Wave propagation analysis using the variance matrix.
The propagation of a coherent laser wave-field through a pseudo-random phase plate is studied using the variance matrix estimated from Shack-Hartmann wavefront sensor data. The uncertainty principle is used as a tool in discriminating the data obtained from the Shack-Hartmann wavefront sensor. Quantities of physical interest such as the twist parameter, and the symplectic eigenvalues, are estimated from the wavefront sensor measurements. A distance measure between two variance matrices is introduced and used to estimate the spatial asymmetry of a wave-field in the experiment. The estimated quantities are then used to compare a distorted wave-field with its undistorted counterpart.


Efforts towards the design of 'teflon' proteins: in vivo translation with trifluorinated leucine and methionine analogues.
In vivo incorporation of monofluorinated noncanonical amino acids into recombinant proteins has been well-established for decades. Proteins fluorinated in this way proved to be useful tools for many practical applications. In contrast, trifluorinated amino acids have been incorporated in only a few peptides and relatively small proteins by using expression systems in living cells. A novel class of proteins with a fluorous core can be envisaged only if full replacement of the core-building hydrophobic and aliphatic amino acids such as leucine or methionine with the related analogues trifluoromethionine and trifluoroleucine would be feasible. However, our systematic efforts to introduce these amino acids in larger proteins (over 10 Da) that contain different structural motifs clearly show that only partial substitutions are possible. The reasons are high toxicity of these substances and difficulties to accommodate them into the compact cores of natural proteins without adverse effects on their structural integrity. Therefore, engineering of such three dimensional 'Teflon'-like structures would require, besides an expansion of the amino acid repertoire of the genetic code, a de novo protein design as well.


Dental Providers' Perspectives on Diagnosis-Driven Dentistry: Strategies to Enhance Adoption of Dental Diagnostic Terminology.
The routine use of standardized diagnostic terminologies (DxTMs) in dentistry has long been the subject of academic debate. This paper discusses the strategies suggested by a group of dental stakeholders to enhance the uptake of DxTMs. Through unstructured interviewing at the 'Toward a Diagnosis-Driven Profession' National Conference held on 19 March 2016 in Los Angeles, CA, USA participants were asked how enthusiastic they were about implementing and consistently using DxTMs at their work. They also brainstormed on strategies to improve the widespread use of DxTMs. Their responses are summarized by recursive abstraction and presented in themes. Conference participants were very enthusiastic about using a DxTM in their place of work. Participants enumerated several strategies to make DxTMs more appealing including: the use of mandates, a value proposition for providers, communication and education, and integration with EHRs and existing systems. All groups across the dental healthcare delivery spectrum will need to work together for the success of the widespread and consistent use of DxTMs. Understanding the provider perspective is however the most critical step in achieving this goal, as they are the group who will ultimately be saddled with the critical task of ensuring DxTM use at the point of care.


[How do I write a scientific article--advice to a young researcher].
Medical care should be based on the best available scientific evidence, and physicians are frequently engaged in research to contribute to the evidence base. Publishing is a prerequisite for science and publication record is an indicator of the merits of a scientist. The predominant format for publication of medical research is journal articles. Writing a journal article can be a daunting task for a neophyte, and the skill is usually adopted with learning by doing, with little formal training available. This review describes the general structure of an article and the essential contents of each section.


The immunological and structural epidermal barrier dysfunction and skin microbiome in atopic dermatitis-an update.
Atopic dermatitis (AD) is a common, chronic and relapsing inflammatory skin disease with various clinical presentations and combinations of symptoms. The pathophysiology of AD is complex and multifactorial. There are several factors involved in the etiopathogenesis of AD including structural and immunological epidermal barrier defect, imbalance of the skin microbiome, genetic background and environmental factors. Alterations in structural proteins, lipids, proteases, and their inhibitors, lead to the impairment of the stratum corneum which is associated with the increased skin penetration and transepidermal water loss. The elevated serum immunoglobulin E levels and blood eosinophilia have been shown in the majority of AD patients. Type 2 T-helper cell immune pathway with increased expression of interleukin (IL)-4, IL-5, and IL-13, has an important role in the etiopathogenesis of AD. Both T cells and keratinocytes contribute to epidermal barrier impairment in AD via a dynamic interaction of cytokines and chemokines. The skin microbiome is another factor of relevance in the etiopathogenesis of AD. It has been shown that during AD flares, Staphylococcus aureus (S. aureus) colonization increased, while Staphylococcus epidermidis (S. epidermidis) decreased. On the contrary, S. epidermidis and species of Streptococcus, Corynebacterium and Propionibacterium increased during the remision phases. However, it is not clear whether skin dysbiosis is one of the symptoms or one of the causes of AD. There are several therapeutic options, targeting these pathways which play a critical role in the etiopathogenesis of AD. Although topical steroids are the mainstay of the treatment of AD, new biological therapies including IL-4, IL-13, and IL-31 inhibitors, as well as Janus kinase inhibitors (JAKi), increasingly gain more importance with new advances in the therapy of AD. In this review, we summarize the role of immunological and structural epidermal barrier dysfunction, immune abnormalities, impairment of lipids, filaggrin mutation and skin microbiome in the etiopathogenesis of AD, as well as the therapeutic options for AD and their effects on these abnormalities in AD skin.


Anomalous left coronary artery from the pulmonary artery: a rare cause of an out-of-hospital cardiac arrest in an adult-a case report.
Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital disorder resulting in ischaemia and myocardial infarction which can act as a potential substrate for life-threatening arrhythmias and sudden cardiac death. A 19-year-old man was admitted to the hospital after successful resuscitation from an out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation occurring during jogging. In the diagnostic work-up of the OHCA, computed tomography identified an ALCAPA. The patient was referred to our tertiary hospital for surgical correction. Direct reimplantation of the left coronary artery in the aorta was performed. During follow-up, 24-h electrocardiogram revealed short episodes of non-sustained ventricular tachycardia (VT). The magnetic resonance imaging at initial admission showed focal wall thinning and transmural late gadolinium enhancement consistent with a previous anterolateral myocardial infarction. Therefore, the aetiology of the OHCA could be due to a scar-related mechanism and not necessarily due to a reversible cause and an implantable cardioverter-defibrillator (ICD) was considered indicated. Given the young age and the lower complication rates, a subcutaneous device was preferred over a transvenous ICD. However, as a subcutaneous ICD (S-ICD) lacks the possibility of anti-tachycardia pacing, programmed electrical stimulation (PES) was performed to test for inducibility of monomorphic, re-entrant VT. After a negative PES, an S-ICD was implanted. ALCAPA is a potential cause of OHCA in young patients. Some of these patients keep an irreversible substrate for ventricular arrhythmias despite full surgical revascularization and might be candidates for (subcutaneous) ICD implantation.


Anti-inflammatory activities of eleven Centaurea species occurring in the Carpathian Basin.
Our study aimed at the identification of anti-inflammatory activities of different fractions of C. sadleriana extract after per os administration in rats, the identification of the active compounds of the plant and the investigation of the in vitro anti-inflammatory activities of Centaurea species native to or cultivated in the Carpathian Basin. The aerial parts of Centaurea sadleriana Janka have been used in Hungarian folk medicine to treat the wounds of sheep. Methanol extract of C. sadleriana was fractioned by solvent-solvent partitioning. The n-hexane fraction was further fractionated and the anti-inflammatory activities of certain subfractions were confirmed in vivo in rats. The n-hexane and chloroform fraction of the methanol extract of C. sadleriana exhibited remarkable COX-1 and COX-2 inhibiting effects in vitro. Chromatographic separation of the fractions led to the identification of the active subfractions and 11 compounds (α-linolenic acid, γ-linolenic acid, stigmasterol, β-sitosterol, campesterol, vanillin, pectolinarigenin, salvigenin, hispidulin, chrysoeriol and apigenin). The in vitro screening for anti-inflammatory activities of further Centaurea species occurring in the Carpathian Basin (C. adjarica, C. bracteata, C. cataonica, C. cynaroides, C. dealbata, C. indurata, C. macrocephala, C. melitensis, C. nigrescens, C. ruthenica) revealed considerable COX-1 and COX-2 inhibitory activities. Because C. sadleriana is an endangered species native only to the Carpathian Basin, the investigation of more prevalent species is reasonable.


[Chemical constituents in the leave of Rhizophora stylosa L and their biological activities].
Ten compounds were isolated from the leaves of Rhizophora stylosa, one kind of mangrove plants distributed in the tropical and subtropical areas of the world. Their structures were identified as taraxerone (1), taraxerol (2), beta-sitosterol (3), careaborin (4), cis-careaborin (5), beta-daucosterol (6), isovanillic acid (7), protocatechuic acid (8), astilbin (9) and rutin (10), among which compound 9 and 10 were reported in this plant for the first time. Of these compounds, Compound 2 has been confirmed to have the abilities to inhibit the growth of Hela and BGC-823 with IC50 of 73.4 micromol x L(-1) and 73.3 micromol x L(-1), respectively. Compound 5 could inhibit the growth of BGC-823 and MCF-7 with IC50 of 45.9 micromol x L(-1) and 116.0 micromol x L(-1), respectively. Compound 9 and 10 were firstly reported to stimulate the proliferation of mice splenic lymphocytes markedly in a dose-dependent manner.


[Influence of substance P on the proliferation and apoptosis of fibroblasts of pathological scars].
To further explore the effects of substance P on the proliferation and apoptosis of fibroblasts obtained from pathological scars in vitro. Fibroblasts from keloid (KSF) , hypertrophic scar (HSF) and normal dermis (NDF) of 12 burn patients were cultured in vitro and divided into control, SP (with 1 x 10 (-6) mol/L SP added to the culture medium) , and SP + spantide( with 1 x 10 (-6) mol/L SP and 3 x 10 (-5) mol/L spantide added to the culture medium) groups. MTT method or flow cytometry assay was used for the determination of the proliferative activities or apoptotic rate of fibroblasts obtained from KSF, HSF and NDF with SP or Spantide. And then the fibroblasts in SP group were subdivided into 1 x 10( -9) -1 x 10 (-5) mol/L groups to examine the time-or dose-effect of SP to fibroblasts from different sources. In control group, different types of fibroblasts exhibited similar proliferative activities and apoptotic rates. But there was significant difference in these indices between control and SP group (the proliferative activity of KSF, HSF, NDF was 0. 656+/-0. 071, 0. 525 +/-0. 064, 0. 404+/-0. 063, respectively; and the apoptotic rate of KSF, HSF, NDF was [( 1.5+/-0.3) % , (4.0+/-0.5) % , (5.5+/-0.7) % , respectively],( P < 0. 05). SP had stronger effect on KSF than it did to HSF, as well as it had stronger effect on HSF than it did to NDF. In SP + spantide group, the effect of SP on KSF was partially inhibited, while it was completely inhibited in cultures of HSF and NDF. KSF was more sensitive to SP and the effect was longer when compared with HSF. SP may play an important role in the process of pathological scar formation due to its diverse effects on fibroblasts from different sources.


Technological quality, mineral profile, and sensory attributes of broiler chicken breasts affected by White Striping and Wooden Breast myopathies.
The aim of the research was to study the impact of white striping and wooden breast myopathies on the technological quality, mineral, and sensory profile of poultry meat. With this purpose, a total of 138 breasts were selected for a control group with normal breasts (N), a group of breasts characterised by white striping (WS) myopathy, and a group of breasts having both white striping and wooden breast myopathies (WSWB). Data revealed that the simultaneous presence of the two myopathies, with respect to the WS lesion individually considered, had a further detrimental effect on pH (6.04 vs. 5.96; P < 0.05), yellowness (11.4 vs. 10.3; P < 0.01), cooking losses (30.4 vs. 27.6%; P < 0.05), toughness instrumental values (22.8 vs. 20.0 N; P < 0.01), and perception (6.22 vs. 5.56; P < 0.01). In addition, mineral contents suggest that a defective ions regulation is also present in white striping and wooden breast myopathies.


Role of hypothalamic adenosine 5'-monophosphate-activated protein kinase in the impaired counterregulatory response induced by repetitive neuroglucopenia.
Antecedent hypoglycemia blunts counterregulatory responses that normally restore glycemia, a phenomenon known as hypoglycemia-associated autonomic failure (HAAF). The mechanisms leading to impaired counterregulatory responses are largely unknown. Hypothalamic AMP-activated protein kinase (AMPK) acts as a glucose sensor. To determine whether failure to activate AMPK could be involved in the etiology of HAAF, we developed a model of HAAF using repetitive intracerebroventricular (icv) injection of 2-deoxy-D-glucose (2DG) resulting in transient neuroglucopenia in normal rats. Ten minutes after a single icv injection of 2DG, both alpha1- and alpha2-AMPK activities were increased 30-50% in arcuate and ventromedial/dorsomedial hypothalamus but not in other hypothalamic regions, hindbrain, or cortex. Increased AMPK activity persisted in arcuate hypothalamus at 60 min after 2DG injection when serum glucagon and corticosterone levels were increased 2.5- to 3.4-fold. When 2DG was injected icv daily for 4 d, hypothalamic alpha1- and alpha2-AMPK responses were markedly blunted in arcuate hypothalamus, and alpha1-AMPK was also blunted in mediobasal hypothalamus 10 min after 2DG on d 4. Both AMPK isoforms were activated normally in arcuate hypothalamus at 60 min. Counterregulatory hormone responses were impaired by recurrent neuroglucopenia and were partially restored by icv injection of 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside, an AMPK activator, before 2DG. Glycogen content increased 2-fold in hypothalamus after recurrent neuroglucopenia, suggesting that glycogen supercompensation could be involved in down-regulating the AMPK glucose-sensing pathway in HAAF. Thus, activation of hypothalamic AMPK may be important for the full counterregulatory hormone response to neuroglucopenia. Furthermore, impaired or delayed AMPK activation in specific hypothalamic regions may play a critical role in the etiology of HAAF.


[The L-arginine-nitric oxide system: physiology, physiopathology and clinical relevance].
In this review we describe what is known about nitric oxide (NO), focusing on its clinical significance. It is now well appreciated that NO is a pivotal endogenous messenger molecule in a variety of physiological and pathophysiological processes. In the cardiovascular system NO participates in the paracrine regulation of vascular tone, body fluid homeostasis and platelet aggregation and adhesion. In the nervous system NO is a neurotransmitter that underpins several functions, including the formation of memory. In addition, NO is produced in large quantities during host defense and immunologic reactions. Perturbation in NO bioactivity has been shown to represent an important pathophysiologic mechanism underlying a number of disease states, such as atherosclerosis, hypertension, diabetes mellitus, and septic shock.


A war against the natural order: Joseph Nicolosi, Reparative Therapy, and the Christian Right.
This article situates Joseph Nicolosi's first book, Reparative Therapy of Male Homosexuality, in historical context. Nicolosi, a Catholic clinical psychologist, was one of the most vocal practitioners of sexual orientation change efforts (SOCE) from the early 1990s until his death in 2017, and in these decades, the Christian Right became a key supporter of SOCE. In this article, I argue that two features of Nicolosi's book appealed to the Christian Right. First, Nicolosi relied on psychoanalytic thought to pathologize not only same-sex sexual desires but also poor parenting. The use of psychoanalytic thought was of particular interest to conservative Christians who believed that American fathers had forfeited their role as strong patriarchs. Second, Nicolosi's approach to therapy, which included changing one's dress and mannerisms and assertiveness training, stressed that same-sex desires could be eliminated through behavioral reconditioning. Nicolosi's psychological eclecticism, a common feature for mental health practitioners at the end of the twentieth century, has not been emphasized in prior scholarship on reparative therapy. Importantly, the psychological eclecticism practiced by Nicolosi became common within the Christian Right after the publication of Reparative Therapy of Male Homosexuality. By offering a close reading of Reparative Therapy of Male Homosexuality, this article demonstrates the interrelationship between one of the core texts of the ex-gay movement and the psychological and religious thought of the Christian Right at the turn of the twenty-first century. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Time course of endothelial adaptation after acute and chronic exercise in patients with metabolic syndrome.
Clustering of cardiovascular risk factors may lead to endothelial dysfunction. Physical exercise is an important factor in prevention and treatment of endothelial dysfunction. We wanted to determine the time course of adaptation to a single bout of exercise at either high or moderate intensity upon endothelial function both before and after a 16-week fitness program in patients with metabolic syndrome. Twenty-eight patients with metabolic syndrome participated in the study and were randomized and stratified (according to age and sex) into an aerobic interval exercise training group (AIT, n = 11), a continuously moderate-intensity exercise training group (CME, n = 8) or to a control group (n = 9). Flow-mediated dilatation (FMD) was determined at baseline, immediately, 24, 48, and 72 hours after 1 bout of exercise and repeated after 16 weeks of exercise. In the untrained state, FMD improved from 5 to 11% (p = 0.003) immediately after a single bout of aerobic interval training (AIT), an effect lasting 72 hours postexercise. In comparison, continuous moderate exercise (CME) improved FMD immediately after a single bout of exercise from 5 to 8% (p = 0.02), an effect lasting 24 hours postexercise (group difference, p < 0.001). In the trained state, a single bout of AIT resulted in a 2% (p = 0.007) acute increase of FMD lasting 48 hours postexercise. The CME increased FMD by 3% (p < 0.01), an effect lasting 24 hours postexercise (group difference p = 0.0012). Blood glucose level decreased after 1 single bout of AIT in the untrained state (p < 0.05), and the effect lasted at least 72 hours postexercise (p < 0.01). Acute CME decreased blood glucose with normalization of the values 24 hours postexercise (p < 0.01). A single bout of exercise in the trained state reduced fasting blood glucose by 10% (p < 0.05) after both AIT and CME. Exercise training, especially high intensity, thus appears to be highly beneficial in reducing blood glucose and improving endothelial function.


Impacts of a disease management program for dually eligible beneficiaries.
The LifeMasters Supported SelfCare demonstration program provides disease management (DM) services to Florida Medicare beneficiaries who are also enrolled in Medicaid and have congestive heart failure (CHF), diabetes, or coronary artery disease (CAD). The population-based program provides primarily telephonic patient education and monitoring services. Findings from the randomized, intent-to-treat design over the first 18 months of operations show virtually no overall impacts on hospital or emergency room (ER) use, Medicare expenditures, quality of care, or prescription drug use for the 33,000 enrollees. However, for beneficiaries with CHF who resided in high-cost South Florida counties, the program reduced Medicare expenditures by 9.6 percent.


Particle size of latex beads dictates IL-1β production mechanism.
Macrophages (Mϕ) are well documented to produce IL-1β through various signaling pathways in response to small particles such as silica, asbestos and urea crystals, in the presence of lipopolysaccharide (LPS). However, it has not been clear to what extent particle size affects the response. To investigate this point, we stimulated bone marrow-derived macrophages (BMDM) with size-defined latex beads (LxB). Although both nano-sized (20 nm) and micro-sized (1,000 nm) LxB induced IL-1β production, only the nano-sized particles formed large intracellular vacuoles. In contrast, 100 nm LxB did not induce either of the responses. The same cellular responses were also observed in primary microglia cells. Although K(+) efflux and NLRP3 activation in BMDM were crucial in response to both 20 and 1,000 nm LxB, only IL-1β production by 20 nm LxB was sensitive to cathepsin B and P2X7, a receptor for ATP. The response by 1,000 nm LxB relied on a robust production of reactive oxygen species (ROS), since IL-1β production was remarkably reduced by ROS inhibitors such as diphenylene iodonium (DPI) and N-acetylcysteine (NAC). In contrast, IL-1β production by 20 nm LxB was augmented by NAC and in BMDM deficient in thioredoxin-binding protein-2 (TBP-2), a negative regulator of the ROS scavenger thioredoxin. These results suggest that the cells responded differently in their secretion of IL-1β depending on particle size, and that there is a range within which neither pathway works.


Computer-assisted stereotactic biopsy of intracranial lesions in pediatric patients.
A computer-assisted stereotactic biopsy technique has been used in 30 patient (ages 5 months to 16 years) with intracranial lesions (supratentorial in 23 and infratentorial in 7). The computer program integrates stereotactically gathered imaging data and permits preoperative planning of a biopsy trajectory. Diagnostic tissue was obtained in 27 cases. In 2 cases, therapeutic interventions--third ventriculostomy and cyst aspiration--were accomplished at the time of the biopsy. There were no major complications related to the procedure; however, 2 patients had transient neurologic deficits. Computer-assisted stereotactic biopsy is a valuable diagnostic procedure in the pediatric patient with an intracranial lesion.


Plasma Level Formaldehyde in Children Receiving Pulpotomy Treatment under General Anesthesia.
Formocresol has long been used by dentists for pulpotomy of primary teeth. Due to some concerns regarding its possible carcinogenicity, formocresol has been the topic of numerous studies. This study sought to assess the changes in plasma level of formaldehyde of children after receiving pulpotomy under general anesthesia. Twenty-five children between 2-6 years requiring dental treatments under general anesthesia were studied. Blood samples were taken of children before and after the procedure. Plasma level of formaldehyde was measured using high performance liquid chromatography (HPLC). A total of 106 pulpotomy treatments were performed in 25 children using 126 cotton pellets dipped in formocresol. An increase and a decrease in plasma level of formaldehyde were noted in 5 (20%) and 20 (80%) children, respectively post-operatively compared to baseline. The t-test showed no significant difference in plasma level of formaldehyde pre- and postoperatively (P=0.12). the plasma level of formaldehyde in children who had higher levels of formaldehyde prior to the operation was also higher than that of others after the operation and this association was statistically significant (P=0.001, r=0.64). The results showed no significant change in the mean plasma level of formaldehyde in children who received pulpotomy under general anesthesia compared to its baseline value.


[Characteristics and regulatory mechanisms of lipid metabolism remodeling after malignant transformation of glioma-associated macrophages].
Objective: To observe the lipid metabolism characteristics of tumor-associated macrophages (TAM) after malignant transformation in the glioma micro-environment, and analyze the biological phenotype changes and regulatory mechanisms after inhibiting the lipid metabolism remodeling. Methods: Twelve male Balb/c mice of 6-8 weeks were used in the study. Macrophages (Mφ) were derived from mouse bone marrow, and malignantly transformed macrophages (tMφ1 and tMφ2) were cloned from the model of glioma stem cell (GSC) through interaction with Mφ in vivo and in vitro. Intracellular lipid droplet formation and cellular cholesterol content were measured respectively in Mφ, tMφ1 and tMφ2. qRT-PCR was performed to detect the genes expression level related with lipid metabolism, including sterol regulatory element binding protein (SREBP), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase (HMG-CoA). Simvastatin (SIM) was used to analyze the proliferation, immigration and invasiveness ability in tMφ1 and tMφ2 after inhibition of the lipid metabolism. Differential expression profiles of miRNAs after SIM treatment were constructed in t-Mφ1 and bio-informatics analysis was screened and verified for miR449a and its target gene sorting micro-tubule connectin 17 (SNX17) associated with lipid metabolism remodeling. The effect on SNX17 by up-regulated miR-449a were analyzed by qRT-PCR and Western blot, meanwhile, the biological phenotype and cholesterol content were observed after up-regulation of miR449a. Low-density lipoprotein receptor (LDLR) protein levels after SNX17 knockdown and intracellular cholesterol content after LDLR knockdown were detected respectively. Results: The numbers of intracellular lipid droplet formation in tMφ1 and tMφ2 were more than that in Mφ (P<0.001). Likewise, the relative contents of cholesterol (3.89±0.68 and 3.56±0.53), SREBP (4.78±0.60 and 2.84±0.41), FASN (4.65±0.70 and 3.01±0.45), and HMG-CoA (5.74±0.55 and 2.97±0.34) were significantly higher in tMφ1 and tMφ2 than those of Mφ (1.01 wel, 1.02 wel and 0.99 wel, respectively) (all P<0.001). The proliferation rates of tMφ1 and tMφ2 decreased from (47.06±5.88) % and (45.29±5.64)% to (23.53±4.70)% and (18.74±5.76)%, respectively after treatment with SIM (both P<0.05). The numbers of migrated cells decreased from 1 025±138 and 350±47 to 205±63 and 99±25, respectively (both P<0.001). And the numbers of invasiveness cells decreased from 919±45 and 527±34 to 220±23 and 114±21, respectively (both P<0.001). While the relative intracellular cholesterol content decreased to 0.52±0.08 and 0.58±0.07 (both P<0.05), respectively. MiR-449a was screened from tMφ1 by SIM, and the target gene was analyzed and verified to be SNX17. SNX17 expression was down-regulated, and the proliferation rate, the number of migration and invasiveness was significantly decreased after miR-449a over-expression (all P<0.05). Low-density lipoprotein receptor (LDLR) expression was down-regulated after knock-down of SNX17, while the cholesterol content was decreased after knock-down of LDLR in tMφ1 and tMφ2 (all P<0.05). Conclusions: Malignantly transformed TAMs undergo lipid metabolism remodeling characterized with enhanced lipid metabolism. MiR-449a regulates the LDLR by targeting SNX17, thereby affecting the lipid metabolism of malignantly transformed macrophages, and subsequently inhibiting its proliferation, migration, and invasion ability. Precise intervention with miR-449a/SNX17/LDLR axis could provide an experimental basis for reversing its tumor-promoting micro-environment remodeled by GSC through metabolic intervention.


Kinetic evidence for the formation of monocationic N,N'-disubstituted phthalamide in tertiary amine-catalyzed hydrolysis of N-substituted phthalimides.
A kinetic study on the aqueous cleavage of N-(2-methoxyphenyl)phthalimide (1) and N-(2-hydroxyphenyl)phthalimide (2), under the buffers of N-methylmorpholine, reveals the equilibrium presence of monocationic amide (Ctam) formed due to nucleophilic reactions of N-methylmorpholine with 1 and 2. Pseudo-first-order rate constants for the reactions of water and HO- with Ctam (formed through nucleophilic reaction of N-methylmorpholine with 1) are 4.60 x 10(-5) s-1 and 47.9 M-1 s-1, respectively. But the cleavage of Ctam, formed through nucleophilic reaction of N-methylmorpholine with 2, involves intramolecular general base (2'-O- group of Ctam)-assisted water attack at carbonyl carbon of cationic amide group of Ctam in or before the rate-determining step.


Serum thyroxine levels in patients receiving L-thyroxine suppression or replacement therapy.
Serum thyroxine (T(4)) and protein-bound iodine (PBI) levels were measured in 140 adult patients receiving L-thyroxine, 0.2 or 0.3 mg. daily for at least six months, as suppression or replacement therapy. All were judged to be clinically euthyroid at the time of the measurements. The mean PBI was 8.3 mug./100 ml. and the mean T(4) was 10.8 mug./100 ml. The range of values for the PBI was 3.5 to 13.2 and for the T(4) was 3.1 to 17.0. Because of the wide range of values, it is considered that the judgement of whether a patient is euthyroid on L-thyroxine therapy should be based primarily on clinical evaluation and only secondarily on serum T(4) or PBI levels.


Perspectives on Ligand/Protein Binding Kinetics Simulations: Force Fields, Machine Learning, Sampling, and User-Friendliness.
Computational techniques applied to drug discovery have gained considerable popularity for their ability to filter potentially active drugs from inactive ones, reducing the time scale and costs of preclinical investigations. The main focus of these studies has historically been the search for compounds endowed with high affinity for a specific molecular target to ensure the formation of stable and long-lasting complexes. Recent evidence has also correlated the in vivo drug efficacy with its binding kinetics, thus opening new fascinating scenarios for ligand/protein binding kinetic simulations in drug discovery. The present article examines the state of the art in the field, providing a brief summary of the most popular and advanced ligand/protein binding kinetics techniques and evaluating their current limitations and the potential solutions to reach more accurate kinetic models. Particular emphasis is put on the need for a paradigm change in the present methodologies toward ligand and protein parametrization, the force field problem, characterization of the transition states, the sampling issue, and algorithms' performance, user-friendliness, and data openness.


Electromagnetic Saturation of Angstrom-Sized Quantum Barriers at Terahertz Frequencies.
Metal-graphene-metal hybrid structures allow angstrom-scale van der Waals gaps, across which electron tunneling occurs. We squeeze terahertz electromagnetic waves through these λ/10 000 000 gaps, accompanied by giant field enhancements. Unprecedented transmission reduction of 97% is achieved with the transient voltage across the gap saturating at 5 V. Electron tunneling facilitated by the transient electric field strongly modifies the gap index, starting a self-limiting process related to the barrier height. Our work enables greater interplay between classical optics and quantum tunneling, and provides optical indices to the van der Waals gaps.


Corticotropin-releasing hormone inhibits melatonin secretion in healthy volunteers--a potential link to low-melatonin syndrome in depression?
Interactions between the hypothalamic-pituitary-adrenocortical (HPA) system and melatonin secretion have been demonstrated, but only the effects of melatonin on the activity of the HPA system have been studied in man. Alterations of melatonin secretion described as low-melatonin syndrome have been demonstrated in patients suffering from a major depressive episode, and an inhibitory factor on melatonin secretion has been postulated. We investigated whether corticotropin-releasing hormone (CRH), which is thought to be involved in HPA abnormalities in depressed patients, can also suppress melatonin secretion in healthy volunteers. Ten healthy male human volunteers in a double-blind study design received randomized hourly intravenous injections from 08.00 to 18.00 h that contained 10 micrograms human CRH, 1 microgram adrenocorticotropic hormone (ACTH), or placebo to simulate pulsatile hormone secretion. Plasma melatonin and cortisol responses during the treatment and nocturnal sleep electroencephalograms after the treatment were recorded. Administration of CRH reduced melatonin secretion significantly below values obtained after administration of placebo and ACTH. Cortisol secretion was significantly enhanced by ACTH in comparison to both placebo and CRH. Electroencephalographic sleep parameters revealed no treatment effects. Our findings suggest that CRH has an inhibitory effect on the pineal secretion of melatonin in normal man. A mechanism via a release of cortisol was not supported by our results. Secondary hormonal effects from changes in nocturnal sleep architecture were excluded. Further investigation of the action of CRH on melatonin secretion as well as the mutual feedback between the HPA system and the pineal gland may extend our knowledge of neuroendocrine alterations mediating the adaptive response to stress and the eventual involvement in the pathogenesis of depression.


Bulging mesothelial cells of the visceral pleura of the rat mimic the network of subpleural lymphatics.
The mesothelial surface of the visceral pleura of the Wistar rat was viewed at high resolution by scanning electron microscopy (SEM). The pleural surface showed exquisite linear arrangements made up of bulging mesothelial cells. They were organized in irregular circles that often presented anastomotic junctures. This arrangement of pleural mesothelial cells mimics the organization of subpleural lymphatics of the lung. A low density of microvilli was seen inside the irregular circles, contrasting with the microvilli-rich mesothelial cells seen on or outside these arrangements. These SEM features of the mesothelium may be related with the formation of microdomains for fluid absorption across the visceral pleura into subpleural lymphatics.


Modern Stereoselective Synthesis of Chiral Sulfinyl Compounds.
Chiral sulfinyl compounds, sulfoxides, sulfoximines, sulfinamides, and other derivatives, play an important role in asymmetric synthesis as versatile auxiliaries, ligands, and catalysts. They are also recognized as pharmacophores found in already marketed and well-sold drugs (e.g., esomeprazole) and used in drug design. This review is devoted to the modern methods of preparation of sulfinyl derivatives in enantiopure or enantiomerically enriched form. Selected new approaches leading to racemic products for which the asymmetric variant can be developed in the future are mentioned as well.


Physician-to-physician telephone consultations for chronic pain patients: A pragmatic randomized trial.
The impact of telephone consultations between pain specialists and primary care physicians regarding the care of patients with chronic pain is unknown. To evaluate the impact of telephone consultations between pain specialists and primary care physicians regarding the care of patients with chronic pain. Patients referred to an interdisciplinary chronic pain service were randomly assigned to either receive usual care by the primary care physician, or to have their case discussed in a telephone consultation between a pain specialist and the referring primary care physician. Patients completed a numerical rating scale for pain, the Pain Disability Index and the Short Form-36 on referral, as well as three and six months later. Primary care physicians completed a brief survey to assess their impressions of the telephone consultation. Eighty patients were randomly assigned to either the usual care group or the standard telephone consultation group, and 67 completed the study protocol. Patients were comparable on baseline pain and demographic characteristics. No differences were found between the groups at six months after referral in regard to pain, disability or quality of life measures. Eighty percent of primary care physicians indicated that they learned new patient care strategies from the telephone consultation, and 97% reported that the consultation answered their questions and helped in the care of their patient. Most primary care physicians reported that a telephone consultation with a pain specialist answered their questions, improved their patients' care and resulted in new learning. Differences in patient status compared with a usual care control group were not detectable at six-month follow-up. While telephone consultations are clearly an acceptable strategy for knowledge translation, additional strategies may be required to actually impact patient outcomes.


[A preliminary study of retinoblastoma-related serum tumor markers].
To screen out retinoblastoma (RB)-related serum tumor markers by measuring the levels of serum alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) in children with RB. The levels of seven serum tumor markers (AFP, CEA, NSE, CA125, CA153, CA199, and CA724) were determined in 20 children with RB and 20 healthy children (control) using a chemiluminescent immunoassay. The serum levels and positive rates of NSE, CA153, and CA199 in the RB group were significantly higher than those in the control group (P<0.05). However, there were no significant differences in the levels of AFP, CEA, CA125, and CA724 between the two groups (P>0.05). NSE had the highest sensitivity, but a relatively low specificity for the diagnosis of RB. CA153 and CA199 had a relatively high specificity, but a relatively low sensitivity for the diagnosis of RB. The serum levels and positive rates of NSE, CA153, and CA199 are high in children with RB. Combined measurement of these three serum tumor markers may have an important diagnostic value for RB.


HIV seropositivity in a burn center's population.
HIV infection in a patient with burn injuries complicates the care of both the patient and the treating burn team. In the patient, HIV slows wound healing and increases the complications seen with burns. For the treating team, HIV is a hazard that infects the large volume of bodily fluids to which the burn team is potentially exposed. At Saint Francis Memorial Hospital, a team of plastic surgeons, infectious disease specialists, medical internists, psychiatrists, social workers, and nurses was established for the care of patients with burn injuries who have HIV. To ascertain the baseline need for this specialized care, we interviewed 103 consecutive patients admitted to the Bothin Burn Center. Those found to be positive by history (3 of 103) were excluded from HIV testing. Of the remaining 100 consecutive patients, all consented to HIV testing. None of these patients, even those with known risk factors, was found to have undiagnosed HIV positivity. We conclude the occult incidence in the population tested is lower than expected, and continued testing is warranted.


5-Methyl-phenanthro[2,3-b]thio-phene.
The title compound, C(17)H(12)S, which crystallises with two molecules in the asymmetric unit, features four fused rings forming an essentially planar mol-ecule, with maximum deviations from the mean plane of 0.078 (2) and 0.080 (2) Å for C atoms of the thio-phene and phenanthrene groups in both the mol-ecules. The crystal packing features weak C-H⋯π inter-actions.


Current stand on systemic therapy in localized soft tissue sarcomas: a clinician's perspective.
Soft tissue sarcomas (STS) are rare heterogenous tumors derived from mesenchymal tissue. While surgery represents the primary treatment modality, the high recurrence rates following surgery alone necessitate consideration for systemic therapy in high-risk sarcomas. Despite multiple trials and meta-analyses over the last 3 decades, the role of chemotherapy remains controversial. It is crucial to accurately identify patients with high-risk diseases who may benefit the most from adjuvant and/or neoadjuvant chemotherapy. There is renewed interest in the potential to improve outcomes in localized resectable STSs with the addition of targeted and immunotherapeutic strategies. The review presented here is a summary of current evidence on systemic therapy in resectable localized STSs of the trunk and extremities to facilitate clinician decision-making.


Population genetics of Camellia granthamiana, an endangered plant species with extremely small populations in China.
Introduction: Camellia, the largest genus of Theaceae, is well-known for having high economic values. Camellia granthamiana demonstrates large beautiful flowers with some primitive characters, such as multiple large and persistent bracteoles and sepals, was listed as Vulnerable species on the IUCN Red List. Methods: In this study, we investigated all possible records of the species, and sampled four natural populations and five cultivated individuals. By applying shallow-genome sequencing for nine individuals and RAD-seq sequencing for all the sampled 77 individuals, we investigated population genetic diversity and population structure of the species. Results and discussion: The results showed that the population sampled from Fengkai, previously identified as C. albogigias, possessed different plastid genome from other species possibly due to plastid capture; the species possesses strong population structure possibly due to the effect of isolation by distance, habitat fragmentation, and self-crossing tendency of the species, whose effective population size declined quickly in the past 4,000 years. Nevertheless, C. granthamiana maintains a medium level of genetic diversity within population, and significant differentiation was observed among the four investigated populations, it is anticipated that more populations are expected to be found and all these extant populations should be taken into instant protection.


The effect of process and formulation variables on the properties of spray-dried beta-galactosidase.
The objective of this study was to evaluate the joint effects of various processing and formulation variables on the properties of spray-dried beta-galactosidase using statistically designed experiments. The key response variables evaluated were product yield, residual enzymatic activity, moisture content and particle size and appearance. The residual enzymatic activity and product yield were significantly affected by the processing variables. The highest product yields were obtained when the drier outlet temperature was relatively high, resulting in extensive protein denaturation. Subsequent experiments, therefore, compared the relative effectiveness of four stabilizers (mannitol, sucrose, arginine hydrochloride and trehalose) in terms of their ability to preserve enzymatic activity during the spray-drying process and during long-term storage. Trehalose was the most suitable stabilizer. The effect of a number of other formulation variables (total solids level, ratio of stabilizer to protein, presence of surfactant and presence of buffer) was also investigated. A final formulation consisting of 6% beta-galactosidase and 10% trehalose in deionized water was selected. Spray-drying at inlet and outlet temperatures of 140 and 95 degrees C, respectively, results in greater than 70% yields of a fully active product with a moisture content of 2-5% and a mean particle size of 2-4 microns.


A comparison of generic drug prices in seven European countries: a methodological analysis.
Policymakers and researchers frequently compare the prices of medicines between countries. Such comparisons often serve as barometers of how pricing and reimbursement policies are performing. The aim of this study was to examine methodological challenges to comparing generic drug prices. We calculated all commonly used price indices based on 2013 IMS Health data on sales of 3156 generic drugs in seven European countries. There were large differences in generic drug prices between countries. However, the results varied depending on the choice of index, base country, unit of volume, method of currency conversion, and therapeutic category. The results also differed depending on whether one looked at the prices charged by manufacturers or those charged by pharmacists. Price indices are a useful statistical approach for comparing drug prices across countries, but researchers and policymakers should interpret price indices with caution given their limitations. Price-index results are highly sensitive to the choice of method and sample. More research is needed to determine the drivers of price differences between countries. The data suggest that some governments should aim to reduce distribution costs for generic drugs.


Interleukin-1 promotes proliferation of vascular smooth muscle cells in coordination with PDGF or a monocyte derived growth factor.
We report that interleukin-1 (IL-1) potentiates the proliferation of vascular smooth muscle cells. Growth of early passage smooth muscle cells was not significantly affected by IL-1 alone. Treatment with IL-1 together with the platelet derived growth factor (PDGF) or another polypeptide growth factor derived from mitogen activated human monocytes (MDGF) resulted in a significant enhancement of cell growth over either PDGF or MDGF alone. DNA synthesis was enhanced only marginally (30-40%) in quiescent cultures treated with an optimal concentration of IL-1 alone. In the presence of 5 units/ml of PDGF or MDGF, IL-1 produced about six- to eightfold higher DNA synthesis than the untreated cultures. Induction of DNA synthesis was linear between 0.1 and 1.0 pM IL-1, dependent on PDGF concentration, and was effectively neutralized by monoclonal antibodies against IL-1 beta. The growth promoting activity of IL-1 was extremely potent producing half-maximum stimulation at a concentration of 0.5 pM. These results suggest that IL-1 may play an important role in the modulation of growth and other activities of vascular smooth muscle cells. These observations are especially important with regard to defining the potential macrophage derived mediators contributing to vascular cell proliferation during inflammation and the pathogenesis of atherosclerosis. It is shown here that elicitation of IL-1 induced growth response requires a coordinated action with another priming growth factor such as PDGF. In this regard, IL-1 mediated proliferation of smooth muscle cells may have analogy with the IL-1 mediated T-cell activation and IL-2 production where concerted actions of antigen/mitogen and IL-1 are required.


Diagnosis of stenosis in a pulmonary valve-conduit using an angioplasty guide and probing catheter.
A 42-year-old man who had undergone previous Blalock-Taussig anastomoses and placement of a homograft aortic valve-root conduit for tetralogy of Fallot presented with dyspnea at rest. Previous catheterization had shown homograft stenosis at the level of the pulmonic valve. Repeat catheterization necessitated the use of angioplasty guide and probing catheters to cross the stenosis, and pullback documented stenoses both across the homografted valve and within the homograft aortic root-native pulmonary artery conduit.


Non-REM sleep with hypertonia in Parkinsonian Spectrum Disorders: A pilot investigation.
From an ongoing multicenter effort toward differentiation of Parkinsonian spectrum disorders (PSD) from other types of neurodegenerative disorders, the sleep biomarker non-rapid-eye-movement sleep with hypertonia (NRH) emerged. This study included in the PSD group patients with dementia with Lewy bodies/Parkinson disease dementia (DLB/PDD = 16), Parkinson disease (PD = 16), and progressive supranuclear palsy (PSP = 13). The non-PSD group included patients with Alzheimer disease dementia (AD = 24), mild cognitive impairment (MCI = 35), and a control group with normal cognition (CG = 61). In-home, multi-night Sleep Profiler studies were conducted in all participants. Automated algorithms detected NRH, characterized by elevated frontopolar electromyographic power. Between-group differences in NRH were evaluated using Logistic regression, Mann-Whitney U and Chi-squared tests. NRH was greater in the PSD group compared to non-PSD (13.9 ± 11.0% vs. 3.1 ± 4.7%, P < 0.0001). The threshold NRH≥5% provided the optimal between-group differentiation (AUC = 0.78, P < 0.001). NRH was independently associated with the PSD group after controlling for age, sex, and SSRI/SNRI use (P < 0.0001). The frequencies of abnormal NRH by subgroup were PSP = 92%, DLB/PDD = 81%, PD = 56%, MCI = 26%, AD = 17%, and CG = 16%. The odds of abnormal NRH in each PSD subgroup ranged from 3.7 to 61.2 compared to each non-PSD subgroup. The night-to-night and test-retest intraclass correlations were excellent (0.78 and 0.84, both P < 0.0001). In this pilot study, NRH appeared to be a novel candidate sleep biomarker for PSD-related neurodegeneration. Future studies in larger cohorts are needed to confirm these findings, understand the etiology of NRH magnitude/duration, and determine whether it is an independent prodromal marker for specific neurodegenerative pathologies.


Therapeutic plasmapheresis and plasma exchange.
Plasma exchange is a process in which large volumes of plasma, usually equivalent to one plasma volume, are exchanged with donor plasma or a plasma substitute. This permits the removal of antibody, immune complexes, inflammatory mediators, paraproteins, drugs, toxins, and other plasma constituents. Plasma exchange may also have an effect on the immune system by enhancing the function of the reticuloendothelial system, removing blocking antibody, increasing clearance of tumor cells, and making lymphocytes more vulnerable to immunosuppressive drugs. Over 100 diseases have been treated with plasma exchange with variable success. Results of controlled studies are less dramatic than those of earlier uncontrolled case reports. Reports of complications and even death have tempered initial enthusiasm. Now, over a decade since the initial promising reports began to appear in the literature, the role of plasma exchange remains undefined.


D-penicillamine induced changes on rat mast cell cyclic GMP levels.
The cGMP accumulation in rat serosal mast cells was measured after cell treatment with D-penicillamine, a sulphydryl containing compound. Preincubating the cells with increasing doses of the drug causes a decrease of basal level of the nucleotide. In cells activated with the degranulating agent 48/80 there is a sharp increase in cGMP intracellular levels. D-Penicillamine prevents the nucleotide accumulation caused by compound 48/80, decreasing even the steady-state level in activated cells. The effect on cGMP metabolism does not correspond to an inhibition of histamine release.


Neonatal brucellosis: A case report.
Although brucellosis is not uncommon in Saudi Arabia, neonatal brucellosis has been infrequently reported. In this case of neonatal brucellosis, Brucella abortus was isolated by blood culture from both the mother and the neonate. Serology was positive only in the mother.


Novel use of an endovascular embolectomy device for retrograde suction decompression-assisted clip ligation of a large paraclinoid aneurysm: technical case report.
Several different methodologies for proximal occlusion and retrograde suction decompression of large paraclinoid aneurysms have been reported previously. In this article, we describe the novel use of an endovascular embolectomy device (F.A.S.T. funnel catheter; Genesis Medical Interventional, Inc., Redwood City, CA) for temporary internal carotid artery occlusion and suction decompression of an intracranial aneurysm to facilitate surgical clip ligation. The combination of atraumatic occlusion technology and large lumen size makes this technique safer and easier. A 53-year-old woman with progressive headaches underwent computed tomographic angiography, which revealed an unruptured large left paraclinoid aneurysm. Cerebral angiography confirmed the diagnosis. The patient did not tolerate a balloon test occlusion for therapeutic Hunterian internal carotid occlusion. The patient was subsequently taken to the operating room for a craniotomy and clip ligation of the aneurysm. A standard left pterional craniotomy was performed with opening of the sylvian fissure and exposure of the left paraclinoid aneurysm. Intraoperative angiography with introduction of a new endovascular embolectomy device was performed. The device was deployed to achieve temporary occlusion of the cervical internal carotid artery, and aspiration through the central lumen allowed for retrograde suction decompression of the aneurysm. Collapse of the aneurysm through this technique permitted visualization of the aneurysmal neck with successful clip ligation. A new endovascular embolectomy device can be used to safely perform suction decompression of large paraclinoid aneurysms to facilitate clip ligation.


Corneal ulcer due to Neocosmospora vasinfecta in an immunocompetent patient.
We report a case of Neocosmospora vasinfecta keratitis in a 55-year-old man. While the patient did not recall any specific trauma or eye injury, he might have sustained a trivial wound during the course of his duties as a farmer. Direct examination of corneal scrapings revealed fungus filaments. As topical treatment with natamycin and econazole and subsequent systemic ketoconazole therapy failed, a full thickness therapeutic keratoplasty was performed. Post-operative treatment with amphotericin B and clotrimazole combined with cyclosporine resulted in a complete cure. The residual corneal infiltration in the recipient cornea became clear in a week. The fungal isolate was initially identified as a Fusarium species, but later reidentified through the use of morphological characteristics and sequence analysis of the internal transcribed spacer region as N. vasinfecta. The latters is a Hypocrealean fungus not hitherto reported as a causative agent of keratomycosis.


Preparation of pH-responsive mesoporous hydroxyapatite nanoparticles for intracellular controlled release of an anticancer drug.
A well-defined core-shell nano-carrier (PAA-MHAPNs) was successfully synthesized based on a graft-onto method by using mesoporous hydroxyapatite nanoparticles (MHAPNs) as the core and polyacrylic acid (PAA) as the shell. Given that MHAPNs are regarded as one of the most promising drug delivery vehicles due to their excellent performance and the nature of their cancer cell anti-proliferative effect, and the grafted PAA, as a pH-responsive switch, could improve the loading amount of the drug doxorubicin hydrochloride (DOX) effectively by electrostatic interactions, all these advantages mean that the designed models show promise for application in pH-responsive drug delivery systems. The loading content and entrapment efficiency of DOX could reach up to 3.3% and 76%, respectively. The drug release levels of the constructed DOX@PAA-MHAPNs were low under normal physiological conditions (pH 7.4), but they could be increased significantly with a decrease of pH. Cytotoxicity assays indicated that the PAA-MHAPNs was biocompatible, and more importantly, the DOX@PAA-MHAPNs demonstrated an obvious ability to induce apoptosis of cancer cells. Overall, the synthesized systems should show great potential as drug nanovehicles with excellent biocompatibility, high drug loading, and pH-responsive features for future intracellular drug delivery.


Recombinant Paragonimus westermani yolk ferritin is a useful serodiagnostic antigen.
A recombinant protein of Paragonimus westermani yolk ferritin was bacterially produced from a previously cloned complementary DNA and was used as an antigen for an enzyme-linked immunosorbent assay (ELISA) against paragonimiasis- and other helminth-infected sera to evaluate its serodiagnostic potential. The ELISA revealed that paragonimiasis westermani had 88.2% sensitivity and 100% specificity. The positive and negative predictive values of the ELISA were calculated to be 100% and 97.1%, respectively. Sera from cats experimentally infected with P. westermani began to produce immunoglobulin G antibodies against the yolk ferritin at 13 weeks after infection, which suggests that the corresponding antigen was derived from the vitellaria in accordance with maturation of P. westermani. These results indicate that the recombinant P. westermani yolk ferritin is a potent serodiagnostic reagent for paragonimiasis westermani from an early stage of the infection.


[Restoration of transcription antitermination of N- bacteriophages in Escherichia coli with a mutant RNA polymerase].
The N protein of bacteriophage lambda modifies Escherichia coli RNA polymerase in such a way that it transcribes through termination signals, in a process called antitermination. In general N-mutants are not able to perform transcription antitermination. In this paper we report the suppression of N7 and Nmar3 mutations by Escherichia coli ron-lon strain. The lon mutation causes the N protein half-life to raise, suggesting that excess of N7 fragment or Nmar3 protein overcome the defect in antitermination. Under these conditions the lambda N-phages produced a titer similar to lambda wild type, although the plaques were smaller. These observations highlight the relevance of N half life in the regulation of transcription antitermination.


The effect of biochar and crop straws on heavy metal bioavailability and plant accumulation in a Cd and Pb polluted soil.
Biochar derived from various materials has been investigated with regard to its ability to decrease the bioavailability of heavy metals in contaminated soils, and thus reduce their potential to enter the food chain. However, little attention has been given to the adsorption capacity of untreated crop straws, which are commonly used as a biochar feedstock, especially in soils. Hence, this study was conducted to investigate the effect of crop straws on heavy metal immobilization and subsequent heavy metal uptake by maize and ryegrass in a soil artificially polluted by Cd and Pb. Bamboo biochar, rice straw, and wheat straw were mixed into soil four weeks before the experiment, enabling them to reach equilibrium at 2% (w/w), 1% (w/w), and 1% (w/w), respectively. The results showed that soil pH for both species was significantly increased by all treatments, except when wheat straw was used for ryegrass cultivation. Soil organic carbon was only improved in the rice straw treatment and the soil alkali-hydrolyzable N content was significantly decreased with all of the amendments, which may have contributed to the lack of an effect on plant biomass. Soil available Cd was significantly lower in the rice straw treatment than in the control soil, while Pb levels clearly decreased in wheat straw treatment. The Cd concentration in shoots of maize was reduced by 50.9%, 69.5%, and 66.9% with biochar, rice straw, and wheat straw, respectively. In addition, shoot Cd accumulation was decreased by 47.3%, 67.1%, and 66.4%, respectively. Shoot Pb concentration and accumulation were only reduced with the rice straw treatment for both species. However, metal uptake in plant roots was more complex, with increased metal concentrations also detected. Overall, the direct application of crop straw could be considered a feasible way to immobilize selected metals in soil, once the long-term effects are confirmed.


Introduction of new laryngeal closure methods for patients with intractable aspiration.
The aging population in Japan has recently resulted in a rapid increase in elderly individuals. Airway management is thus being required more and more often. Aspiration pneumonia is a life-threatening problem among patients with swallowing problems. Several new surgical methods of laryngeal closure that are easier and safer than previous methods have been developed. Among these new methods, we have performed the Kano method as closure of the larynx using double flaps of the divided craniad vocal folds and the divided caudad vocal folds with partial resection of the thyroid and cricoid cartilages for patients with intractable aspiration. We encountered minor leakage in two patients, but these soon closed spontaneously. This procedure is less invasive than other methods such as total laryngectomy and tracheal separation and has great advantages in terms of low blood loss and short duration of the operation.


Altered Ca2+ signalling in human neutrophils from inflammatory sites.
To determine whether the intracellular store release of Ca2+ in neutrophils from patients with rheumatoid arthritis, other joint disease and active leg ulceration was different from normal neutrophils. The release into the cytosol of Ca2+ from stores within individual neutrophils was determined using ratiometric imaging of fura2. The size of the elevated Ca2+ 'cloud' and its concentration were quantified in neutrophils from the circulation of patients with rheumatoid arthritis, other joint diseases, and leg ulcers and from the joints of those with joint disease. In neutrophils isolated from both the synovial fluid of patients with rheumatoid arthritis and other joint conditions, and also arising from leg ulcers, the amount of the cell cytosol occupied by elevated Ca2+ was significantly increased compared with neutrophils from healthy subjects; for neutrophils from rheumatoid, non-rheumatoid joints and leg ulcers p values were 0.0006, < 0.0001, 0.016 respectively (Student's t test). There was also a significant increase in Ca2+ release from circulating neutrophils from patients with rheumatoid arthritis (p = 0.09), but not in circulating neutrophils from patients with leg ulcers or non-rheumatoid joint conditions. It is proposed that the increased release of free Ca2+ into the cytosol of neutrophil at inflammatory sites results in increased oxidase activation.


Three cases of urolithiasis associated with sarcoidosis: a review of Japanese cases.
We report three cases of urolithiasis associated with sarcoidosis and reviewed the Japanese published reports. All cases had hypercalcemia, hyperuricemia, hypercalciuria and renal dysfunction. A serum level of 1,25-(OH)2D3 was elevated and intact parathyroid hormone (PTH) was decreased. Stone components were predominantly calcium oxalate. Abnormal calcium metabolism is a well-known feature of sarcoidosis and the reported prevalence of urolithiasis in patients with sarcoidosis was 1.3-14.0% in the English published reports. However, urolithiasis associated with sarcoidosis is uncommon in Japan and we could find only 16 documented cases including ours. Abnormal calcium metabolism is caused by an increase in serum concentration of 1,25-(OH)2D3, which is derived from endogenous overproduction in the pulmonary macrophages. If patients with urolithiasis have abnormal calcium metabolism, renal impairment and suppression of PTH, the possibility of sarcoidosis should be considered for a differential diagnosis. Also, it should be emphasized that the presence or developing of urolithiasis is to be monitored during follow up of patients with sarcoidosis.


Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis.
Silymarin, a plant flavonoid from milk thistle (Silybum marianum [L.] GAERTNER) was first evaluated for its protective effect against UV irradiation-induced apoptosis in human malignant melanoma cells (A375-S2 cells). Treatment with silymarin 500 microM for 12 h significantly inhibited UV irradiation (2.4 J/cm(2), 5 min)-induced apoptosis in A375-S2 cells. Activities of caspase-9 and caspase-3 in UV-irradiated A375-S2 cells were effectively reduced by silymarin in a dose-dependent manner, while the expression of the inhibitor of caspase-activated DNase (ICAD), protein expression of Bcl-x(L) (Bcl-2 family member), and the activity of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) were increased simultaneously. It is suggested that the inhibitory effect of silymarin is exerted by blockage of the caspase/ICAD pathway after increased expression of Bcl-x(L) protein and activation of the ERK/MAPK pathway.


Unilateral choroidal neovascular membrane as a herald lesion for Crohn's disease.
Crohn's disease is a diffuse inflammatory disease primarily affecting the gastrointestinal tract but with associated ophthalmologic complications that often appear after the initial diagnosis. The authors report a case in which the appearance of a choroidal neovascular membrane prior to the final diagnosis of Crohn's disease suggests its role as an advance lesion heralding an inflammatory state. A 13-year-old boy was referred for evaluation of a clinically isolated, unilateral choroidal neovascular membrane, which stabilized after treatment with intravitreal bevacizumab. Two years later, the patient was diagnosed with Crohn's disease. Choroidal neovascular membranes, reported previously as a complication of Crohn's disease following diagnosis, may be a precursor lesion.


The kinetic analysis of the N-methylation of 4-phenylpyridine by nicotinamide N-methyltransferase: Evidence for a novel mechanism of substrate inhibition.
The N-methylation of 4-phenylpyridine produces the neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+). We investigated the kinetics of 4-phenylpyridine N-methylation by nicotinamide N-methyltransferase (NNMT) and its effect upon 4-phenylpyridine toxicity in vitro. Human recombinant NNMT possessed 4-phenylpyridine N-methyltransferase activity, with a specific activity of 1.7 ± 0.03 nmol MPP+ produced/h/mg NNMT. Although the Km for 4-phenylpyridine was similar to that reported for nicotinamide, its kcat of 9.3 × 10-5 ± 2 × 10-5 s-1 and specificity constant, kcat/Km, of 0.8 ± 0.8 s-1 M-1 were less than 0.15% of the respective values for nicotinamide, demonstrating that 4-phenylpyridine is a poor substrate for NNMT. At low (<2.5 mM) substrate concentration, 4-phenylpyridine N-methylation was competitively inhibited by dimethylsulphoxide, with a Ki of 34 ± 8 mM. At high (>2.5 mM) substrate concentration, enzyme activity followed substrate inhibition kinetics, with a Ki of 4 ± 1 mM. In silico molecular docking suggested that 4-phenylpyridine binds to the active site of NNMT in two non-redundant poses, one a substrate binding mode and the other an inhibitory mode. Finally, the expression of NNMT in the SH-SY5Y cell-line had no effect cell death, viability, ATP content or mitochondrial membrane potential. These data demonstrate that 4-phenylpyridine N-methylation by NNMT is unlikely to serve as a source of MPP+. The possibility for competitive inhibition by dimethylsulphoxide should be considered in NNMT-based drug discovery studies. The potential for 4-phenylpyridine to bind to the active site in two binding orientations using the same active site residues is a novel mechanism of substrate inhibition.


Effects of communication burstiness on consensus formation and tipping points in social dynamics.
Current models for opinion dynamics typically utilize a Poisson process for speaker selection, making the waiting time between events exponentially distributed. Human interaction tends to be bursty though, having higher probabilities of either extremely short waiting times or long periods of silence. To quantify the burstiness effects on the dynamics of social models, we place in competition two groups exhibiting different speakers' waiting-time distributions. These competitions are implemented in the binary naming game and show that the relevant aspect of the waiting-time distribution is the density of the head rather than that of the tail. We show that even with identical mean waiting times, a group with a higher density of short waiting times is favored in competition over the other group. This effect remains in the presence of nodes holding a single opinion that never changes, as the fraction of such committed individuals necessary for achieving consensus decreases dramatically when they have a higher head density than the holders of the competing opinion. Finally, to quantify differences in burstiness, we introduce the expected number of small-time activations and use it to characterize the early-time regime of the system.


Diacetyl emissions and airborne dust from butter flavorings used in microwave popcorn production.
In microwave popcorn workers, exposure to butter flavorings has been associated with fixed obstructive lung disease resembling bronchiolitis obliterans. Inhalation toxicology studies have shown severe respiratory effects in rats exposed to vapors from a paste butter flavoring, and to diacetyl, a diketone found in most butter flavorings. To gain a better understanding of worker exposures, we assessed diacetyl emissions and airborne dust levels from butter flavorings used by several microwave popcorn manufacturing companies. We heated bulk samples of 40 different butter flavorings (liquids, pastes, and powders) to approximately 50 degrees C and used gas chromatography, with a mass selective detector, to measure the relative abundance of volatile organic compounds emitted. Air sampling was conducted for diacetyl and for total and respirable dust during the mixing of powder, liquid, or paste flavorings with heated soybean oil at a microwave popcorn plant. To further examine the potential for respiratory exposures to powders, we measured dust generated during different simulated methods of manual handling of several powder butter flavorings. Powder flavorings were found to give off much lower diacetyl emissions than pastes or liquids. The mean diacetyl emissions from liquids and pastes were 64 and 26 times larger, respectively, than the mean of diacetyl emissions from powders. The median diacetyl emissions from liquids and pastes were 364 and 72 times larger, respectively, than the median of diacetyl emissions from powders. Fourteen of 16 powders had diacetyl emissions that were lower than the diacetyl emissions from any liquid flavoring and from most paste flavorings. However, simulated handling of powder flavorings showed that a substantial amount of the airborne dust generated was of respirable size and could thus pose its own respiratory hazard. Companies that use butter flavorings should consider substituting flavorings with lower diacetyl emissions and the use of ventilation and enclosure engineering controls to minimize exposures. Until controls are fully implemented, companies should institute mandatory respiratory protection for all exposed workers.


Nonuniform speaker normalization using affine transformation.
In this paper, a well-motivated nonuniform speaker normalization model that affinely relates the formant frequencies of speakers enunciating the same sound is proposed. Using the proposed affine model, the corresponding universal-warping function that is required for normalization is shown to have the same parametric form as the mel scale formula. The parameters of this universal-warping function are estimated from the vowel formant data and are shown to be close to the commonly used formula for the mel scale. This shows an interesting connection between nonuniform speaker normalization and the psychoacoustics based mel scale. In addition, the affine model fits the vowel formant data better than commonly used ad hoc normalization models. This work is motivated by a desire to improve the performance of speaker-independent speech recognition systems, where speaker normalization is conventionally done by assuming a linear-scaling relationship between spectra of speakers. The proposed affine relation is extended to describe the relationship between spectra of speakers enunciating the same sound. On a telephone-based connected digit recognition task, the proposed model provides improved recognition performance over the linear-scaling model.


Influence of Group 15 elements on the [3 + 2] cycloaddition reactivity of G15 = G15-G15-based 1,3-dipoles with cyclooctyne.
The influence of Group 15 elements (G15s) on the reactivity of the cycloaddition reactions of inorganic 1,3-dipolar analogs with cyclooctyne was computationally explored with density functional theory. To this end, the G15G15G15'-based 1,3-dipole, an interestingly representative model molecule of 1,3-dipole chemistry, was selected. The present computational investigations suggest that all NNG15-Rea and G15G15P-Rea molecules can be energetically feasible to undergo 1,3-dipolar cycloaddition reactions with cyclic alkynes, except for only the NNN-Rea 1,3-dipole molecule. The key factor, which can greatly affect the activation barriers, is quantitatively analyzed in detail through the frontier molecular orbital (FMO) theory, the activation strain model (ASM), and the energy decomposition analysis (EDA) approach. Our theoretical findings based on the FMO theory and the EDA suggest that two types of bonding interactions occur in such 1,3-dipolar cycloaddition reactions: forward bonding (filled p-π orbital (cyclooctyne) → the empty p-π* orbital (G15 = G15)) and back bonding (empty p-π* orbital (cyclooctyne) ← the lone pair (G15')). Notably, the bonding interactions of the former mechanism are much stronger than those of the latter mechanism. Evidence from the ASM reveals that the activation barriers of G15G15G15'-based 1,3-dipolar cycloaddition reactions strongly depend on the atomic radius of the G15 element. These theoretical conclusions allow a number of predictions to be made.


EFNS guidelines on management of narcolepsy.
Management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioral measures can be of notable value. Guidelines on the management of narcolepsy have already been published. However contemporary guidelines are necessary given the growing use of modafinil to treat excessive daytime sleepiness in Europe within the last 5-10 years, and the decreasing need for amphetamines and amphetamine-like stimulants; the extensive use of new antidepressants in the treatment of cataplexy, apart from consistent randomized placebo-controlled clinical trials; and the present re-emergence of gamma-hydroxybutyrate under the name sodium oxybate, as a treatment of all major symptoms of narcolepsy. A task force composed of the leading specialists of narcolepsy in Europe has been appointed. This task force conducted an extensive review of pharmacological and behavioral trials available in the literature. All trials were analyzed according to their class evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive daytime sleepiness and irresistible episodes of sleep in association with behavioral measures. However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Given the availability of modafinil and methylphenidate, and the forseen registration of sodium oxybate for narcolepsy (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in Europe, the place of other compounds will become fairly limited. Since its recent registration cataplexy sodium oxybate has now become the first-line treatment of cataplexy. Second-line treatments are antidepressants, either tricyclics or newer antidepressants, the later being increasingly used these past years despite few or no randomized placebo-controlled clinical trials. As for disturbed nocturnal sleep the best option is still hypnotics until sodium oxybate is registered for narcolepsy. The treatments used for narcolepsy, either pharmacological or behavioral, are diverse. However the quality of the published clinical evidences supporting them varies widely and studies comparing the efficacy of different substances are lacking. Several treatments are used on an empirical basis, specially antidepressants for cataplexy, due to the fact that these medications are already used widely in depressed patients, leaving little motivation from the manufacturers to investigate efficacy in relatively rare indications. Others, in particular the more recently developed substances, such as modafinil or sodium oxybate, are evaluated in large randomized placebo-controlled trials. Our objective was to reinforce the use of those drugs evaluated in randomized placebo-controlled trials and to reach a consensus, as much as possible, on the use of other available medications.


[Expression of ERK1/2 protein in lung tissues of newborn rats with hyperoxia-induced chronic lung disease].
To study the expression of extracellular signal regulated protein kinase (ERK) 1/2 in lung tissues of newborn rats with chronic lung disease (CLD) caused by hyperoxia. Forty-eight full-term newborn rats were randomly divided into two groups: hyperoxia and control. The two groups were exposed to a hyperoxic gas mixture (0.90 O(2)) for an induction of CLD and room air within 12 hrs after birth, respectively. The levels of ERK1/2 protein and mRNA in lung tissues were measured using immunohistochemistry, Western blot and real-time PCR methods on postnatal days 3, 7 and 14. The severity of pulmonary fibrosis was evaluated. The expression of p-ERK protein in lung tissues in the hyperoxia group was significantly higher than that in the control group on postnatal days 7 and 14 (P<0.01). There were no significant differences in the levels of total ERK1/2 protein and ERK1/2 mRNA. The activation of phosphorated ERK1/2 may lead to lung fibrosis caused by hyperoxia in newborn rats.


Frequent Harderian gland adenocarcinomas in inbred white-footed mice (Peromyscus leucopus).
In 1997, three lines of inbred Peromyscus leucopus--GS109A, GS16A1, and GS16B--were acquired by the Peromyscus Genetic Stock Center. Since then, records have been kept on tumors detected by visible inspection of live animals. The inbred lines GS109A and GS16A1 presented tumors with frequencies substantially higher than that of the other inbred line or of random-bred P. leucopus stock. The average age of detection was 456 +/- 75 days (n = 24) for GS109A and 568 +/- 168 days (n = 12) for GS16A1 respectively. Surprisingly, the majority of the tumors (23 of 24 for GS109A and 8 of 12 for GS16A1) appeared to be Harderian gland lesions. During the same time period only a single tumor, a fibrosarcoma, was noted in the other inbred strain (GS16B), and one Harderian gland tumor was detected in the random bred stock. On the basis of the number of animals born to each group, tumor frequencies were approximately 22.7%, 8.3%, 0.67%, and 0.07%, for GS109A, GS16A1, GS16B, and randombred P. leucopus stock, respectively. The periocular tumors appeared to be highly malignant, with elevated mitotic indices, marked anaplasia, and metastases to regional lymph nodes and lungs. The tumors were readily transplantable to other animals of the same line. Among various other species, malignant Harderian gland tumors are relatively rare.


Magnetic dichroism and spin structure of antiferromagnetic NiO(001) films.
We find that Ni L2 edge x-ray magnetic linear dichroism is fully reversed for NiO(001) films on materials with reversed lattice mismatch. We relate this phenomenon to a preferential stabilization of magnetic S domains with main spin component either in or out of the plane, via dipolar interactions. This suggests a way to selectively control spin structures in 3d systems with small spin-orbit coupling.


Energetics of Water Polyhedra with Square Faces.
In ice and other icelike systems, the structural variety of tetrahedrally coordinated systems increases strongly due to proton disorder. Configurations that differ from each other only by the arrangement of hydrogen atoms (protons) in hydrogen bonds are nonequivalent. Polyhedral water clusters are interesting objects of study since the analysis of the energetics of these tetrahedrally coordinated systems reveals very simple regularities. For water polyhedra of the most regular shape, the simplified physical model of strong and weak effective H bonds (the SWEB model) has been developed. This model allows predicting the classes of the most stable proton configurations. The number of H bonds that are more preferable from the point of view of Coulomb interaction is the only classification criterion for this model. For water polyhedra with square faces, this model becomes less accurate. However, for such clusters, there is another essential topological indicator: the number of molecules that are completely located in the planes of square faces. The results of numerous calculations show that these two topological indices largely determine the energetics of a huge number of proton configurations in water polyhedra with square faces.


Epidemiology of Diphtheria in India, 1996-2016: Implications for Prevention and Control.
Diphtheria is an acute disease caused by exotoxin-producing Corynebacterium diphtheriae. Globally, diphtheria has been showing a declining trend due to effective childhood vaccination programs. A substantial proportion of global burden of diphtheria is contributed by India. Hospital-based surveillance studies as well as diphtheria outbreaks published in last 20 years (1996-2016) indicate that diphtheria cases are frequent among school-going children and adolescents. In some Indian states, Muslim children are affected more. As per the national level health surveys, coverage of three doses of diphtheria vaccine was 80% during 2015-2016. Information about coverage of diphtheria boosters is not routinely collected through these surveys, but is expected to be low. Few studies also indicate low diphtheria immunity among school-going children and adults. The strategies for prevention of diphtheria need to focus on improving coverage of primary and booster doses of diphtheria vaccines administered as a part of Universal Immunization Program as well as introducing diphtheria vaccine for school-going children.


Sex determination from metacarpals and the first proximal phalanx.
Sex determination using metacarpals and the first proximal phalanx was carried out on a sample (n = 60) of documented sex. Six measurements were taken on each of metacarpals 1 to 5 and the first proximal phalanx. Regression equations were calculated for determining sex from the bones. The equations were then applied to a second sample (n = 20) also of documented sex to establish the degree of accuracy they produced in assigning sex. The equations for metacarpal 1 produced the highest degree of correct sex determination and overall the degree of accuracy ranged from 74% to 94%.


Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of alpha2 and beta1 integrins and CD44.
The three-step model of cell migration consisting of protrusion of a leading lamella, attachment to the substrate, and contraction of the cell body is well established for fibroblasts migrating across planar surfaces. However, it is not resolved to what extent the migration of cancer cells in a 3-dimensional tissue environment follows similar principles. Here, we present evidence that the migration of highly invasive MV3 melanoma cells in 3-dimensional collagen matrices follows the three-step concept of migration but also results in characteristic reorganization of the extracellular matrix. After incorporation in the lattice, MV3 cells spontaneously developed a slow type of migration (mean velocity, 0.19 microm/min), leading to alignment of collagen fibers at attachment sites, as detected from unfixed and fixed samples by confocal reflection contrast in combination with immunofluorescence staining. In the process of migration, the formation of focal clusters or stripes of alpha2 and beta1 integrins colocalized with binding sites to collagen fibrils at the leading as well as the trailing edge. In contrast, CD44 was nonclustered and redistributed toward the rear end of the cell. At detachment sites, dynamic fiber traction, localized fiber disruption, and the release of cell surface determinants, including alpha2beta1 integrins and CD44, resulted in circumscribed matrix reorganization. Not infrequently, these emerging tube-like paths of least resistance bordered by a dense fiber network facilitated the reorientation and contact guidance of proximate MV3 cells to migrate along the preexisting path. In conclusion, the migration of MV3 cells in 3-dimensional collagen lattices resulted in dynamic tissue reorganization and receptor shedding the consequences of which were directly visualized by combining confocal reflection imaging with immunofluorescence.


Comparison of Laparoscopic Common Bile Duct Exploration with Endoscopic Retrograde Cholangiopancreatography for Common Bile Duct Stones After Cholecystectomy.
Background: Few studies have focused on the treatment of common bile duct (CBD) stones after cholecystectomy, for which optimal treatment options remain unclear. Aims: To compare the safety and efficacy of laparoscopic common bile duct exploration (LCBDE) versus endoscopic retrograde cholangiopancreatography (ERCP) for CBD stone treatment after cholecystectomy. Materials and Methods: A total of 201 patients were enrolled in this retrospective cohort study, of whom 134 with ≤3 stones and a maximum stone diameter of <15 mm were classified as subgroup 1, and 67 with >3 stones or a maximum stone diameter of ≥15 mm were classified as subgroup 2. Perioperative characteristics were also analyzed. Results: ERCP subgroup 1 exhibited a shorter operative time (P < .001), postoperative hospital stay (P < .001), and lower incidence of bile leakage (P = .034) than LCBDE subgroup 1. ERCP subgroup 2 exhibited a shorter operative time (P < .001) and shorter postoperative hospital stay (P < .001) than LCBDE subgroup 2. However, LCBDE subgroup 2 exhibited a greater rate of complete stone removal (P = .044) and a lower incidence of acute pancreatitis (P = .037) than ERCP subgroup 2. Conclusions: For treatment of CBD stones after cholecystectomy, ERCP was superior in cases involving ≤3 stones and a maximum stone diameter of <15 mm. Among those with >3 stones or maximum stone diameter of ≥15 mm, LCBDE demonstrated certain advantages.


Acute renal failure due to nontraumatic rhabdomyolysis.
Twenty-one patients developed acute renal failure in association with nontraumatic rhabdomyolysis and myoglobinuria. The illness followed an overdose of ethanol, heroin, or other depressant drug in 18 patients. Lethargy or coma was present in 17 patients and muscle swelling in 11. Evidence of rhabdomyolysis included markedly elevated creatine phosphokinase, myoglobinuria, and aldolase in blood. Initial biochemical findings were similar to those of acute renal failure due to other causes, but the abnormalities were exaggerated. There was a disproportionate rise in serum creatinine concentration in relation to serum urea nitrogen concentration. Profound hyperuricemia was present in most patients. Transient hypercalcemia developed during the diuretic phase in 5 patients. One patient died. We conclude that nontraumatic myoglobinuria with acute renal failure is not infrequent and may occur after an overdose of ethanol or heroin. The disease has good prognosis despite severe hypercatbolism and untreated profound hyperuricemia.


Deterministic modelling and stochastic simulation of biochemical pathways using MATLAB.
The analysis of complex biochemical networks is conducted in two popular conceptual frameworks for modelling. The deterministic approach requires the solution of ordinary differential equations (ODEs, reaction rate equations) with concentrations as continuous state variables. The stochastic approach involves the simulation of differential-difference equations (chemical master equations, CMEs) with probabilities as variables. This is to generate counts of molecules for chemical species as realisations of random variables drawn from the probability distribution described by the CMEs. Although there are numerous tools available, many of them free, the modelling and simulation environment MATLAB is widely used in the physical and engineering sciences. We describe a collection of MATLAB functions to construct and solve ODEs for deterministic simulation and to implement realisations of CMEs for stochastic simulation using advanced MATLAB coding (Release 14). The program was successfully applied to pathway models from the literature for both cases. The results were compared to implementations using alternative tools for dynamic modelling and simulation of biochemical networks. The aim is to provide a concise set of MATLAB functions that encourage the experimentation with systems biology models. All the script files are available from www.sbi.uni-rostock.de/ publications_matlab-paper.html.


[Concentrations of kininogen and prekallikrein in plasma and activity of plasma renin depending on the type of blood pressure response to captopril in patients with arterial hypertension].
The dynamics was analysed of changes of arterial blood pressure, plasma kininogen and prekallikrein concentrations and plasma renin activity (PRA) in 50 patients with arterial hypertension, in relation to the type of blood pressure response to captopril. It was shown that after three weeks of treatment with captopril 150 mg daily, in 23 patients (46%) normalization of systolic and diastolic blood pressure occurred, and in 27 patients (54%), despite a significant reduction, blood pressure normalization was not achieved. In both groups of patients a significant decrease of plasma kininogen concentration and an increase of plasma prekallikrein level were found, indicating kininogenase activation and PRA increase. However, only in patients with arterial blood pressure normalization, a return of kininogen concentration to normal value was observed and a twofold increase of PRA in relation to the initial value was noted. Our studies indicate that in patients with arterial hypertension treated with captopril a correlation appears between the changes of plasma kinin system and PRA which determines the mode of blood pressure reaction to captopril.


Principles of evaluation of the diagnostic value of subgingival bacteria.
This paper describes steps in the process of evaluating subgingival bacteria assays for the diagnosis of periodontal disease. The first step examines the infectious etiology of periodontal disease in pointing to specific oral bacteria as periodontal pathogens. Second is characterization of the laboratory test to detect and quantitate these pathogens as to sensitivity, specificity, and positive and negative predictive value. Third is the role of the laboratory test in the diagnosis of the different forms of periodontal disease which is related to the current clinical rather than microbiological definition of these diseases. The fourth and most important step is an analysis of the significance of subgingival bacterial tests in clinical decision-making.


Cytoprotective effect of short-term pretreatment with proanthocyanidin on human gingival fibroblasts exposed to harsh environmental conditions.
Our previous study showed that exposing mouse fibroblasts to proanthocyanidin (PA) for only 1 min accelerated cell proliferation in a concentration-dependent manner. In this study, exposing human gingival fibroblasts (HGFs) to PA for 1 min similarly accelerated the proliferative response of the cells. Besides the accelerated proliferative response, PA showed a cytoprotective effect on HGFs exposed to harsh environmental conditions; short-term exposure of HGFs in the mitotic phase to pure water or physiological saline resulted in a lower recovery of viable cells. Pretreatment and concomitant treatment with PA improved the low recovery of cells exposed to pure water or physiological saline. In addition, HGFs exposed to PA for 1 min proliferated well even after being cultured in serum-free medium. In 100% confluent HGFs, being cultured in serum-free medium resulted in a high intracellular reactive oxygen species (ROS) level, but pretreatment with PA prevented the cells from increasing intracellular ROS. Thus, the results suggest that a short-term PA treatment exerts cytoprotective effects on HGFs exposed to harsh environmental conditions by improving the intracellular oxidative stress response.


[Antisense oligonucleotides containing 1-(beta-D-2'-deoxy-threo-pentofuranosyl)thymine at the 3'- and 5'-end].
Oligonucleotides with 3'- and 5'-terminal 1-(beta-D-2'-deoxy-threo-pentafuranosyl)thymin residues (inversion at C3'-atom) were obtained by the automatic phosphoramidite synthesis. The modifications protect oligonucleotides from the nuclease degradation and do not affect the stability of nucleic acid duplexes.


Indoor Self-Powered Perovskite Optoelectronics with Ultraflexible Monochromatic Light Source.
Self-powered skin optoelectronics fabricated on ultrathin polymer films is emerging as one of the most promising components for the next-generation Internet of Things (IoT) technology. However, a longstanding challenge is the device underperformance owing to the low process temperature of polymer substrates. In addition, broadband electroluminescence (EL) based on organic or polymer semiconductors inevitably suffers from periodic spectral distortion due to Fabry-Pérot (FP) interference upon substrate bending, preventing advanced applications. Here, ultraflexible skin optoelectronics integrating high-performance solar cells and monochromatic light-emitting diodes using solution-processed perovskite semiconductors is presented. n-i-p perovskite solar cells and perovskite nanocrystal light-emitting diodes (PNC-LEDs), with power-conversion and current efficiencies of 18.2% and 15.2 cd A-1 , respectively, are demonstrated on ultrathin polymer substrates with high thermal stability, which is a record-high efficiency for ultraflexible perovskite solar cell. The narrowband EL with a full width at half-maximum of 23 nm successfully eliminates FP interference, yielding bending-insensitive spectra even under 50% of mechanical compression. Photo-plethysmography using the skin optoelectronic device demonstrates a signal selectivity of 98.2% at 87 bpm pulse. The results presented here pave the way to inexpensive and high-performance ultrathin optoelectronics for self-powered applications such as wearable displays and indoor IoT sensors.


Aggressive desmoplastic fibromatosis - a clinicians dilemma case report and review of literature.
Fibromatoses are a heterogeneous group of distinct entities which differ in biological behaviour, but arehistologically very similar. This group of fibrous tumor or tumor like lesions, present considerable difficulties in pathologic diagnosis. Aggressive fibromatosis (AF) of the oral or para-oral structures is a very uncommon finding and its intra-osseous component is even relatively unusual. Such lesions with their origin from within the bone are termed desmoplastic fibromatosis (DF). These lesions must be distinguished from other fibroblastic tumors of the head and neck such as benign fibrous histiocytoma (BFH), fibrosarcoma, nerve sheath tumors and tumors of muscular origin. The major challenge in dealing with lesions of fibromatosis is to avoid an overdiagnosis of fibrosarcoma or an underdiagnosis of reactive fibrosis.Problems of differential diagnosis concern a wide range of diseases and immunohistochemical analysis may be helpful in diagnosis. With respect to the patient's post-operative well-being and if periodic follow-ups are guaranteed, the tumor should be carefully resected with only narrow safety margins. A rare case of aggressive desmoplastic fibromatosis in a 12-year-old girl is presented in this article with emphasis on the need and challenges for diagnosing such lesions as they have to be differentiated from other soft tissue tumors which display borderline pathological features regarding benign or malignant behaviour. Synonyms listed for the same include extra-abdominal desmoids, extra-abdominal fibromatosis, desmoids tumor, aggressive fibromatosis, juvenile desmoids-type fibromatosis, infantile fibromatosis.


Self-monitoring personality at work: a meta-analytic investigation of construct validity.
The validity of self-monitoring personality in organizational settings was examined. Meta-analyses were conducted (136 samples; total N = 23,191) investigating the relationship between self-monitoring personality and work-related variables, as well as the reliability of various self-monitoring measures. Results suggest that self-monitoring has relevance for understanding many organizational concerns, including job performance and leadership emergence. Sample-weighted mean differences favoring male respondents were also noted, suggesting that the sex-related effects for self-monitoring may partially explain noted disparities between men and women at higher organizational levels (i.e., the glass ceiling). Theory building and additional research are needed to better understand the construct-related inferences about self-monitoring personality, especially in terms of the performance, leadership, and attitudes of those at top organizational levels.