Effects of normal aging on prefrontal area 46 in the rhesus monkey.
This review is concerned with the effects of normal aging on the structure and function of prefrontal area 46 in the rhesus monkey (Macaca mulatta). Area 46 has complex connections with somatosensory, visual, visuomotor, motor, and limbic systems and a key role in cognition, which frequently declines with age. An important question is what alterations might account for this decline. We are nowhere near having a complete answer, but as will be shown in this review, it is now evident that there is no single underlying cause. There is no significant loss of cortical neurons and although there are a few senile plaques in rhesus monkey cortex, their frequency does not correlate with cognitive decline. However, as discussed in this review, the following do correlate with cognitive decline. Loss of white matter has been proposed to result in some disconnections between parts of the central nervous system and changes in the structure of myelin sheaths reduce conduction velocity and the timing in neuronal circuits. In addition, there are reductions in the inputs to cortical neurons, as shown by regression of dendritic trees, loss of dendritic spines and synapses, and alterations in transmitters and receptors. These factors contribute to alterations in the intrinsic and network physiological properties of cortical neurons. As more details emerge, it is to be hoped that effective interventions to retard cognitive decline can be proposed.


Effect of the Rhinoplasty Technique and Lateral Osteotomy on Periorbital Edema and Ecchymosis.
The present study aimed to compare edema and ecchymosis in the early and late postoperative periods following the application of different surgical techniques (open and endonasal) and different types of lateral osteotomy (internal and external). The files and photographs of a total of 120 patients whose records were regularly maintained/updated and who underwent septorhinoplasty operation with the same surgeon were retrospectively evaluated. Sixty-nine (57.5%) patients were women and 51 (43.5%) were men. The patients were divided into 4 different groups according to the operations they underwent as follows--Group I: open technique septorhinoplasty + internal/continuous lateral osteotomy; Group II: endonasal rhinoplasty + internal/continuous lateral osteotomy; Group III: open technique septorhinoplasty + external/perforating lateral osteotomy; and Group IV: endonasal rhinoplasty + external/perforating lateral osteotomy. Postoperative edema and ecchymosis, and lateral nasal wall mucosal damage because of osteotomy were evaluated. Postoperative second day edema and ecchymosis scores were statistically significantly better in patients in Group II compared with the patients in Group I (P = 0.010 and P = 0.004, respectively). Postoperative first day edema and postoperative seventh day ecchymosis scores were statistically significantly better in the patients in Group IV compared with the patients in Group III (P = 0.025 and P = 0.011, respectively). Intraoperative bleeding was similar in all groups. The nasal tip was more flexible in patients who underwent closed technique rhinoplasty. Unilateral mucosal damage occurred in 3 patients (4%) with internal lateral osteotomy, whereas no mucosal damage was present in patients with external osteotomy. The difference in the rate of edema and ecchymosis in the early postoperative period between the closed technique rhinoplasty and the open surgical approach was statistically significant, whereas osteotomy did not cause a significant difference. According to these results, the authors suggest endonasal surgery to prevent the development of edema and ecchymosis, whereas the choice of lateral osteotomy should be dependent on the experience of the surgeon.


Shoot has important roles in strigolactone production of rice roots under sulfur deficiency.
Strigolactones (SLs) are a class of plant hormones that control plant architecture. SL levels in roots are determined by the nutrient conditions in the rhizosphere, especially the levels of nitrogen (N) and phosphorus (P). Our previous research showed that SL production is induced in response to deficiency of sulfur (S) as well as of N and P, and inhibits shoot branching, accelerates leaf senescence, and regulates lamina joint angle in rice. Here we show biomass, total S contents, and SL levels in rice under S-sufficient and S-deficient conditions using a split-root system. When one part of the root system was cultured in S-sufficient medium and the other in S-deficient medium (+S/-S), shoot fresh weight was unaffected relative to the +S/+S condition. The shoot weight significantly decreased in -S/-S condition. In contrast, there was no significant difference in root fresh weight between +S and -S conditions. In +S/-S condition, SL levels were systemically reduced in both parts, the shoot S content increased, but the root S content in S-deficient medium was unaffected relative to the -S/-S condition. These results suggest that shoots, not roots, recognize S deficiency, which induces SL production in roots.


Alloreactive Immune Response Associated to Human Mesenchymal Stromal Cells Treatment: A Systematic Review.
The well-known immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) are the reason why they are being used for the treatment of many diseases. Because they are considered hypoimmunogenic, MSCs treatments are performed without considering histocompatibility barriers and without anticipating possible immune rejections. However, recent preclinical studies describe the generation of alloantibodies and the immune rejection of MSCs. This has led to an increasing number of clinical trials evaluating the immunological profile of patients after treatment with MSCs. The objective of this systematic review was to evaluate the generation of donor specific antibodies (DSA) after allogeneic MSC (allo-MSC) therapy and the impact on safety or tolerability. Data from 555 patients were included in the systematic review, 356 were treated with allo-MSC and the rest were treated with placebo or control drugs. A mean of 11.51% of allo-MSC-treated patients developed DSA. Specifically, 14.95% of these patients developed DSA and 6.33% of them developed cPRA. Neither the production of DSA after treatment nor the presence of DSA at baseline (presensitization) were correlated with safety and/or tolerability of the treatment. The number of doses administrated and human leucocyte antigen (HLA) mismatches between donor and recipient did not affect the production of DSA. The safety of allo-MSC therapy has been proved in all the studies and the generation of alloantibodies might not have clinical relevance. However, there are very few studies in the area. More studies with adequate designs are needed to confirm these results.


Cognitive functioning in young "social drinkers": is there impairment to detect?
Literature on the cognitive effects of nonexcessive alcohol use suggests that relatively high-quantity-per-occasion use may be related to subsequent decreases in sober-state abstracting skills in adults, but provides no clear prediction for youth. The need to identify persistent alcohol-intake effects on cognition is particularly acute for the period of adolescence and young adulthood because even slight damage may impair developmentally significant skills. We examine the relation between multiple measures of neuropsychological status and both continuous and categorical measures of alcohol-use patterns in an age- and sex-stratified sample of 1,308 18-, 21-, and 24-year-olds. The results of correlational and hierarchial regression analyses suggest that cognitive performance bears little direct relation to drinking behaviors in young nonclinical males and females. Although the data provide no strong support for the hypothesis of a causal relationship between alcohol use and cognitive functioning, there is a slight suggestion that frequent high-quantity consumption may become a salient parameter of use as subjects age. Prospective longitudinal data are needed to explore the directional causality of effects.


[Genetic polymorphism of 6 short tandem repeat loci in Chinese Korean].
To analyze genetic polymorphism of D16S539 D7S820 D13S317 CSF1PO TPOX and TH01 in Chinese Korean. One hundred unrelated individuals were analyzed by PCR amplification fragment length polymorphism analysis. Six alleles and 18 genotypes of D16S539 locus, 7 alleles and 22 genotypes of D7S820 locus, 7 alleles and 23 genotypes of D13S317 locus, 6 alleles and 16 genotypes of CSF1PO locus, 6 alleles and 11 genotypes of TPOX locus, 5 alleles and 12 genotypes of TH01 locus. The genotype distribution of all the 6 short tandem repeat(STR) in Chinese Korean met Hardy-Weinberg equilibrium, and have higher heterozygosities. The data obtained can be used in human identity and paternity testing, and in other genetic researches and population investigation.


[Prevalence of exfoliatin-producing strains in phage group II "Staphylococcus aureus" (author's transl)].
Prevalence of exfoliatin production has been investigated in 100 strains of Staphylococcus aureus, bacteriophage group II, by inoculation into newborn mice. Serotyping, detection of protein A and antibiotic susceptibility tests have also been performed. Thirty-one strains (31%) were toxin producers; they all produced a yellow pigment; there was no difference in phage attacks between toxinogenic and non-toxinogenic strains; but exfoliatin production was significantly associated to the presence of agglutinogens h2 and 263-2; rate of protein-A presence and of antibiotic susceptibility did not differ between the two groups of strains. In addition, toxin production has been investigated in 31 isolates from various skin lesions; 9 were found toxinogenic (8 amongst them had been cultivated from bullous lesions); most of them belonged to phage group II and possessed agglutinogens h2 and 263-2. So, in order to carry out the diagnosis of some bacterial skin infections, clinical symptoms, pathological and bacteriological data must be compared; the latter must include phage-typing, serotyping and exfoliatin detection.


Haplodiploidy and the evolution of eusociality: split sex ratios.
It is generally accepted that from a theoretical perspective, haplodiploidy should facilitate the evolution of eusociality. However, the "haplodiploidy hypothesis" rests on theoretical arguments that were made before recent advances in our empirical understanding of sex allocation and the route by which eusociality evolved. Here we show that several possible promoters of the haplodiploidy effect would have been unimportant on the route to eusociality, because they involve traits that evolved only after eusociality had become established. We then focus on two biological mechanisms that could have played a role: split sex ratios as a result of either queen virginity or queen replacement. We find that these mechanisms can lead haplodiploidy to facilitating the evolution of helping but that their importance varies from appreciable to negligible, depending on the assumptions. Furthermore, under certain conditions, haplodiploidy can even inhibit the evolution of helping. In contrast, we find that the level of promiscuity has a strong and consistently negative influence on selection for helping. Consequently, from a relatedness perspective, monogamy is likely to have been a more important driver of eusociality than the haplodiploidy effect.


Dying young in traffic.
There were 469 unnatural deaths among the Sheffield child population between 1947 and 1979, 226 of which were caused by traffic accidents. The annual incidence of these fatal traffic accidents has risen steadily since the early 1960s with boys being consistently more vulnerable. Fatal accidents were disproportionately higher among socially deprived families and in poorer areas of the city. The environment rather than the child may be 'accident prone' and there is an urgent need for safer play areas in deprived areas.


Rhombencephalitis caused by Francisella tularensis.
Common presentations of tularemia include pneumonia and ulceroglandular, oropharyngeal, or typhoidal disease. Neuromeningeal involvement is extremely rare. We report a case of a severe rhombencephalitis due to Francisella tularensis. Diagnosis was possible thanks to a very precise interview, and the patient dramatically improved after specific antibiotherapy.


The expression patterns and putative function of nitrate transporter 2.5 in plants.
Nitrate transporter 2.5 (NRT2.5) was originally characterized as the transporter for nitrogen (N) limitation. In Arabidopsis, NRT2.5 is expressed mainly under extremely low NO3- and N starvation conditions, and this must work in conjunction with NAR2.1. NRT2.5 is expressed both in the roots and leaves in Arabidopsis, poplars, tea trees and cassava. This is also expressed in the seeds of Arabidopsis and wheat. In wheat, NRT2.5 is expressed in the embryo and shell and plays a role in the accumulation of NO3- in the seeds. In maize, this is also expressed in silk, cobs and tassel husk leaves. In rice, OsNRT2.5 (also known as OsNRT2.3a) may help the species to remove NO3- from the roots to shoots. In addition, NRT2.5 may interact with TGA3, MYC1, LBD37, LBD38, TaNAC2 and other transcription factors and participate in the transmission of NO3- signals. The present review summarizes the functions of NRT2.5 in different plant species, which may help plant breeders and molecular biologists to improve crop yield. Abbreviations: NRT, Nitrate transporter; NUE, nitrogen use efficiency; PTR, peptide transporter; NPF, nitrate peptide transporter family; CLC, chloride channel; LAC1/SLAH, slow anion channel-associated 1 homolog 3; LATS, low-affinity transporter systems; HATS, high-affinity transport systems; NNP, nitrate-nitrite-porter; MFS, major facilitator superfamily.


Development of an immunoassay for rapid detection of ganglioside GM(1) mimicry in Campylobacter jejuni strains.
Mimicry of peripheral nerve gangliosides by Campylobacter jejuni lipopolysaccharides (LPSs) has been proposed to induce cross-reacting antiganglioside antibodies in Guillain-Barré syndrome (GBS). Because current methods for LPS characterization are labor-intensive and inhibit the screening of large numbers of strains, a rapid GM(1) epitope screening assay was developed. Biomass from two agar plates of confluent growth yielded sufficient LPS using a novel phenol-water and ether extraction procedure. Extracts of LPS were reacted with cholera toxin (GM(1) ligand), peanut agglutinin (Gal beta1-->3GalNAc ligand), and anti-GM(1) antibodies. After the assay was validated, 12 of 59 (20%) C. jejuni serostrains, including four serotypes that have not previously been associated with GBS, reacted with two or more anti-GM(1) ganglioside reagents. Subsequently, LPS extracts from 5 of 7 (71%) C. jejuni isolates and 2 of 3 (67%) C. jejuni culture collection strains bore GM(1) structures. Overall, the assay system was reliable, efficient, and reproducible and may be adapted for large-scale epidemiological studies.


Lessons from the lysozyme of phage T4.
An overview is presented of some of the major insights that have come from studies of the structure, stability, and folding of T4 phage lysozyme. A major purpose of this review is to provide the reader with a complete tabulation of all of the variants that have been characterized, including melting temperatures, crystallographic data, Protein Data Bank access codes, and references to the original literature. The greatest increase in melting temperature (T(m)) for any point mutant is 5.1 degrees C for the mutant Ser 117 --> Val. This is achieved in part not only by hydrophobic stabilization but also by eliminating an unusually short hydrogen bond of 2.48 A that apparently has an unfavorable van der Waals contact. Increases in T(m) of more than 3-4 degrees C for point mutants are rare, whereas several different types of destabilizing substitutions decrease T(m) by 20 degrees C or thereabouts. The energetic cost of cavity creation and its relation to the hydrophobic effect, derived from early studies of "large-to-small" mutants in the core of T4 lysozyme, has recently been strongly supported by related studies of the intrinsic membrane protein bacteriorhodopsin. The L99A cavity in the C-terminal domain of the protein, which readily binds benzene and many other ligands, has been the subject of extensive study. Crystallographic evidence, together with recent NMR analysis, suggest that these ligands are admitted by a conformational change involving Helix F and its neighbors. A total of 43 nonisomorphous crystal forms of different monomeric lysozyme mutants were obtained plus three more for synthetically-engineered dimers. Among the 43 space groups, P2(1)2(1)2(1) and P2(1) were observed most frequently, consistent with the prediction of Wukovitz and Yeates.


Artificial urinary sphincter implantation for neurogenic bladder: a multi-institutional study in 107 children.
To evaluate the outcome of implantation of the AMS 800 artificial urinary sphincter in children with neurogenic bladder. The records of 107 children (74 boys and 33 girls) treated for neurogenic urinary incontinence by implantation of the AMS 800 artificial sphincter between 1983 and 1993 were reviewed retrospectively. The underlying cause of incontinence in 92 patients was spina bifida, the mean age at implantation was 13.7 years and 30 patients had undergone previous bladder neck surgery. Implantation was carried out in combination with another surgical procedure in 24.3% of patients. The mean follow-up was 61 months (minimum 12). The mean operational life of the sphincter was 56 months. No deaths occurred but removal of the artificial sphincter was necessary in 20 patients (19%). Surgical revision was not required in 44 patients (41%) but at least one revision was performed in 63 and more than one in 42. There were 21 mechanical failures, 40 surgical complications and 39 cases involving changes in the dynamics of bladder function. Of the 87 children (81%) in whom the device is still in place, 72 are completely continent (83%), 10 are slightly wet, and five are incontinent. The overall success rate was 77%. The results emphasize that for successful implantation of an artificial urinary sphincter in children, the pre-operative bladder capacity must be sufficient and previous surgery should not have been performed on the bladder neck, the site of choice for implantation in children. Sphincterotomy is not always necessary in paediatric patients. Children and parents should be informed of the high complication rate and the need for long-term follow-up.


Polyols Induce the Production of Antifungal Compounds by Lactobacillus plantarum.
Mycotoxins may be present in nuts, coffee, cereals, and grapes, among other products. Increasing concerns about human health and environmental protection have driven the application of biological control techniques that can inhibit fungal contaminants. In this study, the growth inhibition of the ochratoxigenic fungus Aspergillus carbonarius Ac 162 was evaluated using 5 lactic acid bacteria (LAB). The LAB studied were Lactobacillus plantarum MZ801739 (J), Lactobacillus plantarum MZ809351 (31) and Lactobacillus plantarum MZ809350 (34), isolated in the Ivory Coast, and Lactobacillus plantarum MN982928 (3) and Leuconostoc citreum MZ801735 (23), isolated in Mexico. J, 31, 34, 3 and 23 are the internal strain codes from our laboratory. LAB were cultivated in De Man, Rogosa and Sharpe (MRS) broth, and different polyols (glycerol, mannitol, sorbitol, and xylitol) were added to the culture broth to stimulate the production of antifungal compounds. The fungal inhibition studies were performed using the poisoned food technique. The highest inhibition of A. carbonarius growth was obtained by cultivating L. plantarum MZ809351 in the presence of xylitol and glycerol. Under these conditions, 1 L of the L. plantarum MZ809351 cultures were used to identify antifungal compounds. The compounds were concentrated by solid-phase extraction and then characterized by GC-MS. In addition to 9-octadecenoic acid, 3 diketopiperazines or cyclic dipeptides were identified, including cyclo (Leu-Leu), cyclo (Pro-Gly) and cyclo (Val-Phe), which were compounds related to microbial antifungal activities. Xylitol and glycerol induced the production of these antifungal compounds against A. carbonarius Ac 162. On the other hand, adding xylitol and glycerol to the MRS broth reduced the Ochratoxin A (OTA) content to 56.8 and 54.7%, respectively. This study shows the potential for using L. plantarum MZ809351 as a biocontrol agent to prevent the growth of A. carbonarius and reduce the production of OTA in foods.


Solubility engineering and crystallization of human apolipoprotein D.
Human apolipoprotein D (ApoD) is a physiologically important member of the lipocalin protein family that was discovered as a peripheral subunit of the high-density lipoprotein (HDL) but is also abundant in other body fluids and organs, including neuronal tissue. Although it has been possible to produce functional ApoD in the periplasm of Escherichia coli and to demonstrate its ligand-binding activity for progesterone and arachidonic acid, the recombinant protein suffers from a pronounced tendency to aggregate and to adsorb to vessel surfaces as well as chromatography matrices, thus hampering further structural investigation. Here, we describe a systematic mutagenesis study directed at presumably exposed hydrophobic side chains of the unglycosylated recombinant protein. As a result, one ApoD mutant with just three new amino acid substitutions--W99H, I118S, and L120S--was identified, which exhibits the following features: (1) improved yield upon periplasmic biosynthesis in E. coli, (2) elution as a monomeric protein from a gel permeation chromatography column, and (3) unchanged binding activity for its physiological ligands. In addition, the engineered ApoD was successfully crystallized (space group I4 with unit cell parameters a = 75.1 A, b = 75.1 A, c = 166.0 A, alpha = beta = gamma = 90 degrees), thus demonstrating its conformationally homogeneous behavior and providing a basis for the future X-ray structural analysis of this functionally still puzzling protein.


National and sub-national exposure to ambient fine particulate matter (PM2.5) and its attributable burden of disease in Iran from 1990 to 2016.
Ambient particulate matter is a public health concern. We aimed (1) to estimate national and provincial long-term exposure of Iranians to ambient particulate matter (PM) < 2.5 μm (PM2.5) from 1990 to 2016, and (2) to estimate the national and provincial burden of disease attributable to PM2.5 in Iran. We used all available ground measurements of PM < 10 μm (PM10) (used to estimate PM2.5) from 91 monitoring stations. We estimated the annual mean exposure to PM2.5 for all Iranian population from 1990 to 2016 through a multi-stage modeling process. By applying comparative risk assessment methodology and using life table for years of life lost (YLL), we estimated the mortality and YLL attributable to PM2.5 for five outcomes. The predicted provincial annual mean PM2.5 concentrations range was between 21.7 μg/m3 (UI: 19.03-24.9) and 35.4 μg/m3 (UI: 31.4-39.4) from 1990 to 2016. We estimated in 2016, about 41,000 deaths (95% uncertainty interval [UI] 35634, 47014) and about 3,000,000 YLL (95% UI: 2632101, 3389342) attributable to the long-term exposure to PM2.5 in Iran. Ischemic heart disease was the leading cause of mortality by 31,363 deaths (95% UI: 27520, 35258), followed by stroke (7012 (5999, 8062) deaths), lower respiratory infection (1210 (912, 1519) deaths), chronic obstructive pulmonary disease (1019 (715, 1328) deaths), and lung cancer (668 (489, 848) deaths). In 2016, about 43% of all PM2.5 related mortality in Iran was, respectively, in the following provinces: Tehran (12.6%), Isfahan (9.3%), Khorasan Razavi (8.0%), Fars (6.5%), and Khozestan (6.4%). In summary, we found that the majority of Iranians were exposed to the levels of ambient particulate matter exceeding the WHO guidelines from 1990 to 2016. Further, we found that there was an increasing trend of total mortality attributed to PM2.5 in Iran from 1990 to 2016 where the slope was higher in western provinces.


Lexical and talker effects on word recognition among native and non-native listeners with normal and impaired hearing.
Evidence suggests that word recognition depends on numerous talker-, listener-, and stimulus-related characteristics. The current study examined the effects of talker variability and lexical difficulty on spoken-word recognition among four groups of listeners: native listeners with normal hearing or hearing impairment (moderate sensorineural hearing loss) and non-native listeners with normal hearing or hearing impairment. The ability of listeners to accommodate trial-to-trial variations in talkers' voice was assessed by comparing recognition scores for a single-talker condition to those obtained in a multiple-talker condition. Lexical difficulty was assessed by comparing word-recognition performance between lexically "easy" and "hard" words as determined by frequency of occurrence in language and the structural characteristics of similarity neighborhoods formalized in the Neighborhood Activation Model. An up-down adaptive procedure was used to determine the sound pressure level for 50% performance. Non-native listeners in both normal-hearing and hearing-impaired groups required greater intensity for equal intelligibility than the native normal-hearing and hearing-impaired listeners. Results, however, showed significant effects of talker variability and lexical difficulty for the four groups. Structural equation modeling demonstrated that an audibility factor accounts for 2-3 times more variance in performance than does a linguistic-familiarity factor. However, the linguistic-familiarity factor is also essential to the model fit. The results demonstrated effects of talker variability and lexical difficulty on word recognition for both native and nonnative listeners with normal or impaired hearing. The results indicate that linguistic and indexical factors should be considered in the development of speech-recognition tests.


Single infrared light pulses induce excitatory and inhibitory neuromodulation.
The excitatory and inhibitory effects of single and brief infrared (IR) light pulses (2 µm) with millisecond durations and various power levels are investigated with a custom-built fiber amplification system. Intracellular recordings from motor axons of the crayfish opener neuromuscular junction are performed ex vivo. Single IR light pulses induce a membrane depolarization during the light pulses, which is followed by a hyperpolarization that can last up to 100 ms. The depolarization amplitude is dependent on the optical pulse duration, total energy deposition and membrane potential, but is insensitive to tetrodotoxin. The hyperpolarization reverses its polarity near the potassium equilibrium potential and is barium-sensitive. The membrane depolarization activates an action potential (AP) when the axon is near firing threshold, while the hyperpolarization reversibly inhibits rhythmically firing APs. In summary, we demonstrate for the first time that single and brief IR light pulses can evoke initial depolarization followed by hyperpolarization on individual motor axons. The corresponding mechanisms and functional outcomes of the dual effects are investigated.


Flexible experimentation in the modeling and simulation framework JAMES II--implications for computational systems biology.
Dry-lab experimentation is being increasingly used to complement wet-lab experimentation. However, conducting dry-lab experiments is a challenging endeavor that requires the combination of diverse techniques. JAMES II, a plug-in-based open source modeling and simulation framework, facilitates the exploitation and configuration of these techniques. The different aspects that form an experiment are made explicit to facilitate repeatability and reuse. Each of those influences the performance and the quality of the simulation experiment. Common experimentation pitfalls and current challenges are discussed along the way.


The effect of the NMDA receptor-dependent signaling pathway on cell morphology and melanosome transfer in melanocytes.
The pigmentation of skin and hair in mammals is driven by the intercellular transfer of melanosome from the melanocyte to surrounding keratinocytes However, the detailed molecular mechanism is still a subject of investigation. To investigate the effects of N-methyl-d-aspartate (NMDA) receptor-dependent signaling pathway on melanocyte morphologic change and melanosome transfer between melanocytes and keratinocytes. The expression and the intracellular distribution of NMDA receptor in human melanocyte were analyzed by Western blot and immunofluorescence staining. Melanocytes were treated with 100μM NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate] and 100μM NMDA receptor agonist NMDA, after which the morphological change of melanocyte dendrites and filopodias were observed by scanning electron microscope. The β-tubulin distribution and intracellular calcium concentration ([Ca2+]i) were observed by immunofluorescence staining and flow cytometry under the same treatment respectively. In addition, melanocytes and keratinocytes were co-cultured with or without treatment of MK-801, and the melanosome transfer efficacy were analyzed by flow cytometry. We show that human epidermal melanocytes expresses NMDA receptor 1, one subtype of the ionotropic glutamate receptors (iGluRs). Stimulation with agonist of NMDA receptor increased the number of melanocyte filopodia. In contrast, blockage of NMDA receptor with antagonist decreased the number of melanocyte filopodia and this morphological change was accompanied by the disorganization of β-tubulin microfilaments in the intracellular cytoskeleton. In melanocyte-keratinocyte co-cultures, numerous melanocyte filopodia connect to keratinocyte plasma membranes; agonist of NMDA receptor exhibited an increased number of melanocyte filopodia attachments to keratinocyte, while antagonist of NMDA receptor led to a decreased. Moreover, antagonist of NMDA receptor decreased the intracellular calcium concentration in melanocytes and reduced the efficacy of melanosome transfer. Our data suggest that filopodia delivery is the major mode of melanosome transfer between melanocytes and keratinocytes. NMDA drives melanosome transfer by promoting filopodia delivery and direct morphological effects on melanocytes, while MK-801 affects the intracellular β-tubulin redistribution and the filopodia delivery between melanocytes and keratinocytes. We hypothesize that NMDA receptor-dependent signaling is involved in melanosome transfer, which is associated with calcium influx, cytoskeleton protein redistribution, dendrites and filopodia formation. A thorough understanding of melanosome transfer is crucial for designing treatments for hyper- and hypo-pigmentary disorders of the skin.


Effect of O-Antigen Chain Length Regulation on the Immunogenicity of Shigella and Salmonella Generalized Modules for Membrane Antigens (GMMA).
Recently, generalized modules for membrane antigens (GMMA) technology has been proposed as an alternative approach to traditional glycoconjugate vaccines for O-antigen delivery. Saccharide length is a well-known parameter that can impact the immune response induced by glycoconjugates both in terms of magnitude and quality. However, the criticality of O-antigen length on the immune response induced by GMMA-based vaccines has not been fully elucidated. Here, Shigella and Salmonella GMMA-producing strains were further mutated in order to display homogeneous polysaccharide populations of different sizes on a GMMA surface. Resulting GMMA were compared in mice immunization studies. Athymic nude mice were also used to investigate the involvement of T-cells in the immune response elicited. In contrast with what has been reported for traditional glycoconjugate vaccines and independent of the pathogen and the sugar structural characteristics, O-antigen length did not result in being a critical parameter for GMMA immunogenicity. This work supports the identification of critical quality attributes to optimize GMMA vaccine design and improve vaccine efficacy and gives insights on the nature of the immune response induced by GMMA.


[Metabolic issues and nutritional strategies in burn wound repair].
Wound is the most fundamental issue of burn injury, and its repair depends not only on effective wound treatment, but also on the good nutritional status of burned patients. Nutrition support is an important means to improve the nutritional status of patients and promote wound healing, and how to make it match the metabolism of burn wounds is a difficult task of nutrition therapy. In this paper, we analyzed the metabolic characteristics of different stages in burn wound healing, focused on the metabolic characteristics of glucose, protein, and glutamine in these stages, and proposed a nutritional strategy that is compatible with wound healing in order to maximize the role of nutrition therapy in wound repair.


Growth factor administration following autologous peripheral blood progenitor cell transplantation.
Hematopoietic growth factor (HGF) administration following autologous peripheral blood progenitor cell transplantation (APBPCT) is a current approach for shortening the duration of high-dose chemotherapy-induced transient peripheral pancytopenia. Several published clinical experiences and a retrospective study reported here show that recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration potentiates polymorphonuclear leukocyte (PMN) and white blood cell (WBC) recovery with some clinical benefits mainly related to the reduction of infectious complications during the shortened period of neutropenia. However, this therapeutic strategy does not produce any enhancement of platelet (PLT) recovery or potentiation of red cell production. Conversely, a recent phase I/II study carried out in our institution showed that the combined administration of rhG-CSF and recombinant human erythropoietin (rhEPO) is able to potentiate trilineage hematopoietic recovery with a reduction of PLT transfusions and to considerably simplify the clinical management of patients as compared to patients treated with APBPCT alone. The post-APBPCT administration of rhEPO with rhGM-CSF decreased the number of days with WBC < 1 x 10(9)/L but failed to produce any appreciable effect on PLT recovery. Both combined treatments significantly reduced the patients' hospital stay and allowed the abrogation of systemic antibiotic administration following APBPCT. A further group of patients were treated with the combined administration of rhEPO, rhG-CSF and rhGM-CSF; they did not show a faster hematopoietic recovery than rhG-CSF plus EPO treated patients and a consistent hyperthermia was observed in most patients as a prominent side effect. Future prospective randomized studies will clarify the efficacy of HGF administration following APBPCT. Moreover, further improvements in the hematopoietic support of transplanted patients may be obtained when stem cell factor, flt3/flk2 tyrosine kinase ligands or megakaryocyte growth and development factor will become clinically available.


The phosphatidylinositol-transfer protein Nir2 binds phosphatidic acid and positively regulates phosphoinositide signalling.
Phosphatidic acid (PA) and phosphoinositides are metabolically interconverted lipid second messengers that have central roles in many growth factor (GF)-stimulated signalling pathways. Yet, little is known about the mechanisms that coordinate their production and downstream signalling. Here we show that the phosphatidylinositol (PI)-transfer protein Nir2 translocates from the Golgi complex to the plasma membrane in response to GF stimulation. This translocation is triggered by PA formation and is mediated by its C-terminal region that binds PA in vitro. We further show that depletion of Nir2 substantially reduces the PI(4,5)P2 levels at the plasma membrane and concomitantly GF-stimulated PI(3,4,5)P3 production. Finally, we show that Nir2 positively regulates the MAPK and PI3K/AKT pathways. We propose that Nir2 through its PA-binding capability and PI-transfer activity can couple PA to phosphoinositide signalling, and possibly coordinates their local lipid metabolism and downstream signalling.


Exploring mediating factors in the association between parental psychological distress and psychosocial maladjustment in adolescence.
Parental psychopathology is associated with increased psychosocial maladjustment in adolescents. We examined, from a psychosocial perspective, the association between parental psychological distress and psychosocial maladjustment in adolescents and assessed the mediating role of psychosocial covariates. This is a cross-sectional survey and the setting include representative sample of Quebec adolescents in 1999. The participants of the study include 13- and 16-year-old children (N = 2,346) in the Social and Health Survey of Quebec Children and Adolescents. The main outcome measures are internalizing disorders, externalizing disorders, substance use, and alcohol consumption. For statistical analysis, we used structural equation modeling to test for mediation. Internalizing and externalizing disorders were significantly associated with parental psychological distress, but not substance use or alcohol consumption. The higher the parental distress, the higher the risk of adolescent mental health disorders. The association between parental psychological distress and internalizing disorders was mediated by adolescent self-esteem, parental emotional support and extrafamilial social support. As for externalizing disorders, these variables only had an independent effect. In conclusion, A family's well being is a necessary condition for psychosocial adjustment in adolescence. Beyond the psychiatric approach, psychosocial considerations need to be taken into consideration to prevent negative mental health outcomes in children living in homes with distressed parents.


Methods of optical spectroscopy in detection of virus in infected samples: A review.
Due to the recent COVID-19 pandemic that occurred worldwide since 2020, scientists and researchers have been studying methods to detect the presence of the virus causing COVID-19 disease, namely SARS-CoV-2. Optical spectroscopy is a method that employs the interaction of light in detecting virus on samples. It is a promising method that might help in detecting the presence of SARS-CoV-2 in samples. Four optical spectroscopy methods are discussed in this paper: ultraviolet (UV), infrared (IR), Raman spectroscopy and fluorescence spectroscopy. UV and IR spectroscopy differ in wavelength range (less than 400 nm for UV, more than 700 nm for IR). Raman spectroscopy involves shift in wavelength due to scattering of light. Fluorescence spectroscopy involves difference in wavelength between absorbed and emitted light due to vibrational relaxation. These four methods had been proven to differentiate healthy samples from virus-infected samples. UV spectroscopy is useful in determining presence of virus based on 260 nm/280 nm absorbance ratio. However, its usefulness is limited due to its destructive properties on virus at sufficiently high intensity. Meanwhile, IR spectroscopy has becoming popular in studies involving virus samples. Mid-infrared (MIR) spectroscopy is most commonly used among IR spectroscopy as it usually provides useful information directly from spectral data. Near infrared (NIR) spectroscopy is also used in studying virus samples, but additional methods such as principal component analysis (PCA) and partial least squares (PLS) are required to process raw spectral data and to identify molecules based on spectral peaks. On the other hand, Raman spectroscopy is useful because spectral data can be analyzed directly in identifying vibrational modes of specific molecules in virus samples. Fluorescence spectroscopy relies on interaction between viral particles and fluorescent tags for the detection of virus based on improvement or quenching of fluorescent signal. Due to non-invasive properties of virus samples, IR, Raman and fluorescence spectroscopy will be used more often in future studies involving virus detection in infected samples.


Myofibrillogenesis in skeletal muscle cells in zebrafish.
The "premyofibril" model of myofibrillogenesis, based on observations in cultured avian muscle cells, proposes that mature myofibrils are preceded by two intermediary structures: premyofibrils and nascent myofibrils. To determine if this model applies to zebrafish skeletal muscle development, we stained developing embryos with antibodies to sarcomeric alpha-actinin and myosin II. In the youngest muscle cells, sarcomeric alpha-actinin and non-muscle myosin II were each localized in linear arrays of small bands that resembled the premyofibrils in avian myocytes. The distribution of muscle-specific myosin II began as scattered short filaments followed in time by overlapping bundles of filaments and organized A-bands in the older somites. Alpha-actinin organization changed from small z-bodies to beaded Z-bands and ordered Z-bands in myofibrils that extended the length of the elongating somites. In older somites with mature myofibrils, premyofibrils were also present at the ends of the mature myofibrils, suggesting that as the cells and somites grew longer, premyofibrils were involved in the elongation of existing mature myofibrils. Fluorescence Recovery After Photobleaching showed that the exchange of proteins (actin, alpha-actinin, FATZ, myotilin and telethonin) between sarcoplasm and the Z-bands of mature myofibrils in zebrafish resembled that seen for the same proteins in cultured avian myotubes, suggesting that myofibril assembly and maintenance in zebrafish share common properties with avian muscle. Cell Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc.


Unveiling the Eigen-Weller ion pair from the excited state proton transfer kinetics of 3-chloro-4-methyl-7-hydroxycoumarin.
The prototropic reactions of the first excited singlet state of 3-chloro-4-methylumbelliferone (3Cl4MU), in dioxane:water mixtures (Dx:H2O), were revisited using ps-time-resolved fluorescence techniques. The data response to the dielectric constant of the mixtures revealed the presence of an additional fourth kinetic species, kinetically coupled to the neutral (N*), the tautomeric (T*), and anionic (A(-)*) forms of 3Cl4MU, which is assigned to the elusive geminate (A(-)*···H(+)) ion pair. From the data analysis, all rate constants of the prototropic and diffusion processes involved were separately evaluated. The results showed that, whenever the geminate ionic pair is not kinetically detected, the evaluated values for deprotonation and protonation rate constants can substantially deviate from the real ones, depending on the efficiencies of pair recombination and dissociation. Finally, the results provide convincing kinetic evidence for the Eigen-Weller mechanism (intermediacy of the geminate ionic pair) in a quasi-aqueous medium, which to our knowledge had not yet been given.


Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study.
Although the associations between serum lipid levels and aneurysms have been investigated in epidemiological studies, causality remains unknown. Thus, this study aimed to investigate the causal relationships of serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) levels on five types of aneurysms, using genetic variants associated with four lipid traits as instrumental variables in a Mendelian randomization (MR) analysis. We performed two-sample Mendelian randomization (MR) analyses to evaluate the associations of HDL-C, LDL-C, TC, and TG levels with risks for five types of aneurysms and those of LDL-C- (HMGCR, NPC1L1, PCSK9, CETP, and LDLR) and TG-lowering targets (ANGPTL3 and LPL) with aneurysms. The sample sizes of the included studies ranged from nearly 80,000 to 410,000. We found inverse associations between genetically predicted HDL-C levels and aortic (OR = 0.74, 95% CI = 0.65-0.85) and abdominal aortic aneurysms (0.58, 0.45-0.75). A 1-SD increase in LDL-C and TC levels was associated with increased risks for aortic (1.41, 1.26-1.58 and 1.36, 1.18-1.56, respectively) and abdominal aortic aneurysms (1.82, 1.48-2.22 and 1.55, 1.25-1.93, respectively). TG levels were significantly associated with aortic (1.36, 1.18-1.56) and lower extremity artery aneurysms (2.76, 1.48-5.14), but limited to cerebral aneurysm (1.23, 1.06-1.42). Secondary analyses revealed a relationship between genetically proxied LDL-C-lowering targets and all types of aneurysms; however, the drug targets remained heterogeneous. We found a weak association between TG-lowering therapies and aortic (ANGPTL3, 0.51, 0.29-0.89) and abdominal aortic aneurysms (LPL, 0.64, 0.44-0.94). According to genetic evidence, lipid dysfunction is a causal risk factor for aneurysms. Lipid-lowering drugs may be a potential effective strategy in preventing and managing aneurysms.


Elevated opsonic activity for Porphyromonas (Bacteroides) gingivalis in serum from patients with a history of destructive periodontal disease. A case: control study.
We have measured the opsonic capacity of serum for the phagocytosis of Porphyromonas (Bacteroides) gingivalis by polymorphonuclear leucocytes (PMN) in 35 patients with a history of destructive periodontitis and 35 matched control subjects. The serum from cases, tested at concentrations of 8% and 0.8% opsonised P. gingivalis for phagocytosis by PMN to a level significantly greater than controls (p < 0.0001 and < 0.01 respectively). IgG antibody levels to P. gingivalis whole cells estimated by ELISA were also significantly higher in the cases (p < 0.0001). The IgG antibody levels correlated significantly with the opsonic capacity of the serum tested at 8% concentration in controls (r = 0.371, p = 0.03) but not in cases (r = 0.235, p = 0.17); in 0.8% serum, the opsonic capacity of the cases and controls were not significantly correlated. Elevated opsonisation by serum was a significant predictor that a subject was a case rather than a control, even after allowing for the effect of elevated IgG antibody in the cases. The data suggest that an elevated capacity of serum to opsonise P. gingivalis is a distinctive feature in patients with past destructive periodontal disease.


Ulcerative colitis: a case of steroid refractory disease.
A 21-year-old lady was admitted to a hospital with an 8-week history of bloody diarrhoea. She had been diagnosed with ulcerative colitis 2 years previously and had remained in remission until the gradual onset of bloody diarrhoea. Her bowel frequency was 20 times per day and associated with significant abdominal pain and weight loss. She was started on intravenous steroids, topical therapy and anti-tumour necrosis factor therapy; however, this failed to achieve symptom control. Histology of tissue obtained from flexible sigmoidoscopy eventually demonstrated cytomegalovirus (CMV)-associated colitis. Intravenous anti-viral valganciclovir was initiated and the patient made a rapid recovery. This case discusses the differentials for steroid-refractory ulcerative colitis, including the common pitfall of inflammatory bowel disease management and CMV infection. This case also discusses CMV pathophysiology including histological features, appropriate investigations and current management guidelines.


[Intercellular gap junctions in corporal smooth muscle].
The contractility of corporal smooth muscle plays a critical role in human penile erectile process. Understanding the initiation, maintenance and modulation of corporal smooth muscle tone is a prequisite to improve understanding, diagnosis and treatment of erectile dysfunction. Despite this fact, indentification of both the precise mechanistic basis by which various agents exert their effects on individual corporal smooth muscle cells, moreover, the process by which these signals are spread among the diverse array of parenchymal cells in the paired corporal, remain somewhat of a physiological enigma. Therefore, this article aims at: 1. to review current knowledge of the regulation of corporal smooth muscle tone at the cellular and molecular level; 2. to review various methods used in the study of gap junction channel.


Adaptation of the refractive indices of antireflection coatings to other surrounding media.
The design of various types of antireflection coating is extensively described in the literature. In practice, however, such designs must often be adapted to other surrounding media or angles of incidence. For such cases, a method is presented in which, starting from a known antireflection coating, a useful reflectance characteristic is obtained for changed situations.


Genetic variation in leptin and leptin receptor genes as a risk factor for idiopathic male infertility.
The aim of this study was to examine whether there is an association among genetic variability in leptin (LEP) and leptin receptor (LEPR) genes and male infertility. We performed a case-control study and were searching for an association between polymorphisms of LEP and LEPR genes and male infertility. The study group consisted of 317 patients with idiopathic infertility and a control group of 241 fertile men from Slovenia. Four single nucleotide polymorphisms (SNPs) in LEP gene and four single nucleotide polymorphisms (SNPs) in LEPR gene were chosen and genotyped. Statistically significant SNP was further validated in additional 255 infertile patients and 168 controls from Serbia and Macedonia. In the Slovenian population, we found a statistically significant difference in genotype distribution for rs10244329 polymorphism in LEP gene (recessive genotype model, p value = 0.048). The trend toward statistically significant difference in genotype distribution for rs10244329 polymorphism was confirmed in the Serbian and Macedonian populations (p value = 0.07). Our data suggest that genetic variability in the LEP gene might be associated with male infertility warranting further confirmation and mechanistic investigations.


Late diagnosis of HIV infection in the era of highly active antiretroviral therapy: consequences for AIDS incidence.
To assess the repercussion of late diagnosis of HIV infection on AIDS incidence in the era of highly active antiretroviral therapy. Analysis of AIDS surveillance data. Spain. AIDS cases reported from 1994 though 2000. Late testers were defined as persons who had a first positive HIV test in the month of or immediately preceding AIDS diagnosis. Their incidence trend was compared against that for the remaining cases, and the influence of demographic factors evaluated. Of 30 778 AIDS cases, 8499 (28%) were late testers, and of these, 1061 (12%) died within 3 months of diagnosis of HIV infection. From 1995 to 2000, AIDS diagnoses declined by 36% among late testers versus 67% for the remainder (P < 0.001). The percentage of late testers increased from 24% in 1994-1996 to 35% in 1998-2000 (P < 0.001). Among the 7825 AIDS cases diagnosed in 1998-2000, late testing was independently associated (P < 0.01) with male sex, age over 44 years, residence in provinces with a lower AIDS incidence, foreign origin, and no record of injecting drug use or prison stay. A growing proportion of AIDS cases involves late diagnosis of HIV infection. Persons who are unaware of their HIV infection cannot benefit from antiretroviral therapy and, hence, early diagnosis would strengthen the impact of such therapy and so reduce AIDS incidence.


Age-related differential growth rate and response to 4-hydroxynonenal in mouse aortic smooth muscle cells.
4-Hydroxynonenal (4-HNE) is a peroxidation product of omega-6-poly-unsaturated fatty acids and exerts growth modifying as well as cytotoxic activities. This aldehyde component of oxidized lipid is increased during the aging process. In this study, to characterize the potential role of the lipid peroxidation product in aging, we studied the effects of 4-HNE on cell proliferation and activation of cell-cycle machinery and the mitogen-activated protein kinase signaling pathway. 4-HNE-treated smooth muscle cells (SMCs) have shown a different cell proliferation rate depending on 4-HNE's incubation time and concentration. Interestingly, a prolonged treatment of 0.1 microM 4-HNE (36 h) resulted in an increase of cell growth in young SMCs but displayed cytotoxicity in aged SMCs. Treatment with 4-HNE enhanced cyclin D1 expression and activation of the extracellular signal-regulated kinase (ERK) signaling pathway, which were stronger in young SMCs compared with aged SMCs. Moreover, 4-HNE-induced cell proliferation and cyclin D1 expression were significantly attenuated by PD98059, the ERK inhibitor, in young SMCs. These data clearly indicate that increased cell proliferation was associated with the induction of cyclin D1 expression which was regulated by ERK in 4-HNE-treated young SMCs for 36 h. In contrast, we found that the cytotoxicity of aged SMCs to 4-HNE was partly related to generation of ROS and that pretreatment with N-acetyl-L-cysteine prevented 4-HNE-induced cell death in aged SMCs. These results suggest that the prolonged treatment of 0.1 microM 4-HNE-induced cell growth inhibition was caused by generation of ROS. Collectively, the age-related different growth rates and responses to 4-HNE are related to the expression level of cyclin D1, activation of the ERK signaling pathway, and regulation of ROS generation in SMCs.


Spatial and temporal variation in vector competence of Culex pipiens and Cx. restuans mosquitoes for West Nile virus.
Vector competence, the probability that a vector will transmit a pathogen after feeding on an infected host, is known to vary among vector species, populations, days since feeding, and temperature during the extrinsic incubation period. However, the extent of spatio-temporal variability and consistency in vector competence of populations is not known. We examined vector competence of Culex pipiens Linnaeus and Cx. restuans Theobald mosquitoes for West Nile virus collected over 3 years from 17 sites to measure spatial and temporal scales of variation in vector competence. We found extreme variation with 0-52% of mosquitoes transmitting West Nile virus at a single site between different sampling periods, and similar variation across populations. However, we also found that within a smaller geographic range, vector competence varied somewhat synchronously, suggesting that environmental and population genetic factors might influence vector competence. These results highlight the spatio-temporal variability in vector competence and the role of local processes.


Ergot alkaloid biosynthesis in Aspergillus fumigatus. Overproduction and biochemical characterization of a 4-dimethylallyltryptophan N-methyltransferase.
The putative gene fgaMT was identified in the biosynthetic gene cluster of fumigaclavines in Aspergillus fumigatus. The coding region of fgaMT was amplified by PCR from a cDNA library, cloned into pQE60, and overexpressed in Escherichia coli. FgaMT comprises 339 amino acids with a molecular mass of about 38.1 kDa. The soluble dimeric His(6)-FgaMT was purified to near homogeneity and characterized biochemically. FgaMT was found to catalyze the N-methylation of 4-dimethylallyltryptophan in the presence of S-adenosylmethionine, resulting in the formation of 4-dimethylallyl-l-abrine, which was identified by NMR and mass spectrometry analysis. Therefore, FgaMT represents the second pathway-specific enzyme in the biosynthesis of ergot alkaloids. The enzyme did not require metal ions for its enzymatic reaction and showed a relatively high specificity toward the prenyl moiety at position C-4 of the indole ring. 4-Dimethylallyltryptophan derivatives with modification at the indole ring were also accepted by FgaMT as substrates. K(m) values for 4-dimethylallyltryptophan and S-adenosylmethionine were determined at 0.12 and 2.4 mm, respectively. The turnover number was 2.0 s(-1).


A new magneto-elastic resonance based technique to determine magneto-mechanical parameters of amorphous ferromagnetic ribbons.
Measurement of the magneto-mechanical parameters characteristics of amorphous ribbons often requires complex or limited methods due to their very small thickness. In this paper, it is shown how one can establish and estimate the characteristics of a magnetostrictive resonator from the experimental frequency response free of any kind of mechanical measurement (stress or elongation). This technique which is completely developed with a ribbon exhibiting good resonator properties, is suitable to estimate the magneto-mechanical coupling coefficient k33 and the Young's modulus and also to establish the magnetostriction curves λ(H) of amorphous ribbons. Results obtained from resonators made of 2605SC and 2826 from Metglas(TM) ribbons confirmed the validity of the present technique. However, measurements performed on a thin foil of nickel demonstrate that the present method cannot be extended to semi-soft magnetic materials. The technique which is proposed, has serious advantages upon others as it is non-destructive, low cost and easy to develop compared to common ones.


What to wear? The influence of attire on the perceived professionalism of dentists and lawyers.
Using a sample of 201 participants and a between-subjects design, the perceived professionalism-suitability, capability, ease to talk to and friendliness-of male and female dentists and lawyers in various attires was examined. Results showed an absolute preference for male dentists and lawyers in professional and formal attire, respectively. Male dentists and lawyers in professional and formal attire were further rated as more suitable, capable, easier to talk to, and friendlier than female professionals, and than those dressed in smart or casual attire. Results are discussed in terms of positive dental outcomes and legal representation. Limitations are considered.


Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor.
Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation within C4BP. We thus provide a detailed picture of an interaction whereby a pathogen evades complement.


Chronic Progressive External Ophthalmoplegia in the Absence of Ptosis.
Classically defined as bilateral, symmetric, and progressive ophthalmoparesis with myopathic ptosis, chronic progressive external ophthalmoplegia (CPEO) rarely has been reported in the absence of ptosis. We describe 2 patients with CPEO and without ptosis who presented with binocular diplopia related to small-angle esodeviations, poor fusional amplitudes, and slow saccades. In both cases, hematological studies and neuroimaging ruled out alternative etiologies, whereas muscle biopsy showed findings of mitochondrial myopathy.


Visual working memory and number sense: Testing the double deficit hypothesis in mathematics.
Evidence exists that there are two main underlying cognitive factors in mathematical difficulties: working memory and number sense. It is suggested that real math difficulties appear when both working memory and number sense are weak, here referred to as the double deficit (DD) hypothesis. The aim of this study was to test the DD hypothesis within a longitudinal time span of 2 years. A total of 670 children participated. The mean age was 4.96 years at the start of the study and 7.02 years at the end of the study. At the end of the first year of kindergarten, both visual-spatial working memory and number sense were measured by two different tasks. At the end of first grade, mathematical performance was measured with two tasks, one for math facts and one for math problems. Multiple regressions revealed that both visual working memory and symbolic number sense are predictors of mathematical performance in first grade. Symbolic number sense appears to be the strongest predictor for both math areas (math facts and math problems). Non-symbolic number sense only predicts performance in math problems. Multivariate analyses of variance showed that a combination of visual working memory and number sense deficits (NSDs) leads to the lowest performance on mathematics. Our DD hypothesis was confirmed. Both visual working memory and symbolic number sense in kindergarten are related to mathematical performance 2 years later, and a combination of visual working memory and NSDs leads to low performance in mathematical performance.


Short and long term effects of growth hormone on circulating levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1, and insulin: a placebo-controlled study.
The short and long term effects of GH on serum concentrations of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin were investigated in women participating in an in vitro fertilization program. In this placebo-controlled study, sterile saline (eight women) or 24 IU GH (eight women) were given im on alternate days, starting on cycle day 4, in combination with GnRH and human menopausal gonadotropin. IGFBP-1 levels decreased significantly during the first 4 h after GH administration, whereas no significant changes were seen in the placebo group. The concentrations of serum IGF-I and insulin did not change during 4 h after GH injection. During the 11-day follow-up period, serum levels of both IGF-I and insulin were significantly higher in GH-treated than in placebo-treated women. These results suggest that the serum concentration of IGFBP-1 is not completely GH independent. They also support the earlier findings that long term treatment with GH increases serum IGF-I and insulin levels.


Immediate Full Weight-Bearing Versus Partial Weight-Bearing After Plate Fixation of Distal Femur Fractures in Elderly Patients. A Randomized Controlled Trial.
After surgery for distal femur fractures in elderly patients, weight-bearing is commonly restricted. Immediate non-restrictive weight-bearing might have beneficial effects. There are no randomized studies on the topic. The purpose of this study was to compare the functional outcome between immediate full weight-bearing (FWB) as tolerated and partial weight-bearing (PWB) during the first 8 weeks following plate fixation of distal femur fractures in elderly patients. Patients aged 65 years or older with distal femur fractures of AO/OTA types 33 A2, A3, B1, B2, C1, and C2 were included. Exclusion criteria were impaired cognitive function, concomitant injuries, or inability to follow the postoperative regimen. Internal fixation was achieved with an anatomical lateral distal femur plate applied as a strictly bridge-plating construct. The primary outcome measure was the function index of the short musculoskeletal functional assessment (SMFA) after 52 weeks from injury. Thirty-two patients were randomized to FWB (n = 11) or PWB (n = 21). After 16 and 52 weeks, there were no differences in the mean SMFA function index between FWB and PWB (36 vs 43, P = .42 and 52 vs 40, P = .18, respectively) nor in the mean EuroQol 5-dimension index or range of motion (ROM). Overall, the SMFA function index was higher at 52 weeks compared with before injury (44 vs 30, P = .001) as was the mean bothersome index (37 vs 21, P = .011). There was no clear difference in the occurrence of adverse events between the treatment groups. There were no differences in functional outcome, adverse events, or ROM between immediate FWB and PWB following plate fixation for a distal femur fracture in elderly patients. A distal femur fracture has a negative effect on the functional status of elderly patients that persists at least up to 1 year following injury.


A CT database for research, development and education: concept and potential.
Both in radiology and in surgery, numerous applications are emerging that enable 3D visualization of data from various imaging modalities. In clinical practice, the patient's images are analyzed on work stations in the Radiology Department. For specific preclinical and educational applications, however, data from single patients are insufficient. Instead, similar scans from a number of individuals within a collective must be compiled. The definition of standardized acquisition procedures and archiving formats are prerequisite for subsequent analysis of multiple data sets. Focusing on bone morphology, we describe our concept of a computer database of 3D human bone models obtained from computed tomography (CT) scans. We further discuss and illustrate deployment areas ranging from prosthesis design, over virtual operation simulation up to 3D anatomy atlases. The database of 3D bone models described in this work, created and maintained by the AO Development Institute, may be accessible to research institutes on request.


Study on Multi-Model Soft Sensor Modeling Method and Its Model Optimization for the Fermentation Process of Pichia pastoris.
The problems that the key biomass variables in Pichia pastoris fermentation process are difficult measure in real time; this paper mainly proposes a multi-model soft sensor modeling method based on the piecewise affine (PWA) modeling method, which is optimized by particle swarm optimization (PSO) with an improved compression factor (ICF). Firstly, the false nearest neighbor method was used to determine the order of the PWA model. Secondly, the ICF-PSO algorithm was proposed to cooperatively optimize the number of PWA models and the parameters of each local model. Finally, a least squares support vector machine was adopted to determine the scope of action of each local model. Simulation results show that the proposed ICF-PSO-PWA multi-model soft sensor modeling method accurately approximated the nonlinear features of Pichia pastoris fermentation, and the model prediction accuracy is improved by 4.4884% compared with the weighted least squares vector regression model optimized by PSO.


Metabolic effects of intensive insulin therapy in critically ill patients.
Our aim was to investigate the effects of glycemic control and insulin concentration on lipolysis, glucose, and protein metabolism in critically ill medical patients. For our methods, the patients were studied twice. In study 1, blood glucose (BG) concentrations were maintained between 7 and 9 mmol/l with intravenous insulin. After study 1, patients entered one of four protocols for 48 h until study 2: low-insulin high-glucose (LIHG; variable insulin, BG of 7-9 mmol/l), low-insulin low-glucose (LILG; variable insulin of BG 4-6 mmol/l), high-insulin high-glucose [HIHG; insulin (2.0 mU . kg(-1).min(-1) plus insulin requirement from study 1), BG of 7-9 mmol/l], or high-insulin low-glucose [HILG; insulin (2.0 mU.kg(-1).min(-1) plus insulin requirement from study 1), BG of 4-6 mmol/l]. Age-matched healthy control subjects received two-step euglycemic hyperinsulinemic clamps achieving insulin levels similar to the LI and HI groups. In our results, whole body proteolysis was higher in patients in study 1 (P < 0.006) compared with control subjects at comparable insulin concentrations and was reduced with LI (P < 0.01) and HI (P = 0.001) in control subjects but not in patients. Endogenous glucose production rate (R(a)), glucose disposal, and lipolysis were not different in all patients in study 1 compared with control subjects at comparable insulin concentrations. Glucose R(a) and lipolysis did not change in any of the study 2 patient groups. HI increased glucose disposal in the patients (HIHG, P = 0.001; HILG, P = 0.07 vs. study 1), but this was less than in controls receiving HI (P < 0.03). In conclusion, low-dose intravenous insulin administered to maintain BG between 7-9 mmol/l is sufficient to limit lipolysis and endogenous glucose R(a) and increase glucose R(d). Neither hyperinsulinemia nor normoglycemia had any protein-sparing effect.


MiRNA-506 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targetting TLR4.
Fibroblast-like synoviocytes (FLSs) play a crucial role in rheumatoid arthritis (RA) pathogenesis. While miRNA (miR)-506 has been implicated in the progression of multiple diseases, its role in RA remains to be explored. The present study evaluated the function of miR-506 in the regulation of RA-FLSs. FLSs were prepared from RA and healthy synovial tissues. The expression of miR-506 was measured by quantitative real time PCR (qRT-PCR). The effects of miR-506 on RA-FLSs proliferation and apoptosis were detected by cell counting Kit-8 and flow cytometry assays, respectively. The determination of TNF-α, IL-6, and IL-1β concentrations in RA-FLSs supernatant were done by ELISA. The levels of miR-506 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the synovial tissues and FLSs of healthy controls. The miR-506 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell cycle arrest at the G0/G1 phase. The overexpression of miR-506 induced apoptosis, along with an increase in activities of caspase-3 and -8. A target gene Toll-like receptor 4 (TLR4) under the direct regulation of miR-506 was identified through the luciferase assay, qRT-PCR and western blot analysis. Forced overexpression of TLR4 in the rescue experiments showed that TLR4 effectively reversed the effect on proliferation and apoptosis in miR-506-overexpressing RA-FLSs. Thus, miR-506 may be a potential target for RA prevention and therapy of RA.


Relationship between plasma antioxidant concentrations and carotid intima-media thickness: the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study.
Few studies have examined the relationship among carotid atherosclerosis, vascular risk factors, and antioxidant plasma concentrations, and those that have reported conflicting results. The aim of this study was to assess the relationship between asymptomatic carotid atherosclerosis, as defined by carotid intima-media thickness (CIMT), and inflammatory markers, plasma lipids and serum antioxidant vitamins. We examined baseline characteristics of the 640 participants in the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study. All participants were asymptomatic with respect to carotid artery disease in 2006-2007 and underwent physical examination with carotid ultrasound investigation, the collection of medical history and laboratory data. Analysis of variance methods were used to examine differences between participants by category of CIMT. Of the 640 participants, 291 did not have evidence of carotid atherosclerosis (CIMT<0.8 mm), 232 were found to have some atherosclerosis (0.8 mm< or =CIMT<1.2 mm), and 117 were found to have extensive atherosclerosis (CIMT>1.2 mm). Among participants with CIMT> or =0.8 mm, body mass index, blood pressures, total cholesterol, LDL cholesterol, triglycerides, uric acid, C-reactive protein, and fibrinogen were significantly higher, whereas concentrations of vitamin A, vitamin E, lycopene, and beta-carotene were all significantly lower when compared with participants who did not show evidence of carotid atherosclerosis (P<0.001). The optimal control of hypertension, diabetes, and dyslipidemia, in addition to smoking cessation and an adequate intake of antioxidant micronutrients from foods represent a key for the prevention of atherosclerotic disease.


The patient lock model©: a continuum of care.
Nursing as a profession has the responsibility to society to protect and promote the health of individuals and communities. The intent of this conceptual model is to center the patient in his or her environment while allowing qualified, expert health professionals to provide timely, effective, cost-efficient care within their levels of competence and expertise. Significant shortages of registered nurses and other health professionals delay timely provision of quality care and affect the effectiveness of care. Care management issues are due to the complexity of individual patient's health care needs, limited access to providers, inability to afford treatment, and delay in seeking care. These challenges to the system slow efficiency in the provision of care across all settings. In presenting this conceptual model, there will be a review of nursing and the internal and external forces that affect the profession. This is an initial development phase of the model: The Patient Lock Model.


Priority of Gender and Racial Disparity in Neurology Journals: A Bibliometric Analysis, 2016-2021.
Medicine and the field of neurology are not immune to gender and racial disparities present more broadly in society. Even within academia there remains a persistent lack of representation of women and racial minorities, but with the recent spotlight on discrimination it is more necessary than ever that prevailing disparities are acknowledged by medical journals and reflected in their publication priorities. This bibliometric study assesses whether social justice trends have influenced the number of articles published that discuss gender and racial disparity in the past 5 years within the top three leading neurological journals. Our assumption is that any trend towards more publications related to gender and racial disparities are reflective of the publication priorities of, and thus the perceived relevance to, the editorial boards of the chosen journals. Using key word search of "gender," "race," and "disparity" in the title or context of published papers, the archives of Lancet Neurology, Nature Reviews Neurology, and Alzheimer's & Dementia were reviewed. The results indicated that although there was a slight overall increase in coverage of the aforementioned topics, it was negligible compared to the broad impact of current social justice movements. Our data suggest an inadequate publication priority for scholarly work on gender and racial disparity in the chosen journals, over the latest 5 years reviewed.


Anomalous systemic arterial supply to the basal lung segments with high serum carbohydrate antigen 19-9 levels-a case report.
Anomalous systemic arterial supply to the basal lung segments is relatively rare. A 39-year-old Japanese man was found to have high serum carbohydrate antigen 19-9 levels during a routine medical examination. He had no medical history and no symptoms. Although his serum carbohydrate antigen 19-9 level was high at 571 U/mL, his abdominal computed tomography (CT), gastrointestinal endoscopy, and abdominal ultrasonography findings were not abnormal. However, his chest CT scan revealed anomalous systemic arterial supply to the basal lung segment of the left lower lobe. He underwent partial resection of the left lung and stapling of the abnormal artery. After surgery, his serum carbohydrate antigen 19-9 level normalized. We consider that bronchiectasis of the basal left lung was involved in carbohydrate antigen 19-9 production and increase in its serum level. It is important to remain aware that various benign lung diseases can cause high serum carbohydrate antigen 19-9 levels.


Social challenges of contemporary psychiatry.
Psychiatry and society are interrelated and the biopsychosocial model continues to dominate the clinical psychiatric practice. Some doubts have been expressed in recent years about the value and the wide acceptance of the biopsychosocial model. Ghaemi (2009)1 considers it to be anti-humanistic and advocates the use of less eclectic, less generic, and less vague alternatives. The fundamental changes that have been witnessed in our times across the spectrum of biology, psychology and sociology have made necessary that a conceptual clarity should prevail. The remarkable advances in neurosciences, neurobiology and genetics tend to swing the emphasis towards a more biological basis. Psychosis for example is the condition often regarded as being biologically constructed and most independent of the social context. The symptoms, however, of hallucinations and delusions in psychosis have social meaning for the person experiencing them and are primarily defined socially.2 Furthermore, vulnerability is often the result of social trauma, whether in the form of recent stressors that trigger onset, or earlier circumstances that shape cognitive and emotional style. Moreover, the approved treatment and management of long term psychiatric disorders has involved interventions that are either directly social, or psychosocial. Furthermore, doubts have also been raised by the endophenotype project,3 related to the genetics of schizophrenia. Cohen4 suggested that there may be more individual genotypic patterns associated with schizophrenia than people with schizophrenia on the planet. A recent alternative interpretation (network approach) is gaining some support. It suggests that a stressor causes symptoms that activate other symptoms, in a circular, self-reinforcing way.5 This theory moves away from psychiatric disorders being traditionally conceptualised as categorical or dimensional models. While psychiatry has shifted its focus to a more biological approach, social factors still have an important role in crosscultural diagnosis, psychiatric disorders relating to social deprivation, rehabilitation and enabling social inclusion. The degree to which society is willing to accept people with mental health problems has an obvious impact on their quality of life. We live in a period of cataclysmic social changes with disastrous wars, increased poverty and growing income inequality. The consequences on mental health are phenomenal with epidemics of self-harm and suicidality, higher rates of depression, and intensifying diagnosis of mood and conduct disorders in children and young adults. Other adversities include the disproportional number of people with mental health problems in prisons and penal institutions, the massive escalation of dementia sufferers and the shortcomings of the aspirations of community mental health care. In addition, there is an escalating social pathology with significant numbers of refugees and asylum seekers and rising numbers of homeless particularly in urban areas of the developed world. We should not, however, overlook the better rates of treatment for mental health problems, the emphasis on human rights, the empowerment and the service users' participation and the development in global mental health. All these social factors are important to contemporary psychiatry presenting complex challenges and demanding urgent attention and action.6 There is a need to embrace the development of evidence-based mental health services and a pluralistic approach, which balances appropriately the relevance of biological, psychological and social factors associated with mental health problems. The concept Meta-Community mental health builds on the successes of biological, psychological, social and community psychiatry.7 It incorporates neurosciences, sociology, psychology and anthropology and is delivered wherever the evidence shows that it makes a difference, whether in community or hospital, prisons, schools, court-room, place of work, refugee camp or battle-front. New technologies should be included for public information and education together with e-mental health, training of providers, tele-psychiatry and self-help methods delivered via IT. The boundaries of mental health are enlarging very rapidly and indeed new stakeholders and partners should be welcomed. This opens exciting possibilities but also creates some risks and strong evidence base should continue to guide us. Likelihood of finding early diagnostic and individualized treatment for psychosis, autism and dementia are likely to be of high financial cost. The importance of the social challenges of modern psychiatry was recognised by including mental health for the first time in the New Sustainable Development Goals of United Nations that will determine the global development by 2030 aiming at the promotion of life expectancy for all.8 Strengthening the prevention and treatment of mental health problems is a massive task for sustainable development as mental health has a direct impact on the whole range of Sustainable Development Goals.


13C NMR studies of the electronic structure of low-spin iron(III) tetraphenylchlorin complexes.
A series of low-spin six-coordinate (tetraphenylchlorinato)iron(III) complexes [Fe(TPC)(L)2]+/- (L = 1-MeIm, CN-, 4-CNPy, and (t)BuNC) have been prepared, and their (13)C NMR spectra have been examined to reveal the electronic structure. These complexes exist as the mixture of the two isomers with the (d(xy))2(d(xz), d(yz))3 and (d(xz), d(yz))4(d(xy))1 ground states. Contribution of the (d(xz), d(yz))4(d(xy))1 isomer has increased as the axial ligand changes from 1-MeIm, to CN(-) (in CD2Cl2 solution), CN- (in CD(3)OD solution), and 4-CNPy, and then to tBuNC as revealed by the meso and pyrroline carbon chemical shifts; the meso carbon signals at 146 and -19 ppm in [Fe(TPC)(1-MeIm)2]+ shifted to 763 and 700 ppm in [Fe(TPC)(tBuNC)2]+. In the case of the CN- complex, the population of the (d(xz), d(yz))4(d(xy))1 isomer has increased to a great extent when the solvent is changed from CD2Cl2 to CD3OD. The result is ascribed to the stabilization of the d(xz) and d(yz) orbitals of iron(III) caused by the hydrogen bonding between methanol and the coordinated cyanide ligand. Comparison of the 13C NMR data of the TPC complexes with those of the TPP, OEP, and OEC complexes has revealed that the populations of the (d(xz), d(yz))4(d(xy))1 isomer in TPC complexes are much larger than those in the corresponding TPP, OEC, and OEP complexes carrying the same axial ligands.


High Value-Added Application of Natural Products in Crop Protection: Semisynthesis and Acaricidal Activity of Limonoid-Type Derivatives and Investigation of Their Biocompatible O/W Nanoemulsions as Agronanopesticide Candidates.
The increasingly serious resistance of Tetranychus cinnabarinus Boisduval to a wide range of insecticides/acaricides poses a major challenge to their control. The citrus processing industry generates a huge quantity of various wastes that contain many limonoids. To effectively utilize these byproducts and discover more potent green acaricidal molecules as sustainable alternatives for traditional resistant pesticides, various limonoid-type derivatives (halogenated/seven-membered lactam derivatives of obacunone and halogenated/oxime esters/oxime ethers/seven-membered lactam derivatives of limonin) were synthesized based on a diversity-oriented synthetic strategy. The key steric configurations of 10 derivatives were further confirmed by X-ray crystallography. Compound 9m, which displayed greater than 9.7-fold potent acaricidal activity of limonin, was of preeminence. In addition, some interesting structure-activity relationships were observed. Moreover, a biocompatible O/W nanoemulsion delivery system was used to prepare the limonin-based agronanoacaricide, which exhibited pronounced control efficiency against T. cinnabarinus Boisduval in the greenhouse. This systematic investigation will provide valuable information and guidance for future value-added applications of novel eco-friendly natural product-based nanopesticides.


A model for assessing information retrieval and application skills of medical students.
To develop and evaluate a model for assessing information retrieval and application skills, and to compare the performances on the assessment exercises of students who were and were not instructed in these skills. The authors developed a set of four examination stations, each with multiple subtasks, and administered the exams to students at two medical schools. Students at one school had intensive instruction in literature searching and filtering skills for information quality (instructed group), and those at the other school had minimal instruction in these areas (uninstructed group). The stations addressed pediatrics content and the skills of searching Medline and the World Wide Web, evaluating research articles, evaluating the accuracy of information from the Web, and using the information to make recommendations to patients. The authors determined the psychometric characteristics of the stations and compared the performances of the two groups of students. Students in the instructed group performed significantly better and with less variability than the uninstructed group on four tasks and no differently on seven tasks. There was no task on which the uninstructed group performed significantly better than the instructed group. The prototype stations showed predictable differences across curricula, indicating that they have promise as assessment tools for the essential skills of information retrieval and application.


The Stapes of Gomphodont Cynodonts: Insights into the Middle Ear Structure of Non-Mammaliaform Cynodonts.
The stapes is known in several non-mammaliaform cynodonts, although it has only been cursorily studied. Here we thoroughly analyze the stapedial anatomy of several basal cynodonts in a phylogenetic framework. Our study shows that the stapedial anatomy is more variable than previously thought. The morphological variation of the stapes led to the recognition of 11 phylogenetic characters that were included in a total evidence data matrix centered in the analysis of gomphodont cynodonts. Stapes morphology does not provide evidence to suggest a direct connection between the stapes and a postquadrate tympanic membrane (if present) and the hypothesis of a dorsal process as the site of attachment of a small ligament or the stapedial muscle is supported. The re-evaluation of the theories concerning the position of the tympanic membrane in non-mammaliaform cynodonts allowed us to conclude that the hypothetical postquadrate tympanic membrane associated with the squamosal sulcus is at best relictual and most likely non-functional (not connected with the stapes). The sound waves were most likely transmitted to the stapes from a postdentary tympanic membrane through the quadrate. Our analysis results in a better understanding of the auditory system in basal cynodonts and its evolution, highlighting the variability of the stapedial anatomy.


Nighttime effectiveness of the pedestrian hybrid beacon, rectangular rapid flashing beacon, and LED-embedded crossing sign.
A large majority of pedestrian fatal crashes occurred during the nighttime. The focus of this research was to identify if the following pedestrian crossing treatments were more or less effective at night: pedestrian hybrid beacon (PHB), rectangular rapid flashing beacon (RRFB), or LED-embedded crossing warning sign (LED-Em). For each treatment, two statistical evaluations were used on the staged pedestrian data: ANCOVA models that considered per site mean yield rates and logistic regression that considered the individual driver response to the crossing pedestrian. For the PHB, essentially no difference was found between the very high daytime and nighttime driver yielding values. The research found RRFBs to be more effective at night, and the LED-Em to be more effective during the day. Using the results from the logistic regression evaluation, higher driver yielding was observed at LED-Em sites in the lower speed limit group (30 or 35 mph (48.3 or 56.3 kph), with 2 lanes (rather than 4 lanes), with narrow lanes of 10.5 or 11 ft (3.2 or 3.4 m) widths (rather than 11.5 or 12 ft (3.5 or 3.7 m) widths), and lower hourly volumes. The results from the ANCOVA model for LED-Ems also showed a statistically significant difference for yield lines (higher yielding when present). This analysis represents the only known study to date on the effectiveness of pedestrian crossing treatments at night. Practical Applications: This study provides additional support for the PHB as a treatment because the PHB was found to be highly effective during the nighttime as well as the daytime. The value of using advance yield lines was also demonstrated. The findings offer a caution regarding the use of the LED-Em treatment on higher speed, higher volume, or wider roads.


Impact of mitral intervention on outcomes of patients with mitral valve dysfunction and annulus calcification.
To compare all-cause mortality in patients with mitral annulus calcification (MAC) and severe mitral valve dysfunction (MVD) who received standard mitral intervention versus no intervention. Patients with MAC often have high surgical risk due to advanced age, comorbidities, and technical challenges related to calcium. The impact of a mitral intervention on outcomes of patients with MAC and severe MVD is not well known. Retrospective review of patients with MAC by transthoracic echocardiography (TTE) in 2015 at a single institution. Patients with severe mitral stenosis (MS) or regurgitation (MR) were analyzed and stratified into two groups: surgical or transcatheter intervention performed <1 year after the index TTE, and no or later intervention. The primary endpoint was all-cause mortality. Of 5502 patients with MAC, 357 had severe MVD (MS = 27%, MR = 73%). Of those, 108 underwent mitral intervention (surgery = 87; transcatheter = 21). They were younger (73 ± 11 vs. 76 ± 11 years, p < 0.01) and less frequently had cardiovascular diseases compared with no-intervention. Frequency in women was similar (45% vs. 50%, p = 0.44). During median follow-up of 3.2 years, the intervention group had higher estimated survival than those without intervention (80% vs. 72% at 1 year and 55% vs. 35% at 4 year, p < 0.01). Adjusted for age, eGFR, LVEF < 50%, and pulmonary hypertension, mitral intervention was an independent predictor of lower mortality (hazard ratio = 0.66, 95% confidence interval 0.43-0.99, p = 0.046). Patients with MAC and severe MVD who underwent mitral intervention <1 year from index TTE had lower mortality than those without intervention. Mitral intervention was independently associated with lower mortality.


[Analysis on the prevalence of central venous catheter-related infection in burn patients and its risk factors].
To investigate the prevalence of central venous catheter-related infection (CRI) in burn patients and its risk factors, so as to guide the clinical practice. Clinical data of 5 026 days of 480 cases of central venous catheterization altogether in 228 burn patients admitted to our ward from June 2011 to December 2014, conforming to the study criteria, were retrospectively analyzed. (1) The incidence of CRI and that of catheter-related bloodstream infection (CRBSI) in patients (the infection rates per thousand days were calculated) and mortality due to them, and detection of concerning bacteria were recorded after each case of catheterization. (2) The incidence of CRI after each case of catheterization in patients was recorded according to the classification of their gender, age, total burn area, full-thickness burn area, cause of injury, severity of inhalation injury, location of catheterization, whether catheterization through wound or not, duration of catheterization, and the data were processed with chi-square test. Indexes with statistically significant differences were selected, and they were processed with multivariate logistic stepwise regression analysis to screen the independent risk factors of CRI. (3) To all cases of catheterization and cases with catheterization through wound, incidence of CRI after each case of catheterization in patients at each time period was recorded according to the sorting of duration of catheterization. Data were processed with chi-square test and Fisher's exact test, and the values of P were adjusted by Bonferroni. (1) Infection rate of CRI per thousand days was 50.14‰ (252/5 026), resulting in the mortality rate of 3.51% (8/228). Infection rate of CRBSI per thousand days was 18.70‰ (94/5 026), resulting in the mortality rate of 2.19% (5/228). Respectively 319 and 105 strains of pathogens were detected in CRI and CRBSI, in which the top four bacteria detected were Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae, and the most common fungus found was smooth Candida. (2) There were no statistically significant differences in the incidence of CRI after each case of catheterization among patients with different gender, age, cause of injury, severity of inhalation injury, and location of catheterization (with χ(2) values from 0.427 to 6.991, P values above 0.05). There were statistically significant differences in the incidence of CRI after each case of catheterization among patients with different total burn area, full-thickness burn area, whether catheterization through wound or not, duration of catheterization (with χ(2) values from 7.202 to 14.246, P<0.05 or P<0.01). (3) Total burn area, whether catheterization through wound or not, and duration of catheterization were the independent risk factors of CRI (with odd ratios respectively 1.495, 1.670, 1.924, 95% confidence intervals respectively 1.096-2.040, 1.077-2.590, 1.303-2.841, P<0.05 or P<0.01). (4) In all cases enduring catheterization, the incidence of CRI in patients after each episode of catheterization was close between cases enduring catheterization shorter than or equal to 3 days and those longer than 3 days and shorter than or equal to 5 days (χ(2) <0.001, P>0.05); the incidence of CRI in patients after each episode of catheterization was significantly higher in cases enduring catheterization longer than 5 days and shorter than or equal to 7 days, longer than 7 days and shorter than or equal to 14 days, and longer than 14 days than the former two periods (with χ(2) values from 3.625 to 13.495, P values below 0.05). In the cases with catheterization through wound, the incidence of CRI of patients after each episode of catheterization was close between cases enduring catheterization shorter than 5 days and those longer than or equal to 5 days and shorter than 7 days (P>0.05); the incidence of CRI of patients after each episode of catheterization was significantly higher in cases enduring catheterization longer than or equal to 7 days and shorter than 14 days and longer than or equal to 14 days than those with longer than or equal to 5 days and shorter than 7 days (with χ(2) values respectively 6.828 and 4.940, P values below 0.05). The infection rate of CRI per thousand days in burn patients is relatively low, while that of CRBSI is relatively high, both resulting in relatively low mortality, and Acinetobacter baumannii is the main pathogen. Total burn area, whether catheterization through wound or not, and duration of catheterization are independent risk factors of CRI in burn patients, and with which its occurrence could be predicted. It is suggested that central venous catheterization should be removed within 5 days, and catheterization through wounds should be avoided as much as possible. If catheterization through wound is unavoidable, removal of the catheter within 7 days is recommended.


Characteristics and mechanism of enzyme secretion and increase in [Ca2+]i in Saikosaponin(I) stimulated rat pancreatic acinar cells.
This investigation was to reveal the characteristics and mechanism of enzyme secretion and increase in [Ca2+]i stimulated by saikosaponin(I) (SA(I)) in rat pancreatic acini. Pancreatic acini were prepared from male Wistar rats. Isolated acinar cells were suspended in Eagle's MEM solution. After adding drugs, the incubation was performed at 37 degrees for a set period of time. Amylase of supernatant was assayed using starch-iodide reaction. Isolated acinar single cell was incubated with Fura-2/AM at 37 degrees, then cells were washed and resuspended in fresh solution and attached to the chamber. Cytoplasm [Ca2+]i of a single cell was expressed by fluorescence ratio F340/F380 recorded in a Nikon PI Ca2+ measurement system. Rate course of amylase secretion stimulated by SA(I) in rat pancreatic acini appeared in bell-like shape. The peak amplitude increased depended on SA(I) concentration. The maximum rate responded to 1 x 10(-5)mol/L SA(I) was 13.1-fold of basal and the rate decreased to basal level at 30 min. CCK-8 receptor antagonist Bt(2)-cGMP markedly inhibited amylase secretion stimulated by SA(I) and the dose-effect relationship was similar to that by CCK-8. [Ca2+]i in a single acinar cell rose to the peak at 5 min after adding 5 x 10(-6)mol/L SA(I) and was 5.1-fold of basal level. In addition, there was a secondary increase after the initial peak. GDP could inhibit both the rate of amylase secretion and rising of [Ca2+]i stimulated by SA(I) in a single pancreatic acinar cell. SA(I) is highly efficient in promoting the secretion of enzymes synthesized in rat pancreatic acini and raising intracellular [Ca2+]i. Signaling transduction pathway of SA(I) involves activating special membrane receptor and increase in cytoplasm [Ca2+]i sequentially.