Cardiovascular and neurohormonal changes following central sympathetic blockade with clonidine in human unilateral renal artery stenosis.
The role of central pressor mechanisms in the maintenance of blood pressure in six hypertensive patients with angiographically proven unilateral renal artery stenosis was investigated by studying the haemodynamic and hormonal responses before and after central sympathetic blockade with clonidine. To assess the dependency of blood pressure on the direct effects of angiotensin II, the same patients were studied on a separate occasion after administration of the angiotensin converting enzyme (ACE) inhibitor, captopril. There was a substantial fall in blood pressure after administration of clonidine with a smaller fall after captopril. Clonidine-induced hypotension was accompanied by a fall in cardiac output, through a reduction in the stroke volume and heart rate. Forearm vascular resistance was unchanged. There was a selective decrease in digital skin vascular resistance and plasma noradrenaline, indicating reduced sympathetic activity. Plasma renin activity and aldosterone levels did not fall. After administration of captopril, there was a fall in cardiac output due to a fall in the stroke volume but not in the heart rate. Forearm vascular resistance, digital skin vascular resistance and plasma noradrenaline were unchanged. Plasma renin activity rose and plasma aldosterone fell. We conclude that in our hypertensive patients with renal artery stenosis, clonidine lowered blood pressure by a reduction in central sympathetic activity independently of renin suppression. In these patients captopril had minimal hypotensive effects, indicating a smaller role for the direct vascular effects of angiotensin II.


Exploring the nature of the liquid-liquid transition in silicon: a non-activated transformation.
In contrast to other glass formers, silicon exhibits a thermodynamic discontinuity between its liquid and amorphous solid states. Some researchers have conjectured that a first-order phase transition occurs between two forms of liquid silicon: the high-density liquid (HDL) and the low-density liquid (LDL). Despite the fact that several computer simulations have supported a liquid-liquid phase transition (LLPT) in silicon, recent work based on surface free energy calculations contradicts its existence and the authors of this work have argued that the proposed LLPT has been mistakenly interpreted [J. Chem. Phys., 2013, 138, 214504]. A similar controversy has also arisen in the case of water because of discrepancies in the calculation of its free energy surface [Nature, 2014, 510, 385; J. Chem. Phys., 2013, 138, 214504]. Current evidence supporting or not supporting the LLPT is mostly derived from the thermodynamic stability of the LDL phase. Provided that the HDL-LDL transition is a first-order transition, the formation of LDL silicon should be an activated process. Following this idea, the nature of the LLPT should be clarified by tracing the kinetic path toward LDL silicon. In this work, we focus on the transformation process from HDL to LDL phases and use the mean first passage time (MFPT) method to examine thermodynamic and dynamic trajectories. The MFPT results show that the presumed HDL-LDL transition is not characterized by a thermodynamic activated process but by a continuous dynamic transformation. LDL silicon is actually a mixture of the high-density liquid and a low-density tetrahedral network. We show that the five-membered Si-Si rings in the LDL network play a critical role in stabilizing the low-density network and suppressing the crystallization.


Establishment of a human corneal epithelial cell line lacking the functional TACSTD2 gene as an in vitro model for gelatinous drop-like dystrophy.
Gelatinous drop-like corneal dystrophy (GDLD) is characterized by subepithelial amyloid deposition that engenders severe vision loss. The exact mechanism of this disease has yet to be elucidated. No fundamental treatment exists. This study was conducted to establish an immortalized corneal epithelial cell line to be used as a GDLD disease model. A corneal tissue specimen was obtained from a GDLD patient during surgery. Corneal epithelial cells were enzymatically separated from the cornea and were dissociated further into single cells. The epithelial cells were immortalized by the lentiviral transduction of the simian virus 40 (SV40) large T antigen and human telomerase reverse transcriptase (hTERT) genes. For the immortalized cells, proliferative kinetics, gene expressions, and functional analyses were performed. The immortalized corneal epithelial cells continued to proliferate despite cumulative population doubling that exceeded 100. The cells showed almost no sign of senescence and displayed strong colony-forming activity. The cells exhibited a low epithelial barrier function as well as decreased expression of tight-junction-related proteins claudin 1 and 7. Using the immortalized corneal epithelial cells derived from a GDLD patient, we tested the possibility of gene therapy. We established an immortalized corneal epithelial cell line from a GDLD patient. The immortalized cells exhibited cellular phenotypes similar to those of in vivo GDLD. The immortalized cells are thought to be useful for the development of new therapies for treating GDLD corneas and for elucidation of the pathophysiology of GDLD.


A novel silanization agent based single used biosensing system: Detection of C-reactive protein as a potential Alzheimer's disease blood biomarker.
This paper illustrates a new and sensitive electrochemical immunosensor for the analysis of C-reactive protein. Indium Tin Oxide (ITO) disposable sheets were modified by using 3-cyanopropyltrimethoxysilane (CPTMS) self-assembled monolayers (SAMs) for the first time for immobilizing the anti-CRP antibody via covalent interactions without the need for any cross-linking agent. Cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS), as well as square wave voltammetry (SWV) methods were applied to characterize immobilization steps of anti-CRP and to determine the CRP concentration. The optimization of the fabricated parameters and the analytical performance of the biosensor were widely evaluated. Charge transfer resistance changes were highly linear and sensitive with CRP concentration of 3.25-208 fg mL-1 range and associated with a limit of detection of 0.455 fg mL-1. This impedimetric biosensing system have excellent repeatability, reproducibility and reusability. Moreover, the binding characterization of CRP to anti-CRP was monitored by a single frequency impedance technique. The amount of CRP in human serum samples were analyzed by fabricated biosensor to determine the feasibility of the biosensing system in medical purposes. We suggest that CPTMS, a new silanization agent, is ideal in biosensor applications.


Sudden death and the competitive athlete: perspectives on preparticipation screening studies.
Sudden death in healthy athletes is uncommon but, when it occurs, the primary mechanism is cardiovascular. The major cause of sudden death in the young athlete is hypertrophic cardiomyopathy or related conditions characterized by left ventricular hypertrophy, aortic rupture due to cystic medial necrosis and congenital coronary artery abnormalities. In the middle-aged or older athlete, coronary artery disease is the most significant cause of sudden death. Noninvasive screening procedures are currently available that can detect most subjects at risk of sudden death. However, although some potentially lethal diseases can be excluded by a relatively simple screening program, other diseases require expensive procedures, such as echocardiography and exercise electrocardiographic stress testing. This means that the sensitivity of detecting diseases leading to sudden death increases in proportion to the financial resources that can be applied to the screening program. Thus, when a screening program designed to identify all cardiac diseases that have the potential to cause sudden death is planned by a community, school or nonprofessional athletic team, the costs will almost undoubtedly be considered prohibitive. The practicality of applying a community- or school-initiated screening program can be questioned because of the very low incidence of sudden unexpected death in young healthy individuals. It is therefore likely that comprehensive screening programs will be confined to individuals or organizations with adequate financial resources. Less expensive, limited screening can be undertaken by individuals or groups to identify some subjects at risk of sudden death during athletic competition.


Cloning and characterization of ribosomal RNA gene of Physarum polycephalum.
As a first step in studies on the structure and expression of rRNA gene of Physarum polycephalum, the cloning of the gene in Escherichia coli with plasmid vector DNAs was performed and 8 different kinds of clones containing 26S, 19S, and 5.85 rRNA genes were obtained. Using these cloned fragments, the location of these rRNA genes was determined by the Southern hybridization and S1 mapping method. Cloning of rDNA fragments made it possible to analyze the fine structure of the rDNA.


Whole-transcriptome analyses identify key differentially expressed mRNAs, lncRNAs, and miRNAs associated with male sterility in watermelon.
Male sterility is a valuable trait for watermelon breeding, as watermelon hybrids exhibit obvious heterosis. However, the underlying regulatory mechanism is still largely unknown, especially regarding the related non-coding genes. In the present study, approximately 1035 differentially expressed genes (DEGs), as well as 80 DE-lncRNAs and 10 DE-miRNAs, were identified, with the overwhelming majority down-regulated in male-sterile floral buds. Enrichment analyses revealed that the general phenylpropanoid pathway as well as its related metabolisms was predicted to be altered in a mutant compared to its fertile progenitor. Meanwhile, the conserved genetic pathway DYT1-TDF1-AMS-MS188-MS1, as well as the causal gene ClAMT1 for the male-sterile mutant Se18, was substantially disrupted during male reproductive development. In addition, some targets of the key regulators AMS and MS188 in tapetum development were also down-regulated at a transcriptional level, such as ABCG26 (Cla004479), ACOS5 (Cla022956), CYP703A2 (Cla021151), PKSA (Cla021099), and TKPR1 (Cla002563). Considering lncRNAs may act as functional endogenous target mimics of miRNAs, competitive endogenous RNA networks were subsequently constructed, with the most complex one containing three DE-miRNAs, two DE-lncRNAs, and 21 DEGs. Collectively, these findings not only contribute to a better understanding of genetic regulatory networks underlying male sterility in watermelon, but also provide valuable candidates for future research.


Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development.
We disrupted the fibroblast growth factor (FGF) receptor 2 (FGFR2) gene by introducing a neo cassette into the IIIc ligand binding exon and by deleting a genomic DNA fragment encoding its transmembrane domain and part of its kinase I domain. A recessive embryonic lethal mutation was obtained. Preimplantation development was normal until the blastocyst stage. Homozygous mutant embryos died a few hours after implantation at a random position in the uterine crypt, with collapsed yolk cavity. Mutant blastocysts hatched, adhered, and formed a layer of trophoblast giant cells in vitro, but after prolonged culture, the growth of the inner cell mass stopped, no visceral endoderm formed, and finally the egg cylinder disintegrated. It follows that FGFR2 is required for early postimplantation development between implantation and the formation of the egg cylinder. We suggest that FGFR2 contributes to the outgrowth, differentiation, and maintenance of the inner cell mass and raise the possibility that this activity is mediated by FGF4 signals transmitted by FGFR2. The role of early FGF signaling in pregastrulation development as a possible adaptation to mammalian (amniote) embryogenesis is discussed.


Cyclization increases the antimicrobial activity and selectivity of arginine- and tryptophan-containing hexapeptides.
Arginine- and tryptophan-rich motifs have been identified in antimicrobial peptides with various secondary structures. We synthesized a set of linear hexapeptides derived from the sequence AcRRWWRF-NH(2) by substitution of tryptophan (W) by tyrosine (Y) or naphthylalanine (Nal) and by replacement of arginine (R) by lysine (K) to investigate the role of cationic charge and aromatic residues in membrane activity and selectivity. A second set of corresponding head-to-tail cyclic analogues was prepared to analyze the role of conformational constraints. The biological activity of the linear peptides followed the order Nal- >> W- > Y-containing compounds and slightly decreased upon R-K substitution. A pronounced activity-improving and bacterial selectivity-enhancing effect was found upon cyclization of the R- and W-bearing parent peptide, whereas the activity-modifying effect of cyclization of Y- and Nal-containing peptides was low. The analysis of the driving forces of peptide interaction with model membranes showed that the activities correlated with the partition coefficients and the depths of peptide insertion into neutral and negatively charged lipid bilayers. Spectroscopic studies, RP-HPLC, and titration calorimetry implied that the combination of cationic and aromatic amino acid composition and conformational rigidity afforded a membrane-active, amphipathic structure with a highly charged face opposed by a cluster of aromatic side chains. However, threshold values of low and high hydrophobicity seemed to exist beyond which the activity-enhancing effect of cyclization was negligible. The results suggest that cyclization of small peptides of an appropriate amino acid composition may serve as a promising strategy in the design of antimicrobial peptides.


Parental origin and mechanism of formation of polysomy X: an XXXXX case and four XXXXY cases determined with RFLPs.
The parental origin and mechanism of formation of polysomy X were studied in five cases (one case of 49,XXXXX; four cases of 49,XXXXY), using various X-linked restriction fragment length polymorphisms as genetic markers. Segregation and densitometric analyses on the polymorphic DNA fragments revealed that, in all five cases, the additional X chromosomes are of maternal origin and the mechanism of formation is most probably a result of three non-disjunctions during maternal meiotic divisions: once at the first meiosis and simultaneously twice at the second meiosis. The identical origin and the identical mechanism of formation among the five cases are unlikely to be coincidental and suggest a common cause in the mothers of the five cases.


Association of Kidney Function With Risk of Adverse Effects of Therapies for Atrial Fibrillation.
Atrial fibrillation (AF) is common in chronic kidney disease (CKD) and is treated with rate control medications, antiarrhythmic medications, as well as anticoagulation and procedures, each of which have associated risks. We aimed to evaluate the association of CKD status with the risks of adverse effects after initiation of AF therapies. This was a cohort study of community-based adults who newly initiated rate control medications, antiarrhythmic medications, warfarin, direct oral anticoagulants (DOACs) or received AF procedures in the 1 year after diagnosis of AF. Baseline estimated glomerular filtration rate (eGFR) was calculated using outpatient serum creatinine measures. Adverse effects within 1 year related to each AF therapy or within 1 month of an AF procedure were ascertained from vital sign databases, electrocardiograms (ECGs), and administrative codes. Fine-Gray hazard models were used to study the association of eGFR categories with risk of adverse effects for each AF therapy. Among 115,564 patients with incident AF, lower eGFR (vs. eGFR ≥60 ml/min per 1.73 m2) was significantly associated with higher adjusted risk of adverse effects after initiation of rate control therapies (most commonly hypotension and bradycardia) as follows: eGFR 45-59 (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.07-1.22), 30-44 (HR 1.15, 95% CI 1.06-1.25), and 15-29 (HR 1.29, 95% CI: 1.12-1.47) ml/min per 1.73 m2. Lower eGFR was associated with higher adjusted risk of adverse effects (most commonly prolonged QRS and QTc intervals) after initiation of an antiarrhythmic medication (vs. eGFR >60 ml/min per 1.73 m2) as follows: eGFR 45-59 (HR 1.12, 95% CI 1.01-1.23) and eGFR<15 (HR 1.43, 95% CI 1.01-2.01) ml/min per 1.73 m2. There was a graded association between lower eGFR and risk of major bleeding with warfarin use, with the greatest risk among those with eGFR <15 ml/min per 1.73 m2 (HR of 2.93, 95% CI 1.99-4.30). There was no association of eGFR with major bleeding in patients receiving DOACs. Rates of adverse effects within 1 month of an AF procedure were low among patients with (n = 18) and without (n = 41) CKD and was underpowered for further analyses. In conclusion, lower eGFR was associated with significantly higher risks of adverse effects after initiation of commonly used therapies to treat AF. These data may help inform the complex therapeutic decisions in patients with CKD and AF.


Pulmonary eosinophilia and granulomatous pulmonary arteritis induced in rats by intravenous Sephadex.
Airway eosinophilia has been proposed as a major pathogenetic event in bronchial asthma and airway hyperresponsiveness. Intravenous injection of Sephadex G200 in rats induces pulmonary and blood eosinophilia and alters pulmonary responsiveness to 5-hydroxytryptamine. To characterize the early pulmonary inflammatory responses following Sephadex administration, and to determine the timing of the onset of pulmonary eosinophilia relative to blood eosinophilia, Sprague-Dawley rats were injected intravenously with Sephadex G200 beads. Lungs and other tissues were examined by light and transmission electron microscopy at 4, 12, 24, 48, 72, and 96 hours after injection. Blood eosinophil counts were determined at 0, 24, and 96 hours after injection. Sephadex beads were trapped initially in small caliber muscular pulmonary arteries associated with terminal bronchioles and in intra-acinar locations. There was marked infiltration of eosinophils and macrophages around the beads and into arterial walls and edematous periarterial and peribronchiolar connective tissue as early as 4 hours after injection. Periarterial-peribronchiolar eosinophil aggregates peaked in density at 24 and 48 hours. Macrophages and multinucleated cells dominated the inflammatory cell responses in arteries immediately surrounding partially degraded Sephadex beads from 24 to 96 hours. Bone marrow eosinophilopoiesis and blood eosinophilia were not detected until 96 hours. We conclude that Sephadex induces pulmonary eosinophilia prior to blood eosinophilia and suggest that Sephadex may induce pulmonary release of one or more eosinophil chemotactic substance(s). This model may prove useful in the study of factors that influence eosinophil migration into the lung in various disease states.


Reassessing the revolving door: a developmental perspective on the young adult chronic patient.
Recent literature has described the young adult chronic patient as a subgroup of the chronically mentally ill whose high demand for a variety of mental health services places a strain on the delivery system. This paper suggests that the revolving door syndrome reflects deficits among the target population at three different levels: intrapsychic, dyadic, and societal. A treatment program that includes strategies responsive to the deficits at each level is described.


Changed clinical chemistry pattern in blood after removal of dental amalgam and other metal alloys supported by antioxidant therapy.
This study aimed to investigate a possible connection between removal of dental amalgam restorations supported by antioxidant therapy and indicative changes of clinical chemistry parameters. A group of 24 patients, referred for complaints related to amalgam restorations, underwent a removal of their amalgams. All patients were treated with antioxidants (vitamin B-complex, vitamin C, vitamin E, and sodium selenite). An age- and sex-matched control group of 22 individuals was also included. The mercury (Hg) and selenium (Se) concentration in plasma, Hg concentration in erythrocytes, and 17 clinical chemistry variables were examined in three groups: patients before amalgam removal (Before), patients after amalgam removal (After), and control individuals (Control). The Hg and Se values decreased (p < 0.05) in plasma, and the Hg concentration decreased (p < 0.05) in erythrocytes after amalgam removal. The variables serum lactate dehydrogenase (serum LDH) and serum sodium differed significantly both when comparing Control with Before (p < 0.01) and Before with After (p < 0.01). The variables white blood cell count (WBC), blood neutrophil count, blood eosinophil count, blood basophil count, blood lymphocyte count, blood monocyte count, serum potassium, and serum creatinine differed in the Before/After test (p < 0.05). Multivariate statistics (discriminant function analysis) could separate the groups Before and After with only one misclassification.


An Enactive-Ecological Approach to Information and Uncertainty.
Information is a central notion for cognitive sciences and neurosciences, but there is no agreement on what it means for a cognitive system to acquire information about its surroundings. In this paper, we approximate three influential views on information: the one at play in ecological psychology, which is sometimes called information for action; the notion of information as covariance as developed by some enactivists, and the idea of information as a minimization of uncertainty as presented by Shannon. Our main thesis is that information for action can be construed as covariant information, and that learning to perceive covariant information is a matter of minimizing uncertainty through skilled performance. We argue that the agent's cognitive system conveys information for acting in an environment by minimizing uncertainty about how to achieve intended goals in that environment. We conclude by reviewing empirical findings that support our view by showing how direct learning, seen as an instance of ecological rationality at work, is how mere possibilities for action are turned into embodied know-how. Finally, we indicate the affinity between direct learning and sense-making activity.


Microbiome diversity in Diaphorina citri populations from Kenya and Tanzania shows links to China.
The Asian citrus psyllid (Diaphorina citri) is a key pest of Citrus spp. worldwide, as it acts as a vector for "Candidatus Liberibacter asiaticus (Las)", the bacterial pathogen associated with the destructive Huanglongbing (HLB) disease. Recent detection of D. citri in Africa and reports of Las-associated HLB in Ethiopia suggest that the citrus industry on the continent is under imminent threat. Endosymbionts and gut bacteria play key roles in the biology of arthropods, especially with regards to vector-pathogen interactions and resistance to antibiotics. Thus, we aim to profile the bacterial genera and to identify antibiotic resistance genes within the microbiome of different populations worldwide of D. citri. The metagenome of D. citri was sequenced using the Oxford Nanopore full-length 16S metagenomics protocol, and the "What's in my pot" (WIMP) analysis pipeline. Microbial diversity within and between D. citri populations was assessed, and antibiotic resistance genes were identified using the WIMP-ARMA workflow. The most abundant genera were key endosymbionts of D. citri ("Candidatus Carsonella", "Candidatus Profftella", and Wolbachia). The Shannon diversity index showed that D. citri from Tanzania had the highest diversity of bacterial genera (1.92), and D. citri from China had the lowest (1.34). The Bray-Curtis dissimilarity showed that China and Kenya represented the most diverged populations, while the populations from Kenya and Tanzania were the least diverged. The WIMP-ARMA analyses generated 48 CARD genes from 13 bacterial species in each of the populations. Spectinomycin resistance genes were the most frequently found, with an average of 65.98% in all the populations. These findings add to the knowledge on the diversity of the African D. citri populations and the probable introduction source of the psyllid in these African countries.


Numb regulates meiotic spindle organisation in mouse oocytes.
Numb is an adaptor protein that controls the fate of cells in different species through asymmetrical inheritance by sibling cells during division. It has been investigated extensively in mitosis, mostly in neural progenitor cells, but its function in meiosis remains unknown. The present study was designed to investigate the expression, subcellular localisation and functional roles of Numb during mouse oocyte meiotic maturation. Using real-time polymerase chain reaction and western blotting, we found that the expression of Numb increased from the germinal vesicle (GV) to MII stages. Immunofluorescent staining revealed that Numb was mainly concentrated in the GV before meiosis resumption, aggregated in the vicinity of the chromosomes after GV breakdown and then localised to the spindle poles from prometaphase I to MII. Nocodazole treatment resulted in spindle destruction and Numb diffusion into the cytoplasm. However, Numb appeared at the spindle poles again once the spindles had formed when nocodazole-treated oocytes were washed and cultured for spindle recovery. Depletion of Numb by RNA interference resulted in chromosome misalignment, spindle deformation and even doubled spindle formation. Our results suggest that Numb is critical for spindle organisation during mouse oocytes meiosis. The present study provides evidence of a new function for Numb in addition to its action as a cell fate-determining factor.


Estimation of poly (C) avid serum ribonuclease in hepatoma patients.
Human poly (C) avid serum ribonuclease (RNase) differs in physico-chemical, electrophoretic, and catalytic properties from ribonuclease activity encountered in liver preparations. The first is reported as "secretory type", the latter, because it is undetectable in body fluids, as "nonsecretory type". We determined RNase activity in 11 hepatoma patients. A statistical difference from a normal control of corresponding age was encountered in both age groups investigated (51-60 years, P less than 0.05; 61-70 years, P less than 0.01). The circumstances mentioned above make the tumor itself unlikely to be the source of RNase elevation. Besides a diminished synthesis of RNase inhibitor by hepatoma cells, tumor-derived polyamines could contribute to enhanced RNase activity. The influence of polyamines on RNase activity has already been demonstrated by in vitro experiments. Simultaneous estimation of polyamines and RNase is required to elucidate in vivo circumstances.


Modified uniportal endoscopic plantar fasciotomy: a technical report.
Several authors have reported the benefits of the recent procedure of the dual portal endoscopic plantar fasciotomy (EPF). However, very little is known concerning its potential capability via the single portal EPF without special cutting device. The present study aimed to demonstrate the effectiveness of uniportal EPF in a patient with severe intractable plantar fasciitis following a failure of several conservative treatments. The recent technique; uniportal EPF under modified method, without a special cutting device, was reviewed in an effort to improve its capability for plantar release and to provide information for the avoidance of this procedure's complications. A patient, with the recalcitrant conditions and the progression of the severe plantar fasciitis of bilateral feet after a failure of the conservative treatments for 13-month period, was included in this report. All data of the preoperative and each successive postoperative period (1, 6 months and last follow-up) were prospectively collected including American Orthopedic Foot and Ankle Society (AOFAS) score, Visual Analogue Scale-Foot and Ankle (VAS-FA) score and any related complications. The operations were carried out by a single surgeon with the modified uniportal EPF via a simple hooked soft-tissue blade, without a special cutting device, on both feet simultaneously. All feet had uniportal EPF with transection of the medial 50% of the plantar fascia. Postoperatively, a patient was instructed to have partial-weight bearing for the first 2 weeks with wearing of full-length silicone insoles. Then, she is allowed to start to fully weightbear with the insoles. She is advised to cautiously return to daily activities and works at 2nd week after the operation. In regard to the EPF in two feet, there were clearly improvements in the comparison between preoperative and last follow-up period in terms of the increasing AOFAS scores, and VAS-FA scores. There were no significant iatrogenic-related complications including the lateral column pain in the present report. The recalcitrant condition of severe plantar fasciitis is not uncommon for several orthopedic surgeons. Regarding the emerging of several minimally invasive procedures for this condition, our modified uniportal EPF with a simple device was encouraging as a treatment option in releasing the plantar fascia with satisfactory effectiveness and lower risks of complications.


Behavior change outcomes in an outpatient cardiac rehabilitation program.
To evaluate the effectiveness of nutrition education within an outpatient cardiac rehabilitation program. Subjects were assigned, according to participation in cardiac rehabilitation programs in two community hospitals within an integrated healthcare system, to either a treatment (n=54), or a control group (n=50). One hundred four men and women, age range 35 to 85 years, participating in a 6-week cardiac rehabilitation program. Most were men (80%) and overweight. The majority presented with the diagnosis of myocardial infarction followed by coronary artery bypass surgery or percutaneous transluminal coronary angiography procedure. Subjects in the control group received usual nonindividualized nutrition education from cardiac rehabilitation therapists. Subjects in the treatment group attended two group nutrition education classes and one individual diet counseling session, all led by the same dietitian. Changes in fat, saturated fat, cholesterol, and carbohydrate intake, and restaurant eating habits as assessed by the Diet Habit Survey; changes in cardiac diet self-efficacy; and changes in health-related quality of life. Statistical analyses performed Group-by-time analysis of variance with repeated measures, chi2 test. The treatment group had greater improvement in Restaurant and Recipes scores on the Diet Habit Survey (2.6 vs 1.0) and a greater cardiac diet self-efficacy mean score (4.3) compared with the control group (3.8), with the greatest change in items related to eating in restaurants, away from home, or when alone. From entry into the program to discharge, the cholesterol-saturated fat index decreased significantly in the control group (from 57 to 48), and in the treatment group (from 51 to 42). The percent of energy from carbohydrate increased significantly in the control group (from 51% to 55%) and in the treatment group (from 53% to 57%). There were no differences between groups over the 3 time periods (baseline, 6 weeks, and 3-month follow-up) (n=39 for control group and n=47 for treatment group for all 3 time periods). Nutrition education within an outpatient cardiac rehabilitation program can improve dietary choices at restaurants and boost self confidence in the ability to adhere to a lipid-lowering diet.


[Public policy, structures of the State and the advocacy of the right to health protection].
Not always public policies for the advocacy of citizen rights meet their goal, among other things, because between their formulation and their implementation there is a lack of appropriate structures to generate, articulate and execute these policies. This has been the case of Mexico regarding the advocacy of the rights of non smokers. Very few has been achieved in this matter in the past. This article lists some of the potential causes of the lack of implementation of public policies. At the same time, explores the highly dynamic nature of the health care system at the present and towards the future. The magnitude of the challenges faced by the health care system requires concerted actions of many actors, not only from the very health care system but also from outside. Thus, public policies have to be considered not just at the governmental level but at the state level. Therefore, the main argument of this paper is that given the need to respond to complex challenges to protect the health of the population and their rights in a very complex context, there is a need to formulate and implement state policies that require the intervention of the appropriate state structures to make sure that the design and execution leads to the expected achievements. One such structure at the state level, among others, is the General Health Council, an organization established in 1841, that was incorporated within the Mexican Constitution in 1917, depending directly from the President of Mexico as Head of State. This Council has been reinforced to improve its assigned role to better participate, along other state structures, in the formulation and implementation of public policies such as those for the advocacy of citizen rights.


Unraveling the complexity of transcriptomic, metabolomic and quality environmental response of tomato fruit.
The environment has a profound influence on the organoleptic quality of tomato (Solanum lycopersicum) fruit, the extent of which depends on a well-regulated and dynamic interplay among genes, metabolites and sensorial attributes. We used a systems biology approach to elucidate the complex interacting mechanisms regulating the plasticity of sensorial traits. To investigate environmentally challenged transcriptomic and metabolomic remodeling and evaluate the organoleptic consequences of such variations we grown three tomato varieties, Heinz 1706, whose genome was sequenced as reference and two "local" ones, San Marzano and Vesuviano in two different locations of Campania region (Italy). Responses to environment were more pronounced in the two "local" genotypes, rather than in the Heinz 1706. The overall genetic composition of each genotype, acting in trans, modulated the specific response to environment. Duplicated genes and transcription factors, establishing different number of network connections by gaining or losing links, play a dominant role in shaping organoleptic profile. The fundamental role of cell wall metabolism in tuning all the quality attributes, including the sensorial perception, was also highlighted. Although similar fruit-related quality processes are activated in the same environment, different tomato genotypes follow distinct transcriptomic, metabolomic and sensorial trajectories depending on their own genetic makeup.


Quality Assessment and Classification of Codonopsis Radix Based on Fingerprints and Chemometrics.
In China, Codonopsis Radix (CR) is frequently consumed both as food and medicine. Here, a comprehensive strategy based on fingerprinting and chemometric approaches was created to explore the influence of origins, storage time and kneading processing on the quality of CR. Firstly, high-performance liquid chromatography with diode array detection was used to obtain the fingerprints of 35 batches of CR from six different origins and 33 batches of CR from varying storage times or kneading procedures. Secondly, chemometric methods including similarity analysis (SA), principal component analysis (PCA), hierarchical clustering analysis (HCA), and two-way orthogonal partial least square with discriminant analysis (O2PLS-DA) were used to evaluate the differences of chemical components in CR so as to identify its source and reflect its quality. Moreover, 13 and 16 major compounds were identified as marker compounds for the discrimination of CR from different origins, storage time and kneading processing, respectively. Furthermore, the relative content of the marker components and the exact content of Lobetyolin were measured, indicating that the contents of these components vary significantly between various CR samples. Meanwhile, the chemical components of CR were identified using Mass spectrometry. According to the findings of our investigation, the quality of CR from Gansu was the best, followed by Shanxi and then Sichuan. The quality of CR from Chongqing and Guizhou was poor. At the same time, the quality of CR was the best when it was kneaded and stored for 0 years, indicating that the traditional kneading process of CR is of great significance. Conclusively, HPLC fingerprint in conjunction with chemical pattern recognition and component content determination can be employed to differentiate the raw materials of different CR samples. Additionally, it is also a reliable, comprehensive and prospective method for quality control and evaluation of CR.


Complete mitochondrial genome of copperband butterflyfish Chelmon rostratus (Teleostei, Perciformes, Chaetodontidae).
In this study, the complete mitochondrial (mt) genome of the copperband butterflyfish Chelmon rostratus from Beibu Bay, China, was determined. It is one of the most common coral reef fish in South China Sea. The total length of C. rostratus mitogenome is 16,538 bp, which consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and a control region, with the genome organization and gene order being identical to other typical vertebrate mitogenomes. The overall nucleotide composition of the H-strand is 28.05% A, 28.94% T, 16.22% G and 26.79% C, with an A + T bias. This study will provide the first complete mitochondrial genome of Chelmon rostratus as useful information for the application of fish phylogenetic relationship analysis within the butterflyfish species.


Electroosmotic Flow Dispersion of Large Molecules in Electrokinetic Migration.
It is a common knowledge that large molecules have small diffusion coefficients. Therefore, it was thought that these molecules should generate very narrow peaks in electropherograms, because longitudinal diffusion was thought to be the only factor that contributes to band broadening in electrophoretic separation systems in capillaries and microfluidics. However, it is also common to observe that large molecules such as proteins and polymers often produce wider peaks than most small molecules. It is demonstrated in this work that dispersion of analytes during electrokinetic migration is also the results of Taylor dispersion. Similar to conventional Taylor dispersion, peak broadening is more pronounced for particles with smaller diffusion coefficients. The theoretical description of band broadening caused by electroosmotic flow dispersion (EOFD) and the experimental verification of this phenomenon are presented in this paper. The dispersion of various sized molecules, from small peptides to large proteins, in capillary electrophoresis is used as examples in this study.


Dynamic modeling of stem water content during the dormant period in walnut trees.
Water content is a key variable in plant physiology, even during the winter period. To simulate stem water content (WC) during the dormant season, a series of experiments were carried out on walnut trees under controlled conditions. In the field, WC was significantly correlated with soil temperature at 50 cm depth (R2 = 0.526). In the greenhouse, WC remained low as long as soil temperature was kept cold (<+5 °C) and increased after soil temperature was warmed to +15 °C, regardless of the date. Stem dehydration rate was significantly influenced by WC and evaporative demand. A parsimonious model with functions describing the main experimental results was calibrated and validated with field data from 13 independent winter dynamics in Juglans regia orchards. Three functions of water uptake were tested and gave equivalent accuracies (RMSE = 0.127-8; RMSEP = 0.116). However, only a sigmoid function describing the relationship between root water uptake and soil temperature gave values in agreement with the experimental results. Finally, the simulated WC provided similar accuracy in predicting frost hardiness compared to the measured WC (RMSE ca. 3 °C) and was excellent in spring (RMSE ca. 2 °C). This model may be a relevant tool for predicting the risk of spring frost in walnut trees. Its genericity should be tested in other fruit and forest tree species.


Fractionation for Resolution of Soluble and Insoluble Huntingtin Species.
The accumulation of misfolded proteins is central to pathology in Huntington's disease (HD) and many other neurodegenerative disorders. Specifically, a key pathological feature of HD is the aberrant accumulation of mutant HTT (mHTT) protein into high molecular weight complexes and intracellular inclusion bodies composed of fragments and other proteins. Conventional methods to measure and understand the contributions of various forms of mHTT-containing aggregates include fluorescence microscopy, western blot analysis, and filter trap assays. However, most of these methods are conformation specific, and therefore may not resolve the full state of mHTT protein flux due to the complex nature of aggregate solubility and resolution. For the identification of aggregated mHTT and various modified forms and complexes, separation and solubilization of the cellular aggregates and fragments is mandatory. Here we describe a method to isolate and visualize soluble mHTT, monomers, oligomers, fragments, and an insoluble high molecular weight (HMW) accumulated mHTT species. HMW mHTT tracks with disease progression, corresponds with mouse behavior readouts, and has been beneficially modulated by certain therapeutic interventions1. This approach can be used with mouse brain, peripheral tissues, and cell culture but may be adapted to other model systems or disease contexts.


Local Embedding and Effective Downfolding in the Auxiliary-Field Quantum Monte Carlo Method.
A local embedding and effective downfolding scheme has been developed and implemented in the auxiliary-field quantum Monte Carlo (AFQMC) method. A local cluster in which electrons are fully correlated is defined, and the frozen orbital method is used on the remainder of the system to construct an effective Hamiltonian, which operates within the local cluster. Local embedding, which involves only the occupied sector, has previously been employed in the context of Co/graphene. Here, the methodology is extended in order to allow for effective downfolding of the virtual sector, thus allowing for significant reduction in the computational effort required for AFQMC calculations. The system size, which can be feasibly treated with AFQMC, is therefore greatly extended as only a single local cluster is explicitly correlated at the AFQMC level of theory. The approximation is controlled by the separate choice of the spatial size of the active occupied region ( Ro) and of the active virtual region ( Rv). The systematic dependence of the AFQMC energy on Ro and Rv is investigated, and it is found that relative AFQMC energies of physical and chemical interest converge rapidly to the full AFQMC treatment (i.e., using no embedding or downfolding).


Macrophage phagocytosis after spinal cord injury: when friends become foes.
After spinal cord injury, macrophages can exert either beneficial or detrimental effects depending on their phenotype. Aside from their critical role in inflammatory responses, macrophages are also specialized in the recognition, engulfment, and degradation of pathogens, apoptotic cells, and tissue debris. They promote remyelination and axonal regeneration by removing inhibitory myelin components and cellular debris. However, excessive intracellular presence of lipids and dysregulated intracellular lipid homeostasis result in the formation of foamy macrophages. These develop a pro-inflammatory phenotype that may contribute to further neurological decline. Additionally, myelin-activated macrophages play a crucial role in axonal dieback and retraction. Here, we review the opposing functional consequences of phagocytosis by macrophages in spinal cord injury, including remyelination and regeneration versus demyelination, degeneration, and axonal dieback. Furthermore, we discuss how targeting the phagocytic ability of macrophages may have therapeutic potential for the treatment of spinal cord injury.


The relationship between foot arch flexibility and medial-lateral ground reaction force distribution.
Overuse running injury susceptibility has previously been associated with the magnitude and slope of ground reaction force profiles, most often in the vertical axis. However, despite the implications of excessive pronation and supination on injury susceptibility, very little research has examined the factors that might affect distribution of force in the medial-lateral directions. The purpose of this study was to consider how foot structure, specifically arch flexibility, affects the distribution of ground reaction force between the medial-lateral and vertical planes of motion. Twenty-five participants were classified as having stiff or flexible arches, and three dimensional kinetic data were gathered while the volunteers ran at 7 mph on an instrumented treadmill. A mixed-effects ANOVA was used to analyze the effect of arch flexibility type on distribution of ground reaction force impulse in the medial and lateral directions. The results suggest that individuals with relatively stiff arches experience a greater proportion of ground reaction force in the medial-lateral plane of motion, as compared with those with more flexible arches (p = 0.03). Further, the results suggest that most individuals, regardless of foot structure, experience greater impulse of force in the lateral than in the medial direction (p < 0.01). Considering previously explored relationships between ground reaction force, foot pronation/supination, and chronic running injuries, the results of this study suggest that arch flexibility could be used as a criterion for assessing injury susceptibility. Further, conclusions drawn from this study add to the discussion on the pros and cons of training or using devices to increase or restrict arch flexibility while running.


Protein hydrolysate from canned sardine and brewing by-products improves TNF-α-induced inflammation in an intestinal-endothelial co-culture cell model.
The anti-inflammatory activity of sardine protein hydrolysates (SPH) obtained by hydrolysis with proteases from brewing yeast surplus was ascertained. For this purpose, a digested and desalted SPH fraction with molecular weight lower than 10 kDa was investigated using an endothelial cell line (EA.hy926) as such and in a co-culture model with an intestinal cell line (Caco-2). Effects of SPH <10 kDa on nitric oxide (NO) production, reactive oxygen species (ROS) inhibition and secretion of monocyte chemoattractant protein 1 (MCP-1), vascular endothelial growth factor (VEGF), chemokine IL-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) were evaluated in TNF-α-treated and untreated cells. Upon TNF-α treatment, levels of NO, MCP-1, VEGF, IL-8, ICAM-1 and endothelial ROS were significantly increased in both mono- and co-culture models. Treatment with SPH <10 kDa (2.0 mg peptides/mL) significantly decreased all the inflammation markers when compared to TNF-α-treated control. This protective effect was more pronounced in the co-culture model, suggesting that SPH <10 kDa Caco-2 cells metabolites produced in the course of intestinal absorption may provide a more relevant protective effect against endothelial dysfunction. Additionally, indirect cross-talk between two cell types was established, suggesting that SPH <10 kDa may also bind to receptors on the Caco-2 cells, thereby triggering a pathway to secrete the pro-inflammatory compounds. Overall, these in vitro screening results, in which intestinal digestion, absorption and endothelial bioactivity are simulated, show the potential of SPH to be used as a functional food with anti-inflammatory properties.


In the grass species Brachypodium distachyon, the production of mixed-linkage (1,3;1,4)-β-glucan (MLG) occurs in the Golgi apparatus.
Mixed-linkage (1,3;1,4)-β-glucan (MLG) is a glucose polymer with beneficial effects on human health and high potential for the agricultural industry. MLG is present predominantly in the cell wall of grasses and is synthesized by cellulose synthase-like F or H families of proteins, with CSLF6 being the best-characterized MLG synthase. Although the function of this enzyme in MLG production has been established, the site of MLG synthesis in the cell is debated. It has been proposed that MLG is synthesized at the plasma membrane, as occurs for cellulose and callose; in contrast, it has also been proposed that MLG is synthesized in the Golgi apparatus, as occurs for other matrix polysaccharides of the cell wall. Testing these conflicting possibilities is fundamentally important in the general understanding of the biosynthesis of the plant cell wall. Using immuno-localization analyses with MLG-specific antibody in Brachypodium and in barley, we found MLG present in the Golgi, in post-Golgi structures and in the cell wall. Accordingly, analyses of a functional fluorescent protein fusion of CSLF6 stably expressed in Brachypodium demonstrated that the enzyme is localized in the Golgi. We also established that overproduction of MLG causes developmental and growth defects in Brachypodium as also occur in barley. Our results indicated that MLG production occurs in the Golgi similarly to other cell wall matrix polysaccharides, and supports the broadly applicable model in grasses that tight mechanisms control optimal MLG accumulation in the cell wall during development and growth. This work addresses the fundamental question of where mixed linkage (1,3;1,4)-β-glucan (MLG) is synthesized in plant cells. By analyzing the subcellular localization of MLG and MLG synthase in an endogenous system, we demonstrated that MLG synthesis occurs at the Golgi in Brachypodium and barley. A growth inhibition due to overproduced MLG in Brachypodium supports the general applicability of the model that a tight control of the cell wall polysaccharides accumulation is needed to maintain growth homeostasis during development.


A case of missed blunt traumatic aortic injury (BTAI).
We are reporting a case of missed blunt traumatic aortic injury (BTAI). A 28 year male presented with chest pain following a motor vehicle accident. He was discharged following normal clinical signs and chest radiograph. The following day he complained of lower limb weakness. Traumatic aortic dissection was revealed via computer tomography (CT) of the thorax. BTAI cannot be ruled out with normal clinical signs and chest radiograph alone. CT thorax is mandatory to rule out BTAI in high impact chest injury.


Peripherally inserted central catheters inserted with current best practices have low deep vein thrombosis and central line-associated bloodstream infection risk compared with centrally inserted central catheters: A contemporary meta-analysis.
Peripherally inserted central catheters and centrally inserted central catheters have numerous benefits but can be associated with risks. This meta-analysis compared central catheters for relevant clinical outcomes using recent studies more likely to coincide with practice guidelines. Several databases, Ovid MEDLINE, Embase, and EBM Reviews were searched for articles (2006-2018) that compared central catheters. Analyses were limited to peer-reviewed studies comparing peripherally inserted central catheters to centrally inserted central catheters for deep vein thrombosis and/or central line-associated bloodstream infections. Subgroup, sensitivity analyses, and patient-reported measures were included. Risk ratios, incidence rate ratios, and weighted event risks were reported. Study quality assessment was conducted using Newcastle-Ottawa and Cochrane Risk of Bias scales. Of 4609 screened abstracts, 31 studies were included in these meta-analyses. Across studies, peripherally inserted central catheters were protective for central line-associated bloodstream infection (incidence rate ratio = 0.52, 95% confidence interval: 0.30-0.92), with consistent results across subgroups. Peripherally inserted central catheters were associated with an increased risk of deep vein thrombosis (risk ratio = 2.08, 95% confidence interval: 1.47-2.94); however, smaller diameter and single-lumen peripherally inserted central catheters were no longer associated with increased risk. The absolute risk of deep vein thrombosis was calculated to 2.3% and 3.9% for smaller diameter peripherally inserted central catheters and centrally inserted central catheters, respectively. On average, peripherally inserted central catheter patients had 11.6 more catheter days than centrally inserted central catheter patients (p = 0.064). Patient outcomes favored peripherally inserted central catheters. When adhering to best practices, this study demonstrated that concerns related to peripherally inserted central catheters and deep vein thrombosis risk are minimized. Dramatic changes to clinical practice over the last 10 years have helped to address past issues with central catheters and complication risk. Given the lower rate of complications when following current guidelines, clinicians should prioritize central line choice based on patient therapeutic needs, rather than fear of complications. Future research should continue to consider contemporary literature over antiquated data, such that it recognizes the implications of best practices in modern central catheterization.


Involvement of Fas system and active caspases in apoptotic signalling in testicular germ cells of ethanol-treated rats.
The Fas system is involved in the regulation of germ cell apoptosis associated with testicular injury in experimental animals exposed to various insults. We tested the hypothesis that enhanced germ cell apoptosis mediated by the up-regulation of the Fas system and the activation of caspases may be involved in ethanol-induced testicular injury. Adult Wistar rats were fed either ethanol in Lieber-DeCarli liquid diet or an isocaloric control diet for 12 weeks. Marked Sertoli cell vacuolization and germ cell degeneration were observed in the testes of ethanol-treated rats (ETR) by both light and electron microscopy. Enhanced apoptosis of germ cells in ETR was detected by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labelling (TUNEL) method, transmission electron microscopy, and was associated with elevated activity of caspase-3, -8 and -9. The expression levels of the Fas ligand (FasL) in Sertoli cells and of both Fas and caspase-3 in germ cells of ETR detected immunohistochemically were higher than those of the control testes. Furthermore, reverse transcriptase-polymerase chain reaction analysis demonstrated an increase in both Fas and FasL mRNA levels in ETR. Fas system up-regulation and the elevated activity of caspases in the testes of ETR may be a reflection of ethanol-induced testicular injury resulting in enhanced germ cells apoptosis, which may be involved in infertility associated with alcohol abuse.


Changes in the activity of the general amino acid permease from Saccharomyces cerevisiae var. ellipsoideus during fermentation.
The evolution of the activity of the general amino acid permease and ethanol and glucose concentrations in the medium were studied in a mild fermentation process carried out by a wine strain of Saccharomyces cerevisiae var. ellipsoideus isolated from grape musts in spontaneous fermentation. The cells displayed a reduction in the activity of the general amino acid permease parallel to the increase of ethanol in the medium. This ethanol increase was not enough to promote a substantial inhibition on the total polypeptide synthesis measured as polyuridylic-acid-directed polyphenylalanine synthesis.


Effect of Calculated Panel Reactive Antibody Value on Waitlist Outcomes for Lung Transplant Candidates.
BACKGROUND We conducted a retrospective cohort study using United Network of Organ Sharing (UNOS) data to determine the effect of the calculated panel reactive antibody (cPRA) value on waitlist outcomes for lung transplant candidates. MATERIAL AND METHODS We divided lung transplant candidates into groups based on their cPRA value at the time of waitlist activation (0-25%, 25.1-50%, 50.1-75%, and 75.1-100%) and compared each group's waitlist outcomes to the lowest quartile ("minimally sensitized") group. The primary outcome was lung transplantation and the secondary outcome was waitlist mortality (a composite of death on the waitlist/delisting for clinical deterioration). RESULTS Compared to the minimally sensitized group, candidates with a cPRA value of 25.1-50% did not have a significantly different likelihood of undergoing lung transplant or waitlist mortality, candidates with a cPRA value of 50.1-75% were 25% less likely to undergo lung transplant and 44% more likely to die on the waitlist, and candidates with a cPRA value of 75.1-100% were 52% less likely to undergo lung transplant and 92% more likely to die on the waitlist. CONCLUSIONS CPRA values of greater than 50% are associated with significantly lower rates of transplantation and higher waitlist mortality.


Fibrin assembly: a comparison of electron microscopic and light scattering results.
To test the validity of a proposed two step fibrin assembly mechanism and directly visualize the molecular species present at various stages of fibrin formation, we have carried out an electron microscopic investigation. Assembly conditions duplicated those of a recent light scattering study and specimens were prepared at different time points with the use of a negative staining technique recently employed to visualize the trinodular structure of fibrinogen. Under near-physiological buffer conditions, protofibrils structurally similar to those postulated by Ferry have been found at early stages of fibrin assembly. In parallel with the light scattering results, a dramatic increase in fiber diameter was found in specimens prepared during the postulated lateral association stage of gelation. Light scattering and electron microscopic results both showed that high ionic strength reduces the rate and extent of fiber formation. Reptilase cleavage is shown to result in typical cross striated fibrin.


Immediate pigment-darkening reaction.
The immediate pigment-darkening reaction (IPD) is a gray-brown discoloration of the skin induced mainly by long-wave ultraviolet (UVA) radiation. The threshold value of IPD can be used as an important parameter in a series of light tests. The principle mechanism of the reaction is a photo-oxidative process causing darkening of preformed melanin and the production of free radicals. It has also been suggested that the reaction involves micromorphological changes in the melanocytes and a changed distribution pattern of melanosomes in the keratinocytes. This concept has recently been questioned by independent investigators. The physiological function of IPD still remains largely unknown. No photoprotective effect of the reaction has been observed. It has been suggested that IPD might have been of value during human evolution.


Diagnostic Value of CYFRA 21-1 in the Cerebrospinal Fluid for Leptomeningeal Metastasis.
Cerebrospinal fluid (CSF) cytology has low sensitivity for leptomeningeal metastasis (LM); thus, new markers are needed to improve the diagnostic accuracy of LM. We measured carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) in paired samples of CSF and serum from patients with LM and patients with nonmalignant neurological diseases (NMNDs) as controls. Receiver operating curve analysis was performed to assess their diagnostic accuracy for LM. In patients with NMNDs, CEA and CYFRA 21-1 levels in the CSF were significantly lower than the serum levels. In patients with LM, there was no significant difference between the CSF and serum CEA levels, whereas the CYFRA 21-1 levels were significantly higher in the CSF than the serum. CSF/serum quotients of CYFRA 21-1 were higher than those of CEA in patients with LM and patients with NMNDs. CSF CYFRA 21-1 and CSF/serum quotient of CYFRA 21-1 had high accuracy for differentiating LM from NMNDs that was similar to CSF CEA and CSF/serum quotient of CYFRA 21-1, whereas serum CYFRA 21-1 is of poor diagnostic value. Measurement of CSF CYFRA 21-1 should not be overlooked in patients with suspected LM, even if the serum CYFRA 21-1 level is within normal limits.


Development of a Surface Plasmon Resonance and Fluorescence Imaging System for Biochemical Sensing.
Surface plasmon resonance (SPR) biosensors are an extremely sensitive optical technique used to detect the changes in refractive index occurring at the sensor interface. Fluorescence involves the emission of light by a substance that has absorbed light or other electromagnetic radiation, and the parameters of the absorbed and emitted radiation are used to identify the presence and the amount of specific molecules in a specimen. SPR biosensors and fluorescence analysis are both effective methods for real-time detection. The combination of these technologies would improve the quantitative detection sensitivity of fluorescence analysis and the specificity of SPR detection. We designed and developed an SPR and fluorescence synchronous detection system. The SPR module was based on two kinds of modulation methods, and the fluorescence module was capable of switching between four wavelengths. The fluorescence microspheres and A549 cells of different concentration were both detected by the SPR and fluorescence method synchronously in real time. The fluorescent signal and the optical signal of the SPR were shown to correlate. The correlation coefficient for fluorescent microspheres detection reached up to 0.9866. The system could be used in cell analysis and molecule diagnosis in the future.


Interrupted Time Series of User-centered Clinical Decision Support Implementation for Emergency Department-initiated Buprenorphine for Opioid Use Disorder.
Adoption of emergency department (ED) initiation of buprenorphine (BUP) for opioid use disorder (OUD) into routine emergency care has been slow, partly due to clinicians' unfamiliarity with this practice and perceptions that it is complicated and time-consuming. To address these barriers and guide emergency clinicians through the process of BUP initiation, we implemented a user-centered computerized clinical decision support system (CDS). This study was conducted to assess the feasibility of implementation and to evaluate the preliminary efficacy of the intervention to increase the rate of ED-initiated BUP. An interrupted time series study was conducted in an urban, academic ED from April 2018 to February 2019 (preimplementation phase), March 2019 to August 2019 (implementation phase), and September 2019 to December 2019 (maintenance phase) to study the effect of the intervention on adult ED patients identified by a validated electronic health record (EHR)-based computable phenotype consisting of structured data consistent with potential cases of OUD who would benefit from BUP treatment. The intervention offers flexible CDS for identification of OUD, assessment of opioid withdrawal, and motivation of readiness to start treatment and automates EHR activities related to ED initiation of BUP (including documentation, orders, prescribing, and referral). The primary outcome was the rate of ED-initiated BUP. Secondary outcomes were launch of the intervention, prescription for naloxone at ED discharge, and referral for ongoing addiction treatment. Of the 141,041 unique patients presenting to the ED over the preimplementation and implementation phases (i.e., the phases used in primary analysis), 906 (574 preimplementation and 332 implementation) met OUD phenotype and inclusion criteria. The rate of BUP initiation increased from 3.5% (20/574) in the preimplementation phase to 6.6% (22/332) in the implementation phase (p = 0.03). After the temporal trend of the number of physician's with X-waiver training and other covariates were adjusted for, the relative risk of BUP initiation rate was 2.73 (95% confidence interval [CI] = 0.62 to 12.0, p = 0.18). Similarly, the number of unique attendings who initiated BUP increased modestly 7/53 (13.0%) to 13/57 (22.8%, p = 0.10) after offering just-in-time training during the implementation period. The rate of naloxone prescribed at discharge also increased (6.5% preimplementation and 11.5% implementation; p < 0.01). The intervention received a system usability scale score of 82.0 (95% CI = 76.7 to 87.2). Implementation of user-centered CDS at a single ED was feasible, acceptable, and associated with increased rates of ED-initiated BUP and naloxone prescribing in patients with OUD and a doubling of the number of unique physicians adopting the practice. We have implemented this intervention across several health systems in an ongoing trial to assess its effectiveness, scalability, and generalizability.


Replication of ColE2 and ColE3 plasmids: two ColE2 incompatibility functions.
We have identified and localized two incompatibility determinants (IncA and IncB) within a 1.3 kb segment of ColE2 sufficient for autonomous replication. The IncA determinant is localized in a region shorter than 250 bp and expresses incompatibility against both ColE2 and ColE3. The region which determines sensitivity to the IncA determinant seems to overlap with the region specifying the IncA determinant. The expression of the trans-acting factor(s) specifically required for replication of ColE2 interferes with expression of the IncA determinant against ColE2 but not against ColE3. The IncA determinant might be at least partly responsible for the copy number control of the plasmid. The IncB determinant is localized in a 50 bp region (origin) which is sufficient for initiation of replication in the presence of the trans-acting factor(s). The IncB determinant is specific for ColE2 and seems to be due to titration of the trans-acting essential replication factor(s) by binding.


Suicidal behaviors and drug abuse: impulsivity and its assessment.
Impulsivity appears to play an important role in suicidal behaviors and drug abuse, which are two psychiatric problems that may interact with one another. Interpretation of the literature on impulsivity in these behaviors may be complicated by the variety of measurement techniques for the assessment of impulsivity. There are three general types of impulsivity assessment: self-report, biological, and laboratory behavioral. Because laboratory behavioral measures both meet an operational definition of impulsivity and are sensitive to state-dependent changes in impulsivity, this paper presents data that focuses on laboratory behavioral performance among samples emitting suicidal behaviors or substance abuse. To better account for influence of impulsivity in these psychiatric disturbances, no single source of measurement should be used without the consideration of other types of instruments.


cAMP-specific phosphodiesterase inhibitors: promising drugs for inflammatory and neurological diseases.
PDEs are key enzymes in the adenosine and guanosine cyclic nucleotides (cAMP and cGMP) signaling cascade. Their inhibition increases cyclic nucleotide levels inside the cell. Thus, pharmacological modulation of PDE activity can have profound effects on the function of cells and organ systems throughout the body. Among the large PDE families, only PDE4, PDE7 and PDE8 are cAMP-specific hydrolyzing enzymes. cAMP is an important second messenger not only by its involvement in a vast number of physiological processes but also by activation of protein kinase A, exchange protein activated by cAMP (Epac) and cAMP response element-binding (CREB) or cyclic nucleotide-gated channels. Clearly, such enzymes represent ideal drug targets for the pharmacological treatment of many pathologies. The discovery and development of small molecules targeting cAMP-specific PDEs reported in the last 5 years is the focus of the present review. The first PDE4 inhibitors recently reached the market, having avoided, by different strategies, their dose-limiting side effects (after more than two decades of drug development). Meanwhile, new cAMP-specific PDE7 and PDE8 inhibitors emerged as effective and safe drugs for severe unmet diseases. The therapeutic potential of these inhibitors will be tested in the near future, as many of these drug candidates are ready to start clinical trials.


Galanin is a physiological regulator of spontaneous pulsatile secretion of growth hormone in the male rat.
To determine whether galanin (GAL), a 29-amino acid neuropeptide, plays a role in the physiological regulation of the pulsatile secretion of GH and PRL in the male rat, secretory patterns of both hormones were studied in freely moving animals after GAL passive immunoneutralization. Adult male Sprague-Dawley rats were equipped with iv and intracerebroventricular catheters. After 7 days, 3 microliters of a specific GAL antiserum (GAL-AS) or normal rabbit serum (NRS; controls) were infused in the third ventricle of 10 rats, 25 and 1 h before the animals were bled every 15 min for 6 h (1000-1600 h). Plasma GH and PRL concentrations were measured by RIA, and the hormonal secretory patterns were analyzed by the PULSAR program. Control rats, treated with NRS, displayed typical GH secretion, with pulses of high amplitude (167 +/- 27 ng/ml) and low frequency (2.4 +/- 0.2 pulses/6 h), separated by periods of low trough levels (3.8 +/- 0.6 ng/ml). Rats treated with GAL-AS had altered pulsatile GH secretion. Pulse height was markedly reduced (77 +/- 15 ng/ml; P less than 0.01 vs. controls), and peak frequency was higher (3.6 +/- 0.5 pulses/6 h; P less than 0.05), while GH baseline levels and integrated GH secretion over the 6-h sampling period remained unaltered. Injection of rat GH-releasing hormone (1 microgram/rat, iv) caused a similar GH stimulation in both groups of rats, as determined by the peak GH response at 5 min (368 +/- 112 vs. 342 +/- 81 ng/ml) or by the integrated GH response over 1 h (5.13 +/- 1.30 vs. 4.77 +/- 1.15 micrograms.min/ml in NRS- and GAL-AS-treated rats, respectively; P less than 0.05). In contrast to GH, pulsatile secretion of PRL was not affected by the GAL-AS treatment. These results indicate that GAL is a physiological regulator of spontaneous pulsatile secretion of GH, but not PRL, in the male rat. The influence of GAL on GH secretion appears to be exerted within the hypothalamus, mainly by a stimulation of GRF secretion. However, the changes in GH pulse frequency observed after GAL immunoneutralization suggest that GAL might also influence the somatostatin inhibitory tone.


Alveolar proteins stabilize cortical microtubules in Toxoplasma gondii.
Single-celled protists use elaborate cytoskeletal structures, including arrays of microtubules at the cell periphery, to maintain polarity and rigidity. The obligate intracellular parasite Toxoplasma gondii has unusually stable cortical microtubules beneath the alveoli, a network of flattened membrane vesicles that subtends the plasmalemma. However, anchoring of microtubules along alveolar membranes is not understood. Here, we show that GAPM1a, an integral membrane protein of the alveoli, plays a role in maintaining microtubule stability. Degradation of GAPM1a causes cortical microtubule disorganisation and subsequent depolymerisation. These changes in the cytoskeleton lead to parasites becoming shorter and rounder, which is accompanied by a decrease in cellular volume. Extended GAPM1a depletion leads to severe defects in division, reminiscent of the effect of disrupting other alveolar proteins. We suggest that GAPM proteins link the cortical microtubules to the alveoli and are required to maintain the shape and rigidity of apicomplexan zoites.


Exploring the later life relationship between adults with cerebral palsy and their non-disabled siblings.
Adults with moderate or severe cerebral palsy often require significant lifetime support from family and formal services. The aim of this study was to use a life course approach to explore how previous life experiences impact on the later life relationships of people with moderate to severe cerebral palsy aged 40 years and over and their non-disabled siblings. Twelve adults with moderate to severe cerebral palsy and 16 of their non-disabled siblings were interviewed twice to explore their relationships. Constructivist grounded theory method was used to analyse the data. Four themes were identified as important in understanding these later life sibling relationships: sharing childhood experiences, contact in adulthood, diminishing parental role and increasing support needs. The life course approach indicated that siblings' growing up together was important for the development and maintenance of emotional closeness later in life. Emotional closeness and familial obligation were important factors in motivating siblings with and without cerebral palsy to maintain or re-establish contact with each other in adulthood. Maintenance of sibling relationships in later life is dependent on health, proximity and the ability to keep in contact with each other. Implications for Rehabilitation As adults with severe cerebral palsy live longer, their relationships with non-disabled siblings often take on increased importance and particularly as their parents may be no longer able to provide support. Service providers have a role in helping ageing siblings with and without disability to maintain and build their relationships, for example, by supporting geographically distant siblings to keep in touch. Service providers have a role in supporting the person with a disability and their siblings to make plans for the future.


Insulin-like Growth Factor 1 Receptor Expression in Advanced Non-small-cell Lung Cancer and its Impact on Overall Survival.
The insulin-like growth factor 1 receptor (IGF1R) expression has been addressed as a potential prognostic marker in non-small-cell lung cancer (NSCLC) in various studies; however, the associations between IGF1R expression and prognosis of advanced NSCLC patients is still controversial. The aim of our observational, cohort study was to evaluate the expression of IGF1R in advanced NSCLC and its prognostic role. A subgroup analysis was performed to address the influence of pre-existing type 2 diabetes mellitus (T2DM) status on IGF1R expression and overall survival (OS). IGF1R expression was evaluated in 167 consecutive advanced NSCLC patients (stage IIIB and IV), diagnosed and treated at one university institution, between 2005 and 2010. All patients received at least one line of standard cytotoxic therapy and 18 of them had pre-existing T2DM. IGF1R expression was determined by immunohistochemical (IHC) staining, with score ≥ 1+ considered as positive. Information on baseline characteristics, as well as patients' follow-up data, were obtained from the hospital registry. Associations of IGF1R expression with clinical characteristics and overall survival were compared. IGF1R expression was positive in 79.6% of patients, significantly more often in squamous-cell carcinoma (SCC) compared to non-squamous-cell (NSCC) histology (88.7% vs. 74.3%; P = 0.03). IGF1R positivity did not correlate with T2DM status or with other clinical features (sex, smoking status, performance status). Median OS was similar between IGF1R positive and IGF1R negative group (10.2 vs. 8.5 months, P = 0.168) and between patients with or without T2DM (8.7 vs. 9.8 months, P = 0.575). Neither IGF1R expression nor T2DM were significant predictors of OS. IGF1R or T2DM status were not significantly prognostic in described above collective of advanced NSCLC treated with at least one line of chemotherapy. In addition, no association between T2DM status and IGF1R expression was found. Further studies on IGF1R expression and its prognostic as well as therapeutic consequences in a larger collective of advanced NSCLC patients, with or without T2DM, are needed.


Decreased serum dehydroepiandrosterone is associated with an increased progression of human immunodeficiency virus infection in men with CD4 cell counts of 200-499.
Dehydroepiandrosterone (DHEA) and its interconvertible sulfate derivative (DHEA-S) are human androgenic steroids that have been reported to inhibit viral expression and have been associated with a decreased risk of cancer. The relationship between serum DHEA and DHEA-S levels and subsequent progression to AIDS was investigated in a sample of human immunodeficiency virus (HIV)-infected men from the San Francisco Men's Health Study followed prospectively since 1984. Among 108 men seropositive for HIV at study entry and with CD4 lymphocyte counts of 200-499 microliters 24 months later, serum DHEA levels below the lower limit of normal (less than 180 ng/dl) at this later date were predictive of subsequent progression to AIDS (relative hazard = 2.34; 95% confidence interval = 1.18-4.63; P = .01) after controlling for hematocrit, age, and log absolute CD4 cell number in a Cox proportional hazards model. This is the first large prospective cohort in which an endocrinologic variable has been observed to independently predict progression to AIDS. These observations, in addition to recent in vitro data, suggest that DHEA might have a protective effect in HIV infection.


Real-time dynamics of strongly correlated fermions using auxiliary field quantum Monte Carlo.
Spurred by recent technological advances, there is a growing demand for computational methods that can accurately predict the dynamics of correlated electrons. Such methods can provide much-needed theoretical insights into the electron dynamics probed via time-resolved spectroscopy experiments and observed in non-equilibrium ultracold atom experiments. In this article, we develop and benchmark a numerically exact Auxiliary Field Quantum Monte Carlo (AFQMC) method for modeling the dynamics of correlated electrons in real time. AFQMC has become a powerful method for predicting the ground state and finite temperature properties of strongly correlated systems mostly by employing constraints to control the sign problem. Our initial goal in this work is to determine how well AFQMC generalizes to real-time electron dynamics problems without constraints. By modeling the repulsive Hubbard model on different lattices and with differing initial electronic configurations, we show that real-time AFQMC is capable of accurately capturing long-lived electronic coherences beyond the reach of mean field techniques. While the times to which we can meaningfully model decrease with increasing correlation strength and system size as a result of the exponential growth of the dynamical phase problem, we show that our technique can model the short-time behavior of strongly correlated systems to very high accuracy. Crucially, we find that importance sampling, combined with a novel adaptive active space sampling technique, can substantially lengthen the times to which we can simulate. These results establish real-time AFQMC as a viable technique for modeling the dynamics of correlated electron systems and serve as a basis for future sampling advances that will further mitigate the dynamical phase problem.


Lack of association between the -2518G/A polymorphism of the MCP-1 gene and ischaemic heart disease: a family-based investigation.
Using two recently described family-based tests of association, the possible role of the functional -2518G/A polymorphism in the promoter region of the monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the MCP-1 -2518G/A polymorphism. Using the combined transmission disequilibrium test and the pedigree disequilibrium test, no association between the MCP-1 -2518G/A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MCP-1 -2518G/A polymorphism is not strongly associated with IHD.


Effects of Metformin and Furosemide on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Implications for Their Use as Probe Drugs in a Transporter Cocktail.
In a recently described probe drug cocktail for clinically relevant drug transporters containing digoxin, furosemide, metformin and rosuvastatin, mutual interactions were essentially absent except for increases in the systemic exposure of rosuvastatin. To optimize the cocktail, we further examined the dose dependence of the effects of metformin and furosemide on rosuvastatin pharmacokinetics. This was a randomized, open label, single center, six-treatment, six-period, six-sequence crossover trial. Eighteen healthy male subjects received 10 mg rosuvastatin as reference treatment and, as test treatments, 10 mg rosuvastatin combined with 10, 50 or 500 mg metformin (T1, T2 and T3) or with 1 or 5 mg furosemide (T4 and T5). Primary pharmacokinetic endpoints were rosuvastatin C max (maximum plasma concentration) and AUC0-tz (area under the plasma concentration-time curve from time zero to the last quantifiable concentration). The relative bioavailability of rosuvastatin was essentially unchanged when administered with metformin in T1 and T2, but in T3 it increased to 152% for AUC0-tz (90% CI 135-171%) and 154% for C max (90% CI 132-180%). Coadministration with furosemide did not change rosuvastatin relative bioavailability in T4, but in T5 it increased slightly to 116% for AUC0-tz (90% CI 102-132%) and 118% for C max (90% CI 98-142%). The increased systemic exposure of rosuvastatin when administered as part of the proposed transporter cocktail is most likely attributable to metformin and only to a minor degree to furosemide. Reduction of the doses of metformin and furosemide is expected to eliminate the previously described interaction. EudraCT no. 2015-003052-46, ClinicalTrials.gov identifier NCT02574845.


[General viewpoints in evaluating findings and making diagnostic decisions].
The process of diagnosis consists of establishment of findings, interpretation of findings and diagnostic decision. The general situation concerning decision is characterized by the fact that incorrect decisions may appear by falsely positive and falsely negative findings. On this assumption a diagnosis can only be confirmed with certain probability or excluded. Unequivocal decisions may be regarded as borderline cases of this situation concerning the decision. Their prerequisites are explained with the help of four-field table and diagrams belonging to this. If these conditions are not given, so that only a probable diagnosis can be made, then the indexes allow of an estimation of the degree of certainty of the evidence. By means of statistical models helps for decision can be obtained. The example of the Bayes-theorem is illustrated with the help of diagrams. In recent years another approach gathers momentum. The methods in question are so-called unclear approaches of the analysis of processes. They essentially support themselves on assessments by experts and on a programmed approach.


Alicyclobacillus dauci sp. nov., a slightly thermophilic, acidophilic bacterium isolated from a spoiled mixed vegetable and fruit juice product.
A novel, moderately thermophilic, acidophilic, Gram-variable, rod-shaped, endospore-forming bacterium was isolated from a spoiled mixed vegetable and fruit juice product that had the off-flavour of guaiacol. The bacterium, strain 4F(T), grew aerobically at 20-50 °C (optimum 40 °C) and pH 3.0-6.0 (optimum pH 4.0) and produced acid from glycerol, d-galactose and d-glucose. It contained menaquinone-7 (MK-7) as the major isoprenoid quinone and the DNA G+C content was 49.6 mol%. The predominant cellular fatty acids of strain 4F(T) were ω-alicyclic (ω-cyclohexane fatty acids), which are characteristic of the genus Alicyclobacillus. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain belongs to the Alicyclobacillus cluster, and is related most closely to the type strains of Alicyclobacillus acidoterrestris (97.4 % similarity) and Alicyclobacillus fastidiosus (97.3 %). Strain 4F(T) produced guaiacol from vanillic acid. It can be distinguished from related species by its acid production type and guaiacol production. On the basis of phenotypic characteristics, phylogenetic analysis and DNA-DNA relatedness values, it can be concluded that the strain represents a novel species of the genus Alicyclobacillus, for which the name Alicyclobacillus dauci sp. nov. is proposed; the type strain is 4F(T) ( = DSM 28700(T) = NBRC 108949(T) = NRIC 0938(T)).


Three new taxa of the genus Cechetra Zolotuhin Ryabov, 2012 (Lepidoptera, Sphingidae) from South-East Asia with notes on other species of the genus.
Two new species and one subspecies of the genus Cechetra Zolotuhin Ryabov, 2012 are described from South-East Asia. Cechetra bryki sp.n. is described from Nepal, Myanmar (Burma), southwestern China and northern Vietnam. This species is most closely related in habitus, male genitalia morphology and COI mtDNA to the sympatric species, C. lineosa (Walker, 1856) and C. scotti (Rothschild, 1920) in habitus, male genitalia morphology and COI mtDNA. Cechetra inconspicua sp.n. is described from Peninsular Malaysia, Borneo and Sumatra. In habitus, it is closest to C. lineosa and C.subangustata (Rothschild, 1920), but its COI mtDNA (COI-5P "barcode region") is very different from all other species in the genus. Cechetra subangustata continentalis ssp.n. is described from continental Indochina and Taiwan. It differs from the nominotypical subspecies in habitus. Cechetra scotti comb. nov. is transferred to Cechetra from Cechenena Rothschild Jordan, 1903.


Persistence of Technosignatures: A Comment on Lingam and Loeb.
In a recent article in this journal, Lingam and Loeb developed an excellent heuristic for searches for biosignatures versus technosignatures. We consider two ways in which their approach could be extended and sharpened, with focus on durability of technosignatures. We also note an important consequence of the adopted heuristic that offers strong support to the ideas of the Dysonian Search for ExtraTerrestrial Intelligence (SETI).


Creation of Educational Videos for Patients Undergoing Nonelective Surgery: Tools for the COVID-19 Era.
Currently, there is a lack of reliable patient-centric educational videos in otolaryngology. In light of COVID-19, otolaryngologists have had to see patients through virtual visits and have been encouraged to send patients home after nonelective surgery. Additionally, most hospitals are not permitting patients' family members and caretakers to enter patient rooms, thus often preventing them from receiving adequate education on postoperative care. Embracing educational videos as a valuable tool will improve communication with patients, especially during the times of COVID-19 and beyond. The goal of this commentary is to describe our early lessons learned in developing educational videos in a streamlined, efficient, and accessible format that can be shared among all members of the multidisciplinary and design production team. Background on the use of multimedia to reduce patient anxiety and frustration with surgical interventions is provided.


Provider experiences with three- and six-month antiretroviral therapy dispensing for stable clients in Zambia.
Multi-month dispensing of antiretroviral therapy (ART) has been taken to scale in many settings in sub-Saharan Africa with the benefits of improved client satisfaction and decreased client costs. Six-month ART dispensing may further increase these benefits; however, data are lacking. Within a cluster-randomized trial of three- versus six-month dispensing in Malawi and Zambia, we performed a sub-study to explore Zambian provider experiences with multi-month dispensing. We conducted 18 in-depth interviews with clinical officers and nurses dispensing ART as part of INTERVAL in Zambia. Interview questions focused on provider perceptions of client acceptability, views on client sharing and selling of ART, and perceptions on provider workload and clinic efficiency, with a focus on differences between three- and six-month dispensing. Interviews were analyzed using inductive thematic analysis to identify key themes and patterns within the data. Providers perceived significant benefits of multi-month dispensing, with advantages of six-month over three-month dispensing related to a reduced burden on clients, and for reductions in their own workload and clinic congestion. Among nearly all providers, the six-month dispensing strategy was perceived as ideal. Further research is needed to quantify clinical outcomes of six-month dispensing and feasibility of scaling-up this intervention in resource-limited settings.Clinical Trial Number: NCT03101592.


Social relationships among adolescents as described in an electronic diary: a mixed methods study.
Social relationships among adolescents with mental disorders are demanding. Adolescents with depressive symptoms may have few relationships and have difficulties sharing their problems. Internet may offer reliable and easy to use tool to collect real-time information from adolescents. The aim of this study is to explore how adolescents describe their social relationships with an electronic diary. Mixed methods were used to obtain a broad picture of adolescents' social relationships with the data gathered from network maps and reflective texts written in an electronic diary. Adolescents who visited an outpatient clinic and used an intervention (N=70) designed for adolescents with signs of depression were invited to use the electronic diary; 29 did so. The quantitative data gathered in the electronic diary were summarized with descriptive statistics, and the qualitative data were categorized using a thematic analysis with an inductive approach. We found that social relationships among adolescents with signs of depression can vary greatly in regards to the number of existing relationships (from lacking to 21) and the quality of the relationships (from trustful to difficult). However, the relationships may change, and the adolescents are also willing to build up their social relationships. Professionals need to be aware of the diversity of adolescents' social relationships and their need for personalized support.


High mobility group protein HMGA1 inhibits retinoblastoma protein-mediated cellular G0 arrest.
Retinoblastoma protein (RB) acts as a tumor suppressor in many tissue types, by promoting cell arrest via E2F-mediated transcriptional repression. In addition to the aberrant forms of the RB gene found in different types of cancers, many viral oncoproteins including the simian virus 40 large T antigen target RB. However, cellular factors that inhibit RB function remain to be elucidated. Here, we report that RB interacts with the high mobility group protein A1 (HMGA1), a-non-histone architectural chromatin factor that is frequently overexpressed in cancer cells. HMGA1 binds the small pocket domain of RB, and competes with HDAC1. Subsequently, overexpression of HMGA1 abolishes the inhibitory effect of RB on E2F-activated transcription from the cyclin E promoter. Under serum starvation, T98G cells had been previously shown to be arrested in the G0 phase in an RB-mediated manner. The G0 phase was characterized by growth arrest and low levels of transcription, together with the hypophosphorylation of RB and the downregulation of HMGA1. In contrast, such serum-depleted G0 arrest was abrogated in T98G cells overexpressing HMGA1. The overexpressed HMGA1 was found to form complexes with cellular RB, suggesting that downregulation of HMGA1 is required for G0 arrest. There were no phenotypic changes in HMGA1-expressing T98G cells in the presence of serum, but the persistent expression of HMGA1 under serum starvation caused various nuclear abnormalities, which were similarly induced in T antigen-expressing T98G cells. Our present findings indicate that overexpression of HMGA1 disturbs RB-mediated cell arrest, suggesting a negative control of RB by HMGA1.


Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss.
Activation of apoptosis is associated with generation of reactive oxygen species. The present research shows that superoxide is produced by mitochondria isolated from apoptotic cells due to a switch from the normal 4-electron reduction of O2 to a 1-electron reduction when cytochrome c is released from mitochondria. Bcl-2, a protein that protects against apoptosis and blocks cytochrome c release, prevents superoxide production when it is overexpressed. The switch in electron transfer provides a mechanism for redox signaling that is concomitant with cytochrome c-dependent activation of caspases. The block of cytochrome c release provides a mechanism for the apparent antioxidant function of Bcl-2.


Indication of pre-surgical radiochemotherapy enhances psychosocial morbidity among patients with resectable locally advanced rectal cancer.
Patients with cancer experience stress-determined psychosocial comorbidities and behavioural alterations. Patients expectation to be cured by the first line surgery and their emotional status can be negatively influenced by the decision to include neoadjuvant long-course radiotherapy prior to surgical intervention. From the patient's perspective such treatment algorithmindicates incurability of the disease. The aim of this study was to analyse the extent and dynamics of stress and related psychosocial disturbances among patients with resectable rectal cancer to whom the neoadjuvant radiochemotherapy before surgery has been indicated.Three standardised assessment tools evaluating psychosocial morbidity of rectal cancer patients have been implemented: The EORTC QLQ C30-3, the EORTC QLQ CR29 module and the HADS questionnaires previously tested for internal consistency were answered by patients before and after long-course radiotherapy and after surgery and the scores of clinical and psychosocial values were evaluated by means of the EORTC and HADS manuals. The most profound psychosocial distress was experienced by patients after the decision to apply neoadjuvant radiotherapy and concomitant chemotherapy before surgical intervention. The involvement of pre-surgical radiotherapy into the treatment algorithm increased emotional disturbances (anxiety, feelings of hopelessness) and negatively influenced patient's treatment adherence and positive expectations from the healing process. The negative psychosocial consequences appeared to be more enhanced in female patients. Despite provided information about advances of neoadjuvant radiotherapy onto success of surgical intervention, the emotional and cognitive disorders improved only slightly. The results clearly indicate that addressed communication and targeted psychosocial support has to find place before pre-surgical radiochemotherapy and as a standard part through the trajectory of the entire multimodal rectal cancer treatment.


Effects of levamisole on the ultrastructure of mitochondria in the liver of Beagle dogs.
Purebred Beagle dogs were treated daily for 6 days with levamisole in oral doses of 10 mg/kg body weight. Liver biopsies taken before and after treatment showed no ultrastructural differences. Intramitochondrial paracrystalline inclusions before, as well as after, the drug administration were rare. Other minor abnormalities, in a few mitochondria, were as frequent before as after the drug treatment.


Posterior cerebral artery occlusion without hemianopia.
A 42-year-old man had ischemic infarction from an occlusion of the left posterior cerebral artery (PCA), but had no visual field defect by examination or Goldmann perimetry. Arteriograms showed distal filling of the occluded PCA, but no collateral blood flow from the carotid circulation, suggesting collateral flow from leptomeningeal anastomoses. Visual field sparing may occur in surgical occlusion of the PCA, but rarely occurs in stroke. An infarction from PCA occlusion is not excluded by complete visual field sparing, and studies looking for other causes of the neurologic deficit may not be necessary.


Tuberculous pericardial effusion--mediastinal lymph glands: the cause and clue to the etiology.
Tuberculous pericardial effusion is most often due to the spread of tuberculosis from the mediastinal lymph glands; however, no attempt has yet been made to study these glands. We studied the mediastinal glands in proven tuberculous pericardial effusion patients and hypothesized that the findings may be of use in the etiological diagnosis of pericardial effusion. We studied 45 patients with large pericardial effusion or tamponade. All underwent chest computed tomographic studies that were reviewed by radiologists blinded to the diagnosis. Of these 45 patients, 27 had tuberculosis and 18 had viral or idiopathic effusion. Pericardial biopsy was done in 25/27 and tuberculin skin test in 22/27 patients with tuberculosis, and all received specific treatment. In patients with tuberculosis the skin test measured 17+/-3.3 mm. All 27 had mediastinal lymph glands > or = 10 mm in size. The mean size of the mediastinal glands was 19.5+/-8.6 mm and the mean number was 2.5+/-1.2. The aortopulmonary glands were the most frequently enlarged (63%), and hilar the least often (14.8%). The glands showed a hypodense center in 52% of the patients. On follow-up of 15.8+/-10.4 months, glands were not seen in 80.9%, and were smaller in size in 19%; none had a hypodense center. Marked lymphadenopathy was not seen in any patient with viral/idiopathic pericardial effusion. Two had glands < or = 5 mm in size. Only patients with tuberculosis had substantial mediastinal lymph gland enlargement and not those with viral or idiopathic pericardial effusion. Such glands disappeared or regressed on treatment. In the appropriate clinical context, marked nonhilar mediastinal lymphadenopathy on chest computed tomographic studies along with a strongly positive tuberculin skin test could be of value in the noninvasive diagnosis of pericardial effusion due to tuberculosis.