Mutation of the Gs protein alpha subunit NH2 terminus relieves an attenuator function, resulting in constitutive adenylyl cyclase stimulation.
G-proteins couple hormonal activation of receptors to the regulation of specific enzymes and ion channels. Gs and Gi are G-proteins which regulate the stimulation and inhibition, respectively, of adenylyl cyclase. We have constructed two chimeric cDNAs in which different lengths of the alpha subunit of Gs (alpha s) have been replaced with the corresponding sequence of the Gi alpha subunit (alpha i2). One chimera, referred to as alpha i(54)/s' replaces the NH2-terminal 61 amino acids of alpha s with the first 54 residues of alpha i. Within this sequence there are 7 residues unique to alpha s, and 16 of the remaining 54 amino acids are nonhomologous between alpha i and alpha s. The second chimera, referred to as alpha i/s(Bam), replaces the first 234 amino acids of alpha s with the corresponding 212 residues of alpha i. Transient expression of alpha i(54)/s in COS-1 cells resulted in an 18- to 20-fold increase in cyclic AMP (cAMP) levels, whereas expression of either alpha i/s(Bam) or the wild-type alpha s polypeptide resulted in only a 5- to 6-fold increase in cellular cAMP levels. COS-1 cells transfected with alpha i showed a small decrease in cAMP levels. Stable expression of the chimeric alpha i(54)/s polypeptide in Chinese hamster ovary (CHO) cells constitutively increased both cAMP synthesis and cAMP-dependent protein kinase activity. CHO clones expressing transfected alpha i/s(Bam) or the wild-type alpha s and alpha i cDNAs exhibited cAMP levels and cAMP-dependent protein kinase activities similar to those in control CHO cells. Therefore, the alpha i(54)/s chimera behaves as a constitutively active alpha s polypeptide, whereas the alpha i/s(Bam) polypeptide is regulated similarly to wild-type alpha s. Expression in cyc-S49 cells, which lack expression of wild-type alpha s, confirmed that the alpha i(54)/s polypeptide is a highly active alpha s molecule whose robust activity is independent of any change in intrinsic GTPase activity. The difference in phenotypes observed upon expression of alpha i(54)/s or alpha i/s(Bam) indicates that the NH2-terminal moieties of alpha s and alpha i function as attenuators of the effector enzyme activator domain which is within the COOH-terminal half of the alpha subunit. Mutation at the NH2 terminus of alpha s relieves the attenuator control of the Gs protein and results in a dominant active G-protein mutant.


Efficacy of crude extracts of Andrographis paniculata nees. on Callosobruchus chinensis L. during post harvest storage of cowpea.
Bioefficacy of different solvent fractions of A. paniculata was tested against the cowpea weevil, C. chinensis in terms of its effect on adult mortality, total egg output and emergence of F1 adults. All the extracts were effective against the weevil, the efficacy was however more significant with respect to methanol and ethyl acetate extracts at the highest concentrations (1,000 ppm) which lead to 72.01 and 67.69% adult mortality respectively. The efficacy was dose dependent. Total egg and percent emergence of Fl adults were lowest for methanol followed by ethyl acetate fractions. Possible role of the principal chemical constituents of this plant in bringing about mortality of the pest, reduction in egg laying and adult emergence are discussed.


Development of Communication Skills Through Virtual Reality on Nursing School Students: Clinical Trial.
Multiple studies demonstrate benefits of virtual simulations as recreation of reality in the development of instrumental skills, but few randomized studies prove its efficacy in the development of communication and interpersonal relationships skills. The objective was to develop a virtual reality simulator to improve communication skills and compare its results with a traditional workshop based on cases and theoretical content explained through video. This is a randomized and controlled clinical trial, with a pretest and a posttest. Participants were first-year students from the Faculty of Nursing, Complutense University of Madrid, Spain (n = 100). The sample was divided into two groups: the intervention group (n = 50) was provided a virtual reality simulation teaching process as a novel resource, whereas the control group was provided with a case-based traditional workshop. Because data followed a normal distribution, it was analyzed with Student t test for independent samples, the group sample comparison, and analysis of variance, to find differences among age subgroups. Significant changes were observed at the time of evaluating the skills for the intervention group ( P < .01) in comparison with the control group. Both interventions are effective after the first evaluation; however, virtual reality-based intervention stands above the usual method and showed better results in older students.


Mapping the discursive dimensions of the reproducibility crisis: A mixed methods analysis.
To those involved in discussions about rigor, reproducibility, and replication in science, conversation about the "reproducibility crisis" appear ill-structured. Seemingly very different issues concerning the purity of reagents, accessibility of computational code, or misaligned incentives in academic research writ large are all collected up under this label. Prior work has attempted to address this problem by creating analytical definitions of reproducibility. We take a novel empirical, mixed methods approach to understanding variation in reproducibility discussions, using a combination of grounded theory and correspondence analysis to examine how a variety of authors narrate the story of the reproducibility crisis. Contrary to expectations, this analysis demonstrates that there is a clear thematic core to reproducibility discussions, centered on the incentive structure of science, the transparency of methods and data, and the need to reform academic publishing. However, we also identify three clusters of discussion that are distinct from the main body of articles: one focused on reagents, another on statistical methods, and a final cluster focused on the heterogeneity of the natural world. Although there are discursive differences between scientific and popular articles, we find no strong differences in how scientists and journalists write about the reproducibility crisis. Our findings demonstrate the value of using qualitative methods to identify the bounds and features of reproducibility discourse, and identify distinct vocabularies and constituencies that reformers should engage with to promote change.


Development and validation of the advance care planning practice preference scale for clinical nurses.
The aim of this study was to develop the advance care planning (ACP) practice preference scale and validate its psychometric properties among clinical nurses. An instrument development and validation study was completed in the following three phases: (a) the generation and revision of the item, (b) the preliminary exploration and evaluation of the item and (c) the psychometric evaluation of the scale. A literature review was conducted to develop the indicator system. A total of 360 clinical nurses (for item analysis) and 688 clinical nurses (for psychometric evaluation) were recruited. The exploratory factor analysis and confirmatory factor analysis were conducted to evaluate the construct validity. The reliability was explored by internal consistency and test-retest reliability. The study was conducted from October 2021 to January 2022. A total of 24 items were finally retained by the item analysis from the initial 78-item pool. In the exploratory factor analysis, the six-factor model explained 79.933% of the total variation. After limiting to three factors, 59.305% of the total variation was explained. Above factor models supported by the confirmatory factor analysis were consistent with the theoretically structure, and the fitting indexes were all satisfactory. Also, the findings showed appropriate internal consistency and test-retest reliability. ACP practice preference scale presents satisfactory psychometric properties among clinical nurses and can be adopted to evaluate the propensity of clinical nurses to practice ACP. ACP practice preference scale can be adopted to understand the training needs of clinical nurses on ACP clinical practice. Clinical nurses participated in the pilot testing and validation of ACP practice preference scale.


SERS and DFT studies of 2-(trichloroacetyl)pyrrole chemisorbed on the surface of silver and gold coated thin films: In perspective of biosensor applications.
The adsorption and orientations of 2-(trichloroacetyl)pyrrole (TCAP) adsorbed on a fabricated silver-coated thin film (SCF), and gold-coated thin film (GCF) were investigated using surface-enhanced Raman scattering (SERS) studies and compared with the normal Raman scattering (nRs) spectrum of TCAP. The observed nRs and SERS spectra of TCAP were validated theoretically using DFT quantum chemical calculations. Initially, the molecular structure of TCAP, TCAP-Ag3 , and TCAP-Au4 molecular systems were optimized and analyzed. The fabricated SCF and GCF are characterized using FESEM analysis, which confirms that the silver and gold nanoparticles of the corresponding films are spherical in shape. The obtained significant red-shift in UV-visible spectra of TCAP added on SCF and GCF surfaces reveal that the TCAP strongly adsorbed on SCF and GCF surfaces. The frontier molecular orbitals analysis authenticates the charge-transfer interaction from Ag3 and Au4 metal clusters to the TCAP molecule, leading to the adsorption of TCAP molecule on Ag3 and Au4 metal clusters, which validates the UV-vis results. SERS spectral analysis confirms that the TCAP chemisorbed on SCF and GCF surfaces with tilted orientation and the corresponding results were validated theoretically. The calculated SERS enhancement factor values illustrate that the GCF surface exhibits a higher SERS signal enhancement than the SCF surface. Therefore, the present investigation will be useful for the development of active SERS substrates and pyrrole-related biosensors.


Enzymatic conversion of adenosine to inosine in the wobble position of yeast tRNAAsp: the dependence on the anticodon sequence.
We have investigated the specificity of the tRNA modifying enzyme that transforms the adenosine at position 34 (wobble position) into inosine in the anticodon of several tRNAs. For this purpose, we have constructed sixteen recombinants of yeast tRNAAsp harboring an AXY anticodon (where X or Y was one of the four nucleotides A, G, C or U). This was done by enzymatic manipulations in vitro of the yeast tRNAAsp, involving specific hydrolysis with S1-nuclease and RNAase A, phosphorylation with T4-polynucleotide kinase and ligation with T4-RNA ligase: it allowed us to replace the normal anticodon GUC by trinucleotides AXY and to introduce simultaneously a 32P-labelled phosphate group between the uridine at position 33 and the newly inserted adenosine at position 34. Each of these 32P-labelled AXY "anticodon-substituted" yeast tRNAAsp were microinjected into the cytoplasm of Xenopus laevis oocytes and assayed for their capacity to act as substrates for the A34 to I34 transforming enzyme. Our results indicate that: 1/ A34 in yeast tRNAAsp harboring the arginine anticodon ACG or an AXY anticodon with a purine at position 35 but with A, G or C but not U at position 36 were efficiently modified into I34; 2/ all yeast tRNAAsp harboring an AXY anticodon with a pyrimidine at position 35 (except ACG) or uridine at position 36 were not modified at all. This demonstrates a strong dependence on the anticodon sequence for the A34 to I34 transformation in yeast tRNAAsp by the putative cytoplasmic adenosine deaminase of Xenopus laevis oocytes.


[Digital metastasis as an unusual primary symptom of cancer].
We describe a rare case in which the presenting symptom of lung cancer was an ulcerating tumour in a patient's distal 4th finger. Such acrometastatic lesions represent only 0.1% of all metastatic osseous involvement and have been described in relation to various cancer types. Symptoms can mimic those of a localized infection and consequently the condition is frequently overlooked or mistreated. This case serves as a reminder that metastases should be considered in patients with refractory digital lesions, not least among high-risk groups.


[Odontogenic keratocysts. Review of the literature and presentation of three clinical cases with different surgical approaches].
The odontogenic keratocyst is an intra-osseous cystic lesion which generally affects the posterior part of the mandible and is characterized by the presence of a keratinized epithelium. Being asymptomatic, it is usually detected through a routine radiographic exam and it is considered to be an important lesion because of its agressiveness and its high recurrence rate. Surgery is the recommended treatment and the mode of management should take into account the agressiveness of the lesion while trying to preserve maximal anatomical and functional integrity for the patient. This paper reviews the recent literature on odontogenic keratocysts and reports our experience with three cases successfully managed in three different ways: marsupialization, decompression followed by enucleation with primary closure and finally by enucleation with packing for secondary intention healing.


JMM Profile: West Nile virus.
West Nile virus (WNV) is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family and is maintained in an enzootic cycle between avian hosts and mosquito vectors. Humans, horses and other mammals are susceptible to infection but are dead-end hosts due to a low viraemia. The disease can manifest itself in a variety of clinical signs and symptoms in people and horses from mild fever to severe encephalitis and morbidity. There are no vaccines licensed for human protection, but parts of Europe, North America, Africa and Australia have vaccines commercially available for horses.


High Levels of Oxidative Stress Create a Microenvironment That Significantly Decreases the Diversity of the Microbiota in Diabetic Chronic Wounds and Promotes Biofilm Formation.
Diabetics chronic wounds are characterized by high levels of oxidative stress (OS) and are often colonized by biofilm-forming bacteria that severely compromise healing and can result in amputation. However, little is known about the role of skin microbiota in wound healing and chronic wound development. We hypothesized that high OS levels lead to chronic wound development by promoting the colonization of biofilm-forming bacteria over commensal/beneficial bacteria. To test this hypothesis, we used our db/db-/- mouse model for chronic wounds where pathogenic biofilms develop naturally after induction of high OS immediately after wounding. We sequenced the bacterial rRNA internal transcribed spacer (ITS) gene of the wound microbiota from wound initiation to fully developed chronic wounds. Indicator species analysis, which considers a species' fidelity and specificity, was used to determine which bacterial species were strongly associated with healing wounds or chronic wounds. We found that healing wounds were colonized by a diverse and dynamic bacterial microbiome that never developed biofilms even though biofilm-forming bacteria were present. Several clinically relevant species that are present in human chronic wounds, such as Cutibacterium acnes, Achromobacter sp., Delftia sp., and Escherichia coli, were highly associated with healing wounds. These bacteria may serve as bioindicators of healing and may actively participate in the processes of wound healing and preventing pathogenic bacteria from colonizing the wound. In contrast, chronic wounds, which had high levels of OS, had low bacterial diversity and were colonized by several clinically relevant, biofilm-forming bacteria such as Pseudomonas aeruginosa, Enterobacter cloacae, Corynebacterium frankenforstense, and Acinetobacter sp. We observed unique population trends: for example, P. aeruginosa associated with aggressive biofilm development, whereas Staphylococcus xylosus was only present early after injury. These findings show that high levels of OS in the wound significantly altered the bacterial wound microbiome, decreasing diversity and promoting the colonization of bacteria from the skin microbiota to form biofilm. In conclusion, bacteria associated with non-chronic or chronic wounds could function as bioindicators of healing or non-healing (chronicity), respectively. Moreover, a better understanding of bacterial interactions between pathogenic and beneficial bacteria within an evolving chronic wound microbiota may lead to better solutions for chronic wound management.


[Construction of HSP47-shRNA and its impact on HSP47 at cellular level].
To construct a short hairpin RNA (shRNA) against HSP47 gene, assess the expression level of HSP47 gene in NIH/3T3 cells, and observe the influence on cell function. The HSP47-shRNA sequence presented at the downstream of the U6 promoter. The shRNA expression constructs were created using PCR- based methods. The PCR product was digested with Nhe I/Hind Ill and ligated into pGCsi/U6/Neo vector to produce HSP47-pGCsi-U6-shRNA (HSP47-1-pGCsi-U6-shRNA, HSP47-2-pGCsi-U6-shRNA and HSP47-3-pGCsi-U6-shRNA). The non-interference vector and non-related interference vector served as control. The vectors were transfected into NIH/3T3 fibroblast cells by liposome mediated gene transfection method. Transfection efficiency and fluorescence intensity were determined by fluorescence microscopy at 12, 24, 48, and 72 hours after transfection, respectively. Cells were collected before transfection, and at 24, and 48 hours post-transfection, respectively, HSP47 mRNA and protein expression levels were assessed by real-time PCR and Western blotting. The mRNA expression of TGF-pl, collagen types I and Ill in NIH/3T3 cells, and TGF-beta1 levels in cell culture supernatant were determined. HSP47-shRNA vector was transfected into NIH/3T3 cells by liposome-mediated transfection. The transfection efficiency in each HSP47-shRNA plasmid interference group was about 60.0%, and there is no statistical difference among the interference groups (P> 0.05). A small amount of green fluorescent cells were found at 12 h post-transfection. The number of green fluorescent cells increased with the transfection time, and reached strongest at 72 h after transfection. shRNA interference significantly inhabited HSP47 expression in NIHI/3T3 cells. At 24 h after transfection with HSP47-1-shRNA, the inhibition effect was the strongest, and the relative silence efficiency of HSP47 mRNA was (25.83?1.79)%, lower than that of control group and non-related group (P<0.05). Collagen synthesis and secretion by NIH/3T3 cells reduced significantly at 24 and 48 hours post-transfection with HSP47-1-shRNA; and there was a significant difference between HSP47-1-shRNA intervention group and non-related controls. After transfection for 24 and 48 h, mRNA expression of collagen types I and IlI decreased to (56.52 +/- 1.64)% and (53.48 +/- 2.54)%, (54.17 +/- 2.63)% and (50.21 +/- 2.34)%, respectively, significantly lower than that of the control group and non-related group (P<0.05); however, no significant difference was found among the interference groups (P>0.05). In each HSP47-shRNA plasmid interference group, TGF-p1 mRNA expression was the lowest at 24 h post-transfection. The relative mRNA expression level was (63.23?2.18)%, (64.5+3.17)%, and (75.19 +/- 4.20)% in HSP47-1-shRNA, HSP47-2-shRNA, HSP47-3-shRNA groups (P>0.05), respectively, lower than that of the control group and non-related group (P<0.01). At 24 and 48 h post-transfection, TGF-P131 expression was the lowest at 24 h post-transfection, and the relative expression level in HSP47-1-shRNA, HSP47-2-shRNA, HSP47-3-shRNA groups was (51.79 +/- 3.12)%, (66.67 +/- 2.13)%, and (69.61 +/- 3.65)%, respectively. Compared with control group, the expression of TGF-beta1 in HSP47-1-shRNA and HSP47-2-shRNA2 groups was significant inhibited, but there was no significantly difference between control group and HSP47-3-shRNA group (P>0.05). HSP47-shRNA. interference plasmid is constructed. HSP47-shRNA effectively inhibits protein expression of HSP47, and results in changes of cell function.


Will esophageal impedance replace pH monitoring?
Esophageal impedance, a technique based on the fact that the passage of a bolus changes the impedance between esophageal segments, is being used more and more. Multiple esophageal impedance combined with pH monitoring is advocated to become the preferred technique to measure acid and nonacid gastroesophageal reflux. Compared with pH monitoring, impedance has the advantage of being independent of pH and, as a consequence, is better adapted to measure reflux (especially in the postprandial period when reflux is buffered) and detect symptoms associated with nonacid- or weakly acid-reflux episodes. Conversely, the analysis of an impedance tracing requires more time and knowledge than a pH tracing and is possibly subjected to higher interobserver variability. Day-to-day reproducibility and interobserver variability are considerable. Episodes detected only by pH monitoring or impedance are numerous in pediatrics; therefore, pH monitoring and impedance should be associated in analyses of multiple esophageal impedance combined with pH monitoring. Up to now, there has been a striking absence of literature showing attempts to link data from diagnostic procedures to clinical outcome in symptomatic patients. Furthermore, data suggesting that impedance does offer a clear-cut benefit in pediatric clinical routine are missing. High cost of the material and the investment in time necessary for interpretation of the recording remain a handicap. However, because pH monitoring is part of impedance technology, it is likely that the latter will soon replace pH monitoring despite the current need of scientific evidence demonstrating a relation between symptoms, esophageal damage or response to reflux treatment, and results of multiple esophageal impedance combined with pH monitoring.


Novel Strategy Utilizing Extracellular Cysteine-Rich Domain of Membrane Receptor for Constructing d-Peptide Mediated Targeted Drug Delivery Systems: A Case Study on Fn14.
The development of proteolysis-resistant d-peptide ligands for targeted drug/gene delivery has been greatly limited, due to the challenge that lies in the chemical synthesis of membrane receptors without altering their structures. In the present research, a novel strategy utilizing self-stabilized extracellular CRD of the membrane receptor was developed to construct d-peptide ligands and their mediated targeted drug delivery systems. Fn14, a cell surface receptor overexpressed in many cancers including pancreatic and triple-negative breast cancers, was selected as the model receptor. Fn14 CRD was synthesized and folded, and used to screen Fn14 binding peptides using phage display (l-peptide) and mirror-image phage display (d-peptide) techniques, respectively. The d-peptide ligand successfully mediated targeted drug delivery to Fn14 positive tumor cells. In addition, the d-peptide possessed better target-binding affinity, stromal barrier permeability, and tumor targeting ability in vivo when conjugated with liposomes. More importantly, d-peptide mediated liposomal paclitaxel delivery significantly inhibited pancreatic tumor growth in a subcutaneous xenograft model and drastically prolonged survival in a lung metastasis of breast cancer mouse model. This study demonstrated that mirror-image phage display based on the CRD of membrane receptor can be a promising strategy to advance active targeted drug delivery via biostable d-peptides.


Transpetrous Clip Occlusion of a Giant Midbasilar Aneurysm Using Hypothermic Cardiac Arrest: 2-Dimensional Operative Video.
Basilar trunk aneurysms are historically associated with extremely high morbidity. The complexity of circumflex perforator arteries responsible for the perfusion of the brainstem makes surgical intervention for these lesions particularly challenging. This patient had a giant midbasilar aneurysm that encompassed multiple perforators but was associated with progressive mass effect and debilitating morbidity. Therefore, a transpetrous approach was used with transposition of the facial nerve and sacrifice of the vestibulocochlear nerve to permit access to the aneurysm. Hypothermic cardiac arrest was used to permit dome manipulation with a tandem fenestrated clipping of the aneurysm. Postoperative imaging demonstrated a reduction in mass effect attributable to the significantly reduced dome size and persistence of flow via a reconstructed basilar trunk. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.


No Spread of SARS-CoV-2 From Infected Symptomatic Children to Parents: A Prospective Cohort Study in a Controlled Hospital Setting.
Introduction: The transmission rates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from children to adults are unclear due to a lack of controlled conditions. Materials and Methods: We investigated the occurrence of SARS-CoV-2 transmission among 12 discordant child-parent pairs in our ward. In each hospital isolation room, caregivers and children lived in close contact during the entire hospitalization period. Results: A total of 136 swab-positive children (mean age, 3.6 ± 4.9 median age, 1; IQR 0-6.2, range 0.1-17) attended by their caregivers were hospitalized. Of those, 12/136 (8.8%, mean age, 6.1 ± 5.3 median age, 4.5) were attended by caregivers who were swab and serology negative at admission despite previous close contact with positive children at home. Three children were completely dependent on their mothers, one of whom was being breastfed. The mean duration of overall exposure to the index case was 20.5 ± 8.2 days. Conclusion: None of the infected children transmitted SARS-CoV-2 infection to their caregivers, raising the hypothesis of a cluster of resistant mothers or of limited transmission from children to adults despite prolonged exposure and close contact. These data might provide reassurance regarding school openings and offer the chance of investigating SARS-CoV-2 variants in the future under the same quasi-experimental conditions.


Defining acute renal dysfunction as a criterion for the severity of Clostridium difficile infection in patients with community-onset vs hospital-onset infection.
Acute renal dysfunction can be used to define severe Clostridium difficile infection (CDI). The Society for Healthcare Epidemiology of America (SHEA) and Infectious Disease Society of America (IDSA) guidelines define acute renal dysfunction as serum creatinine (SrCr) ≥1.5 times the premorbid level. To determine the ability to assess premorbid SrCr in hospitalized patients with CDI, stratified into community-onset CDI (CO-CDI) and hospital-onset CDI (HO-CDI); and to evaluate differing definitions for premorbid SrCr as a criterion for acute renal dysfunction. Hospitalized patients with CDI were stratified into CO-CDI and HO-CDI. The ability to assess premorbid SrCr was determined, and the incidence of acute renal dysfunction and the severity of CDI were compared using varying definitions of premorbid SrCr. In total, 293 patients with CDI were evaluated; of these, 135 (46%) had CO-CDI and 158 (54%) had HO-CDI. Premorbid SrCr data were not available for 37 (27%) patients with CO-CDI and one (<1%) patient with HO-CDI (P < 0.0001). Depending on the definition of premorbid SrCr used, acute renal dysfunction ranged from 17% to 24% for patients with CO-CDI (P = 0.26), and from 13% to 14% for HO-CDI (P = 0.81). The severity of CDI could not be determined for 43 out of 293 (15%) patients, primarily due to the lack of premorbid SrCr data (N = 38). Assessment of acute renal dysfunction and the severity of CDI was not possible for many patients with CO-CDI using the current SHEA/IDSA guidelines. Given the increasing incidence of CO-CDI, an alternative definition of acute renal dysfunction may be required.


Thiacetazone skin reaction in Papua New Guinea.
Thiacetazone is used as a first-line antituberculosis drug in most of the developing countries of the South Pacific. Skine reactions are considered the major side effects of this drug. In Papua New Guinea, 2.5% of Melanesian patients who received thiacetazone for the treatment of tuberculosis developed skin reactions. The reaction appears to be caused by hypersensitivity rather than by toxicity and has distinct clinical features. The therapeutic regimen for tuberculosis in the developing countries of the South Pacific is not likely to change in the near future. Recognition of this potentially fatal complication of thiacetazone is important in the mamnagement of patients with tuberculosis in countries where the drug is used.


Argon laser trabeculoplasty as initial therapy for glaucoma.
Argon laser trabeculoplasty (ALT) was used as the initial treatment in 30 eyes of 20 patients with uncontrolled open-angle glaucoma in Egypt. None of the patients had received previous medical or surgical therapy. The average reduction of intraocular pressure with ALT alone was 10.1 mm Hg. Medical and surgical glaucoma therapy was avoided in 83% (25 eyes) of the treated eyes during an average follow-up period of 7 1/2 months. The data indicate that ALT can be used as a safe and effective initial treatment for glaucoma in developing countries where socioeconomic factors make the medical treatment of glaucoma impractical.


β-Sheet Breaker Peptide-HPYD for the Treatment of Alzheimer's Disease: Primary Studies on Behavioral Test and Transcriptional Profiling.
Background: Alzheimer's disease (AD), is a progressive neurodegenerative disease that is characterized by cognitive loss. Most researchers believe that aggregation and accumulation of β-amyloid peptides (Aβ) in brain cells are the central pathological hallmark of this disease. Methods: Based on the amyloid hypothesis, a 10 amino acids β-sheet breaker peptide HPYD (His-Lys-Gln-Leu-Pro-Phe-Tyr-Glu-Glu-Asp) was designed according to the structure and sequence of the previous designed peptide H102. Accelerated stability test, thioflavine T (ThT) fluorescence spectral analysis and transmission electron microscopy (TEM) imaging were performed to detect the stability and inhibitory effects on the aggregation of Aβ1-42 by H102 and HPYD. FITC-labeled HPYD was first tested to determine whether it could be transferred along the olfactory pathway to the brain after nasal administration to mice. Subsequently, the Morris Water Maze (MWM) test for behavioral analysis was used to investigate the learning and memory ability of APP/PS1 transgenic mice by HPYD. Immunohistochemistry and western blot analysis was performed to determine the role of HPYD on Aβ and APP protein levels. In addition, microarray analysis was used to evaluate the effect of HPYD on gene expression in AD mouse models. Results: Our in vitro results demonstrated that HPYD had enhanced stability and inhibitory effects on Aβ1-42 aggregation compared to H102. HPYD could be delivered into the brain through nasal administration and improved the learning and memory ability in APP/PS1 transgenic mouse models by reducing Aβ and APP protein levels. In addition, microarray analyses suggested that several genes related to the inflammatory pathway, AD and gluco-lipid metabolism were dysregulated and could be restored to almost normal levels after HPYD administration to mice. Conclusions: Our results demonstrated that HPYD could be a potential therapeutic drug candidate for the treatment of AD.


Changes in Tracheal Respiratory Mucosa After Thyroidectomy: A Rat Model.
This study aimed to investigate changes in the tracheal mucosa after thyroidectomy, that can be a cause of post-thyroidectomy discomfort. Forty rats were divided into normal controls and 3 surgical groups: (i) thyroid isthmectomy with cauterization, (ii) isthmectomy by a cold instrument without hemostasis, and (iii) sham (exposure of the trachea and thyroid gland without thyroidectomy by dissection through pretracheal fascia). Animals were euthanized at 1 and 4 weeks. Mucosal edema and glandular hyperplasia were measured. Mucin production and basal cell activities were evaluated by mucin 5AC (MUC5AC) and keratin 5 (KRT5) using immunofluorescence staining. Larger mucosal areas were observed in all surgical groups at 1 and 4 weeks. More submucosal glandular hyperplasia was noted in the group with isthmectomy without hemostasis. MUC5AC and KRT5 expressions were significantly higher in the surgical groups. The tracheal mucosa may change after surgery, which could explain postoperative discomfort after thyroidectomy.


The place of closed mitral valvotomy in the modern cardiac surgery era.
The study aim was to investigate the long-term efficacy of closed mitral valvotomy (CMV). Data obtained over a 36-year period from 1,134 patients who underwent CMV were analyzed. The analysis was carried out retrospectively from hospital records, with follow up examinations being conducted mainly at the outpatient clinic. In-hospital mortality (< or = 30 days after surgery) was 0.4% (n = 5, all closed procedures). Cardiac failure was the main cause of early death, and postoperative peripheral embolism occurred in five cases (0.5%). Freedom from thromboembolism was 99.0 +/- 0.5% at 36 years. Operative results were satisfactory in most patients, and severe mitral incompetence was seen only in three cases. Post-valvotomy mitral regurgitation occurred in 88 patients (7.7%) during the first year after CMV. Reoperation was performed in 500 patients (44.1%). The mean interval between CMV and reoperation was 141.1 +/- 80.8 months (range: 1-436 months). Fourteen patients were reoperated on for mitral regurgitation, 485 for mitral restenosis, and five for mixed mitral valve disease (stenosis and regurgitation). Freedom from reoperation after CMV was 81.4 +/- 1.3% at 10 years, 16.4 +/- 2.1% at 20 years, 3.1 +/- 1.2% at 20 years, and 0% at 36 years. Cox regression analysis indicated that impaired functional capacity, reduced mitral valve area, gradual increase in left atrial diameter and postoperative mitral insufficiency increased the reoperation rate after CMV. When compared with percutaneous balloon or surgical open valvotomy, CMV represents a satisfactory technique in terms of simplicity, high efficacy and lower cost.


Task-specific strength increases after lower-limb compound resistance training occurred in the absence of corticospinal changes in vastus lateralis.
What is the central question of the study? Are corticospinal responses to acute and short-term squat resistance training task-specific? What is the main finding and its importance? A single bout of resistance training increased spinal excitability, but no changes in corticospinal responses were noted following 4 weeks of squat training despite task-specific increases in strength. The present data suggest that processes along the corticospinal pathway of the knee extensors play a limited role in the task-specific increase in strength following resistance training. Neural adaptations subserving strength increases have been shown to be task-specific, but responses and adaptation to lower-limb compound exercises such as the squat are commonly assessed in a single-limb isometric task. This two-part study assessed neuromuscular responses to an acute bout (Study A) and 4 weeks (Study B) of squat resistance training at 80% of one-repetition-maximum, with measures taken during a task-specific isometric squat (IS) and non-specific isometric knee extension (KE). Eighteen healthy volunteers (25 ± 5 years) were randomised into either a training (n = 10) or a control (n = 8) group. Neural responses were evoked at the intracortical, corticospinal and spinal levels, and muscle thickness was assessed using ultrasound. The results of Study A showed that the acute bout of squat resistance training decreased maximum voluntary contraction (MVC) for up to 45 min post-exercise (-23%, P < 0.001). From 15-45 min post-exercise, spinally evoked responses were increased in both tasks (P = 0.008); however, no other evoked responses were affected (P ≥ 0.240). Study B demonstrated that following short-term resistance training, participants improved their one repetition maximum squat (+35%, P < 0.001), which was reflected by a task-specific increase in IS MVC (+49%, P = 0.001), but not KE (+1%, P = 0.882). However, no training-induced changes were observed in muscle thickness (P = 0.468) or any evoked responses (P = 0.141). Adjustments in spinal motoneuronal excitability are evident after acute resistance training. After a period of short-term training, there were no changes in the responses to central nervous system stimulation, which suggests that alterations in corticospinal properties of the vastus lateralis might not contribute to increases in strength.


A Simple Non-invasive Method for Temporary Knockdown of Upper Limb Proprioception.
Proprioception may be the least well measured of all contributors to the neural control of movement. New precise, reliable measures of proprioception are needed for clinical diagnosis of impairment, and to measure outcomes of proprioceptive training. The purpose of this simple, non-invasive method is to temporarily knockdown upper limb proprioception in healthy adults, to an extent that would be useful in the development and testing of upper limb proprioception measures. Knockdown models have two main advantages over studying humans with impaired proprioception: participant availability and the ability to control the extent of impairment across participants. Current published methods of temporary proprioception knockdown of the upper limb, such as ischemic nerve blocks and cryotherapy, are invasive, impractical, or uncomfortable for the participant. Here, vibration over the ulnar groove was used to reduce upper limb proprioception. High frequency vibration may reduce proprioceptive acuity by inhibiting pacinian corpuscle-induced input. The effect of vibration used in this protocol was confirmed using two quantitative measures. This method was simple to administer, comfortable for participants, and practical.


Gadolinium-Based Nanoparticles Sensitize Ovarian Peritoneal Carcinomatosis to Targeted Radionuclide Therapy.
Ovarian cancer (OC) is the most lethal gynecologic malignancy (5-y overall survival rate, 46%). OC is generally detected when it has already spread to the peritoneal cavity (peritoneal carcinomatosis). This study investigated whether gadolinium-based nanoparticles (Gd-NPs) increase the efficacy of targeted radionuclide therapy using [177Lu]Lu-DOTA-trastuzumab (an antibody against human epidermal growth factor receptor 2). Gd-NPs have radiosensitizing effects in conventional external-beam radiotherapy and have been tested in clinical phase II trials. Methods: First, the optimal activity of [177Lu]Lu-DOTA-trastuzumab (10, 5, or 2.5 MBq) combined or not with 10 mg of Gd-NPs (single injection) was investigated in athymic mice bearing intraperitoneal OC cell (human epidermal growth factor receptor 2-positive) tumor xenografts. Next, the therapeutic efficacy and toxicity of 5 MBq of [177Lu]Lu-DOTA-trastuzumab with Gd-NPs (3 administration regimens) were evaluated. NaCl, trastuzumab plus Gd-NPs, and [177Lu]Lu-DOTA-trastuzumab alone were used as controls. Biodistribution and dosimetry were determined, and Monte Carlo simulation of energy deposits was performed. Lastly, Gd-NPs' subcellular localization and uptake, and the cytotoxic effects of the combination, were investigated in 3 cancer cell lines to obtain insights into the involved mechanisms. Results: The optimal [177Lu]Lu-DOTA-trastuzumab activity when combined with Gd-NPs was 5 MBq. Moreover, compared with [177Lu]Lu-DOTA-trastuzumab alone, the strongest therapeutic efficacy (tumor mass reduction) was obtained with 2 injections of 5 mg of Gd-NPs/d (separated by 6 h) at 24 and 72 h after injection of 5 MBq of [177Lu]Lu-DOTA-trastuzumab. In vitro experiments showed that Gd-NPs colocalized with lysosomes and that their radiosensitizing effect was mediated by oxidative stress and inhibited by deferiprone, an iron chelator. Exposure of Gd-NPs to 177Lu increased the Auger electron yield but not the absorbed dose. Conclusion: Targeted radionuclide therapy can be combined with Gd-NPs to increase the therapeutic effect and reduce the injected activities. As Gd-NPs are already used in the clinic, this combination could be a new therapeutic approach for patients with ovarian peritoneal carcinomatosis.


PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT/mTOR pathway.
Growing evidence shows that protein kinase D (PKD) plays an important role in the development of pressure overload-induced cardiac hypertrophy. However, the mechanisms involved are not clear. This study tested our hypothesis that PKD might mediate cardiac hypertrophy by negatively regulating autophagy using the technique of PKD knockdown by siRNA. Cardiac hypertrophy was induced in 8-week old male C57BL/6 mice by transverse aortic constriction (TAC). TAC mice were then divided into five groups receiving the treatments of vehicle (DMSO), an autophagy inducer rapamycin (1 mg/kg/day, i.p.), control siRNA, lentiviral PKD siRNA (2×108 transducing units/0.1 ml, i.v. injection in one day after surgery, and repeated in 2 weeks after surgery), and PKD siRNA plus 3-methyladenine (3-MA, an autophagy inhibitor, 20 mg/kg/day, i.p.), respectively. Four weeks after TAC surgery, echocardiographic study, hematoxylin and eosin (HE) staining, and Masson's staining showed mice with TAC had significantly hypertrophy and remodeling compared with sham animals. Treatments with PKD siRNA or rapamycin significantly ameliorated the cardiac hypertrophy and dysfunction. Moreover, PKD siRNA increased cardiac autophagic activity determined by electron micrographic study and the biomarkers by Western blot, accompanied with the downregulated AKT/mTOR/S6K signaling pathway. All the cardiac effects of PDK knockdown were inhibited by co-treatment with 3-MA. These results suggest that PKD is involved in the development of cardiac hypertrophy by inhibiting cardiac autophagy via AKT/mTOR pathway.


Economic Evaluation of the Use of Drug-Eluting Stents versus Bare-Metal Stents in Adults with Ischemic Cardiomyopathy Requiring Angioplasty.
The value of drug-eluting stents in preventing cardiovascular events has not been investigated in Mexico. To conduct a cost-effectiveness analysis of early and new-generation drug-eluting stents from the perspective of a healthcare provider. We conducted a cost-effectiveness analysis of early and new-generation drug-eluting stents in patients with ischemic cardiomyopathy attending a Cardiology Hospital of the Mexican Social Security Institute. The health endpoint used was major acute cardiovascular events prevented. The effectiveness by stent type was obtained from the literature. A retrospective chart review study was conducted to collect cost data on cardiovascular events including seven cost categories. Average and incremental cost-effectiveness ratios were estimated. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of estimates. Incremental cost-effectiveness ratios in base-case were 28,910 and US$ 35,590 for early and new-generation stents, respectively. In an optimal scenario, incremental-cost effectiveness ratio was 24,776 and US$ 25,262 for early and new stents, respectively. Probabilistic sensitivity analysis suggested that 90% of cases were cost-effective when willingness-to-pay was 58,000 and US$ 66,000 for early and new-generation stents, respectively. The cost-effectiveness ratios of early and new-generation stents were significantly higher than corresponding bare-metal stents.


In non-follicular lymphoproliferative disorders, IGH/BCL2-fusion is not restricted to chronic lymphocytic leukaemia.
The translocation t(14;18) and its t(2;18) and t(18,22) variants, which involve the BCL2 genetic hallmark for follicular lymphoma (FL), have been reported in several cases of chronic B-cell lymphoproliferative disease (CLPD) and frequently in chronic lymphocytic leukaemia (CLL). We describe here the clinical, morphological, immunological, cytogenetic and molecular findings from 37 cases of t(14;18)-positive CLPD, identified from our series of non-FL B-cell neoplasms (n=993) that were routinely analysed in peripheral blood by conventional cytogenetics analyses. The FL diagnosis was excluded by morphology and immunology (the samples were CD10 negative in all cases). The BCL2 translocations were observed in 22 CLL cases, including 7 monoclonal B-cell lymphocytosis (MBL) cases re-classified according to the new International Workshop on CLL criteria, six small lymphocytic lymphoma (SLL) cases, 1 splenic marginal zone lymphoma (SMZL) case and eight cases of unclassifiable CLPD with overlapping CLL/MZL features. In the CLL cases, the IGH/BCL2 fusion was remarkably associated with trisomy 12 (13/22) and mutated IGHV status (20/21) and did not affect the outcome. Moreover, most of these CLLs harboured a low mutation load of BCL6 gene and unmutated FAS (CD95) loci, which points to a post-germinal-centre cellular origin.


Morphological, cytogenetic and molecular characterisation of FLT3 mutations in Pakistani patients with de novo acute myeloid leukaemia: A single centre experience.
Mutations in FLT3 are the most commonly reported genetic changes in AML patients. These mutations are normally identified in approximately one third of newly diagnosed patients and are reported to have prognostic significance. Peripheral blood samples was collected from 63 AML patients to study their morphological, cytogenetic and molecular features. PCR was used to determine the prevalence of FLT3 mutations; internal tandem duplication (ITD) and tyrosine kinase domain (TKD) in AML patients. Among 63 AML patients, 42 were males and 21 were females with male to female ratio 2:1 with median age of 32 years. AML-M2 was the predominant French-American-British (FAB) subtype (42%) followed by M4 (27%), M3 (8%), M1 (8%), M0 (8%) and M5 (7%) respectively. Cytogenetic analysis of 60 patients showed 58% as cytogenetically normal (CN) whereas 42% had aberrant karyotype.The most frequent aberrations were trisomy8, t(8;21), t(15;17) (8.3%) each, inversion16 (5%), and different deletions (12%) respectively. FAB-M4 subtype showed most of the chromosomal anomalies. Among 63 AML patients, 22% showed FLT3/ITD while 6.4% had D835 mutation after molecular analysis. FLT3 mutations were found in most of the FAB subtypes and cytogenetic groups. FLT3/ITD mutations were more common in patients with normal karyotype (26%) and usually present with hyperleukocytosis but association between two was not significant. The cytogenetic data of adult AML from Pakistan showed presence of favourable prognostic karyotype with comparable prevalence as reported in international data. Moreover, FLT3/ITD mutations are commonly found in our patients as determined by molecular analysis. Therefore, inclusion of this unfavourable prognostic marker should be routine in molecular diagnostic testing of AML.


Pericyte-coverage of human tumor vasculature and nanoparticle permeability.
Nano drug delivery systems (nanoDDS) are a promising strategy for treatment of human tumors. As indicated by our previous work, the extent of pericyte-coverage of tumor vasculature is important to determining nanoDDS efficacy since intratumoral accumulation of nanoDDS is less in tumor models with pericyte-covered vasculature. Here we investigated the clinical relevance of our previous observations in animal models, by determining pericyte coverage using immunohistochemistry of smooth muscle actin (SMA) with CD34: a vascular endothelial marker, in human tumor tissue samples. The investigation revealed that tumor vasculature coverage by pericytes in pancreatic and diffuse-type gastric cancers was significantly greater than in ovarian, colon, and intestinal-type gastric cancers. The latter group of cancers is easier to treat clinically. These observations are consistent with our previous findings in animal models. On the basis of these findings we believe optimization of nanoDDS delivery should be done depend upon a clear understanding of the effects of pericyte vascular coverage.


Barley anther culture: assessment of carbohydrate effects on embryo yield, green plant production and differential plastid development in relation with albinism.
Sugars and polyols were tested at different steps of anther culture in barley (Hordeum vulgare L.) to elucidate their influence on both the overall yield of androgenesis and the structure of plastids in relation to albinism. During the pretreatment period, the osmotic regulation in the medium was beneficial to microspore embryogenesis regardless of the type and concentration of the tested osmoticum. The use of mannitol (300 mOsm/kg), sorbitol (180 mOsm/kg), PEG (240 mOsm/kg) and sucrose (180 mOsm/kg) gave the best results in terms of green plant production, although the influence of each substance differed according to the studied parameter. Similarly, during anther culture the regulation of the osmotic pressure in the medium had various effects, according to the osmoticum used. The best results were obtained using mannitol (364 mOsm/kg), providing 139.7 green plants per 100 plated anthers. Plastids were examined by electron microscopy following both pretreatment and culture. In the presence of mannitol and PEG, plastids did not accumulate starch at any stage of the protocol but they started to differentiate into chloroplasts in the microspore-derived embryos. Using sorbitol and sucrose, plastids differentiated poorly but accumulated large amounts of starch, suggesting that these sugars are metabolized by micropores and microspore derived structures. However, the accumulation of starch was not correlated with the occurrence of albinism. These results indicated that, in barley, the osmotic regulation was favourable to switch the microspore gametophytic program toward a sporophytic program regardless of the nature of the osmoticum. In addition, during the pretreatment period, mannito was found to be the most suitable osmoticum for subsequent embryo development.


Neurovirulence of polytropic murine retrovirus is influenced by two separate regions on opposite sides of the envelope protein receptor binding domain.
Changes in the envelope proteins of retroviruses can alter the ability of these viruses to infect the central nervous system (CNS) and induce neurological disease. In the present study, nine envelope residues were found to influence neurovirulence of the Friend murine polytropic retrovirus Fr98. When projected on a three-dimensional model, these residues were clustered in two spatially separated groups, one in variable region B of the receptor binding site and the other on the opposite side of the envelope. Further studies indicated a role for these residues in virus replication in the CNS, although the residues did not affect viral entry.


Hydrodynamic radius coincides with the slip plane position in the electrokinetic behavior of lysozyme.
The zeta potential (ζ) is the effective charge energy of a solvated protein, describing the magnitude of electrostatic interactions in solution. It is commonly used in the assessment of adsorption processes and dispersion stability. Predicting ζ from molecular structure would be useful to the structure-based molecular design of drugs, proteins, and other molecules that hold charge-dependent function while remaining suspended in solution. One challenge in predicting ζ is identifying the location of the slip plane (XSP ), a distance from the protein surface where ζ is theoretically defined. This study tests the hypothesis that the XSP can be estimated by the Stokes-Einstein hydrodynamic radius (Rh ), using globular hen egg white lysozyme as a model system. Although the XSP and Rh differ in their theoretical definitions, with the XSP being the position of the ζ during electrokinetic phenomena (e.g., electrophoresis) and the Rh being a radius pertaining to the edge of solvation during diffusion, they both represent the point where water and ions no longer adhere to a molecule. This work identifies the limited range of ionic strengths in which the XSP can be determined using diffusivity measurements and the Stokes-Einstein equation. In addition, a computational protocol is developed for determining the ζ from a protein crystal structure. At low ionic strengths, a hyperdiffusivity regime exists, requiring direct measurement of electrophoretic mobility to determine ζ. This work, therefore, supports a basic tenant of EDL theory that the electric double layer during diffusion and electrophoresis are equivalent in the Stokes-Einstein regime.


[Adult T-cell lymphoblastic lymphoma associated with quiescent multiple myeloma].
We report the case history of a female patient suffering of a T lymphoblastic lymphoma with an atypical presentation and evolution, consisting of pleuropericardiac effusion without mediastinic masses that coexists with a plasma cell dyscrasia that fulfils the criteria for stationary multiple myeloma. The possible pathogenic relationship between both processes is discussed, emphasizing the functional evolutive dissociation between the cellular constituents of both neoplasias, immature T lymphoblasts and plasma cells, respectively; this constitutes the first reported case in literature.


Unrestrained caspase-dependent cell death caused by loss of Diap1 function requires the Drosophila Apaf-1 homolog, Dark.
In mammals and Drosophila, apoptotic caspases are under positive control via the CED-4/Apaf-1/Dark adaptors and negative control via IAPs (inhibitor of apoptosis proteins). However, the in vivo genetic relationship between these opposing regulators is not known. In this study, we demonstrate that a dark mutation reverses catastrophic defects seen in Diap1 mutants and rescues cells specified for Diap1- regulated cell death in development and in response to genotoxic stress. We also find that dark function is required for hyperactivation of caspases which occurs in the absence of Diap1. Since the action of dark is epistatic to that of Diap1, these findings demonstrate that caspase-dependent cell death requires concurrent positive input through Apaf-1-like proteins together with disruption of IAP-caspase complexes.


Lessons learned while building an integrated ICU workstation.
The project LUCY (Linked Ulm Care sYstem) is described. The goal of this project was to build a research workstation in an Intensive Care Unit which enables evaluation of data/information processing and presentation concepts. Also evaluation of new devices and functions considering not only one device but the workplace as an entirety was an aim of the project. We describe the complete process of building from the stage of design until its testing in clinical routine. LUCY includes a patient monitor, a ventilator, 4 infusion pumps and 8 syringe pumps. All devices are connected to a preprocessing computer via serial interfaces. A high performance graphic workstation is used for central display of physiological and therapeutic variables. A versatile user interface provides touch screen, keyboard and mouse interaction. For fluid administration a bar code based control and documentation facility was included. While our scheduled development efforts were below 4 man-years, the overall man-power needed until the first routine test amounts to 8 man-years. Costs of devices and software sum up to 160,000 US$. First experiences in clinical routine show good general acceptance of the workplace concept. Analysing the recorded data we found 90% of the items to be redundant: individual filtering algorithms are necessary for each of nowaday's devices. The flexibility of the system concerning the implementation of new features is far from our expectations. Technical maintenance of the system during clinical operation requires continuous effort which we cannot afford in the current situation.


Partitioning of chemical contaminants to microplastics: Sorption mechanisms, environmental distribution and effects on toxicity and bioaccumulation.
There is an increasing awareness of the threats posed by the worldwide presence of microplastics (MPs) in the environment. Due to their high persistence, MPs will accumulate in the environment and their quantities tend to increase with time. MPs end up in environments where often also chemical contaminants are present. Since the early 2000s, the number of studies on the sorption of chemicals to plastic particles has exponentially increased. The objective of this study was to critically review the literature to identify the most important factors affecting the sorption of chemical contaminants to MPs. These factors include the physicochemical properties of both the MPs and the chemical contaminants as well as environmental characteristics. A limited number of studies on soil together with an increased notion of the importance of this compartment as a final sink for MPs was observed. Therefore, we assessed the distribution of model chemicals (two PCBs and phenanthrene) in the soil compartment in the presence of MPs using a mass balance model. The results showed a high variation among chemicals and microplastic types. Overall, a higher partitioning to MPs of chemical contaminants in soil is expected in comparison to aquatic environments. As sorption to a large extent determines bioavailability, the effects of combined exposure to chemicals and MPs on the toxicity and bioaccumulation in biota are discussed. Finally, some considerations regarding sorption and toxicity studies using MPs are given.


First-trimester transabdominal fetal echocardiography.
Fetal echocardiography is usually done during the second trimester of pregnancy, but waiting until that time can lead to anxiety for the parents if the fetus is at high risk of having cardiac abnormalities. We report the feasibility of transabdominal first-trimester fetal echocardiography for early reassurance of normality or a prenatal diagnosis of a cardiac malformation. We did first-trimester fetal echocardiography and colour-flow mapping with a 5 MHz curvilinear transducer at 13 weeks' gestation (range 12-13+6 days) in 15 fetuses at risk of cardiac defects. The fetus was judged to be normal if the investigation showed normal visceral situs, four-chamber view, and two normally related great arteries of similar size. We did second-trimester scans and neonatal follow-up for the women who continued with their pregnancies; necropsy was done in two cases of pregnancy termination. Ten fetuses had normal hearts at the time of the first scan, which was confirmed during second-trimester assessment. In one fetus, the four-chamber view was asymmetrical and a moderate-sized apical muscular ventricular septal defect (VSD) was diagnosed after birth. In another two fetuses we diagnosed small muscular VSD on the second-trimester scans. A complex cardiac malformation was correctly diagnosed in one fetus at 12 weeks of gestation. Thus, in 11 fetuses, the imaging was of sufficient quality to reassure the family or to diagnose an abnormality. In the other four fetuses, the investigation was judged to be incomplete, but no definite cardiac abnormality was identified. Transabdominal fetal echocardiography in the first trimester of pregnancy is feasible. In most patients the resolution of images is sufficient to allow assessment of basic cardiac anatomy, when normal, or detection of complex malformations, when present.


[Inhibitory effects of Salvia miltiorrhiza injection coordinated with dexamethasone on interleukin-13 and eotaxin expression in lung of asthmatic rats].
To investigate the molecular mechanism of inhibitory effect of Salvia miltiorrhiza Injection (SMI) coordinated with dexamethasone (DXM) on allergic airway inflammation in asthmatic rats. Forty SD rats were randomly divided into 5 groups equally: the normal group, the asthma model group, the DXM group, the SMI group and the DXM + SMI group, they were treated with correspondant herbal medicines. Pathologic changes of lung tissue were obseved with HE stain, count of WBC and eosinophil (Eos) in bronchoalveolar lavage fluid (BALF) were estimated and the expressions of interleukin-13 (IL-13) and Eotaxin in lung tissue were measured by RT-PCR and SP method of immunohistochemistry assay. There was moderate inflammation in lung tissue in the SMI group, and mild inflammation in the DXM + SMI and the DXM group, which was similar to that in the normal group. Compared with the asthma model group, Eos and WBC count in BALF and the expression of IL-13 and Eotaxin in the lung tissue were significantly lower in the three treated groups (P < 0.05), particularly in the DXM + SMI group, showing a significant difference as compared with the other two groups (P < 0.05 or P < 0.01). Additionally, IL-13 expression was positively correlated with Eotaxin expression (r = 0.92, P < 0.01). SMI could inhibit the expression of IL-13 and Eotaxin in the lung of asthmatic rats, showing inhibitory effects synergistic with DXM on airway inflammation.


When fate hands you lemons: A moderated moderation model of bullying victimization and psychological distress among Chinese adolescents during floods and the COVID-19 pandemic.
Bullying is a major problem worldwide and has numerous detrimental effects on the mental health of victims. The link between bullying and psychological distress in adolescents is well known. However, few studies have analyzed the impact of combined interpersonal, peer, and cultural factors on psychological distress using a social-ecological system framework in Eastern countries. Negotiable fate is a cultural belief common in Eastern societies that suggests that people can negotiate with fate for more control by exercising personal agency within the limits of what fate has determined. This study examined the moderating effects of neuroticism and negotiable fate on the relationship between bullying victimization and psychological distress among Chinese adolescents. Moreover, human society commonly suffers from multiple disasters that lead to severe mental health problems. There are few empirical studies on the effects of bullying among adolescents in multiple disaster contexts. This study included participants who experienced floods and COVID-19 simultaneously in 2021. We conducted a cross-sectional cluster sampling study from August 6 to 9, 2021, approximately 2 weeks after the start of the Zhengzhou City flooding and 7 days after the new wave of the COVID-19 outbreak in Zhengzhou City. The study included 1,207 participants (52.4% men, n = 633; M age = 14.36, SD = 0.94) from a middle school in Zhengzhou City, China. The results revealed that bullying was positively linked to psychological distress (β = 0.5.34, p < 0.001, [0.73, 9.95]). Neuroticism and negotiable fate significantly moderated the relationship between the effects of bullying and psychological distress (β = -3.58, p < 0.05, 95% CI [-6.12, -1.04]). Specifically, high neuroticism increased the risk of psychological distress in adolescents bullied before a disaster. High or low neuroticism and high negotiable fate buffered the link between bullying and psychological distress. This study showed that neuroticism and negotiable fate moderated the relationship between bullying victimization and psychological distress in Chinese students with COVID-19 and flood disasters. High negotiable fate and high or low neuroticism could help adolescents bullied in school to be immune from psychological distress in catastrophe. The results highlight the importance of considering the interplay between bullying, neuroticism, and a sense of controllable destiny when examining adolescents' psychological distress.


[Neonatal hypoxic-ischemic brain injury: pathogenesis and neuropathology].
The perinatal period represents a clinical setting of potential risk for injury to developing brain secondary to many causes, with the chance for long-lasting, profound neurocognitive deficits. Neonatal hypoxic-ischemic brain injury leads to serious long-term morbidities. The leading pathogenetic mechanisms are hypoxia and/or ischemia, as a result of perinatal asphyxia. Understanding of the underlying pathophysiology will help the physicians in the general supportive management and neuroprotection of the neonatal brain.


Synchronization by dynamical relaying in electronic circuit arrays.
We experimentally study the synchronization of two chaotic electronic circuits whose dynamics is relayed by a third parameter-matched circuit, to which they are coupled bidirectionally in a linear chain configuration. In a wide range of operating parameters, this setup leads to synchronization between the outer circuits, while the relaying element remains unsynchronized. The specifics of the synchronization differ with the coupling level: for low couplings a state of intermittent synchronization between the outer circuits coexists with one of antiphase synchronization. Synchronization becomes in phase for moderate couplings, and for strong coupling identical synchronization is observed between the outer elements, which are themselves synchronized in a generalized way with the relaying element. In the latter situation, the middle element displays a triple-scroll attractor that is not possible to obtain when the chaotic oscillator is isolated.


Antagonistic Coevolution of MER Tyrosine Kinase Expression and Function.
TYRO3, AXL, and MERTK (TAM) receptors are a family of receptor tyrosine kinases that maintain homeostasis through the clearance of apoptotic cells, and when defective, contribute to chronic inflammatory and autoimmune diseases such as atherosclerosis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and Crohn's disease. In addition, certain enveloped viruses utilize TAM receptors for immune evasion and entry into host cells, with several viruses preferentially hijacking MERTK for these purposes. Despite the biological importance of TAM receptors, little is understood of their recent evolution and its impact on their function. Using evolutionary analysis of primate TAM receptor sequences, we identified strong, recent positive selection in MERTK's signal peptide and transmembrane domain that was absent from TYRO3 and AXL. Reconstruction of hominid and primate ancestral MERTK sequences revealed three nonsynonymous single nucleotide polymorphisms in the human MERTK signal peptide, with a G14C mutation resulting in a predicted non-B DNA cruciform motif, producing a significant decrease in MERTK expression with no significant effect on MERTK trafficking or half-life. Reconstruction of MERTK's transmembrane domain identified three amino acid substitutions and four amino acid insertions in humans, which led to significantly higher levels of self-clustering through the creation of a new interaction motif. This clustering counteracted the effect of the signal peptide mutations through enhancing MERTK avidity, whereas the lower MERTK expression led to reduced binding of Ebola virus-like particles. The decreased MERTK expression counterbalanced by increased avidity is consistent with antagonistic coevolution to evade viral hijacking of MERTK.


The impact of body mass index on the pregnancy outcomes and risk of perinatal depression: Findings from a multicenter Italian study.
Body Mass Index (BMI) is an informative factor on body fatness which has been associated to higher levels of Perinatal Depression (PD) and complications during pregnancy. We aimed to explore the impact of pre-pregnancy and postnatal BMI on the risk of Perinatal Depression and pregnancy outcomes among women recruited at their third trimester of pregnancy. We report on findings from a large multi-centre study conducted in the South of Italy and involving 1611 women accessing three urban gynaecological departments from July to November 2020. Pregnant women were assessed at their third trimester of pregnancy (T0) and after the childbirth (T1) ;The Edinburgh Postnatal Depression Scale (EPDS) has been employed for the screening of PD over time (T0 and T1) as well as other standardized measures for neuroticism, resilience, and quality of life at baseline. BMI (T0 and T1) and other socio-demographic and clinical characteristics have been collected. Over-weight and obesity (higher levels of BMI) were associated with higher risk of PD (higher scores of EPDS), higher neuroticism and poorer subjective psychological well-being among enrolled women. Also, obesity and over-weight were associated with lower education, higher number of physical comorbidities, medical treatments and complications during pregnancy. Over-weight and obesity may impact on mental health and pregnancy outcome of women enrolled. Psycho-educational interventions aimed to improve the management of physical and emotional issues may reduce the risk of PD and complications during pregnancy.


Muscle metaboreflex activation during dynamic exercise vasoconstricts ischemic active skeletal muscle.
Metabolite accumulation due to ischemia of active skeletal muscle stimulates group III/IV chemosensitive afferents eliciting reflex increases in arterial blood pressure and sympathetic activity, termed the muscle metaboreflex. We and others have previously demonstrated sympathetically mediated vasoconstriction of coronary, renal, and forelimb vasculatures with muscle metaboreflex activation (MMA). Whether MMA elicits vasoconstriction of the ischemic muscle from which it originates is unknown. We hypothesized that the vasodilation in active skeletal muscle with imposed ischemia becomes progressively restrained by the increasing sympathetic vasoconstriction during MMA. We activated the metaboreflex during mild dynamic exercise in chronically instrumented canines via graded reductions in hindlimb blood flow (HLBF) before and after α1-adrenergic blockade [prazosin (50 μg/kg)], β-adrenergic blockade [propranolol (2 mg/kg)], and α1 + β-blockade. Hindlimb resistance was calculated as femoral arterial pressure/HLBF. During mild exercise, HLBF must be reduced below a threshold level before the reflex is activated. With initial reductions in HLBF, vasodilation occurred with the imposed ischemia. Once the muscle metaboreflex was elicited, hindlimb resistance increased. This increase in hindlimb resistance was abolished by α1-adrenergic blockade and exacerbated after β-adrenergic blockade. We conclude that metaboreflex activation during submaximal dynamic exercise causes sympathetically mediated α-adrenergic vasoconstriction in ischemic skeletal muscle. This limits the ability of the reflex to improve blood flow to the muscle.


De-dimerization of PTB is catalyzed by PDI and is involved in the regulation of p53 translation.
Polypyrimidine tract-binding protein (PTB) is an RNA binding protein existing both as dimer and monomer and shuttling between nucleus and cytoplasm. However, the regulation of PTB dimerization and the relationship between their functions and subcellular localization are unknown. Here we find that PTB presents as dimer and monomer in nucleus and cytoplasm respectively, and a disulfide bond involving Cysteine 23 is critical for the dimerization of PTB. Additionally, protein disulfide isomerase (PDI) is identified to be the enzyme that catalyzes the de-dimerization of PTB, which is dependent on the CGHC active site of the a' domain of PDI. Furthermore, upon DNA damage induced by topoisomerase inhibitors, PTB is demonstrated to be de-dimerized with cytoplasmic accumulation. Finally, cytoplasmic PTB is found to associate with the ribosome and enhances the translation of p53. Collectively, these findings uncover a previously unrecognized mechanism of PTB dimerization, and shed light on the de-dimerization of PTB functionally linking to cytoplasmic localization and translational regulation.


Stat1 is an inducible transcriptional repressor of neural stem cells self-renewal program during neuroinflammation.
A central issue in regenerative medicine is understanding the mechanisms that regulate the self-renewal of endogenous stem cells in response to injury and disease. Interferons increase hematopoietic stem cells during infection by activating STAT1, but the mechanisms by which STAT1 regulates intrinsic programs in neural stem cells (NSCs) during neuroinflammation is less known. Here we explored the role of STAT1 on NSC self-renewal. We show that overexpressing Stat1 in NSCs derived from the subventricular zone (SVZ) decreases NSC self-renewal capacity while Stat1 deletion increases NSC self-renewal, neurogenesis, and oligodendrogenesis in isolated NSCs. Importantly, we find upregulation of STAT1 in NSCs in a mouse model of multiple sclerosis (MS) and an increase in pathological T cells expressing IFN-γ rather than interleukin 17 (IL-17) in the cerebrospinal fluid of affected mice. We find IFN-γ is superior to IL-17 in reducing proliferation and precipitating an abnormal NSC phenotype featuring increased STAT1 phosphorylation and Stat1 and p16ink4a gene expression. Notably, Stat1-/- NSCs were resistant to the effect of IFN-γ. Lastly, we identified a Stat1-dependent gene expression profile associated with an increase in the Sox9 transcription factor, a regulator of self-renewal. Stat1 binds and transcriptionally represses Sox9 in a transcriptional luciferase assay. We conclude that Stat1 serves as an inducible checkpoint for NSC self-renewal that is upregulated during chronic brain inflammation leading to decreased self-renewal. As such, Stat1 may be a potential target to modulate for next generation therapies to prevent progression and loss of repair function in NSCs/neural progenitors in MS.


RA-Induced Transcriptional Silencing of Checkpoint Kinase-2 through Promoter Methylation by Dnmt3b Is Required for Neuronal Differentiation of P19 Cells.
In a previous study, we identified several novel targets of Dnmt3b using a chromatin library from retinoic acid (RA)-treated P19 cells. The present study describes the regulation of expression and function of checkpoint kinase (Chk2), which was one of the target genes of Dnmt3b. Chromatin immunoprecipitation followed by quantitative PCR analysis showed that recruitment of Dnmt3b on Chk2 promoter is induced following RA treatment of P19 cells. Both bisulfite genomic sequence and COBRA analyses showed that the methylation level of Chk2 promoter is progressively increased during RA-induced neuronal differentiation of P19 cells. Concomitantly, both mRNA and protein expression of Chk2 are reduced as determined by real-time PCR and Western blot analysis, respectively. Suppression of Dnmt3b expression by lentiviral-mediated shRNA resulted in increased expression and reduced methylation of Chk2, which clearly showed that Dnmt3b is responsible for transcriptional silencing of Chk2 gene in RA-treated P19 cells. Neuronal differentiation of P19 cells was inhibited upon enforced Chk2 expression in P19 cells, which showed that the decrease in endogenous expression of Chk2 is essential for normal differentiation. Ectopic Chk2 expression also negatively regulated cell cycle arrest and apoptosis following RA treatment, which could also contribute to impaired neuronal differentiation. Together, this study described the regulation of Chk2 expression through promoter methylation and also presented a novel role of Chk2 during neuronal differentiation, which is independent of its previously known function in DNA damage response.


HLA-G1 and HLA-G5 active dimers are present in malignant cells and effusions: the influence of the tumor microenvironment.
Dimers of the nonclassical HLA-G class I molecule have recently been shown to be active structures that mediate inhibition of NK-cell cytotoxic activity through interaction with the immunoglobulin-like transcript (ILT)-2 inhibitory receptor. However, this has only been proven in trophoblasts and HLA-G transfectants. Here, we document for the first time the existence of HLA-G dimers in cancer. Indeed, we identified both surface and soluble HLA-G dimers in tumor cells and malignant ascites respectively. Interestingly, factors from the tumor microenvironment, such as interferons, enhanced the formation of HLA-G dimers and increased the protection of tumors from NK cell-mediated lysis. These data emphasize the impact of HLA-G conformation on its efficiency at inhibiting the antitumor response and thus favoring tumor progression. In view of these results, the effect of the tumor microenvironment on upregulation of HLA-G function deserves particular attention when designing cancer immunotherapy protocols.


Role of ICOS pathway in autoimmune and alloimmune responses in NOD mice.
Islet allografts are subject to alloimmune and autoimmune destruction when transplanted into autoimmune prone animals or humans. The ICOS-B7h pathway plays a role in alloimmune responses, but its function in autoimmunity against islet cells is controversial. We investigated the role of ICOS signaling in autoimmune and alloimmune responses in NOD mice. ICOS blockade prevents development of spontaneous disease in pre-diabetic NOD mice. Furthermore, while ICOS blockade prolongs graft survival in a fully mismatched non-autoimmune islet allograft model in C57BL/6 recipients, it has no beneficial effect in reversing diabetes in models of islet transplantation in NOD mice involving autoimmunity alone or both allo- and autoimmunity. Interestingly, ICOS blockade is effective in prolonging heart allograft (not subject to tissue-specific autoimmunity) survival in NOD mice. We conclude that in islet transplantation and autoimmune diabetes, ICOS blockade can be effective in inhibiting alloimmunity and preventing autoimmunity but is ineffective in inhibiting recurrence of autoimmunity.


Comparison of Natural Language Processing Techniques in Analysis of Sparse Clinical Data: Insulin Decline by Patients.
We present a comparative evaluation of a range of popular Natural Language Processing (NLP) approaches for Information Extraction (IE) in clinical documents to detect cases of patients declining medication that has been recommended by their providers. More specifically, we tackle the task of identifying diabetics who decline insulin, using a training set of 51k randomly selected provider notes. Analysis shows that decline of insulin by patients is a rare phenomenon, with a document-level prevalence of approx. 0.1%. We examine the effectiveness of some of the most popular IE approaches, including sentence-level support vector machines (SVM)-based classification, token- level sequence labelling using conditional random fields (CRFs), and rule-based detection based on encoding human knowledge. Our results on a held-out test set show that the generalization of rule-based approach (F1=0.97) outperforms the SVM (F1=0.61) and CRF models (F1=0.40).


Determination of tramadol by dispersive liquid-liquid microextraction combined with GC-MS.
Dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-mass spectrometry (GC-MS) has been developed for preconcentration and determination of tramadol, ((±)-cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol-HCl), in aqueous and biological samples (urine, blood). DLLME is a simple, rapid and efficient method for determination of drugs in aqueous samples. Efficient factors on the DLLME process has defined and optimized for extraction of tramadol including type of extraction and disperser solvents and their volumes, pH of donor phase, time of extraction and ionic strength of donor phase. Based on the results of this study, under optimal conditions and by using 2-nitro phenol as internal standard, tramadol was determined by GC-MS, and the figures of merit of this work were evaluated. The enrichment factor, relative recovery and limit of detection were obtained 420, 99.2% and 0.08 µg L(-1), respectively. The linear range was between 0.26 and 220.00 µg L(-1) (R(2) = 0.9970). The relative standard deviation for 50.00 µg L(-1) of tramadol in aqueous samples by using 2-nitro phenol as IS was 3.6% (n = 7). Finally, the performance of DLLME was evaluated for analysis of tramadol in urine and blood.


The Primary Photochemistry of Vision Occurs at the Molecular Speed Limit.
Ultrafast photochemical reactions are initiated by vibronic transitions from the reactant ground state to the excited potential energy surface, directly populating excited-state vibrational modes. The primary photochemical reaction of vision, the isomerization of retinal in the protein rhodopsin, is known to be a vibrationally coherent reaction, but the Franck-Condon factors responsible for initiating the process have been difficult to resolve with conventional time-resolved spectroscopies. Here we employ experimental and theoretical 2D photon echo spectroscopy to directly resolve for the first time the Franck-Condon factors that initiate isomerization on the excited potential energy surface and track the reaction dynamics. The spectral dynamics reveal vibrationally coherent isomerization occurring on the fastest possible time scale, that of a single period of the local torsional reaction coordinate. We successfully model this process as coherent wavepacket motion through a conical intersection on a ∼30 fs time scale, confirming the reaction coordinate as a local torsional coordinate with a frequency of ∼570 cm-1. As a result of spectral features being spread out along two frequency coordinates, we unambiguously assign reactant and product states following passage through the conical intersection, which reveal the key vibronic transitions that initiate the vibrationally coherent photochemistry of vision.


Factors Affecting Healthful Eating Among Touring Popular Musicians and Singers.
Maintaining good health is essential for touring musicians and singers. The stressful demands of touring may impact food choices, leading to detrimental effects on health and performance. This exploratory pilot study aimed to assess factors affecting healthful eating of touring musicians and singers. A 46-item survey was used to assess food- and nutrition-related attitudes, knowledge and behaviors, and environmental factors, as well as lifestyle, musical background, and demographic data. Participants (n=35) were recruited from a musicians' assistance foundation as well as touring musical theater productions and a music festival. Results indicate that touring musicians and singers had positive attitudes regarding healthful foods. Of 35 respondents, 80.0% indicated eating healthful food was important to them. Respondents reported feeling confident selecting (76.5%) and preparing (82.4%) healthful foods; however, they showed uncertainty when determining if carbohydrate-containing foods should be consumed or avoided. Respondents indicated environmental factors including availability and cost of healthy food options and tour schedules limited access to healthful foods. Venues (73.5%), fast food restaurants (67.6%), and airports (64.7%) were the most frequently identified locations in need of offering more healthful food choices. Respondents (52.9%) indicated more support from others while touring would help them make healthier food choices. More research is needed to develop mobile wellness programs as well as performance-based nutrition guidelines for musicians and singers that address the unique demands associated with touring.


A new type of thermoelectric material, EuZn2Sb2.
Polycrystalline EuZn(2)Sb(2) is prepared by direct reaction of the elements. Its composition, structure, magnetism, heat capacity, and thermoelectric properties have been investigated. EuZn(2)Sb(2) crystallizes in p3m space group with a=4.4932(7) A and c=7.6170(10) A. Antiferromagnetic ordering is detected at the Neel temperature of 13.06 K, and the saturation magnetization reaches 6.87mu(B)Eu at 2 K and 7 T. Eu ion has +2 valence. Its Hall effects are characterized by a high positive Hall coefficient of +0.226 cm(3)C, proper carrier concentration of 2.77x10(19)cm(3), and high carrier mobility of 257 cm(2)V s at 300 K. This compound shows high p-type Seebeck coefficient (+122 to +181 muVK), low lattice thermal conductivity (1.60-0.40 Wm K), and high electrical conductivity (1137-524 Scm). The obtained figure of merit and powder factor reach 0.92 and 20.72 muWcm K(2), respectively. The thermoelectric properties of EuZn(2)Sb(2) are encouraging.


[Retiform hemangioendothelioma].
Hemangioendotheliomas are vascular tumors of intermediate malignancy considered as low-grade angiosarcomas. The authors report two cases of a distinctive type, named retiform hemangioendothelioma because of its particular morphologic features, and recently delineated by Calonje and al. This tumor of the skin recurs frequently but has a very low metastatic rate.


Choristoma of the intracranial maxillary nerve in a child. Case report.
This report describes what the authors believe to be the first reported case of choristoma of the intracranial maxillary nerve. This 12-year-old girl presented with a 5-year history of severe isolated left-sided trigeminal neuralgia. Computerized tomography and magnetic resonance imaging revealed a mass below the anterior portion of the left cavernous sinus, enlarging the foramen rotundum. Total resection was achieved via a pterional extradural approach. Histological examination revealed a choristoma composed of smooth-muscle fibers. The histogenesis of these tumors when they develop in a nerve remains unclear. They may represent abnormal migration or proliferation of neuroectodermal tissue in or close to a peripheral nerve. Total removal of these tumors should be attempted at initial diagnosis.


The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane Chemokine CXCL16.
Reverse signaling is a signaling mechanism where transmembrane or membrane-bound ligands transduce signals and exert biological effects upon binding of their specific receptors, enabling a bidirectional signaling between ligand and receptor-expressing cells. In this study, we address the question of whether the transmembrane chemokine (C-X-C motif) ligand 16, CXCL16 is able to transduce reverse signaling and investigate the biological consequences. For this, we used human glioblastoma cell lines and a melanoma cell line as in vitro models to show that stimulation with recombinant C-X-C chemokine receptor 6 (CXCR6) or CXCR6-containing membrane preparations induces intracellular (reverse) signaling. Specificity was verified by RNAi experiments and by transfection with expression vectors for the intact CXCL16 and an intracellularly-truncated form of CXCL16. We showed that reverse signaling via CXCL16 promotes migration in CXCL16-expressing melanoma and glioblastoma cells, but does not affect proliferation or protection from chemically-induced apoptosis. Additionally, fast migrating cells isolated from freshly surgically-resected gliomas show a differential expression pattern for CXCL16 in comparison to slowly-migrating cells, enabling a possible functional role of the reverse signaling of the CXCL16/CXCR6 pair in human brain tumor progression in vivo.


Birthplace effects on the development of female athletic talent.
This study examined the extent to which an athlete's place of birth can influence the likelihood of playing professional sport. Information regarding the birthplace of all American female athletes in the Ladies Professional Golf Association and Women's United Soccer Association was gathered from official league websites. Monte Carlo simulations were used to determine if the birthplace of these professional athletes differed in any systematic way from official census population distributions. Odds-ratios were determined for cities within specific population ranges to ascertain if the likelihood of playing professional sport was influenced in any systematic way by city size. The analyses revealed that female professional soccer players born in cities of less than 1,000,000 were over-represented, as were female professional golfers born in cities of less than 250,000. Results are consistent with those of male professional athletes in suggesting that areas of lower population provide conditions more conducive to the development of expertise than do larger city environments.


Electrochemical properties of yolk-shell-structured Zn-Fe-S multicomponent sulfide materials with a 1:2 Zn/Fe molar ratio.
Yolk-shell-structured Zn-Fe-S multicomponent sulfide materials with a 1:2 Zn/Fe molar ratio were prepared applying a sulfidation process to ZnFe2O4 yolk-shell powders. The Zn-Fe-S powders had mixed sphalerite (Zn,Fe)S and hexagonal FeS crystal structures. The discharge capacities of the Zn-Fe-S powders sulfidated at 350 °C at a constant current density of 500 mA g(-1) for the first, second, and fiftieth cycles were 1098, 912, and 913 mA h g(-1), respectively. The powders exhibited a high discharge capacity of 602 mA h g(-1) even at the high current density of 10 A g(-1). The synergistic effect of yolk-shell structure and multicomponent composition improved the electrochemical properties of Zn-Fe-S powders.


Raman spectroscopic analysis of Tet repressor-operator DNA interaction in deuterium oxide.
Tet repressor (TetR) plays a central role in the regulation of its own gene and in that of TetA, a resistance protein against the antibiotic tetracycline (Tc). In the absence of Tc, the TetR dimer binds with two alpha-helix-turn-alpha-helix motifs to two successive major grooves of operator DNA. In order to elucidate structural features of the TetR:operator complex, we measured the Raman spectra of the TetR protein, a 18-mer oligonucleotide with sequence corresponding to TetR operator DNA, and the TetR:operator complex in D2O. The spectra confirm and extend previously obtained results in H2O: i) B-DNA conformation is conserved with only small perturbations of the backbone geometry; ii) TetR and operator DNA interact at major groove sites, as evident from intensity changes of thymine and guanine bands; iii) Minor changes of TetR secondary structure are indicated upon operator binding, and iv) Local environments of aromatic amino acids are altered in the complex. These spectroscopic findings are consistent with a molecular model proposed of the basis of genetic and biochemical studies.


Inhibitory effects of nisin-coated multi-walled carbon nanotube sheet on biofilm formation from Bacillus anthracis spores.
Multi-walled carbon nanotube (MWCNT) sheet was fabricated from a drawable MWCNT forest and then deposited on poly(methyl methacrylate) film. The film was further coated with a natural antimicrobial peptide nisin. We studied the effects of nisin coating on the attachment of Bacillus anthracis spores, the germination of attached spores, and the subsequent biofilm formation from attached spores. It was found that the strong adsorptivity and the super hydrophobicity of MWCNTs provided an ideal platform for nisin coating. Nisin coating on MWCNT sheets decreased surface hydrophobicity, reduced spore attachment, and reduced the germination of attached spores by 3.5 fold, and further inhibited the subsequent biofilm formation by 94.6% compared to that on uncoated MWCNT sheet. Nisin also changed the morphology of vegetative cells in the formed biofilm. The results of this study demonstrated that the anti-adhesion and antimicrobial effect of nisin in combination with the physical properties of carbon nanotubes had the potential in producing effective anti-biofilm formation surfaces.


When bigger is faster: A self-Van Hove analysis of the enhanced self-diffusion of non-commensurate guest particles in smectics.
We investigate the anomalous dynamics in smectic phases of short host rods where, counter-intuitively, long guest rod-shaped particles diffuse faster than the short host ones due to their precise size mismatch. In addition to the previously reported mean-square displacement, we analyze the time evolution of the self-Van Hove functions G(r, t), as this probability density function uncovers intrinsic heterogeneous dynamics. Through this analysis, we show that the dynamics of the host particles parallel to the director becomes non-Gaussian and therefore heterogeneous after the nematic-to-smectic-A phase transition, even though it exhibits a nearly diffusive behavior according to its mean-squared displacement. In contrast, the non-commensurate guest particles display Gaussian dynamics of the parallel motion, up to the transition to the smectic-B phase. Thus, we show that the self-Van Hove function is a very sensitive probe to account for the instantaneous and heterogeneous dynamics of our system and should be more widely considered as a quantitative and complementary approach of the classical mean-squared displacement characterization in diffusion processes.


Oral administration of acidic xylooligosaccharides prevents the development of atopic dermatitis-like skin lesions in NC/Nga mice.
We examined whether two types of xylooligosaccharides (neutral or acidic xylooligosaccharides) derived from hardwood kraft pulp ameliorate the development of atopic dermatitis (AD)-like skin lesions induced by repeated application of picryl chloride (PiCl) in NC/Nga mice. Oral administration of acidic xylooligosaccharides at a daily dose of 100 mg/kg significantly prevented the development of AD-like skin lesions. Serum histamine level was significantly suppressed, but serum total IgE level was not significantly suppressed. Moreover, the secretion of inflammatory cytokine IL-12 from splenic lymphocytes was significantly suppressed. On the other hand, neutral xylooligosaccharides showed no significant preventive effect on the development of AD-like symptoms. These results suggest that oral administration of acidic xylooligosaccharides may be effective in preventing the development of AD-like skin disease and one of the mechanisms is the suppressive effect on IL-12.


Concomitant capecitabine with hepatic delivery of drug eluting beads in metastatic colorectal cancer.
Effectiveness and toxicity of transcatheter arterial injection of irinotecan-eluting beads (DEBIRI) with and without concurrent capecitabine in pre-treated patients with metastatic colorectal cancer (CRC). An Institutional Review Board-approved, multi-institutional registry from 5/2008 to 8/2013 was reviewed. Patients who received DEBIRI with (X-DEBIRI) or without (DEBIRI) capecitabine were compared. Twenty-two X-DEBIRI and 149 DEBIRI patients were compared. There was no difference in the two groups with regards to adverse events (p=0.56). During a 3- and 6-month evaluation, the disease control rate (DCR) was similar in both groups. During the 12-month evaluation, there was better DCR in the X-DEBIRI group (p=0.03). Median survival was 13 months in the DEBIRI group and 22 months in the X-DEBIRI group (log-rank test, p=0.217). There is no additional toxicity when adding capecitabine with DEBIRI. Concurrent capecitabine may offer more durable disease control rate compared to DEBIRI-alone. Survival benefit with concurrent capecitabine was not statistically significant but there may be a trend towards improved survival.


Sensitized luminescence of Sm3+,Eu(3+)-codoped TiO2 nanoparticles.
Sm3+,Eu(3+)-codoped TiO2 nanoparticles were prepared by a facile sol-gel-solvothermal method. Sm3+ and Eu3+ were successfully incorporated into a TiO2 lattice and resulted in intense emission lines with resolved crystal-field splitting, in spite of a large mismatch in ionic radius between trivalent lanthanides (Ln3+) and Ti4+. The intense sensitized emissions of Sm3+ and Eu3+ ions by TiO2 host were obtained at room temperature. In this case, Sm3+ also acts as a bridge to transfer energy from TiO2 host to Eu3+ ions, which was not observed in Eu(3+)-doped TiO2 nanoparticles. In comparison with direct excitation of lanthanide ions, the luminescence lifetimes of 4G5/2 of Sm3+ and 5D0 of Eu3+ were observed to be significantly prolonged upon excitation above TiO2 band-gap. A sensitization mechanism to illustrate the energy transfer from TiO2 to Sm3+ and Eu3+ was proposed based on the optical behaviors of the codoped nanoparticles.


Lisfranc injuries.
Injury to the tarsometatarsal joint is a relatively rare occurrence that is commonly missed, leading to debilitating outcomes. For this reason, it is considered a red flag in general practice. This article reviews the current literature on tarsometatarsal injuries and describes clinical assessment, imaging and management. Lisfranc injuries refer to the displacement of the metatarsals from the tarsus, with special attention placed on the second tarsometa-tarsal joint and Lisfranc ligament. These injuries can occur in numerous circumstances, such as motor vehicle accidents, crush inju-ries and falls. Indirect mechanisms include axial force through the foot or twisting on a plantar flexed foot. Suggestive examination signs include plantar ecchymosis, mid-foot pain and positive findings in the provocative tests described in the article. Weight-bearing radiographs are vital for diagnosis. Correct and prompt management is key to avoiding posttraumatic arthritis, a devastating but common complication of Lisfranc injuries.


Coronary reperfusion for the treatment of acute myocardial infarction: postischemic ventricular dysfunction.
There has been recent interest in treating acute myocardial infarction with coronary reperfusion by fibrinolytic therapy. Experimental studies have shown that myocardial infarct size can be reduced by coronary reperfusion. However, return of cardiac function, high energy phosphate metabolism, and cardiac ultrastructure may be delayed within tissue which is salvaged by coronary reperfusion. This postischemic ventricular dysfunction is transient and has been termed the 'stunned myocardium' phenomenon. Although reperfused infarcts are hemorrhagic, the hemorrhage is confined well within tissue which is already necrotic and does not appear to exacerbate the extent of necrosis. Clinical trials designed to assess the benefits of reperfusion for the therapy of acute myocardial infarction should concentrate on long-term rather than short-term changes in cardiac function.