Outcomes of a newly established transitional urology outpatient clinic: a real-world experience.
To evaluate the demographic and clinical characteristics of patients who visited our transitional urology (TU) outpatient clinic formed by pediatric urologists with urology background within the first year upon its establishment. Files of 130 consecutive patients who visited our TU outpatient clinic, which was established in 01 March 2021, between 01 March 2021 and 01 March 2022 were retrospectively collected. Patients were divided into two groups: those with a previous follow-up in our pediatric urology department (Group I, n: 81, 62.3%) and those who were followed up in other clinics during childhood (Group II, n: 49, 37.7%) afterwards. Demographic characteristics, complaints at admission, previous medical history, and management plans at the recent clinical visit were noted. We defined a successful and smooth transition from childhood to adult care as not being without follow-up within the first year after the age of 18 years and not requiring extraordinary medical assistance (e.g., emergency room visits, hospitalization, intensive care unit admissions) from the last urological control to the TU outpatient clinic visits. The most common diagnoses were vesicoureteral reflux (n: 32, 24.6%), neuropathic bladder accompanied by spina bifida (n: 31, 23.8%), obstructive uropathy (n: 25, 19.2%), hypospadias (n: 20, 15.3%), non-neurogenic lower urinary tract dysfunction (n: 19, 14.6%), and bladder exstrophy (n: 8, 6.1%). The distribution of primary diagnosis in the two patient groups was similar. The median time from the last pediatric urology visit to the current TU clinical visit was significantly longer in Group II (12 vs. 60 months, p < 0.001),consequently, the median patient age at admission was significantly higher in Group II (21 vs. 23 years, p = 0.020). The rate of a successful and smooth transition was 86.4% in Group I, whereas Group II had a completely unsuccessful transition period. Upon admission to TU outpatient clinic, the requirement of a surgical intervention was lower in Group I (21% vs. 38.8%, p = 0.028).Also,the need for medical treatment changes was higher in Group II (9.9% vs. 53.1%, p < 0.001). Our findings emphasize the importance of patient referral to a TU clinic that deal with lifelong problems of congenital genitourinary diseases. Delays in receiving medical or surgical treatments during transition from childhood to adulthood may be associated with higher need for subsequent surgical interventions in this vulnerable patient population.


Unusual phenotype of hemoglobin EE with hemoglobin H disease: a pitfall in clinical diagnosis and genetic counseling.
Two unrelated individuals previously diagnosed as hemoglobin (Hb) EE were found to be, in fact, Hb EE with Hb H disease. This globin genotype normally results as Hb EF Bart disease. This unusual genotype-phenotype interaction highlights the need for molecular analysis in affected individuals with Hb E disorders before appropriate genetic counseling and genetic risk estimation in offspring can be given.


Increased vertebral body area, disc and facet joint degeneration throughout the lumbar spine in patients with lumbosacral transitional vertebrae.
Lumbosacral transitional vertebrae (LSTV), developmental spinal canal stenosis, lumbar disc and facet joint degeneration are all common lumbar spine conditions. This study explores the relationship between these entities. Five hundred and five patients (254 females, 251 males), mean age 57 ± 13 years, who underwent abdominopelvic CT examinations were studied. Vertebral body cross-sectional area (CSA), spinal canal CSA, width and depth were measured from L1 to L5. The presence of LSTV was documented and the severity of disc/facet joint degeneration graded. LSTV was present in 155 (31%) of 505 patients, being twice as common in males than in females. After controlling for age, height and weight, vertebral body CSAs from L1 to L5 in male LSTV patients were, on average, 9.8% larger than those in male non-LSTV patients (p < 0.0001 for all) while vertebral body areas at L3 and L4 were 4.5% larger in female LSTV patients than in non-LSTV female patients. Disc degeneration from L2/3 to L5/S1 and facet joint degeneration from L2/3 to L4/5 were more severe in LSTV patients. LSTV Castellvi Type II patients appear to be most prone to disc and facet degeneration. LSTV patients, and particularly male patients, have an increased vertebral body CSA compared to non-LSTV patients throughout the lumbar spine. LSTV patients also have more severe disc and facet joint degeneration. The increase in vertebral body area may be contributing to the increased lumbar and facet joint degeneration seen in LSTV patients. • LSTV patients have increased vertebral body cross-sectional area throughout their lumbar spine compared to non-LSTV patients. This vertebral body area increase was more pronounced in male patients and also apparent in younger patients with LSTV. • LSTV patients have increased disc and facet joint degeneration affecting most of the lumbar spine than non-LSTV patients. • Increased vertebral body area may contribute to the increased lumbar disc and facet joint degeneration seen in LSTV patients.


Progesterone rapidly alters the use of place and response memory during spatial navigation in female rats.
17β-Estradiol (E2) and progesterone (P) influence place and response memory in female rats in spatial navigation tasks. Use of these memory systems is associated with the hippocampus and the dorsal striatum, respectively. Injections of E2 result in a well-established bias to use place memory, while much less is understood about the role of P. A total of 120 ovariectomized female rats were tested within a dual-solution T-maze task and treated with either low E2 (n = 24), high E2 (10 μg/kg; n = 24), or high E2 in combination with P (500 μg/kg) at three time points before testing: 15 min (n = 24), 1 h (n = 24), and 4 h (n = 24). Given alone, high E2 biases rats to the use of place memory, but this effect is reversed when P is given 1 h or 4 h before testing. This indicates that P may be playing an inhibitory role in the hippocampus during spatial tasks, which is consistent with past findings. Our findings show that P acts rapidly (within an hour) to affect performance during spatial tasks.


Isolation and Characterization of Novel Lignolytic, Cellulolytic, and Hemicellulolytic Bacteria from Wood-Feeding Termite Cryptotermes brevis.
In a natural ecosystem, various organisms digest and hydrolyze lignocellulose biomass efficiently. Termites are one of them. They digest lignocellulose biomass with the help of symbiotic microorganisms in their gut. Therefore, termites gut may harbor potential sources of microorganisms capable to degrade lignocellulose biomass. In this study, termite gut microbiomes of Cryptotermes brevis species were isolated and identified for their capability to degrade lignin and polysaccharides. Alkali lignin, carboxymethylcellulose, and xylan were used as the only carbon sources in the medium to isolate lignin-, cellulose-, and hemicellulose-degrading bacteria. By this method, two bacteria strains, Bacillus sp. BMP01 and Ochrobactrum oryzae BMP03 strain were isolated and identified. Bacillus sp. BMP01 strain has capabilities to hydrolyze carboxymethylcellulose and xylan to glucose and xylose, respectively. This strain showed high xylanase activity (about 0.21 U/ml) and carboxymethyl cellulase activity (about 0.25 U/ml). The ability to hydrolyze both carboxymethylcellulose and xylan makes it superior to other known cellulolytic bacteria. Ochrobactrum oryzae BMP03 strain showed laccase activity, which indicates its ability to depolymerize lignin. Lignocellulose-degrading bacteria play a vital role in the biological conversion of lignocellulose biomass to biofuel. Overall, this study shows that termite's gut microbiomes are potential sources of lignocellulose-degrading bacteria that can be cultured and used in the biological conversion of lignocellulose biomass to biofuel.


Recurrent abortion associated with a balanced 22;22 translocation, or isochromosome 22q in a monozygous twin.
A 45,XX,t(22;22)(p11;q11) or 45,XX,i(22q) chromosomal rearrangement was found in a woman with a history of recurrent abortion. A twin sister did not have the translocation even though marker studies indicate that the twins are probably monozygotic.


Cytology of desmoplastic small round cell tumor.
Desmoplastic small round cell tumor (DSRCT) is a high-grade malignant tumor that has a predilection for adolescent males and usually affects the abdominal cavity. The cytology literature regarding DSRCT, including aspirates and ascitic fluid, is limited. To the authors' knowledge, findings in ThinPrep slides have not been described previously. Seven cytologic specimens from five patients with histologically confirmed DSRCT were reviewed. Five specimens were fine-needle aspiration biopsies (FNABs), (liver, flank soft tissue, abdomen, and two resected colons [pericolic]) and two specimens were ascitic fluid. Cytologic features were studied in ThinPrep slides and direct smears, which included hematoxylin and eosin, Papanicolaou, and Quik-Dip stains. All specimens showed moderate to high cellularity. The tumor cells were arranged singly and in clusters. The cells demonstrated high nuclear/cytoplasmic ratios, granular chromatin reminiscent of small cell carcinoma, usually inconspicuous nucleoli, smooth to irregular nuclear membranes, and frequent nuclear molding. The cytoplasm was scant to moderate, pale blue, and occasionally vacuolated. Pseudorosettes were observed in six specimens. One ThinPrep slide and the direct smears contained cells with perinuclear, cytoplasmic densities. Stromal fragments were present in the direct smears but were uncommon in ThinPrep. Three specimens were diagnosed as being consistent with DSRCT. Two specimens were diagnosed as malignant small cell tumor. Molecular studies performed on histologic material in four cases confirmed the presence of the diagnostic translocation, t(11;22)(p13;q12). DSRCT may be diagnosed accurately in cytology specimens. Characteristic cytologic features include granular chromatin, smooth to irregular nuclear membranes, nuclear molding, cytoplasmic vacuoles, pseudorosettes, and metachromatic stroma. Cytoplasmic densities may be observed in direct smears and ThinPrep slides.


The Ebola epidemic and public health response.
An unprecedented global effort has been required to tackle the Ebola outbreak in West Africa. In this paper, we describe the contribution of Public Health England (PHE) in West Africa and the UK. Public Health England The epidemic has been a humanitarian crisis for the three worst affected countries. PHE contributions have included expertise in outbreak control and microbiology services in West Africa, and UK preparedness for an imported case. National and international systems require change to enhance the response to the next international public health crisis. Legacy planning following the epidemic will be crucial, supporting the recovery of the health and public health systems in West Africa and ensuring that the knowledge gained during this outbreak is put to best use. Ongoing PHE-associated research includes efforts to understand the pathogenicity of Ebola virus disease, improve diagnostic capability, explore therapeutic options and develop new vaccines.


Association between Weight Change and Mortality in Community Living Older People Followed for Up to 14 Years. The Hordaland Health Study (HUSK).
To study the importance of weight change with regard to mortality in older people. Prospective cohort study. The cohort includes participants in the Hordaland Health Study, Norway, 1997-99 (N=2935, age 71-74 years) who had previously participated in a survey in 1992-93. Participants with weight measured at both surveys were followed for mortality through 2012. Cox proportional hazards models were used to calculate risk of death according to changes in weight. Hazard ratios (HR) with 95% confidence intervals (CIs) for people with stable weight (± <5% weight change) were compared to people who lost (≥5%) or gained (≥5%) weight. Cox regression with penalized spline was used to evaluate the association between weight change (in kg) and mortality. Analyses were adjusted for age, sex, physical activity, smoking, diabetes, hypertension, and previous myocardial infarction or stroke. Participants with cancer were excluded. Compared to those with stable weight, participants who lost ≥5% weight had an increased mortality risk (HR 1.59 [95% CI: 1.35-1.89]) while the group with weight gain ≥5% did not (HR 1.07 [95% CI 0.90-1.28]). Penalized spline identified those who lost more than about three kg or gained more than about 12 kg as having increased risk of death. Even a minor weight loss of ≥5% or >3 kg were significantly associated with increased risk of mortality. Thus, weight should be routinely measured in older adults.


Analysis of aztreonam-inducing proteome changes in nondividing filamentous Helicobacter pylori.
When stressed, bacteria can enter various nondividing states. In the present study, nondividing filamentous form in Helicobacter pylori was induced by a β-lactam antibiotic, aztreonam. In order to find possible cell division checkpoints in H. pylori, 2-DE was used to compare the proteomic profile of nondividing filamentous H. pylori with its spiral form. In total, 21 proteins involved in various cellular processes showed differential expression. One protein induced by aztreonam was a cell division inhibitor (minD), related to cell division. We then constructed the deletion mutant of minD in H. pylori 26695. Scanning electron microscope observation showed that the deletion of this protein provoked some bacteria to change into a short rod-shape and the viability of the mutant is lower than that of the wild type. Moreover, sequence comparison showed that minD of H. pylori and that of Escherichia coli share 50 % amino acid identity. This suggested that this protein possibly plays the similar part in H. pylori as in E. coli.


β-cell dysfunction in adolescents and adults with newly diagnosed type 2 diabetes mellitus.
To compare β-cell function in adolescents and adults with newly diagnosed type 2 diabetes (T2DM). Thirty-nine adolescents with T2DM, 38 age- and weight-matched control subjects, and 19 adults with T2DM were studied. The adolescent subjects with diabetes were divided on the basis of whether they needed insulin to control their initial hyperglycemia. The primary outcome variable was the disposition index, computed from the acute insulin response to glucose corrected for insulin sensitivity (1/Homeostatic model assessment of insulin resistance). The disposition index was significantly reduced in all 3 diabetic groups (control n=3360, adolescents with T2DM without insulin n=630, adolescents with T2DM with insulin n=120, adults with T2DM n=200; P<.001), and the adolescents with more severe hyperglycemia at diagnosis had lower disposition index than those with a more modest presentation (P<.05). At the time of diagnosis, adolescents with T2DM have significant β-cell dysfunction, comparable with adults newly diagnosed with T2DM. Thus, severe β-cell impairment can develop within the first two decades of life and is likely to play a central role in the pathogenesis of T2DM in adolescents.


CHD7 missense variants and clinical characteristics of Chinese males with infertility.
Isolated hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are rare genetic diseases that cause male infertility. The chromodomain helicase DNA-binding protein 7 (CHD7) gene is commonly associated with KS and IHH. We speculated that CHD7 variants may be associated with male infertility. Two hundred males with azoospermia and 120 with oligozoospermia were recruited. The patients underwent clinical examination and reproductive hormone testing. A panel of genes including CHD7 and others related to spermatogenic failure was sequenced by targeted-gene exome sequencing. Three patients with severe oligozoospermia had CHD7 variants (a detection rate of 0.94% (3/320)). After prediction software analysis, two of the variants c.3464G>A (p.R1155H) and c.4516G>A (p.G1506S) were predicted to be likely pathogenic. Although predicted to be benign, the variants of c.2824A>G (p.T942A) located in the chromodomain 2 could not be excluded as disease causing. The patients with variants had small testicular volumes. In particular, the testes of the patient with a p.G1506S variant varied in size (left, 8 ml; right, 4.5 ml). Two patients (patients 31 and 120) had low E2 levels and two (patients 83 and 120) had low T levels. Ultimately, these variants were classified as "variants of unknown significant" that may be associated with male infertility. There may be a relationship between the CHD7 gene missense variants and male infertility. These variants are easier to find in patients with azoospermia and severe oligospermia whose testosterone levels are decreased.


[Visualization of different types of hapten-cell membrane interaction by fluorine high-field nuclear magnetic resonance].
Using a high field spectrometer (5.9 Tesla) 19F-NMR spectrum of soluble material from 4 trifluoromethyl 2,6 dinitrobenzene sulphonate (CF3-DNBS) treated murine lymphocytes was recorded. CF3-DNBS is a fluorinated analog of 2,4,6 trinitrobenzene sulphonate (TNBS), and these compounds have been found to create cross-reacting antigenic modifications of cell surface. At least 4 distinguishable signals have been detected, and we think that 19F-NMR could be used to study, at a molecular level, some immunochemical problems concerning modification with TNBS.


Aorto-cutaneous fistula from an infected ascending aorta graft resulting in massive hemorrhage after a Valsalva maneuver for a heavy weight lift.
In the setting of an infected prosthetic ascending thoracic aorta, prompt and definitive surgical treatment is mandatory to avoid catastrophic bleeding complications.


Neuroendocrine carcinoma and mixed neuroendocrine‒non-neuroendocrine neoplasm of the stomach: a clinicopathological and exome sequencing study.
The gene mutation profiles of gastric neuroendocrine neoplasms are incompletely understood. The purpose of this study was to characterize the molecular pathology of poorly differentiated neuroendocrine carcinoma (NEC) and mixed neuroendocrine‒non-neuroendocrine neoplasm (MiNEN) of the stomach. Surgical cases of gastric NEC (n = 7) and MiNEN (n = 6) were examined by clinical review, immunohistochemistry, microsatellite instability (MSI) analysis and whole-exome sequencing. NEC cases consisted of small- (n = 2) and large-cell types (n = 4). All cases of MiNEN were histologically composed of large-cell type NEC and tubular adenocarcinoma. Whole-exome sequencing analysis detected recurrent mutations in TP53 in 8 cases (62%), and they were more frequently observed in MiNEN than in NEC (100% vs. 29%). Frameshift mutations of APC were observed in two cases of MiNEN. One case of large-cell type NEC had a frameshift mutation with loss of heterozygosity in RB1. The other mutated genes (e.g., ARID1 and KRAS) were detected in a single case each. A high level of MSI was confirmed in one case of MiNEN, which harbored mutations in two well-differentiated neuroendocrine tumor (NET)-related genes (MEN1 and ATRX1). In cases of MiNEN, two histological components shared mutations in TP53, APC and ZNF521, whereas alterations in CTNNB1, KMT2C, PTEN and SPEN were observed in neuroendocrine components only. In conclusion, TP53 is a single, frequently mutated gene in gastric NEC and MiNEN, and alterations in other genes are less common, resembling the mutation profiles of gastric adenocarcinomas. Gene mutations frequently observed in well-differentiated NET were uncommon but not entirely exclusive.


Portacaval anastomosis in rats: effects on behavior and brain serotonin metabolism.
The behavior of male rats with chronic end-to-side portacaval shunts or control surgery were evaluated in a complex enclosed maze, an open-field arena, and a swim canal. Subsequently, serotonin and 5-hydroxyindoleacetic acid levels were measured for hypothalamus, striatum, hippocampus, and midbrain-medulla. Chronic portacaval anastomosis did not significantly alter any of the behavioral parameters evaluated in the diverse test situations studied, despite a significant elevation of 5-hydroxyindoleacetic acid levels in all brain regions analyzed and the elevation of serotonin levels in hypothalamus and midbrain-medulla.


Meaning matters in children's plural productions.
The English plural is about the number of individuals in a set of like kinds. Two-year-old children use the plural but do not do so in all obligatory contexts. The present report asks whether the limitations on their production of the plural are related to aspects of meaning. In two Experiments plural productions were elicited from 2-year-old children for sets of size two and four and for instances of basic-level categories that were either similar or identical. Children were much more likely to produce the plural of these well-known nouns when there were four rather than two and when the instances were identical rather than merely similar. The results provide new evidence on children's acquisition of the English plural, showing that children's early productions are not just limited by knowledge of the noun and its plural form but also is limited by properties of the labeled sets in ways that are relevant to the underlying meaning of the plural.


Antidepressants, sex steroids and pituitary-adrenal response in sheep.
The importance of sex differences in major affective diseases such as depression is providing a new focus for investigating the interactions between sex, sex steroids and antidepressants. In this study, we examined the acute effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) and imipramine, a tricyclic antidepressant (TCA) on the endocrine endpoints, adrenocorticotropin (ACTH) and cortisol secretion in gonadectomised male and female sheep. Each sheep was treated with an acute subcutaneous (s.c.) injection containing vehicle, sertraline (5 and 10 mg/kg), or imipramine (10 mg/kg) in the presence and absence of sex steroid replacement. In males, SSRI treatment consisted of testosterone (2 x 200 mg s.c. pellets), and in females, estradiol (1 cm s.c. implant) plus an intravaginal controlled internal drug release device containing 0.3 g progesterone. ACTH and cortisol were measured in jugular blood. Female sheep responded to sertraline treatment with dose-dependent ACTH and cortisol increases that were unchanged by sex steroid replacement. In castrated males, however, only the highest dose of sertraline increased ACTH and cortisol, and this increase was abolished in the presence of testosterone replacement. Imipramine affected neither ACTH nor cortisol secretion in either the sex or sex steroid condition. We conclude that the sex and sex steroid-related differences in the male and female responses to sertraline treatment may reflect sex and sex steroid dependent differences in serotonergic activation of the HPA axis. This highlights the potential significance of sex and circulating sex steroids in modulating neuroendocrine responses to antidepressants, and may have an impact on our understanding of the actions of these drugs in men and women.


A new second intermediat host of genus Paragonimus.
1. Metacercariae were found from 6 samples among 4,382 Parlemon nipponensis which were caught at Podu, Kohung, Korea. 2. The metacercaria was inclined as a larval stage of Paragonimus westermani by following reason; i)Semisulcospira libertina was the only one species which lives in Podu area. ii)No other metacercaria except Paragonimus westermani were found from the craw or cray fish which were caught in the endemic aera. iii)Metacercariae, ovary, testes and cuticular spines resmbled the characteristics of Paragonimus westermani, which have been described by previous workers.


Alveolar hypoxia, inhibition of hypoxic pulmonary vasoconstriction, and permeability edema.
We previously reported that regional alveolar hypoxia reduces oleic acid-induced permeability edema formation [Cheney et al. (1987). J. Appl. Physiol. 62: 1690-1697]. In order to define the role of hypoxic pulmonary vasoconstriction (HPV) on this effect, we studied the effects of regional alveolar hypoxia on permeability edema formation with this response inhibited. Dogs weighing 25 +/- 1 kg in which the HPV response had been inhibited by the administration of minoxidil (1 mg/kg i.v.) were anesthetized, mechanically ventilated and had a bronchial divider placed so the left lower lobe (LLL) could be ventilated with an FIO2 = 0.05 or FIO2 = 1, while the right lung was continuously ventilated with an FIO2 = 1.0. In 10 study animals the LLL was ventilated with an FIO2 = 0.05 for 4 h after induction of bilateral permeability pulmonary edema with 0.05 ml/kg of intravenous oleic acid. In six control animals the LLL was ventilated with an FIO2 = 1 for 4 h after the same injury. Postmortem gravimetric analysis indicates that alveolar hypoxia of the LLL with the HPV response inhibited had no effect on pulmonary edema formation. We conclude that inhibition of HPV abolishes the protective effect of regional alveolar hypoxia on oleic acid-induced permeability edema formation.


Disparities among crop species in the evolution of growth rates: the role of distinct origins and domestication histories.
Growth rates vary widely among plants with different strategies. For crops, evolution under predictable and high-resource environments might favour rapid resource acquisition and growth, but whether this strategy has consistently evolved during domestication and improvement remains unclear. Here we report a comprehensive study of the evolution of growth rates based on comparisons among wild, landrace, and improved accessions of 19 herbaceous crops grown under common conditions. We also examined the underlying growth components and the influence of crop origin and history on growth evolution. Domestication and improvement did not affect growth consistently, that is growth rates increased or decreased or remained unchanged in different crops. Crops selected for fruits increased the physiological component of growth (net assimilation rate), whereas leaf and seed crops showed larger domestication effects on morphology (leaf mass ratio and specific leaf area). Moreover, climate and phylogeny contributed to explaining the effects of domestication and changes in growth. Crop-specific responses to domestication and improvement suggest that selection for high yield has not consistently changed growth rates. The trade-offs between morpho-physiological traits and the distinct origins and histories of crops accounted for the variability in growth changes. These findings have far-reaching implications for our understanding of crop performance and adaptation.


Response shift bias: a problem in evaluating nutrition training using self-report measures.
The Cooperative Extension Service has been a key partner in the design, implementation, and evaluation of school nutrition training. To evaluate the effectiveness of their training and the effects of response shift bias on outcomes using a self-report measure, 162 foodservice staff from eight rural schools participated in this food-handling behavior study. Nutrition staff were assigned to one of two treatment groups or to the control group. Two different evaluation designs (pretest/ post-test and then/post) were used. The then/post design asks participants to first report their behavior or understanding as a result of the training (post) and then to retrospectively report this behavior before the training. The then/post evaluation design provided more significant change data than did the traditional pretest/post-test design, indicating that a response shift occurred. Such differences in evaluation findings suggest that the educational benefit of such training may be underestimated when using the traditional pre/post evaluation design.


Waterlogging-induced increase in sugar mobilization, fermentation, and related gene expression in the roots of mung bean (Vigna radiata).
The objective of this study was to examine the role of root carbohydrate levels and metabolism in the waterlogging tolerance of contrasting mung bean genotypes. An experiment was conducted with two cultivated mung bean (Vigna radiata) genotypes viz., T44 (tolerant) and Pusa Baisakhi (PB) (susceptible), and a wild Vigna species Vigna luteola under pot-culture to study the physiological and molecular mechanism of waterlogging tolerance. Waterlogging resulted in decrease in relative water content (RWC), membrane stability index (MSI) in root and leaf tissues, and chlorophyll (Chl) content in leaves, while the Chl a/b ratio increased. Waterlogging-induced decline in RWC, MSI, Chl and increase in Chl a/b ratio was greater in PB than V. luteola and T44. Waterlogging caused decline in total and non-reducing sugars in all the genotypes and reducing sugars in PB, while the content of reducing sugar increased in V. luteola and T44. The pattern of variation in reducing sugar content in the 3 genotypes was parallel to sucrose synthase (SS) activity. V. luteola and T44 also showed fewer declines in total and non-reducing sugars and greater increase in reducing sugar and SS activity than PB. Activity of alcohol dehydrogenase (ADH) increased up to 8d of waterlogging in V. luteola and T44, while in PB a marginal increase was observed only up to 4d of treatment. Gene expression studies done by RT-PCR in 24h waterlogged plants showed enhanced expression of ADH and SS in the roots of V. luteola and T44, while in PB there was no change in expression level in control or treated plants. PCR band products were cloned and sequenced, and partial cDNAs of 531, 626, and 667; 702, 736, and 744bp of SS and ADH, respectively were obtained. The partial cDNA sequences of cloned SS genes showed 93-100 homologies among different genotypes and with D10266, while in case of ADH the similarity was in the range of 97-100% amongst each other and with Z23170. The results suggest that the availability of sufficient sugar reserve in the roots, activity of SS to provide reducing sugars for glycolytic activity and ADH for the recycling of NADH, and for the continuation of glycolysis, could be one of the important mechanisms of waterlogging tolerance of V. radiata genotype T44 and wild species V. luteola. This was reflected in better RWC and Chl content in leaves, and membrane stability of leaf and root tissue in V. luteola and T44.


Severe Sepsis Secondary to Persistent Lysinibacillus sphaericus, Lysinibacillus fusiformis and Paenibacillus amylolyticus Bacteremia.
Lysinibacillus and Paenibacillus are pervasive bacteria rarely associated with human disease. Less sophisticated microbiology techniques may frequently incorrectly identify these genera as Bacillus spp., often regarded as environmental contamination. This report describes a case of severe sepsis due to persistent Lysinibacillus and Paenibacillus bacteremia, identified by matrix-assisted laser desorption and ionization time-of-flight mass spectroscopy and 16S rRNA gene sequencing.


Gender differences in the association between sleep duration and body mass index, percentage of body fat and visceral fat area among chinese adults: a cross-sectional study.
The relationship between sleep duration and anthropometric indices are still unclear. This study aimed to explore the association between sleep duration and body mass index (BMI), percentage of body fat (PBF) and visceral fat area (VFA) among Chinese adults, further to explore gender difference in it. We analyzed part of the baseline data of a cohort study among adult attendees at two health-screening centers in China. Sleep duration was self-reported and categorized into short (< 7 h/day), optimal (7-9 h/day) and long sleep (≥ 9 h/day). BMI, PBF and VFA were assessed by bioelectric impedance analysis. Demographic characteristics, chronic diseases and medication history, physical activity, smoking and alcohol drinking behaviors were measured by an investigator-administrated questionnaire. A total of 9059 adult participants (63.08% were females) were included in the analysis. The participants aged from 19 to 91 years with the mean age of 45.0 ± 14.6 years. Short sleep was independently associated with elevated odds of general obesity (defined using BMI) and visceral obesity (defined using VFA) among the total study population, and gender differences were observed in these associations. Among women, short sleep was associated with 62% increased odds of general obesity (OR = 1.62, 95% CI: 1.24-2.12) and 22% increased odds of visceral obesity (OR = 1.22, 95% CI: 1.02-1.45). Among men, long sleep duration was associated with 21% decreased odds of visceral obesity (OR = 0.79, 95% CI: 0.64-0.99). No association was observed between sleep duration and PBF in both sexes. Sleep duration was associated with increased odds of general and visceral obesity, and this association differed between men and women. No association was observed between sleep duration and PBF among either males or females.


Age-related differences in the degree of lipid peroxidation and state of antioxidant protection under the influence of alloxan.
Alloxan-induced hyperglycemia was accompanied by activation of lipid peroxidation processes with different degree of their completeness depending on the age of experimental animals. Lipid peroxidation in young animals mainly resulted in the formation of end-products, while in adult animals the initial stage of oxidation prevailed. Alloxan inhibited the enzymatic and nonenzymatic systems of antioxidant protection, which impaired adaptation and caused oxidative stress.


Inductions of superoxide dismutases in Escherichia coli under anaerobic conditions. Accumulation of an inactive form of the manganese enzyme.
Escherichia coli growing anaerobically respond to NO3- with a 3-fold induction of the iron-containing superoxide dismutase. Mutants lacking nitrate reductase do not show this response. Anaerobically grown cells also contain an inactive form of the manganese-containing superoxide dismutase (MnSOD) which can be activated by addition of Mn(II) salts in the presence of acidic guanidinium chloride, followed by dialysis against neutral buffer. Direct addition of Mn(II) to a neutral solution of the inactive MnSOD does not impart activity. This inactive MnSOD thus behaves as would the apoenzyme or the enzyme bearing a metal other than Mn(II) at its active sites. Terminal electron acceptors, such as NO3- or trimethylamine N-oxide, increase the amount of inactive MnSOD produced by anaerobic E. coli. Paraquat, which is itself ineffective in this regard, markedly augments the effect of these terminal electron acceptors. It appears that flow of electrons to sinks such as NO3- or trimethylamine N-oxide, facilitated by paraquat, is sufficient to elicit biosynthesis of the MnSOD protein and that O2- is not needed for this process. Yet, oxygenation and concomitant O2- production do appear important for the insertion of manganese into the growing MnSOD polypeptide, possibly because O-2 oxidizes Mn(II) to Mn(III), and the latter is the valence state most effective in combining with the apoenzyme.


Papillotomy Performance Scoring Scale--a pilot validation study focused on the cut axis.
No published Papillotomy Performance Scoring Scale exists. To develop such a scale and to apply it to stratify the quality of performance of recorded papillotomies. Expert biliary endoscopists were polled regarding their opinion of a 'perfect' biliary papillotomy and experience with complications in relation to the cut axis. Based on these responses a scoring scale encompassing two components - wire alignment and cut orientation, was proposed. This scoring scale was presented to experienced and trainee endoscopists, who scored recording of five biliary papillotomies. The mean final combined score was used for stratification. The experts' opinion of a 'perfect' biliary papillotomy is one cut along the axis of the distal bile duct and papilla. Their reported experience with complications occurring outside of the perfect axis validated their consensus. Application of the scoring scale stratified recorded papillotomies based on the mean final combined scores. These pilot data support the hypothesis that a scoring scale focused on the cut axis can be constructed based on expert opinion, experience and consensus. The possibility of stratification of mean final combined scores that are significantly different validates application of the scoring scale for assessment of papillotomy performance.


Imaging and guiding intervention for tricuspid valve disorders using 3-dimensional transesophageal echocardiography in pediatric and congenital heart disease.
In the pediatric and congenital heart disease (CHD) population, tricuspid valve (TV) disorders are complex due to the variable TV morphology, its sophisticated interaction with the right ventricle as well as associated congenital and acquired lesions. While surgery is the standard of care for TV dysfunction in this patient population, transcatheter treatment for bioprosthetic TV dysfunction has been performed successfully. Detailed and accurate anatomic assessment of the abnormal TV is essential in the preoperative/preprocedural planning. Three-dimensional transthoracic and 3D transesophageal echocardiography (3DTEE) provides added value to 2-dimensional imaging in the characterization of the TV to guide therapy and 3DTEE serves as an excellent tool for intraoperative assessment and procedural guidance of transcatheter treatment. Notwithstanding advances in imaging and therapy, the timing and indication for intervention for TV disorders in this population are not well defined. In this manuscript, we aim to review the available literature, provide our institutional experience with 3DTEE, and briefly discuss the perceived challenges and future directions in the assessment, surgical planning, and procedural guidance of (1) congenital TV malformations, (2) acquired TV dysfunction from transvenous pacing leads, or following cardiac surgeries, and (3) bioprosthetic TV dysfunction.


Determination of the surface tension of biological cells using the freezing front technique.
The freezing front technique for solid surface tension measurements was used to obtain the surface tensions of glutaraldehyde-fixed human erythrocytes, and fresh human lymphocytes and granulocytes in aqueous media. The results agree well with the values obtained by other methods and indicate that the freezing front technique is sufficiently sensitive to detect small differences (of the order of 0.1 ergs/cm2) in surface tension. This property, along with a number of applications for which it is uniquely suited, makes the freezing front technique an important new approach to the measurement of the surface tensions of biological cells and of small particles in general.


Small inhibitory cerebellar interneurons grow in a perpendicular orientation to granule cell neurites in culture.
When explants or reaggregates of small neurons from early postnatal mouse cerebella are plated on a mixture of laminin and poly-D-lysine, one observes small cells with an orientation of processes largely perpendicular to the direction of granule cell neurites after several days. These cells first have a bipolar morphology and then elaborate a rich dendritic arbor-like structure opposite a long, thin axon-like process. Several lines of evidence suggest that these cells are the small inhibitory interneurons of the cerebellar cortex: They take up GABA, express high levels of the embryonic form of N-CAM, do not express L1, the oligodendrocyte marker O4, or the glial marker vimentin, and display ultrastructural features reminiscent of stellate and/or basket cells in vivo. These observations suggest that the elaboration of directional positioning of small inhibitory interneurons can be studied in culture, thus offering the possibility to elucidate the cellular and molecular mechanisms underlying the orientation of particular neural cells with regard to others.


ppGpp negatively impacts ribosome assembly affecting growth and antimicrobial tolerance in Gram-positive bacteria.
The stringent response is a survival mechanism used by bacteria to deal with stress. It is coordinated by the nucleotides guanosine tetraphosphate and pentaphosphate [(p)ppGpp], which interact with target proteins to promote bacterial survival. Although this response has been well characterized in proteobacteria, very little is known about the effectors of this signaling system in Gram-positive species. Here, we report on the identification of seven target proteins for the stringent response nucleotides in the Gram-positive bacterium Staphylococcus aureus We demonstrate that the GTP synthesis enzymes HprT and Gmk bind with a high affinity, leading to an inhibition of GTP production. In addition, we identified five putative GTPases--RsgA, RbgA, Era, HflX, and ObgE--as (p)ppGpp target proteins. We show that RsgA, RbgA, Era, and HflX are functional GTPases and that their activity is promoted in the presence of ribosomes but strongly inhibited by the stringent response nucleotides. By characterizing the function of RsgA in vivo, we ascertain that this protein is involved in ribosome assembly, with an rsgA deletion strain, or a strain inactivated for GTPase activity, displaying decreased growth, a decrease in the amount of mature 70S ribosomes, and an increased level of tolerance to antimicrobials. We additionally demonstrate that the interaction of ppGpp with cellular GTPases is not unique to the staphylococci, as homologs from Bacillus subtilis and Enterococcus faecalis retain this ability. Taken together, this study reveals ribosome inactivation as a previously unidentified mechanism through which the stringent response functions in Gram-positive bacteria.


New derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors: Synthesis, biological testing and solubility in pharmaceutically relevant solvents.
The derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors have been synthesized. The different substituents were introduced into position 8 of the carboline fragment of the molecule: methyl-, methoxy-, fluorine- and chlorine-. Biological tests have shown that all the studied compounds can modulate glutamate-dependent uptake of calcium ions in rats' cerebral cortex synaptosomes. The shake-flask method was used to measure the solubility of the compounds in the buffer solution (pH 7.4), hexane and 1-octanol within the temperature interval of 293.15-313.15 К. All the derivatives have been found to have low solubility (not exceeding 8 ∙ 10-4 mole fractions) in the mentioned solvents. The effect of thermophysical and protolytic properties of the compounds on the solubility have been studied and the thermodynamic functions of compounds dissolution in the solvents used have been calculated.


Prokinetics and fundic relaxants in upper functional GI disorders.
Gastrointestinal prokinetics are a heterogeneous class of drugs that stimulate smooth muscle contractions to enhance gastric emptying and intestinal transit. Recently studied prokinetics include antidopaminergic agents (itopride), serotonergic agents (tegaserod and others), and motilin receptor agonists and ghrelin receptor agonists (mitemcinal, TZP101). It has been difficult to establish symptomatic benefit with prokinetic drugs in gastroparesis and functional dyspepsia, because of pathophysiological heterogeneity of the patient populations, a lack of well-accepted endpoints, and inconsistent relationships between changes in motor function and symptomatic outcome. Fundic relaxant drugs are a recent different approach to treatment of gastric motility disorders. Recently studied drugs include drugs under investigation including nitrates, serotonin reuptake blockers, 5-HT(1A) receptor agonists (buspirone and R137696), and muscarinc M1/M2 receptor antagonists (acotiamide or Z-338).


The influence of ants on the survival of mountain birches during an Oporinia autumnata (Lep., Geometridae) outbreak.
The present study reports the influence of ants on the survival of mountain birch (Betula pubescens ssp. tortuosa) during an Oporinia autumnata (Lep., Geometridae) outbreak. Undamaged "green islands" with a radius of 15-20 m were observed around Formica aquilonia mounds in a defoliated area in Finnish Lapland. The herbivore densities and grazing pressure were shown to be low within this radius. The foraging strategy of ants and their influence on birch growth are discussed.


Feasibility of definitive chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly patients with esophageal squamous cell carcinoma: A retrospective study.
This study was designed to retrospectively analyze the safety and efficacy of chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly patients with esophageal squamous cell carcinoma. Eligible patients were aged 76 years or older, had a histopathologic diagnosis of esophageal squamous cell carcinoma, and were treated at the Kitasato University Hospital between January 2010 and March 2016. Chemotherapy consisted of nedaplatin in an intravenous dose of 90 mg/m2 on day 1 and 5-fluorouracil in an intravenous dose of 800 mg/m2 on days 1 to 5, repeated every 4 weeks for 2 cycles. Radiation therapy consisted of 50.4 Gy in 28 fractions for thoracic tumors and 61.2 Gy for cervical tumors. Twenty-five patients were studied. Patient characteristics were as follows: median age 79 years (range, 76-85 years), clinical stage I/II/III/IV (7/8/8/2, respectively), and surgically resectable/unresectable (17/8, respectively). The completion rates of radiation therapy and chemoradiation therapy were 100% and 84%, respectively. Grade ≥3 acute toxicities included neutropenia (76%), leukopenia (72%), thrombocytopenia (32%), anemia (28%), anorexia (32%), oral mucositis (20%), febrile neutropenia (12%), and esophagitis (8%). Grade ≥3 late toxicities included esophageal stenosis (12%) and pleural effusion (4%). The complete response rate was 64%. In the median follow-up period of 18.9 months, the 1-year overall survival rate was 68%. Definitive chemoradiation therapy with nedaplatin and 5-fluorouracil may be a feasible treatment option for elderly patients with esophageal squamous cell carcinoma.


Physicochemical property changes of Dendrobium officinale leaf polysaccharide LDOP-A and it promotes GLP-1 secretion in NCI-H716 cells by simulated saliva-gastrointestinal digestion.
A polysaccharide LDOP-A with a molecular weight of 9.9 kDa was isolated and purified from Dendrobium officinale leaves by membrane separation, cellulose column, and dextran gel column. The Smith degradable products, methylation products, and nuclear magnetic resonance analysis showed that LDOP-A may be composed of →4)-Glc-(1→, →3,6)-Man-(1→, and →6)-Glc-(1→sugar residues. In vitro, simulated digestion assays showed that LDOP-A could be partially digested in the stomach and small intestine, and produced a large amount of acetic acid and butyric acid during colonic fermentation. Further cell experiment results illustrated that LDOP-A-I (LDOP-A digested by gastrointestinal tract) could induce glucagon-like peptide-1 (GLP-1) secretion in NCI-H716 cells without showing any cytotoxicity.


Triangular relationship among risky sexual behavior, addiction, and aggression: A systematic review.
Risky sexual behavior (RSB), addiction, and aggression are three important personal and social factors which influence each other. To overview the potential relationship among RSB, addiction, and aggression to conduct an interactive model for the pathology and management of human behavior. This review article was carried out by searching studies in PubMed, Medline, Web of Science, Ebsco, IEEE, Scopus, Springer, MagIran, and IranMedex databases from the year 1993 to 2013. The search terms were violence, aggression, drug abuse, substance abuse, illicit drug, psychoactive drug, intravenous drug users, addiction and high-risk sexual relationships, unprotected sex, high risk sexual behavior, and sexual risk-taking. In this study, forty-nine studies were accepted for further screening, and met all our inclusion criteria (in English or Persian, full text, and included the search terms). Forty-nine articles were included; 17 out of 26 studies showed a significant correlation between addiction and risky sexual behavior, 15 out of 19 articles indicated a statistically significant correlation between aggression and addiction, and 9 out of 10 articles reported significant correlation between aggression and risky sexual behavior. According to the results, the triangle hypothesis of sex, addiction, and aggression led to the definition of the relationship among the variables of the hypothetical triangle based on the reviewed studies; and the proposed dual and triple relationship based on the conducted literature review was confirmed. This is not a meta-analysis, and there is no analysis of publication bias.


Combined incubation of cadmium, docosahexaenoic and eicosapentaenoic acid results in increased uptake of cadmium and elevated docosapentaenoic acid content in hepatocytes in vitro.
Human hepatocellular cells Hep G2 were used to mimic and investigate the effect of the intake of cadmium (Cd(2+)) contaminated fish on cytotoxicity, fatty acid (FA) and phospholipid class composition. Cells were incubated with a combination of Cd(2+) and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) fish specific FA. We measured a significant increased proportion of EPA and DHA in the treated cells compared to the control line confirming the uptake. While doses of 25 μM DHA showed to be toxic to the cells, repeated short term incubations (2 h) at lower doses resulted in an increased uptake of DHA. The resarzurin assay, evaluating cell viability, showed a significant decrease in cell viability between Cd(2+) incubation time and, further, the pre-incubation with BSA-FA complex resulted in significantly increased cell viability. On the metabolic level, increased concentrations of EPA and DHA resulted in an increased proportion of docosapentaenoic acid (DPA) which indicated an increased metabolism. Also 24-h combined incubations of 5 μM Cd(2+) and EPA and DHA showed a significant increase DPA in the total lipid fraction of the cells. In addition, incubation with 5 μM Cd(2+) for 24 h also decreased the total cardiolipin (CL) fraction from the identified phospholipids. We confirmed that the applied FA were taken up by the cells. A combination of EPA, DHA and Cd(2+) influenced lysosomal integrity, cell viability and lipid metabolism in the cells. The most important finding is that DHA and EPA reduced the detrimental effect of Cd(2+) on cell viability. The exact effects and kinetics behind our observations still need further evaluation.


Transport and retention of engineered Al2O3, TiO2, and SiO2 nanoparticles through various sedimentary rocks.
Engineered aluminum oxide (Al2O3), titanium dioxide (TiO2), and silicon dioxide (SiO2) nanoparticles (NPs) are utilized in a broad range of applications; causing noticeable quantities of these materials to be released into the environment. Issues of how and where these particles are distributed into the subsurface aquatic environment remain as major challenges for those in environmental engineering. In this study, transport and retention of Al2O3, TiO2, and SiO2 NPs through various saturated porous media were investigated. Vertical columns were packed with quartz-sand, limestone, and dolomite grains. The NPs were introduced as a pulse suspended in aqueous solutions and breakthrough curves in the column outlet were generated using an ultraviolet-visible spectrophotometer. It was found that Al2O3 and TiO2 NPs are easily transported through limestone and dolomite porous media whereas NPs recoveries were achieved two times higher than those found in the quartz-sand. The highest and lowest SiO2-NPs recoveries were also achieved from the quartz-sand and limestone columns, respectively. The experimental results closely replicated the general trends predicted by the filtration and DLVO calculations. Overall, NPs mobility through a porous medium was found to be strongly dependent on NP surface charge, NP suspension stability against deposition, and porous medium surface charge and roughness.


Effect of coordinated therapeutic assays using C. parvum, interferon and arginine butyrate on spontaneous disease and survival of AKR mice.
AKR mice, known to develop spontaneous leukemia in almost 100% of cases, were studied throughout their life-span. Different treatments combining a potent immune stimulator, Corynebacterium parvum (CP), with interferon (IFN) and arginine butyrate were initiated at the 15th week of life. In a preliminary series of experiments, CP (200 micrograms), IFN (20,000 units) and butyrate 50 mM) were employed in a well-defined chronological order. In controls, the mean survival time (MST) was 35.17 +/- 1.67 weeks and the final survival rates was 0/50 mice for all experiments. Only CP associated with arginine butyrate significantly augmented the MST (42.5 +/- 3.66 weeks) and final survival rate (9/35 mice). In an adjusted set of experiments, reducing the IFN concentration to 10,000 and 5,000 units and that of butyrate to 6 mM greatly improved the results. The MST was substantially increased with the combinations of CP + IFN + butyrate (41.4 +/- 1.86 weeks), CP + IFN (42.73 +/- 3.29 weeks) and butyrate + IFN (41 +/- 2.34 weeks), as well as the final survival rates (8/15, 10/15 and 6/15 mice respectively). An important finding was that when CP and IFN were used separately, they were ineffective.


Improvement of door-to-imaging time in acute stroke patients by implementation of an all-points alarm.
In patients with acute ischemic stroke, thrombolysis offers an opportunity to effectively reduce disability and dependency. The success of this treatment is time-dependent. The crucial diagnostic step before initiation of treatment is cerebral imaging. With the aim of reducing in-hospital delays, our hospital's interdisciplinary stroke management group implemented an all-points alarm to improve in-hospital time delay (the period between arrival to the emergency department and performance of cerebral imaging). The alarm simultaneously alerted all involved staff (from the neurologist to in-hospital transport) to the arrival of a patient potentially eligible for thrombolysis. Time delay, sociodemographic, and clinical data were assessed prospectively at 4 months before and 8 months after alarm implementation. Data were examined by analysis of covariance for both the intention-to-treat and per-protocol groups. During the assessment, 689 patients with symptoms compatible with stroke arrived at our hospital. Among those, 111 patients (16%) were eligible for thrombolysis (median age, 71 years; median National Institutes of Health Stroke Scale score, 11; 44% female). Patient characteristics (ie, age, sex, insurance status, National Institutes of Health Stroke Scale score, cardiovascular risk factors, and prehospital delay) did not differ significantly before (n = 34) and after (n = 77) alarm implementation. The median "door-to-imaging time" for patients eligible for thrombolysis was significantly reduced, from 54 minutes before implementation of the alarm to 35 minutes after implementation. Adjusted analysis of covariance demonstrated a significant influence of the intervention (P = .001) on differences in time delay. The proportion of ischemic stroke patients receiving thrombolysis rose from 42% to 66% (P = .04). The per-protocol analysis confirmed these results. The implementation of an all-points alarm can result in significant reduction of the time needed for in-hospital pathways for acute stroke patients.


The development of prostate cancer despite late onset androgen deficiency.
Androgen withdrawal causes the regression of prostate cancer and is used in therapy, but the role of androgens in the development of prostate cancer is uncertain. We present a case of prostate cancer diagnosed in a man who had been clinically androgen deficient for some years. This case and reviewed literature suggest that while early androgen exposure may be important in the prostatic carcinogenesis, late onset androgen deficiency is not protective. Thus, hypogonadal men considering androgen replacement therapy need to be adequately counseled, screened for prostate cancer and followed closely during treatment.


Role of Perineuronal nets in the cerebellar cortex in cocaine-induced conditioned preference, extinction, and reinstatement.
Perineuronal nets (PNNs) are cartilage-like structures of extracellular matrix molecules that enwrap in a net-like manner the cell-body and proximal dendrites of special subsets of neurons. PNNs stabilize their incoming connections and restrict plasticity. Consequently, they have been proposed as a candidate mechanism for drug-induced learning and memory. In the cerebellum, PNNs surround Golgi inhibitory interneurons and both inhibitory and excitatory neurons in the deep cerebellar nuclei (DCN). Previous studies from the lab showed that cocaine-induced conditioned memory increased PNN expression in the granule cell layer of the posterior vermis. The present research aimed to investigate the role of cerebellar PNNs in cocaine-induced conditioned preference. For this purpose, we use the enzyme chondroitinase ABC (ChABC) to digest PNNs at different time points of the learning process to ascertain whether their removal can affect drug-induced memory. Our results show that PNN digestion using ChABC in the posterior vermis (Lobule VIII) did not affect the acquisition of cocaine-induced conditioned preference. However, the removal of PNNs in Lobule VIII -but not in the DCN- disrupted short-term memory of conditioned preference. Moreover, although PNN digestion facilitated the formation of extinction, reinstatement of cocaine-induced conditioned preference was encouraged under PNN digestion. The present findings suggests that PNNs around Golgi interneurons are needed to maintain cocaine-induced Pavlovian memory but also to stabilize extinction memory. Conversely, PNN degradation within the DCN did not affect stability of cocaine-induced memories. Therefore, degradation of PNNs in the vermis might be used as a promising tool to manipulate drug-induced memory.


Correction to: Phases and Mechanisms of Embryonic Cardiomyocyte Proliferation and Ventricular Wall Morphogenesis.
The original version of this article unfortunately contained a mistake. In reviewing the phenotype associated with Mapk14 (p38alpha MAPK) mutation as evaluated by Adams et al. (2000) using tetraploid aggregation chimeric embryos, the authors mistakenly stated that rescue of embryo lethality was short-lived and that embryos died two days later of non-placenta-related causes. In fact, as reported by Adams et al. (2000), when the placental defect of global null embryos was rescued, p38alpha(-/-) embryos developed to term and were normal in appearance. The authors apologize for the error.


Differences in clinical characteristics of head injuries to snowboarders by skill level.
Many reports have compared head injuries between snowboarding and skiing. However, detailed studies comparing snowboarding head injuries between beginners and intermediates/experts have been lacking. The authors investigated differences in clinical characteristics of head injuries to snowboarders between beginners (group B) and intermediates/experts (group IE). Descriptive epidemiology study. The study population included 2367 patients treated at Saito Memorial Hospital and Yuzawa Community Health Medical Center, Niigata Prefecture, Japan, during 9 seasons from 1999-2000 to 2007-2008. Group B comprised 959 patients (mean age, 23.0 years; 52% males). Group IE comprised 1408 patients (mean age, 24.8 years; 72% males). Accidents in group B predominantly occurred as falls on gentle slopes (37%) and intermediate slopes (33%), whereas accidents in group IE occurred mostly during jumping (48%). The impact point on the head was predominantly occipital in both groups, but group IE showed a significantly higher frequency of trauma to the frontal region. The ratio of neurologic abnormalities was significantly higher in group IE. However, the ratio of surgical cases was significantly higher in group B (n = 10, 1.04%) than in group IE (n = 5, 0.36%). More acute subdural hematomas were seen in group B, but more fractures, contusions, and acute epidural hematomas were seen in group IE. Four moderate disabilities, 2 comatose patients, and 2 deaths were seen in group B, and 1 moderate disability, 2 severe disabilities, and 1 death were seen in group IE during this study. The data suggest significant differences in clinical states between beginners and intermediates/experts. Preventive methods for severe head injuries among snowboarders need to be devised based on differences in skill levels.


Action of substance P and an SP-hexapeptide analogue on avoidance learning in rats.
The effects of Substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2) and of a SP hexapeptide analogue (SP-A) (Lys-Phe-Ile-Gly-Leu-MetNH2) on active avoidance learning were investigated in spontaneously hypertensive rats (SHR) and Wistar rats. Active avoidance learning was slower in SHR than in Wistar rats. SP-A "normalized" the slower active avoidance learning in SHR, whereas SP did not. Some possible causes of this difference as well as the mechanism of the normalizing effect of SP-A are discussed.


Seroprevalence of SARS-CoV-2 antibodies among blood donors in Québec: an update from a serial cross-sectional study.
We previously estimated the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies following the first pandemic wave at 2.23% in Québec, Canada. Following the much bigger second wave in fall 2020 and early 2021, we estimated the seroprevalence of anti-SARS-CoV-2 in Québec during the first months of 2021. Blood samples from regular, asymptomatic (for ≥ 14 days) donors were collected between January 25, 2021 and March 11, 2021. Anti-SARS-CoV-2 seropositivity was assessed using an enzyme-linked immunosorbent assay that captures antibodies directed against the receptor binding domain of the SARS-CoV-2 spike (and hence cannot discriminate between infection- and vaccine-induced seropositivity). Seroprevalence estimates were adjusted for regional distribution, age, and sex. Samples from 7924 eligible donors were analyzed, including 620 (7.8%) vaccinated donors and 7046 (88.9%) unvaccinated donors (vaccination status unknown for 258 (3.3%) donors). Overall, median age was 51 years; 46.4% of donors were female. The adjusted seroprevalence was 10.5% (95% CI = 9.7-11.3) in the unvaccinated population and 14.7% (95% CI = 13.8-15.6) in the overall population. Seroprevalence gradually decreased with age and was higher among donors who self-identified as having a racial/ethnic background other than white, both in the overall and in the unvaccinated populations. The seroprevalence of SARS-CoV-2 antibodies significantly increased in Québec since spring 2020, with younger persons and ethnic minorities being disproportionately affected. When compared with the cumulative incidence rate reported by public health authorities (i.e., 3.3% as of March 11, 2021), these results suggest that a substantial proportion of infections remain undetected despite improvements in access to COVID-19 testing.


Different susceptibility of spores and hyphae of Trichophyton rubrum to methylene blue mediated photodynamic treatment in vitro.
In recent years, methylene blue mediated-photodynamic therapy (MB-PDT) has proved to be an effective inhibitor to a variety of microorganisms, including Trichophyton rubrum, the most common dermatophyte worldwide. However, previous studies mainly focused on the spore form of T rubrum, but rarely on its hyphal form, although the latter is the main pathogenic form of T rubrum in vivo. To investigate the inhibitory effect of MB-PDT on T rubrum in different growth phases in vitro. The suspensions of spores and hyphae obtained from T rubrum (ATCC28188) were prepared, respectively, incubated with MB solution (0.15-40 μg/mL) and irradiated with 635 nm red light. Varied light energy and MB concentration were used. The specimen in the absence of light exposure or/and MB served as controls. MIC determination, colony counts and MTT assay were employed to evaluate the antifungal effect of MB-PDT. The MICs of MB-PDT for hyphae and spores of T. rubrum were 6.300 ± 1.072 μg/mL and 1.984 ± 1.072 μg/mL, respectively, at a fixed light dose of 60 J/cm2 . CFU counts gave the minimum critical combinations of MB concentration and light dose to achieve 100% inhibitory rate. For hyphae, they were 5 μg/mL + 100 J/cm2 or 10 μg/mL + 60 J/cm2 . For spores, they were 1.25 μg/mL + 40 J/cm2 or 5 μg/mL + 20 J/cm2 . The outcomes of MTT assay were consistent with those of CFU counts, but less accurate. MB-PDT is a potent inhibitor to both spores and hyphae of T. rubrum in vitro, and the spores are more sensitive to it. Its antifungal efficacy is positively correlated with the concentration of MB and light dose.


Supramolecular chemistry enables vat photopolymerization 3D printing of novel water-soluble tablets.
Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate monomer, [2-(acryloyloxy)ethyl]trimethylammonium chloride (TMAEA), and a co-monomer, 1-vinyl-2-pyrrolidone (NVP), were prepared to produce paracetamol-loaded printlets. 1H NMR spectroscopy analysis confirmed the integration of TMAEA and NVP in the polymer, and residual TMAEA monomers were found to be present only in trace amounts (0.71 - 1.37 %w/w). The apparent molecular mass of the photopolymerised polymer was found to exceed 300,000 Da with hydrodynamic radii of 15 - 20 nm, estimated based on 1H DOSY NMR measurements The loaded paracetamol was completely released from the printlets between 45 minutes to 5 hours. In vivo single-dose acute toxicity studies in rats suggest that the printlets did not cause any tissue damage. The findings reported in this study represent a significant step towards the adoption of vat photopolymerization-based 3DP to produce personalised medicines.


Genes from Carboxypeptidase A, glutathione S-transferase, and cytochrome b families were found involved in lead transport in insect Musca domestica.
Lead (Pb) is a typical toxic contamination source all over the world. In this research, larvae of the housefly (Musca domestica) were fed a Pb-contaminated diet at different Pb doses of 0, 20 and 5000 mg/kg. RNA sequencing was used to identify genes that were differentially expressed in relation to lead transport or detoxification. RNA interference (RNAi) was carried on 12 candidate genes. The results showed that three luminal pH regions of mid-gut were at pH values of 6.33, 3.10, and 7.80. With increasing Pb concentration, the pH of the middle mid-gut decreased by one unit. The expression levels of carboxypeptidase A (CPA1), glutathione S-transferase (GST), and cytochrome b (Cyt b) were linked to Pb treatments, particularly high Pb concentration of 5000 mg/kg. RNAi-mediated down expression of CPA1, GST2, and CYTb-c1 resulted in low Pb accumulation in the larvae of 5000 mg/kg Pb group. These proteins played key roles in Pb transport and detoxification in M. domestica larvae.


Effect of in vitro administration of LH, prolactin separately, and LH and prolactin in mixture on cultured Leydig cells from mouse testes: II. Age-related alterations of androgen secretion.
The effect of gonadotropic hormones on androgen level in media of cultured Leydig cells isolated from mouse testes of various age was investigated. Changes of androgen level were connected with the age of mice. The highest secretory level of androgen was found in cultures of Leydig cells from mature 60 day old animals, which then decreased in 7 month old mice. Stimulating effect of LH and PRL on hormonal secretion by cultured Leydig cells was observed.


[History of a vaccination of proximity].
The Grand-Est region was one of the first affected by the severe acute respiratory syndrome coronavirus 2 in March 2020. The liberal nurses were in the first line to bring their competences to the service of the patients. Motivated and involved, they took the initiative to open a vaccination center in January 2021 and demonstrated the added value of working together. Sharing of experience by a private nurse in this region.


N-acetylaspartylglutamate (NAAG) and glutamate carboxypeptidase II: An abundant peptide neurotransmitter-enzyme system with multiple clinical applications.
N-Acetylaspartylglutamate (NAAG) is the third most prevalent neurotransmitter in the mammalian nervous system, yet its therapeutic potential is only now being fully recognized. Drugs that inhibit the inactivation of NAAG by glutamate carboxypeptidase II (GCPII) increase its extracellular concentration and its activation of its receptor, mGluR3. These drugs warrant attention, as they are effective in animal models of several clinical disorders including stroke, traumatic brain injury and schizophrenia. In inflammatory and neuropathic pain studies, GCPII inhibitors moderated both the primary and secondary pain responses when given systemically, locally or in brain regions associated with the pain perception pathway. The finding that GCPII inhibition also moderated the motor and cognitive effects of ethanol intoxication led to the discovery of their procognitive efficacy in long-term memory tests in control mice and in short-term memory in a mouse model of Alzheimer's disease. NAAG and GCPII inhibitors respectively reduce cocaine self-administration and the rewarding effects of a synthetic stimulant. Most recently, GCPII inhibition also has been reported to be efficacious in a model of inflammatory bowel disease. GCPII was first discovered as a protein expressed by and released from metastatic prostate cells where it is known as prostate specific membrane antigen (PSMA). GCPII inhibitors with high affinity for this protein have been developed as prostate imaging and radiochemical therapies for prostate cancer. Taken together, these data militate in favor of the development and application of GCPII inhibitors in more advanced preclinical research as a prelude to clinical trials.


Small intestine submucosa as a corporal body graft in the repair of severe chordee.
We describe our experience with single and 4-layer small intestine submucosa in the repair of proximal hypospadias and severe chordee. Between 2000 and 2004, 15 boys with proximal hypospadias and/or severe ventral chordee underwent SIS grafting to correct the curvature. Single layer and 4-layer small intestine submucosa were used for corporal grafting. Reassessment was performed by artificial erection at the time of the 2nd-stage reconstruction or at follow-up visit. 1st-stage chordee repair with corporal body incision and graft coverage was performed on 15 patients between June 2000 and March 2004. Single layer SIS was used in 6 cases and 4-layer was used in 9 cases. Twelve of the 15 boys underwent a planned 2nd-stage urethroplasty. Median age at 1st-stage repair was 12 months. A 15-month-old boy underwent single stage chordee correction and penoscrotal hypospadias repair. Two boys without hypospadias underwent chordee correction with SIS. There were no complications related to the use of SIS for chordee repair. Median age of the 12 boys at 2nd-stage hypospadias repair was 24 months. At the time of the 2nd-stage procedures, the graft site did not show more significant scarring than has been our experience in 2-stage procedures performed without SIS. No patients had recurrence of chordee with follow up ranging from 2 to 75 months. Our outcomes suggest that small intestine submucosa is safe and effective for corporal body grafting in the correction of severe chordee, especially in the setting of a multistage hypospadias and chordee repair.


Effects of the terbuthylazine metabolite terbuthylazine-desethyl on common carp embryos and larvae.
Toxicity of terbuthylazine-desethyl to embryos and larvae of common carp (Cyprinus carpio) was assessed. Based on mortality, the lethal concentration of terbuthylazine-desethyl was estimated to be 31days LC50=441.6μg/L. Carp exposed to terbuthylazine-desethyl at 1800μg/L exhibited lower weight and length at 7days of exposure compared to the control group. By day 20, carp exposed to 900μg/L terbuthylazine-desethyl showed lower weight and length compared to control group. Terbuthylazine-desethyl in concentrations (180, 900, and 1800μg/L) caused delay in ontogenetic development. Total superoxide dismutase activity was significantly lower in all exposed groups. Exposure to 180 and 900μg/L terbuthylazine-desethyl was associated with alteration of the caudal kidney tubular system including peritubular dilatation detachment of epithelial cells from the basal lamina, and focal autolytic disintegration of the tubular epithelia. Chronic terbuthylazine-desethyl exposure affected survival, growth, ontogenetic development, and the antioxidant system and caused pathological changes to the caudal kidney.


The incidence of shopping cart-related injuries in the United States, 2002--2006.
Shopping cart-related injuries are an important cause of childhood injury in the United States (US). To date, few studies have investigated the epidemiology and incidence of these injuries. The National Electronic Injury Surveillance System was utilized to identify shopping cart-related injuries from 2002 to 2006. Injury rates were calculated using the 2006 US population estimates for gender (male and female), age group (<5 years, 5-9 years, and 10-14 years), and race (White, Black, and other). The overall injury rate was 37.8 per 100,000 person years (PY). Injury rates did not differ significantly by gender or race. However, injury rates decreased markedly with increasing age and were highest among children <5 years of age (97.8 per 100,000 PY), followed by children 5-9 years (13.9 per 100,000 PY), and children 10-14 years (2.9 per 100,000 PY). Shopping carts continue to be an important cause of injuries among children. Directing safety awareness toward those families with children <5 years, mandatory safety standards, and modification of shopping cart design may decrease injury rates.


Protection Efficacy of the Infectious Laryngotracheitis (ILT) Serva CEO Vaccine Strain in Broiler Chickens Under Different Vaccination Coverage Conditions.
Mass vaccination against infectious laryngotracheitis virus (ILTV) in drinking water can result in variable initial vaccine take. Partial initial vaccine coverage of 20% with an Australian ILT vaccine (A20) previously resulted in significant protection against virulent ILTV challenge. This follow-up study used the international Serva ILT vaccine strain in a factorial design testing four levels of vaccination coverage (0%, 10%, 20%, or 100% of chicks eye-drop vaccinated with the live vaccine at 7 days of age) and three levels of ILTV challenge (no challenge or challenge at 7 or 21 days postvaccination [DPV]). The increase in ILTV load in choanal cleft swabs detected by qPCR after challenge was significantly reduced by 20% and 100% but not by 10% vaccination coverage. Vaccination reduced weight gain in unchallenged birds. Daily weight gain of birds was not affected by ILTV challenge at 7 DPV in any group, but following challenge at 21 DPV, it was significantly reduced in unvaccinated and 10% vaccinated groups relative to 20% and 100% vaccinated groups. Vaccination of 20% of the chickens provided substantial but incomplete protection (protective index range 44%-70%) against the severity of clinical signs and mortality following challenge while 10% vaccination coverage provided limited or no protection. Clinical signs were more severe and appeared earlier following challenge at 21 DPV than at 7 DPV. Within the vaccination treatments, eye-drop-vaccinated birds were better protected than their in-contact cohorts. In conclusion, partial vaccination of 20%, but not 10% of chickens, induced substantial protection against subsequent challenge. However, the attendant risks of reduced protection against early challenge and the possible reversion to virulence of vaccine virus when transmitted to unvaccinated chickens make it essential that 100% initial vaccine take be the goal of mass vaccination programs.


Effects of the mini-clinical evaluation exercise teaching mode based on nurse-faculty cooperation in Fundamentals of Nursing course: A quasi-experimental study.
This study aimed to explore the effects of the mini-clinical evaluation exercise (mini-CEX) teaching model based on nurse-faculty collaboration in Fundamentals of Nursing course. A quasi-experimental design was conducted. A total of 111 nursing students of two parallel classes were recruited from a nursing college in Guilin, China from February to December 2022, and allocated to the intervention group (n = 56) and control group (n = 55). The intervention group received a mini-CEX teaching model based on nurse-faculty collaboration, the teaching-learning process included scenario creation (10 min), inquiry-based learning (30 min), case report (30 min), scenario simulation exercise (40 min), and effectiveness evaluation (10 min). While the control group received conventional teaching method. All students were invited to complete the College Classroom Climate Assessment Scale (CCCA) and the Chinese version of the Competency Inventory for Nursing Students (CINS-CV) before and after the intervention. Course achievement of students was evaluated. After the intervention, the intervention group was asked an open-ended question to explore the difficulties or challenges they had encountered. After intervention, the CCCA score (208.36 ± 23.25 vs. 190.60 ± 28.83), CINS-CV score(106.95 ± 14.48 vs. 99.55 ± 14.60), the oretical exam score (83.01 ± 4.27 vs. 79.75 ± 5.45), and scenario simulation exam score (89.23 ± 3.17 vs. 81.42 ± 7.19) of intervention group were higher than those of the control group (P<0.01). The open-ended questionnaire survey revealed that the difficulties or challenges faced by the intervention group were mainly related to case analysis, group cooperation, learning material acquisition, and teacher guidance. Applying the mini-CEX teaching model based on nurse-faculty collaboration could cultivate nursing students' competency, build a positive classroom climate, and improve the course achievement of students.


The role of hydration in an enzyme reaction.
The aim of the work was to elucidate the role of water in the reaction between acetylcholinesterase (acetylcholine hydrolase, EC 184.108.40.206) and methanesulfonyl fluoride, accelerated by accelerators. The reaction between the enzyme and methanesulfonyl fluoride in the presence of individual monovalent cations of the Hofmeister series was investigated. The results obtained were analyzed in comparison with the effect of methanesulfonylation of the specific accelerators tetramethylammonium and tetraethylammonium under various experimental conditions. The monovalent cations of the Hofmeister series accelerate the reaction. Their effect--as well as that of specific accelerators--significantly correlates with the effect of these agents on the structure of water. These findings, together with others, led to the following model of the role of hydration water in acylation of acetylcholinesterase. The accelerator, which may also be the cationic head of the natural substrate, binds to the anionic site of the enzyme and reduces the hydration of the nucleophilic serine -OH in the esteratic site, thus enhancing the nucleophilicity of -OH. This results in an improvement of the binding between the acylating agent and the esteratic site of acetylcholinesterase.


Idiopathic pulmonary fibrosis: diagnosis and epidemiology.
In 2000, the American Thoracic Society and European Respiratory Society published the first consensus statement providing guidelines on the diagnosis and treatment of idiopathic pulmonary fibrosis (IPF). This statement presented, for the first time, diagnostic criteria for IPF and recommendations for treatment. Results from several studies have reshaped the thinking on IPF, and as a result, the guidelines have been recently revised using an evidence-based approach. Meanwhile, several epidemiologic studies have yielded data that identify potential risk factors and that better define the societal burden of IPF. This article summarizes the approach to diagnosing IPF and reviews epidemiologic data on IPF.


speedingCARs: accelerating the engineering of CAR T cells by signaling domain shuffling and single-cell sequencing.
Chimeric antigen receptors (CARs) consist of an antigen-binding region fused to intracellular signaling domains, enabling customized T cell responses against targets. Despite their major role in T cell activation, effector function and persistence, only a small set of immune signaling domains have been explored. Here we present speedingCARs, an integrated method for engineering CAR T cells via signaling domain shuffling and pooled functional screening. Leveraging the inherent modularity of natural signaling domains, we generate a library of 180 unique CAR variants genomically integrated into primary human T cells by CRISPR-Cas9. In vitro tumor cell co-culture, followed by single-cell RNA sequencing (scRNA-seq) and single-cell CAR sequencing (scCAR-seq), enables high-throughput screening for identifying several variants with tumor killing properties and T cell phenotypes markedly different from standard CARs. Mapping of the CAR scRNA-seq data onto that of tumor infiltrating lymphocytes further helps guide the selection of variants. These results thus help expand the CAR signaling domain combination space, and supports speedingCARs as a tool for the engineering of CARs for potential therapeutic development.


A Longitudinal, Population-Level, Big-Data Study of Helicobacter pylori-Related Disease across Western Australia.
Helicobacter pylori, responsible for chronic ulcers and most stomach cancers, infects half of the world's population. The Urea Breath Test (UBT) is one of the most accurate and reliable non-invasive methods for diagnosing active H. pylori infection. The objective was to use longitudinal, population-wide UBT data for Western Australia to look for H. pylori-related disease patterns. We collected 95,713 UBT results from 77,552 individuals for the years 2010-2015, likely representing all of the UBT samples analysed in Western Australia. Data collected also included sex, age and residential postcode. Other data reported here were inferred via a comparison with the 2011 Australian Census using a specially written Python program. While women appear to have more H. pylori-related disease than men, there is no difference in the disease rates once women's higher rates of presentation for testing are taken into account. On the other hand, while the treatment strategy for H. pylori infection is generally very effective in Western Australia, failure of the first-line treatment is significantly more common in women than men. Migrants and Aboriginal Australians have elevated rates of H. pylori-related disease, while the rate for non-Aboriginal Australian-born West Australians is very low. However, no significant associations were found with other socio-economic indicators. We conclude that, for some people, H. pylori-related disease is not a solved problem.


The structural and functional consequences of melatonin and serotonin on human αB-crystallin and their dual role in the eye lens transparency.
Crystallins are the major soluble lens proteins, and α-crystallin, the most important protective protein of the eye lens, has two subunits (αA and αB) with chaperone activity. αB-crystallin (αB-Cry) with a relatively wide tissue distribution has an innate ability to interact effectively with the misfolded proteins, preventing their aggregation. Melatonin and serotonin have also been identified in relatively high concentrations in the lenticular tissues. This study investigated the effect of these naturally occurring compounds and medications on the structure, oligomerization, aggregation, and chaperone-like activity of human αB-Cry. Various spectroscopic methods, dynamic light scattering (DLS), differential scanning calorimetry (DSC), and molecular docking have been used for this purpose. Based on our results, melatonin indicates an inhibitory effect on the aggregation of human αB-Cry without altering its chaperone-like activity. However, serotonin decreases αB-Cry oligomeric size distribution by creating hydrogen bonds, decreases its chaperone-like activity, and at high concentrations increases protein aggregation.


Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis.
Intravesical instillations of hyaluronic acid (HA) and chondroitin sulfate (CS) may lead to regeneration of the damaged glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome (IC/BPS). Twenty-two patients with IC/BPS received intravesical instillations (40 ml) of sodium HA 1.6% and CS 2.0% in 0.9% saline solution (IALURIL, IBSA) once weekly for 8 weeks, then once every 2 weeks for the next 6 months. The score for urgency was reduced from 6.5 to 3.6 (p = 0.0001), with a reduction in pain scores from an average of 5.6 to 3.2 (p = 0.0001). The average urine volume increased from 129.7 to 162 ml (p < 0.0001), with a reduction in the number of voids in 24 h, from 14 to 11.6 (p < 0.0001). The IC Symptom and Problem Index decreased from 25.7 to 20.3 (p < 0.0001), and the Pain Urgency Frequency score, from 18.7 to 12.8 (p < 0.0001). The treatment appeared to be effective and well tolerated in IC/BPS in this initial experience.


Associations of weight and body composition at birth with body composition and cardiometabolic markers in children aged 10 y: the Ethiopian infant anthropometry and body composition birth cohort study.
Although birth weight (BW) has been associated with later cardiovascular disease and type 2 diabetes, the role of birth fat mass (BFM) and birth fat-free mass (BFFM) on cardiometabolic health is unclear. To examine associations of BW, BFM, and BFFM with later anthropometry, body composition, abdominal fat, and cardiometabolic markers. Birth cohort data on standardized exposure variables (BW, BFM, and BFFM) and follow-up information at age 10 y on anthropometry, body composition, abdominal fat, and cardiometabolic markers were included. A linear regression analysis was used to assess associations of exposures with outcome variables, adjusting for maternal and child characteristics at birth and current body size in separate models. Among 353 children, mean (SD) age was 9.8 (1.0) y, and 51.5% were boys. In the fully adjusted model, 1-SD higher BW and BFFM were associated with 0.81 cm (95% CI: 0.21, 1.41 cm) and 1.25 cm (95% CI: 0.64, 1.85 cm) greater height at 10 y, respectively. The 1-SD higher BW and BFM were associated with 0.32 kg/m2 (95% CI: 0.14, 0.51 kg/m2) and 0.42 kg/m2 (95% CI: 0.25, 0.59 kg/m2) greater fat mass index at 10 y, respectively. In addition, 1-SD higher BW and BFFM were associated with 0.22 kg/m2 (95% CI: 0.09, 0.34 kg/m2) greater FFM index, whereas a 1-SD greater BFM was associated with a 0.05 cm greater subcutaneous adipose tissue (95% CI: 0.01, 0.11 cm). Furthermore, 1-SD higher BW and BFFM were associated with 10.3% (95% CI: 1.4%, 20.0%) and 8.3% (95% CI: -0.5%, 17.9%) greater insulin, respectively. Similarly, 1-SD higher BW and BFFM were associated with 10.0% (95% CI: 0.9%, 20.0%) and 8.5% (95% CI: -0.6%, 18.5%) greater homeostasis model assessment of insulin resistance, respectively. BW and BFFM rather than BFM are predictors of height and FFM index at 10 y. Children with higher BW and BFFM showed higher insulin concentrations and homeostasis model assessment of insulin resistance at 10 y of age. This trial was registered at ISRCTN as ISRCTN46718296.


A simple and fast system for cloning influenza A virus gene segments into pHW2000- and pCAGGS-based vectors.
The reverse genetics system for influenza A viruses described by Hoffmann et al. (Virology 267(2):310-317, 2000, Proc Natl Acad Sci USA 97(11):6108-6113, 2000, ArchVirol 146(12):2275-2289, 2001) is one of the most commonly used. However, this cloning strategy is rather time-consuming and lacks a selection marker to identify positive clones carrying viral genes. We report here the optimization of the cloning protocol of viral genes into pHW2000 by (i) introducing a selection marker and (ii) simplifying the cloning strategy: now the cloning reaction takes only a few minutes and, in addition, is independent of internal restriction sites for BsmBI/Esp3I, BsaI or AarI. In order to accelerate the whole cloning protocol for the generation of recombinant viruses, we first introduced a lacP/Z-element (lac-promoter/lacZα-fragment) between the two BsmBI sites of pHW2000 to allow selection of positive clones by blue/white screening. Then we optimized the digestion/ligation-protocol: In our system, enzymatic digestion and ligation of PCR products into the vector is performed in a single "one-tube" reaction. Due to this strategy, time and material consumption is reduced by a great amount, as vector and cDNA do not have to be digested and purified prior to the ligation. Therefore, this one-tube reaction yields positive clones with high efficiency and fidelity, again saving time and material, which were formerly required for screening and analyzing clones. Finally, to add more versatility to the system, we also created an entry vector based on TA-cloning. This entry vector provides several advantages: inserted genes can easily be modified, e.g., by site-directed mutagenesis or tag attachment, and then subcloned into pHW2000 or other plasmids containing a similar cloning site (e.g., our modified pCAGGS-Esp-blue) by the same rapid and reliable one-tube reaction protocol described here. In fact, the presented protocol is suitable to be adapted to other reverse genetics systems (e.g., those for members of the order Mononegavirales or the family Bunyaviridae) or cloning of genes in general.


Analysis of wines, grape juices and cranberry juices forAlternaria toxins.
Sixty six samples of red and white wine from Ontario (VQA), British Columbia (VQA), Québec ("vins artisanaux"), imported wines (from Italy, South America and USA) and Canadian and US grape and cranberry juices were analysed for theAlternaria mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME). After cleanup on aminopropyl SPE columns, AOH and AME were initially determined by reversed phase LC with UV detection. Positive sample extracts were re-analysed by LC-tandem negative ion electrospray mass spectrometry (MS/MS) in multiple reaction mode. Overall mean method recoveries measured by LC-UV were 93% for AOH and 81% for AME. Limits of detection in wine (and juice) by LC-UV for AOH were 0.8 (0.4) ng/ml and for AME were 0.5 (0.4) ng/ml; they were below 0.01 ng/ml by LC-MS/MS. As determined by LC-MS/MS, AOH was found in 13/17 Canadian red wines at levels of 0.03 to 5.02 ng/ml and in 7/7 imported red wines at 0.27-19.4 ng/ml, usually accompanied by lower concentrations of AME. Red grape juices (5 positive/10 samples) contained only sub ng/ml levels of AOH or AME except for one sample (39 ng AME/ml). White wines (3/23 samples), white grape juices (0/4 samples) and cranberry juices (1/5 samples) contained little AOH/AME (≤1.5 ng/ml).


Signal complexity and modular organization of the courtship behaviours of two sibling species of wolf spiders (Araneae: Lycosidae).
In this study, we compare the courtship behaviours of Pardosa proxima and P. vlijmi, two species of wolf spiders up to now regarded as "ethospecies", by means of motion analysis methodologies. In particular, we investigate the features of the signals, aiming at understanding the evolution of the courtship and its role in species delimitation and speciation processes. In our model, we highlight a modular structure of the behaviours and the presence of recurring units and phases. According to other similar cases concerning animal communication, we observed one highly variable and one stereotyped phase for both species. The stereotyped phase is here regarded as a signal related to species identity or an honest signal linked directly to the quality of the signaler. On the contrary, the variable phase aims to facilitate signal detection and assessment by the female reducing choice costs or errors. Variable phases include cues arisen from Fisherian runaway selection, female sensory exploitation and remaining of past selections.


National occupational research agenda (NORA) future directions in occupational musculoskeletal disorder health research.
Musculoskeletal disorders are among the most costly health care problems facing society today. The scientific literature has indicated that psychosocial factors, individual factors, workplace physical requirements, and workplace organizational factors have been associated with risk. Since musculoskeletal risk is multi-dimensional, the magnitude of risk attributable to various factors can be of importance to scientists and policy makers in designing countermeasures to reduce injury incidence. Traditionally, the disciplines of biomechanics, physiology, and psychophysics have dominated the body of knowledge that has defined exposure limitations to work. However, recent research has explored the association of psychosocial and work organization factors with musculoskeletal problems. Advances have been made to better quantify the levels of occupational exposure by improved exposure metrics, quantification of three-dimensional loads experienced by certain joints (e.g. the spine), identification of tissue tolerance limits and tissue response to mechanical stresses, and the impact of psychosocial stresses. However, efforts to quantitatively link epidemiological, biomechanical loading, soft tissue tolerance, and psychosocial studies should be pursued to establish a better understanding of the pathways of injury and resultant preventive strategies. Although we are beginning to understand how the major risk factors influence the load-tolerance relationship of human tissue, how these risk factors interact is virtually unexplored. Since the impact of the interactions may be far greater than that of any individual factor, the impact of the interactions between risk factors must be delineated so that work-related risk can be better quantified. Efforts to quantitatively link epidemiological, biomechanical loading, soft tissue tolerance, and psychosocial studies should be pursued to establish a better understanding of the pathways of injury and resultant preventive strategies.


Training law enforcement to respond to opioid overdose with naloxone: Impact on knowledge, attitudes, and interactions with community members.
Training law enforcement officers (LEOs) to administer naloxone to opioid overdose victims is increasingly part of comprehensive efforts to reduce opioid overdose deaths. Such efforts could yield positive interactions between LEOs and community members and might ultimately help lower overdose death rates. We evaluated a pilot LEO naloxone program by (1) assessing opioid overdose knowledge and attitudes (competency in responding, concerns about naloxone administration, and attitudes towards overdose victims) before and after a 30min training on overdose and naloxone administration, and (2) conducting qualitative interviews with LEOs who used naloxone to respond to overdose emergencies after the training. Eighty-one LEOs provided pre- and post-training data. Nearly all (89%) had responded to an overdose while serving as an LEO. Statistically significant increases were observed in nearly all items measuring opioid overdose knowledge (p's=0.04 to <0.0001). Opioid overdose competencies (p<0.001) and concerns about naloxone administration (p<0.001) significantly improved after the training, while there was no change in attitudes towards overdose victims (p=0.90). LEOs administered naloxone 11 times; nine victims survived and three of the nine surviving victims made at least one visit to substance abuse treatment as a result of a LEO-provided referral. Qualitative data suggest that LEOs had generally positive experiences when they employed the skills from the training. Training LEOs in naloxone administration can increase knowledge and confidence in managing opioid overdose emergencies. Perhaps most importantly, training LEOs to respond to opioid overdose emergencies may have positive effects for LEOs and overdose victims.