Vaginal application of testosterone: A study on pharmacokinetics and the sexual response in healthy volunteers.
Androgen substitution is advocated to improve sexual functioning in women with androgen insufficiency. Nevertheless, the role of androgens in female sexual functioning is not yet unraveled. Even less is known about changes in androgens and the female sexual response. The aim of the study is to describe the pharmacokinetics of a single dose of vaginally applied testosterone. In addition, the study aims to gain more insight into the relation between acute changes in testosterone levels and the sexual response in women. A randomized, double-blind, crossover study design was used to compare a single vaginal dose of testosterone propionate (2 mg) with placebo. Ten healthy premenopausal women participated. Serum levels of testosterone, free testosterone, and estradiol were measured. The sexual response was measured before application of medication and 4 and 8 hours after application. Erotic video fragments and erotic fantasies were used as stimuli. The genital sexual response was measured using vaginal plethysmography. The subjective sexual response was measured using a visual analog scale. Vaginal administration of testosterone propionate induced a significant rise in serum testosterone levels and free testosterone levels, but not in serum estradiol levels. Peak levels were reached after 5.5 hours (range 2-12 hours). Mean peak levels of testosterone were 7.71 nmol/L after testosterone propionate and 2.99 nmol/L after placebo (P < 0.005). Mean peak levels of free testosterone were 0.12 nmol/L after testosterone propionate and 0.04 nmol/L after placebo (P < 0.005). Despite marked elevated levels of androgens this study was unable to detect a direct effect on the genital or subjective sexual response. A single dose of vaginally applied testosterone propionate elevates serum levels of testosterone and free testosterone within 6 hours. Nevertheless, this acute rise in androgens has no effects on the female sexual response.


Classification of lower cervical spine injuries.
Blinded assessment by multiple observers of consecutive case series. Measure the reliability of a new system of determining stability in subaxial cervical spine injuries. Classification is fundamental to allow communication, determine prognosis, and direct treatment. Current systems have many limitations, including difficultly of use, lack of proven reliability and validity, and no assessment of stability. A new system to assess instability is proposed. A literature review of the most commonly described classification systems is reported. The Cervical Spine Injury Severity Score was tested for reliability by 10 examiners who graded 35 consecutive cases of cervical trauma. Plain radiographs and CT were saved as read using Efilm Lite in random order. Each was scored and intraobserver and interobserver agreement was measured using intraclass correlation coefficients (ICC). Intraobserver agreement was excellent with ICC ranging from 0.97 to 0.99. Interobserver agreement was also excellent with mean 0.80 ranging from 0.75 to 0.98. A new cervical spine classification system of injury is paramount to treatment and outcomes. A new system may increase reliability and therefore allow more accurate determination of stability and dictate treatment.


Fatigue level in spinal cord injury AIS D community ambulatory subjects.
Cross-sectional study. The objective of our study was to determine the level of fatigue in ASIA impairment scale (AIS) D spinal cord injury (SCI) in community ambulatory subjects and correlate fatigue with other clinical symptoms. Outpatient Rehabilitation Unit, FLENI Institute, Escobar. Buenos Aires, Argentina. We included twenty-six patients with AIS D SCI that attended therapies at FLENI Institute between 2002 and 2009. We measured the demographic and clinical characteristics of the subjects. All patients were administered the fatigue severity scale (FSS). A cut-score for over four was indicative of significant fatigue. We used the Spearman's coefficient correlation to analyze associations among the FSS with pain (Visual analog scale), depression (Beck depression inventory), and physical activity (hours per week). The median score of the FSS scale was 2.82 (1-5). Fatigue was found in 5 individuals (19.2%). There was a significant correlation between FSS scale and the Beck questionnaire. No association was found between FSS and pain or physical activity. The findings of this study suggest that fatigue is a relevant problem for people with SCI AIS D, and is a disabling symptom when present. There is a significant relationship between fatigue and depression. FLENI Rehabilitation Institute.


Photoacoustic tomography of the mouse cerebral cortex with a high-numerical-aperture-based virtual point detector.
The mouse cerebral cortex was imaged in situ by photoacoustic tomography (PAT). Instead of a flat ultrasonic transducer, a virtual point detector based on a high numerical aperture (NA), positively focused transducer was used. This virtual point detector has a wide omnidirectional acceptance angle, a high sensitivity, and a negligible aperture effect. In addition, the virtual point detector can be located much more closely to the object during the detection. Compared with a finite-size flat transducer, images generated by using this virtual point detector have both uniform signal-to-noise ratio (SNR) and resolution.


Refinement of a quantitative trait locus on equine chromosome 5 responsible for fetlock osteochondrosis in Hanoverian warmblood horses.
In this report, we provide 29 new informative microsatellites distributed over a region of 21 Mb on horse chromosome (ECA) 5 and refine a quantitative trait locus (QTL) for fetlock osteochondrosis dissecans (OCD) to a genome-wide significant interval between 78.03 and 90.23 Mb on ECA5. Genotyping was performed in 211 Hanoverian warmblood horses from 14 paternal half-sib groups. Within this OCD-QTL, collagen type XXIV alpha 1 was identified as a potential functional candidate gene for equine osteochondrosis. This report is a further step towards unravelling the genes that cause equine osteochondrosis.


Bizarre pathologic tooth migration.
An extreme example of pathologic tooth migration associated with bruxism and severe periodontitis is presented. The prognosis of the tooth was deemed hopeless; it subsequently was extracted. Various etiological factors of abnormal tooth displacement are discussed.


Risk factors for focal nodular hyperplasia of the liver: an Italian case-control study.
Risk factors for focal nodular hyperplasia (FNH) of the liver are largely unknown, except for a possible role of female hormones. We evaluated the role of tobacco smoking and some lifestyle and dietary factors in its etiology. A hospital-based case-control study was conducted in Italy between January, 1999 and February, 2000 on 28 patients with histologically confirmed FNH of the liver and 115 controls in the hospital for acute, nonneoplastic, non-liver related diseases. Odds ratios (OR) and 95% confidence intervals (CI) were computed using multiple logistic regression equations. Compared to those who never smoked the multivariate ORs were 1.9 (95% CI = 0.6-6.0) in ex-smokers and 3.5 (95% CI = 1.2-9.7) in current smokers, and the risk increased with number of cigarettes smoked to 8.0 (95% CI = 1.7-37.4) for > or = 20 cigarettes/day. Intake of whole-grain foods was inversely related to risk, with an OR of 0.3 (95% CI = 0.1-0.7) in consumers versus nonconsumers. No significant association was observed with education, alcohol drinking, and selected indicator foods. This study indicates that cigarette smoking is an indicator of elevated risk for FNH of the liver, whereas whole grain and, possibly, vegetable intake seems to be a favorable indicator.


The modulation of Amyotrophic Lateral Sclerosis risk by ataxin-2 intermediate polyglutamine expansions is a specific effect.
Full expansions of the polyglutamine domain (polyQ≥34) within the polysome-associated protein ataxin-2 (ATXN2) are the cause of a multi-system neurodegenerative disorder, which usually presents as a Spino-Cerebellar Ataxia and is therefore known as SCA2, but may rarely manifest as Levodopa-responsive Parkinson syndrome or as motor neuron disease. Intermediate expansions (27≤polyQ≤33) were reported to modify the risk of Amyotrophic Lateral Sclerosis (ALS). We have now tested the reproducibility and the specificity of this observation. In 559 independent ALS patients from Central Europe, the association of ATXN2 expansions (30≤polyQ≤35) with ALS was highly significant. The study of 1490 patients with Parkinson's disease (PD) showed an enrichment of ATXN2 alleles 27/28 in a subgroup with familial cases, but the overall risk of sporadic PD was unchanged. No association was found between polyQ expansions in Ataxin-3 (ATXN3) and ALS risk. These data indicate a specific interaction between ATXN2 expansions and the causes of ALS, possibly through altered RNA-processing as a common pathogenic factor.


[Role of lipoic acid in health and disease].
Oxidative stress disturbs organism's homeostasis and leads to excessive reactive oxygen species (ROS) production. Researchers are still focused on antioxidants that help to reduce oxidative stress level and are helpful in treatment of diseases were ROS overproduction is observed. Among those antioxidants is lipoic acid (LA). When applied systemically LA accumulates in tissues and is converted to dihyrolipoic acid (DHLA) by lipoamide dehydrogenase. Both LA and DHLA are biologically active. LA scavenges hydroxyl radical, subchloric acid and singlet oxygen. Moreover, LA is able to chelate transient ions. Therefore, LA is used in diabetic nephropaties, fungi or heavy metal intoxication, liver diseases, neurodegenerative and cardiovascular diseases. This review surveys the antioxidant ability of LA and its role in pathological states where increased concentration of ROS is observed.


Development of a stable isotope dilution assay for an accurate quantification of protein-bound N(epsilon)-(1-deoxy-D-fructos-1-yl)-L-lysine using a (13)C-labeled internal standard.
Syntheses of the labeled Amadori compound [(13)C(6)]-N(epsilon)-(1-deoxy-D-fructos-1-yl)-L-lysine ([(13)C(6)]-DFLys) and the labeled glycated tetrapeptide Ala-[(13)C(6)]-DFLys-Leu-Gly are presented. The compounds were used in the development of stable isotope dilution assays for the quantification of the degree of glycosylation of bovine serum albumin treated for 20 min at 95 degrees C in the presence of glucose. The experiments revealed that the use of the labeled standards in combination with LC/MS allowed the exact quantification of protein-bound DFLys with the high recovery rate of 95% (at a spike level of 150 nmol/mg of protein) and a low detection limit of 5 nmol/mg of protein. The data revealed, however, that DFLys is significantly degraded during the enzymic hydrolysis of the protein backbone generally needed in the quantification procedure and, furthermore, incomplete digestion of the protein was observed. Both sources of errors were clearly overcome by using in particular the labeled peptide as the internal standard.


Design of the pH profile for asymmetric bioreduction of ethyl 4-chloro-3-oxobutyrate on the basis of a data-driven method.
The goal of this paper was to design the optimal time-varying operating pH profile in the asymmetric reduction of ethyl 4-chloro-3-oxobutyrate by baker's yeast. Ethyl (S)-4-chloro-3-hydroxybutyrate was produced to reach two important quality indices: reaction yield and product optical purity. The method integrated an orthogonal function approximation and an orthogonal array. The technique used a set of orthonormal functions as the basis for representing the possible profile. The optimal profile could be obtained if the orthogonal coefficients were properly adjusted. The orthogonal array was used to design and analyze the effect of each orthogonal coefficient in order to reach the optimal objective (quality) function. The performance based on the proposed strategy was significantly improved by over 10% compared with the traditional fixed pH or uncontrolled pH values during the reaction. The proposed method can be applied to the required dynamic profile in the bioreactor process to effectively improve the product quality, given good design directions and the advantage of the traditional statistical approach.


[Embolization of carotid-cavernous fistulas by retrograde catheterization via superior ophthalmic vein].
Six patients with traumatic carotid-cavernous fistula (CCF), which was failed to the standard endoarterial embolization for various reasons, were successfully cured by retrograde catheterization via the superior ophthalmic vein (SOV). The well dilated SOV was easily exposured (4 cases) or punctured (2 cases). Catheterization was performed under X-ray monitoring and reached into the cavernous sinus. Detachable balloon was used in 4 and IBCA glue in 2 cases for embolization. There were no intra or post-operative complication. All the symptoms and signs were disappeared in all the 6 cases after treatment. The authors suggest that in some CCF cases the SOV route is a promising approach.


Baculoviruses hijack the visual perception of their caterpillar hosts to induce climbing behaviour thus promoting virus dispersal.
Baculoviruses can induce climbing behaviour in their caterpillar hosts to ensure they die at elevated positions to enhance virus transmission, providing an excellent model to study parasitic manipulation of host behaviour. Here, we demonstrate that climbing behaviour occurred mostly during daylight hours, and that the height at death of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV)-infected larvae increases with the height of the light source. Phototaxic and electroretinogram (ERG) responses were enhanced after HearNPV-infection in host larvae, and ablation of stemmata in infected larvae prevented both phototaxis and climbing behaviour. Through transcriptome and quantitative PCR, we confirmed that two opsin genes (a blue light-sensitive gene, HaBL; and a long wave-sensitive gene, HaLW) as well as the TRPL (transient receptor potential-like channel protein) gene, all integral to the host's visual perception pathway, were significantly upregulated after HearNPV infection. Knockout of HaBL, HaLW, or TRPL genes using the CRISPR/Cas9 system resulted in significantly reduced ERG responses, phototaxis, and climbing behaviour in HearNPV-infected larvae. These results reveal that HearNPV alters the expression of specific genes to hijack host visual perception at fundamental levels-photoreception and phototransduction-in order to induce climbing behaviour in host larvae.


Myofascial trigger points in subjects presenting with mechanical neck pain: a blinded, controlled study.
The aim of this study was to describe the differences in the presence of myofascial trigger points (TrPs) in the upper trapezius,sternocleidomastoid, levator scapulae and suboccipital muscles between patients presenting with mechanical neck pain and control healthy subjects. Twenty subjects with mechanical neck pain and 20 matched healthy controls participated in this study. TrPs were identified, by an assessor blinded to the subjects' condition, when there was a hypersensible tender spot in a palpable taut band, local twitch response elicited by the snapping palpation of the taut band, and reproduction of the referred pain typical of each TrP. The mean number of TrPs present on each neck pain patient was 4.3 (SD: 0.9), of which 2.5 (SD: 1.3) were latent and 1.8 (SD: 0.8) were active TrPs. Control subjects also exhibited TrPs (mean: 2; SD: 0.8). All were latent TrPs. Differences in the number of TrPs between both study groups were significant for active TrPs (P < 0.001), but not for latent TrPs (P > 0.5). Moreover, differences in the distribution of TrPs within the analysed cervical muscles were also significant (P < 0.01) for all muscles except for both levators capulae. All the examined muscles evoked referred pain patterns contributing to patients' symptoms. Active TrPs were more frequent in patients presenting with mechanical neck pain than in healthy subjects.


Plant antitumor agents. 30. Synthesis and structure activity of novel camptothecin analogs.
A large number of camptothecin (CPT) analogs have been prepared in the 20S, 20RS, and 20R configurations with a number of ring A substituents. Topoisomerase I (T-I) inhibition data (IC50) have been obtained by standard procedures. In general, substitution at the 9 or 10 positions with amino, halogeno, or hydroxyl groups in compounds with 20S configuration results in compounds with enhanced T-I inhibition. Compounds in the 20RS configuration were less active in vitro and in vivo and those in the 20R configuration were inactive. Compounds with 10,11-methylenedioxy substitution on ring A displayed a marked increase in potency in the T-I inhibition assay. The activities of some of the analogs as determined in a variety of in vivo assays including the L-1210 mouse leukemia assay were, in general, in accord with T-I inhibition. A number of water-soluble analogs such as 20-glycinate esters, 9-glycinamides, or hydrolyzed lactone salts were prepared and tested in in vitro and in vivo assays. In general, these compounds were less active than CPT both in terms of T-I inhibition and life prolongation in the L-1210 assay. However, certain 20-glycinate esters showed good in vivo activity after iv administration.


[Toxicogenetics of antiretroviral treatment (II): neurotoxicity, hepatotoxicity, lactic acidosis, kidney damage, and other adverse effects of antiretroviral drugs].
Several pharmacogenetics studies have analyzed the influence of specific genetic polymorphisms on the toxicity of antiretroviral treatment. The present review describes some of the adverse effects of antiretroviral drugs in which a genetic predisposition may be involved: efavirenz-induced neurological toxicity, generally associated with the 516G>T polymorphism of liver enzyme cytochrome P450 2B6 (CYP2B6); hypersensitivity reactions to nevirapine, associated with specific alleles of major histocompatibility complex, mainly the HLA-DRB1*0101 allele, which, in combination with a high CD4 lymphocyte count, has been associated with systemic reactions and hepatitis in Caucasians, and the HLA-Cw8 allele, which is associated with hypersensitivity reactions in persons from the Italian island of Sardinia and from Japan; nevirapine-induced hepatotoxicity associated with the C>T polymorphism in position 3435T of the ABCB1 (MDR-1) gene codifying for glycoprotein P (lower risk); hyperbilirubinemia in patients exposed to atazanavir or indinavir carrying the UGT1A1*28 polymorphism; peripheral neuropathy with nucleoside analogues associated with haplogroup T of the mitochondrial genome (higher risk) and with the HFE C282Y genotype of the hemochromatosis gene (lower risk); the mutation in codon 964 (R964C) of the POLG gene that codifies the mitochondrial polymerase DNA gamma described in a Thai patient with lactic acidosis; the ABCC2 gene haplotypes associated with tenofovir-induced proximal tubulopathy, and the risk of pancreatitis in persons with mutations in the CFTR and SPINK-1 genes.


[The mongoloid nose].
The more precise term "mongoloid" should be used in the place of "oriental" and "asian". The nose of the Han race constitutes the most typical example. The description of "intermediary", usually used to describe this nose is insufficient, as it has a very particular type which contributes to the "Asian triad". A study conducted by Chengdu tries to overcome this deficiency. This information is particularly useful in that aesthetic rhinoplasty, performed increasingly frequently for this type of nose, raises specific problems and requires particular caution to avoid excessive correction which may be disastrous in a small face.


Higher Cardiorespiratory Fitness in Older Trained Women is Due to Preserved Stroke Volume.
Previous literature has shown that sedentary older women rely on peripheral adaptations to improve cardiorespiratory fitness with endurance training i.e. they show minimal increases in central parameters (cardiac output, Q) in response to endurance training. The purpose of this study therefore was to determine whether endurance trained older women were able to preserve maximal exercise Q and were characterized by a high stroke volume (SV) when compared to physically inactive older women. Trained (n = 7) and untrained (n = 1 0) women attended two maximal and one submaximal laboratory session. Breath-by-breath analysis was conducted using mass spectrometry and Q was assessed using acetylene open circuit inert gas wash-in. Multivariate analysis of variance and paired samples t-tests were used to determine between and within group differences. Trained women had a significantly higher VO2max (37.5 vs. 24.1 ml(-1)·kg·min(-1)) compared to untrained women. There were no differences for peripheral oxygen extraction (VO2/Q) at either submaximal or maximal work rates; however trained women had a significantly higher SV at maximal (119.3 vs. 94.6 ml) exercise compared to untrained women. In both trained and untrained women, SV did not rise significantly between submaximal and maximal exercise. Highly fit, endurance trained older women are able to preserve central parameters of VO2max. Peripheral oxygen extraction is similar between older trained and untrained women.


Effect of nitric oxide in the nucleus isthmi on the hypoxic and hypercarbic drive to breathing of toads.
Nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain that has been reported to participate in CO(2) chemoreception and in the ventilatory response to hypoxia. However, no information exists about the modulators and/or mediators involved. In the present study, we assessed the participation of nitric oxide (NO) in the hypoxic and hypercarbic drive to breathing, specifically in the NI. We compared the ventilatory and cardiovascular responses with hypoxia and hypercarbia after microinjecting 100 nmol/0.5 microliter of N(G)-nitro-L-arginine methyl ester (L-NAME; an NO synthase blocker) into the NI of toads (Bufo paracnemis). L-NAME had no effect under resting conditions. Hypoxia elicited an increase in ventilation in control and vehicle toads by elevating tidal volume (V(T)). Hypercarbia caused hyperventilation in all groups due to an increase in both V(T) and frequency. The microinjection of L-NAME into the NI elicited an increase in ventilatory response to hypoxia and hypercarbia due to a higher V(T.) We conclude that NO in the NI has an inhibitory effect when the respiratory drive is high, acting on V(T).


[The inhibitory effects of hepatocyte targeting pH-sensitive liposome mediated phosphorothioate antisense oligonucleotide on gene expression controlled by HCV 5'NCR].
Antisense oligodeoxynucleotide is a negative charged macromolecule and hence is difficult to penetrate cell membrane and liable to degradation. To increase the effective concentration of antisense drugs in the target cells, a hepatocyte-targeting liposome directed to asialoglycoprotein receptors exclusively expressing on the hepatocyte membrane was designed and prepared based on the receptor-mediated gene transfer. In order to accelerate endosomal exit of nucleic acid drugs, the liposomal formulation with pH-sensitive property was adopted. The hepatocyte-targeting and pH-sensitivity of liposome were analyzed by galactose-receptor competitive inhibition and hemolysis of chicken red blood cell. Antisense oligodeoxynucleotide, HCV363 against HCV 5'NCR, was delivered via prepared liposome to transgenic cell HepG2.9706 and evaluated for its inhibitory effect on luciferase expression controlled by HCV 5'NCR in HepG2.9706 using Luciferase Assay System The results showed that different concentrations (10, 20, 30 mmol/L) of galactose solutions reduce the delivery effects of liposome to some extend that were up to saturation when the concentrations of galactose solution exceed 20 mmol/L. Prepared liposomes mixed with chicken RBC are put into PBS buffers with different pH values(4.0-8.0), it was observed that the amount of heme is greatly released in acidic PBS (pH < 6) due to the fusion of liposome and RBC membranes. Liposome-mediated HCV363 has dose-dependent inhibitory activities on luciferase expression controlled by HCV 5'NCR in HepG2.9706 and the inhibitory rate is 86% at a concentration of 1.0 mumol/L. In conclusion, the liposome is proven to be a hepatocyte-targeting pH-sensitive delivery system that can increase the pharmaceutical effects of antisense drugs.


Geographic variation in the advertisement call of Trachycephalus typhonius Anura: Hylidae) based on South American samples.
Previously described calls of Trachycephalus typhonius (Linnaeus, 1758) correspond to several populations from Central and South America, but in general, these descriptions were brief and often based on a single recorded individual. Here, based on an expressive sample, we re-describe the advertisement calls of T. typhonius using recordings from populations in Brazil and Argentina. Additionally, we discuss geographical variation of calls, comment on their frequency band structure and compare calls with those described for other species of Trachycephalus. Calls of 32 males were recorded and temporal and spectral features of 269 calls were measured. To search for discrimination among three populations sampled we used the Random Forest (RF) model, Multidimensional Scaling Analysis (MDS) and Wilcoxon-Mann-Whitney Rank Sum Test. The advertisement calls of T. typhonius consist of a multipulsed note of 343-540 ms of duration, emitted at regular intervals, with up to three emphasized frequency bands. Dominant frequency ranged between 1705-2750 Hz. Calls from Rondônia (Brazil) were significantly different from those recorded in Argentina and Minas Gerais (Brazil) in relation to pulse rate and dominant frequency. Populations from Minas Gerais and Argentina differed in dominant frequency of calls. Such population differences can be partly attributed to differences in prevalence of calling sites (immersed in water vs. perches on vegetation), but can also hint at the existence of cryptic species diversity under this taxon.


Identification and characterization of a novel CXC chemokine in xenograft tumor induced by mas-overexpressing cells.
Overexpressions of G protein-coupled receptor (GPCR) with elevated downstream signaling events have been reported in various tumors. However, the cellular mechanism that GPCR overexpression leads to tumor formation is largely unknown. The orphan GPCR mas was originally isolated from a human epidermoid carcinoma. In vivo studies of mas-overexpressing cells suggested that xenograft tumor formation was positively correlated with the levels of mas expression. Histochemical analysis indicated that xenograft tumor consisted of mas-transfected and stromal cells. Biochemical analyses revealed that cells overexpressing mas exhibited significantly increased anchorage-independent growth, whereas there was no significant difference in cell proliferation in comparison with empty vector-transfected control cells. Expression profiling using mRNA differential display and Northern analysis indicated an elevated expression of GRO and a novel CXC chemokines, tumor-induced factor (TIF), in mas-transfected cells and xenograft tumor. Bacterially expressed recombinant TIF was found to act as a neutrophil chemoattractant in a chemotactic assay. These results suggest that mas overexpression enables anchorage-independent growth of transformed cells, and interplays of secreted chemokines with stromal cells modulate xenograft tumor formation. Importantly, a novel CXC chemokine, TIF, was identified in the xenograft tumor tissues.


FOXO3a and Its Regulators in Prostate Cancer.
Forkhead box O3 (FOXO3a) is a member of a subfamily of forkhead transcription factors involved in the basic processes within a cell, including proliferation, apoptosis, cell cycle regulation, and DNA damage. As a transcription factor, FOXO3a is involved in the response to cellular stress, UV radiation, or oxidative stress. Its regulation is based on the modification of proteins as well as regulation by other proteins, e.g., growth factors. FOXO3a is commonly deregulated in cancer cells, and its inactivation is associated with initiation and progression of tumorigenesis, suggesting its role as a tumor suppressor; however, its role is still disputed and seems to be dependent on upstream signaling. Nevertheless, FOXO3a serves as an interesting potential target in therapies as it is regulated during treatment with very common anti-cancer drugs such as paclitaxel, cisplatin, docetaxel, and doxorubicin. This review aims to update the reported role of FOXO3a in prostate cancer (PCa), with a focus on its regulators that might serve as potential therapeutic agents in PCa therapy.


Personal identifying number as a unique patient identifier in database on clinically treated patients in Belgrade: its use, advantages and drawbacks.
Database on clinically treated patients in Belgrade served as an example for analysis of possibilities for the use of Personal Identifying Number (PIN) as an Unique Patient Identifier. In the first part of the paper we analyzed filling up of the fields which contained data on PIN within complete databases in 1981, 1991 and 1996. Filling up of PIN was significantly changed in the three observed years: it was 18% in 1981; 68% in 1991, and 56% in 1996 respectively. Analysis of interactions among the chosen factors (type of hospital, demographic and social characteristics of patients, length of stay in hospital, manner of treatment, main diagnosis, treatment outcome) and measuring time, showed a different degree of statistical significance. In the second part of our paper we analyzed the unexpected decrease in filling up of PIN in 1996 (as compared to 1991) ussing the method of logistic regression, on 1% samples from the databases for the two respective years. On the basis of obtained models of filling up of UPI data, taken as dependent variable and the above factors (predictors) we analyzed the advantages and drawbacks of UPI application as an unique patient identifier.


EBSD investigation of Al/(Al13 Fe4 +Al2 O3 ) nanocomposites fabricated by mechanical milling and friction stir processing.
The application of ball-milling for reactant powders (Fe2 O3 +Al) to form in situ nanosized reaction products in the stir zone of 1050 aluminium alloy was examined and the evolution of microstructure, grain boundaries and microtexture of the fabricated Al/(Al13 Fe4 +Al2 O3 ) nanocomposite was investigated. The mean matrix grain size of the fabricated nanocomposites by the combination of ball milling and friction stir processing were found to be ∼3.2, 3.1 and 2.1 μm for 1, 2 and 3 h milled powder mixtures, respectively. The fraction of high-angle grain boundaries increased markedly in the stir zone indicating the occurrence of dynamic restoration of the aluminium matrix. This was also associated with increasing of the fraction of low ∑CSL boundaries. In addition, the fraction of high-angle grain boundaries increased as the reaction product increased. The developed textures were compared with the most important deformation and recrystallisation texture components of cubic close packed structure. Some of the main texture components formed due to the restoration of aluminium in the stir zone of the material with no powder addition were CubeND {001}<310>, BR {236}<385> and R (or retained S{123} <634>); these are usually found in the rolled materials. However, the presence of nanosized reaction products in the fabricated nanocomposite changed the texture components to the dominant Goss {011}<100>, P {011}<122> and R{124}<211> textures.


[Seminona of stage I: strategies compared].
Testicular cancer is an infrequent disease, accounting for 1% to 2% of all malignant neoplasms in men. However, it represents the most common solid malignancy among men between 15 and 35 years old. The standard initial treatment for stage I seminoma is radical inguinal orchiectomy. Since the mid-20th century, the traditional treatment after surgery had consisted in external photon beam radiotherapy directed to the para-aortic and pelvic lymph nodes. Patients receiving radiotherapy achieve cause-specific survival rates approaching 100%, with virtually no relapses within the radiation portal. At the moment, the options for the management of stage I seminoma consist of surveillance, adjuvant radiation therapy and adjuvant chemotherapy usually done with carboplatin. Patients should be informed of all treatment options and of potential benefits and side effects of each choice. Significant treatment-related morbidities following radiotherapy have been reported. Acute toxicities are generally mild and self-timing, but patients treated with adjuvant radiotherapy alone had a significantly increased risk of second primary malignances (SPMs) and gonadal toxicity. The Medical Research Council (MRC) TE10 and TE18 randomized trials have investigated the reduction of the treatment volume and total dose to decrease the risk of radiation-related side effects. The MRC TE19 randomized trial compared radiotherapy and a single course of carboplatin AUC7. The preliminary results, reported in 2005, and also the updated results, reported in 2008 and 2011, confirm the non inferiority of single-dose carboplatin.


Evaluating and comparing imaging techniques: a review and classification of study designs.
The designs of studies to evaluate and compare imaging techniques are reviewed. Thirteen principles for the design of studies of diagnostic accuracy are given. Because of the "independence principle" these studies are not able directly to evaluate the contribution of a technique to clinical management. For the latter, the "clinical value" study design is recommended. A classification of study designs is proposed in parallel with the standard classification of clinical trials. Studies of diagnostic accuracy are analogous to Phase II, whereas studies evaluating the contribution to clinical management correspond to the Phase III category. Currently the majority of published studies employ the Phase II design. More emphasis on Phase III studies is required.


Comparison of exhaled nitric oxide measurement with conventional tests in steroid-naive asthma patients.
Nitric oxide (NO) is a molecule with potent biological activity that plays an important role in the physiology of the respiratory system. Increased expression of inducible nitric oxide synthase (iNOS) and elevated fractional concentration of exhaled nitric oxide (F(ENO)) are seen in asthmatic patients. Measurement of F(ENO) has become increasingly recognized for use in the evaluation of bronchial inflammation during monitoring of antiinflammatory treatment. The aim of this study was to evaluate F(ENO) in a group of steroid-naive asthmatics and assess the relationship of this parameter with the results of other tests used in the diagnosis of asthma and monitoring of antiinflammatory treatment in asthmatic patients. The study was conducted in a group of 101 steroid-naive asthmatics (56 allergic and 45 nonallergic) and 39 healthy volunteers. All patients underwent measurement of F(ENO), skin prick tests with common inhaled allergens, analysis of serum eosinophil cationic protein (ECP) and blood eosinophilia, and flow-volume spirometry. When the forced expiratory volume in the first second (FEV1) was less than 80% of predicted, reversibility of airway obstruction with a beta2-agonist was assessed. A nonspecific bronchial provocation test with histamine was carried out in asthmatic patients with a baseline FEV1 of more than 70% of predicted. Compared to the healthy volunteers, F(ENO) was elevated in both groups of asthmatics. F(ENO) in the allergic asthma group was higher than in the group of nonallergic asthmatics. In allergic and nonallergic asthmatics, F(ENO) was significantly correlated with bronchial hyperresponsiveness to histamine, reversibility of airway obstruction, serum ECP levels, and blood eosinophilia. F(ENO) did not correlate with baseline FEV, in either group of asthmatics. In 31% of nonallergic and 9% of allergic patients, F(ENO) was less than 20 parts per billion. We suggest that measurement of F(ENO) could be clinically useful in steroid-naive asthmatics and should be more widely used in clinical practice. Measurement of F(ENO) is a noninvasive, simple, and reproducible procedure, the results of which correlate with other routinely used methods in the diagnosis of asthma. However, it is worth noting that some patients, especially those with nonallergic asthma, do not display elevated F(ENO).


Cerebrovascular brainstem diseases with isolated cranial nerve palsies.
There is a significant number of individual patients with cranial nerve palsies as the sole manifestation of MRI- and, less frequently, CT-documented small brainstem infarctions or hemorrhages. The 3rd and 6th nerves are most commonly involved and, less frequently, the 4th, 5th, 7th, and 8th nerves. An intra-axial basis for such lesions may be underestimated if the diagnosis is based solely on MRI. The electrophysiologic abnormalities indicating brainstem lesions may be independent of MRI-documented morphological lesions. This paper reviews the literature on cerebrovascular brainstem diseases manifesting as isolated cranial nerve palsies. It supports the concept that small pontine and mesencephalic infarctions are the main cause of non-traumatic cranial nerve palsies in the middle-aged and elderly population. Microvascular infarction of the respective extra-axial cranial nerve segments seem to be less important.


Association between acute respiratory failure requiring mechanical ventilation and the production of advanced glycation end products.
Patients with acute respiratory failure often have hyperglycemia. Elevated glucose levels could cause acute lung injury through the production of advanced glycation end products. We measured glucose, advanced glycation end products, glycated albumin, circulating glycated hemoglobin, and soluble receptor for advanced glycation end product (sRAGE) levels on admission, at 24 hours, and at 72 hours in 40 patients with acute respiratory failure requiring mechanical ventilation. We compared these values with healthy control subjects. The mean age was 63.3±11.2 years. Fifty percent of the patients were women. Thirteen patients (32.5%) died during this hospitalization. The mean maximum glucose level on the day of admission was 215.7±171.1 mg/dL. Compared with control subjects, there was a significant reduction in advanced glycation end product levels (p=0.0001) in the patients at all 3 time points. Circulating glycated hemoglobin levels were significantly higher in patients compared with control subjects. We also observed a moderate increase in glycated albumin levels on admission and at 24 hours when compared with the control samples. Overall sRAGE levels were similar to controls, but patients with dense infiltrates on chest X-ray had increased levels compared with patients who did not have these dense infiltrates on the day of admission. Patients with acute respiratory failure requiring mechanical ventilation have decreased levels of advanced glycation end products and increased levels of circulating glycated hemoglobin. The results from this pilot study suggest that the acute stress associated with respiratory failure might create glycated proteins which could contribute to disease pathogenesis.


First charge breeding of a rare-isotope beam with the electron-beam ion trap of the ReA post-accelerator at the National Superconducting Cyclotron Laboratory.
An electron-beam ion trap (EBIT) charge breeder is being brought into operation at the National Superconducting Cyclotron Laboratory at Michigan State University. The EBIT is part of the ReA post-accelerator for reacceleration of rare isotopes, which are thermalized in a gas "stopping" cell after being produced at high energy by projectile fragmentation. The ReA EBIT has a distinctive design; it is characterized by a high-current electron gun and a two-field superconducting magnet to optimize the capture and charge-breeding efficiency of continuously injected singly charged ion beams. Following a brief overview of the reaccelerator system and the ReA EBIT, this paper presents the latest commissioning results, particularly, charge breeding and reacceleration of the highly charged rare isotopes, (76)Ga(24 +, 25 +).


Nanostructured Inorganic Chalcogenide-Carbon Nanotube Yarn having a High Thermoelectric Power Factor at Low Temperature.
As power-conversion devices, flexible thermoelectrics that enable conformal contact with heat sources of arbitrary shape are attractive. However, the low performance of flexible thermoelectric materials, which does not exceed those of brittle inorganic counterparts, hampers their practical applications. Herein, we propose inorganic chalcogenide-nanostructured carbon nanotube (CNT) yarns with outstanding power factor at a low temperature using electrochemical deposition. The inorganic chalcogenide-nanostructured CNT yarns exhibit the power factors of 3425 and 2730 μW/(m·K2) at 298 K for the p- and n-type, respectively, which is higher than those of previously reported flexible TE materials. On the basis of excellent performance and geometry advantage of the nanostructured CNT yarn for modular design, all-CNT based thermoelectric generators have been easily fabricated, showing the maximum power densities of 24 and 380 mW/m2 at ΔT = 5 and 20 K, respectively. These results provide a promising strategy for the realization of high-performance flexible thermoelectric materials and devices for flexible/or wearable self-powering systems.


An overview of the multimodal approach to TMJ disorders.
This article presents the reader with an overview of the current therapeutic approaches employed in the treatment of TMJ disorders. Included are synopses of the various medications, appliances, and adjunct therapies utilized, as well as brief descriptions of their effects.


A note about insensitivity to pitch-change direction.
Some listeners are insensitive to the direction of pure-tone frequency changes when the standard frequency is roved widely over trials, but less so when the standard frequency is fixed and trial-by-trial feedback is provided. The present experiment tested the hypothesis that fixing the standard frequency and providing feedback is advantageous for direction-impaired listeners because under these conditions the listeners can learn to respond correctly without genuinely perceiving frequency-change direction. This hypothesis was ruled out by the experiment. It appears instead that direction-impaired listeners find it difficult to ignore the irrelevant frequency changes introduced by roving.


New members of the ctrA regulon: the major chemotaxis operon in Caulobacter is CtrA dependent.
The Caulobacter crescentus che promoter region consists of two divergent promoters, directing expression of the major chemotaxis operon and a novel gene cagA (chemotaxis associated gene A). Analyses of start sites by primer extension and alignment of the divergent promoters revealed significant similarities between them at the -35 promoter region. Both mcpA and cagA are differentially expressed in the cell cycle, with maximal activation of transcription in predivisional cells. The main difference between the mcpA and cagA promoters is that, in common with the fljK flagellin, cagA is expressed in swarmer cells. A cagA--lacZ promoter fusion that contains 36 bases of untranslated mRNA has sufficient information to segregate the lacZ transcript to swarmer cells. Expression of mcpA and cagA was dependent on DNA replication. Transcriptional epistasis experiments were performed to identify potential regulators in the flagellar hierarchy. The sigma factor RpoN, which is required for flagellar biogenesis, is not required for mcpA and cagA expression. Mutations in the genes for the MS-ring and the switch complex (flagellar class II mutants) do not affect expression of mcpA and cagA. However, CtrA, an essential response regulator of flagellar gene transcription, is required.


Proposed initiatives for healthy children orphaned by AIDS.
The epidemiology of AIDS has changed greatly in recent years and increasing numbers of poor, minority women with children now contract HIV/AIDS. As infected women succumb to AIDS, many of their children become orphans. The paper explores the ability and appropriateness of the current child welfare system to care for healthy children orphaned by AIDS, and the likelihood of adoption for this population. The study includes a wide-ranging literature review of information about children orphaned by AIDS, and relevant information about the child welfare system, including racial bias. To determine current support for children orphaned by AIDS, the author surveyed social service departments and private agencies in eight major cities about programs available. Based on this information, the author proposes a series of policy initiatives aimed at alleviating the flight of children orphaned because of AIDS.


Human FEZ1 protein forms a disulfide bond mediated dimer: implications for cargo transport.
The human proteins FEZ1 (fasciculation and elongation protein zeta 1) and FEZ2 are orthologs of the protein UNC-76 from C. elegans, involved in the growth and fasciculation of the worms axon. Pull down assays showed that the protein FEZ1 interacts with other proteins (e.g., the protein SCOCO, short coiled-coil protein), mitochondria, and vesicles. These components may therefore represent cargoes to be transported along the microtubule, and the transport may be mediated through FEZ1 reported binding to kinesins (KIF3A). We previously showed that FEZ1 dimerizes in its N-terminal region and interacts with other proteins, including the candidate cargoe proteins, through its C-terminus. Here, we studied the fragment FEZ1(92-194) as well as full-length 6xHis-FEZ1 (1-392) in vitro and endogenous FEZ1 isolated from HEK 293 cells and were able to demonstrate the formation of an intermolecular disulfide bond through FEZ1 Cys-133, which appears to be essential for dimerization. This disulfide bond may be important for the FEZ1 role as a dimeric and bivalent transport adaptor molecule, since it establishes a strong link between the monomers, which could be a prerequisite for the simultaneous binding of two cargoes.


Interaction between human polymorphonuclear leucocytes and Staphylococcus aureus in the presence and absence of opsonins.
Phagocytosis of Staphylococcus aureus by human polymorphonuclear leucocytes (PMN) in the presence and absence of opsonins was studied with an assay which allows interaction between PMN and bacteria on a surface. The kinetics of uptake, the activity of the metabolic burst, and the degranulation during phagocytosis of opsonized and unopsonized bacteria were compared. Uptake of unopsonized S. aureus proceeded at a slower rate, but unopsonized staphylococci induced metabolic activity and degranulation in the PMN to the same extent as opsonized bacteria. Treatment of PMN with a metabolic inhibitor (2-deoxy-D-glucose) or with an inhibitor of microfilament function (cytochalasin B) totally inhibited the capacity of PMN to ingest unopsonized S. aureus, whereas uptake of opsonized bacteria was much less affected. Treatment of the PMN with pronase prevented uptake of unopsonized bacteria, but had no effect on the uptake of opsonized bacteria. Uptake was not inhibited by mannose. Recognition of S. aureus by the PMN was not dependent on the presence of the cell wall components protein A or teichoic acid. The presence of a capsule inhibited uptake.


Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines.
Amblyomma sculptum is the main tick associated with human bites in Brazil and the main vector of Rickettsia rickettsii, the causative agent of the most severe form of Brazilian spotted fever. Molecules produced in the salivary glands are directly related to feeding success and vector competence. In the present study, we identified sequences of A. sculptum salivary proteins that may be involved in hematophagy and selected three proteins that underwent functional characterization and evaluation as vaccine antigens. Among the three proteins selected, one contained a Kunitz_bovine pancreatic trypsin inhibitor domain (named AsKunitz) and the other two belonged to the 8.9 kDa and basic tail families of tick salivary proteins (named As8.9kDa and AsBasicTail). Expression of the messenger RNA (mRNA) encoding all three proteins was detected in the larvae, nymphs, and females at basal levels in unfed ticks and the expression levels increased after the start of feeding. Recombinant proteins rAs8.9kDa and rAsBasicTail inhibited the enzymatic activity of factor Xa, thrombin, and trypsin, whereas rAsKunitz inhibited only thrombin activity. All three recombinant proteins inhibited the hemolysis of both the classical and alternative pathways; this is the first description of tick members of the Kunitz and 8.9kDa families being inhibitors of the classical complement pathway. Mice immunization with recombinant proteins caused efficacies against A. sculptum females from 59.4% with rAsBasicTail immunization to more than 85% by immunization with rAsKunitz and rAs8.9kDa. The mortality of nymphs fed on immunized mice reached 70-100%. Therefore, all three proteins are potential antigens with the possibility of becoming a new tool in the control of A. sculptum.


A possible cause and remedy for the clinical failure of 5-fluorouracil plus eniluracil.
Eniluracil is a potent inactivator of dihydropyrimidine dehydrogenase (uracil reductase), the enzyme that rapidly catabolizes 5-fluorouracil (5-FU). Although eniluracil in combination with 5-FU was promising in phase I and II studies, in 2 multicenter phase III colorectal cancer studies, eniluracil dosed in a 10-to-1 ratio to 5-FU produced less antitumor benefit than the standard regimen of 5-FU/leucovorin without eniluracil. The current study tested whether the high eniluracil doses caused the clinical failure. The effect of excess eniluracil versus adequate eniluracil on 5-FU antitumor activity was studied in rats bearing large transplanted colon tumors. The rats were divided into 3 groups: group A received no treatment, group B was treated with eniluracil 1 mg/kg (adequate) 1 hour before 5 mg/kg 5-FU, and group C was treated identically to group B but also received eniluracil 25 mg/kg (excess) 5 minutes before 5-FU administration. The rate of complete tumor regression (cure) was 0% in group A (no treatment), 88% in group B (adequate eniluracil), and 25% in group C (excess eniluracil). Toxicity was minimal. Only slight weight loss occurred in all groups. When the eniluracil dose is in 5-fold excess to 5-FU (as in the phase III clinical trials), the antitumor activity of 5-FU was significantly diminished. Moreover, to maximize the antitumor activity of 5-FU, eniluracil must not be present in excess over 5-FU in rats bearing tumors. Simple strategies to achieve optimal antitumor efficacy are presented.


Determinants of amino acid bioavailability from ingested protein in relation to gut health.
The current review provides an update on the recent research developments regarding amino acid bioavailability in conditions of both good health and gut disorders. Determination of amino acid bioavailability is complex and invasive. Minimally invasive methods using stable isotopes have been developed for humans. Data were collected in different models - humans, pigs and rats with various procedures - leading to interstudy variability. They mainly focused on either plant protein or the effect of food processing on animal protein. Plant protein in their original food matrix (legumes, grains, nuts) are generally less digestible (about 80%) than animal protein (meat, egg, milk; about 93%). Food processing has a limited impact on animal protein but its effect might be higher on plant protein. Few studies have documented the effect of gut disorders on protein digestibility, except in gastric bypass where paradoxical effects were reported. Data are needed to identify the amplitude of protein malabsorption in diseases such as inflammatory bowel disease or environmental enteric dysfunction. The past 5 years have seen a renewed interest in amino acid bioavailability in view of assessing protein quality to support current shifts in protein sourcing. Methodological developments have been performed and several studies have reported values in various models. The question of protein digestibility in gut disorders remains poorly addressed.


Pharmacological preconditioning with gemfibrozil preserves cardiac function after heart transplantation.
While heart transplantation (HTX) is the definitive therapy of heart failure, donor shortage is emerging. Pharmacological activation of soluble guanylate cyclase (sGC) and increased cGMP-signalling have been reported to have cardioprotective properties. Gemfibrozil has recently been shown to exert sGC activating effects in vitro. We aimed to investigate whether pharmacological preconditioning of donor hearts with gemfibrozil could protect against ischemia/reperfusion injury and preserve myocardial function in a heterotopic rat HTX model. Donor Lewis rats received p.o. gemfibrozil (150 mg/kg body weight) or vehicle for 2 days. The hearts were explanted, stored for 1 h in cold preservation solution, and heterotopically transplanted. 1 h after starting reperfusion, left ventricular (LV) pressure-volume relations and coronary blood flow (CBF) were assessed to evaluate early post-transplant graft function. After 1 h reperfusion, LV contractility, active relaxation and CBF were significantly (p < 0.05) improved in the gemfibrozil pretreated hearts compared to that of controls. Additionally, gemfibrozil treatment reduced nitro-oxidative stress and apoptosis, and improved cGMP-signalling in HTX. Pharmacological preconditioning with gemfibrozil reduces ischemia/reperfusion injury and preserves graft function in a rat HTX model, which could be the consequence of enhanced myocardial cGMP-signalling. Gemfibrozil might represent a useful tool for cardioprotection in the clinical setting of HTX surgery soon.


Moderating effects of brooding on the link between functional impairment and interpersonal needs in survivors of serious trauma.
Trauma and resulting functional limitations demonstrate associations with perceived burdensomeness and thwarted belongingness, factors contributing to elevated risk for suicidal ideation. However, survivors display differential risk in response to impairment, highlighting the need for research on exacerbating factors. The current study examined the impact of brooding on the association of functional impairment with burdensomeness and belongingness among trauma-exposed undergraduates (N = 262). Trauma was assessed via clinical interview with questionnaires for study variables. Regression models examined the unique and interactive effects of physical impairment, emotional impairment, and brooding on burdensomeness and thwarted belongingness. An interaction of brooding and impairment due to emotional difficulties was observed for burdensomeness with impairment linked to elevated burdensomeness at high (β = -0.46; p < 0.001), but not low (β = -0.07; p = 0.476) brooding. Impairment due to emotional difficulties (β = -0.38; p < 0.001) and brooding (β = 0.25; p < 0.001) were associated with belongingness. Findings identify brooding as a potential target for assessment and intervention in trauma-exposed individuals.


High prevalence of abnormal glucose metabolism and poor sensitivity of fasting plasma glucose in the chronic phase of stroke.
Cardiovascular disease is the leading cause of death in long-term stroke survivors, and whole-body glucose metabolism is strongly linked to cardiovascular disease risk. This study provides important preliminary information on the prevalence of abnormal glucose metabolism in chronic stroke patients (mean 3 years after stroke) and reports on the utility of screening for abnormalities using fasting plasma glucose (FPG) in this population. Two hundred and sixteen chronic hemiparetic stroke patients were screened for diabetes status by medical history and FPG. A subset (n = 80) was evaluated by oral glucose tolerance test to assess the utility of screening for abnormalities using FPG alone. Seventy-five of the 216 (35%) had type 2 diabetes by medical history. Another 70 were either diabetic (n = 11) or had impaired fasting glucose (n = 59) based on a single blood draw at the time of screening. FPG among non-diabetic stroke patients had a sensitivity of 49% for predicting abnormalities in the 2-hour glucose level during oral glucose tolerance test. Cumulative results identify 77% as abnormal (impaired or diabetic) on the basis of medical history, fasting plasma glucose, and/or 2-hour glucose level. The prevalence of abnormal glucose metabolism is extremely high in chronic stroke and is underestimated on the basis of FPG.


Efficacy of Omega-3 in Treatment of Recurrent Aphthous Stomatitis: A Randomised, Double-blind, Placebo-controlled Study.
To evaluate the potential of omega-3 polyunsaturated fatty acid supplement as an effective, safe and inexpensive medicine for the treatment of recurrent aphthous stomatitis. In this double-blind clinical trial, 50 patients with recurrent aphthous stomatitis were randomly divided into the omega-3 group and placebo group. Patients in the omega-3 group received 1000 mg omega-3 group capsules (Daroupakhsh Company, Tehran, Iran) for 6 months; while those in the placebo group received placebo capsules with the same instructions. The pain, size, duration and recurrence rate of ulcers were recorded in each follow-up phase. Follow-up was done weekly in the first month of drug prescriptions and then monthly in the next 5 months. The data were analysed with SPSS-20 through the Mann-Whitney test to compare the groups with respect to each variable and the Wilcoxon and Friedman tests to compare the groups over time. Values were significant at P < 0.05. In the omega-3 group, pain was lessened from 4.96 to 3.04, irritation was reduced from 5.88 to 4.00 (P = 0.0627) and the size of ulcers was decreased from 2.30 to 1.48 mm (P = 0.062). No significant change was observed in the aforementioned variables in the placebo group. Moreover, the number of ulcers indicated a significant reduction in the fourth, fifth and sixth months in comparison with the placebo group (P = 0.00). The recurrence of ulcers in the omega-3 group showed a significant decrease in the fifth and sixth months compared with the placebo group (P < 0.05). The current study indicated that omega-3 consumption decreased the symptoms of recurrent aphthous stomatitis.


Sources of Free IAA in the Mesocotyl of Etiolated Maize Seedlings.
Sources of free indole-3-acetic acid (IAA) for the mesocotyl of intact etiolized maize ((Zea mays L.) seedlings are evaluated. The coleoptile unit, which includes the primary leaves and the coleoptilar node, is the main source of free IAA for the mesocotyl. The seed and the roots are not immediate sources of IAA supply. Dependence of the apical growing region of the mesocotyl on the coleoptile unit as a source of free IAA is almost total. One-half or more of the supply of IAA comes from the coleoptile tip, the rest mainly from the primary leaves. Removal of the coleoptile tip results in inhibition of mesocotyl elongation. The hypothesis that growth of the mesocotyl is regulated by auxin supplied by the coleoptile is supported. Conjugated forms of IAA appear to play little part in regulating the levels of free IAA in the shoot.


Delayed traumatic superior mesenteric arteriovenous fistula after a stab wound: case report.
Eight cases of superior mesenteric arteriovenous fistula (SMAVF) occurring after an abdominal stab wound have been reported. Seven of these patients manifested symptoms within 1 month after the stab wound. We report the case of a 28-year-old man whose SMAVF occurred 31 months after an abdominal stab wound. A SMAVF must be considered even when considerable time has elapsed between penetrating abdominal trauma and symptoms of abdominal pain, unexplained diarrhea, or an abdominal bruit or thrill.


Nested PCR for the Diagnosis of Feline Sporotrichosis From Formalin-Fixed and Paraffin-Embedded Samples Using Different DNA Extraction Protocols.
Sporotrichosis is a chronic, cosmopolitan granulomatous mycosis that affects humans and animals. The infection is caused by the dimorphic fungi Sporothrix sp. The aims of the present study were to evaluate, standardize and validate a nested PCR technique using two DNA purification kits for the extraction of DNA from formalin fixed and paraffin-embedded tissues (FFPE) for Sporothrix sp. detection. FFPE mycological culture pellet samples of different Sporothrix species (S. chilensis, S. mexicana, S. pallida, S. globosa, S. brasiliensis and S. schenckii) were used as positive controls and clinical FFPE tissue samples of animals positive for Cryptococcus sp., Leishmania infantum and Histoplasma sp. were used as negative controls. Ten clinical FFPE skin samples from cats with sporotrichosis were used to validate the nested PCR. These samples were cut into two distinct paraffin sectioning protocols (5 and 16 μm thick). The paraffin sections were subjected to two different DNA extraction kits (chemical and thermal extractions). A nested PCR was performed on the extracted DNA to identify the genus Sporothrix. The chemical extraction protocol with the 5 μm thick paraffin section was more effective in extracting DNA from Sporothrix sp. from FFPE samples and the nested PCR technique showed the highest sensitivities (100% in the positive controls and of 50% in the skin samples of cats) and specificity (100%). Therefore, the nested PCR using this protocol has great potential to be applied in Sporothrix sp. diagnosis in FFPE samples of cats.


Integrating Cultural Humility Into Infant Safe Sleep Counseling: A Pediatric Resident Simulation.
Co-sleeping with infants is a common practice across cultures, but pediatricians may struggle to engage in patient-centered conversations about infant sleep practices with non-native English- speaking families. Cultural humility is a critical skill to utilize when engaging in cross-cultural conversations. We designed a simulation for pediatric residents to counsel on safe sleep and enhance skills in self-perceived cultural humility and preparedness when caring for diverse patient populations. We created a simulation for the second year and senior pediatric residents at a large academic institution focused on a co-sleeping parent and infant from the Burmese community. The Multidimensional Cultural Humility Scale (MCHS) was administered prior to and after the simulation. We also included additional questions regarding changes in knowledge and preparation in engaging in co-sleeping conversations across cultures. Fifty-seven residents participated. Overall, the mean score of the MCHS significantly increased after the simulation, indicating an increase in self-perceived cultural humility. All participants felt more prepared to have conversations about co-sleeping and to engage in difficult conversations with diverse patient populations, and all learned valuable skills to improve care for future patients. Comments regarding the scenario noted an appreciation for learning more about the Burmese population and understanding new approaches to safe sleep counseling. After this simulated scenario, residents reported increased self-perceived cultural humility, preparedness in counseling on co-sleeping, and skills to engage in difficult conversations with diverse patient populations. Topics such as cultural humility can be incorporated into simulation-based medical education to help improve the care of diverse patient populations.


Neonatal Rhizomelic Chondrodysplasia Punctata Type 1: Weaving Evidence Into Clinical Practice.
Rhizomelic chondrodysplasia punctata (RCDP) is a rare genetic peroxisome biogenesis disorder with a reported incidence of 1 in 100 000 live births. The 3 genetic subtypes of RCDP are acquired by an autosomal recessive inheritance pattern. RCDP type 1 accounts for greater than 90% of all aggregate cases. Differentiating between the 3 subtypes of RCDP, as well as disorders characterized by similar punctate cartilaginous changes, is essential to guide an appropriate postnatal plan of care. Management strategies are focused toward associated clinical manifestations and require an interdisciplinary approach including ophthalmology, cardiovascular, endocrine, physical and occupational therapy, and neurology. Purposeful and frequent collaboration among all members of the neonatal/pediatric interdisciplinary team is necessary to optimize outcomes for the neonate and the family unit. The purpose of this article is to anticipate the needs of both patients with known and prenatal diagnosis of RCDP type 1 and patients with suspected clinical diagnosis of RCDP type 1 in the immediate neonatal period and to guide the appropriate plan of care. This article presents a case report of type I RCDP, as well as describes genetic influences, symptoms, diagnosis, management, and prognosis.


[Calcium 2+ Response of Lymphocytes to Standard Test-Substances in Patients With Ischemic Heart Disease and Heart Failure]
Changes of [Ca 2+]i were studied in peripheral blood lymphocytes of patients with ischemic heart disease and heart failure. Basal [Ca 2+]i and its changes under action of mitogenes (PHA, Con A; 10 mcg/ml), butylhydroxyquinone (BHQ; 9-14 mcM) and arachidonic acid (3-10 mc/M) were measured. Patients with heart failure had pronounced changes of kinetics and amplitude of Ca 2+ response of lymphocytes to mitogenes, significantly higher amplitudes of responses to BHQ (in patients with stage IIB and III heart failure), as well as additional increment of [Ca 2+]i in response to rachidonic acid during action of optimal concentrations of BHQ. This data allowed to propose presence of supplementary inositol triphosphate insensitive calcium depots in cells of patients with heart failure. Furthermore it was possible to assume lowering of sensitivity of Ca 2+ ATP-ase of plasmatic membranes to its natural regulators.


Surgery of acute peptic ulcer haemorrhage.
During the years 1973-1985, 145 patients with acute peptic ulcer haemorrhage were treated surgically at the Department of Surgery, Turku University Central Hospital. The bleeding site was gastric ulcer in 76 patients; 58 of these were treated by gastric resection and 17 by ulcer excision combined with vagotomy and pyloroplasty. Forty-two out of 69 patients with bleeding duodenal ulcer were treated with partial gastrectomy, the remaining with transfixion and vagotomy and pyloroplasty. The rebleeding rate was 2% and reoperation rate 9% among the patients who had a resection. In contrast 19% of the transfixed and 12% of ulcer excision cases rebled. The primary overall mortality was 12%; 44% of the patients with recurrent bleeding died. Because rebleeding was the most important cause of mortality, partial gastrectomy in bleeding gastric as well as duodenal ulcer may be preferable.


Dosage of chloramphenicol in typhoid and paratyphoid in children.
Over a period of 12 years, 109 children with salmonella enteric fever were treated with chloramphenicol: 65 children were given the drug at 50 mg/kg/24 h (Group A) and 44 received 100 mg/kg/24 h (Group B). Treatment failed in 63% with the lower dose and in 24% of children treated with the higher dose (P less than 0.001). In the children who received only chloramphenicol, the higher dose produced a clinical response in 5.4 (1.8) (mean (S.D.] days compared with 7 (2.6) days with the lower dose (P less than 0.01). Chloramphenicol in an initial dose of 100 mg/kg/24 h is recommended in the treatment of typhoid and paratyphoid in children.


Participation of endogenous opioids in the antinociception induced by resistance exercise in rats.
Exercise is a low-cost intervention that promotes health and contributes to the maintenance of the quality of life. The present study was designed to investigate the influence of different resistance exercise protocols on the nociceptive threshold of rats. Female Wistar rats were used to perform exercises in a weight-lifting exercise model. The following groups were examined (N = 6 per group): untrained rats (control group); an acute protocol group consisting of rats submitted to 15 sets of 15 repetitions of resistance exercise (acute group); rats exercised with 3 sets of 10 repetitions, three times per week for 12 weeks (trained group), and a group consisting of trained rats that were further submitted to the acute protocol (trained-acute group). The nociceptive threshold was measured by the paw-withdrawal test, in which the withdrawal threshold (escape reaction) was measured by an apparatus applying force to the plantar surface of the animal paw. The opioid antagonist naloxone (2 mg/kg) was administered subcutaneously 10 min before the exercise protocols. The trained group demonstrated antinociception only up to day 45 of the 12-week training period. A significant increase (37%, P < 0.05) in the nociceptive threshold was produced immediately after exercise, decreasing to 15% after 15 min, when the acute exercise protocol was used. Naloxone reversed this effect. These data show that the acute resistance exercise protocol was effective in producing antinociception for 15 min. This antinociceptive effect is mediated by the activation of opioid receptors.


Vertical structure in chlorophyll profiles: influence on primary production in the Arctic Ocean.
Subsurface chlorophyll maximum (SCM) layers are prevalent throughout the Arctic Ocean under stratified conditions and are observed both in the wake of retreating sea ice and in thermally stratified waters. The importance of these layers on the overall productivity of Arctic pelagic ecosystems has been a source of debate. In this study, we consider the three principal factors that govern productivity within SCMs: the shape of the chlorophyll profile, the photophysiological characteristics of phytoplankton and the availability of light in the layer. Using the information on the biological and optical parameters describing the vertical structure of chlorophyll, phytoplankton absorption and photosynthesis-irradiance response curves, a spectrally resolved model of primary production is used to identify the set of conditions under which SCMs are important contributors to water-column productivity. Sensitivity analysis revealed systematic errors in the estimation of primary production when the vertical distribution of chlorophyll was not taken into account, with estimates of water-column production using a non-uniform profile being up to 97% higher than those computed using a uniform one. The relative errors were shown to be functions of the parameters describing the shape of the biomass profile and the light available at the SCM to support photosynthesis. Given that SCM productivity is believed to be largely supported by new nutrients, it is likely that the relative contribution of SCMs to new production would be significantly higher than that to gross primary production. We discuss the biogeochemical and ecological implications of these findings and the potential role of new ocean sensors and autonomous underwater vehicles in furthering the study of SCMs in such highly heterogeneous and remote marine ecosystems. This article is part of the theme issue 'The changing Arctic Ocean: consequences for biological communities, biogeochemical processes and ecosystem functioning'.


Factors affecting the transmission of SARS-CoV-2 in school settings.
Several studies have reported SARS-CoV-2 outbreaks in schools, with a wide range of secondary attack rate (SAR; range: 0-100%). We aimed to examine key risk factors to better understand SARS-CoV-2 transmission in schools. We collected records of 35 SARS-CoV-2 school outbreaks globally published from January 2020 to July 2021 and compiled information on hypothesized risk factors. We utilized the directed acyclic graph (DAG) to conceptualize risk mechanisms, used logistic regression to examine each risk-factor group, and further built multirisk models. The best-fit model showed that the intensity of community transmission (adjusted odds ratio [aOR]: 1.11, 95% CI: 1.06-1.16, for each increase of 1 case per 10 000 persons per week) and individualism (aOR: 2.72, 95% CI: 1.50-4.95, above vs. below the mean) was associated higher risk, whereas preventive measures (aOR: 0.25, 95% CI: 0.19-0.32, distancing and masking vs. none) and higher population immunity (aOR: 0.57, 95% CI: 0.46-0.71) were associated with lower risk of SARS-CoV-2 transmission in schools. Compared with students in high schools, the aOR was 0.47 (95% CI: 0.23-0.95) for students in preschools and 0.90 (95% CI: 0.76-1.08) for students in primary schools. Preventive measures in schools (e.g., social distancing and mask wearing) and communal efforts to lower transmission and increase vaccination uptake (i.e., vaccine-induced population immunity) in the community should be taken to collectively reduce transmission and protect children in schools.


Imbalance in obesity and mental health among "little emperors" in China.
Previous research has indicated that only children (i.e., those living with no siblings) have higher odds of obesity during childhood and young adulthood, compared with those living with siblings. However, little is known about whether the developing difference in overweight/obesity is accompanied by a difference in mental health (i.e., internalizing symptoms of depression and anxiety). The subjects for this prospective study were a randomly generated cohort of 1348 high-school students in Guangzhou, China. Participants completed assessments of anthropometric indices, lipid profiles, family-based factors, lifestyle, and internalization of symptoms (including those of depression and anxiety). Compared to their peers with siblings, only children (adjusted odds ratio [aOR] = 1.68, 95% confidence interval [CI] [1.06, 2.65]) had significantly higher risk for obesity. However, only children with overweight/obesity had lower OR for depression at follow-up (aOR = 0.19, 95% CI [0.34, 0.86]), compared to individuals who were overweight/obese with siblings. This relationship was not significant for non-overweight individuals. No significant relationship between the number of siblings and anxiety at follow-up was observed, regardless of body mass index (BMI). Although being an only child was significantly associated with overweight and obesity among adolescents in China, participants with history of overweight/obesity are less likely to experience symptoms of depression associated with being an only child.


Degradation of dyestuff wastewater using visible light in the presence of a novel nano TiO2 catalyst doped with upconversion luminescence agent.
A new upconversion luminescence agent, 40CdF2 x 60BaF2 x 0.8Er2O3, was synthesized and its fluorescent spectra were determined. This upconversion luminescence agent can emit five upconversion fluorescent peaks shown in the fluorescent spectra whose wavelengths are all below 387 nm under the excitation of 488 nm visible light. This upconversion luminescence agent was mixed into nano rutile TiO2 powder by ultrasonic and boiling dispersion and the novel doped nano TiO2 photocatalyst utilizing visible light was firstly prepared. The doped TiO2 powder was charactered by XRD and TEM and its photocatalytic activity was tested through the photocatalytic degradation of methyl orange as a model compound under the visible light irradiation emitted by six three basic color lamps. In order to compare the photocatalytic activities, the same experiment was carried out for undoped TiO2 powder. The degradation ratio of methyl orange in the presence of doped nano TiO2 powder reached 32.5% under visible light irradiation at 20 h which was obviously higher than the corresponding 1.64% in the presence of undoped nano TiO2 powder, which indicate the upconversion luminescence agent prepared as dopant can effectively turn visible lights to ultraviolet lights that are absorbed by nano TiO2 particles to produce the electron-cavity pairs. All the results show that the nano rutile TiO2 powder doped with upconversion luminescence agent is a promising photocatalyst using sunlight for treating the industry dye wastewater in great force.


The efficacy of postdivorce intervention programs for children: A meta-analytical review.
Preventive postdivorce interventions aim to help children cope with divorce and promote their adjustment. Nevertheless, questions remain regarding the concrete outcomes of these interventions and the intervention characteristics that influence them. This meta-analysis of 30 studies analyzes the efficacy of postdivorce interventions on children's symptomatology, personal resources, and adaptation to divorce. Likewise, it explores whether the intervention impacts the putative mediators from the family context and whether the characteristics of the studies themselves also influence the results. Using a data set of N = 4344 individuals, 258 effect sizes were calculated. Random effects analyses evidenced the impact of the interventions on specific variables instead of on children's global adjustment. There were no significant effects on children's mental health outcomes, and none of these effects were qualified by the moderators that were examined. Preventive postdivorce interventions had significant effects, specifically on children's divorce adjustment and self-esteem. The study of the moderators found that the interventions were generally homogeneous, and only one of the 20 moderators examined had a significant effect. Based on children's age, the interventions had an impact on family functioning only when they involved younger children, but this result should be interpreted with caution due to the small sample of studies. This meta-analysis provides evidence of the relevance of postdivorce interventions to critical variables as well as information about the role of the intervention characteristics in the effects and makes suggestions for future research on divorce interventions that encompass both practical and empirical developments.


Evolutionary conservation of the WASH complex, an actin polymerization machine involved in endosomal fission.
WASH is the Arp2/3 activating protein that is localized at the surface of endosomes, where it induces the formation of branched actin networks. This activity of WASH favors, in collaboration with dynamin, the fission of transport intermediates from endosomes, and hence regulates endosomal trafficking of several cargos. We have purified a novel stable multiprotein complex containing WASH, the WASH complex, and we examine here the evolutionary conservation of its seven subunits across diverse eukaryotic phyla. This analysis supports the idea that the invention of the WASH complex has involved the incorporation of an independent complex, the CapZ alpha/beta heterodimer, forming the so-called Capping Protein (CP), as illustrated by the yeasts S. cerevisiae and S. pombe, which possess the CP heterodimer but no other subunits of the WASH complex. The alignements of the orthologous genes that we have generated give a view on the conservation of the different subunits and on their organization into domains. Moreover, we propose here a unique nomenclature for the different subunits to prevent future confusions in the field.


One novel quinoxaline derivative as a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation.
Cyclophilin A (CypA) is a ubiquitous cellular enzyme playing critical roles in many biological processes, and its inhibitor has been reported to have potential immunosuppressive activity. In this work, we reported a novel quinoxaline derivative, 2,3-di(furan-2-yl)-6-(3-N,N-diethylcarbamoyl-piperidino)carbonylamino quinoxaline (DC838, 3), which was confirmed to be a potent inhibitor against human CypA. By using the surface plasmon resonance (SPR) and fluorescence titration techniques, the kinetic analysis of CypA/DC838 interaction was quantitatively performed. CypA peptidyl prolyl cis-trans isomerase (PPIase) activity inhibition assay showed that DC838 demonstrated highly CypA PPIase inhibitory activity. In vivo assay results showed that DC838 could inhibit mouse spleen cell proliferation induced by concanavalin A (Con A). Molecular docking simulation further elucidated the specific DC838 binding to CypA at the atomic level. The current work should provide useful information in the discovery of immunosuppressor based on CypA inhibitor.


Pediatric Open Globe Injury in Central China.
To describe the characteristics, managements, and outcomes of pediatric open globe injury (OGI) in central China. Retrospective chart review of pediatric diagnosis in patients with OGI between 2017 and 2020 at Henan Eye Hospital. Four hundred and one eyes of the patients younger than 17 years were included in this study. Open globe injury was classified according to the Birmingham Eye Trauma Terminology system (BETT). Age, sex, history, cause, month of trauma, treatment received, and outcomes were recorded. Visual acuity was documented according to standard visual acuity chart (decimals). Four hundred and one eyes of patients were included in the study. The mean age was 6.6 ± 3.4 years with the range from 8 months to 16 years. Open globe injuries (OGIs) occurred most frequently in the 2-8 year age and significant male predominance was noted (70.8%). The incidence of pediatric OGIs was lowest in summer months while it increased in the winter months. The most common type of pediatric OGI was penetration (89%). Scissors/knife accounted for 22%, followed by pen/pencil (15.2%), and wood/bamboo sticks (14.5%) of all the pediatric OGIs. Among the injuries, the most frequently involved is the zone I (76.1%). Initially, 70.8% of the eyes received primary debridement and wound closure without any additional intervention, while only one eye has no possibility of anatomical reconstruction when it received an evisceration. After the initial management, 198 eyes received subsequent operation, including 44 eyes that underwent cataract removal + intraocular lens (IOL) implantation, and 24 eyes underwent IOL implantation. Finally, over 6 months of follow-up, 129 eyes (32.2%) got visual acuity (VA) of 0.3-1.5 and, 63 eyes (15.7%) got VA of 0.01-0.25, while 11 eyes (2.7%) were eviscerated. This study showed that pediatric OGIs in central China are most seen in 2-8-year age group with significant male predominance. Scissors/knife, pen/pencil, and wood/bamboo sticks accounted for over half of all cases. Pediatric OGIs often result in significant vision loss. In some severe cases (2.7%), evisceration was ultimately performed. We should call on the public to pay more attention to their children and build a safer environment for them.


Antimony thin films demonstrate programmable optical nonlinearity.
The use of metals of nanometer dimensions to enhance and manipulate light-matter interactions for emerging plasmonics-enabled nanophotonic and optoelectronic applications is an interesting yet not highly explored area of research beyond plasmonics. Even more importantly, the concept of an active metal that can undergo an optical nonvolatile transition has not been explored. Here, we demonstrate that antimony (Sb), a pure metal, is optically distinguishable between two programmable states as nanoscale thin films. We show that these states, corresponding to the crystalline and amorphous phases of the metal, are stable at room temperature. Crucially from an application standpoint, we demonstrate both its optoelectronic modulation capabilities and switching speed using single subpicosecond pulses. The simplicity of depositing a single metal portends its potential for use in any optoelectronic application where metallic conductors with an actively tunable state are important.


Changes in invasive pneumococcal disease serotypes in a regional area of Australia following three years of 7vPCV introduction.
Invasive pneumococcal disease (IPD) is a serious bacterial disease. Vaccination can prevent disease for many of the current serotypes. The aim of this investigation was to describe the notification rates of IPD in a regional area of Australia, explore changes in rates since the introduction of the population vaccine programmes in 2005 and to describe changes in the distribution of serotypes in relation to the available vaccines after three years. Annualized IPD notification rates were calculated for residents of a regional area in northern New South Wales. Rates were analysed according to serotypes covered by available vaccines. Changes in serotypes were compared for the periods 2002-2004 and 2008-2010. The annualized notification rate of IPD in all ages for the period 2002-2004 was 13.7 per 100 000 population, and 8.3 per 100 000 population for the period 2008-2010 (rate ratio [RR], 0.61, confidence interval [CI]: 0.51-0.72). The largest decline was observed in 7-valent pneumococcal conjugate vaccine (7vPCV) types across all age groups (RR, 0.17, CI: 0.12-0.24) and in the zero to four year age group (RR, 0.03, CI: 0.01-0.11). The six serotypes included in the new 13-valent pneumococcal conjugate vaccine, but not in the 7vPCV, accounted for 40.6% of IPD cases in the zero to four year age group during the period of 2008-2010. The introduction of 7vPCV significantly reduced the overall notification rate of IPD caused by the serotypes contained in this vaccine. This decline in IPD rates in children can be directly attributed to the use of 7vPCV, and in adults it is most likely an indirect effect of the 7vPCV programme in children.


Diet-Intestinal Microbiota Axis in Osteoarthritis: A Possible Role.
Intestinal microbiota is highly involved in host physiology and pathology through activity of the microbiome and its metabolic products. Osteoarthritis (OA) is a common form of arthritis characterized by articular cartilage destruction and osteophyte formation. Although various person-level risk factors, such as age, sex, and obesity, have been proposed for the pathogenesis of OA, the underlying links between these person-level factors and OA are still enigmatic. Based on the current understanding in the crosstalk between intestinal microbiota and these risk factors, intestinal microbiota could be considered as a major hidden risk factor that provides a unifying mechanism to explain the involvement of these person-level risk factors in OA.


Review: Mitral valve aneurysms in infective endocarditis: mechanisms, clinical recognition, and treatment.
The mitral valve frequently becomes secondarily infected in aortic valve endocarditis. A number of mechanisms have been invoked to explain this association, including: (i) aortic regurgitation (jet lesions); (ii) vegetation prolapse into the left ventricular outflow tract ('kissing lesions'); and (iii) a contiguous spread of infected tissue. A variety of secondary lesions can develop on the mitral valve, including partial thickness ulcerations, perforations, vegetations, and aneurysms. The clinical recognition and treatment of mitral valve aneurysms in primary aortic valve endocarditis are of particular interest and comprise the main focus of this review. Echocardiographically, mitral valve aneurysms appear as narrow-necked, saccular echolucencies protruding into the left atrium. These structures must be distinguished from mitral valve prolapse, congenital diverticula and blood cysts. Mitral regurgitation can result from aneurysm perforation or from the mass effect produced by lesions critically located along the lines of leaflet closure. Aneurysms harboring clot are a potential source of systemic embolization. Treatment is generally surgical; however, otherwise uncomplicated aneurysms have been safely followed using a more conservative strategy.


Input-output properties of the soleus stretch reflex in spastic stroke patients and healthy subjects during walking.
The input-output properties of the soleus stretch reflex during walking and sitting were examined in 11 spastic stroke patients and 10 healthy subjects. In the early swing phase, the threshold of the input-output relation was significantly lower in the patient group - on average 108°/s compared to 309°/s in the control group (P=0.02). The slope of the input-output properties was unchanged in patients and in control subjects (P=0.39). In stroke patients we found a minor, but significant, difference in threshold with 108°/s in the early swing phase compared to 74°/s in sitting position at matched TA EMG activity (P=0.01). Furthermore, we found an unchanged slope of 0.25μVs/° during walking and 0.28μVs/° in the sitting position (P=0.21). In contrast, control subjects showed a large difference in the threshold in the early swing phase during walking (309°/s) compared with findings in the sitting position at a matched TA EMG activity (71°/s, P=0.004). The slope was unchanged during walking and when the subject was sitting (P=0.22). There was a significant correlation between clinical spasticity score and stretch reflex threshold in the early swing phase (P=-0.61, P=0.04) and between clinical spasticity score and the slope in the early swing phase (P=0.72, P=0.009). It is concluded that in the early swing phase, the markedly reduced soleus stretch reflex threshold was preventing the stroke patients from making fast dorsiflexion of the foot at the ankle joint and thereby impairing the walking speed.


An Integrated Pest Management Intervention Improves Knowledge, Pest Control, and Practices in Family Child Care Homes.
To reduce young children's exposure to pesticides when attending family child care homes (FCCHs), we developed an integrated pest management (IPM) intervention for FCCH directors. First, we developed IPM educational materials and resources to provide the foundation for an IPM educational intervention for FCCHs. Next, we conducted and evaluated a six-month nurse child care health consultant (CCHC)-led education and consultation IPM intervention to increase IPM knowledge, IPM practices, IPM policies, and decrease the presence or evidence of pests. The pilot intervention study was conducted by three CCHCs in 20 FCCHs in three counties in California. Pre- and post-intervention measures were completed by the FCCH directors and observation measures were completed by the CCHCs. Results indicated significant increases in IPM knowledge, (t-statistic (degrees of freedom), (t(df) = 2.55(10), p < 0.05), increases in IPM practices (t(df) = -6.47(17), p < 0.05), and a 90% reduction in the prevalence of pests. There were no significant differences in changes in IPM practices based on director education, FCCH county, or IPM intervention intensity or duration. A nurse-led IPM education and consultation intervention can reduce exposures of young children attending family child care homes to harmful chemicals.


Dietary phytogenics and galactomannan oligosaccharides in low fish meal and fish oil-based diets for European sea bass (Dicentrarchus labrax) juveniles: Effects on gut health and implications on in vivo gut bacterial translocation.
European sea bass were fed four low FM/FO (10%/6%) diets containing galactomannan oligosaccharides (GMOS), a mixture of garlic oil and labiatae plants oils (PHYTO), or a combination of both functional products (GMOSPHYTO) for 63 days before exposing the fish to an intestinal Vibrio anguillarum infection combined with crowding stress. In order to evaluate functional diets efficacy in terms of gut health maintenance, structural, cellular, and immune intestinal status were evaluated by optical and electron microscopy and gene expression analyses. A semi-automated software was adapted to determine variations in goblet cell area and mucosal mucus coverage during the challenge test. Feeding with functional diets did not affect growth performance; however, PHYTO and GMOS dietary inclusion reduced European sea bass susceptibility to V. anguillarum after 7 days of challenge testing. Rectum (post-ileorectal valve) showed longer (p = 0.001) folds than posterior gut (pre-ileorectal valve), whereas posterior gut had thicker submucosa (p = 0.001) and higher mucus coverage as a result of an increased cell density than rectum. Functional diets did not affect mucosal fold length or the grade of granulocytes and lymphocytes infiltration in either intestinal segment. However, the posterior gut fold area covered by goblet cells was smaller in fish fed GMOS (F = 14.53; p = 0.001) and PHYTO (F = 5.52; p = 0.019) than for the other diets. PHYTO (F = 3.95; p = 0.049) reduced posterior gut goblet cell size and increased rodlet cell density (F = 3.604; p = 0.068). Dietary GMOS reduced submucosal thickness (F = 51.31; p = 0.001) and increased rodlet cell density (F = 3.604; p = 0.068) in rectum. Structural TEM analyses revealed a normal intestinal morphological pattern, but the use of GMOS increased rectum microvilli length, whereas the use of PHYTO increased (p≤0.10) Ocln, N-Cad and Cad-17 posterior gut gene expression. After bacterial intestinal inoculation, posterior gut of fish fed PHYTO responded in a more controlled and belated way in terms of goblet cell size and mucus coverage in comparison to other treatments. For rectum, the pattern of response was similar for all dietary treatments, however fish fed GMOS maintained goblet cell size along the challenge test.


Crystal structure of type II NADH:quinone oxidoreductase from Caldalkalibacillus thermarum with an improved resolution of 2.15 Å.
Type II NADH:quinone oxidoreductase (NDH-2) is a respiratory enzyme found in the electron-transport chain of many species, with the exception of mammals. It is a 40-70 kDa single-subunit monotopic membrane protein that catalyses the oxidation of NADH and the reduction of quinone molecules via the cofactor FAD. NDH-2 is a promising new target for drug development given its essential role in many bacterial species and intracellular parasites. Only two bacterial NDH-2 structures have been reported and these structures are at moderate resolution (2.3-2.5 Å). In this communication, a new crystallization platform is reported that produced high-quality NDH-2 crystals that diffracted to high resolution (2.15 Å). The high-resolution NDH-2 structure was used for in silico quinone substrate-docking studies to investigate the binding poses of menadione and ubiquinone molecules. These studies revealed that a very limited number of molecular interactions occur at the quinone-binding site of NDH-2. Given that the conformation of the active site is well defined, this high-resolution structure is potentially suitable for in silico inhibitor-compound screening and ligand-docking applications.


Important role for angiotensin III and IV in the brain renin-angiotensin system.
Considerable evidence now suggests that the precursors and enzymes necessary for the formation and degradation of biologically active forms of angiotensins are present in brain tissues, accompanied by at least three specific binding sites. It also appears that several forms of angiotensin may serve as signaling agents at these sites. There is accumulating support for the notion that AngII must be converted to AngIII in order to bind at the AT1 and AT2 receptor subtypes, and AngIII must be converted to AngIV in order to activate the AT4 receptor subtype. Further, AngII(1-7) may activate a separate binding site concerned with antidiuresis, however, characterization of this site has not been completed. The AT1 site appears to mediate the classic angiotensin functions concerned with body water balance, maintenance of blood pressure, and cyclicity of reproductive hormones and sexual behaviors. This receptor site also exerts some control over the secretion of pituitary hormones. Less is known about the functional importance of the AT2 site, however, it has been implicated in vascular growth, control of blood flow, and perhaps modulation of NMDA receptors. The AT4 site is heavily distributed in neocortex, hippocampus, cerebellum, and basal ganglia structures, as well as several peripheral tissues. This site appears to mediate memory acquisition and retrieval, the regulation of blood flow, neurite outgrowth, angiogenesis, and kidney function. In addition to the well-studied functions of the brain renin-angiotensin system, additional less well investigated responses are reviewed. These include electrophysiological activation, tachyphylaxis, long term potentiation, learning and memory, and cognitive affect.


Insights into coral reef benthic dynamics from nonlinear spatial forecasting.
Nonlinear time-series forecasting, or empirical dynamic modelling, has been used extensively in the past two decades as a tool for distinguishing between random temporal behaviour and nonlinear deterministic dynamics. Previous authors have extended nonlinear time-series forecasting to continuous spatial data. Here, we adjust spatial forecasting to handle discrete data and apply the technique to explore the ubiquity of nonlinear determinism in irregular spatial configurations of coral and algal taxa from Palmyra Atoll, a relatively pristine reef in the central Pacific Ocean. We find that the spatial distributions of coral and algal taxa show signs of nonlinear determinism in some locations and that these signals can change through time. We introduce the hypothesis that nonlinear spatial determinism may be a signal of systems in intermediate developmental (i.e. successional) stages, with spatial randomness characterizing early (i.e. recruitment dominated) and late-successional (i.e. 'climax' or attractor) phases. Common state-based metrics that sum community response to environmental forcing lack resolution to detect dynamics of (potential) recovery phases; incorporating signal of spatial patterning among sessile taxa holds unique promise to elucidate dynamical characters of complex ecological systems, thereby enhancing study and response efforts.