature thus far-is an effective therapy in localized peripheral pulmonary parenchymal endometriosis.


Dividing attention in the flash-lag illusion.
A dual-task paradigm was used to examine the effect of withdrawing attentional and/or cognitive resources from the flash-lag judgment. The flash-lag illusion was larger, and performance in a detection task was generally poorer, under dual-task conditions than in single-task control conditions. These effects were particularly pronounced when decisions in the two tasks were required simultaneously, as compared to when they could be made sequentially. The results suggest that a time-consuming process is involved in the flash-lag decision, of such a nature that prolonging the process increases the magnitude of the illusion.


Genetic Testing in the Diagnosis and Biology of Myeloid Neoplasms (Excluding Acute Leukemias).
The 2017 Workshop of the Society for Hematopathology/European Association for Haematopathology reviewed the role of genetic testing in the diagnosis of hematopoietic neoplasms, including non-acute leukemia myeloid malignancies. The workshop panel assigned 98 submitted cases to the category of non-acute leukemia myeloid neoplasms, of which 13 were selected for oral presentation. Data from both conventional karyotyping and genetic sequencing had important impact on diagnosis, classification, and prognostication. However, some cases had genetic results that appeared discordant from the morphology and/or clinical features. Thus, the workshop underscored the need for careful management of genetic data by the pathologist and clinician, in the context of other findings. The workshop cases highlighted the significance of genetic aberrations in the diagnosis and treatment of non-acute leukemia myeloid neoplasms. Many genetic data have already been incorporated in the most recent World Health Organization classification, and undoubtedly they will factor increasingly in future classifications.


Cytosine detection by a fluorescein-labeled probe containing base-discriminating fluorescent nucleobase.
We report on a new method for the detection of a base at a specific site in a DNA sequence by monitoring the fluorescence emission of fluorescein. To achieve this goal, we developed a new base-discriminating fluorescent (BDF) nucleobase, naphthodeazaadenine ((ND)A). The fluorescence spectrum of the duplex possessing a cytosine base as a complementary base of (ND)A showed a fluorescence peak at 383 nm when using an excitation wavelength of 350 nm. When the complementary base of (ND)A was one of the other bases, the fluorescence intensity was very low. The fluorescence emission spectrum of (ND)A overlapped with the fluorescence excitation spectrum of fluorescein in the wavelength range of 400-500 nm. Thus, we designed FRET-BDF probes containing (ND)A as the FRET donor and fluorescein as the acceptor. The interaction of these two fluorophores, which are separated by defined base pairs, allowed an efficient energy transfer that resulted in a dominant fluorescence emission of fluorescein at 520 nm when using an excitation wavelength of 350 nm. Fluorescence emission from FRET-BDF probes was observed only when the complementary base of (ND)A is C, thus achieving a clear distinction of a C base on the complementary DNA strand. However, the general utility of our method is limited due to the quenching of the (ND)A fluorescence by a G/C base pair flanking (ND)A.


Smoothened stimulation by membrane sterols drives Hedgehog pathway activity.
Hedgehog signalling is fundamental to embryonic development and postnatal tissue regeneration1. Aberrant postnatal Hedgehog signalling leads to several malignancies, including basal cell carcinoma and paediatric medulloblastoma2. Hedgehog proteins bind to and inhibit the transmembrane cholesterol transporter Patched-1 (PTCH1), which permits activation of the seven-transmembrane transducer Smoothened (SMO) via a mechanism that is poorly understood. Here we report the crystal structure of active mouse SMO bound to both the agonist SAG21k and to an intracellular binding nanobody that stabilizes a physiologically relevant active state. Analogous to other G protein-coupled receptors, the activation of SMO is associated with subtle motions in the extracellular domain, and larger intracellular changes. In contrast to recent models3-5, a cholesterol molecule that is critical for SMO activation is bound deep within the seven-transmembrane pocket. We propose that the inactivation of PTCH1 by Hedgehog allows a transmembrane sterol to access this seven-transmembrane site (potentially through a hydrophobic tunnel), which drives the activation of SMO. These results-combined with signalling studies and molecular dynamics simulations-delineate the structural basis for PTCH1-SMO regulation, and suggest a strategy for overcoming clinical resistance to SMO inhibitors.


[Gastroesophageal reflux and pulmonary disease].
Gastroesophageal reflux (GER) is a functional entity which is defined as "the involuntary reflux of the gastric contents in the oesophagus, without vomiting and without the involvement of either the gastric, abdominal or diaphragmatic muscles". It is therefore a question of a syndrome which is independent of the anatomical abnormalities in the cardio-tuberositic region (i.e. hiatal hernia). It may also show itself through digestive symptoms, thoracic pains, ENT symptoms and breathing complications. The presence of the latter has been clearly established in certain circumstances: --in infants, GER can cause obstructive apneas, which are responsible for sudden inexplicable deaths (SID): GER and SID have very similar epidemiological characteristics; polygraphic recordings showed that a reflux may immediately precede the onset of obstructive apnea; the instillation of 0.1 N hydrochloric acid in the oesophagus of children with GER causes an apnea. Medical or surgical treatment of the reflux prevents the recurrence of these accidents; --in adults, and older children, GER is responsible for coughs, recurring bronchopneumopathies and asthma; long-term recordings of the oesophageal pH have proved that there is a time-relationship between the two events. Scintigraphic studies have shown the pulmonary contamination by a radioactive isotope placed in the stomach the previous evening. GER has been equally suspected for conditions such as lung abscess, bronchiectasis and hemoptysis, but here it is more difficult to prove. With certain pulmonary fibroses, histological lesions have been compared with those observed during inhalation bronchopneumopathies, but it is difficult to establish a link with a reflux; --functional respiratory studies have not produced a specific functional entity for patients with GER; --careful medical treatment or surgical correction of GER lead to the sedation of respiratory symptoms (RS) in the majority of cases; --the association frequency of a GER and of RS is difficult to establish because of the diversity of the means of diagnosis employed in the past and also because of the heterogeneity of the studied populations, but the frequency is nevertheless high, indeed significantly higher than the prevalence of GER in the general population. The mechanisms which link GER and RS are not well known: first of all, there is the failure of normal antireflux mechanisms and also certain hormonal, alimentary (coffee, alcohol, tobacco, etc.) and therapeutic (theophylline, betamimetics) factors, which facilitate the reflux.(ABSTRACT TRUNCATED AT 400 WORDS)


Traumatic Neuroma Causing Biliary Stricture After Orthotopic Liver Transplant, Treated With Hepaticojejunostomy: A Case Report.
Traumatic neuromas of the biliary tract have occasionally been reported to cause strictures at the cystic duct stump as a late complication of cholecystectomy with common bile duct exploration. The incidence of symptomatic traumatic biliary neuroma appears to be low after orthotopic liver transplant, as only 25 patients have been described previously in the English-language literature. Traumatic (amputation) neuroma is a reactive proliferation of pericholangial nerve fibers induced by injury, but it is not a true neoplasm. The diagnosis of traumatic neuroma is possible only by histopathologic examination; the diagnostic finding is a mass of hyperplastic nerve bundles. We report a patient with a traumatic neuroma causing an early biliary stricture with intrahepatic extension after an orthotopic liver transplant. The lesion failed to respond to repeated endoscopic stenting and eventually required hepaticojejunostomy. A biopsy of the liver graft, performed in the 13th month after transplant, showed chronic ductopenic rejection.


Nematic stability of discotic liquid crystals with orientation-dependent interactions.
Technological applications of discotic nematogens are limited by the robustness of the columnar phases. This investigation employs Monte Carlo simulations to explore the potentiality of tailoring specific interactions of either stacking or peripheral type in order to enhance nematic stability. It is concluded that the nematic phase is favored for discotic particles systems with homogeneous or weakly directional interactions. However, a substantial increase in the directionality of the interaction (stacking or edge-to-edge) leads systematically to a suppression of the nematic domains in favor of the columnar phases.


B1 Field Correction of T1 Estimation Should Be Considered for Breast Dynamic Contrast-enhanced MR Imaging Even at 1.5 T.
Purpose To prospectively quantify the effect of T1 estimation in fat by B1 correction in breast magnetic resonance (MR) imaging at 1.5 T and to examine the subsequent quantitative dynamic contrast material-enhanced parameters in breast cancer with and without B1 correction. Materials and Methods This study had institutional review board approval, and informed consent was obtained from 72 patients with breast cancer before breast MR imaging studies were performed between January and July 2015. B1+ field and variable flip angle (FA) mapping were included in the dynamic contrast-enhanced breast MR imaging protocol with a 1.5-T MR imaging system. Precontrast T1 relaxation in fat and breast tumors was computed with and without B1 correction. The pharmacokinetic parameters of breast cancer were calculated by using the Tofts model with T1 values before and after B1 correction. The Mann-Whitney U test and linear regression model were used for statistical analysis. Results The FA was 19% higher in the left breast and 3% lower in the right breast than the prescribed value. This 22% average FA difference created a 43% T1 estimation bias in fat between the breasts. The T1 variation in fat was reduced to 0.96% after B1 correction. There was a 50% overestimation and a 7% underestimation of tumor T1 in the left breast and the right, respectively, associated with B1 error. Assuming T1 after B1 correction represents the true tumor T1, 41% underestimation in the left breast and 10% overestimation in the right without B1 correction were seen in the dynamic contrast-enhanced parameters (including the volume transfer constant, or Ktrans, fraction of extracellular extravascular space, or ve, and blood normalized initial area under the gadolinium concentration curve to 90 seconds, or IAUGCBN90). Conclusion B1 correction for more accurate T1 values should be considered for quantitative dynamic contrast-enhanced breast MR imaging, even at 1.5 T, to offset significant systemic error. © RSNA, 2016.


[Psychiatric disorders after early brain damage in children and adolescents - four case reports].
Neuropsychological assessment is an important diagnostic tool that can provide additional information for diagnosing mental disorders during childhood and adolescence. While in the past, the challenge of a neuropsychological assessment was to detect whether or not the child had suffered brain damage, this aim changed with the development of better, non-invasive brain-imaging techniques. On the basis of four single cases it is demonstrated that brain damage causes not only direct, but also indirect deficits. In particular, the indirect consequences of early brain lesions, such as behavioral disorders and persistent neuropsychological deficits, are very often reasons to seek clinical treatment. The characteristics of children and adolescents with organic mental disorders with regard to diagnosis and intervention will be exemplified and discussed within the following four case studies.


Finite Element Analysis of Dynamic Recrystallization Model and Microstructural Evolution for GCr15 Bearing Steel Warm-Hot Deformation Process.
Warm deformation is a plastic-forming process that differs from traditional cold and hot forming techniques. At the macro level, it can effectively reduce the problem of high deformation resistance in cold deformation and improve the surface decarburization issues during the hot deformation process. Microscopically, it has significant advantages in controlling product structure, refining grain size, and enhancing product mechanical properties. The Gleeble-1500D thermal-mechanical physical simulation system was used to conduct isothermal compression tests on GCr15 bearing steel. The tests were conducted at temperatures of 600-1050 °C and strain rates of 0.01-5 s-1. Based on the experimental data, the critical strain model and dynamic recrystallization model for the warm-hot forming of GCr15 bearing steel were established in this paper. The model accuracy is evaluated using statistical indicators such as the correlation coefficient (R). The dynamic recrystallization model exhibits high predictive accuracy, as indicated by an R-value of 0.986. The established dynamic recrystallization model for GCr15 bearing steel was integrated into the Forge® 3.2 numerical simulation software through secondary program development to simulate the compression process of GCr15 warm-hot forming. The dynamic recrystallization fraction was analyzed in various deformation regions. The grain size of the severe deformation zone, small deformation zone, and difficult deformation zone was compared based on simulated compression specimens under the conditions of 1050 °C and 0.1 s-1 with the corresponding grain size obtained with measurement based on metallographic photos; the relative error between the two is 5.75%. This verifies the accuracy of the established dynamic recrystallization and critical strain models for warm-hot deformation of GCr15 bearing steel. These models provide a theoretical basis for the finite element method analysis and microstructure control of the warm-hot forming process in bearing races.


Mediating Effect of Humanism on the Relationship between Task Performance Competence and Holistic Nursing Competence for Clinical Nurses.
This is a cross-sectional descriptive study that investigates the mediating effect of humanism on the relationship between task performance and holistic nursing competence among clinical nurses. The participants were nurses with more than one year of work experience in general hospitals in South Korea, recruited using convenience sampling. A total of 227 data samples were collected. A self-reported questionnaire including the task performance competence scale, holistic nursing competence scale, and humanism scale was used for the survey. Data were analyzed using the t-test, analysis of variance, Pearson's correlation coefficients, and hierarchical multiple regression after checking for normal distribution. The results showed that task performance competence, holistic nursing competence, and humanism differed according to characteristics such as gender, age, educational level, marital status, position, length of career, and job and salary satisfaction. Task performance competence was positively correlated with holistic nursing competence and humanism. A positive correlation was also observed between holistic nursing competence and humanism. A partial mediating effect of humanism in the relationship between task performance competence and holistic nursing competence was confirmed. Thus, to increase nurses' holistic nursing competence, it is necessary to improve task performance competence and formulate a continuous and repetitive education program that includes humanism.