Biological, familial, and peer influences on dating in early adolescence.
The current study examined the joint contributions of pubertal maturation, parental monitoring, involvement in older peer groups, peer dating, and peer delinquency on dating in a sample of early adolescent boys and girls. The sample consisted of 784 adolescents (394 boys, 390 girls) enrolled in grades 5, 6, and 7 who were followed for one year. In addition to measures of pubertal maturation and parental monitoring, adolescents and their peer group members completed indices of dating and delinquency. Average dating and delinquency scores for each participant's peer group network were computed. Results indicated that it was the combination of pubertal maturation, peer delinquency, and peer dating that explained increases in early dating. For boys only, parental monitoring was a significant predictor. The more knowledgeable parents were about their boys' activities, the lower the number of dating activities reported. These results highlight the importance of considering the joint effects of these biological and social predictors in understanding early dating. When rapid changes occur in all three domains, early dating is most likely to ensue. The findings of this study have practical importance. Parents and professionals who work closely with youth should attend to the special vulnerability of early maturing adolescents in the face of peer pressure and to the important role of parental monitoring in regulating dating activities.


Nut consumption is associated with better nutrient intakes: results from the 2008/09 New Zealand Adult Nutrition Survey.
A limited number of studies have examined associations between nut consumption and nutrient intakes or diet quality. None has investigated these associations in the Southern Hemisphere. The purpose of this study was to examine associations between nut consumption and nutrient intakes among adult New Zealanders. Data from the 24-h recalls of 4721 participants from the cross-sectional 2008/09 New Zealand Adult Nutrition Survey (2008/09 NZANS) were used to determine whole nut intake and total nut intake from all sources as well as nutrient intakes. Regression models, both unadjusted and adjusted for potential confounders, were used to estimate differences in nutrient intakes between those consuming and those not consuming nuts. From adjusted models, compared with non-whole nut consumers, whole nut consumers had higher intakes of energy and percentage of energy from total fat, MUFA and PUFA, whereas percentage of energy from SFA and carbohydrate was lower (all P≤0·025). After the additional adjustment for energy intake, whole nut consumers had higher intakes of dietary fibre, vitamin E, folate, Cu, Mg, K, P and Zn (all P≤0·044), whereas cholesterol and vitamin B12 intakes were significantly lower (both P≤0·013). Total nut consumption was associated with similar nutrient profiles as observed in whole nut consumers, albeit less pronounced. Nut consumption was associated with better nutrient profiles, especially a lower intake of SFA and higher intakes of unsaturated fats and a number of vitamins and minerals that could collectively reduce the risk for chronic disease, in particular for CVD.


The right pleuromediastinal reflection in children.
The authors review the anatomy of the pleural reflection of the right lung against the middle mediastinum in childhood. In 505 consecutive normal frontal radiographs of children, from birth to sixteen years, this pleural reflection (also known as the pleuro-esophageal line) was visible in 83%. The entire reflection from thoracic inlet to diaphragm was clearly seen in 13%, chiefly in upright, deep-inspiration, well penetrated radiographs. It is a radiographic landmark in the middle mediastinum, particularly well seen in childhood, and its use in assessment of mass lesions, cardiomegaly and lung collapse is described.


Singularity and medicine: is there a place for heteronomy in medical ethics?
In medicine and in clinical practice, autonomy is opposed to heteronomy or paternalism. While autonomy comes down to free choice, independence or self-fulfillment, heteronomy or paternalism are associated with restraints from outside, lack of free choice or dependence. Despite several mediating concepts such as relational autonomy, this opposition stands firm in medical discourse. Reflecting upon his own heart transplantation but also falling back upon the whole of his oeuvre, we want to analyze what the impact of Nancy's thought can be on the concept of autonomy in medicine. As in Nancy's theory, autonomy and heteronomy are intertwined, how then to understand the autonomous individual in a clinical context? Nancy developed in his book Corpus, the untranslatable French word 'expeausition' to express the exposure of surfaces to one another - playing on the term 'exposition': 'peau', in French, means skin. Skin is literally exposed to contact with another skin or surface. Such exposure and such contact is 'world' he argues, in the same way that a product exchange between two people is. Heteronomy therefore is constitutive for autonomy, not a restraint of it. Analyzed from the work of French philosopher Jean-Luc Nancy, there is no such thing as autonomy because every 'self' or 'I' is always already intruded by something from outside. There is no autonomy without heteronomy, he argues and he therefore prefers to speak of an individual as being exposed to the outer world.


Vascular proteomics.
The characterization of patients with acute coronary syndromes (ACS) at the molecular and cellular levels provides a novel vision for understanding the pathological and clinical expression of the disease. Recent advances in proteomic technologies permit the evaluation of systematic changes in protein expression in many biological systems and have been extensively applied to cardiovascular diseases (CVD). The cardiovascular system is in permanent intimate contact with blood, making blood-based biomarker discovery a particularly worthwhile approach. Thus, proteomics can potentially yield novel biomarkers reflecting CVD, establish earlier detection strategies, and monitor response to therapy. Here we review the different proteomic strategies used in the study of atherosclerosis and the novel proteins differentially expressed and secreted by atherosclerotic lesions which constitute novel potential biomarkers (HSP-27, Cathepsin D). Special attention is paid to MS-Imaging of atheroma plaque and the generation, for the first time, of 2-D images of lipids, showing the distribution of these molecules in the different areas of the atherosclerotic lesions. In addition new potential biomarkers have been identified in plasma (amyloid A1α, transtherytin), circulating cells (protein profile in monocytes from ACS patients) and individual cells constituents of atheroma plaques (endothelial, VSMC, macrophages) which provide novel insights into vascular pathophysiology.


The ultrastructure of the neuromuscular junctions of mammalian red, white, and intermediate skeletal muscle fibers.
Distinct ultrastructural differences exist at the neuromuscular junctions of red, white, and intermediate fibers of a mammalian twitch skeletal muscle (albino rat diaphragm). The primary criteria for recognizing the three fiber types are differences in fiber diameter, mitochondrial content, and width of the Z line. In the red fiber the neuromuscular relationship presents the least sarcoplasmic and axoplasmic surface at each contact. Points of contact are relatively discrete and separate, and axonal terminals are small and elliptical. The junctional folds are relatively shallow, sparse, and irregular in arrangement. Axoplasmic vesicles are moderate in number, and sarcoplasmic vesicles are sparse. In the white fiber long, flat axonal terminals present considerable axoplasmic surface. Vast sarcoplasmic surface area is created by long, branching, closely spaced junctional folds that may merge with folds at adjacent contacts to occupy a more continuous and widespread area. Axoplasmic and sarcoplasmic vesicles are numerous. Both axoplasmic and sarcoplasmic mitochondria of the white fiber usually contain intramitochondrial granules. The intermediate fiber has large axonal terminals that are associated with the most widely spaced and deepest junctional folds. In all three fiber types, the junctional sarcoplasm is rich in free ribosomes, cisternae of granular endoplasmic reticulum, and randomly distributed microtubules.


Bone-anchored hearing device surgery: a 3- to 6-year follow-up with life table and worst-case scenario calculation.
Published studies on complications for the bone-anchored hearing devices can present different outcomes. Unfortunately, data are often difficult to interpret, compare, or use in meta-analysis owing to missing data. This study presents a sensitivity analysis of presenting cohort data, which considers incomplete follow-up data. An example is given using life table calculations and worst-case scenarios for implant losses and revision surgeries after installing BAHA. A retrospective case review of all patients consecutively operated on for BAHA between 2005 and 2007 with a 1-stage procedure. Life table calculations were used to handle incomplete follow-up data, including 50% of patients lost to follow-up as failures. In addition, a worst-case scenario was calculated, in which 100% of patients lost to follow-up were considered to be failures. A total of 138 patients were operated on at Sahlgrenska, with a follow-up time of 3 to 5 years. Within the study cohort, 9 patients (6.5%) lost the implant. Reasons for incomplete follow-up data were as follows: "lost to follow-up" (n = 4), "not using BAHA" (n = 3), and "patient was deceased" (n = 2). Life table calculation gave a calculated implant loss of 9.8%. The worst-case scenario gave an implant loss frequency of 13%. Revision surgery was performed in 3 (2.2%) of 138 patients in the study cohort. With life table and worst-case scenario calculations, the frequency of revision surgery was 6.2% and 10.1%, respectively. Incomplete follow-up data can theoretically affect outcome data considerably. Therefore, outcome data should also be presented with life table and worst-case scenario. This would enhance the possibility to interpret and compare data.


Magnetic resonance imaging findings of sclerosing Sertoli cell tumor of the testis.
We present a case of sclerosing Sertoli cell tumor of the testis that was examined preoperatively by magnetic resonance imaging. A 28-year-old male presented to the urology department of our hospital complaining of a painless mass in the right testicle that had been present for the past 2 years. Levels of the tumor markers AFP, hCG, and LDH were all within the standard ranges. T2-weighted MR images showed a well-demarcated lobular hypointensity 15 mm in size in the right testis. Contrast enhancement of this mass after gadolinium administration was homogeneous, with slightly stronger enhancement than the normal testis tissue. Tumor enucleation was performed, and the tumor was diagnosed as a sclerosing Sertoli cell tumor.


Regulatory mechanisms of dynamin-dependent endocytosis.
Extensive studies on endocytosis in the last decade have resulted in identification of several key molecules that function in clathrin- and dynamin-dependent endocytosis. Most endocytic molecules contain multiple binding motifs that mediate protein-protein or protein-lipid interactions, which must be modulated spatially and temporally during endocytosis. Regulation of these interactions is the molecular basis of regulatory mechanisms involved in endocytosis. This review first describes current models of the mechanism of dynamin-dependent fission, then introduces several mechanisms that modulate dynamin GTPase activity and dynamin-dependent vesicle formation. Such mechanisms include regulation by inositol phospholipids, especially phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)], and their metabolism. It concludes by describing the regulation of dynamin 1 by its binding partner, amphiphysin 1, and regulation by cyclin-dependent kinase 5 (Cdk5)-dependent phosphorylation of dynamin 1 and amphiphysin 1. These mechanisms help endocytic molecules to function properly, and cooperatively regulate dynamin-dependent endocytosis.


[Gasless versus conventional laparoscopic cholecystectomy. A randomized trial with regard to technical problems, postoperative course and convalescence].
The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery may induce pathophysiological changes. Concern about these changes has led to the introduction of a gasless technique. The aim of the present study was to compare the gasless CLC and GLC with regard to exposure, technical problems, operation time, postoperative pain, clinical course, and convalescence. Fifty consecutive patients with symptomatic gallstones were randomised to conventional (CLC) or gasless laparoscopic cholecystectomy (GLC), with special reference to overall patient satisfaction, technical difficulties, duration of surgery, postoperative pain, and recovery. The overall exposure of the operative field was poorer in the GLC group, whereas the duration of surgery, steps involved in the cholecystectomy technique, length of hospital stay, and postoperative pain score did not differ significantly. The period to return to normal activity was significantly shorter in the GLC group, six days compared to 8.5 days in the CLC group (p < 0.05). No differences were found in terms of fatigue, dizziness and nausea, and overall satisfaction with the outcome. This study shows that convalescence is significantly shorter after laparoscopic cholecystectomy by the gasless technique than by the conventional CO2 technique. However, exposure of the operative field was less than optimal with the gasless technique.


Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation.
Sequence analysis of the ADAMTS13 locus of 2 patients with hereditary thrombotic thrombocytopenic purpura (TTP) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of ADAMTS13 deficiency. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on ADAMTS13 secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced ADAMTS13-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of ADAMTS13 secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases.


Effect of Three Different Sedatives on Electroretinography Recordings in Domestic Pigeons (Columba livia).
This study was conducted to compare the effects of 3 different sedative agents on electroretinography (ERG) in domestic pigeons (Columba livia). Six pigeons were sedated with alfaxalone, xylazine, and medetomidine at separate times with a 1-week washout period between sedative administration. After sedation with each agent, pigeons underwent the modified ERG protocol adapted from the standardized protocol for dogs. The scotopic mixed rod and cone response was recorded after 20 minutes of dark adaptation, and the photopic cone response and photopic flicker response were recorded after 10 minutes of light adaptation. Either a 1-way analysis of variance or a Kruskall-Wallis test was used to compare the a-wave and b-wave implicit time and amplitude. No significant differences were observed in the scotopic mixed rod and cone response among all 3 sedatives used. Compared with alfaxalone, medetomidine significantly prolonged the a-wave implicit time, depressed the b-wave amplitude of photopic cone response, and prolonged the peak implicit time of the photopic flicker response (P < .05). These results show that medetomidine has a depressant effect on photopic ERG in pigeons at a dosage that produces light sedation.


Nanoscale organization of hedgehog is essential for long-range signaling.
Hedgehog (Hh) plays crucial roles in tissue-patterning and activates signaling in Patched (Ptc)-expressing cells. Paracrine signaling requires release and transport over many cell diameters away by a process that requires interaction with heparan sulfate proteoglycans (HSPGs). Here, we examine the organization of functional, fluorescently tagged variants in living cells by using optical imaging, FRET microscopy, and mutational studies guided by bioinformatics prediction. We find that cell-surface Hh forms suboptical oligomers, further concentrated in visible clusters colocalized with HSPGs. Mutation of a conserved Lys in a predicted Hh-protomer interaction interface results in an autocrine signaling-competent Hh isoform--incapable of forming dense nanoscale oligomers, interacting with HSPGs, or paracrine signaling. Thus, Hh exhibits a hierarchical organization from the nanoscale to visible clusters with distinct functions.


Thrombotic thrombocytopenic purpura treated with high-dose intravenous gamma globulin.
Plasma infusion and/or plasma exchange has become standard therapy in the treatment of thrombotic thrombocytopenic purpura (TTP). The management of patients in whom such primary therapy fails is difficult and uncertain. We have described a patient who obtained a sustained remission with the use of high-dose IV gamma globulin after an initial response to aggressive plasma exchange was followed by prompt relapse. Our case and others suggest that high-dose IV IgG may induce remission in patients with TTP who do not respond to standard plasma infusion and/or exchange.


Concomitant Regulation by a LacI-Type Transcriptional Repressor XylR on Genes Involved in Xylan and Xylose Metabolism and the Type III Secretion System in Rice Pathogen Xanthomonas oryzae pv. oryzae.
The hypersensitive response and pathogenicity (hrp) genes of Xanthomonas oryzae pv. oryzae, the causal agent of bacterial leaf blight of rice, encode components of the type III secretion system and are essential for virulence. Expression of hrp genes is regulated by two key hrp regulators, HrpG and HrpX; HrpG regulates hrpX and hrpA, and HrpX regulates the other hrp genes on hrpB-hrpF operons. We previously reported the sugar-dependent quantitative regulation of HrpX; the regulator highly accumulates in the presence of xylose, followed by high hrp gene expression. Here, we found that, in a mutant lacking the LacI-type transcriptional regulator XylR, HrpX accumulation and hrp gene expression were high even in the medium without xylose, reaching the similar levels present in the wild type incubated in the xylose-containing medium. XylR also negatively regulated one of two xylose isomerase genes (xylA2 but not xylA1) by binding to the motif sequence in the upstream region of the gene. Xylose isomerase is an essential enzyme in xylose metabolism and interconverts between xylose and xylulose. Our results suggest that, in the presence of xylose, inactivation of XylR leads to greater xylan and xylose utilization and, simultaneously, to higher accumulation of HrpX, followed by higher hrp gene expression in the bacterium.


Diuranal rhythms in 2- and 8-week-old infants: sleep-waking state organization as a function of age and stress.
Time of day differences in sleep-waking state organization were studied in 2- and 8-week-old infants by means of videotape recordings. Observations were made prior to and following adaptation to standard laboratory conditions previously found to be stressful. Diurnal rhythms occurred for a number of component sleep-waking states under the nonstressful conditions only, and increased with age.


Visual Outcomes and Clinical Manifestations of Pediatric Optic Neuritis in Indian Population: An Institutional Study.
Optic neuritis in children is an uncommon disorder which usually occurs after a viral illness or vaccination and, less frequently, occurs as a manifestation of a demyelinating disorder. Pediatric optic neuritis usually is bilateral and presents with optic disc edema, recovers rapidly with steroid therapy, and generally has low conversion rate to multiple sclerosis or neuromyelitis optica spectrum disorder. We report the clinical features and treatment outcomes of pediatric optic neuritis in Indian population, for which little data are available. We reviewed the medical case records of patients with optic neuritis who were younger than 18 years, from 1999 to 2016. All patients were assessed and managed in the Neuro-Ophthalmology Department of Sankara Nethralaya, a unit of Medical Research Foundation and Pediatric Neurology Department of Kanchi Kamakoti-Childs Trust Hospital, Chennai, India. One hundred seventeen eyes of 78 children with mean age of 11.84 (±4.58) years were identified. Forty-two (53.8%) were females and 36 (46.2%) were males. Thirty-nine patients (50%) had bilateral involvement and a similar number had unilateral involvement. Fifty-nine eyes (50.4%) had optic disc edema, 20 eyes (17.1%) had disc pallor, and 38 eyes (32.4%) had normal discs. Of 63 patients who had neuroimaging, 36 had MRI, and 27 underwent computed tomography. Eighty-four eyes (of 59 patients) received steroid therapy according to the protocol of the Optic Neuritis Treatment Trial (ONTT). Thirty-three eyes that were treated with other steroid protocols were excluded from the final visual outcome analyses. Sixty of the 84 eyes (72.3%) recovered visual acuity of 20/40 or better. Visual acuity improvement was statistically significant between initial and final visual acuity (logMAR) in our patients treated with the ONTT protocol (P ≤ 0.001). Our Indian pediatric population had good visual recovery after steroid treatment for optic neuritis. Profound loss of visual acuity on presentation and bilateral involvement were significantly associated with poor visual outcome.


[Prolonged drug-induced erection. Treatment and prevention].
The efficiency of intracavernous injection (ICI) of drugs for impotence is unfortunately counteracted by a real morbidity. The main danger lies in the persistence of this artificial erection. This pharmacologically induced prolonged erection (PIPE) appears like a real no-ischemic priapism. The risk of ischemic transformation must orientate the treatment of this frequent iatrogenic priapism. A decompressive puncture is often adequate. When ineffective, ICI of anti-erectogenic drugs will be indicated. But, this new treatment of priapism is not always effective, and most importantly, it can be dangerous, requiring considerable prudence for both indications and technics (risks of cavernous necrosis and of severe hypertensive crisis). The morbidity of this new pharmacological method is the major handicap to its wide use. Prevention now seems possible by carefully selection of indications for ICI and of the choice of both drugs and dosage, especially for high risk PIPE groups (neurologic and psychogenic impotence).


[A method of determining subpopulations of B-lymphocytes using a flow cytometer].
A method was developed for measuring human B-lymphocyte subpopulations with a flow cytometer making use of monospecific porcine antisera to FITC-labeled human immunoglobulins. The results of B-lymphocyte measurements with the traditional fluorescent microscopy and the suggested flow cytometry were in high correlation.


A novel transcriptional mechanism of cell type-specific regulation of vascular gene expression by glucose.
Vascular diabetic complications are associated with abnormal extracellular matrix and dysfunction of vascular cells, which later result in aberrant angiogenesis and development of atherosclerotic lesions. The tissue and cell specificity of the effects of high glucose are well recognized, but the underlying cell type-specific molecular mechanisms controlled by glucose are still unclear. We sought to identify cell type-specific mechanisms by which high glucose regulates transcription of genes in vascular cells. Thrombospondin-1 is a potent antiangiogenic protein associated with development of several diabetic complications and regulated by high glucose in multiple cell types. We report that distinct cell type-specific mechanisms regulate thrombospondin-1 gene (THBS1) transcription in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in response to high glucose: although a proximal fragment of 280 nucleotides is sufficient to drive transcription in ECs, THBS1 was regulated cooperatively by interaction between proximal (-272 to -275) and distal (-1016 to -1019) promoter elements in VSMCs. Transcription factors activated by high glucose in VSMCs were cell type-specific. The formation of a single complex interacting with both distal and proximal glucose-responsive elements of THBS1 promoter in VSMCs was confirmed using gel-shift assays, binding sequence decoy oligomers, and specific mutant promoter fragments. Transcriptional response of vascular cells to high glucose is cell type-specific and involves activation of distinct transcription factors, providing a basis for tissue-specific changes of vasculature in diabetics.


Cognitive anthropologists: who needs them?
During the last decades, the cognitive sciences and cognitive anthropology have increasingly veered away from each other. Cognitive anthropologists have become so rare within the cognitive sciences that Beller, Bender, and Medin (this issue) even propose a division of the cognitive sciences and cognitive anthropology. However, such a divorce might be premature. This commentary tries to illustrate the benefits that cognitive anthropologists have to offer, not despite, but because of their combination of humanistic and scientific elements. It argues that the cognitive sciences (among others) profit from these benefits, as culture will become crucial for cognitive research. At the same time, problems within cognitive anthropology are discussed, including, for example, the responsibility of cognitive anthropologists to promote young academics. Finally, ideas are presented that might support future interdisciplinary collaboration.


A strategic sampling design revealed the local genetic structure of cold-water fluvial sculpin: a focus on groundwater-dependent water temperature heterogeneity.
A key piece of information for ecosystem management is the relationship between the environment and population genetic structure. However, it is difficult to clearly quantify the effects of environmental factors on genetic differentiation because of spatial autocorrelation and analytical problems. In this study, we focused on stream ecosystems and the environmental heterogeneity caused by groundwater and constructed a sampling design in which geographic distance and environmental differences are not correlated. Using multiplexed ISSR genotyping by sequencing (MIG-seq) method, a fine-scale population genetics study was conducted in fluvial sculpin Cottus nozawae, for which summer water temperature is the determinant factor in distribution and survival. There was a clear genetic structure in the watershed. Although a significant isolation-by-distance pattern was detected in the watershed, there was no association between genetic differentiation and water temperature. Instead, asymmetric gene flow from relatively low-temperature streams to high-temperature streams was detected, indicating the importance of low-temperature streams and continuous habitats. The groundwater-focused sampling strategy yielded insightful results for conservation.


Quality of life and upper limb disability in Charcot-Marie-Tooth disease: A pilot study.
Charcot-Marie-Tooth (CMT) patients present mainly lower limbs disability, with slowly progressive distal muscle weakness and atrophy, but hands impairment is a relevant problem affecting the quality of life (QoL). The evaluation of the upper limb is of primary importance. Often these patients present subclinical disorders or report difficulties in manipulating objects, with little evidence in the most used outcome measures. We aim to investigate the impact of hand impairment in the perceived QoL of CMT persons and secondly whether the Disability of Arm, Shoulder and Hand (DASH) scale can be useful in assessing upper limb abilities in CMT. We recruited 23 patients with confirmed genetic diagnosis of CMT. We performed a clinical evaluation with Sollerman Hand Function Test (SHFT), Thumb Opposition Test (TOT) and CMT examination score (CMTES). We completed the clinical assessment with DASH scale and the Short form 36 (SF36) questionnaire for a subjective evaluation of upper limb disability and quality of life. All patients also underwent an instrumental evaluation with a hand-held dynamometer measuring hand grip and tripod pinch and a sensor-engineered glove test (SEGT) to evaluate finger opposition movements in a quantitative spatial-temporal way. As expected, we found significant differences between CMT and control group performances in both clinical and instrumental assessment. Concerning QoL, we found that total score of SF36 and the SF36 Physical Composite Score (PCS) correlate with all clinical and instrumental Outcome Measures (OMs), particularly with Tripod pinch strength and TOT, which are considered major determinants of manual dexterity in CMT. DASH scale correlates with most clinical and instrumental OMs. Not surprisingly, we also found a correlation with DASH work, because CMT affects young patients engaged in work activities. However, we found a low correlation with the TOT and the dynamometer suggesting that DASH may not be the best scale for remote monitoring of upper limb disorders in CMT patients. Nevertheless, the results of our study confirm the usefulness of SF36 in recognizing the impact of upper limb disability in these subjects suggesting its use even in the remote monitoring of physical functioning.


Chromosomal instability detected by interphase fluorescence in situ hybridization and its relation to p53 alteration in prostate carcinoma in Saudi patients.
Chromosomal instability (CIN) is a feature of human neoplasm. The p53 mutation has been shown to be associated with CIN in many human dysplastic and neoplastic lesions. The objective of this study was to examine CIN and p53 mutations in prostate carcinoma (Pca) resected from Saudi patients. Testing of p53 alteration using immunohistochemistry was performed on 28 archived prostatic carcinoma specimens containing Pca foci from Saudi patients seen at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Chromosomal instability was evaluated in the same tissues by interphase in situ hybridization (IFISH) using centromere probes for chromosome 7 and 8. Immunohistochemistry and IFISH were performed at Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada in 2001. The p53 immunoreactivity was found in 29% in Pca and 0% in benign epithelium. Interphase in situ hybridization revealed numerical chromosomal alterations in keeping with CIN in 63% of p53 positive and 20% p53 negative Pca. No evidence of CIN was seen in non-neoplastic epithelium. We concluded that CIN as determined by IFISH is present in Pca from Saudi patients similarly to those reported in western countries. The p53 mutation occurs relatively infrequently in Pca and is associated with the presence of CIN at least in a subset of Pca.


Micronucleus evaluation of exfoliated buccal epithelial cells using liquid-based cytology preparation.
Micronuclei (MN) are biomarkers that can be applied to buccal epithelial cells to assess populations occupationally exposed to potentially carcinogenic agents. Liquid-based cytology (LBC) is a way to improve and refine the results obtained by this test. Exfoliated buccal cells were collected from 40 subjects (20 construction workers from the Barretos Cancer Hospital and 20 administrative staff from the same institution). LBC and three stains (Feulgen/fast green, Papanicolaou and Giemsa) were used to prepare the slides. Student's t test was applied for statistical comparisons of the data. A p value of <0.05 was considered statistically significant. Regardless of the stain employed, the frequency of MN was greater in the case group (Feulgen/fast green: 5.15; Papanicolaou: 29; Giemsa: 26) than in the control group (Feulgen/fast green: 2.30; Papanicolaou: 17; Giemsa: 15). Using LBC to prepare slides and evaluate the frequency of MN potentially serves as a screening option for more comprehensive studies of cancer risk among populations occupationally exposed to potentially carcinogenic agents. In addition, the residual fluid enables the preparation of slides for DNA-specific stains that can be compared to those with Papanicolaou stain.


Competitive Coronary Flow between the Native Left Anterior Descending Artery and Left Internal Mammary Artery Graft: Is It a Surrogate Angiographic Marker of Over-or-Unnecessary Revascularization Decision in Daily Practice?
Overdiagnosis and overtreatment are often thought of as relatively recent phenomena in modern medicine, influenced by a contemporary combination of technology, specialization, payment models, marketing, and supply-related demand. Several investigators have reported discrepancies between the angiographic and functional severity of coronary angiographic stenosis. However, the visual anatomic assessment of the coronary lesion severity continues in daily practice. We evaluated the consecutive all coronary angiograms performed between January 2015 and December 2015 and examined only patients who had previous coronary artery bypass grafting (CABG) to analyze the cases with regard to presence of the competitive flow (CF) between the native left anterior descending coronary artery (LAD) and left internal mammary artery (LIMA) graft. A total of 8,248 diagnostic coronary angiographies were performed between January 2015 and December 2015 at our facility. Of these, 886 coronary angiographies of CABG patients were detected. Whereas LIMA graft occlusion detected in 19 patient (2.1%), the LIMA-LAD CF rate was found in 86 (9.7%) CABG patients. The angiographic severity of the LAD stenosis in CF group evaluated as mild in 20 (25%), moderate in 61 (70%), and severe coronary artery disease in 4 (5%) patients. Our results showed that there is 9.7% rate of LIMA-LAD CF. Therefore, some unnecessary coronary stenting or CABG procedures might have been performed due to limited use of functional testing for clinical decision making. The functional angiography should play a more prominent role in catheterization laboratories as recommended by current revascularization guidelines to prevent overdiagnosis, misdiagnosis, or incorrect treatment decisions.


Anti-U3 ribonucleoprotein antibody-positive inflammatory myopathy: a case report.
The discovery of myositis-specific autoantibodies and myositis-associated autoantibodies has led to a new serological classification. Human U3 RNP, which consists of the U3 small nucleolar RNA and anti-U3 RNP antibody, is directed against one of the subunits. Anti-U3 RNP antibodies have been detected in 5-8 % of patients with systemic sclerosis, and antibody-positive patients with systemic sclerosis have shown more frequent skeletal muscle involvement than that of antibody-negative patients with systemic sclerosis. A 74-year-old Japanese man positive for anti-U3 RNP antibody was referred to our hospital because of gait disturbance and dysphagia. His serum myoglobin and creatine kinase levels were elevated, and myopathic changes were observed in his proximal legs by needle electromyography. A muscle biopsy was performed at the quadriceps femoris muscle, which showed high signal intensity on fat-suppressed and T2-weighted magnetic resonance images. The patient was diagnosed with probable polymyositis because CD8-positive lymphocytes had invaded only the endomysium and not into the muscle fibers. Severe proliferation of the interstitial connective tissue and edematous changes were observed. Oral prednisolone therapy was started, and the patient's muscle weakness of the proximal limbs improved remarkably within 1 month. Dysphagia caused by incomplete function of the cricopharyngeal muscle persisted for 5 years. Our findings indicate that mild muscle weakness with steroid-resistant dysphagia may be a clinical feature of patients with anti-U3 RNP antibody-positive inflammatory myopathy.


Knoevenagel Adducts as Trimethylenemethane Dipole Surrogates.
Knoevenagel adducts derived from readily available acetoxyacetone and malonic acid derivatives served as trimethylenemethane surrogates for formal 1,3-difunctionalization through a sequence of selective γ-deprotonation/α-alkylation and palladium(0)-catalyzed allylic alkylation. Herein, we report the discovery and development of a three-component 1,3-difunctionalization of Knoevenagel adducts as well as a unique palladium(0)-catalyzed branch-selective allylic alkylation.


Where next for delirium research?
Clinicians who manage delirium must do so without key information required for evidence-based practice, not least lack of any clearly effective treatment for established delirium. Both the nature of delirium and the methods used to research it contribute to difficulties. Delirium is heterogeneous, with respect to motor subtype, aetiology, setting and the co-existence of dementia, and may be almost inevitable towards the end of life. Elements of assessment are subjective, so diagnosis can be uncertain or unreliable. Defining objectives of care and outcomes is sometimes unclear. Better identification and case definition, including seeking biomarkers, stratification by type, or aetiology, and application of more complex models of causation may help. This will likely require further observational epidemiology, imaging and laboratory-based research before further rounds of large-scale randomised controlled trials. Application of trial methodologies designed for drug treatments of better-defined conditions may have failed to take account of the complexities both of diagnosis and complex intervention in delirium. Both drug and complex intervention trials need sufficient preliminary work to ensure that the right dose, duration or intensity of treatment is delivered and a range of 'intermediate' and 'distal' outcome measures assessed. Re-purposing of established drugs may provide a source of investigational products. Greater use of alternative research methodologies (qualitative and realist), or adjuvants to trials (process evaluation), will help answer questions about focus, generalisability and why interventions succeed or fail. Delirium research will have to embrace both a 'back to basics' approach with increased breadth of methodologies to make progress.


Rates of anterior tooth wear in Middle Pleistocene hominins from Sima de los Huesos (Sierra de Atapuerca, Spain).
This study presents quantitative data on the rates of anterior tooth wear in a Pleistocene human population. The data were obtained for the hominin sample of the Sima de los Huesos site in Atapuerca, Spain. The fossil record belongs to a minimum of 28 individuals of the same biological population, assigned to the species Homo heidelbergensis. We have estimated the original and the preserved crown height of the mandibular incisors (I1 and I2) of 11 individuals, whose age at death can be ascertained from the mineralization stage and tooth eruption. Results provide a range of 0.276-0.348 and 0.288-0.360 mm per year for the mean wear rate of the mandibular I1 and I2, respectively, in individuals approximately 16-18 years old. These data suggest that incisors' crowns would be totally worn out toward the fifth decade of life. Thus, we expect the life expectancy of this population to be seriously limited. These data, which could be contrasted with results obtained on hominins at other sites, could be of interest for estimating the death age of adult individuals.


Loading a Calcium Dye into Frog Nerve Endings Through the Nerve Stump: Calcium Transient Registration in the Frog Neuromuscular Junction.
One of the most feasible methods of measuring presynaptic calcium levels in presynaptic nerve terminals is optical recording. It is based on using calcium-sensitive fluorescent dyes that change their emission intensity or wavelength depending on the concentration of free calcium in the cell. There are several methods used to stain cells with calcium dyes. Most common are the processes of loading the dyes through a micropipette or pre-incubating with the acetoxymethyl ester forms of the dyes. However, these methods are not quite applicable to neuromuscular junctions (NMJs) due to methodological issues that arise. In this article, we present a method for loading a calcium-sensitive dye through the frog nerve stump of the frog nerve into the nerve endings. Since entry of external calcium into nerve terminals and the subsequent binding to the calcium dye occur within the millisecond time-scale, it is necessary to use a fast imaging system to record these interactions. Here, we describe a protocol for recording the calcium transient with a fast CCD camera.


The role of illness perceptions: psychological distress and treatment-seeking delay in patients with genital warts.
This study examined the relationships between illness perceptions, psychological distress and treatment-seeking delay in genital warts patients. Sixty-six genital warts patients were approached while attending a sexual health clinic. They completed a questionnaire assessing their illness perceptions, psychological distress and treatment-seeking delay. Negative perceptions of illness consequences and control and a perceived cyclical timeline were associated with increased psychological distress. Perceived illness consequences maintained significance in a multiple regression equation, which accounted for 25% variance in distress. Depression was associated with treatment-seeking delay (r = 0.28, P = 0.03). In conclusion, illness perceptions may play an important role in the experience of psychological distress in genital warts patients. The implications of these findings for the design of health-care interventions are discussed.


Endobronchial metastasis from adenocarcinoma of gastric cardia 7 years after potentially curable resection.
Endobronchial metastasis (EBM) is a rare form of metastasis from extrapulmonary malignant tumors, although there are few reports of EBM from gastric cancer specifically. We report the case of a 51-year-old woman who had undergone gastrectomy for advanced gastric cancer seven years previously but was diagnosed with a solitary lung tumor by follow-up computed tomography. On diagnosis of primary lung cancer, she underwent pulmonary lobectomy, but immunohistochemical examination confirmed the resected tumor to be an EBM from the gastric cancer. Six months later, she was diagnosed with peritoneal metastases and underwent chemotherapy with gastric cancer regimen. She is still alive at 33 mo after the lobectomy. Generally, the prognosis for EBM is poor although multidisciplinary treatment can lead to long-term survival. Precise diagnosis on the basis of detailed pathological and immunohistochemical evaluation can contribute to deciding the most effective treatment and improving prognosis.


Iron(II) Complexes of 2,4-Dipyrazolyl-1,3,5-triazine Derivatives-The Influence of Ligand Geometry on Metal Ion Spin State.
Seven [FeL2][BF4]2 complex salts were prepared, where L is a 6-substituted 2,4-di(pyrazol-1-yl)-1,3,5-triazine (bpt) derivative. The complexes are all crystallographically high-spin, and exhibit significant distortions from an ideal D2d-symmetric coordination geometry. In one case, an unusual type of metal ion disorder was observed among a cubic array of ligands in the crystal lattice. The complexes are also high-spin between 3 and 300 K in the solid state and, where measured, between 239 and 333 K in CD3CN solution. This result is unexpected, since homoleptic iron(II) complexes of related 2,6-di(pyrazol-1-yl)pyridine, 2,6-di(pyrazol-1-yl)pyrazine, and 2,6-di(pyrazol-1-yl)pyrimidine derivatives often exhibit thermal spin-crossover behavior. Gas-phase density functional theory calculations confirm the high-spin form of [Fe(bpt)2]2+ and its derivatives is stabilized relative to iron(II) complexes of the other ligand types. This reflects a weaker Fe/pyrazolyl σ-bonding interaction, which we attribute to a small narrowing of the chelate ligand bite angle associated with the geometry of the 1,3,5-triazinyl ring. Hence, the high-spin state of [Fe(bpt)2]2+ centers does not reflect the electronic properties of its heterocyclic ligand donors but is imposed by the bpt ligand conformation. A high-spin homoleptic iron(III) complex of one of the bpt derivatives was also synthesized.


Social support from family, associated factors and relationship with glycemic control among diabetic patients in Uganda: a cross-sectional study.
social support from family members in diabetes management is a predictor of optimal glucose control. There is limited evidence of the relationship in Uganda. The objective was to determine association of social support from family and glycemic control, and association of social demographic and clinical characteristics with family support among diabetic patients in eastern Uganda. this was a cross-sectional study involving 405 adult patients attending diabetic clinics between May 2021 and June 2021. Socio-demographics, clinical characteristics, social support from family, and glycemic control data were collected. Descriptive statistics were done and associations were determined using Pearson chi-square and Fisher´s exact tests. Generalized linear model was used to determine independent association with social support from family. the mean age was 52 years, (60%) were female, majority (49.4%) were 45-64 years old. Perceived social support from family (PSS-fa) and good glucose control were found in; (95.3%) and (20.99%) respectively. PSS-fa was associated with good glucose control. Financial contribution from family members to cost of care, cohesion among family members in support of care, being (married/cohabiting) and monthly income ≥28 USD were associated with PSS-fa. Factors independently associated with PSS-fa were; female gender, financial contribution to cost of care and cohesion among family in support of care. social support from family was associated with good glycemic control. Factors associated with PSS-fa were; female gender, financial contribution from family to cost of care and cohesion among family in support of care.


[Statistical studies and results of treatment of patients with perioral dermatitis].
279 patients suffering from perioral rosaceiform dermatitis have been treated during the past 5 years. With the exception of two men and one five-year-old girl, all patients were female adults, mostly in their thirties. Skin eruptions had been present for 1--2 years in 73% of the cases. Two third of the patients had been treated locally with corticosteroids and one tenth of this group had previously undergone systemic therapy. In 22,2% of the patients, typical signs of local corticosteroid overtreatment were seen. There was a great number of patients holding rather high-ranking jobs and showing remarkable zeal to advance either in their habitual professional field or in a new career. 90% of the perioral dermatitis patients suffered from concomitant vegetative disturbances, especially nervousness, insomnia, headaches and fatigue. In 40% of the cases, symptoms of general neurovascular lability were stated and 60% complained of digestive troubles, particularly obstipation. Out of 220 patients, 206 (=93%) supervised since the end of our treatment showed no relapse of their dermatosis. Our therapeutic program since 1970 consists of mild, corti-costeroid-free local treatment and psychotherapy (see A. Thurn). In the majority of cases, the skin lesions disappeared during the first 3 months and in 90% after 6 months. In 33 cases, under conditions of stress and conflict, one or several relapses occured before final recovery was attained. The evaluation of therapy results showed a progredient reduction of recovery time corresponding to the increasing psychoanalytical experience of our interdisciplinary team. However, in perioral dermatitis patients showing no concomitant vegetative symptoms (10%), a conspiciously longer recovery time was noted, when compared with the remainder of our cases. Patients suffering from several concomitant vegetative symptoms may possibly stop, taking out' psychic problems on their skin when partially resolved by short-term therapy, tending instead to ,somatize' their conflicts in other susceptible organs.


Metallic copper nanostructures synthesized by a facile hydrothermal method.
A facile hydrothermal route has been developed for the synthesis of nearly spherical copper nanoparticles, copper nanocubes and ribbon-like network nanostructures. The as-prepared copper nanostructures were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), and UV-vis spectrum analysis. These copper products were fabricated in the presence of surfactant sodium dodecyl benzenesulfonate (SDBS) acting not only as stabilizer but also as size and shape controller via hydrothermal reduction process. HRTEM revealed that the surface of the copper nanostructures was packed with a thin layer of impurities such as oxide combined surfactant or amorphous surfactant. The influence of surfactant concentration and temperature on the resultant copper nanostructures was investigated in details. UV-vis spectra indicated that strong red shift existed for the copper ribbon-like network nanostructures due to the novel morphology as well as the presence of impurities on the surface.


Light symptoms following a high-dose intentional L-thyroxine ingestion treated with cholestyramine.
Adult exposure to L-thyroxine has a wide range of presentations: most adults either do not develop symptoms or only become minimally symptomatic. Appropriate treatments after exposure to L-thyroxine have yet to be established. A 26-year-old woman with a suicidal intention was witnessed to ingest approximately 50 L-thyroxine tablets, each containing 0.1 mg L-thyroxine (total dose 5 mg). Cholestyramine was administered (4 g every 8 h p.o.). Vital signs were monitored every 6 h and the hormone levels (L-thyroxine and thyroid-stimulating hormone) every 24 h. The thyroxine levels increased, and the thyroid-stimulating hormone levels decreased, with a normalization of the L-thyroxine level on postingestion day 6. Hypertension, dysrhythmias, and delusions did not appear in our patient. Only distal tremor and diaphoresis appeared on day 1 after ingestion. Cholestyramine has been used in cases of iatrogenic hyperthyroidism, in patients with Graves' disease, and in patients with digoxin intoxications, with good responses in all cases and a low incidence of side effects. This case illustrates the potential utility of cholestyramine to treat L-thyroxine intoxications.


A first-principles investigation of the linear thermal expansion coefficients of BeF2: giant thermal expansion.
We present the results of a theoretical investigation of the linear thermal expansion coefficients (TECs) of BeF2, within a direct Grüneisen formalism where symmetry-preserving deformations are employed. The required physical quantities such as the optimized crystal structures, elastic constants, mode Grüneisen parameters, and phonon density of states are calculated from first-principles. BeF2 shows an extensive polymorphism at low pressures, and the lowest energy phases [α-cristobalite with space group (SG) P41212 and its similar phase with SG P43212] are considered in addition to the experimentally observed α-quartz phase. For benchmarking purposes, similar calculations are performed for the rutile phase of ZnF2, where the volumetric TEC (α v), derived from the calculated linear TECs along the a (α a ) and c (α c ) directions, is in very good agreement with experimental data and previous theoretical results. For the considered phases of BeF2, we do not find any negative thermal expansion (NTE). However we observe diverse thermal properties for the distinct phases. The linear TECs are very large, especially α c of the α-cristobalite phase and its similar phase, leading to giant α v (∼175 × 10-6 K-1 at 300 K). The giant α v arises from large Grüneisen parameters of low-frequency phonon modes, and the C 13 elastic constant that is negatively signed and large in magnitude for the α-cristobalite phase. The elastic constants, high-frequency dielectric constants, Born effective charge tensors, and thermal properties of the above phases of BeF2 are reported for the first time and hence serve as predictions.


Detection of lymphocyte subsets in renal graft biopsy by monoclonal antibodies.
Monoclonal antibodies were used to study infiltrating cell subpopulations in 12 graft biopsy specimens taken from 12 patients during rejection episodes. A preponderance of T lymphocytes in the renal interstitium was observed in most cases, with a higher percentage of suppressor/cytotoxic cells. No correlation was documented between the type and severity of rejection and the percentage of the various infiltrating cells.


Suffering of patients developing lymphedema following gynecological cancer surgery.
Lymphedema developing in the lower extremities following gynecological cancer surgery (LE-GCS) produces various kinds of sufferings, including impacts on quality of life (QOL) and body image. This research will serve as a basic resource for the care of patients with this type of lymphedema (LE). A qualitative discursive research method: Thirteen patients suffering from LE-GCS were interviewed in a semi-organized manner. Analysis involved extracting and codifying from transcripts and expressions related to the suffering of LE. Next, these codes were arranged into categories and subcategories under the supervision of qualitative researchers. Furthermore, this study was conducted with the approval of the Research Ethics Review Specialist Committee, which targets individuals affiliated with the public university corporation of Shiga Prefectural University. Based on the interviews with 13 patients aged 47-79 (median age 62), two core categories were created: 1). Suffering of LE Developing in Lower Extremities (570 codes, seven categories, 23 subcategories); and 2). Supports that Allow Patients to Face Suffering of LE (254 codes, four categories, 14 subcategories). Patients with LE-GCS live with the fear that LE exacerbation will produce adverse life changes, and this may exceed the fear of cancer itself. The aggravation of their condition results in immense pain as well as reduced mobility, change in appearance, and loss of self-worth. The symptoms fluctuate, and may lead to chronic misery, which does not manifest, but occasionally flares-up because of both, worsening physical disability as well as ordinary events. Additionally, every patient subjectively described the strength they found within themselves to face the suffering. They cited the support of family and friends, existence of compassionate therapists and doctors, acquisition of knowledge, and self-care.


Overcoming structural barriers to sharing power with communities in global health research priority-setting: Lessons from the Participation for Local Action project in Karnataka, India.
Community engagement is gaining prominence in global health research. But communities rarely have a say in the agendas or conduct of the very health research projects that aim to help them. This paper provides new evidence on how to share power in priority-setting in ways that seek to overcome structural constraints created by the funding environment. The five strategies were identified through case study research on the Participation for Local Action project in Karnataka, India. That project was carried out by researchers in partnership with the Zilla Budakattu Girijana Abhivrudhhi Sangha, an indigenous community development organisation representing the Solega people. The paper describes each identified strategy for sharing power in priority-setting, followed by a report of the pitfalls and challenges that arose when implementing it. Thus, the study also demonstrates that even where actions and strategies are used to address power imbalances, pitfalls will arise that need to be navigated. Given those challenges, considerations to reflect upon before employing the identified strategies are suggested. Ultimately, the paper aims to communicate strategies for sharing power during and after priority-setting and lessons on how to implement them effectively that can be used by global health researchers in the current funding environment.


Alloantibodies can discriminate class I major histocompatibility complex molecules associated with various endogenous peptides.
Molecules encoded by a single major histocompatibility complex class I gene can associate with any one of a large number of peptide ligands. T-cell receptors have the capacity to discriminate among these peptide-class I complexes and in many cases bind only a single peptide-class I complex with sufficient affinity to trigger effector function. In contrast, it is generally assumed that class I-specific alloantibodies are indifferent to peptide heterogeneity, being directed toward allele-specific determinants on the molecule. In this report, three monoclonal antibodies were used to precipitate Kb molecules from cell lysates. Surprisingly, in each case a different set of peptides was found to be associated with Kb as detected by peptide-dependent Kb-specific alloreactive cytolytic T lymphocytes or by biochemical resolution. These results demonstrate that the affinity of binding by alloantibodies can be affected by the endogenous peptide ligand.


Why does the bioluminescent fungus Armillaria mellea have luminous mycelium but nonluminous fruiting body?
By determining the components involved in the bioluminescence process in luminous and nonluminous organs of the honey fungus Armillaria mellea, we have established causes of partial luminescence of this fungus. The complete set of enzymes and substrates required for bioluminescence is formed only in the mycelium and only under the conditions of free oxygen access. Since the synthesis of luciferin precursor (hispidin) and 3-hydroxyhispidin hydroxylase in the fruiting bodies is blocked, the formation of luciferin-the key component of fungal bioluminescent system-was not observed. That is why the fruiting body of Armillaria mellea is nonluminous despite the presence of luciferase, the enzyme that catalyzes the oxidation of luciferin with a photon emission.


Successful oral delivery of poorly water-soluble drugs both depends on the intraluminal behavior of drugs and of appropriate advanced drug delivery systems.
Poorly water-soluble drugs continue to be a problematic, yet important class of pharmaceutical compounds for treatment of a wide range of diseases. Their prevalence in discovery is still high, and their development is usually limited by our lack of a complete understanding of how the complex chemical, physiological and biochemical processes that occur between administration and absorption individually and together impact on bioavailability. This review defines the challenge presented by these drugs, outlines contemporary strategies to solve this challenge, and consequent in silico and in vitro evaluation of the delivery technologies for poorly water-soluble drugs. The next steps and unmet needs are proposed to present a roadmap for future studies for the field to consider enabling progress in delivery of poorly water-soluble compounds.


A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation.
Electron microscopy of ECADCOMP, a recombinant E-cadherin ectodomain pentamerized by the assembly domain of cartilage oligomeric matrix protein, has been used to analyze the role of cis-dimerization and trans-interaction in the homophilic association of this cell adhesion molecule. The Ca2+ dependency of both interactions was investigated. Low Ca2+ concentrations (50 microM) stabilized the rod-like structure of E-cadherin. At medium Ca2+ concentration (500 microM), two adjacent ectodomains in a pentamer formed cis-dimers. At high Ca2+ concentration (>1 mM), two cis-dimers from different pentamers formed a trans-interaction. The X-ray structure of an N-terminal domain pair of E-cadherin revealed two molecules per asymmetric unit in an intertwisted X-shaped arrangement with closest contacts in the Ca2+-binding region between domains 1 and 2. Contrary to previous data, Trp2 was docked in the hydrophobic cavity of its own molecule, and was therefore not involved in cis-dimerization of two molecules. This was supported further by W2A and A80I (a residue involved in the hydrophobic cavity surrounding Trp2) mutations in ECADCOMP which both led to abrogation of the trans- but not the cis-interaction. Structural and biochemical data suggest a link between Ca2+ binding in the millimolar range and Trp2 docking, both events being essential for the trans-association.


Nitric oxide pathways in Alzheimer's disease and other neurodegenerative dementias.
Nitric oxide (NO) is an enzymatic product of nitric oxide synthase (NOS). NO has significant physiological functions and an increasing body of evidence suggests that NO pathways are implicated in a number of neurological disorders, including Alzheimer's disease (AD) and other neurodegenerative dementias. NO is continuously released by endothelial cells in the vascular system, whereas advanced age in the presence of vascular risk factor causes a decrease in cerebral blood flow, involving microvasculopathy with impaired NO release, which in turn results in regional metabolic dysfunction. This finding suggests that vascular pathology plays a crucial role in the pathogenesis of so-called neurodegenerative dementias. Inflammatory responses are commonly found in the brain under a variety of neurodegenerative dementias, including AD and dementia with Lewy bodies, in which up-regulation of NOS expression, suggesting overproduction of NO, is found in neurons and glia. NO is thought to be involved in such neuroinflammation due to its free radical properties, which compromise cellular integrity and viability via mitochondrial damage. Further studies to elucidate NO pathways in neurodegenerative dementias could lead to a better understanding of their pathogenesis and improved therapeutic strategies, and therefore are certainly warranted.


Impact of variables of the P-selectin - P-selectin glycoprotein ligand-1 axis on leukocyte-platelet interactions in cardiovascular disease.
The formation of leukocyte-platelet aggregates (LPA), through the P-selectin - P-selectin glycoprotein ligand (PSGL)-1 axis, plays a pivotal role in atherothrombosis. In order to investigate the influence of platelet (pP-selectin) and soluble P-selectin (sP-selectin), and of variations in the genes encoding for P-selectin (SELP) and PSGL-1 (SELPLG) on LPA formation, we assessed monocyte (MPA)- and neutrophil-platelet aggregates (NPA) as well as pP-selectin by flow cytometry in 263 patients undergoing angioplasty and stenting. sP-selectin was determined by ELISA, the SELP Pro715 allele and the SELPLG Ile62 allele were determined by allele specific PCR. The Pro715 allele was significantly associated with lower levels of in vivo pP-selectin and sP-selectin, while agonists´ inducible pP-selectin was not influenced by the Pro715 allele. PP-selectin was significantly associated with MPA and NPA formation. The in vivo formation of MPA and NPA depended to 19 % and 7.4 %, respectively, on in vivo pP-selectin, irrespective of the Pro715 allele and the Ile62 allele carrier status. TRAP-6 inducible MPA and NPA depended to 34 % and 27 %, respectively, on TRAP-6 inducible pP-selectin, but were independent of the Pro715 allele carrier status. Carriers of the Ile62 allele showed a stronger correlation between TRAP-6 inducible pP-selectin and TRAP-6 inducible MPA/NPA than non-carriers. Furthermore, TRAP-6 inducible NPA were higher in Ile62 allele carriers, which suggests higher thrombin sensitivity. In conclusion, our findings point to the significant role of pP-selectin for MPA and NPA formation, while other variables like sP-selectin, the SELP Pro715 allele and the SELPLG Ile62 allele have less influence.


A comprehensive review of an unmet public health issue: resistant hypertension.
Resistant hypertension is an intractable problem to patients and physicians. In recent decades, a substantial amount of basic and epidemiological studies provide us a vast number of valuable evidence and information about this once elusive disease. Better understanding about this entity could help physicians improve diagnostic and therapeutic accuracy. In present review, therefore, we first will detail the definition and diagnosis of resistant hypertension between cardiology societies, and followed by the information of prevalence of resistant hypertension around the world, and then briefly discuss currently used different nomenclature of resistant hypertension, and finally present diagnostic and therapeutic strategies of resistant hypertension.


A metabolic prototype for eliminating tryptophan from the genetic code.
We set out to reduce the chemical constitution of a living organism to 19 amino acids. A strain was constructed for reassigning the tryptophan codon UGG to histidine and eliminating tryptophan from Escherichia coli. Histidine codons in the gene for an essential enzyme were replaced with tryptophan codons and the restoration of catalytic activity by missense suppressor His-tRNA bearing a CCA anticodon was selected. We used automated cultivation to assess the stability of this genetic construct during evolution. Histidine to tryptophan mutation at codon 30 in the transketolase gene from yeast and its cognate suppressor tRNA were stably propagated in a tktAB deletant of E. coli over 2500 generations. The ratio of histidine misincorporation at tryptophan sites in the proteome increased from 0.0007 to 0.03 over 300 days of continuous culture. This result demonstrated that the genetic code can be forced to evolve by permanent metabolic selection.


Testing the Model of Stigma Communication with a Factorial Experiment in an Interpersonal Context.
Stigmas may regulate intergroup relationships; they may also influence interpersonal actions. This study extends the previous test of the model of stigma communication (Smith, 2012) with a factorial experiment in which the outcomes refer to a hypothetical acquaintance. New affective reactions, sympathy and frustration, and a new personality trait, disgust sensitivity, were explored. In addition, perceived severity and susceptibility of the infection were included as alternative mechanisms explaining the effects. The results (n = 318) showed that message content, message reactions (emotional and cognitive), and disgust sensitivity predicted intentions to regulate the infected acquaintance's interactions and lifestyle (R2 = .79) and participants' likelihood of telling others about the acquaintance's infection (R2 = .35). The findings generally provided support for MSC and directions for improvement.


Latency characteristics in specific pathogen-free chickens 21 and 35 days after intra-tracheal inoculation with vaccine or field strains of infectious laryngotracheitis virus.
Latency is an important feature of infectious laryngotracheitis virus (ILTV) yet is poorly understood. This study aimed to compare latency characteristics of vaccine (SA2) and field (CL9) strains of ILTV, establish an in vitro reactivation system and examine ILTV infection in peripheral blood mononuclear cells (PBMC) in specific pathogen-free chickens. Birds were inoculated with SA2 or CL9 ILTV and then bled and culled at 21 or 35 days post-inoculation (dpi). Swabs (conjunctiva, palatine cleft, trachea) and trigeminal ganglia (TG) were examined for ILTV DNA using PCR. Half of the TG, trachea and PBMC were co-cultivated with cell monolayers to assess in vitro reactivation of ILTV infection. ILTV DNA was detected in the trachea of approximately 50% of ILTV-inoculated birds at both timepoints. At 21 dpi, ILTV was detected in the TG only in 29% and 17% of CL9- and SA2-infected birds, respectively. At 35 dpi, ILTV was detected in the TG only in 30% and 10% of CL9- and SA2-infected birds, respectively. Tracheal organ co-cultures from 30% and 70% of CL9- and SA2-infected birds, respectively, were negative for ILTV DNA at cull but yielded quantifiable DNA within 6 days post-explant (dpe). TG co-cultivation from 30% and 40% of CL9-and SA2-infected birds, respectively, had detectable ILTV DNA within 6 dpe. Latency characteristics did not substantially vary based on the strain of virus inoculated or between sampling timepoints. These results advance our understanding of ILTV latency and reactivation. RESEARCH HIGHLIGHTS Following inoculation, latent ILTV infection was detected in a large proportion of chickens, irrespective of whether a field or vaccine strain was inoculated. In vitro reactivation of latent ILTV was readily detected in tracheal and trigeminal ganglia co-cultures using PCR. ILTV latency observed in SPF chickens at 21 days post-infection was not substantially different to 35 days post-infection.


Finite-Sample Analysis of Deep CCA-Based Unsupervised Post-Nonlinear Multimodal Learning.
Canonical correlation analysis (CCA) has been essential in unsupervised multimodal/multiview latent representation learning and data fusion. Classic CCA extracts shared information from multiple modalities of data using linear transformations. In recent years, deep neural networks-based nonlinear feature extractors were combined with CCA to come up with new variants, namely the ``DeepCCA'' line of work. These approaches were shown to have enhanced performance in many applications. However, theoretical supports of DeepCCA are often lacking. To address this challenge, the recent work of Lyu and Fu (2020) showed that, under a reasonable postnonlinear generative model, a carefully designed DeepCCA criterion provably removes unknown distortions in data generation and identifies the shared information across modalities. Nonetheless, a critical assumption used by Lyu and Fu (2020) for identifiability analysis was that unlimited data is available, which is unrealistic. This brief paper puts forth a finite-sample analysis of the DeepCCA method by Lyu and Fu (2020). The main result is that the finite-sample version of the method can still estimate the shared information with a guaranteed accuracy when the number of samples is sufficiently large. Our analytical approach is a nontrivial integration of statistical learning, numerical differentiation, and robust system identification, which may be of interest beyond the scope of DeepCCA and benefit other unsupervised learning paradigms.


Automatic lumbar vertebrae detection based on feature fusion deep learning for partial occluded C-arm X-ray images.
Automatic and accurate lumbar vertebrae detection is an essential step of image-guided minimally invasive spine surgery (IG-MISS). However, traditional methods still require human intervention due to the similarity of vertebrae, abnormal pathological conditions and uncertain imaging angle. In this paper, we present a novel convolutional neural network (CNN) model to automatically detect lumbar vertebrae for C-arm X-ray images. Training data is augmented by DRR and automatic segmentation of ROI is able to reduce the computational complexity. Furthermore, a feature fusion deep learning (FFDL) model is introduced to combine two types of features of lumbar vertebrae X-ray images, which uses sobel kernel and Gabor kernel to obtain the contour and texture of lumbar vertebrae, respectively. Comprehensive qualitative and quantitative experiments demonstrate that our proposed model performs more accurate in abnormal cases with pathologies and surgical implants in multi-angle views.


Honokiol Inhibits Atrial Metabolic Remodeling in Atrial Fibrillation Through Sirt3 Pathway.
Background and Purpose: Atrial metabolic remodeling plays a critical role in the pathogenesis of atrial fibrillation (AF). Sirtuin3 (Sirt3) plays an important role in energy homeostasis. However, the effect of Sirt3 agonist Honokiol (HL) on AF is unclear. Therefore, the aim of this study is to determine the effect of HL on atrial metabolic remodeling in AF and to explore possible mechanisms. Experimental Approach: irt3 and glycogen deposition in left atria of AF patients were examined. Twenty-one rabbits were divided into sham, P (pacing for 3 weeks), P + H treatment (honokiol injected with pacing for 3 weeks). The HL-1 cells were subjected to rapid pacing at 5 Hz for 24 h, in the presence or absence of HL and overexpression or siRNA of Sirt3 by transfection. Metabolic factors, circulating metabolites, atrial electrophysiology, ATP level, and glycogens deposition were detected. Acetylated protein and activity of its enzymes were detected. Key Results: Sirt3 was significantly down-regulated in AF patients and rabbit/HL-1cell model, resulting in the abnormal expression of its downstream metabolic key factors, which were significantly restored by HL. Meanwhile, AF induced an increase of the acetylation level in long-chain acyl-CoA dehydrogenase (LCAD), AceCS2 and GDH, following decreasing of activity of it enzymes, resulting in abnormal alterations of metabolites and reducing of ATP, which was inhibited by HL. The Sirt3 could regulate acetylated modification of key metabolic enzymes, and the increase of Sirt3 rescued AF induced atrial metabolic remodeling. Conclusion and Implications: HL inhibited atrial metabolic remodeling in AF via the Sirt3 pathway. The present study may provide a novel therapeutical strategy for AF.


A prospective study of drugs and pregnancy. II. Anti-emetic drugs.
In a prospective study of anti-emetic drug use during 6 376 pregnancies, the previously demonstrated negative correlation between the use of such drugs and miscarriage was confirmed. It is probably completely due to less frequent and possibly less severe morning sickness complaints in pregnancies ending with a miscarriage. A slight positive correlation is found between the use of anti-emetics and infant malformation. A detailed analysis showed that this was mainly due to a high incidence of drug use (mainly promethazine) among women giving birth to infants with congenital dislocation of the hip. The probable indirect relationship is discussed.


Severe transmural myocardial ischemia after dipyridamole administration implicating coronary steal.
Myocardial perfusion imaging with coronary vasodilators is routinely used for patients with suspected coronary disease who are unable to exercise. Since these agents work by increasing blood flow without significantly changing myocardial oxygen demand, they generally do not produce ischemia. A minority of patients show evidence of ischemia which some investigators suggest is due to a coronary steal phenomenon, but this has been challenged by several investigators. We present the case of a patient who developed severe transmural myocardial ischemia manifested by ST-segment elevation and severe perfusion defects which occurred after dipyridamole administration and which were reversed with aminophylline and nitroglycerin. This case supports the notion that coronary vasodilation with dipyridamole can induce a coronary steal.


Smoking and lung cancer: current trends in Austria.
Despite a recent decline in smoking behavior in many European countries, lung cancer rates remain high, especially in Central and Eastern Europe. This paper aims to describe trends in smoking behavior and lung cancer incidence and mortality, including histopathological classification of lung cancer, in a Central European country: Austria. Using data from the Austrian Central Cancer Registry, we calculated age-standardized incidence, histopathology-specific incidence, and age-standardized and birth cohort-specific mortality rates for all lung cancer cases in Austria. Using national survey data, we estimated prevalence of smoking in the Austrian population. Our analysis covers the time period from 1970 to 2009. In 2009, lung cancer incidence rates were 41.3/100,000 and 18.5/100,000 and mortality rates were 36.3/100,000 and 14.5/100,000, for males and females, respectively. Male lung cancer rates declined but increased steadily in females over the past three decades. In 2009, the most common histological type is adenocarcinoma, which reflects a shift from predominantly squamous cell carcinoma and large cell carcinoma in the mid 1980s. In 2009, 27 % of men and 19 % of women were smokers, which represent a rise of smoking rates in women, especially in younger women, and a decline in the men. While in Austrian men the lung cancer rates, in accordance with their decreasing prevalence of smoking, declined over the past 30 years, the increasing smoking prevalence and lung cancer rates in women remain a public health concern. Antismoking laws and public health initiatives to curtail smoking habits are needed in Austria, especially targeting younger women.


Ruthenium-Catalyzed Chemo- and Enantioselective Hydrogenation of Isoquinoline Carbocycles.
A chemoselective hydrogenation of isoquinoline carbocycles was achieved by using the catalyst prepared from Ru(methallyl)2(cod) and trans-chelate chiral ligand PhTRAP. The unique chemoselectivity achieved in this hydrogenation could be ascribed to the trans-chelation of the chiral ligand. The procedure for preparing the catalyst strongly affects the reproducibility of the carbocycle hydrogenation. Various 5-, 6-, 7-, and 8-substituted isoquinolines were selectively hydrogenated at their carbocycles to afford 5,6,7,8-tetrahydroisoquinolines as major products in high yields with moderate or good enantioselectivities. Some mechanistic studies suggested that the stereogenic center was created during the initial addition of H2 to the aromatic ring in the hydrogenation of 5-substituted isoquinolines. In other words, the stereochemical control was accompanied by the dearomatization.


Digitalis: dead or alive?
Over 200 years age, William Withering described the advantages which might be gained by the considered use of extracts of the foxglove, digitalis purpurea, in patients with congestive heart failure, particularly if the rhythm was irregular. In the subsequent years many patients undoubtedly benefited from the use of this drug. The introduction of diuretics in the present century provided an alternative, more effective and safer treatment for heart failure. More recently, angiotensin-converting enzyme inhibitors have become available. The use of digoxin in the treatment of heart failure is now indicated almost solely for the control of a fast heart rate in patients with atrial fibrillation.


Beam quality measure for vector beams.
Vector beams have found a myriad of applications, from laser materials processing to microscopy, and are now easily produced in the laboratory. They are usually differentiated from scalar beams by qualitative measures, for example, visual inspection of beam profiles after a rotating polarizer. Here we introduce a quantitative beam quality measure for vector beams and demonstrate it on cylindrical vector vortex beams. We show how a single measure can be defined for the vector quality, from 0 (purely scalar) to 1 (purely vector). Our measure is derived from a quantum toolkit, which we show applies to classical vector beams.


Long-term psychiatric and medical consequences of anabolic-androgenic steroid abuse: a looming public health concern?
The problem of anabolic-androgenic steroid (AAS) abuse has recently generated widespread public and media attention. Most AAS abusers, however, are not elite athletes like those portrayed in the media, and many are not competitive athletes at all. This larger but less visible population of ordinary AAS users began to emerge in about 1980. The senior members of this population are now entering middle age; they represent the leading wave of a new type of aging former substance abusers, with specific medical and psychiatric risks. We reviewed the evolving literature on long-term psychiatric and medical consequences of AAS abuse. Long-term use of supraphysiologic doses of AAS may cause irreversible cardiovascular toxicity, especially atherosclerotic effects and cardiomyopathy. In other organ systems, evidence of persistent toxicity is more modest, and interestingly, there is little evidence for an increased risk of prostate cancer. High concentrations of AAS, comparable to those likely sustained by many AAS abusers, produce apoptotic effects on various cell types, including neuronal cells--raising the specter of possibly irreversible neuropsychiatric toxicity. Finally, AAS abuse appears to be associated with a range of potentially prolonged psychiatric effects, including dependence syndromes, mood syndromes, and progression to other forms of substance abuse. However, the prevalence and severity of these various effects remains poorly understood. As the first large wave of former AAS users now moves into middle age, it will be important to obtain more systematic data on the long-term psychiatric and medical consequences of this form of substance abuse.


Clinical findings on human blood with the KONE ISE for Mg2+.
Ionized magnesium was measured using a clinical analyzer MICROLYTE 6 (KONE, Finland). Total magnesium was measured colorimetrically. The influence of anion-ligands on Mg-ISE responses was investigated. Ionized magnesium (iMg) concentration changes with pH were made to observe the accuracy of results. The dependence of iMg and iCa on heparin (used as anticoagulant in plasma samples) was made. Less than 40 units per 1 ml of blood decreased the concentration of iMg and iCa less than 1.5%. The range of iMg and total Mg in serum and plasma of healthy and ill adults (short bowel syndrome, myocardial infarct) was investigated and compared to each other. In both illnesses, the concentration of ionized and/or total magnesium is significantly different from the range for healthy people. The range of iMg and total Mg as well as the percentage of iMg against total Mg seem to be specific for given illness. The range of iMg and total Mg in blood serum of healthy children was also investigated.


Comparative survival analysis of p53 gene mutations and protein accumulation in colorectal cancer.
Immunohistochemical reactivity for p53 protein is common in various human malignancies. Increased intracellular concentration of p53, which is frequently, but not systematically, related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 alterations, we screened a series of 72 colorectal carcinomas for overexpression and mutation of the p53 gene. Mutations in exons 5-9 of the p53 gene were assayed by single-strand conformation polymorphism and direct DNA sequencing, whereas p53 protein accumulation was detected in 10-microm frozen tissue by immunostaining using 2 different monoclonal antibodies (PAb 1801 and DO7). Thirty-six tumors (50%) showed p53 overexpression. Nineteen of the 36 tumors which contained high levels of p53 protein were found to have missense point mutations. Using a multivariate survival analysis, stage, differentiation, p53 immunoreactivity and p53 mutation emerged as risk factors, but only the stage was significant. In univariate analysis, stage, differentiation and p53 immunoreactivity were significant prognostic indicators, while p53 mutation was at the borderline of significance.


Preliminary Prognostication for Good Neurological Outcomes in the Early Stage of Post-Cardiac Arrest Care.
We investigated prognostic strategies for predicting good outcomes in the early stage of post-cardiac-arrest care using multiple prognostic tests that are available until 24 h after the return of spontaneous circulation (ROSC). A retrospective analysis was conducted on 138 out-of-hospital cardiac-arrest patients who underwent prognostic tests, including the gray-white-matter ratio (GWR-BG), the Glasgow Coma Scale motor (GCS-M) score before sedative administration, and the neuron-specific enolase (NSE) level measured at 24 h after the ROSC. We investigated the prognostic performances of the tests as single predictors and in various combination strategies. Classification and regression-tree analysis were used to provide a reliable model for the risk stratification. Out of all the patients, 55 (44.0%) had good outcomes. The NSE level showed the highest prognostic performance as a single prognostic test and provided improved specificities (>70%) and sensitivities (>98%) when used in combination strategies. Low NSE levels (≤32.1 ng/mL) and high GCS-M (≥4) scores identified good outcomes without misclassification. The overall accuracy for good outcomes was 81.8%. In comatose patients with low NSE levels or high GCS-M scores, the premature withdrawal of life-sustaining therapy should be avoided, thereby complying with the formal prognostication-strategy algorithm after at least 72 h from the ROSC.


Ultrafast dynamic control of spin and charge density oscillations in a GaAs quantum well.
We use subpicosecond laser pulses to generate and monitor in real time collective oscillations of electrons in a modulation-doped GaAs quantum well. The observed frequencies match those of intersubband spin- and charge-density excitations. Light couples to coherent density fluctuations through resonant stimulated Raman scattering. Because the spin- and charge-related modes obey different selection rules and resonant behavior, the amplitudes of the corresponding oscillations can be independently controlled by using shaped pulses of the proper polarization.


The Effect of High-concentration Insulin Glarigine on the Quality of Life of Patients with Type 2 Diabetes Mellitus: A Pre-post Study (HIGH-QOL STUDY).
Objective We compared the pain accompanying the injection of high-concentration (300 units/mL) insulin glargine (U300G) with that accompanying the injection of conventional (100 units/mL) insulin glargine (U100G). Methods U100G was switched to U300G at basically the same dosage. Visual analog scales were used to assess the quality of life (QOL). The primary outcome was the change in the pain accompanying injections in those using ≥30 units of U100G compared with those using <30 units at baseline. Standardized mean differences (Cohen's d) were used to measure the effect size. Patients Adult patients with type 2 diabetes mellitus using U100G. Results One hundred and eight patients were recruited. The numbers of patients who used U100G at ≥30 units, 20 to <30 units, 10 to <20 units, and <10 units were 13, 14, 34, and 47, respectively. The improvement in the pain score was not significant for ≥30 units compared with <30 units (-50.3±24.0 vs. -40.4±28.5, p=0.25, d=0.38), but a significant difference was observed for ≥20 units compared with <20 units (-50.8±22.7 vs. -38.4±29.1, p=0.03, d=0.48), as well as for ≥10 units compared with <10 units (-48.1±25.0 vs. -33.0±29.7, p<0.01, d=0.56). When all patients were analyzed together, significant improvements in the pain score (-41.5±28.0, p<0.01), ease of use score (-37.5±32.2, p<0.01), force needed to inject score (-46.5±28.6, p<0.01), and preference for U300G compared with U100G score (-45.8±33.1, p<0.01) were observed. Conclusion There is possibility that switching from U100G to U300G might be associated with better QOL for patients who require insulin glargine injections. To prove this hypothesis, a randomized controlled trial (preferably double-blinded) will be required in the future.


An economic evaluation and assessment of environmental impact of the municipal solid waste management system for Taichung City in Taiwan.
Municipal solid waste management (MSWM) is an important environmental challenge and subject in urban planning. For sustainable MSWM strategies, the critical management factors to be considered include not only economic efficiency of MSW treatment but also life-cycle assessment of the environmental impact. This paper employed linear programming technique to establish optimal MSWM strategies considering economic efficiency and the air pollutant emissions during the life cycle of a MSWM system, and investigated the correlations between the economical optimization and pollutant emissions. A case study based on real-world MSW operating parameters in Taichung City is also presented. The results showed that the costs, benefits, streams of MSW, and throughputs of incinerators and landfills will be affected if pollution emission reductions are implemented in the MSWM strategies. In addition, the quantity of particulate matter is the best pollutant indicator for the MSWM system performance of emission reduction. In particular this model will assist the decision maker in drawing up a friendly MSWM strategy for Taichung City in Taiwan. Recently, life-cycle assessments of municipal solid waste management (MSWM) strategies have been given more considerations. However, what seems to be lacking is the consideration of economic factors and environmental impacts simultaneously. This work analyzed real-world data to establish optimal MSWM strategies considering economic efficiency and the air pollutant emissions during the life cycle of the MSWM system. The results indicated that the consideration of environmental impacts will affect the costs, benefits, streams of MSW, and throughputs of incinerators and landfills. This work is relevant to public discussion and may establish useful guidelines for the MSWM policies.


The use of chemical derivatization to enhance liquid chromatography/tandem mass spectrometric determination of 1-hydroxypyrene, a biomarker for polycyclic aromatic hydrocarbons in human urine.
This article presents an analytical approach that used chemical derivatization to enhance mass spectrometric (MS) response in electrospray ionization (ESI) mode of 1-hydroxypyrene (1-OHP), a commonly used biomarker to monitor human exposure to polycyclic aromatic hydrocarbons (PAHs). The enhancement successfully enabled the desired detection of 50 pg/mL in human urine. The introduction of an MS-friendly dansyl group to 1-OHP enhanced both ionization efficiency in the ESI source and collision-activated dissociation (CAD) in the collision cell. The response increase was estimated to be at least 200-fold, and enabled the reduction of sample size to only 100 microL. The selective MS detection also facilitated a fast (run time 3 min) liquid chromatography (LC) method which successfully resolved the analyte and interferences. The sample processing procedure included enzymatic hydrolysis of glucuronide and sulfate conjugates, liquid-liquid extraction, derivatization with dansyl chloride and a final liquid-liquid extraction to generate clean extracts for LC/MS/MS analysis. This approach has been validated as sensitive, linear (50-1000 pg/mL), accurate and precise for the quantitation of 1-OHP in human urine. This is the first report of using chemical derivatization to enhance MS/MS detection with fast chromatography in the determination of 1-OHP in human urine.


Coronary thrombolysis with intravenously administered human tissue-type plasminogen activator produced by recombinant DNA technology.
Coronary thrombolysis was induced by intravenous infusion of human tissue-type plasminogen activator (recombinant human t-PA or rt-PA) obtained by expression of the cloned gene in a mammalian cell system. Thrombolysis was detected by the appearance of reperfusion arrhythmia and confirmed by repeat angiography in anesthetized dogs with 1-hr-old thrombi of the left anterior descending coronary artery that were induced with a copper coil. Infusion of 1000 IU (10 micrograms)/kg/min intravenous rt-PA (n = 9) elicited reperfusion within 13.7 +/- 1.9 min (mean +/- SE) without producing systemic fibrinolysis or distal coronary embolization. Infusion of urokinase at the same rate elicited thrombolysis in seven of 10 dogs within an average of 19.3 +/- 2.2 min. However, distal coronary embolization occurred in two dogs and systemic fibrinolysis was observed in all. In three dogs treated with urokinase thrombolysis was obtained only with subsequent intracoronary infusion. Restoration of myocardial perfusion and metabolism assessed with positron-emission tomography was consistently noted in dogs treated with rt-PA. Thus, rt-PA, a clot-selective thrombolytic agent that does not activate the fibrinolytic system systemically and that is potentially available in large quantities, in view of its synthesis by recombinant DNA technology, offers a promising practical approach for coronary thrombolysis in patients with acute myocardial infarction.


Sleep and Sport Performance.
Elite athletes and coaches believe sleep is the most important recovery strategy and widely consider it critical to optimal performance. Despite this perceived importance, there are numerous circumstances that can reduce sleep quantity and quality in athletic populations. Because of the effects of sleep loss on various physical, neurophysiological, and cognitive parameters, such perturbations can have consequences for performance and recovery outcomes. Although peer-reviewed literature examining the interaction between sleep, performance, and recovery in athletes is increasing, understanding of these issues remains equivocal. Perhaps most pertinently, the effect of sleep on sport performance does not align with a one-size-fits-all approach and rather depends on numerous factors such as type of sport, scheduling, time of the season, and the intraindividual requirements for sleep. The relationship between brain plasticity and memory, which in turn can influence learning processes and long-term memory consolidation, suggests that sleep may play an important role in learning new skills and tactics for both elite and developing athletes. The aim of this special issue review was to analyze the evidence of sleep loss on sport performance and recovery, with a specific focus on elite athletes. An assessment of these sleep-compromising situations that elite athletes may face during a typical season and practical considerations for alleviating these issues is also provided to further the understanding for medical professionals, scientists, and applied sporting practitioners alike.


High capacity Na-storage and superior cyclability of nanocomposite Sb/C anode for Na-ion batteries.
A Sb/C nanocomposite was synthesized and found to deliver a reversible 3 Na storage capacity of 610 mA h g(-1), a strong rate capability at a very high current of 2000 mA g(-1) and a long-term cycling stability with 94% capacity retention over 100 cycles, offering practical feasibility as a high capacity and cycling-stable anode for room temperature Na-ion batteries.


[Hyperlipoproteinemia in patients with arteriosclerotic occlusive diseases of the lower extremities].
After exclusion of a manifest diabetes mellitus occurrence and distribution of hyperlipoproteinaemias in 250 patients with atherosclerotic obstructive diseases of the lower extremities were examined. 54,8% of the patients showed increased serum lipid levels, in which cases most frequently hypercholesterolaemias (type IIa and IIb) could be proved. Patients with obstructions of the pelvic arteries had significantly more frequent hyperlipoproteinaemias than patients with more distal obstructions.


cxcl12a plays an essential role in pharyngeal cartilage development.
Background: Neural crest cells constitute a distinct set of multipotent cells that undergo migration along predefined pathways, culmination in the differentiation into a plethora of cell types, including components of the pharyngeal cartilage. The neurocranium is composite structure derived from both cranial neural crest and mesoderm cells, whereas the pharyngeal skeletal elements-including the mandibular and branchial arches-are exclusively formed by craniofacial neural crest cells. Previous studies have elucidated the critical involvement of the chemokine signaling axis Cxcl12b/Cxcr4a in craniofacial development in zebrafish (Danio rerio). Nonetheless, the function contribution of Cxcl12a and Cxcr4b-the homologous counterparts of Cxcl12b and Cxcr4a-remain largely unexplored. Methods: In the present study, mutant lines for cxcl12a and cxcr4b were generated employing CRISPR/Cas9 system. Temporal and spatial expression patterns of specific genes were assessed using in situ hybridization and dual-color fluorescence in situ hybridization techniques. High-resolution confocal microscopy was utilized for in vivo imaging to detect the pharyngeal arch or pouch patterning. Additionally, cartilage formation within the craniofacial region was analyzed via Alcian blue staining, and the proliferation and apoptosis rates of craniofacial neural crest cells were quantified through BrdU incorporation and TUNEL staining. Results: Our data reveals that the deletion of the chemokine gene cxcl12a results in a marked diminution of pharyngeal cartilage elements, attributable to compromised proliferation of post-migratory craniofacial neural crest cells. Subsequent experiments confirmed that Cxcl12a and Cxcl12b exhibit a synergistic influence on pharyngeal arch and pouch formation. Conclusion: Collectively, the present investigation furnishes compelling empirical evidence supporting the indispensable role of Cxcl2a in craniofacial cartilage morphogenesis, albeit cxcr4b mutants exert a minimal impact on this biological process. We delineate that Cxcl12a is essential for chondrogenesis in zebrafish, primarily by promoting the proliferation of craniofacial neural crest cells. Furthermore, we proposed a conceptual framework wherein Cxcl12a and Cxcl12b function synergistically in orchestrating both the pharyngeal arch and pouch morphogenesis.