Aging rate, environmental risk and production efficiency of the low-density polyethylene (LDPE) films with contrasting thickness in irrigated region.
Physical thickness of low-density polyethylene (LDPE) films might determine the release rate of phthalic acid esters (PAEs) & structural integrity and affect production efficiency. However, this critical issue is still unclear and little reported. Aging effects were evaluated in LDPE films with the thickness of 0.006, 0.008, 0.010 and 0.015 mm in a maize field of irrigation region. The Scanning electron microscope (SEM) results showed that the proportion of damaged area (Dam) to total area of LDPE films was massively lowered with increasing thickness after aging. The highest and lowest Dam was 32.2% and 3.5% in 0.006 and 0.015 mm films respectively. Also, the variations in peak intensity of asymmetric & symmetrical stretching vibrations (ASVI & SSVI) were detected using Fourier transform infrared spectrum (FTIR), indicating that the declines in peak intensity tended to be slower with thickness. Interestingly, the declines in physical integrity were tightly associated with increasing exhalation rate of PAEs. Average releasing rate of PAEs was 38.2%, 31.4%, 31.5% and 19.7% in LDPE films from 0.006 to 0.015 mm respectively. Critically, thicker film mulching can lead to greater soil water storage at plough layer (SWS-PL) and better thermal status, accordingly harvesting higher economic benefit. Therefore, LDPE film thickening may be a solution to reduce environmental risk but improve production efficiency in arid region.


Characterization of Enterococcus species isolated from marine recreational waters by MALDI-TOF MS and Rapid ID API® 20 Strep system.
MALDI-TOF Mass Spectrometry Biotyping has proven to be a reliable method for identifying bacteria at the species level based on the analysis of the ribosomal proteins mass fingerprint. We evaluate the usefulness of this method to identify Enterococcus species isolated from marine recreational water at Brazilian beaches. A total of 127 Enterococcus spp. isolates were identified to species level by bioMérieux's API® 20 Strep and MALDI-TOF systems. The biochemical test identified 117/127 isolates (92%), whereas MALDI identified 100% of the isolates, with an agreement of 63% between the methods. The 16S rRNA gene sequencing of isolates with discrepant results showed that MALDI-TOF and API® correctly identified 74% and 11% of these isolates, respectively. This discrepancy probably relies on the bias of the API® has to identify clinical isolates. MALDI-TOF proved to be a feasible approach for identifying Enterococcus from environmental matrices increasing the rapidness and accuracy of results.


Symptom profiles and explanatory models of first-episode psychosis in African-, Caribbean- and European-origin groups in Ontario.
To assess variability in symptom presentation and explanatory models of psychosis for people from different ethnic groups. Clients with first-episode psychosis (n = 171) who identified as black African, black Caribbean or white European were recruited from early intervention programmes in Toronto and Hamilton. We compared results by ethnic group for symptom profiles and explanatory models of illness. Clients of black Caribbean origin had a lower odds of reporting that they were speaking incomprehensibly (OR = 0.36; 95% CI: 0.14-0.90) and black African clients had a greater odds of reporting persistent aches or pains (OR = 2.92; 95% CI: 1.32-6.50). Black African clients had a lower odds of attributing the cause of psychosis to hereditary factors (OR = 0.41; 95% CI: 0.19-0.89) or to substance abuse (OR = 0.29; 95% CI: 0.13-0.67) and had a lower odds of assigning responsibility for their illness to themselves (OR = 0.41; 95% CI: 0.19-0.89). Understanding the differences in illness models for ethnic minority groups may help improve the cultural competence of mental health services.


Separate origins of left anterior descending, left circumflex and intermediate arteries from the left coronary aortic sinus.
We describe a patient with an unusual coronary anatomic variance in which separate origins of the left anterior descending, left circumflex and the intermediate arteries arose from the left coronary aortic sinus. The importance of demonstrating the separate ostium of an intermediate artery is emphasized.


IgG subclasses serum concentrations in a population of children with Down syndrome: comparative study with siblings and general population.
Serum total IgG and subclasses were determined in three different groups of children: with Down syndrome, their siblings and general pediatric population. Several cases of IgG2 and IgG4 deficiency were identified, predominantly in children with Down syndrome. The differences, considering three age groups, were statistically significant for both groups in relation to the general population group, with an increase of IgG1 and IgG3 and a decrease in serum concentrations of IgG2 and IgG4. Down syndrome children and their siblings tend o have a similar variation of the IgG4 serum concentration levels (P < 0.05). The mechanisms of this concordance are not well understood. The results point out that an adequate strategy to improve the immune status of Down syndrome children could have a positive manifestation in the immune profile of their brothers.


HLA antigens in different age groups.
HLA typing was performed for 17 antigens on cells from 189 unrelated, normal white Caucasians. No significant differences (p greater than 0.05) in distributions of different markers were found among the age groups. There does not seem to be a relation between heterozygosity at HLA-A and HLA-B loci and survival until old age.


The Training and Support Programme for parents of children with Cerebral Palsy: a process evaluation.
The aim of this process evaluation was to better understand the practice implications of an intervention designed to train parents to massage their children with Cerebral Palsy. Seventy parents completed the Training and Support Programme (TSP) with their children. Data were collected by Home Record Sheets and Observation Sheets completed by parents and therapists, respectively. Implications for practice included therapist's sensitivity to the needs of each parent and child, the need for flexibility in the delivery of the TSP, and the implementation of strategies to ensure the TSP ran smoothly. Such strategies may be of value in the delivery of other similar interventions.


The prognostic impact of human leukocyte antigen (HLA) class I antigen abnormalities in salivary gland cancer. A clinicopathological study of 288 cases.
To study abnormalities of proteins of the major histocompatibility complex class I in a series of 288 salivary gland carcinomas, and to correlate findings with patients' overall survival (OS). Protein expression of human leukocyte antigen (HLA)-A, heavy chain (HC)-10, β2 -microglobulin, low molecular weight polypeptides (LMP) 2 and 7, transporters associated with antigen processing (TAP) 1 and 2, calnexin, calreticulin, endoplasmic reticulum (ER) p57 and tapasin was evaluated by immunohistochemistry and semiquantitatively analyzed. As compared with normal salivary gland tissue, HLA-A, LMP7, TAP2 and HLA class I were significantly down-regulated in salivary gland carcinomas, whereas β2 -microglobulin, calnexin, LMP2, and TAP1 were upregulated. Expression of calreticulin, ERp57 and tapasin was unaltered. In univariate Kaplan-Meier analyses, low expression of LMP7 (P = 0.005) and high expression of β2 -microglobulin (P = 0.028), HLA-A (P < 0.001), TAP1 (P = 0.01), and tapasin (P < 0.001) were significantly associated with shorter OS. In multivariate analysis incorporating tumour stage, nodal/distant metastasis, and grade, HLA-A (P = 0.014), LMP7 (P = 0.033), and tapasin (P = 0.024), as well as distant metastasis (P = 0.012) and high tumour grade (P < 0.001), remained statistically significant. The prognostic influence of up-regulated HLA-A and tapasin and down-regulated LMP7 may provide a rationale for targeting these specific components of the antigen processing and presentation pathway in salivary gland carcinomas.


Metabolomic biomarkers in a model of asthma exacerbation: urine nuclear magnetic resonance.
Airway obstruction in patients with asthma is associated with airway dysfunction and inflammation. Objective measurements including sputum analysis can guide therapy, but this is often not possible in typical clinical settings. Metabolomics is the study of molecules generated by metabolic pathways. We hypothesize that airway dysfunction and inflammation in an animal model of asthma would produce unique patterns of urine metabolites measured by multivariate statistical analysis of high-resolution proton nuclear magnetic resonance ((1)H NMR) spectroscopy data. To develop a noninvasive means of monitoring asthma status by metabolomics and urine sampling. Five groups of guinea pigs were studied: control, control treated with dexamethasone, sensitized (ovalbumin, administered intraperitoneally), sensitized and challenged (ovalbumin, administered intraperitoneally, plus ovalbumin aerosol), and sensitized-challenged with dexamethasone. Airway hyperreactivity (AHR) to histamine (administered intravenously) and inflammation were measured. Multivariate statistical analysis of NMR spectra based on a library of known urine metabolites was performed by partial least-squares discriminant analysis. In addition, the raw NMR spectra exported as xy-trace data underwent linear discriminant analysis. Challenged guinea pigs developed AHR and increased inflammation compared with sensitized or control animals. Dexamethasone significantly improved AHR. Using concentration differences in metabolites, partial least-squares discriminant analysis could discriminate challenged animals with 90% accuracy. Using only three or four regions of the NMR spectra, linear discriminant analysis-based classification demonstrated 80-90% separation of the animal groups. Urine metabolites correlate with airway dysfunction in an asthma model. Urine NMR analysis is a promising, noninvasive technique for monitoring asthma in humans.


Plastic reconstructive surgery techniques using VRAM or gracilis flaps in order to successfully treat complex urogenital fistulas.
Urogenital fistulas are devastating complications occurring after tumors or trauma. Surgical treatment is challenging. Thus, further surgical repair options are needed for treatment of complex fistulas within the pelvic region. Twelve patients with urogenital fistulas were surgically treated in our department from 2004 to 2012. These selected cases fulfilled eligibility criteria for continence-preserving surgery - a history of fistula recurrences with ongoing incontinence after receiving at least two surgical attempts. Five VRAM and eight gracilis flaps were used to cover up given tissue defects and to perform functional continence-preserving reconstruction with mean follow-up of 6.3 years. Data were retrospectively reviewed, and standardized survey was performed to evaluate quality of life of all living patients (n = 10). In all cases, final surgical treatment of the given fistulae by VRAM or gracilis flaps could be achieved, with mean operating time of 5:31 h (range: 4:50-6:48 h) for VRAM flap and 3:11 h (range: 2:04-4:42 h) for gracilis flap. Outcome measures were primarily to avoid fistula recurrence after plastic surgical treatment, and secondary quality of life and survival. All patients had their continence preserved, but two patients died during follow-up period. Postoperative assessment revealed the following: VRAM flap patients (n = 3) showed slight incontinence during the follow-up period, whereas continence was restored in all patients with gracilis flap reconstruction (n = 7). Quality-of-life assessment indicated restoration of quality of life in comparison to general population (women > men). Furthermore, key points of the two presented surgical techniques are demonstrated in detail. With preformed VRAM or gracilis flaps, complex urogenital fistulas can be successfully eradicated and continence is restored. The main focus should be the recovery of quality of life, which could be successfully regained. Nevertheless, the continence success rate has to be defined on an individual, case-by-case basis. Original work, cohort study level III.


Porous and Partially Dehydrogenated Fe2+ -Containing Iron Oxyhydroxide Nanosheets for Efficient Electrochemical Nitrogen Reduction Reaction (ENRR).
The design and development of efficient catalysts for electrochemical nitrogen reduction reaction (ENRR) under ambient conditions are critical for the alternative ammonia (NH3 ) synthesis from N2 and H2 O, wherein iron-based electrocatalysts exhibit outstanding NH3 formation rate and Faradaic efficiency (FE). Here, the synthesis of porous and positively charged iron oxyhydroxide nanosheets by using layered ferrous hydroxide as a starting precursor, which undergoes topochemical oxidation, partial dehydrogenated reaction, and final delamination, is reported. As the electrocatalyst of ENRR, the obtained nanosheets with a monolayer thickness and 10-nm mesopores display exceptional NH3 yield rate (28.5 µg h-1 mgcat. -1 ) and FE (13.2%) at a potential of -0.4 V versus RHE in a phosphate buffered saline (PBS) electrolyte. The values are much higher than those of the undelaminated bulk iron oxyhydroxide. The larger specific surface area and positive charge of the nanosheets are beneficial for providing more exposed reactive sites as well as retarding hydrogen evolution reaction. This study highlights the rational control on the electronic structure and morphology of porous iron oxyhydroxide nanosheets, expanding the scope of developing non-precious iron-based highly efficient ENRR electrocatalysts.


Gasification of municipal solid waste (MSW) as a cleaner final disposal route: A mini-review.
The production of hydrogen-rich syngas from municipal solid waste (MSW) by pyrolysis/gasification is one of the most promising waste-to-energy pathways for realizing a circular bioeconomy. This mini-review provides an overview of current research and development efforts in the field, focusing on the development of syngas upgrades and novel gasification processes, with the ultimate goal of making MSW gasification a sustainable and affordable route for the final disposal of MSW. A graphical assessment protocol is proposed to support comprehension of the main reactions that are involved in the MSW gasification. MSW gasification studies are reviewed with the prospects considered to provide a reference for future work.


Conservative management of interstitial pregnancy using operative laparoscopy.
Interstitial pregnancy has been treated so far mainly by either resection of the cornu or hysterectomy. In this article, two patients with cornual pregnancy were operated upon laparoscopically with an uneventful postoperative recovery. This laparoscopic treatment is simple, does not require extensive operative laparoscopic expertise, and is relatively short and less expensive than laparotomy. We suggest that laparoscopic conservative repair be used to replace cornual resection by laparotomy or hysterectomy in cases of early diagnosed interstitial pregnancy.


Accuracy of antigen tests for meningococcal meningitis in cerebrospinal fluid: A diagnostic meta-analysis.
Neisseria meningitidis is one of the major pathogens of meningitis in children worldwide and causes invasive meningococcal disease (IMD), which is a critical illness that mainly presents as meningitis and/or septicemia in children. Identification of N. meningitidis in cerebrospinal fluid (CSF) is the gold standard for the diagnosis of meningococcal meningitis, but antigen tests have advantages such as timely results, relatively low cost, and convenience. Yet, the diagnostic accuracy of antigen tests remains uncertain. Therefore, the aim of this meta-analysis was to evaluate the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We searched the PubMed, Embase, and Cochrane Library databases for studies evaluating the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We included studies that provided sufficient data to construct a 2 × 2 table on a per-sample basis. To determine the overall sensitivity and specificity of the antigen tests, we used polymerase chain reaction (PCR) as the reference standard and employed the hierarchical summary receiver operating characteristic model. Nine studies with 4533 CSF samples were included. The meta-analysis yielded a pooled sensitivity of 91.2% (95% confidence interval [CI]: 80.0%-100.0%) and a pooled specificity of 93.8% (95% CI: 83.9%-100.0%). A subgroup analysis of 2 studies that reported the outcomes of MeningoSpeed yielded a pooled sensitivity of 93.4% (95% CI: 90.0%-95.8%) and a pooled specificity of 91.9% (95% CI: 88.6%-94.4%). Antigen testing for the N. meningitidis serogroup X had a pooled sensitivity of 92.4% (95% CI: 85.2%-96.2%) and a pooled specificity of 99.2% (95% CI: 78.7%-100.0%). The studied antigen tests had high sensitivity and specificity for the diagnosis of meningococcal meningitis in CSF specimens. Antigen testing could serve as an accurate diagnostic method for assessing patients who have a suspected N. meningitidis infection.


Analysis of female voiding dysfunction: a prospective, multi-center study.
Female voiding dysfunction lacks clear definitions or objective data even to this day due to the relatively low prevalence and complex etiologies of voiding dysfunction in women compared to men. The prevalence varies widely from 2.7 to 23 % (Nitti et al. in J Urol 161(5):1535-1540, 1999; Rees et al. in Br J Urol 47(7):853-860, 1975; Groutz et al. in Neurourol Urodyn 19(3):213-220, 2000; Farrar et al. in Br J Urol 47(7):815-822, 1975; Massey and Abrams in Br J Urol 61(1):36-39, 1988; Chassagne et al. in Urology 51(3):408-411, 1998). Diagnostic criteria and management of female voiding dysfunction have not yet been established. We performed a prospective, multi-center study at nine hospitals to investigate the characteristics and prevalence of female voiding dysfunction. A total of 1,415 women visited urology clinics in nine hospitals from September to December 2005. Among them, 792 patients presented with lower urinary tract symptoms (LUTS). We analyzed their urinary symptoms with an International Prostate Symptom Score (IPSS) and obtained objective data using uroflowmetry, residual urine volume, and urinalysis. The authors hereby define female voiding dysfunction as maximum flow rate (Q max) of 15 ml/s or less, which may be due to either bladder outlet obstruction (BOO) or bladder dysfunction caused by detrusor underactivity. BOO was defined as Q max <15 ml/s with detrusor pressure >20 cmH2O at Q max, and detrusor underactivity was defined as Q max <15 ml/s with detrusor pressure <20 cmH2O at Q max on pressure flow studies. Hundred and two patients (12.8 %) from a total of 792 LUTS patients complained of voiding difficulty. Mean total IPSS score, mean IPSS subscores for voiding and storage symptom was 19.5 ± 7.9, 12.0 ± 5.0, and 8.4 ± 3.4, respectively. Among the seven categories of IPSS, incomplete emptying was the most common symptom followed by weak stream. Eighty-nine patients (87.2 %) from a total of 102 voiding dysfunction patients showed BOO, while 13 patients (12.8 %) showed detrusor underactivity. Concomitant diseases observed with voiding dysfunctions were overactive bladder (32 patients), stress urinary incontinence (25), detrusor underactivity (13), previous stress urinary incontinence surgery (12), pelvic organ prolapse (4), and anatomical obstruction (3 patients). The prevalence of voiding difficulty in female urology patients who visit urologic office clinic was 7.2 and 12.8 % in female LUTS patients. Voiding symptoms were more common than storage symptoms, while functional BOO was more prevalent than detrusor underactivity in female voiding difficulty patients. We may expect alpha blockers to be an effective treatment option in female voiding difficulty due to functional BOO.


Small-Sample Estimation of the Mutational Support and Distribution of SARS-CoV-2.
We consider the problem of determining the mutational support and distribution of the SARS-CoV-2 viral genome in the small-sample regime. The mutational support refers to the unknown number of sites that may eventually mutate in the SARS-CoV-2 genome while mutational distribution refers to the distribution of point mutations in the viral genome across a population. The mutational support may be used to assess the virulence of the virus and guide primer selection for real-time RT-PCR testing. Estimating the distribution of mutations in the genome of different subpopulations while accounting for the unseen may also aid in discovering new variants. To estimate the mutational support in the small-sample regime, we use GISAID sequencing data and our state-of-the-art polynomial estimation techniques based on new weighted and regularized Chebyshev approximation methods. For distribution estimation, we adapt the well-known Good-Turing estimator. Our analysis reveals several findings: First, the mutational supports exhibit significant differences in the ORF6 and ORF7a regions (older versus younger patients), ORF1b and ORF10 regions (females versus males) and in almost all ORFs (Asia/Europe/North America). Second, even though the N region of SARS-CoV-2 has a predicted 10% mutational support, mutations fall outside of the primer regions recommended by the CDC.


Spirometry: what paper speed?
Controversy still exists regarding the paper speed necessary for accurate measurements from records of maneuvers for forced vital capacity. Twenty-four spirometric wave forms of known characteristics were plotted by a computer at 1, 2, and 3 cm/sec and were measured in random order by 12 experienced readers. We found that all readers made a surprisingly large number of major errors. The speed of the paper was found to be an important determinant for accurately measuring the forced expiratory volume in one second and the mean forced expiratory flow during the middle half of the forced vital capacity. A minimum paper speed of at least 3 cm/sec is important if spirograms are to be accurately measured by hand. Human errors in measurement may be minimized by obtaining results from at least three acceptable curves, by making duplicate reading of curves, and by making use of validated computerized measurement systems.


Resource availability and meiofauna in sediment of tropical seagrass beds: local versus global trends.
Characterisation of productivity-diversity relationships forms an essential step towards a better understanding of biodiversity. In terrestrial systems this is a topical subject and most studies reported a hump-shaped relationship. For marine systems, however, the number of studies dedicated to this is low despite the high interest in this productivity-diversity relationship. The present study reports on meiofauna density/diversity patterns in relation to resource availability as an indicator for the productivity of the ecosystem. Standardised meiofauna samples were collected in tropical seagrass beds from three localities (Kenya, Mexico, the Philippines) in order to contrast local patterns with a more global scale. Although these sites were physically comparable, a range of resource availabilities was found. These differences between localities were mainly due to different tidal regimes and related input of organic matter. At all sites a significant positive effect of resource increase on meiofauna densities was found. This positive effect was less clear for meiofauna diversity. Highest density and diversity levels were reported for the Kenyan site and this is probably linked to a high tidal range. Pooling all localities together resulted in a significant positive linear relationship between resource availability and meiofauna density/diversity. Caution should be taken when choosing resource indicators. Chlorophyll a concentrations, for example, resulted in a positive density-productivity relationship while organic carbon content, an indicator for more refractory material, showed a negative relationship. In all cases, no hump-shaped relationship could be found suggesting that each ecosystem and each group of organisms may show a particular productivity-diversity/density relationship.


Femoral head avascular necrosis in COVID-19 survivors: a systematic review.
The current systematic review aimed to document published cases of femoral head avascular necrosis (FHAVN) post-COVID-19, to report the COVID-19 disease characteristics and management patients received, and to evaluate how the FHAVN were diagnosed and treated among various reports. A systematic literature review was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through a comprehensive English literature search on January 2023 through four databases (Embase, PubMed, Cochrane Library, and Scopus), including studies reporting on FHAVN post-COVID-19. Fourteen articles were included, ten (71.4%) were case reports, and four (28.6%) case series reported on 104 patients having a mean age of 42.2 ± 11.7 (14:74) years, in which 182 hip joints were affected. In 13 reports, corticosteroids were used during the COVID-19 management plan for a mean of 24.8 ± 11 (7:42) days, with a mean prednisolone equivalent dose of 1238.5 ± 492.8 (100:3520) mg. A mean of 142.1 ± 107.6 (7:459) days passed between COVID-19 diagnosis and FHAVN detection, and most of the hips were stage II (70.1%), and concomitant septic arthritis was present in eight (4.4%) hips. Most hips (147, 80.8%) were treated non-surgically, of which 143 (78.6%) hips received medical treatment, while 35 (19.2%) hips were surgically managed, 16 (8.8%) core decompression, 13 (7.1%) primary THA, five (2.7%) staged THA and three (1.6%) had first stage THA (debridement and application of antibiotic-loaded cement spacer). The outcomes were acceptable as regards hip function and pain relief. Femoral head avascular necrosis post-COVID-19 infection is a real concern, primarily attributed to corticosteroid usage, besides other factors. Early suspicion and detection are mandatory, as conservative management lines are effective during early stages with acceptable outcomes. However, surgical intervention was required for progressive collapse or patients presented in the late stage.


First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo.
The response to centrally acting drugs is highly variable between individuals and does not always correlate with plasma drug levels. Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations. CYP2D metabolizes codeine to the active morphine metabolite. We investigated the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia. Rats received intracerebroventricular injections of CYP2D inhibitors (20 μg propranolol or 40 μg propafenone) or vehicle controls. Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: (a) lower analgesia in the tail-flick test (p<0.05) and lower areas under the analgesia-time curve (p<0.02) within the first hour after 30 mg/kg subcutaneous codeine, (b) lower morphine concentrations and morphine to codeine ratios in the brain (p<0.02 and p<0.05, respectively), but not in plasma (p>0.6 and p>0.7, respectively), tested at 30 min after 30 mg/kg subcutaneous codeine, and (c) lower morphine formation from codeine ex vivo by brain membranes (p<0.04), but not by liver microsomes (p>0.9). Analgesia trended toward a correlation with brain morphine concentrations (p=0.07) and correlated with brain morphine to codeine ratios (p<0.005), but not with plasma morphine concentrations (p>0.8) or plasma morphine to codeine ratios (p>0.8). Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine's therapeutic efficacy, side-effect profile and abuse liability. Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally acting drugs.


Characterisation of two novel CYP4 genes from the marine polychaete Nereis virens and their involvement in pyrene hydroxylase activity.
Cytochrome P450 enzymes (CYP enzymes) catalyse the initial step in biotransformation of xenobiotics like polycyclic aromatic hydrocarbons (PAHs). The marine polychaete Nereis virens has a high capacity for biotransformation of PAHs. In the present study, the complete cDNA sequences of two novel CYP genes isolated from N. virens gut tissue are reported. One named CYP342A1, the first member of a new family and the other named CYP4BB1, the first member of a new subfamily. This is the first investigation of specific CYP enzymes from marine polychaetes in which catalytic activity has been determined. Both CYP enzymes had monooxygenase activity and catalysed hydroxylation of pyrene to 1-hydroxypyrene. Based on the present results it is likely that both CYP4BB1 and CYP342A1 are involved in xenobiotic biotransformation. Furthermore, site-directed mutagenesis of the conserved cysteine residue of the heme binding domain resulted in complete loss of monooxygenase activity of both CYP enzymes, indicating that this cysteine residue is indispensable for monooxygenase activity of invertebrate CYP enzymes, as has been well documented in vertebrates. Considering the important role of CYP enzymes in biotransformation of xenobiotics and the presence of N. virens in estuarine environments that accumulates organic xenobiotics, our results are important in understanding the molecular mechanism of biotransformation in marine polychaetes.


Uteroglobin: physiological role in normal glomerular function uncovered by targeted disruption of the uteroglobin gene in mice.
Blastokinin or uteroglobin (UG) is an evolutionarilly conserved, steroid-inducible, homodimeric, multifunctional, secreted protein with potent Immunomodulatory/antiinflammatory properties. Recently, a UG-receptor expressed on several malignant and normal cell types has been characterized. Although the biochemistry, structural, and molecular biology of UG have been extensively studied, its physiological function(s), until recently, remained unknown. By generating UG-null (UG-/-) mice, we determined that an essential role of UG is to prevent severe renal disease caused by an abnormal deposition of predominantly multimeric fibronectin (Fn) and collagen in the glomerulus. The molecular mechanisms by which UG prevents this disease in control (UG+/+) mice, at least in part, is attributable to its high-affinity binding to Fn and the formation of Fn-UG heteromers, which counteract both Fn-Fn and Fn-collagen interactions, required for abnormal tissue deposition. In addition, by inhibiting secretory phospholipase A2 (sPLA2) activity and decreasing the level of lysophosphatidic acid (LPA), UG may indirectly prevent the activation of integrins (eg, alpha5beta1) that enhance abnormal tissue deposition of Fn. The mechanism(s) of UG action is likely to be even more complex, because it also functions through a receptor-mediated pathway that has not yet been clearly defined. Nevertheless, the UG gene-knockout mice provide a valuable animal model for investigation of human glomerulopathies in general and familial Fn-deposit glomerulopathy in particular.


DNA Methylation Is a Main Key for Bacteria-Related Colon Carcinogenesis.
Colorectal cancer (CRC) is the second most common cause of cancer deaths in men and women combined [...].


Neuregulin-1 suppresses muscarinic receptor expression and acetylcholine-activated muscarinic K+ channels in cardiac myocytes.
The neuregulin-1 family of growth factors regulates nicotinic acetylcholine receptor synthesis in skeletal muscle, but its role in cardiac myogenesis remains unclear. Here, we investigate the involvement of neuregulins in the development of cardiac cholinergic responsiveness. Treatment of chick cardiac myocytes with neuregulin-1 inhibited mRNA expression of the M4 muscarinic receptor, but not the M2 receptor. In addition, mRNA levels of GIRK1 were reduced in myocytes by treatment with neuregulin-1. Activation of cholinergic receptors in cultured chick atrial myocytes by carbachol produced an outward potassium current (I(K(ACh))), which was attenuated by 24-48-h pre-treatment with neuregulin-1. These data suggest that neuregulins can regulate cardiac parasympathetic tone and may be involved in the pathogenesis of cardiac arrhythmias and heart failure.


RECQ1 plays a distinct role in cellular response to oxidative DNA damage.
RECQ1 is the most abundant RecQ homolog in humans but its functions have remained mostly elusive. Biochemically, RECQ1 displays distinct substrate specificities from WRN and BLM, indicating that these RecQ helicases likely perform non-overlapping functions. Our earlier work demonstrated that RECQ1-deficient cells display spontaneous genomic instability. We have obtained key evidence suggesting a unique role of RECQ1 in repair of oxidative DNA damage. We show that similar to WRN, RECQ1 associates with PARP-1 in nuclear extracts and exhibits direct protein interaction in vitro. Deficiency in WRN or BLM helicases have been shown to result in reduced homologous recombination and hyperactivation of PARP under basal condition. However, RECQ1-deficiency did not lead to PARP activation in undamaged cells and nor did it result in reduction in homologous recombination repair. In stark contrast to what is seen in WRN-deficiency, RECQ1-deficient cells hyperactivate PARP in a specific response to H₂O₂treatment. RECQ1-deficient cells are more sensitive to oxidative DNA damage and exposure to oxidative stress results in a rapid and reversible recruitment of RECQ1 to chromatin. Chromatin localization of RECQ1 precedes WRN helicase, which has been shown to function in oxidative DNA damage repair. However, oxidative DNA damage-induced chromatin recruitment of these RecQ helicases is independent of PARP activity. As other RecQ helicases are known to interact with PARP-1, this study provides a paradigm to delineate specialized and redundant functions of RecQ homologs in repair of oxidative DNA damage.


Shaping of amplified beam from a highly multimode Yb-doped fiber using transmission matrix.
The transmission matrix of an ytterbium doped multimode fiber with gain was measured. It was shown to vary owing to the pump power level. Amplified beam focusing, beam steering and shaping were demonstrated using the measured matrix for input wavefront shaping, with an efficiency similar to the case of a passive fiber. The impact of weak gain saturation was lastly investigated.


Arginine selective biosensor based on arginase-urease immobilized in gelatin.
Arginase and urease enzymes were immobilized on the surface of pH electrode by using gelatin membrane which is then cross-linked with glutaraldehyde. Sensor response was maximum when 2.5 mM, Tris-HCl buffer (pH 8.5) was used at 25 degrees C. The biosensor response depends linearly on arginine concentration between 0.025-0.310 mM with response time 10 min. Furthermore, application of the system for the arginine detection in serum samples was also tested.


Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model.
Acute cerebral ischemia causes hypoxic neuronal cell death by necrosis and apoptosis. Expression of anti-apoptotic transgenes in ischemic brain may provide a useful therapeutic strategy for alleviation of postischemic damage. The present study investigates liposome-mediated transfer of the human bcl-2 protein in a rat model of focal transient ischemia due to middle cerebral artery (MCA) occlusion. Two different types of plasmid vectors were used for bcl-2 expression: one driven by the constitutive cytomegalovirus promoter (pCMV) and another based on the hypoxia-inducible human vascular endothelial growth factor promoter (pHRE). Cationic liposome/plasmid DNA complexes (lipoplexes) were injected directly into the cerebrospinal fluid (CSF) of rats immediately after MCA occlusion. The brains of treated and control animals were analyzed 48 h later. Infarct volumes and numbers of apoptotic cells were quantified. Occlusion of the MCA resulted in ipsilateral cerebral infarcts in all study animals. Transfer of the bcl-2 gene resulted in high level widespread protein expression in the case of the pCMV-bcl2 plasmid, while animals treated with the pHRE-bcl2 vector showed lower expression levels of bcl2 which were in addition limited to the ischemic area. Treatment with pCMV-bcl2, but not with pHRE-bcl2, was able to significantly reduce the infarct volume, which was 109 +/- 8 mm(3) for pCMV-bcl2, 152 +/- 29 mm(3) for pHRE-bcl2, and 155 +/- 18 mm(3) for control animals. Animals transfected with either vector showed a significant reduction in numbers of apoptotic cells in the infarct and penumbra area compared with controls. There were no short-term neurological side-effects of the CSF injection of lipoplexes or of bcl-2 expression. In conclusion, the hypoxia-inducible bcl-2 expression mediated by intrathecal lipoplexes may represent a novel, biologically safe and lesion-selective therapeutic approach for neuroprotection after acute cerebral ischemia. DOI: 10.1038/sj/gt/3301676


GPR30 agonist G1 combined with hypothermia alleviates cognitive impairment and anxiety-like behavior after subarachnoid hemorrhage in rats.
This study aimed to investigate the treatment effect of G protein-coupled receptor 30 (GPR30) agonist G1 combined with hypothermia (HT) on cognitive impairment and anxiety-like behavior after subarachnoid hemorrhage (SAH) in rats. Fifty male rats were randomly assigned to one of five groups: Sham group, SAH group, SAH + G1 group, SAH + HT group, and SAH + G1 + HT group. The SAH rat model was established by modified endovascular puncture in all groups except the Sham group. Neurological function after the operation was assessed by Garcia scoring. The degree of rat cerebral edema was determined using dry-wet weighing method on the 28th day after operation. Moreover, the behavioral test was performed on rats on the 4th and 28th days after operation. Compared with Sham group, the Garcia score of each SAH rat model group decreased significantly on the first day and thereafter increased gradually. However, the recovery rate of each treatment group was higher than the SAH group (no treatment), and the Garcia score of SAH + G1 + HT group was much higher than the SAH group on the seventh day after operation. In addition, each treatment group could obviously reduce the cerebral edema degree of SAH rats, among which rats in SAH + G1 + HT group had lower cerebral edema degree than SAH + G1 group and SAH + HT group. Behavioral test results showed that the combination of GPR30 agonist G1 and HT markedly improved the learning and memory ability of SAH rats, alleviated their anxiety- and emotion-related behavior, and enhanced their social interaction. GPR30 agonist G1 combined with HT reduces cognitive impairment and anxiety-like behavior in rats with SAH.


Memory modulation: An introduction to the special issue.
This Special Issue of Cognitive Neuroscience highlights recent research on the cognitive neuroscience of episodic memory, with an emphasis on interventions designed to modulate memory processes. Collectively, the nine included papers provide a timely overview of the state of memory modulation, including work on pharmacological manipulations, motivational states, and targeted brain stimulation.


Identification of paddy blast disease field images using multi-layer CNN models.
Farmers and agricultural experts can take action on many areas of paddy crop handling and management practices with the use of actionable information from the in-field diagnosis of paddy blast disease. To successfully diagnose the blast disease affecting fifteen different paddy crop varieties, three transfer learning multi-layer convolutional neural network (CNN) models, such as CapsNet, EfficientNet-B7, and ResNet-50, are presented in this paper. The field images of blast disease are captured and classified based on disease severity levels, such as low, medium, high, and severe. The study employing the CapsNet model with a dataset consisting of a total of 20,000 labeled images demonstrated significant results with a testing efficiency of 90.79% and a validation efficiency of 93.29%. The ResNet-50 and EfficientNet-B7 models have yielded average testing efficiencies of 85.10% and 88.72%, respectively. On the held out blast disease affected paddy field image dataset, the CapsNet model outperformed the EfficientNet-B7 and ResNet-50 CNN models in terms of both classification efficiency and computational efficiency.


Approaches for informing optimal dose of behavioral interventions.
There is little guidance about to how select dose parameter values when designing behavioral interventions. The purpose of this study is to present approaches to inform intervention duration, frequency, and amount when (1) the investigator has no a priori expectation and is seeking a descriptive approach for identifying and narrowing the universe of dose values or (2) the investigator has an a priori expectation and is seeking validation of this expectation using an inferential approach. Strengths and weaknesses of various approaches are described and illustrated with examples. Descriptive approaches include retrospective analysis of data from randomized trials, assessment of perceived optimal dose via prospective surveys or interviews of key stakeholders, and assessment of target patient behavior via prospective, longitudinal, observational studies. Inferential approaches include nonrandomized, early-phase trials and randomized designs. By utilizing these approaches, researchers may more efficiently apply resources to identify the optimal values of dose parameters for behavioral interventions.


Diagnosis and treatment of nasal airway obstruction due to inferior turbinate hypertrophy.
Bilateral inferior turbinate hypertrophy is the most common cause of nasal airway obstruction. Treatment by resection is advised. Following this, a significantly improved airway has been demonstrated and no adverse sequelae have been observed or reported.


Magnetic metal-organic frameworks coated stir bar sorptive extraction coupled with GC-MS for determination of polychlorinated biphenyls in fish samples.
In this work, several kinds of the metal-organic framework (MOF) were evaluated the adsorption performance to PCB. Finally, MOF-5(Fe) was introduced in stir bar sorptive extraction (SBSE) as the adsorbent to extract six polychlorinated biphenyls (PCBs). Nd-Fe-B permanent magnet was employed as stir bar, which was then coated with Fe3O4-MOF-5(Fe) composite magnetic material, which was prepared by solvothermal method. The stir bar was then employed to extract and enrich six indicator PCBs (2,2',5,5'-tetrachlorobiphenyl, 2,2',4,5,5'-pentachlorobiphenyl, 2,2',3,4,4',5-hexachlorobiphenyl, 2,3,4,4,5-pentachlorobiphenyl, 2,2',4,4',5,5'-hexachlorobiphenyl, 2,2',3,4,4',5,5'-heptachlorobiphenyl) under stirring, then eluted by n-hexane under ultrasound. Its saturated adsorption amount was found to be 17.0-17.8 mg g(-1) and only 30 min were needed to reach adsorption equilibrium. The MOF-stir bar can be reused for 60 times with the recovery above 80%, which exhibited good stability. Under the optimal experimental conditions, MOF-5(Fe) based SBSE was coupled with GC-MS for detecting six PCBs. The limits of detection (S/N=3) of the developed method were 0.061-0.096 ng g(-1), with enrichment factors of 50-100 fold. And the linear ranges were 0.01-500 μg L(-1). The new method was successfully applied to assess PCBs in fish samples with satisfactory recovery ranging from 94.3% to 97.5%.


Environmental health in environmental protection.
The health of the population and the environment are inextricably linked. To improve both, a holistic approach is required for environmental protection procedures. The primary approach for improvement is integration; more specifically an increase in communication between official departments and agencies, and mechanisms for stakeholder involvement from the inception of projects. There is also a need to combine HIAs and EIAs, and to apply them to wider issues, such as planning, policy or legislative changes, as well as traditional industrial development projects. It needs to be more widely appreciated that the economy and public health are ultimately substantially determined by the condition of the environment.


Gastroenteritis and the novel picornaviruses aichi virus, cosavirus, saffold virus, and salivirus in young children.
During the last few years many new human picornaviruses have been discovered due to advances in metagenomics and other molecular biological approaches. The clinical significance and the occurrence are only sparsely described. To determine the epidemiology and clinical significance of infections with the novel human picornaviruses, aichi virus, cosavirus, salivirus, and saffold virus in infants in Denmark. We tested 1393 stool samples from a birth cohort of 454 children for these viruses. Samples were collected at ages 6, 10 and 15 months, and at episodes of gastroenteritis. Samples were tested by real-time reverse-transcriptase polymerase chain reaction assays. Each study participant had a diary, where the parents reported episodes of disease, including gastroenteritis. Aichi virus, salivirus and saffold virus were detected in 6, 9 and 38 of the children, respectively, but cosavirus was not detected in any of the children. There was a clear seasonal variation with most infections occurring in autumn and winter. A statistically significant association between the findings of salivirus and gastrointestinal disease was demonstrated. There was no association between gastrointestinal disease and the presence of aichi virus or saffold virus. The newly discovered human picornaviruses aichi virus, saffold virus, and salivirus are circulating in Danish children, with the most common being saffold virus. Saffold virus was seen almost exclusively in the autumn and winter period. Salivirus was the only virus, which was significantly associated with gastroenteritis, although the number of positive samples was rather low.


Relationships between the antral follicle count, steroidogenesis, and secretion of follicle-stimulating hormone and anti-Müllerian hormone during follicular growth in cattle.
The antral follicle count (AFC) in mammalian ovaries positively correlates with female fertility. To clarify the causes of differences in fertility between low and high AFC cows, we investigated follicular growth dynamics and hormone concentrations in plasma, follicular fluid, and in vitro growth (IVG) media at different stages of follicular growth. Seven cows were divided into high AFC (n = 4, > 30 follicles) and low AFC (n = 3, < 30 follicles) groups based on the peak AFC detected by ultrasonography. These cows were subjected to estrous synchronization, daily ovarian ultrasonography, and blood collection. Their follicular fluid was collected from dominant follicles at different stages (selection, luteal, and ovulatory phases). In another experiment, we cultured oocyte-cumulus-granulosa cell complexes collected from early antral follicles (< 1 mm) for 12 days. Estradiol-17β (E2), testosterone (T), progesterone (P4), and anti-Müllerian hormone (AMH) concentrations in follicular fluids and plasma were measured. Plasma follicle-stimulating hormone (FSH) concentrations were examined. E2, P4, and AMH concentrations were also measured in IVG media. The numbers of small (< 4 mm) and intermediate (4-8 mm) follicles were larger in the high AFC group than in the low AFC group (P < 0.05). The number of intermediate follicles was stable in the low AFC group, indicating consistent development. However, the number of these follicles fluctuated in the high AFC group. Plasma FSH concentrations were higher, whereas E2 and T concentrations were lower in the low AFC group (P < 0.05). E2 concentrations and the E2/P4 ratio in ovulatory follicles and IVG media on day 8 were higher in the high AFC group (P < 0.05). AMH concentrations in plasma and IVG media (P < 0.01) were higher in the high AFC group. The weaker response to FSH of granulosa cells caused low E2 production in the low AFC group, resulting in high FSH concentrations and the consistent development of intermediate follicles. Conversely, higher E2 concentrations suppressed FSH secretion in the high AFC group. Granulosa cells in the high AFC group had the ability to produce more AMH than those in the low AFC group throughout IVG culture.


The Effects of Tobacco Coverage in the Public Communication Environment on Young People's Decisions to Smoke Combustible Cigarettes.
In today's complex media environment, does media coverage influence youth and young adults' (YYA) tobacco use and intentions? We conceptualize the "public communication environment" and effect mediators, then ask whether over time variation in exogenously measured tobacco media coverage from mass and social media sources predicts daily YYA cigarette smoking intentions measured in a rolling nationally representative phone survey (N = 11,847 on 1,147 days between May 2014 and June 2017). Past week anti-tobacco and pro-tobacco content from Twitter, newspapers, broadcast news, Associated Press, and web blogs made coherent scales (thetas = 0.77 and 0.79). Opportunities for exposure to anti-tobacco content in the past week predicted lower intentions to smoke (Odds ratio [OR] = 0.95, p < .05, 95% confidence interval [CI] = 0.91-1.00). The effect was stronger among current smokers than among nonsmokers (interaction OR = 0.88, p < .05, 95% CI = 0.77-1.00). These findings support specific effects of anti-tobacco media coverage and illustrate a productive general approach to conceptualizing and assessing effects in the complex media environment.


Binding characteristics of [3H]14-methoxymetopon, a high affinity mu-opioid receptor agonist.
The highly potent micro -opioid receptor agonist 14-methoxymetopon (4,5alpha-epoxy-3-hydroxy-14beta-methoxy-5beta,17-dimethylmorphinan-6-one) was prepared in tritium labelled form by a catalytic dehalogenation method resulting in a specific radioactivity of 15.9 Ci/mmol. Opioid binding characteristics of [3H]14-methoxymetopon were determined using radioligand binding assay in rat brain membranes. [3H]14-Methoxymetopon specifically labelled a single class of opioid sites with affinity in low subnanomolar range (Ki = 0.43 nm) and maximal number of binding sites of 314 fmol/mg protein. Binding of [3H]14-methoxymetopon was inhibited by ligands selective for the micro -opioid receptor with high potency, while selective kappa-opioids and delta-opioids were weaker inhibitors. 14-Methoxymetopon increased guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding with an EC50 of 70.9 nm, thus, providing evidence for the agonist character of this ligand. The increase of [35S]GTPgammaS binding was inhibited by naloxone and selective micro -opioid antagonists, indicating a micro -opioid receptor-mediated action. [3H]14-Methoxymetopon is one of the few nonpeptide mu-opioid receptor agonists available in radiolabelled form up to now. Due to its high affinity and selectivity, high stability and extremely low nonspecific binding (<10%), this radioligand would be an important and useful tool in probing mu-opioid receptor mechanisms, as well as to promote a further understanding of the opioid system at the cellular and molecular level.


Pancreatic lipoma: An incydentaloma which can resemble cancer - analysis of 13 cases studied with CT and MRI.
The purpose of this article is to present computed tomography (CT) and magnetic resonance imaging (MRI) findings of rare pancreatic lipomas. The analysis covered 13 patients (7 men and 6 women, aged 47-88, average: 65.6 years), with 13 pancreatic lipomas, whose cases constituted the basis for 10 contrast-enhanced CT and 5 MRI studies. Lipomas measured from 6 mm to 32 mm (average 12.8 mm) and were located in the pancreatic head (n=7), body (n=2), tail (n=3) and uncinate process (n=1). Most lesions (n=11) were homogenous, well-circumscribed. On contrast-enhanced CT scans, macroscopic fat (<-30 HU) was present in 9 lipomas. In one case (10 mm lesion) the density was -20 HU and the lesion was poorly circumscribed with septations, which altogether made it difficult to precisely characterize its contents. On MR scans fat was demonstrated in all studied cases (n=5). Lipomas are rare, small, homogenous and well-circumscribed pancreatic tumours. The most important feature, decisive for the diagnosis and distinguishing them from pancreatic carcinoma, is detection of fatty tissue on CT and MR scans. In these cases differential diagnosis includes other rare fatty tumours of the pancreas (focal fatty infiltration, teratoma, liposarcoma).


Unveiling catalyst-free electro-photochemical reactivity of aryl diazoesters and facile synthesis of oxazoles, imide-fused pyrroles and tetrahydro-epoxy-pyridines via carbene radical anions.
Herein, we report a reagent-less (devoid of catalyst, supporting electrolyte, oxidant and reductant) electro-photochemical (EPC) reaction [electricity (50 μA) and blue LED (5 W)] of aryl diazoesters to generate radical anions which are subsequently reacted with acetonitrile or propionitrile and maleimides to generate diversely substituted oxazoles, diastereo-selective imide-fused pyrroles and tetrahydroepoxy-pyridines in good to excellent yield. Thorough mechanistic investigation including a 'biphasic e-cell' experiment supports the reaction mechanism involving a carbene radical anion. The tetrahydroepoxy-pyridines could be fluently converted to fused pyridines resembling vitamin B6 derivatives. The source of the electric current in the EPC reaction could be a simple cell phone charger. The reaction was efficiently scaled up to the gram level. Crystal structure, 1D, 2D NMRs and HRMS data confirmed the product structures. This report demonstrates a unique generation of radical anions via electro-photochemistry and their direct applications in the synthesis of important heterocycles.


Synapses of the cerebellar cortex molecular layer after chronic alcohol consumption.
The cerebellar molecular layer of chronic alcohol treated rats showed degenerated parallel fiber boutons and vacated Purkinje cell spines after 6 months of alcohol feeding; degenerated Purkinje cell dendrites were concomitantly observed. The number of synapses between parallel fibers and Purkinje cell spines decreased after 6 months whereas their mean synaptic diameter increased throughout the experiment. Conversely, synapses between parallel fibers and dendrites of interneurons increased in 18-month alcohol-fed group. Quantifications were done using a discrete unfolding procedure. It was also observed that some parallel fiber terminals simultaneously established synapses with multiple Purkinje cell spines and with dendrites of interneurons. These results were obtained from groups of 6 rats alcohol-fed for 1, 3, 6, 12 and 18 months and compared with age-matched pair-fed controls. Previous reports of alcohol-induced degenerative changes in the adult rat central nervous system were, thus, fully corroborated. Furthermore, there was evidence of remodeling processes pointing to compensatory plastic mechanisms in the cerebellar circuitry albeit not sufficient to overcome its alcohol-induced deterioration.


Mechanism of action of antipsychotic drugs: from dopamine D(2) receptor antagonism to glutamate NMDA facilitation.
The fundamental pathologic processes associated with schizophrenia remain uncertain. The goal of this article was to review imaging evidence suggesting that schizophrenia is associated with excessive stimulation of D(2) receptors, as well as imaging experiments supporting the hypothesis that this dysregulation might be secondary to N- methyl-d-aspartate (NMDA) dysfunction. Recent imaging data support the association of schizophrenia with a dopamine endophenotype involving excessive subcortical dopamine function. Animal and imaging data are consistent with the idea that this abnormality might be secondary to a synaptic disconnectivity involving the prefrontal cortex, which is well modeled by NMDA antagonist administration. In turn, this dopamine dysregulation might worsen synaptic connectivity and NMDA function. Thus, both glutamate/dopamine and dopamine/glutamate interactions may be relevant to schizophrenia pathophysiology and treatment. A deficit in glutamate transmission may lead to the dopamine endophenotype associated with this illness, and dopamine alterations in turn might exacerbate glutamate transmission deficits. The view that NMDA alterations are primary and dopamine alterations are secondary is probably oversimplistic, as both sets of abnormalities reinforce each other. A consequence of this general model is that direct intervention to support NMDA function might be beneficial as an augmentation strategy for the treatment of schizophrenia. Thus, it is proposed that schizophrenia is associated with strongly interconnected abnormalities of glutamate and dopamine transmission: NMDA hypofunction in the prefrontal cortex and its connections might generate a pattern of dysregulation of dopamine systems that, in turn, further weakens NMDA-mediated connectivity and plasticity.


Age-related changes in the completeness of the circle of Willis in children.
The circle of Willis is a circulatory anastomosis that supplies blood to the brain. If any of the bridging segments are hypoplastic or absent, the capacity for collateral flow in the setting of large vessel occlusion may be decreased. Outside of the neonatal period, the prevalence of a complete circle of Willis (CoW) in the pediatric population has not been well described. Our objectives include determining the prevalence of a complete CoW in children and identifying if there is an age-related "loss" of arterial segments. Following IRB approval, angiograms of the CoW performed on a 3-T MR platform from 2016 to 2020 on patients 21 years or younger were retrospectively reviewed. Any patient with underlying arterial pathology that may affect the CoW was excluded. Patient age and gender at the time of imaging were obtained. In total, 592 pediatric CoW were assessed. Frequencies of completeness were calculated in two different fashions: scenario 1 where a CoW was characterized as complete even if it contained hypoplastic vessels (88.8%), and scenario 2 where it was characterized as complete after excluding hypoplastic vessels (44.0%). In both scenarios, our data showed that older age was more associated with an incomplete CoW (p < 0.0001). In addition, we found a higher percentage of males with an incomplete CoW compared with females (p < 0.0001). The presence of a complete CoW is greater in our pediatric population than what has been reported in adults. The prevalence of an incomplete circle of Willis also increases significantly with age.


Glycerol monolaurate improved intestinal barrier, antioxidant capacity, inflammatory response and microbiota dysbiosis in large yellow croaker (Larimichthys crocea) fed with high soybean oil diets.
Glycerol monolaurate (GML) is a potential candidate for regulating metabolic syndrome and inflammatory response. However, the role of GML in modulating intestinal health in fish has not been well determined. In this study, a 70-d feeding trial was conducted to evaluate the effect of GML on intestinal barrier, antioxidant capacity, inflammatory response and microbiota community of large yellow croaker (13.05 ± 0.09 g) fed with high level soybean oil (SO) diets. Two basic diets with fish oil (FO) or SO were formulated. Based on the SO group diet, three different levels of GML 0.02% (SO0.02), 0.04% (SO0.04) and 0.08% (SO0.08) were supplemented respectively. Results showed that intestinal villus height and perimeter ratio were increased in SO0.04 treatment compared with the SO group. The mRNA expressions of intestinal physical barrier-related gene odc and claudin-11 were significantly up-regulated in different addition of GML treatments compared with the SO group. Fish fed SO diet with 0.04% GML addition showed higher activities of acid phosphatase and lysozyme compared with the SO group. The content of malonaldehyde was significantly decreased and activities of catalase and superoxide dismutase were significantly increased in 0.02% and 0.04% GML groups compared with those in the SO group. The mRNA transcriptional levels of inflammatory response-related genes (il-1β, il-6, tnf-α and cox-2) in 0.04% GML treatment were notably lower than those in the SO group. Meanwhile, sequencing analysis of bacterial 16S rRNA V4-V5 region showed that GML addition changed gut microbiota structure and increased alpha diversity of large yellow croaker fed diets with a high level of SO. The correlation analysis results indicated that the change of intestinal microbiota relative abundance strongly correlated with intestinal health indexes. In conclusion, these results demonstrated that 0.02%-0.04% GML addition could improve intestinal morphology, physical barrier, antioxidant capacity, inflammatory response and microbiota dysbiosis of large yellow croaker fed diets with a high percentage of SO.


Tracheal repair in children: reduction of mortality with advent of slide tracheoplasty.
Severe tracheal stenosis is a rare life-threatening condition that often requires early surgical intervention. The management of this anomaly has been associated with significant mortality and morbidity. We describe our experience with repair of this condition. From 1986 to 2011, 20 patients underwent repair of tracheal stenosis at the Royal Children's Hospital (median age 4.9 months) and were retrospectively reviewed. Tracheal repair techniques used were as follows: patch tracheoplasty (n=8; 40%, 8 out of 20), slide tracheoplasty (n=7; 35%, 7 out of 20), end-to-end anastomosis (n=5; 25%, 5 out of 20). Six patients (30%, 6 out of 20) had coexisting congenital intracardiac anomalies. There were 12 pulmonary artery sling (60%, 12 out of 20) patients. Overall operative mortality was 15% (n=3; 3 out of 20). Operative mortality was 20% (n=2; 2 out of 10) from 1986 to 2001 and decreased to 10% (n=1; 1 out of 10) from 2002 to 2011. All early deaths occurred in patients who had undergone patch tracheoplasty. Since 2004, there were no operative deaths. Seven patients (35%, 7 out of 20) required tracheal reintervention postoperatively. There were three late deaths (17.6%, 3 out of 17) at 8, 9 and 22 months after surgery. At last follow-up (mean 5.3±6.6 years; range 1 month to 18 years), all 14 survivors remained asymptomatic. Repair of tracheal stenosis in children has been associated with high morbidity and mortality. Since the introduction of slide tracheoplasty, a multidisciplinary team approach and abandonment of patch tracheoplasty, the mortality has been reduced. Survival beyond 2 years after surgery is associated with an excellent outcome.


Pyrosequencing-based validation of a simple cell-suspension polymerase chain reaction assay for Campylobacter with application of high-processivity polymerase and novel internal amplification controls for rapid and specific detection.
Although Campylobacter is an important food-borne human pathogen, there remains a lack of molecular diagnostic assays that are simple to use, cost-effective, and provide rapid results in research, clinical, or regulatory laboratories. Of the numerous Campylobacter assays that do exist, to our knowledge none has been empirically tested for specificity using high-throughput sequencing. Here we demonstrate the power of next-generation sequencing to determine the specificity of a widely cited Campylobacter-specific polymerase chain reaction (PCR) assay and describe a rapid method for direct cell suspension PCR to quickly and easily screen samples for Campylobacter. We present a specific protocol which eliminates the need for time-consuming and expensive genomic DNA extractions and, using a high-processivity polymerase, demonstrate conclusive screening of samples in <1 h. Pyrosequencing results show the assay to be extremely (>99%) sensitive, and spike-back experiments demonstrated a detection threshold of <10(2) CFU mL(-1). Additionally, we present 2 newly designed broad-range bacterial primer sets targeting the 23S rRNA gene that have wide applicability as internal amplification controls. Empirical testing of putative taxon-specific assays using high-throughput sequencing is an important validation step that is now financially feasible for research, regulatory, or clinical applications.


Stabilization of an axially moving accelerated/decelerated system via an adaptive boundary control.
In this study, an adaptive boundary control is developed for vibration suppression of an axially moving accelerated/decelerated belt system. The dynamic model of the belt system is represented by partial-ordinary differential equations with consideration of the high acceleration/deceleration and unknown distributed disturbance. By utilizing adaptive technique and Lyapunov-based back stepping method, an adaptive boundary control is proposed for vibration suppression of the belt system, a disturbance observer is introduced to attenuate the effects of unknown boundary disturbance, the adaptive law is developed to handle parametric uncertainties and the S-curve acceleration/deceleration method is adopted to plan the belt׳s speed. With the proposed control scheme, the well-posedness and stability of the closed-loop system are mathematically demonstrated. Simulations are displayed to illustrate the effectiveness of the proposed control.


The Xenopus Nieuwkoop center and Spemann-Mangold organizer share molecular components and a requirement for maternal Wnt activity.
In Xenopus embryos, the dorso-ventral and antero-posterior axes are established by the Spemann-Mangold organizer. According to the prevalent model of early development, the organizer is induced by the dorsalizing Nieuwkoop signal, which is secreted by the Nieuwkoop center. Formation of the center requires the maternal Wnt pathway, which is active on the dorsal side of embryos. Nevertheless, the molecular nature of the Nieuwkoop signal remains unclear. Since the Nieuwkoop center and the organizer both produce dorsalizing signals in vitro, we asked if they might share molecular components. We find that vegetal explants, the source of Nieuwkoop signal in recombination assays, express a number of organizer genes. The product of one of these genes, chordin, is required for signaling, suggesting that the organizer and the center share at least some molecular components. Furthermore, experiments with whole embryos show that maternal Wnt activity is required in the organizer just as it is needed in the Nieuwkoop center in vitro. We conclude that the maternal Wnt pathway generates the Nieuwkoop center in vitro and the organizer in vivo by activating a common set of genes, without the need of an intermediary signaling step.


Psychological distress during the COVID-19 epidemic in Chile: The role of economic uncertainty.
Previous research has shown that the COVID-19 outbreak, social distancing, and lockdown can affect people's psychological well-being. The aims of this study were (1) to estimate the extent to which perceptions and expectations regarding the social, economic, and domestic effects of the COVID-19 outbreak are associated with psychological distress and (2) to identify some demographic, psychosocial, and economic factors associated with increased vulnerability to psychological distress during the COVID-19 outbreak in Chile. 1078 people participated in a telephone survey between May 30 and June 10, 2020. The sample is representative of the Chilean adult population. Psychological distress was assessed through a questionnaire of anxious and depressive symptoms (Patient Health Questionnaire-4). We analyzed the data set using ordinary least-squares regression models, first estimating models for the entire sample, and then stratifying the sample into different groups to explore differences by gender and age. 19.2% of participants displayed significant psychological distress (PHQ-4 ≥ 6), with moderate to severe anxiety-depression symptoms being more prevalent in women than in men (23.9% vs 14.1%, χ2 16.78, p<0.001). The results of this study suggest that being a woman, feeling lonely and isolated, living in the areas hit hardest by the pandemic and lockdown, expecting a lack of income due to having to stop working as a consequence of the pandemic, and having a history of diagnosed mental disorders are significantly associated with psychological distress (p<0.05). The results of this study highlight the need to implement psychosocial programs to guard people's psychological well-being and social policies to address economic uncertainty during the current COVID-19 outbreak in Chile.


[Not Available].
To examine the biotransformation of Deoxynivalenol (DON) by the normal gut flora of pigs (in reliance on toxin-source) an in-vitro system was established. Suspensions of rectum contents from different treated animals were incubated with pure DON. Despite fast adaptation of microflora (Deepoxidation of DON) of animals fed wheat diet, no effects on reduced feed consumption and weight gain were seen. Even fast adaptation of microflora (lower intestine) couldn't avoid DON-effects in vivo.


Natural occurrence of zearalenone in rice and soybean produced in Korea.
88 rice and 75 soybean samples were collected from 8 provinces of Korea from March through September in 1988. The Fusarium mycotoxins, zearalenone was analyzed by direct competitive enzyme linked immunosorbent assay. 10.2% of rice and 9.3 % of soybean samples contained detectable zearalenone.The average levels of zearalenone of rice and soybean samples were 11.78μg/kg and 7.70μ/kg, respectively.


Multiple independent spike foci and epilepsy, with special reference to a new epileptic syndrome of "severe epilepsy with multiple independent spike foci".
Markand and Blume first realized the specificity of the EEG pattern of multiple independent spike foci (MISF) in the late 1970s; its close relation with hypsarrhythmia and slow spike-waves, extensive bilateral brain lesion, and intractable seizures. But they did not recognize it as an epileptic syndrome. On the other hand, the authors had been taken notice of severe epilepsy with MISF (SE-MISF) as a peculiar clinico-electrical entity showing "generalized seizures", and pointed out its close relation to Lennox-Gastaut syndrome (LGS) from the long-term follow-up of LGS. SE-MISF is characterized by (1) interictal EEG showing multiple independent spike foci (three or more foci in both hemisphere, i.e. at least one in each hemisphere) and diffuse slowing of the background activity. Diffuse epileptic discharges are rare. (2) The main seizure type is frequent generalized minor seizures, often tonic spasms. (3) Mutual transition is often observed between the age-dependent epileptic encephalopathies, i.e. Ohtahara syndrome, West syndrome and LGS. (4) The age at epilepsy onset is early, but the onset of SE-MISF is variable. (5) It is often associated with mental retardation and neurological abnormalities, usually severe. (6) Etiology is variable and largely nonspecific, including prenatal, perinatal, and postnatal cerebral pathologies. (7) Prognoses for seizures and psychomotor development are poor. Seizures are very intractable and may cause psychomotor deterioration. SE-MISF may be classified into symptomatic generalized epilepsy, namely a diffuse encephalopathy with mutual transition between other age-dependent epileptic encephalopathies. This characteristic entity may be acknowledged as a new epileptic syndrome.


Periostin is an extracellular matrix protein required for eruption of incisors in mice.
A characteristic tooth of rodents, the incisor continuously grows throughout life by the constant formation of dentin and enamel. Continuous eruption of the incisor is accompanied with formation of shear zone, in which the periodontal ligament is remodeled. Although the shear zone plays a role in the remodeling, its molecular biological aspect is barely understood. Here, we show that periostin is essential for formation of the shear zone. Periostin-/- mice showed an eruption disturbance of incisors. Histological observation revealed that deletion of periostin led to disappearance of the shear zone. Electron microscopy revealed that the disappearance of the shear zone resulted from a failure in digestion of collagen fibers in the periostin-/- mice. Furthermore, immunohistochemical analysis using anti-periostin antibodies demonstrated the restricted localization of periostin protein in the shear zone. Periostin is an extracellular matrix protein, and immunoelectron microscopy showed a close association of periostin with collagen fibrils in vivo. These results suggest that periostin functions in the remodeling of collagen matrix in the shear zone.


Breast mass segmentation in ultrasound with selective kernel U-Net convolutional neural network.
In this work, we propose a deep learning method for breast mass segmentation in ultrasound (US). Variations in breast mass size and image characteristics make the automatic segmentation difficult. To address this issue, we developed a selective kernel (SK) U-Net convolutional neural network. The aim of the SKs was to adjust network's receptive fields via an attention mechanism, and fuse feature maps extracted with dilated and conventional convolutions. The proposed method was developed and evaluated using US images collected from 882 breast masses. Moreover, we used three datasets of US images collected at different medical centers for testing (893 US images). On our test set of 150 US images, the SK-U-Net achieved mean Dice score of 0.826, and outperformed regular U-Net, Dice score of 0.778. When evaluated on three separate datasets, the proposed method yielded mean Dice scores ranging from 0.646 to 0.780. Additional fine-tuning of our better-performing model with data collected at different centers improved mean Dice scores by ~6%. SK-U-Net utilized both dilated and regular convolutions to process US images. We found strong correlation, Spearman's rank coefficient of 0.7, between the utilization of dilated convolutions and breast mass size in the case of network's expansion path. Our study shows the usefulness of deep learning methods for breast mass segmentation. SK-U-Net implementation and pre-trained weights can be found at github.com/mbyr/bus_seg.


Prospective evaluation of bacterial antigen detection in cerebral spinal fluid in the diagnosis of bacterial meningitis in a predominantly adult hospital.
The results of all CSF latex agglutination (LA) tests performed in a large predominantly adult hospital over 1 yr are reviewed. Eight cases of bacterial meningitis were recognized during this time, and of these only three were due to organisms detectable by commercially available LA kits. In one case, the LA was uninterpretable, and in the second the LA was not performed because less than 5 x 10(6) WBC/L were seen in the CSF. In the third case the Gram stain was positive. No cases of partially treated meningitis were diagnosed. In this setting, the LA test did not contribute significantly to patient management.


Multilevel cervical reconstruction with no remaining hardware: the potential of a vascularised fibular strut graft.
We present a case of a cervical chordoma extending from C3 to C6, treated by surgical resection followed by reconstruction in two stages with a vascularised fibular strut graft anteriorly and fibular allografts posteriorly. The goal was to achieve a stable reconstruction without any metal hardware to allow for increased accuracy of the adjuvant radiotherapy. The advantages of a vascularised fibula flap to realise this are discussed.


Characterization of corticosteroid receptors in natural killer cells: comparison with circulating lymphoid and myeloid cells.
Lymphocytes mediating natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities are relatively refractory to the changes in circulatory traffic and intrinsic function induced in other cell types by in vivo and in vitro corticosteroids (CS). To investigate if such drug resistance could be attributed to differences in the CS receptor number of affinity (Kd) of these cells, these characteristics were determined in purified populations of large granular lymphocytes (LGL), monocytes, neutrophils (PMN), and T cells. All cell types displayed a single class of CS receptor of uniform affinity; however, LGL resembled monocytes and PMN in receptor number and Kd while T cells had significantly fewer sites per cell with lower Kd. These studies suggest that the unresponsiveness of NK activity to CS is not secondary to differences in CS receptor capacity or affinity.


Current Situation and Causes Analysis of Cadmium Pollution in the Kakehashi River Basin.
Cadmium (Cd) pollution is a public environmental problem worthy of attention. Long-term exposure to Cd may have adverse effects on human health. Our previous study showed that urinary concentration of Cd (U-Cd) in the residents decreased when Cd-polluted paddy soil was removed. However, from 2008 to 2014, the concentration of U-Cd increased. At the same time, the concentration of urinary β2-microglobulin (β2-MG), which is considered to be an early sign of cadmium-induced renal dysfunction, increased continuously. To find the cause of elevated urinary cadmium (U-Cd) in residents of cadmium-contaminated areas, we measured the concentration of cadmium in the blood (B-Cd) of 29 elderly residents (15 female and 14 male) and edible rice (R-Cd), and correlations between R-Cd, B-Cd, and U-Cd were analyzed in the formerly cadmium-polluted areas (the Kakehashi River basin). In 2016, we collected blood, urine, and rice samples from each participant. The analysis showed a significant correlation between age and B-Cd, U-Cd, and β2-MG. However, there was no significant correlation between R-Cd and U-Cd, B-Cd, or β2-MG concentrations. Although we found a slightly higher level of Cd in rice and urine than reported in 2008, we cannot be sure that it indicates an increased Cd contamination in the Kakehashi River basin because larger studies are required for such a conclusion. The increased urinary Cd concentrations in this area may be because Cd in tissues and organs returns to blood and urine as participants age, which leads to an increasing trend.


A protocol for the identification and validation of novel genetic causes of kidney disease.
Genetic renal diseases (GRD) are a heterogeneous and incompletely understood group of disorders accounting for approximately 10 % of those diagnosed with kidney disease. The advent of Next Generation sequencing and new approaches to disease modelling may allow the identification and validation of novel genetic variants in patients with previously incompletely explained or understood GRD. This study will recruit participants in families/trios from a multidisciplinary sub-specialty Renal Genetics Clinic where known genetic causes of GRD have been excluded or where genetic testing is not available. After informed patient consent, whole exome and/or genome sequencing will be performed with bioinformatics analysis undertaken using a customised variant assessment tool. A rigorous process for participant data management will be undertaken. Novel genetic findings will be validated using patient-derived induced pluripotent stem cells via differentiation to renal and relevant extra-renal tissue phenotypes in vitro. A process for managing the risk of incidental findings and the return of study results to participants has been developed. This investigator-initiated approach brings together experts in nephrology, clinical and molecular genetics, pathology and developmental biology to discover and validate novel genetic causes for patients in Australia affected by GRD without a known genetic aetiology or pathobiology.


Combined stress myocardial CT perfusion and coronary CT angiography as a feasible strategy among patients presenting with acute chest pain to the emergency department.
A combined approach of myocardial CT perfusion (CTP) with coronary CT angiography (CTA) was shown to have better diagnostic accuracy than coronary CTA alone. However, data on cost benefits and length of stay when compared to other perfusion imaging modalities has not been evaluated. Therefore, we aim to perform a feasibility study to assess direct costs and length of stay of a combined stress CTP/CTA and use SPECT myocardial perfusion imaging (SPECT-MPI) as a benchmark, among chest pain patients at intermediate-risk for acute coronary syndrome (ACS) presenting to the emergency department (ED). This is a prospective two-arm clinical trial (NCT02538861) with 43 patients enrolled in stress CTP/CTA arm (General Electric Revolution CT) and 102 in SPECT-MPI arm. Mean age of the study population was 65 ± 12 years; 56% were men. We used multivariable linear regression analysis to compare length of stay and direct costs between the two modalities. Overall, 9 out of the 43 patients (21%) with CTP/CTA testing had an abnormal test. Of these 9 patients, 7 patients underwent invasive coronary angiography and 6 patients were found to have obstructive coronary artery disease. Normal CTP/CTA test was found in 34 patients (79%), who were discharged home and all patients were free of major adverse cardiac events at 30 days. The mean length of stay was significantly shorter by 28% (mean difference: 14.7 h; 95% CI: 0.7, 21) among stress CTP/CTA (20 h [IQR: 16, 37]) compared to SPECT-MPI (30 h [IQR: 19, 44.5]). Mean direct costs were significantly lower by 44% (mean difference: $1535; 95% CI: 987, 2082) among stress CTA/CTP ($1750 [IQR: 1474, 2114] compared to SPECT-MPI ($2837 [IQR: 2491, 3554]). Combined stress CTP/CTA is a feasible strategy for evaluation of chest pain patients presenting to ED at intermediate-risk for ACS and has the potential to lead to shorter length of stay and lower direct costs.


Pharmacological anti-tumor effects of natural Chamaecyparis obtusa (siebold & zucc.) endl. Leaf extracts on breast cancer.
Chamaecyparis obtusa (C. obtusa, cypress species) is a plant that grows mainly in the temperate Northern Hemisphere and has long been used as a traditional anti-inflammatory treatment in East Asia. C. obtusa contains phytoncides, flavonoids, and terpenes, which have excellent anti-cancer effects and have been reported to prevent the progression of various cancers. However, the detailed mechanisms underlying the anti-cancer effects of C. obtusa extracts are unknown. We sought to confirm the anti-cancer effects of C. obtusa leaf extracts and to reveal the mechanism of action, with the possibility of its application in the treatment or prevention of cancer. The cytotoxicity of C. obtusa leaf extracts was confirmed using an MTT assay. Intracellular changes in protein levels were measured by immunoblotting, and mRNA levels were measured with qRT-PCR. Wound healing assay and transwell migration assay were used to evaluate the metastatic potential of breast cancer cells. The extract-induced apoptosis was observed using IncuCyte Annexin V Red staining analysis. A syngeneic breast cancer mouse model was established by injecting 4T1-Luc mouse breast cancer cells into the fat pad of female BALB/c mice, and the extract was administered orally. Luciferin solution was injected intraperitoneally to assess primary tumor development and metastasis by bioluminescence. C. obtusa leaf extracts were extracted with boiling water, 70% EtOH, and 99% EtOH. Among the extracts, the 99% EtOH extract of C. obtusa leaf (CO99EL) most clearly inhibited the tyrosine phosphorylation of Signal Transducer and Activator of Transcription 3 (pY-STAT3) in MDA-MB-231 breast cancer cells at a concentration of 25 and 50 μg/mL. In addition, CO99EL strongly inhibited not only endogenous pY-STAT3 levels but also IL-6-induced STAT3 activation in various types of cancer cells, including breast cancer. CO99EL inhibited metastatic potential by downregulating the expression of N-cadherin, fibronectin, TWIST, MMP2, and MMP9 in MDA-MB-231 breast cancer cells. CO99EL also induced apoptotic cell death by increasing cleaved caspase-3 and decreasing anti-apoptotic proteins Bcl-2 and Bcl-xL. In an in vivo syngeneic breast cancer mouse model, 100 mg/kg CO99EL suppressed tumor growth and induced apoptosis of cancer cells. Moreover, CO99EL significantly inhibited lung metastasis from primary breast cancer. Our study demonstrated that 100 mg/kg CO99EL has potent anti-tumor effects against breast cancer, thus suggesting that 100 mg/kg CO99EL has potential applications in the treatment and prevention of breast cancer.


Diagnostic performance of CT lung severity score and quantitative chest CT for stratification of COVID-19 patients.
Lung severity score (LSS) and quantitative chest CT (QCCT) analysis could have a relevant impact to stratify patients affected by COVID-19 pneumonia at the hospital admission. The study aims to assess LSS and QCCT performances in severity stratification of COVID-19 patients. From April 19, 2020, until May 3, 2020, patients with chest CT suggestive for interstitial pneumonia and tested positive for COVID-19 were retrospectively enrolled and stratified for hospital admission as Group 1, 2 and 3 (home isolation, low intensive care and intensive care, respectively). For LSS, lungs were divided in 20 regions and visually assessed by two radiologists who scored for each region from non-lung involvement as 0, < 50% assigned as 1 and > 50% as 2. QCCT was performed with a dedicated software that extracts pulmonary involvement expressed in liters and percentage. LSS and QCCT were analyzed with ROC curve analysis to predict the performance of both methods. P values < 0.05 were considered statistically significant. Final population enrolled included 136 patients (87 males, mean age 66 ± 16), 19 patients in Group 1, 86 in Group 2 and 31 in Group 3. Significant differences for LSS were observed in almost all comparisons, especially in Group 1 vs 3 (AUC 0.850, P < 0,0001) and Group 1 + 2 vs 3 (AUC 0.783, P < 0,0001). QCCT showed significant results in almost all comparisons, especially between Group 1 vs 3 (AUC 0.869, P < 0,0001). LSS and QCCT comparison between Group 1 and Group 2 did not show significant differences. LSS and QCCT could represent promising tools to stratify COVID-19 patient severity at the admission.


Symptoms of influenza virus infection in hospitalized patients.
During influenza outbreaks, fever and cough are the most accurate symptoms in predicting influenza virus infection in the community. To determine the usefulness of fever, cough, and other symptoms for diagnosing influenza virus infection in hospitalized patients. Prospective cohort study. Three wards (pulmonology, internal medicine and infectious diseases, and geriatrics) of a tertiary care hospital in the Netherlands. All patients staying in the wards during peak national influenza activity in the 2005-2006 and 2006-2007 influenza seasons. During peak influenza activity, the presence of fever, cough, and/or other symptoms possibly associated with influenza was monitored for all patients, and nose and throat swab samples were taken twice weekly for virologic analysis. Of 264 patients, 23 (9%) tested positive for influenza virus. The positive predictive value of fever and cough for the diagnosis of influenza virus infection was 23% (95% confidence interval, 0%-62%), and the sensitivity was 35% (95% confidence interval, 11%-58%). The combination of symptoms with the highest positive predictive value (40%) was that of cough, chills, and obstructed nose or coryza. The combination of cough and chills or fever had the highest sensitivity (60%). None of the combinations of symptoms had both a positive predictive value and a sensitivity higher than 40%. Both the sensitivity and the positive predictive value of fever, cough, and/or other symptoms for the diagnosis of influenza virus infection in hospitalized patients are low. The use of these common symptoms for treatment decisions and infection control management will probably be insufficient to contain a nosocomial outbreak, because many influenza cases will remain unidentified.


[Adolescent scoliosis : From deformity to treatment].
Scoliosis affects up to 6 % of the population. The resulting spine deformity, the increasing risk of back pain, cosmetic aspects, pulmonary disorders if the Cobb angle is > 80°, and the progress of the deformity to > 50° after the end of growth indicate non-operative or operative therapy. In daily clinical practice, the classifications of scoliosis allow the therapy to be adapted. Classifications consider deformity, topography of the scoliosis, and the age at diagnosis. This publication gives an overview of the relevant and most common classifications in the treatment of adolescent scoliosis. For evaluation, the deformity measurement on the coronary radiographic projection of the total spine (Cobb angle) is relevant to therapy. The classification of topography, form, and the sagittal profile of the deformity of the spine are useful for preoperative planning of the fusion level. Classifications that take into account the age at the time of the diagnosis of scoliosis differentiate among early onset scoliosis (younger than 10 years of age), adolescent scoliosis (up to the end of growth), and adult scoliosis. Early onset scoliosis is subdivided by age and etiology. Therapy is derived from the classification of clinical and radiological findings. Classifications that take into account clinical and radiological parameters are essential components of modern scoliosis therapy.


Seasonal variation of manic and depressive symptoms in bipolar disorder.
Analyses of seasonal variation of manic and depressive symptoms in bipolar disorder in retrospective studies examining admission data have yielded conflicting results. We examined seasonal variation of mood symptoms in a prospective cohort with long-term follow-up: the Collaborative Depression Study (CDS). The CDS included participants from five academic centers with a prospective diagnosis of bipolar I or II disorder. The sample was limited to those who were followed for at least 10 years of annual or semi-annual assessments. Time series analyses and autoregressive integrated moving average (ARIMA) models were used to assess seasonal patterns of manic and depressive symptoms. A total of 314 individuals were analyzed (bipolar I disorder, n = 202; bipolar II disorder, n = 112), with both disorders exhibiting the lowest frequency of depressive symptoms in summer and the highest around the winter solstice, though the winter peak in symptoms was statistically significant only with bipolar I disorder. Variation of manic symptoms was more pronounced in bipolar II disorder, with a significant peak in hypomanic symptomatology in the months surrounding the fall equinox. Significant seasonal variation exists in bipolar disorder, with manic/hypomanic symptoms peaking around the fall equinox and depressive symptoms peaking in the months surrounding the winter solstice in bipolar I disorder.


Synthesis, characterization, and anticancer evaluation of novel 4-hydrazinothiazole analogs.
Single-step synthesis of novel 4-hydrazinothiazole derivatives 6a-e was achieved under mild conditions using the sequential four-components method involving isothiocyanate, aminoguanidine, carbonyl adduct, and α-haloketone derivatives. Deprotection of these hydrazinothiazoles was influenced by acylation, providing a novel group of diacylated molecular structures with a broader scope for the design of thiazolyl-containing drugs 7a and 7b. FTIR, 1 H/13 C NMR, LC-MS spectroscopy, and CHN elemental analyses were used to study the compound chemical structures. Using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on human periodontal ligament fibroblast (HPDLF) cells, the 4-hydrazinothiazole derivatives were screened for cytotoxicity in an in vitro cytotoxicity investigation. The 4-hydrazinothiazole compound 6b bearing an isopropylidene-hydrazino group demonstrated strongly potent cytotoxicity against CAKI1 (IC50 = 1.65 ± 0.24 μM) and A498 (IC50 of 0.85 ± 0.24 μM). Furthermore, the chloroacetyl-containing thiazole compound 7a displayed efficient inhibition of growth against the test cell lines CAKI1 and A498 at low micromolar concentrations, IC50 0.78 and 0.74 μM, respectively.


An anatomical and electrophysiological study of the centrifugal visual system in the lamprey (Lampetra fluviatilis).
The centrifugal visual system of the lamprey Lampetra fluviatilis was investigated using various neurohistophysical methods: intraocular injections of [3H]adenosine, fluorescent tracer (Evans Blue) and the iontophoretic deposit of HRP on the optic nerve. Retrogradely labeled neurons were identified bilaterally within the nucleus M5 of Schober and contralaterally in the reticular mesencephalic area (RMA). Comparison of the various orthograde and retrograde labeling results indicated that the neurons of M5 and RMA were labeled via retrograde axonal transport of the different tracers in the retinopetal system and not by orthograde transneuronal processes or from extraretinal pathways. Part of the anatomical data regarding RMA as a site of origin of the centrifugal visual system was confirmed using electrophysiological techniques involving evoked potential and unit cell recordings in RMA following electrical stimulation of the optic nerve. The experiments were performed in the curarized animal under conditions of either normal blood circulation, perfusions of adapted physiological saline, or with a solution known to block chemical synaptic transmission. Various electrophysiological criteria, including the results obtained during the conditions of reversible chemical synaptic blockade, indicated that the responses in RMA reflect an antidromic process. The anatomical organization of the centrifugal visual system in the lamprey is compared to that found in different gnathostome vertebrate species. Several hypotheses concerning the marked interspecies differences related either to the number and the topographical location of the centrifugal neurons as well as the evolution of this system are advanced.


A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction.
We used nuclear magnetic resonance data to determine ensembles of conformations representing the structure and dynamics of calmodulin (CaM) in the calcium-bound state (Ca(2+)-CaM) and in the state bound to myosin light chain kinase (CaM-MLCK). These ensembles reveal that the Ca(2+)-CaM state includes a range of structures similar to those present when CaM is bound to MLCK. Detailed analysis of the ensembles demonstrates that correlated motions within the Ca(2+)-CaM state direct the structural fluctuations toward complex-like substates. This phenomenon enables initial ligation of MLCK at the C-terminal domain of CaM and induces a population shift among the substates accessible to the N-terminal domain, thus giving rise to the cooperativity associated with binding. Based on these results and the combination of modern free energy landscape theory with classical allostery models, we suggest that a coupled equilibrium shift mechanism controls the efficient binding of CaM to a wide range of ligands.


Flunitrazepam and triazolam: a comparison of behavioral effects and abuse liability.
The performance, observer-rated, and participant-rated effects of orally administered placebo, and two benzodiazepines, flunitrazepam (2, 4 and 8 mg/70 kg) and triazolam (0.25, 0.5 and 1 mg/70 kg), were compared in 14 sedative drug abusers using a double-blind crossover design. Both flunitrazepam and triazolam produced dose-related decrements in memory and psychomotor/cognitive performance, and increases in many participant- and observer-rated measures. Effects of flunitrazepam had an earlier onset and a longer duration than those of triazolam. Although there was evidence that the flunitrazepam doses selected for study were somewhat higher overall relative to the selected triazolam doses, analysis of the participant-rated measures collected 24 h after drug administration (next-day) suggests that flunitrazepam may have a greater abuse liability than triazolam when abuse liability is assessed 24 h after drug administration. The highest flunitrazepam dose produced effects that were significantly greater than those of the highest triazolam dose on next-day ratings of good effects, take again, and worth; all tested flunitrazepam doses produced effects greater than any triazolam dose on next-day ratings of liking and take again. The highest flunitrazepam dose, but no triazolam dose, significantly increased the maximum dollar value at which participants chose drug over money in a Drug versus Money Choice Procedure.


Pressuring children to learn versus developmentally appropriate education.
Preschool and kindergarten programs have changed focus from an emphasis on play to an emphasis on formal academics. This trend is evaluated in light of research on children's development and learning. An alternative model of a developmentally appropriate program for young children is discussed.