Mixed atomistic and coarse-grained molecular dynamics: simulation of a membrane-bound ion channel.
The recently developed multiscale coarse-graining (MS-CG) method (Izvekov, S.; Voth, G. A. J. Phys. Chem. B 2005, 109, 2469; J. Chem. Phys. 2005, 123, 134105) is used to build a mixed all-atom and coarse-grained (AA-CG) model of the gramicidin A (gA) ion channel embedded in a dimyristoylphosphatidylcholine (DMPC) lipid bilayer and water environment. In this model, the gA peptide was described in full atomistic detail, while the lipid and water molecules were described using coarse-grained representations. The atom-CG and CG-CG interactions in the mixed AA-CG model were determined using the MS-CG method. Molecular dynamics (MD) simulations were performed using the resulting AA-CG model. The results from simulations of the AA-CG model compare very favorably to those from all-atom MD simulations of the entire system. Since the MS-CG method employs a general and systematic approach to obtain effective interactions from the underlying all-atom models, the present approach to rigorously develop mixed AA-CG models has the potential to be extended to many other systems.


Prevalence of obstructive sleep apnea in children and adolescents with sickle cell anemia.
To estimate the prevalence of obstructive sleep apnea syndrome (OSAS) in children and adolescents with sickle cell anemia (SCA); to investigate the possible correlation between mean annual hemoglobin level and total sleep time with SpO2 < 90%, as well as between mean annual hemoglobin level and total sleep time with SpO2 < 80%; and to investigate the possible correlation between apnea-hypopnea index (AHI) and painful crisis. The study involved 85 patients with SCA. The patients completed a questionnaire, were submitted to polysomnography and underwent clinical evaluation (by a pediatrician and an otolaryngologist). An AHI > 1 was considered indicative of a diagnosis of OSAS. The prevalence of OSAS was 10.6%. We found a negative correlation between mean annual hemoglobin level and total sleep time with SpO2 < 90% (r = micro0.343; p = 0.002), as well as between mean annual hemoglobin level and total sleep time with SpO2 < 80% (r = micro0.270; p = 0.016). There was no association between AHI and painful crisis. The prevalence of OSAS in this population was high (10.6%). Therefore, it is important to identify signs of OSAS as soon as possible and to determine the mean annual hemoglobin level because of the inverse correlation between that level and the total sleep time with SpO2 < 90% or < 80%.


An investigation of Jezebel stereotype awareness, gendered racial identity and sexual beliefs and behaviours among Black adult women.
Evidence suggests that the intersectional nature of Black women's race and gender identities influence their awareness of sexual scripts such as the hypersexual, Jezebel stereotype. This study examined the role of the Jezebel stereotype and Black women's identity beliefs on their sexual beliefs and behaviours. Specifically, we investigated the role of gendered racial identity beliefs on the relationship between Jezebel stereotype awareness and Black women's sexual behaviours (sexual assertiveness, sexual satisfaction, sexual guilt and attachment avoidance in relationships). A diverse national sample of Black women completed measures of gendered racial identity beliefs, Jezebel stereotype awareness and sexual behaviours. Black women who felt more positively connected to their Black woman identity reported greater sexual assertiveness and satisfaction. Consistent with past research, more awareness of the Jezebel stereotype was associated with higher sexual guilt and attachment avoidance. We discuss the enduring legacy of the Jezebel stereotype in relation to Black women's gendered racial identity beliefs, as well as the importance of promoting positive sexual beliefs and a sense of sexual agency among Black women in the USA.


Picture perfect staffing in today's economy.
This article describes the methods one Cancer Registry Department used to justify adequate staffing and obtain approval for an increase in full-time employees (FTEs). Each day it is getting more difficult to keep up with registry work while hospitals are compensating for loss of income by implementing changes that often impact staffing. Departments such as Cancer Registries, which are historically understaffed, must find ways to keep up with increasing workloads. If a hospital intends to maintain accreditation by the American College of Surgeons (ACoS) Commission on Cancer (CoC) and the treatment facility of choice for cancer patients, it is the opinion of this author that administrators must realize that adequate staff for the Cancer Registry Department is essential.


The expression and alternative splicing of alpha-neurexins during Xenopus development.
The neurexins are involved in the formation and function of synapses. Each of three genes encodes alpha- and beta-neurexins. Additional diversity (particularly of alpha-neurexins) arises from alternative splicing, resulting in a large number of protein isoforms, the significance of which is currently unclear. We have analysed alpha neurexin expression and alternative splicing during development of the frog Xenopus laevis. Surprisingly, each alpha-neurexin gene is expressed in immature oocytes. During embryonic development, each Xenopus neurexin (nrxn) gene has a distinct temporal expression pattern, with expression being almost exclusively within the neuroepithelium. The spatial expression of nrxnIalpha and nrxnIIalpha is similar in the developing CNS, with staining being observed in the optic cup and in dorsolateral regions of anterior neural tube, but not adjacent to the ventral midline. The pattern of nrxnIIIalpha expression is more restricted, in several domains of the anterior neural tube. In the forebrain, expression was confined to an area in the ventrolateral neural tube; nrxnIIIalpha was also expressed in the hindbrain and spinal cord. By stage 32, a period when synaptogenesis occurs, nrxnIIIalpha is expressed midway along the neural tube's dorso-ventral axis in the hindbrain and anterior spinal cord, at the site of the primary interneuron column. Because of the striking diversity of neurexin isoforms, we analysed alternative splicing of Xenopus transcripts during development and found examples of alternative splice variants of each neurexin. The data demonstrate differential regulation of the alpha neurexins with respect to the gene temporal and spatial expression and alternative splicing.


[Identification of AP1 cis-element and transcriptional effect on cytokeratin 13 gene expression].
To identify the type of CTGAATCA from -nt.199 to -nt.192 of the cytokeratin 13(CK13) gene 5' flanking region and determine its transcriptional effect on CK13 gene expression. The CAT systems were used to assess the effects of different motifs of CK13 gene 5' flanking region on transcription. The clones of pCAT-enhancer with the total length, -nt.207 to +nt.63 and the same length of -nt.207 to +nt.63, but the T, G of -nt.198, -nt.197 being changed to A, T of the CK13 gene 5' flanking region, were constructed and transferred to HeLa cells with the help of lipofectin. Then work was done to detect the instant CAT expression of different clones and evaluate the effects of CTGAATCA of the 5' flanking region on CK13 gene expression. The type of the cis-element of CTGAATCA was identified with electrophoretic mobility shift assay (EMSA) and competition-EMSA. CTGAATCA in the CK13 gene 5' flanking region is an AP1 cis-element by EMSA and competition-EMSA, it promotes CK13 gene expression. CTGAATCA from -nt.199 to nt.192 of the CK13 gene 5' flanking region is an AP1 reaction element, not a cAMP reaction element. It promotes transcriptional activity of CK13 gene 5' flanking region.


Spore Germination and Rhizoid Differentiation in Onoclea sensibilis: A Two-Dimensional Electrophoretic Analysis of the Extant Soluble Proteins.
Following a geometrically asymmetrical cell division during germination of spores of the fern Onoclea sensibilis L., the small cell differentiates into a rhizoid and the large cell divides to form the protonema. Using silver-staining of two-dimensional gels, we have examined the soluble proteins of spores during germination and of separated rhizoid protoplasts and protonemal cells. Of over 500 polypeptides followed, nearly 25% increased or decreased in prominence during spore germination and the initial phases of rhizoid elongation. Soluble proteins from purified protoplasts of young rhizoids were quantitatively different from those of protonemal cells and germinated spores. Nine polypeptides which appeared after cell division were substantially more prominent in rhizoid protoplasts than in whole germinated spores and have been putatively designated rhizoid-specific polypeptides. The differences in the soluble protein composition of young rhizoids and protonemal cells probably reflect the differential organelle distribution between the two cells as well as differential net protein synthesis in the cytoplasms of the two cells.


A study on fracture lines of the quadrilateral plate based on fracture mapping.
Quadrilateral plate fractures are a challenging group of acetabular fractures to manage. However, there is little literature that describes the fracture lines of the quadrilateral plate. The aim of this study was to explore the fracture lines of the quadrilateral plate and relevant clinical significance. CT data from a series of acetabular fractures were retrospectively analyzed. According to the X-ray, CT, and operative records of the patients, Judet-Letournel classification was carried out for acetabular fractures involving quadrilateral plate. Then, the fracture maps of different types of acetabular fractures in the quadrilateral plate were drawn. To facilitate the characterization of fracture maps, we defined six basic fracture lines. The fracture lines of the three types of acetabular fractures (double-column fracture, T-type fracture, and anterior column with posterior hemitransverse fracture) mainly included upper transverse lines and upper oblique lines. Although the fracture lines of posterior wall fracture and anterior column fracture were mainly upper transverse lines, the fracture lines of the former were in a low position. The fracture lines of transverse fracture and transverse with posterior wall fracture were similar, both of which were mainly upper oblique lines. The fracture lines of posterior column fractures mainly included posterior vertical lines. The fracture lines of different types of acetabular fractures have certain regularity respectively. Observation of the fracture lines of the quadrilateral plate based on fracture mapping can help orthopedic surgeons to enhance the understanding of the Judet-Letournel classification, which may have some significant guidance on the choice of operation approach and the design of internal fixation devices.


Two bradykinin binding sites with picomolar affinities.
Bradykinin (BK) and related peptides exert a wide range of effects on several organ systems. We have attempted to sort out these effects by studying the binding interaction of [3H]BK at the membrane level with in vitro receptor binding techniques. High specific activity [3H]BK and an enzyme inhibitor "cocktail" has enabled us to label two BK binding sites with different affinity and peptide specificity in several guinea-pig tissues. In the guinea-pig ileum the high-affinity site has an equilibrium dissociation constant (Kd) for [3H]BK of 13 pM and a maximal number of binding sites of 8.3 pmol/g of tissue wet weight. The low-affinity guinea-pig ileum site displays a Kd of 910 pM, a maximum number of binding sites of 14 pmol/g of tissue wet weight and shows a greater selectivity for BK analogs over Lysyl-BK analogs. Two similar sites can also be discriminated in kidney and heart. The potencies of a series of BK analogs at the high-affinity guinea-pig ileum site correlate well with their potencies in contracting ileal smooth muscle. The binding of [3H]BK in the guinea-pig ileum is inhibited by physiological concentrations of monovalent and divalent cations.


[Study on the best sampling time and the time distribution of atmospheric bacterial particle].
The changes of atmospheric bacterial particle concentrations in three areas--Beijing, Tianjin and Shenyang, were investigated in different seasons and period of one day. The samplers used in this study were MF-45 and HTK-201 air microbial samplers. The results showed that the concentrations of atmospheric bacterial particle in Beijing and Tianjin are higher in spring than those in other seasons. They are 2053/m3 and 2556/m3 respectively in spring, 995/m3 and 1064/m3 respectively in summer. The concentrations of atmospheric bacterial particle in Shenyang is higher in autumn (10108/m3) and lower in winter (1294/m3). The changes of atmospheric bacterial particle concentrations have two peak values during a day. The two high peak values are at 6:00 to 7:00 and 18:00, while the two low values are at 11:00 to 13:00 and 1:00 to 2:00. We sampled the atmospheric bacterial particles at 4 different combinations of sampling time in the three cities. They were 12, 8, 6 and 4 times a day. The sampling time combination was analyzed by mathematical statistics according to the results. The best sampling time was decided by the statistics results and time distribution character of atmospheric bacterial particle concentration in different seasons and period of one day. The concentration of atmospheric bacterial particle should be detected in the middle month of the four seasons: January, April, July and October. Sampling time at 7:00, 10:00, 13:00, 16:00, 19:00, 22:00, 1:00 and 4:00 could be selected for 8 times sampling a day. The sampling time sequence should be at 5:00, 11:00, 17:00 and 23:00 for 4 times sampling a day. The four times sampling at daytime in spring and fall should be at 6:00, 9:00, 12:00 and 19:00; 5:00, 9:00, 13:00 and 17:00 in summer; 7:00, 10:00, 13:00 and 16:00 in winter.


Identification of a multifunctional binding site on Ubc9p required for Smt3p conjugation.
Ubiquitin-like proteins (ub-lps) are conjugated by a conserved enzymatic pathway, involving ATP-dependent activation at the C terminus by an activating enzyme (E1) and formation of a thiolester intermediate with a conjugating enzyme (E2) prior to ligation to the target. Ubc9, the E2 for SUMO, synthesizes polymeric chains in the presence of its E1 and MgATP. To better understand conjugation of ub-lps, we have performed mutational analysis of Saccharomyces cerevisiae Ubc9p, which conjugates the SUMO family member Smt3p. We have identified Ubc9p surfaces involved in thiolester bond and Smt3p-Smt3p chain formation. The residues involved in thiolester bond formation map to a surface we show is the E1 binding site, and E2s for other ub-lps are likely to bind to their E1s at a homologous site. We also find that this same surface binds Smt3p. A mutation that impairs binding to E1 but not Smt3p impairs thiolester bond formation, suggesting that it is the E1 interaction at this site that is crucial. Interestingly, other E2s and their relatives also use this same surface for binding to ubiquitin, E3s, and other proteins, revealing this to be a multipurpose binding site and suggesting that the entire E1-E2-E3 pathway has coevolved for a given ub-lp.


Differences in Mood, Optimism, and Risk-Taking Behavior Between American and Chinese College Students.
Mood and optimism have been demonstrated to influence risk-taking decisions; however, the literature on mood, optimism, and decision-making is mixed and conducted primarily with western samples. This study sought to address this gap in the literature by examining the impact of mood and dispositional optimism on risk-taking and whether these associations differed between undergraduate students from the United States (N = 141) and the People's Republic of China (N = 90). Both samples completed a dispositional optimism questionnaire and an autobiographical mood induction task. They were then tasked with choosing to complete the Raven's Advanced Progressive Matrices reasoning task on easy, medium, or hard difficulty for hypothetical money. Selecting harder difficulties was interpreted as more risk-taking due to a higher chance of failure. More positive mood and higher dispositional optimism were associated with decreased risk-taking, i.e., selecting easier puzzle difficulties, in the American sample but increased risk-taking decisions, i.e., selecting harder difficulties, in the Chinese sample (p < 0.05 for all). These findings suggest that the effect of mood and optimism on decision-making may differ by nationality and/or culture.


High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide.
High-density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that HDL might also inhibit atherogenesis by combating inflammation. To identify potential antiinflammatory mechanisms, we challenged macrophages with lipopolysaccharide, an inflammatory microbial ligand for Toll-like receptor 4. HDL inhibited the expression of 30 (277 of 911) of the genes normally induced by lipopolysaccharide, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by Toll-like receptor 4 and the TRAM/TRIF signaling pathway. Unexpectedly, the ability of HDL to inhibit gene expression was independent of macrophage cholesterol stores. Immunofluorescent studies suggested that HDL promoted TRAM translocation to intracellular compartments, which impaired subsequent signaling by Toll-like receptor 4 and TRIF. To examine the potential in vivo relevance of the pathway, we used mice deficient in apolipoprotein A-I, the major protein of HDL. After infection with Salmonella typhimurium, a Gram-negative bacterium that expresses lipopolysaccharide, apolipoprotein A-I-deficient mice had 6-fold higher plasma levels of interferon-β, a key regulator of the type I interferon response, than did wild-type mice. HDL inhibits a subset of lipopolysaccharide-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection.


Visible light OCT improves imaging through a highly scattering retinal pigment epithelial wall.
Here we provide a counter-example to the conventional wisdom in biomedical optics that longer wavelengths aid deeper imaging in tissue. Specifically, we investigate visible light optical coherence tomography of Bruch's membrane (BM) in the non-pathologic eyes of humans and two mouse strains. Surprisingly, we find that shorter visible wavelengths improve the visualization of BM in pigmented eyes, where it is located behind a highly scattering layer of melanosomes in the retinal pigment epithelium (RPE). Monte Carlo simulations of radiative transport suggest that, while absorption and scattering are higher at shorter wavelengths, detected multiply scattered light from the RPE is preferentially attenuated relative to detected backscattered light from the BM.


[Appropriate use of antibiotics--practices we should employ now: appropriate use of antibiotics for pharmacists in general hospitals].
An authorization system regarding infection has been devised for various occupations in the field of infection control. An infection control team (ICT) consists of authorized, specialized staff, and plays an important role in clinical practice, considering the appropriate use of antibiotics. Board-certified infection control pharmacy specialists also belong to this team. The appropriate use of antibiotics, which I emphasize, indicates the absence of the inappropriate selection of broad-spectrum agents and chronic administration, considering the following 3 points: the selection of antibiotics whose spectra involve causative bacteria (drug sensitivity), prescription of antibiotics using an appropriate administration method/dose based on their transfer to the infected site (pharmacokinetics), and relief of symptoms of infectious diseases (therapeutic effects). In this study, we introduce cases of pharmacists' intervention in Nakamura Memorial South Hospital with respect to the appropriate use of antibiotics by general hospital pharmacists. The contents of pharmacists' intervention included accompanying physicians on their rounds/support regarding prescription, therapeutic drug monitoring, the preparation of guidelines for the hospital use of antibiotics, culture data collection/preparation of antibiograms, ICT/Infection Control Committee (ICC) activities, hospital rounds, preparation of antibiotic injections, and gram staining of sputum. In the future, health care professionals should always consider the appropriate use of antibiotics, contributing to a medical environment in which current options can be maintained for future infectious disease treatment.


Rapid oxidation of ring methyl groups is the primary mechanism of biotransformation of gemfibrozil by the fungus Cunninghamella elegans.
The hypolipidemic agent gemfibrozil (GEM), which has been studied for its metabolism in humans and animals, was investigated to elucidate its primary metabolism by Cunninghamella elegans. The fungus produced ten metabolites (FM1-FM9 and FM6') from the biotransformation of GEM. Based on LC/MS/MS and NMR analyses, a major metabolite, FM7, was identified as 2'-hydroxymethyl GEM. FM6 was considered to be 5'-hydroxymethyl GEM, after comparison of results LC/MS, LC/MS/MS, and UV absorption spectra to FM7. The combined concentration of FM6 and FM7 was found to increase up to 0.83 mM by day 2, and then decreased gradually with incubation time, followed by a noticeable increase in the biotransformation product, FM1, up to 0.86 mM by day 15. NMR analyses confirmed that FM1 was 2',5'-dihydroxymethyl GEM. Further minor oxidations of the aromatic ring and carboxylic acid intermediates were also detected. Based upon these findings, the major fungal metabolic pathway for GEM is likely to occur via production of 2',5'-dihydroxymethyl GEM from 2'-hydroxymethyl GEM. These relatively rapid and diverse biotransformations of GEM by C. elegans suggest that depending upon conditions, it may also follow a similar biodegradation fate when released into the natural environment.


Proton pump inhibitor therapy and osteoporosis.
Osteoporotic fractures, particularly hip fractures, can have a devastating impact on the well-being of the elderly population. Recently, two population-based observational studies reported a highly important association between the use of potent acid suppressive therapy and an increased risk of hip fractures. The mechanisms underlying such an association are not clear. However, a careful review of the existing evidence seems to suggest that the main physiologic consequences of proton pump inhibitor therapy may each have a theoretical influence on bone metabolism. Specifically, inhibition of the osteoclastic proton pumps may reduce bone resorption, while profound acid suppression could potentially hamper intestinal calcium absorption, and secondary hypergastrinemia may enhance bone resorption through the induction of parathyroid gland hyperplasia. However, the existing data are clearly too limited for us to draw any definitive conclusions, and more studies are urgently needed to delineate the physiologic relevance of these theoretical mechanistic links, individually and collectively.


TMEM100 negatively regulated by microRNA‑106b facilitates cellular apoptosis by suppressing survivin expression in NSCLC.
Non‑small cell lung cancer (NSCLC) is a common malignant tumour. Nevertheless, the 5‑year survival rate of NSCLC patients remains poor. Thus, identifying critical factors involved in regulating the progression of NSCLC is important for providing potential treatment targets. In the present study, it was observed that transmembrane protein 100 (TMEM100) was significantly downregulated in NSCLC tissues compared with paired peritumoral tissues. Decreased TMEM100 expression was associated with poor clinical outcomes in NSCLC patients. Moreover, TMEM100 overexpression inhibited colony formation and facilitated apoptosis by suppressing survivin expression in NSCLC cells, whereas TMEM100 knockdown had the opposite effect. In addition, microRNA (miR)‑106b, a miR with controversial roles in different human cancers, was upregulated in NSCLC and directly downregulated TMEM100 expression. The roles of miR‑106b in cell survival were mitigated by the restoration of TMEM100. The aforementioned results indicated that TMEM100 induced cell apoptosis and inhibited cell survival by serving as a tumour suppressor and that miR‑106b‑mitigatedTMEM100 expression defined a potentially oncogenic pathway in NSCLC.


Humanitarianism under attack.
Attacks on humanitarianism are threefold. First, in conflict zones, over the past decade attacks on humanitarian health facilities and personnel are increasingly documented, along with a decline in respect for core humanitarian principles by state and non-state actors, and this will continue. Second, growing instrumentalisation, a failure to adequately fund the sector, antimigrant/refugee populism on the rise and the protracted nature of many crises are provoking a shift away from humanitarian to development healthcare aid over the next decade, intended to keep refugees far away from developed countries by encouraging their integration into immediate neighbouring states. This undermines humanitarian healthcare emergency response capacity. Third, the climate crisis will massively increase humanitarian healthcare needs among the most vulnerable over the next decade and challenge the sector to respond across all its programmes, not least as it absorbs a renewed youthful agency elsewhere in climate protest.


National audit of the management of peritonsillar abscess.
An anonymous postal survey of 200 consultants was used to audit the current prevalent practices in the management of quinsy in the UK; 101 responded. The findings reveal that on average an otolaryngology department treats 29 cases per year, the vast majority (94%) on an inpatient basis. The main initial treatment was needle aspiration combined with intravenous antibiotics. Interestingly, those departments treating more than 20 cases a year are more likely to use needle aspiration, while departments in England and Wales use significantly more incision and drainage than those in Scotland. Incision and drainage (52%) was the most common form of treatment of non-resolving patients. The median hospital stay was two days.


Hepatitis C infection in cadaver organ donors: strategies to reduce transmission of infection and prevent organ waste.
The transmission of hepatitis C virus (HCV) by organ transplantation has been unequivocally demonstrated. Among recipients of organs from anti-HCV-positive donors, 57%-96% test positive for HCV RNA. Consequently, several organ procurement organizations have adopted a policy restricting the use of anti-HCV-positive donors to life-saving transplants (heart, liver, or lung). The differences in the rate of transmission of HCV infection by anti-HCV-positive donors could be related to the prevalence of HCV RNA among these donors. In a national collaborative study of 3,078 cadaver organ donors from eight organ procurement organizations in the United States, the prevalence of anti-HCV antibodies and HCV RNA were 4.2% and 2.4%, respectively. The sensitivity and negative predictive value of anti-HCV antibodies for HCV RNA were 100%. However, despite a specificity of 98.1%, the positive predictive value was only 55.1%. Discarding organs from enzyme-linked immunosorbent assay 2-positive donors would eliminate transmission, but organs from 1.88% of donors would be wasted. Clinical and laboratory characteristics did not distinguish anti-HCV-positive donors with and without HCV RNA. Hence, to reduce waste it is necessary to develop confirmatory tests with a higher specificity for HCV RNA than those that are currently available. Even if anti-HCV-positive but HCV RNA-negative donors could be identified and utilized, 2.4% of cadaver organ donors that test positive for serum HCV RNA would remain unsuitable for transplantation of non-life-saving organs. Hence, several authors have suggested the use of kidneys from anti-HCV-positive donors in recipients with pre-existing HCV infection.(ABSTRACT TRUNCATED AT 250 WORDS)


Sharpening of ultrasonic scalers.
Instruments suitable for removing calculus, plaque and necrotic cementum, which hinder normal periodontal reattachment, are extremely important for successful therapy. The test was carried out in order to see if a standard scaler used for ultrasonic tartar removal maintains its physical features when sharpened. 6 scalers, compatible with piezo-electric generators, were tested and 2 diameters, A and B, weights and resonance frequencies were measured. Scalers no. 2, 3, 4, 5, were sharpened and was used as control. All measurements were taken again at the end of the test. Statistical analysis reveals significant variations, after sharpening, of A diameter (t = 4.14 greater than 3.55, p less than 0.01), B diameter (t = 5.34 greater than 3.355, p less than 0.01) and resonance frequency (t = 2.82 greater than 2.306, p less than 0.05); in contrast, there is no significant change of weights (t = 1.17 less than 2.306, p greater than 0.05). These results suggest that sharpening slightly modifies the physical features of ultrasonic tips, so that sharpening ultrasonic scalers, from a physical point of view, can be carried out, paying attention not to damage the water cooling system.


Nd:YAG-pumped periodically poled LiNbO3 optical parametric generator seeded with the narrowband output of a 532-nm pumped optical parametric generator.
We present a simple scheme to generate a continuously tunable pulsed narrow-bandwidth infrared wave. An Nd:YAG-pumped periodically poled lithium niobate optical parametric generator (OPG) is seeded with the output of another OPG pumped by the second harmonic (0.532 microm) of the Nd:YAG laser. A tunable idler wave from the 0.532-microm pumped OPG, operated away from the degenerate point, provides a narrow linewidth seed source for the 1.064-microm pumped broadband OPG. Seeding forces the second OPG to operate in a narrowband operation comparable with that of the seed source. Linewidth of the YAG-pumped OPG is 5-25 nm, in the tuning range of 1.61-1.83 microm (signal), narrowed to 1.48-1.05 nm. Methods of further reduction of linewidth also have been discussed.


Advanced imaging in acute ischemic stroke: an updated guide to the hub-and-spoke hospitals.
The purpose of this review is to summarize the role of the hub-and-spoke system in acute stroke care, highlight the role of advanced imaging and discuss emerging concepts and trials relevant to the hub-and-spoke model. The advent of advanced stroke multimodal imaging has provided increased treatment options for patients, particularly in rural and regional areas. When used in the hub-and-spoke model, advanced imaging can help facilitate and triage transfers, appropriately select patients for acute therapy and treat patients who may otherwise be ineligible based on traditional time metrics.Recent, ongoing trials in this area may lead to an even greater range of patients being eligible for acute reperfusion therapy, including mild strokes and patients with large core infarct volumes. Integration of advanced imaging into a hub-and-spoke system, when complemented with other systems including telemedicine, improves access to acute stroke care for patients in regional and rural areas.


Neurophysiological features of the migrainous brain.
Migraine is a disorder in which central nervous system (CNS) dysfunction might play a pivotal role. As there are no consistent structural disturbances, clinical neurophysiology methods seem particularly suited to study its pathophysiology. This chapter will focus on a review of neurophysiological studies that have provided an insight into migraine pathogenesis. The results are in part contradictory, which may be due to the methodology, patient selection or timing of study. Nonetheless, quantitative electroencephalography and magnetoencephalography recordings during migraine attacks provide strong, though indirect, evidence favouring the occurrence of spreading cortical depression during attacks of migraine with, and possibly without, aura. Evoked cortical potential and nociceptive blink reflex studies demonstrate that lack of habituation during repetitive stimulation is a reproducible CNS dysfunction interictally in both migraine with and without aura. Transcranial magnetic stimulations show excitability changes of the visual cortex. The interictal migrainous CNS dysfunction is likely to play a role in migraine pathogenesis, has a familial character and undergoes periodic modulations with quasi-normalisation just before, during an attack and after treatment with certain prophylactic agents. In addition, neurophysiological methods have revealed subclinical abnormalities of cerebellar function and neuromuscular transmission, which may improve phenotyping of migraineurs for genetic and therapeutic studies.


Sex-ratio meiotic drive in Drosophila simulans is related to equational nondisjunction of the Y chromosome.
The sex-ratio trait, an example of naturally occurring X-linked meiotic drive, has been reported in a dozen Drosophila species. Males carrying a sex-ratio X chromosome produce an excess of female offspring caused by a deficiency of Y-bearing sperm. In Drosophila simulans, such males produce approximately 70-90% female offspring, and 15-30% of the male offspring are sterile. Here, we investigate the cytological basis of the drive in this species. We show that the sex-ratio trait is associated with nondisjunction of Y chromatids in meiosis II. Fluorescence in situ hybridization (FISH) using sex-chromosome-specific probes provides direct evidence that the drive is caused by the failure of the resulting spermatids to develop into functional sperm. XYY progeny were not observed, indicating that few or no YY spermatids escape failure. The recovery of XO males among the progeny of sex-ratio males shows that some nullo-XY spermatids become functional sperm and likely explains the male sterility. A review of the cytological data in other species shows that aberrant behavior of the Y chromosome may be a common basis of sex-ratio meiotic drive in Drosophila and the signal that triggers differential spermiogenesis failure.


Can breast cancer molecular subtype help to select patients for preoperative MR imaging?
To assess whether breast cancer molecular subtype classified by surrogate markers can be used to predict the extent of clinically relevant disease with preoperative breast magnetic resonance (MR) imaging. In this HIPAA-compliant, institutional review board-approved study, informed consent was waived. Preoperative breast MR imaging reports from 441 patients were reviewed for multicentric and/or multifocal disease, lymph node involvement, skin and/or nipple invasion, chest wall and/or pectoralis muscle invasion, or contralateral disease. Pathologic reports were reviewed to confirm the MR imaging findings and for hormone receptors (estrogen and progesterone subtypes), human epidermal growth factor receptor type 2 (HER2 subtype), tumor size, and tumor grade. Surrogates were used to categorize tumors by molecular subtype: hormone receptor positive and HER2 negative (luminal A subtype); hormone receptor positive and HER2 positive (luminal B subtype); hormone receptor negative and HER2 positive (HER2 subtype); hormone receptor negative and HER2 negative (basal subtype). All patients included in the study had a histologic correlation with MR imaging findings or they were excluded. χ(2) analysis was used to compare differences between subtypes, with multivariate logistic regression analysis used to assess for variable independence. Identified were 289 (65.5%) luminal A, 45 (10.2%) luminal B, 26 (5.9%) HER2, and 81 (18.4%) basal subtypes. Among subtypes, significant differences were found in the frequency of multicentric and/or multifocal disease (luminal A, 27.3% [79 of 289]; luminal B, 53.3% [24 of 45]; HER2, 65.4% [17 of 26]; basal, 27.2% [22 of 81]; P < .001) and lymph node involvement (luminal A, 17.3% [50 of 289]; luminal B, 35.6% [26 of 45]; HER2, 34.6% [nine of 26]; basal 24.7% [20 of 81]; P = .014). Multivariate analysis showed that molecular subtype was independently predictive of multifocal and/or multicentric disease. Preoperative breast MR imaging is significantly more likely to help detect multifocal and/or multicentric disease and lymph node involvement in luminal B and HER2 molecular subtype breast cancers. Molecular subtype may help to select patients for preoperative breast MR imaging.


Impact of the dietary fatty acid intake on C-reactive protein levels in US adults.
Growing evidence suggests that the effects of diet on cardiovascular disease (CVD) occur through mechanisms involving subclinical inflammation. We assessed whether reported dietary fatty acid intake correlates with a serum high-sensitivity C-reactive protein (hs-CRP) concentration in a population-based sample of US men and women.In this cross-sectional analysis, participants were selected from the US National Health and Nutrition Examination Survey (NHANES) and restricted to those with available data on dietary intake, biochemical and anthropometric measurements from 2001 to 2010. All statistical analyses accounted for the survey design and sample weights by using SPSS Complex Samples v22.0 (IBM Corp, Armonk, NY).Of the 17,689 participants analyzed, 8607 (48.3%) were men. The mean age was 45.8 years in the overall sample, 44.9 years in men, and 46.5 years in women (P = 0.047). The age-, race-, and sex-adjusted mean dietary intakes of total polyunsaturated fatty acids (PUFAs), PUFAs 18:2 (octadecadienoic), and PUFAs 18:3 (octadecatrienoic) monotonically decreased across hs-CRP quartiles (P < 0.001), whereas dietary cholesterol increased across hs-CRP quartiles (P < 0.001)This study provides further evidence of an association between fatty acid intake and subclinical inflammation markers. hs-CRP concentrations are likely modulated by dietary fatty acid intake. However, the causality of this association needs to be demonstrated in clinical trials.


Formulation and Pharmacokinetic Evaluation of Microcapsules Containing Pravastatin Sodium Using Rats.
Pravastatin Sodium has a cholesterol lowering agent. It has shorter half-life and undergoes first-pass metabolism. Frequent dose is required in case of conventional dosage form. The purpose of the study is to formulate and evaluate microcapsules containing Pravastatin Sodium by complex with cholestyramine resins coated with Eudragit RLPO and Eudragit RSPO polymers for achieving control release. Complexation of drug on resin was carried out by batch method. Microencapsulation was carried out by nonaqueous solvent evaporation method. Pharmacokinetic studies were done by using rats. The intermediate stability studies were carried out on the most satisfactory formulations. FTIR, X-ray diffraction, and DSC spectra of drug, drug-resinates, and polymers revealed no chemical interaction. The % DEE and % yield were observed for formulations of f1 to f7 that were varied from 97.1 ± 0.8 to 98.9 ± 0.5% and 95.0 ± 3.25 to 98.8 ± 7.1%, respectively. Most satisfactory formulation, f6, showed drug release up to 72.6%. No changes in % DEE and % CDR were observed after stability studies. Microcapsules of f6 formulation achieved best performance regarding in vitro drug release and from pharmacokinetic evaluation mean residence time was found to be 6.3 h, thus indicated, Pravastatin Sodium microcapsules were released and absorbed slowly over a prolonged period of time.


Effects of therapeutic hypercapnia on inflammation and apoptosis after hepatic ischemia-reperfusion injury in rats.
Therapeutic hypercapnia (TH) has been demonstrated to protect several organs ischemia-reperfusion injury. The study aimed to investigate the effects of therapeutic hypercapnia on hepatic ischemia-reperfusion injury (HIRI). Thirty adult male Wistar rats weighing (250+/-20) g were randomized into 3 groups (n=10 in each), group C (control group), group A (hypercapnia group) and group B (CO2 preconditioning group). A segmental ischemia of the liver was induced by interrupting the blood vessels including the bile duct to the median and left lateral lobes for 60 minutes and all the animals were sacrificed after 240 minutes observation period of reperfusion. Mean arterial pressure (MAP) and the blood gases were measured before ischemia (baseline) and at 30, 60, 120, 180 and 240 minutes after reperfusion. Arterial blood samples were obtained for determination of serum levels of TNF-alpha, IL-10, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histopathology of liver tissues was evaluated by light microscopy. The NF-kappaB expression and apoptotic hepatocytes were respectively determined by immunohistochemistry and TUNEL assay. The serum levels of liver enzymes and TNF-alpha were significantly decreased while the IL-10 level was significantly increased in groups A and B than in group C (P<0.05), and group B surpassed group A (P<0.05). The histopathological scores, the NF-kappaB immunohistochemical score (IHS) and apoptotic index were significantly lower in groups A and B than in group C (P<0.05), and the decrease in group B was more obvious than in group A (P<0.05). Therapeutic hypercapnia attenuates ischemia-reperfusion injury to the liver. Moreover, the effects of CO2 preconditioning are outstandingly notable.


Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels.
Metformin is a drug widely used to treat type 2 diabetes. It enhances insulin sensitivity by improving glucose utilization in tissues like liver or muscle. Metformin inhibits respiration, and the decrease in cellular energy activates the AMP-activated protein kinase that in turn switches on catabolic pathways. Moreover, metformin increases lipolysis and beta-oxidation in white adipose tissue, thereby reducing the triglyceride stores. The uncoupling proteins (UCPs) are transporters that lower the efficiency of mitochondrial oxidative phosphorylation. UCP2 is thought to protect against oxidative stress although, alternatively, it could play an energy dissipation role. The aim of this work was to analyse the involvement of UCP2 on the effects of metformin in white adipocytes. We studied the effect of this drug in differentiating 3T3-L1 adipocytes and found that metformin causes oxidative stress since it increases the levels of reactive oxygen species (ROS) and lowers the aconitase activity. Variations in UCP2 protein levels parallel those of ROS. Metformin also increases lipolysis in these cells although only when the levels of ROS and UCP2 have decreased. Hence, UCP2 does not appear to be needed to facilitate fatty acid oxidation. Furthermore, treatment of C57BL/6 mice with metformin also augmented the levels of UCP2 in epididymal white adipose tissue. We conclude that metformin treatment leads to the overexpression of UCP2 in adipocytes to minimize the oxidative stress that is probably due to the inhibition of respiration caused by the drug.


The endoplasmic reticulum: a dynamic and well-connected organelle.
The endoplasmic reticulum forms the first compartment in a series of organelles which comprise the secretory pathway. It takes the form of an extremely dynamic and pleomorphic membrane-bounded network of tubules and cisternae which have numerous different cellular functions. In this review, we discuss the nature of endoplasmic reticulum structure and dynamics, its relationship with closely associated organelles, and its possible function as a highway for the distribution and delivery of a diverse range of structures from metabolic complexes to viral particles.


Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking.
Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.


Directly and Simultaneously Expressing Absolute and Relative Treatment Effects in Medical Data Models and Applications.
Logistic regression is widely used in the analysis of medical data with binary outcomes to study treatment effects through (absolute) treatment effect parameters in the models. However, the indicative parameters of relative treatment effects are not introduced in logistic regression models, which can be a severe problem in efficiently modeling treatment effects and lead to the wrong conclusions with regard to treatment effects. This paper introduces a new enhanced logistic regression model that offers a new way of studying treatment effects by measuring the relative changes in the treatment effects and also incorporates the way in which logistic regression models the treatment effects. The new model, called the Absolute and Relative Treatment Effects (AbRelaTEs) model, is viewed as a generalization of logistic regression and an enhanced model with increased flexibility, interpretability, and applicability in real data applications than the logistic regression. The AbRelaTEs model is capable of modeling significant treatment effects via an absolute or relative or both ways. The new model can be easily implemented using statistical software, with the logistic regression model being treated as a special case. As a result, the classical logistic regression models can be replaced by the AbRelaTEs model to gain greater applicability and have a new benchmark model for more efficiently studying treatment effects in clinical trials, economic developments, and many applied areas. Moreover, the estimators of the coefficients are consistent and asymptotically normal under regularity conditions. In both simulation and real data applications, the model provides both significant and more meaningful results.


[Opinions on ideal number of children in selected European countries].
"Comparison of the opinions of 14 European countries' population on ideal number of children in the family recorded...in 1994...[shows] a considerable homogeneity of European countries, especially that of the young generation.... The [comparison indicated]...differences among individual countries, which issued from their own cultural and religious traditions. It was confirmed that...young Europeans share...the opinion that the childless life is not empty and dull and that the parents...need not try to keep the family together with respect to their children. This fact indicates, together with a low attractiveness of the institution of marriage, [continuation] of a low fertility level even in the future." (SUMMARY IN ENG)


From Heart Murmur to Echocardiography - Congenital Heart Defects Diagnostics Using Machine-Learning Algorithms.
The most common clinical sign in pediatric cardiology is heart murmur, which can often be uncharacteristic. The aim of this research was to present the results of development of a classifier based on machine learning algorithms whose purpose is to classify organic murmur that occur in congenital heart defect (CHD). The study is based on the data collected at Pediatric Clinic, Clinical Center University of Sarajevo during three-year period. Totally, 116 children aged from 1 to 15 years were enrolled in the study. Input parameters for classification are parameters obtained during basic physical examination and assessment of patient. First, analysis of relevance of the feature for classification was done using InfoGain, GainRatio, Relief and Correlation method. In the second step, classifiers based on Naive Bayes, Logistic Regression, Decision Tree, Random Forest and Support Vector Machine were developed and compared by performance. The results of this research suggest that high accuracy (>90%) classifier for detection of CHD based on 16 parameters can be developed. Such classifier with appropriate user interface would be valuable diagnostic aid to doctors and pediatricians at primary healthcare level for diagnostic of heart murmurs.


Dealing with DRGs: analysis of serum theophylline assays in Medicare patients.
To investigate the therapeutic and economic implications of serum theophylline assay (STA) use in Medicare patients classified in diagnosis-related group 88 as having chronic obstructive pulmonary disease, a retrospective audit was conducted of all serum theophylline assays ordered for these patients in a large teaching hospital during a 6-month period. Based on established pharmacokinetic principles of theophylline therapy, analysis was conducted on rational indication for assay use (n = 146), correct sampling procedure regarding steady-state and peak/trough concentrations (n = 99), and appropriateness of physician response (n = 100). Percentages of appropriate use found for these three parameters were 79.2%, 56.6%, and 85.0%, respectively. Overall compliance regarding all three considerations was 52.1%; this figure declined to 29.9% when admission level assays were excluded from consideration. A need is identified to improve STA sampling procedures in order to insure availability of accurate and valid results on which to make indicated changes in drug therapy.


[Science in atherosclerosis].
Ischemic heart disease and cerebral vascular accident are major cause of death in Japan. Development of these diseases is based on atherosclerosis, which would become evident in the middle-aged. Atherosclerosis is a process of aging, because its progression is closely associated with increase in age. Other factors such as smoking, eating habits and obesity are known to facilitate it. Therefore, it is very important for each one of us to learn the risk factors of atherosclerosis and to prevent it by paying attention to our life style. In this citizen joint symposium, we focused on the strategy for treatment and prevention of atherosclerosis by summarizing its mechanisms and consequences. Participation in the symposium could hopefully stimulate our civil activities against atherosclerosis and help promoting our health care in Hokkaido.


Oleate lipase activity in Gardnerella vaginalis and reconsideration of existing biotype schemes.
Gardnerella vaginalis is a facultative gram positive organism that requires subculture every 1-2 days to maintain viability. It has been linked with bacterial vaginosis (BV), a syndrome that has been associated with increased risk for preterm delivery, pelvic inflammatory disease and HIV acquisition. About 10% of the G. vaginalis isolates have been reported to produce sialidase, but there have not been any studies relating sialidase production and biotype. Sialidase activity is dramatically increased in the vaginal fluid of women with BV and bacterial sialidases have been shown to increase the infectivity of HIV in vitro. There are 8 different biotypes of G. vaginalis. Biotypes 1-4 produce lipase and were reported to be associated with BV and the association of these biotypes with BV is under dispute. Other studies have demonstrated that G. vaginalis biotype 1 can stimulate HIV-1 production. Because of the discrepancies in the literature we compared the methods used to biotype G. vaginalis and investigated the relationship of biotype and sialidase production. A new medium for maintenance of Gardnerella vaginalis which allows survival for longer than one week is described. Some isolates only grew well under anaerobic conditions. Sialidase producing isolates were observed in 5 of the 6 biotypes tested. Using 4-methylumbelliferyl-oleate to determine lipase activity, instead of egg yolk agar, resulted in erroneous biotypes and does not provide reliable results. Previous studies associating G. vaginalis biotype with bacterial vaginosis were methodologically flawed, suggesting there is not an association of G. vaginalis biotypes and bacterial vaginosis. Sialidase activity was observed in 5 of the 8 biotypes.


Hydrocephalus and subdural effusion with extracranial extension complicating meningitis.
Post-meningitic subdural effusion does not extend extracranially. To our knowledge, the association of hydrocephalus and extracranial extension of a subdural effusion has not been previously reported. We present a case of an 8-year-old boy who presented with progressive head enlargement and worsening pulsatile peri-orbital swelling of 1 year duration. Cranial computerized tomographic scan confirmed communicating hydrocephalus and bilateral subdural effusion worse on the right side. The patient had a ventriculo-peritoneal shunt, with resolution of the subdural effusion and his hydrocephalus.


Advances in hemorrhage control resuscitation.
Despite significant advances in trauma management over the last twenty years, uncontrolled hemorrhage remains the leading cause of preventable death in trauma. We review recent changes affecting hemorrhage control resuscitation. Early blood product usage has become well established as a standard of care in trauma hemorrhage control. To enable this, low titer group A liquid plasma and group O whole blood are increasingly utilized. Single donor apheresis platelets have now replaced pooled donor platelets in the USA and are often pathogen reduced, which has implications for trauma resuscitation. Further work is examining timing and dosing of tranexamic acid and the debate in factor concentrate usage in trauma induced coagulopathy continues to evolve. The 'Stop the bleed' campaign has highlighted how important the use of hemostatic dressings are in hemorrhage control, as too is the expanded use of endovascular aortic occlusion. We highlight the ongoing research into desmopressin use and the undetermined significance of ionized calcium levels in trauma. Finally, we discuss our own hospital experience with coagulation testing and the paucity of evidence of improved outcomes with viscoelastic testing. Improving trauma coagulopathy diagnostics and hemorrhage control are vital if we are to decrease the mortality associated with trauma.


Fidelity and factors influencing implementation of Healthy Me, Healthy: process evaluation of a social marketing campaign for diet and physical activity behaviors of children in childcare.
The effectiveness of interventions targeting children's eating and physical activity behaviors through childcare settings is inconsistent. To enhance public health impact, it is imperative to evaluate fidelity of implementing complex interventions in real-world settings. This study evaluated fidelity and contextual factors influencing implementation of Healthy Me, Healthy We (HMHW). HMHW was an 8-month social marketing campaign delivered through childcare to support children's healthy eating and physical activity. HMHW required two levels of implementation support (research team and childcare providers) and two levels of campaign delivery (childcare providers and parents). Process evaluation was conducted among childcare centers in the intervention group (n=48) of the cluster-randomized control trial. Measures included attendance logs, self-report surveys, observation checklists, field notes, and semi-structured interviews. A 35-item fidelity index was created to assess fidelity of implementation support and campaign delivery. The fidelity with which HMHW was implemented by childcare providers and parents was low (mean 17.4 out of 35) and decreased between childcare providers and parents. Childcare providers had high acceptability of the program and individual components (80 - 93%). Only half of parents felt intervention components were acceptable. Frequently cited barriers to implementation by childcare providers included time constraints, parent engagement, staff turnover, and restrictive policies. The lack of observable effect of HMHW on children's dietary or physical activity behaviors may be due to inadequate implementation at multiple levels. Different or additional strategies are necessary to support implementation of multilevel interventions, particularly when individuals are expected to deliver intervention components and support others in doing so.


Tailoring homochirality at surfaces: going beyond molecular handedness.
Chirality can be bestowed upon a surface by the adsorption of molecules and is usually discussed in terms of the molecular handedness. However, the adsorption process often leads to a new manifestation of chirality in the form of the adsorption footprint, which can also be chiral and generate mirror-images in 2-D. Therefore, in describing the chirality of the interface, one must consider both the handedness and the adsorption 'footedness' of the system. Specifically, the creation of a truly homochiral surface must ensure that a single chirality is expressed for each aspect, and requires not only the control of molecule handedness but also direct control over footedness. Here, we demonstrate the ability to engineer homochiral footedness by a structural modification of enantiopure (S)-proline, which normally creates a (4 × 2) organization on a Cu(110) surface with heterochiral footedness. This modification of proline via the addition of a double bond within the pyrrolidine ring, yielding 3-pyrroline-2-carboxylic acid (PCA), is sufficient to drive the footprints of the entire (4 × 2) assembly from heterochiral to homochiral, leading to the creation of a truly homochiral interface The effects of modifications upon the footprint arrangements were characterized at the single-molecule level by scanning tunnelling microscopy, reflection absorption infrared spectroscopy and periodic density functional theory calculations. The control of adsorption footprints is not only pivotal to tailoring chirality at surfaces but also plays a key role in dictating the organization, the outward facing functionalities and the response of the organic-inorganic interface.


Phytohabitans flavus sp. nov., Phytohabitans rumicis sp. nov. and Phytohabitans houttuyneae sp. nov., isolated from plant roots, and emended description of the genus Phytohabitans.
An actinomycete strain, designated K09-0627(T), was isolated from the roots of an orchid collected in Okinawa Prefecture, Japan. Two actinomycete strains K11-0047(T) and K11-0057(T) were isolated from the roots of Rumex acetosa and Houttuynia cordata collected in Kanagawa Prefecture, Japan. 16S rRNA gene sequence analyses indicated that the isolates belonged to the genus Phytohabitans, and that they were closely related to each other and to Phytohabitans suffuscus K07-0523(T). The DNA-DNA relatedness values between the three isolates and Phytohabitans suffuscus were below 70%. On the basis of phylogenetic analysis, DNA-DNA relatedness values and phenotypic characteristics, the strains should be classified as novel species in the genus Phytohabitans, for which the names Phytohabitans flavus sp. nov. (type strain, K09-0627(T)=JCM 17387(T)=NBRC 107702(T)=DSM 45551(T)), Phytohabitans rumicis sp. nov. (type strain, K11-0047(T)=JCM 17829(T)=NBRC 108638(T)=BCC 48146(T)) and Phytohabitans houttuyneae sp. nov. (type strain, K11-0057(T)=JCM 17830(T)=NBRC 108639(T)=BCC 48147(T)) are proposed.


Improving cellular uptake and cytotoxicity of chitosan-coated poly(lactic-co-glycolic acid) nanoparticles in macrophages.
Aim: This research aims to identify important formulation parameters for the enhancement of nanoparticle (NP) uptake and decreasing the cytotoxicity in macrophages. Materials & methods: Fluorescent poly(lactic-co-glycolic acid) (PLGA) nanocarriers were characterized for size distributions, zeta potential and encapsulation efficiency. Incubation time, size class, PLGA derivative and chitosan derivative were assessed for uptake kinetics and cell viability. Results: The major determining factor for enhancing cellular uptake were chitosan coatings, combined with acid-terminated PLGA and small NP size. Moreover, cytotoxicity was more favorable for small, chitosan glutamate-coated, acid-terminated PLGA NPs compared with its plain chitosan-coated counterparts. Conclusion: Chitosan glutamate has been shown to be a valuable alternative coating material for acid-terminated PLGA NPs to efficiently and safely target macrophages.


Perivascular Inflammation in Pulmonary Arterial Hypertension.
Perivascular inflammation is a prominent pathologic feature in most animal models of pulmonary hypertension (PH) as well as in pulmonary arterial hypertension (PAH) patients. Accumulating evidence suggests a functional role of perivascular inflammation in the initiation and/or progression of PAH and pulmonary vascular remodeling. High levels of cytokines, chemokines, and inflammatory mediators can be detected in PAH patients and correlate with clinical outcome. Similarly, multiple immune cells, including neutrophils, macrophages, dendritic cells, mast cells, T lymphocytes, and B lymphocytes characteristically accumulate around pulmonary vessels in PAH. Concomitantly, vascular and parenchymal cells including endothelial cells, smooth muscle cells, and fibroblasts change their phenotype, resulting in altered sensitivity to inflammatory triggers and their enhanced capacity to stage inflammatory responses themselves, as well as the active secretion of cytokines and chemokines. The growing recognition of the interaction between inflammatory cells, vascular cells, and inflammatory mediators may provide important clues for the development of novel, safe, and effective immunotargeted therapies in PAH.


Controlling the motion of multiple objects on a Chladni plate.
The origin of the idea of moving objects by acoustic vibration can be traced back to 1787, when Ernst Chladni reported the first detailed studies on the aggregation of sand onto nodal lines of a vibrating plate. Since then and to this date, the prevailing view has been that the particle motion out of nodal lines is random, implying uncontrollability. But how random really is the out-of-nodal-lines motion on a Chladni plate? Here we show that the motion is sufficiently regular to be statistically modelled, predicted and controlled. By playing carefully selected musical notes, we can control the position of multiple objects simultaneously and independently using a single acoustic actuator. Our method allows independent trajectory following, pattern transformation and sorting of multiple miniature objects in a wide range of materials, including electronic components, water droplets loaded on solid carriers, plant seeds, candy balls and metal parts.


Development of Photosynthetic Activity following Anaerobic Germination in Rice-Mimic Grass (Echinochloa crus-galli var oryzicola).
Shoots of anaerobically germinated Echinochloa crus-galli var oryzicola are nonpigmented whether germinated in light or dark, and chlorophyll synthesis is minimal for the first 12 to 18 hours of greening after exposure to ambient conditions. When chlorophyll development is compared between greening anoxic and etiolated shoots, there is a 100-fold difference in chlorophyll levels at 8 hours, an 8-fold difference at 24 hours, but roughly equal amounts at 60 hours. The chlorophyll a/b ratio approaches 3 earlier in greening anoxic shoots than in greening etiolated shoots, relative to total chlorophyll. The long lag in chlorophyll synthesis can be shortened by giving dark-grown anoxic shoots a 24-hour midtreatment of air before light.Development of photosynthetic activity in etiolated shoots, determined by CO(2) gas exchange, (14)CO(2) uptake, and activity of carboxylating enzymes closely parallels development of chlorophylls. However, development of photosynthetic capability in greening anoxic shoots does not parallel chlorophyll development; ability to fix carbon lags behind chlorophyll synthesis. A reason for this lag is the very low activity of RuBP carboxylase during the first 36 hours of greening in anoxic shoots. The activity of phosphoenolpyruvate carboxylase is also delayed, but its kinetics more closely match those of chlorophyll development.


[Relative adrenal insufficiency in septic shock: comparison of the response to hydrocortisone in patients diagnosed through random cortisol measurement versus corticotropin test].
The incidence of relative adrenal insufficiency (RAI) in patients with septic shock is high and has a significant impact on survival. The purpose of this study was to determine whether a random cortisol concentration < 25 mg/dL was as good as a low dose (1 mg) corticotrophin stimulation test in the diagnosis of RAI in patients with septic shock as assessed by the hemodynamic response to hydrocortisone. Patients were randomized to a single cortisol determination or to a low dose corticotrophin stimulation test. After blood collection to cortisol determinations, hydrocortisone (100 mg every 8 hrs) was administered for all patients in the first 36 hours. RAI was defined by a random cortisol concentration < 25 mg/dL or a D cortisol concentration < 9 mg/dL in the corticotrophin test. Sixty patients (G1 = 30; G2 = 30) were included in the analysis and were comparable regarding to demographic data, nosologies and disease severity. The time to norepinephrin withdrawal in group 1 patients with RAI diagnostic criteria was not different from the patients with cortisol > 25 mg/dL. In group 2 patients with D cortisol < 9 mg/dL had a shorter time of norepinephrin infusion (3 days) compared to patients with D cortisol > 9 (6 days). This study suggests that 1 mg corticotrophin test is better than a random cortisol determination < 25 mg/dL to the diagnosis of relative adrenal insufficiency in septic shock patients.


Capecitabine-Associated Terminal Ileitis.
Capecitabine is an oral fluoropyrimidine used as adjuvant and palliative chemotherapy in patients with colorectal cancer. Diarrhea is a well-known side effect of capecitabine and 5-fluorouracil agents. We present a case with terminal ileitis as a rare adverse event of capecitabine treatment. Capecitabine-induced terminal ileitis is likely to be underreported. It should be considered more often as a cause of severe and atypical complaints of diarrhea during treatment with capecitabine or other 5-fluorouracil agents.


Hypoxia: a window into Mycobacterium tuberculosis latency.
Tuberculosis is a massive public health problem on a global scale and the success of Mycobacterium tuberculosis is linked to its ability to persist within humans for long periods without causing any overt disease symptoms. Hypoxia is predicted to be a key host-induced stress limiting growth of the pathogen in vivo. However, multiple studies in vitro and in vivo indicate that M. tuberculosis adapts to oxygen limitation by entering into a metabolically altered state, while awaiting the opportunity to reactivate. Molecular signatures of bacteria adapted to hypoxia in vitro are accumulating, although correlations to human disease are only now being established. Similarly, defining the mechanisms that control this adaptation is an active area of research. In this review we discuss the historical precedents linking hypoxia and latency, and the gathering knowledge of M. tuberculosis hypoxic responses. We also examine the role of these responses in tuberculosis latency, and identify promising avenues for future studies.


Proliferating cell nuclear antigen in developing and adult rat cardiac muscle cells.
During early development, rat cardiac muscle cells actively proliferate. Shortly after birth, division of cardiac muscle cells ceases, whereas DNA synthesis continues for approximately 2 weeks at a progressively diminishing rate. Little DNA synthesis or cell division occurs in adult cardiocytes. Thus, developing cardiac muscle cells are an ideal system in which to examine the expression of cell cycle-regulated genes during development. We chose to examine proliferating cell nuclear antigen (PCNA), a gene expressed at the G1/S phase boundary of the cell cycle. Northern blots of RNA from cardiac muscle cells from 18-day-old rat fetuses and from day 0, 5, and 14 neonatal as well as adult rat hearts revealed that the PCNA mRNA was found in cardiac muscle cells from all ages. However, because it was possible that this was a result of fibroblast PCNA gene expression, we used reverse transcription followed by polymerase chain reaction to see if it was possible to detect the message for PCNA in cardiac muscle cells from all ages. Because of the great sensitivity of this technique, RNA was recovered from 25 isolated adult cardiac muscle cells. Polymerase chain reaction amplification products for PCNA produced from the RNA isolated from these cells conclusively demonstrated that mRNA for this gene, which normally is associated with proliferating cells, is expressed in adult cardiac muscle cells that no longer divide. Furthermore, Western blot analysis demonstrated that the PCNA protein was found only in embryonic and neonatal cells and not in adult rat cardiac muscle cells. Therefore, it might be inferred from these data that PCNA might be regulated at the posttranscriptional level in adult cardiac muscle cells.


Evidence of a probable role for 25-hydroxyvitamin D in the regulation of human calcium metabolism.
1,25-Dihydroxyvitamin D [1,25-(OH)2D] is the principal mediator of the biologic effects of vitamin D. We showed previously that obese white subjects have low serum vitamin D and 25-hydroxyvitamin D (25-OHD) with increased serum-immunoreactive parathyroid hormone (PTH) and 1,25-(OH)2D, low urinary calcium, and increased urinary cyclic adenosine 3',5'-monophosphate (cyclic AMP) compared with nonobese white individuals. To determine whether 25-OHD modulates calcium metabolism, the effects of 25-OHD3, 40-100 micrograms/day for 9 days, were compared in seven obese and seven nonobese white subjects who were between the ages of 20 and 34 years. Each of them was hospitalized on a metabolic ward and given a constant daily diet that contained 400 mg calcium, 900 mg phosphate, and 18 mEq magnesium. Whereas 25-OHD3 increased mean serum 25-OHD from 7 +/- 1 to 37 +/- 5 ng/ml (P less than 0.01) and urinary calcium from 102 +/- 18 to 146 +/- 17 mg/day (P less than 0.001) and decreased mean serum 1,25-(OH)2D from 40 +/- 2 to 28 +/- 2 pg/ml (P less than 0.01) and urinary cyclic AMP from 3.23 +/- 0.57 to 2.00 +/- 0.17 nM/dl GF (P less than 0.05), it did not change mean serum calcium, ionized calcium, phosphate, magnesium, immunoreactive PTH or urinary phosphate, or creatinine clearance in the obese subjects. In contrast, 25-OHD3 increased mean serum 25-OHD from 16 +/- 1 to 46 +/- 4 pg/ml (P less than 0.001) but did not alter mean serum 1,25-(OH)2D or urinary calcium or cyclic AMP in the nonobese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of oligofructose supplementation on body weight in overweight and obese children: a randomised, double-blind, placebo-controlled trial.
Limited evidence suggests that the dietary inclusion of oligofructose, an inulin-type fructan with prebiotic properties, may increase satiety and, thus, reduce energy intake and body weight in overweight and obese adults. The aim of the present study was to assess the effect of oligofructose supplementation for 12 weeks on the BMI of overweight and obese children. A total of ninety-seven children aged 7-18 years who were overweight and obese (BMI >85th percentile) were randomly assigned to receive placebo (maltodextrin) or oligofructose (both at an age-dependent dose: 8 g/d for children aged 7-11 years and 15 g/d for children aged 12-18 years) for 12 weeks. Before the intervention, all children received dietetic advice and they were encouraged to engage in physical activity. The primary outcome measure was the BMI-for-age z-score difference between the groups at the end of the intervention. Data from seventy-nine (81%) children were available for analysis. At 12 weeks, the BMI-for-age z-score difference did not differ between the experimental (n 40) and control (n 39) groups (mean difference 0.002, 95% CI - 0.11, 0.1). There were also no significant differences between the groups with regard to any of the secondary outcomes, such as the mean BMI-for-age z-score, percentage of body weight reduction and the difference in total body fat. Adverse effects were similar in both groups. In conclusion, oligofructose supplementation for 12 weeks has no effect on body weight in overweight and obese children.


Long-range interactions between like homonuclear alkali metal diatoms.
Long-range electrostatic and van der Waals coefficients up to terms of order R(-8) have been evaluated by the sum over states method using ab initio and time-dependent density functional theory. We employ several widely used density functionals and systematically investigate the convergence of the calculated results with basis set size. Static electric moments and polarizabilities up to octopole order are also calculated. We present values for Li(2) through K(2) which are in good agreement with existing values, in addition to new results for Rb(2) and Cs(2). Interaction potential curves calculated from these results are shown to agree well with high level ab initio theory. Preliminary results are reported that demonstrate the applicability of the method to larger alkali clusters.


[Progress in research of HIV transmission network analysis methods and metrics].
HIV transmission network analysis plays a significant role in the precise prevention and control of AIDS. The current studies inferred the HIV transmission networks mainly based on the social network methods and molecular network methods and interpret the structural characteristics using individual-level and network-level metrics. To provide references for further researches, we summarized the principles, advantages or disadvantages, and application of HIV transmission network analysis methods and metrics in this paper.


Comparison of enalapril and hydrochlorothiazide in mild hypertension and changes in plasma lipid concentrations during therapy.
An open, randomized, parallel clinical study comparing the antihypertensive efficacy and tolerability of the angiotensin converting enzyme inhibitor enalapril and the diuretic hydrochlorothiazide was carried out in 40 patients with mild uncomplicated essential hypertension. Changes in plasma lipid profiles were also studied. The results show that the two treatments were equally efficacious in controlling blood pressure and were generally well tolerated. Favorable changes in the plasma lipid profile were observed during the 12-week treatment period with enalapril. However, adverse alterations in the plasma lipid profile were observed during treatment with hydrochlorothiazide. These included a significant increase in the total cholesterol/high density lipoprotein cholesterol ratio and the low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio. Further studies are needed to confirm these plasma lipid findings and to determine their clinical significance.


Mitogen-activated protein kinase cascade and transcription factors: the opposite role of MKK3/6-p38K and MKK1-MAPK.
Recent studies have revealed that mitogen-activated protein kinase (MAPK) consists of at least three subfamilies, namely classical MAPK (also known as ERK), stress-activated protein kinase/c-Jun N-terminal kinase (JNK) and p38 kinase. TGF-beta-activating kinase (TAK)-1 is a novel MAPKKK which is reported to stimulate p38K and/or the JNK pathway. To elucidate the functional roles of the TAK1 pathway, we transfected its constitutive active form (TAK1dN) and negative form (TAK1K63W) into LLC-PK1 cells. TAKdN inhibited [3H]thymidine uptake and reduced the percentages of S and G2/M phases. TAK1K63W ameliorated the inhibitory effects of TGF-beta on [3H]thymidine uptake and increased the percentages of S and G2/M phases. Western blot analysis demonstrates that the level of cyclin D1 protein was regulated negatively by overexpression of TAK1dN. Moreover, overexpression of TAK1dN inhibited cyclin D1 promoter activity. In contrast, constitutive active MKK1, the classical p42/44 MAPK activator, increased cyclin D1 promoter activity and level of protein. Overexpression of the active form of MKK1 increased [3H]thymidine uptake, while the inactive form decreased the uptake. In conclusion, cyclin D1 promoter activity and cell cycle progression are regulated negatively by the TAK1 pathway and positively by the classical MAPK pathway.


Cardiometabolic Risk Profile Among Young Adult Females With a History of Premature Adrenarche.
Premature adrenarche (PA) is associated with childhood overweight and hyperinsulinemia; the long-term cardiometabolic outcome is unknown. To study cardiometabolic profile in adult women with previous PA. Thirty women with PA and 41 control subjects were followed from prepuberty to young adulthood. Prevalence of the metabolic syndrome (MetS) and clinical and biochemical cardiovascular risk factors. There were no differences in the prevalence of MetS or in any parameters indicating dyslipidemia, hypertension, hepatosteatosis, atherosclerosis, or low-grade inflammation between the study groups. However, prevalence of insulin resistance (IR; P = 0.014) and acanthosis nigricans (P = 0.010) was higher in the PA group. Neither fasting glucose nor insulin concentrations differed between the study groups, but HbA1c [adjusted for body mass index (BMI) P = 0.011] and Homeostatic Model Assessment of Insulin Resistance (P = 0.044; BMI-adjusted P = nonsignificant) were higher in the PA group. Although BMI and fat percentage were comparable between the study groups, the PA group had higher central fat mass than the control group. In the whole study population, MetS and IR were associated with greater adult fat mass, but no prepubertal factors predicting later IR were found. PA does not seem to be associated with MetS, dyslipidemia, hypertension, atherosclerosis, or low-grade inflammation in young adult women. However, some women with PA may be at an increased risk of unfavorable glucose metabolism, which is associated with increased central adiposity at adult age rather than determined by prepubertal factors.


Dendritic ionic liquids based on imidazolium-modified poly(aryl ether) dendrimers.
A series of dendritic ionic liquids (DILs) based on imidazolium-modified poly(aryl ether) dendrimers IL-Br-Gn (n=0-3) were synthesized by a modified convergent approach and "click" chemistry. The resulting DILs exhibited high thermal resistance with decomposition temperatures up to 270 °C and low glass transition temperatures in the range of approximately -5-0 °C. All IL-Br-Gn were found to be miscible with water at any ratio and could encapsulate hydrophobic molecules. The reversible phase transfer of the DILs between the aqueous and organic phases was accomplished by simple anion exchange between the hydrophilic Br(-) anion and the hydrophobic bis(trifluoromethylsulfonyl)amide anion (NTf2(-)). IL-Br-Gn could be used as transporters to shuttle hydrophobic molecules between the organic and aqueous phases efficiently. The present work provides a new kind of transporting materials with potential applications in substance separation, drug delivery, and biomolecule transport.


Expression pattern and secretion of human and chicken heparanase are determined by their signal peptide sequence.
Cleavage of heparan sulfate (HS) proteoglycans affects the integrity and function of tissues and thereby fundamental phenomena, involving cell migration and response to changes in the extracellular microenvironment. The role of HS-degrading enzymes, commonly referred to as heparanases, in normal development has not been identified. The present study focuses on cloning, expression, and properties of a chicken heparanase and its distribution in the developing chicken embryo. We have identified a chicken EST, homologous to the recently cloned human heparanase, to clone and express a functional chicken heparanase, 60% homologous to the human enzyme. The full-length chicken heparanase cDNA encodes a 60-kDa proenzyme that is processed at the N terminus into a 45-kDa highly active enzyme. The most prominent difference between the chicken and human enzymes resides in the predicted signal peptide sequence, apparently accounting for the chicken heparanase being readily secreted and localized in close proximity to the cell surface. In contrast, the human enzyme is mostly intracellular, localized in perinuclear granules. Cells transfected with a chimeric construct composed of the chicken signal peptide preceding the human heparanase exhibited cell surface localization and secretion of heparanase, similar to cells transfected with the full-length chicken enzyme. We examined the distribution pattern of the heparanase enzyme in the developing chicken embryo. Both the chicken heparanase mRNA and protein were expressed, as early as 12 h post fertilization, in cells migrating from the epiblast and forming the hypoblast layer. Later on (72 h), the enzyme is preferentially expressed in cells of the developing vascular and nervous systems. Cloning and characterization of heparanase, the first and single functional vertebrate HS-degrading enzyme, may lead to identification of other glycosaminoglycan degrading enzymes, toward elucidation of their significance in normal and pathological processes.


Photocontrol of the Germination of Onoclea Spores: II. Analysis of Germination Processes by Means of Anaerobiosis.
The oxygen requirements during the three phases of photoinduced germination of Onoclea sensibilis L. spores were analyzed by temporarily applying nitrogen atmosphere. The dark preinduction phase, during which the spores imbibe water and establish sensitivity to irradiation, involves an oxidative process which can be reversibly inhibited and stimulated by nitrogen and air, respectively. The induction phase of germination is characterized by a pure photochemical reaction, independent of temperature and oxygen. The postinduction phase, when the photoproduct triggers dark processes eventually leading to the protrusion of the rhizoidal or protonematal cells, involves an oxidative process which occurs within the first 10 hours of this phase. This oxidative process differs in kinetic characteristics from that in the preinduction phase. The oxidative process is inhibited by nitrogen treatment, but following nitrogen inhibition the ability of the spores to germinate can be reinstated by a long period of air intervening between the nitrogen treatment and a second irradiation. This suggests that enzymes or reactants which are needed in the postinduction process decay under anaerobic conditions and are resynthesized when the spores are transferred to air. Spores take up acetocarmine stain towards the latter part of the postinduction phase. Stain uptake is apparently succeeded very closely by cell division, and some time later by protrusion of the germling cells.


Homicide and schizophrenia: maybe treatment does have a preventive effect.
BACKGROUND: Persons with schizophrenia have been found to be at increased risk for homicide as compared with the general population. The increased risk may be associated with the implementation of the policy of deinstitutionalization. METHOD: Persons with schizophrenia who had committed or attempted homicide in the German state of Hessen from 1992 to 1996 and in the Federal Republic of Germany from 1955 to 1964 were compared. RESULTS: Schizophrenia increased the risk of homicide 16.6 times (95% CI 11.2-24.5) in the recent cohort and 12.7 times (95% CI 11.2-14.3) in the older cohort. These odds ratios are not statistically different. The lack of appropriate services for chronic high-risk patients and the non-use of mental health services by first episode, acutely psychotic patients were associated with homicide. CONCLUSION: There has been no increase in the risk of homicide among persons with schizophrenia since the implementation of the policy of deinstitutionalization. The examination of the recent period suggests that the provision of specialized long-term care to persons with schizophrenia who are at high risk for violent behaviour and the use of mental health services by acutely psychotic persons may reduce the risk of homicide.


How does growth hormone releasing hexapeptide self-assemble in nanotubes?
Growth hormone releasing peptide, GHRP-6, a hexapeptide (His-(D-Trp)-Ala-Trp-(D-Phe)-Lys-NH2, MW = 872.44 Da) that belongs to a class of synthetic growth hormone secretagogues, can stimulate growth hormone secretion from somatotrophs in several species including humans. In the present study, we demonstrate that GHRP-6 dispersed in aqueous solution, at pH 7.0, room temperature of 22 °C, is able to form long nanotubes, which is evidenced by combining small angle X-ray scattering (SAXS), transmission electron microscopy and molecular dynamics simulation results. Such nanotubes possess inner and outer cross-sections equal to 6.7(2) nm and 13.4(5) nm, respectively. The mechanism of peptide self-assembly was determined by molecular dynamics simulations revealing that the peptides self-assemble like amphiphilic molecules in aqueous solution in a partially interdigitated structure. In this case, the position of the positively charged amino terminus is located at the peptide-water interface, whereas the neutral NH2-capped carboxy terminus remains buried at the hydrophobic core. In contrast, the long side chain of Lys-6 stretches out of the hydrophobic core positioning its positive charge near the cylinder surface. The peptide configuration in the nanotube wall comes from the interplay between the hydrophobic interactions of the aromatic side chains of GHRP-6 and the electrostatic repulsion of its cationic charges. On increasing the peptide concentration, the long nanotubes self-arrange in solution displaying a bi-dimensional hexagonal-like packing in the SAXS curves, with a center-to-center distance of ∼15 nm. Further, we also show that the nanostructure formed in solution is quite stable and is preserved following transfer to a solid support.


Prenatal Cadmium Exposure Alters Proliferation in Mouse CD4+ T Cells via LncRNA Snhg7.
Prenatal cadmium (Cd) exposure leads to immunotoxic phenotypes in the offspring affecting coding and non-coding genes. Recent studies have shown that long non-coding RNAs (lncRNAs) are integral to T cell regulation. Here, we investigated the role of long non-coding RNA small nucleolar RNA host gene 7 (lncSnhg7) in T cell proliferation. RNA sequencing was used to analyze the expression of lncRNAs in splenic CD4+ T cells with and without CD3/CD28 stimulation. Next, T cells isolated from offspring exposed to control or Cd water throughout mating and gestation were analyzed with and without stimulation with anti-CD3/CD28 beads. Quantitative qPCR and western blotting were used to detect RNA and protein levels of specific genes. Overexpression of a miR-34a mimic was achieved using nucleofection. Apoptosis was measured using flow cytometry and luminescence assays. Flow cytometry was also used to measure T cell proliferation in culture. Finally, lncSnhg7 was knocked down in splenic CD4+ T cells with lentivirus to assess its effect on proliferation. We identified 23 lncRNAs that were differentially expressed in stimulated versus unstimulated T cells, including lncSnhg7. LncSnhg7 and a downstream protein, GALNT7, are upregulated in T cells from offspring exposed to Cd during gestation. Overexpression of miR-34a, a regulator of lncSnhg7 and GALNT7, suppresses GALNT7 protein levels in primary T cells, but not in a mouse T lymphocyte cell line. The T cells isolated from Cd-exposed offspring exhibit increased proliferation after activation in vitro, but Treg suppression and CD4+ T cell apoptosis are not affected by prenatal Cd exposure. Knockdown on lncSnhg7 inhibits proliferation of CD4+ T cells. Prenatal Cd exposure alters the expression of lncRNAs during T cell activation. The induction of lncSnhg7 is enhanced in splenic T cells from Cd offspring resulting in the upregulation of GALNT7 protein and increased proliferation following activation. miR-34a overexpression decreased GALNT7 expression and knockdown of lncSnhg7 inhibited proliferation suggesting that the lncSnhg7/miR-34a/GALNT7 is an important pathway in primary CD4+ T cells. These data highlight the need to understand the consequences of environmental exposures on lncRNA functions in non-cancerous cells as well as the effects in utero.


Applications of cell resealing to reconstitute microRNA loading to extracellular vesicles.
MicroRNAs (miRNAs) are cargo carried by extracellular vesicles (EVs) and are associated with cell-cell interactions. The response to the cellular environment, such as disease states, genetic/metabolic changes, or differences in cell type, highly regulates cargo sorting to EVs. However, morphological features during EV formation and secretion involving miRNA loading are unknown. This study developed a new method of EV loading using cell resealing and reconstituted the elementary miRNA-loading processes. Morphology, secretory response, and cellular uptake ability of EVs obtained from intact and resealed HeLa cells were comparable. Exogenously added soluble factors were introduced into multivesicular endosomes (MVEs) and their subsequent secretion to the extracellular region occurred in resealed HeLa cells. In addition, miRNA transport to MVEs and miRNA encapsulation to EVs followed a distinct pathway regulated by RNA-binding proteins, such as Argonaute and Y-box binding protein 1, depending on miRNA types. Our cell-resealing system can analyze disease-specific EVs derived from disease model cells, where pathological cytosol is introduced into cells. Thus, EV formation in resealed cells can be used not only to create a reconstitution system to give mechanistic insight into EV encapsulation but also for applications such as loading various molecules into EVs and identifying disease-specific EV markers.


Awareness and Acceptance of Hematopoietic Stem Cell Transplantation for Sickle Cell Disease in Jazan Province, Saudi Arabia.
Sickle cell diseases (SCD) are a group of inherited disorders that lead to abnormal beta subunits of hemoglobin (Hb) and are characterized by several complications which can be life-threatening. The prevalence of this disease is high in Jazan province, Saudi Arabia. The current protocol for the treatment of SCD is mainly based on alleviating signs and symptoms to avoid severe complications. Hematopoietic stem cell transplant (HSCT) is considered a definitive therapy for SCD. However, there is a long patient waiting list for HSCT in Saudi Arabia. A lack of community awareness and incorrect information about the importance of HSCT in SCD treatment is believed to be contributing to the shortage in HSCT. Thus, this study aims to assess community awareness and attitudes toward HSCT as a cure for SCD in Jazan province, Saudi Arabia. An observational cross-sectional retrospective study was conducted in Jazan province. General and demographic data were collected and pretested survey including questions about public knowledge and attitude toward HSCT for SCD were answered. Both t-test and chi-square tests were used for analysis. 1167 participants were included in this study with a mean age of 26 (SD: 8). About 50% of the study participants believed that SCD can be treated and 78% of the study participants already have heard about HSCT. About 57% of the participants defined HSCT correctly and 42% were willing to donate. Better knowledge and positive attitude toward HSCT were significantly reported among patients with SCD or their relatives as well as among people with higher education and healthcare workers (HCW). About 57% of the study participants were able to define HSCT and most related questions were answered correctly. A positive correlation was found between the knowledge about HSCT and people with higher education or those who were diagnosed with SCD or their relatives and friends. Further, only 42% of our study participants were willing to donate, a percent that is positively associated with better knowledge about HSCT. National education programs are needed to enhance the overall awareness of Jazan communities toward HSCT which could contribute to reducing the number of patients waiting for HSCT.


Time for a paradigm change? Tracing the institutionalisation of health impact assessment in the Republic of Ireland across health and environmental sectors.
This paper presents a critical analysis of health impact assessment (HIA) in the Republic of Ireland (ROI) in the context of institutional policy and practice. It begins with a brief background to the origins and aims of HIA. Core developments in health and environmental sectors pertaining to HIA in the ROI are then considered. A series of significant developments have taken place in these sectors over the past decade that are positively associated with the promotion of HIA in the ROI. However, it is argued that in spite of various institutional facilitators, the practice of implementing HIAs in the ROI is significantly underdeveloped, and it continues to lag behind several of its European Union counterparts. It is contended that a paradigm change is required in order to address the current policy-action gap. An organisation theory framework is used to assess the implementation problem and a number of suggestions are highlighted as potential facilitators of this process.


A Comparison of 3D and 2D FE Frictional Heating Models for Long and Variable Applications of Railway Tread Brake.
The article proposes two 3D and 2D numerical FE models of frictional heating for the estimation of temperature distributions in railway tread brake in 1xBg configuration during repeated long-term braking. The results of computations were compared with the time courses of temperature measured using thermocouples throughout the duration of the tests on a full-scale dynamometer for two different brake shoe materials in combination with a steel wheel. The resulting temperature distributions calculated using the proposed models agreed well with the experimental measurements, and the maximum difference in temperature values does not exceed 20%. It has been proven that 2D FE model can be as efficient as 3D model to estimate the temperature distribution during long-term and variable braking in the considered friction node. The differences in the calculation of the temperature values using these models did not exceed 3%, and the calculation time for the 2D model, compared to the 3D model, was shorter approximately 85 times for the braking cycle lasting 5032 s, and approximately 45 times for the braking cycle lasting 3297 s.


EEG, cognitive and psychopathological abnormalities in children irradiated in utero.
Computerised EEG, a clinical neuropsychiatric examination, and IQ tests were examined in 50 randomly selected prenatally irradiated 9-10-year-old children and compared with 50 randomly selected non-exposed control children of the same age. In the prenatally irradiated children a disorganised EEG-pattern with slow and paroxysmal activity (acute and high-voltage delta-waves, sometimes: spike-waves) in the left fronto-temporal region was disclosed. There was also a significant predominance of delta- and beta (dominant frequency: 20 Hz)-power in the frontal lobe, particularly, in the left fronto-temporal region, together with depressed spectral theta-power. The more disorganised EEG-patterns were observed in those children exposed at 8-15 weeks of prenatal development, while left-hemisphere abnormalities were more typical for those exposed later at 16-25 weeks of gestation. There was also a significant increase of borderline and low range (70-90) IQ scores and a significant decrease of high verbal (> 110) IQ scores. Disorders of psychological development, particularly specific developmental disorders of speech, language, and scholastic skills were more common and correlated with left-sided slow- and fast-wave activity. Behavioural and emotional disorders (social estrangement, exhaustion, emotional lability, tearfulness, apathy) were also more common and associated with a L > R imbalance in arousal. We hypothesise that the cerebral basis of mental disorders in the prenatally irradiated children is the malfunction of the left hemisphere limbic-reticular structures, particularly in those exposed at the most critical period of cerebrogenesis (16-25 weeks of gestation). We propose that the left hemisphere is more vulnerable to prenatal irradiation than the right.