Unusual presentation of haemophilia in two paediatric patients.
Haemophilia A is a rare X-linked recessive bleeding disorder caused by deficiency or functional defects in coagulation factor VIII (FVIII). Here, we report two cases of challenging diagnosis of haemophilia A because of unusual presentation. The first case is a 10-month-old female, admitted to our hospital because a neck mass appeared within the previous 24 h, who had a past medical history consistent with recurrent spontaneous haematomas but no family history of bleeding disorders. Despite several radiological evaluations, only the histology of the mass defined the presence of a haematoma. Chromosomal analysis revealed a normal female karyotype and a de-novo mutation into the FVIII intron 22 associated with a skewed X chromosome inactivation. The second case is a male neonate with a history of seizures who underwent brain MRI that showed a suspicious vascular malformation on the quadrigeminal cistern, causing cerebellum compression and hydrocephalus. The clinical conditions of the child progressively worsened and blood tests revealed a severe deficit of FVIII levels. The radiological images were re-evaluated; vascular anomalies were excluded and the diagnosis of haematoma was made. Family history was negative for coagulation disorders. Molecular studies revealed a rearrangement of the FVIII gene involving intron 22. The haemophilia A diagnosis can be challenging. Lack of family history, difficulties in detecting haematomas by imaging techniques, female sex and neonatal age represent misleading factors that can delay the diagnosis.


[Screening of hearing in children up to 18 months of age].
In the Netherlands the hearing screening of young children is carried out at the age of nine months by the Ewing or 'Compact Amsterdam paedo-audiometric screener' (CAPAS) test. These screening tests do not always lead to the necessary follow-up diagnostics, mainly because the different disciplines disagree. Recently a consensus concerning the follow-up of children with a poor test result was reached by the Youth Health Care institutions, general practitioners, paediatricians, ENT physicians and audiologic centres. Each party has its own responsibilities and commits itself to complete the diagnostics before the age of 18 months. Until new screening methods have been validated it is advised to refer all children with poor screening test results for special diagnostics, if necessary after they have been treated for otitis media with effusion. Currently the most appropriate method for final diagnosis is the measurement of oto-acoustic emissions.


[Epidemiology of methicillin-resistance among Staphylococci strains isolated in risk units and effects of the vancomycin on the expression of methicillin-resistance].
Four hundred Staphylococci strains, isolated from different in intensive care unit hospitalized patients, were analyzed. 53% of all strains were resistant to methicillin. Against methicillin-resistant S. aureus (MRSA), teicoplanin and vancomycin (100% of susceptibility), rifampin (76.3%) and co-trimoxazole (73%) emerged as the most potent drugs tested; the 15% of the strains were susceptible to ciprofloxacin, erythromycin, clindamycin and gentamicin. Only one MRSA strain (0.8%) resulted hetero-resistant to vancomycin. Among 100 strains exposed to serial concentration of vancomycin (0.25-32 mg/L for 30 days), 57 were selected with intermediate-level of resistance to the glycopeptides; the MRSA strains have shown to acquire resistance in vitro more easily than methicillin-susceptible. These results indicate that in the clones of Staphylococci circulating in our region, the evolution of glycopeptides-resistance is not a rapid process and the loss of effectiveness of these antibiotics cannot be predicted to short term. In particular, the restriction profile analysis of chromosomal DNA from MRSA strains, selected in vitro with intermediate -level of vancomycin resistance, demonstrated that at the moment in the hospital departments studied, the diffusion of a clone able to acquire resistance more easily than others is not present.


H3K27 Methylation Dynamics during CD4 T Cell Activation: Regulation of JAK/STAT and IL12RB2 Expression by JMJD3.
The changes to the epigenetic landscape in response to Ag during CD4 T cell activation have not been well characterized. Although CD4 T cell subsets have been mapped globally for numerous epigenetic marks, little has been done to study their dynamics early after activation. We have studied changes to promoter H3K27me3 during activation of human naive and memory CD4 T cells. Our results show that these changes occur relatively early (1 d) after activation of naive and memory cells and that demethylation is the predominant change to H3K27me3 at this time point, reinforcing high expression of target genes. Additionally, inhibition of the H3K27 demethylase JMJD3 in naive CD4 T cells demonstrates how critically important molecules required for T cell differentiation, such as JAK2 and IL12RB2, are regulated by H3K27me3. Our results show that H3K27me3 is a dynamic and important epigenetic modification during CD4 T cell activation and that JMJD3-driven H3K27 demethylation is critical for CD4 T cell function.


Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine.
Cell therapy involves the transplantation of human cells to replace or repair the damaged tissues and modulate the mechanisms underlying disease initiation and progression in the body. Nowadays, many different types of cell-based therapy are developed and used to treat a variety of diseases. In the past decade, cell-free therapy has emerged as a novel approach in regenerative medicine after the discovery that the transplanted cells exerted their therapeutic effect mainly through the secretion of paracrine factors. More and more evidence showed that stem cell-derived secretome, i.e., growth factors, cytokines, and extracellular vesicles, can repair the injured tissues as effectively as the cells. This finding has spurred a new idea to employ secretome in regenerative medicine. Despite that, will cell-free therapy slowly replace cell therapy in the future? Or are these two modes of treatment still needed to address different diseases and conditions? This review provides an indepth discussion about the values of stem cells and secretome in regenerative medicine. In addition, the safety, efficacy, advantages, and disadvantages of using these two modes of treatment in regenerative medicine are also critically reviewed.


Role of angiotensin in ameliorating the renal actions of norepinephrine.
To determine the importance of the arterial pressure effects of angiotensin II (ANG II) on renal function during acute renal adrenergic stimulation, we examined the effects of a 2-h intrarenal arterial infusion of norepinephrine (NE) at 0.1 and 0.25 micrograms.kg-1.min-1 on renal function in five conscious dogs during 1) control conditions, 2) servo-control of renal arterial pressure (RAP) at control levels, and 3) chronic captopril administration. The low rate of NE infusion produced an approximately 20% decrease in glomerular filtration rate (GFR) and renal plasma flow (RPF) and an approximately 8-mmHg increase in RAP in association with an approximately 2.5-fold rise in plasma renin activity (PRA). The high rate of NE infusion produced greater increments in both PRA and RAP and an approximately 50% reduction in GFR and RPF. Neither servo-control of RAP nor captopril administration significantly affected the above renal responses to the low rate of NE infusion. In marked contrast, when increases in RAP (approximately 20 mmHg) were prevented at the high rate of NE infusion by servo-control of RAP, both the PRA and renal responses were enhanced. Furthermore, when RAP was reduced (approximately 25 mmHg) as a result of chronically blocking the renin-angiotensin system with captopril, the renal responses to the high rate of NE infusion were exaggerated even further; in four of five dogs, total renal ischemia occurred in response to NE. These results indicate that ANG II indirectly ameliorates the renal actions of renal adrenergic stimulation by increasing RAP.


Next-generation sequencing for genetic testing of hearing loss populations.
Hearing loss is a common sensorineural disease with genetic heterogeneity. More than 140 genes are known to cause hereditary hearing loss. We aim to uncover the etiologies of hearing loss and provide patients with reasonable reproductive choices. Total 825 participants were recruited, including 74 individuals, 47 couples, and 219 families, to identify the molecular etiologies of hearing loss using next-generation sequencing (NGS). Novel mutations were verified with a minigene splicing assay and the construction of three-dimensional protein models. A positive molecular diagnosis was obtained for 244 patients, a rate of 63.05 %. Total 470 mutations were identified in 18 causative genes in positive patients. The most common genes mutated were GJB2 and SLC26A4. 47 novel mutations were identified. Further analysis predicted that two splicing mutations would cause abnormal mRNA splicing and three missense mutations would affect the protein structure. The results of prenatal diagnosis showed that the genotypes of 15 fetuses were the same as the probands. Our findings expand the mutation spectrum of hearing loss and highlight the importance of genetic diagnosis and prenatal diagnosis to allow accurate and personalized guidance for those at high risk of deafness.


The utility of platelet, mean platelet volume, and red cell distribution width in the diagnosis of active Crohn's disease and intestinal tuberculosis.
To evaluate the diagnostic utility of platelet count (PLT), mean platelet volume (MPV), and red cell distribution width (RDW) in patients with active Crohn's disease (CD) and intestinal tuberculosis (ITB). This study was conducted in the Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China. Sixty-eight patients with active CD, 35 with ITB, and 22 as control group were recruited. Blood routine test including white blood cell, red blood cell, PLT, MPV, RDW, and so forth was investigated. Patients with active CD and ITB have increased PLT and RDW (both p<0.001), and decreased MPV (p=0.002). The RDW performed preferably in predicting both active CD (odds ratio [OR]=2.390, p=0.007), and ITB (OR=2.338, p=0.017), and had better diagnostic value (area under the receiver operating characteristics curve [AUC] - 0.812; p<0.001) than CRP (AUC - 0.716; p=0.007) and ESR (AUC - 0.804; p<0.001) in ITB diagnosis. Among the laboratory markers, RDW not only possessed the favorable capability to predict active CD, but also showed outstanding predicting capability, and good diagnostic value in ITB.


Retrospective evaluation of three treatment methods for primary hyperparathyroidism in dogs.
The medical records of 110 dogs treated for primary hyperparathyroidism were reviewed. Dogs were treated via parathyroidectomy (n=47), percutaneous ultrasound-guided ethanol ablation (n=15), or percutaneous ultrasound-guided heat ablation (n=48). Forty-five of 48 (94%) parathyroidectomies resulted in control of hypercalcemia for a median of 561 days. Thirteen of 18 (72%) ethanol ablation procedures resulted in control of hypercalcemia for a median of 540 days. Forty-four of 49 (90%) heat-ablation treatments resulted in control of hypercalcemia for a median of 581 days.


Fatty acid-binding protein activity in tissues from pigs fed diets containing 0 and 20% high oleate oil.
Eight pigs (four sets of littermates) were allotted to either a control sorghum-soybean meal diet or a test diet containing 20% canola oil. The pigs were slaughtered at approximately 100 kg live weight. Subcutaneous adipose tissue, longissimus dorsi muscle and liver samples were collected immediately after slaughter. Fatty acid-binding protein (FABP) was measured in 104,000 x g supernatant fractions. Characterization of the FABP assay with liver supernatants indicated that FABP exhibited sigmoidal kinetics, with an apparent Kd of 0.75 microM. Doubling the protein amount in the assay did not affect the FABP activity. FABP was demonstrated in liver, with an activity of 3448 pmol bound/g liver, and in adipose tissue, with an activity of 276 pmol bound/g adipose tissue. No activity was observed in the muscle tissue. FABP activity of liver and adipose tissue from swine fed 20% canola oil was higher on a per gram tissue basis than that in tissues from pigs fed the control diet.


Intralipid Restoration of Myocardial Contractions Following Bupivacaine-Induced Asystole: Concentration- and Time-Dependence In Vitro.
The concentration- and time-response relationships of lipid emulsion (LE; Intralipid) on the recovery of myocardial contractility following bupivacaine (BPV)-induced asystole are poorly defined. After achieving asystole by 500-μM BPV, varied concentrations of LE were applied to determine the recovery of stimulated contractile responses and contractions in the cardiac tissues of guinea pigs at a 1.2-Hz stimulation rate. These experiments were performed with LE in either a recirculating (2%-16%) or washout (nonrecirculating) condition (0.05%-12%) for 60 minutes. The effect of LE itself (0.05%-12%) was examined. Oxfenicine was used to evaluate the metabolic action of LE to reverse asystole. BPV concentrations in solution and myocardial tissues were measured. In the recirculation condition, partial recovery of contractile forces was observed for 60 minutes at 4%, 8%, and 12% LE. A contracture followed after exposure to 16% LE in some asystolic muscles. In the washout experiments, following asystole, LE (0.05%-12%) had no effect on the recovery time of the first and regular contractile responses. LE (0.1%-8%) restored contractility to baseline levels after 45 minutes; partial recovery was shown with lower (0.05%) and higher (12%) concentrations. Oxfenicine did not alter the recovery of contractile forces. Contractile depression was observed with 12% LE alone. Concentration-related reduction of tissue BPV concentration by LE was observed in both circulating conditions. LE induced time- and concentration-dependent recovery of stimulated myocardial contractions from BPV-induced asystole. The lipid uptake effect, along with other undefined mechanisms of LE, seems to contribute to the recovery of contractile function; however, the LE effect on myocardial metabolism is less likely involved at this concentration (500 μM) of BPV.


Non-Coding RNAs in Human Breast Milk: A Systematic Review.
Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied. PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989.


The structure and function of Escherichia coli penicillin-binding protein 3.
Escherichia coli penicillin-binding protein PBP3 is a key element in cell septation. It is presumed to catalyse a transpeptidation reaction during biosynthesis of the septum peptidoglycan but, in vitro, its enzymatic activity has only been demonstrated with thiolester analogues of the natural peptide substrate. It has no detectable transglycosylase activity with lipid II as substrate. This tripartite protein is constructed of an N-terminal membrane anchor-containing module that is essential for cell septation, a non-penicillin-binding (n-PB) module of unknown function and a C-terminal penicillin-binding (PB) module exhibiting all the characteristic motifs of penicilloyl serine transferases. The n-PB module, which is required for the folding and stability of the PB module, may provide recognition sites for other cell division proteins. Initiation of septum formation is not PBP3-dependent but rests on the appearance of the FtsZ ring, and is thus penicillin-insensitive. The control of PBP3 activity during the cell cycle is briefly discussed.


Ultrastructural evaluation of mesenchymal stem cells from inflamed periodontium in different in vitro conditions.
This research aimed to observe the behavior of mesenchymal stem cells (MSCs) isolated from periodontal granulation tissue (gt) when manipulated ex vivo to induce three-dimensional (3D) spheroid (aggregates) formation as well as when seeded on two bone scaffolds of animal origin. Periodontal gt was chosen as a MSC source because of its availability, considering that it is eliminated as a waste material during conventional surgical therapies. 3D aggregates of cells were generated; they were grown for 3 and 7 days, respectively, and then prepared for transmission electron microscopic analysis. The two biomaterials were seeded for 72 h with gtMSCs and prepared for scanning electronic microscopic observation. The ultrastructural analysis of 3D spheroids remarked some differences between the inner and the outer cell layers, with a certain commitment observed at the inner cells. Both scaffolds showed a relatively smooth surface at low magnification. Macro- and micropores having a scarce distribution were observed on both bone substitutes. gtMSCs grew with relative difficulty on the biomaterials. After 72 h of proliferation, gtMSCs scarcely covered the surface of bovine bone scaffolds, demonstrating fibroblast-like or star-like shapes with elongated filiform extensions. Our results add other data on the possible usefulness of gtMSC and could question the current paradigm regarding the complete removal of chronically inflamed gts from the defects during periodontal surgeries. Until optimal protocols for ex vivo manipulation of MSCs are available for clinical settings, it is advisable to use biocompatible bone substitutes that allow the development of progenitor cells.


The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus.
We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. One hundred thirty-four FVL mutation carriers were identified among 4,885 gravidas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0-2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95% confidence interval 0.02-0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0-5.2, P = .05). Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated. II-2.


The dual effects of root-cap exudates on nematodes: from quiescence in plant-parasitic nematodes to frenzy in entomopathogenic nematodes.
To defend themselves against herbivores and pathogens, plants produce numerous secondary metabolites, either constitutively or de novo in response to attacks. An intriguing constitutive example is the exudate produced by certain root-cap cells that can induce a state of reversible quiescence in plant-parasitic nematodes, thereby providing protection against these antagonists. The effect of such root exudates on beneficial entomopathogenic nematodes (EPNs) remains unclear, but could potentially impair their use in pest management programmes. We therefore tested how the exudates secreted by green pea (Pisum sativum) root caps affect four commercial EPN species. The exudates induced reversible quiescence in all EPN species tested. Quiescence levels varied with the green pea cultivars tested. Notably, after storage in root exudate, EPN performance traits were maintained over time, whereas performances of EPNs stored in water rapidly declined. In sharp contrast to high concentrations, lower concentrations of the exudate resulted in a significant increase in EPN activity and infectiousness, but still reduced the activity of two plant-parasitic nematode species. Our study suggests a finely tuned dual bioactivity of the exudate from green pea root caps. Appropriately formulated, it can favour long-term storage of EPNs and boost their infectiousness, while it may also be used to protect plants from plant-parasitic nematodes.


Laser-Assisted Periodontal Management of Drug-Induced Gingival Overgrowth under General Anesthesia: A Viable Option.
Gingival overgrowth/hyperplasia can be attributed to several causes, but drug-induced gingival overgrowth/hyperplasia arises secondarily to prolonged use of antihypertensive drugs, anticonvulsants and immunosuppressants. The management is complex in nature considering the multitude of factors involved such as substitution of drug strict plaque control along with excision of the tissue to be performed under local anesthesia as outpatient. In the recent times, the patient's psychological fear of the treatment with the use of surgical blade and multiple visits has developed the concept of single visit treatment under general anesthesia incorporating a laser as viable option. The present case highlights the new method of management of gingival overgrowth.


Prevalence and risk factors for cancer of the uterine cervix among women living in Kinshasa, the Democratic Republic of the Congo: a cross-sectional study.
Cancer of the uterine cervix is the leading cause of cancer-related death among women in Sub-Saharan Africa, but information from the Democratic Republic of the Congo (DRC) is scarce. The study objectives were to: 1/ assess prevalence of (pre)cancerous cervical lesions in adult women in Kinshasa, 2/ identify associated socio-demographic and behavioural factors and 3/ describe human papillomavirus (HPV) types in cervical lesions. A cross-sectional study was conducted in Kinshasa. Between 2006 and 2013, four groups of women were recruited. The first two groups were included at HIV screening centres. Group 1 consisted of HIV-positive and group 2 of HIV-negative women. Group 3 was included in large hospitals and group 4 in primary health centres. Pap smears were studied by monolayer technique (Bethesda classification). Low- or high-grade squamous intraepithelial lesions or carcinoma were classified as LSIL+. HPV types were determined by INNO-LiPA®. Bivariate and multivariable analyses (logistic regression and generalised estimating equations (GEE)) were used to assess associations between explanatory variables and LSIL+. LSIL+ lesions were found in 76 out of 1018 participants. The prevalence was 31.3 % in group 1 (n = 131 HIV-positive women), 3.9 % in group 2 (n = 128 HIV-negative women), 3.9 % in group 3 (n = 539) and 4.1 % in group 4 (n = 220). The following variables were included in the GEE model but did not reach statistical significance: history of abortion, ≥3 sexual partners and use of chemical products for vaginal care. In groups 3 and 4 where this information was available, the use of plants for vaginal care was associated with LSIL+ (adjusted OR 2.70 (95 % confidence interval 1.04 - 7.01). The most common HPV types among HIV-positive women with ASCUS+ cytology (ASCUS or worse) were HPV68 (12 out of 50 samples tested), HPV35 (12/50), HPV52 (12/50) and HPV16 (10/50). Among women with negative/unknown HIV status, the most common types were HPV52 (10/40), HPV35, (6/40) and HPV18 (5/40). LSIL+ lesions are frequent among women in Kinshasa. The use of plants for vaginal care deserves attention as a possible risk factor for LSIL+. In this setting, HPV16 is not the most frequent genotype in samples of LSIL+ lesions.


Genome-Wide and Transcriptome Analysis of Jacalin-Related Lectin Genes in Barley and the Functional Characterization of HvHorcH in Low-Nitrogen Tolerance in Arabidopsis.
The jacalin-related lectins (JRLs) are widely distributed in plants and are involved in plant development and multiple stress responses. However, the characteristics of the HvJRL gene family at the genome-wide level and the roles of JRLs in barley's response to low-nitrogen (LN) stress have been rarely reported. In this study, 32 HvJRL genes were identified and unevenly distributed at both ends of the seven chromosomes in barley. HvJRL proteins generally exhibited low sequence similarity but shared conserved jacalin domains by multiple sequence analysis. These proteins were classified into seven subfamilies based on phylogenetic analysis, with a similar gene structure and conserved motifs in the same subfamily. The HvJRL promoters contained a large number of diverse cis-elements associated with hormonal response and stress regulation. Based on the phylogenetic relationships and functionally known JRL homologs, it was predicted that some HvJRLs have the potential to serve functions in multiple stress responses but not nutrition deficiency stress. Subsequently, nine differentially expressed genes (DEGs) encoding eight HvJRL proteins were identified in two barley genotypes with different LN tolerance by transcriptome analysis. Furthermore, 35S:HvHorcH transgenic Arabidopsis seedlings did enhance LN tolerance, which indicated that HvHorcH may be an important regulator of LN stress response (LNSR). The HvJRL DEGs identified herein could provide new candidate genes for LN tolerance studies.


Distribution and developmental changes of IL-21 immunopositive cells in the bursa of Fabricius of Jinhu silky chicken.
Bursa of Fabricius (BOF) is a unique immune organ of birds. It is the place where lymphocytes develop, differentiate and mature. Young chicken BOF is susceptible to infection and damage, and even atrophy, causing immune suppression, and bringing huge economic losses to chicken production. Therefore, studying the regulatory mechanism of chicken bursa development is of great practical significance for disease prevention and diagnosis. Jinhu silky chicken (JSC) is a local excellent breed in the Fujian Province of China and with strong disease resistance. However, studies on the disease resistance of JSC are scarce. This study aimed to provide a theoretical basis for reproduction and disease control of JSC. Developmental features of the structure and the IL-21-positive cell (IL-21 PC) distribution on the BOF in JSC were measured from 7 to 300 days of age. Bursas of chicken (n = 36) were taken at 7, 35, 70, 150, 240, and 300 days of age for preparation of paraffin sections and stained with hematoxylin-eosin (HE) and immunohistochemistry. The microstructure of JSC's BOF was similar to that of other poultry. The cortical-medullary boundary of the bursa nodule was not obvious at 7 days of age, but it was evident after 35 days of age. Before 70 days of age, IL-21 positive cells (PC) were scattered on the BOF. At 150 days of age, the number of IL-21 PC in the bursa were the highest and the nuclei were clear. The level of IL-21 PC gradually decreased with age. The BOF degenerated and disappeared in 300-day-old JSC. The histological structure of the BOF was similar to that of other poultry. IL-21 PC were widespread in the BOF at different ages, but the numbers were different.


Leverage points in the financial sector for seafood sustainability.
Can finance contribute to seafood sustainability? This is an increasingly relevant question given the projected growth of seafood markets and the magnitude of social and environmental challenges associated with seafood production. As more capital enters the seafood industry, it becomes crucial that investments steer the sector toward improved sustainability, as opposed to fueling unsustainable working conditions and overexploitation of resources. Using a mixed-methods approach, we map where different financial mechanisms are most salient along a seafood firm's development trajectory and identify three leverage points that can redirect capital toward more sustainable practices: loan covenants, stock exchange listing rules, and shareholder activism. We argue that seafood sustainability requirements need to be integrated into traditional financial services and propose key research avenues for academic, policy, and practice communities. While our study focuses on the role of finance in seafood sustainability, the insights developed are also of high relevance to other extractive industries.


Epidemiologic inference from the distribution of tuberculosis cases in households in Lima, Peru.
Tuberculosis (TB) often occurs among household contacts of people with active TB. It is unclear whether clustering of cases represents household transmission or shared household risk factors for TB. We used cross-sectional data from 764 households in Lima, Peru, to estimate the relative contributions of household and community transmission, the average time between cases, and the immunity afforded by a previous TB infection. The distribution of cases per household suggests that almost 7 of 10 nonindex household cases were infected in the community rather than in the household. The average interval between household cases was 3.5 years. We observed a saturation effect in the number of cases per household and estimated that protective immunity conferred up to 35% reduction in the risk of disease. Cross-sectional household data can elucidate the natural history and transmission dynamics of TB. In this high-incidence setting, we found that the majority of cases were attributable to community transmission and that household contacts of case patients derive some immunity from household exposures. Screening of household contacts may be an effective method of detecting new TB cases if carried out over several years.


Essential oil compositions of Teucrium fruticans, T. scordium subsp. scordioides and T. siculum growing in Sicily and Malta.
In the present study, the chemical composition of the essential oils from the aerial parts of Teucrium fruticans L. collected in Sicily and Malta, Teucrium scordium subsp. scordioides (Schreb.) Arcang. and Teucrium siculum (Raf.) Guss., collected in Sicily, were evaluated by GC-MS. The main volatile components of both T. fruticans collections were germacrene D (29.4% and 50.0%), (E)-β-caryophyllene (19.6% and 21.9%), and 1-octen-3-ol (19.7% and 7.4%); T. scordium subsp. scordioides essential oil was rich in caryophyllene oxide (25.8%), α-pinene (19.4%) and β-pinene (8.5%); T. siculum essential oil was rich in (E)-β-caryophyllene (30.9%), 1-octen-3-ol (9.0%), α-humulene (8.6%) and germacrene D (8.0%). The chemotaxonomic relationship with other members of the respective botanical sections was discussed.


Comprehensive analysis reveals key genes and environmental toxin exposures underlying treatment response in ulcerative colitis based on in-silico analysis and mendelian randomization.
UC is increasingly prevalent worldwide and represents a significant global disease burden. Although medical therapeutics are employed, they often fall short of being optimal, leaving patients struggling with treatment non-responsiveness and many related complications. The study utilized gene microarray data and clinical information from GEO. Gene enrichment and differential expression analyses were conducted using Metascape and Limma, respectively. Lasso Regression Algorithm was constructed using glmnet and heat maps were generated using pheatmap. ROC curves were used to assess diagnostic parameter capability, while XSum was employed to screen for small-molecule drugs exacerbating UC. Molecular docking was carried out using Autodock Vina. The study also performed Mendelian randomization analysis based on TwoSampleMR and used CTD to investigate the relationship between exposure to environmental chemical toxicants and UC therapy responsiveness. Six genes (ELL2, DAPP1, SAMD9L, CD38, IGSF6, and LYN) were found to be significantly overexpressed in UC patient samples that did not respond to multiple therapies. Lasso analysis identified ELL2 and DAPP1 as key genes influencing UC treatment response. Both genes accurately predicted intestinal inflammation in UC and impacted the immunological infiltration status. Clofibrate showed therapeutic potential for UC by binding to ELL2 and DAPP1 proteins. The study also reviews environmental toxins and drug exposures that could impact UC progression. We used microarray technology to identify DAPP1 and ELL2 as key genes that impact UC treatment response and inflammatory progression. Clofibrate was identified as a promising UC treatment. Our review also highlights the impact of environmental toxins on UC treatment response, providing valuable insights for personalized clinical management.


Degradation of a Metal-Polymer Interface Observed by Element-Specific Focused Ion Beam-Scanning Electron Microscopy.
The degradation of a metal-polymer interface was studied in three dimensions using focused ion beam-scanning electron microscopy (FIB-SEM) with energy-dispersive X-ray spectroscopy. A brass-rubber interface, which is important for tires, was examined as an example of a metal-polymer interface. Brass-plated steel cords were embedded in rubber, which was then vulcanized. The brass-rubber interface was treated at 70 °C under 96% humidity for up to 14 days (a wet-heat aging treatment). FIB-SEM provided clear three-dimensional images of the adhesive layer consisting of brass (CuZn), CuxS, and ZnO/ZnS between the steel cords and rubber. During degradation, CuxS at the interfaces diffused into the rubber, resulting in the direct contact of bare steel with rubber. The lack of a substantial adhesive layer explained the degradation of mechanical properties after the wet-heat treatment. In addition, electron diffraction and electron energy loss spectroscopy revealed that the Cu2S crystals in the adhesive layer changed to crystal-like CuS during the degradation, which also caused a degradation of mechanical properties because a high Cu valence of x ≈ 2 in CuxS leads to stronger adhesion than a valence of x = 1.


Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acid.
This study was performed to investigate the hypothesis that supplementation of conjugated linoleic acid (CLA) changes the concentrations of retinol and tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a CLA-free rumen-protected control fat (control group, n = 20) or the same amount of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks 1, 3, 5, 8 and 11 of lactation) were analysed for retinol, α- and γ-tocopherol concentrations. Milk of cows supplemented with CLA had higher concentrations of retinol (+34%), α-tocopherol (+44%) and γ-tocopherol (+21%) than milk of control cows (p < 0.05). The daily output of these vitamins via milk was also greater in cows of the CLA group than in cows of the control group (+36, 50 and 24% for retinol, α-tocopherol and γ-tocopherol, respectively, p < 0.05). In agreement with higher concentrations of tocopherols, concentrations of thiobarbituric acid-reactive substances, determined in milk of week 5, were lower in cows of the CLA group than in control cows, indicative of a lower susceptibility of milk lipids to peroxidation. Plasma concentrations of retinol and α-tocopherol, determined at 1 and 5 weeks post-partum, were not different between the two groups of cows. In conclusion, this study shows that supplementing dairy cows with a moderate amount of CLA causes an increase of the concentrations of vitamins A and E in the milk and results in an increased output of those vitamins via milk. These effects might be beneficial with respect to the nutritional value of dairy products and the susceptibility of milk fat to oxidative deterioration.


Ehlers-Danlos syndrome type IV.
Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae) are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular complication in a patient suffering from EDS type IV. Surgery may, however, be required urgently to treat potentially fatal complications.


Analysis of complex vascular systems in plants: optical shuttle method.
The "optical shuttle" is an improved method of photographing with a motion-picture camera, one by one, sequential sections mounted on separate slides. The optical output from two microscopes is combined so that the images can be focused on a single film plane. Slides are photographed alternately through the microscopes. Simultaneous viewing of two successive sections in the microscopes enables initial precise alignment of images. Complex anatomical structures can thus be analyzed with relative ease.


Diagnosis of type 1 and type 2 myocardial infarction using a high-sensitivity cardiac troponin I assay with sex-specific 99th percentiles based on the third universal definition of myocardial infarction classification system.
The frequency and characteristics of myocardial infarction (MI) subtypes per the Third Universal Definition of MI (TUDMI) classification system using high-sensitivity (hs) cardiac troponin assays with sex-specific cutoffs is not well known. We sought to describe the diagnostic characteristics of type 1 (T1MI) and type 2 (T2MI) MI using an hs-cardiac troponin I (hs-cTnI) assay with sex-specific cutoffs. A total of 310 consecutive patients with serial cTnI measurements obtained on clinical indication were studied with contemporary and hs-cTnI assays. Ninety-ninth percentile sex-specific upper reference limits (URLs) for the hs-cTnI assay were 16 ng/L for females and 34 ng/L for males. The TUDMI consensus recommendations were used to define and adjudicate MI based on each URL. A total of 127 (41%) patients had at least 1 hs-cTnI exceeding the sex-specific 99th percentiles, whereas 183 (59%) had hs-cTnI within the reference interval. Females had more myocardial injury related to supply/demand ischemia than males (39% vs 18%, P = 0.01), whereas males had more multifactorial or indeterminate injury (52% vs 33%, P = 0.05). By hs-cTnI, there were 32 (10%) acute MIs, among which 10 (3%) were T1MI and 22 (7%) were T2MI. T2MI represented 69% (22 out of 32) of all acute MIs, whereas T1MI represented 31% (10 out of 32). Ninety-five patients (31%) had an increased hs-cTnI above the 99th percentile but did not meet criteria for acute MI. The most common triggers for T2MI were tachyarrhythmias, hypotension/shock, and hypertension. By contemporary cTnI, more MIs (14 T1MI and 29 T2MI) were diagnosed. By contemporary cTnI, there were 43 MIs, 14 T1MI, and 29 T2MI. Fewer MI diagnoses were found with the hs-cTnI assay, contrary to the commonly accepted idea that hs-cTnI will lead to excessive false-positive diagnoses.


Is aspiration necessary before tympanostomy tube insertion?
Aspiration of middle ear fluid after myringotomy is performed routinely, although investigators imply a cause-and-effect relationship between suction noise and acoustic trauma. This prospective randomized study investigated if aspiration was necessary. Fifty-one myringotomies and 50 tympanostomy tube insertions were performed on 27 patients. A suction instrument was utilized in 24 ears and was not used in 27 ears. In a follow-up period, no difference was observed between the two groups. The authors did not establish that aspiration is indeed harmful, but tympanostomy tube insertion can be performed without suctioning middle ear effusion.


Identification of novel and downregulated biomarkers for alcoholism by surface enhanced laser desorption/ionization-mass spectrometry.
Since personal and verbal reporting of alcohol use is not necessarily accurate, objective markers to assess alcohol consumption are required. The currently available markers, however, are limited in sensitivity and specificity for screening of excessive alcohol drinkers. Therefore, searches for novel markers are warranted. Recently, surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) has been successfully used to detect disease-associated proteins in complex biological specimens. We used the ProteinChip SELDI technology to generate comparative protein profiles of the consecutive serum samples obtained during abstinence from a total of 16 chronic alcoholic patients hospitalized for a rehabilitation program. We recognized two peaks (5.9 and 7.8 kDa), both of which had been downregulated on admission, the expression level of which significantly increased after a one-week abstinence. These changes were also seen in nonresponders of gamma-glutamyltransferase. These two proteins were partially purified and subjected to amino acid sequencing. The 5.9 kDa protein was identified as a fragment of fibrinogen alphaE chain and the 7.8 kDa was a fragment of apoprotein A-II. These novel protein fragments may be promising biomarkers for excessive alcohol drinking.


Effects of ethidium bromide on the mitochondrial adenosine triphosphatase from Trypanosoma cruzi.
Culturing of Trypanosoma cruzi in the presence of ethidium bromide (EB; 1.0-2.5 microM), for 5 days, affected the biogenesis of the Fo/F1-ATPase complex, presumably by EB interference with the expression of the putative Fo-sector subunits encoded by maxicircle DNA. In vitro, EB inhibited ATP hydrolysis by the Fo/F1-ATPase complex and also by soluble F1, the former preparation being the most strongly affected (EB I50, 250 microM). Analysis of EB effect at increasing MgATP concentrations, as well as combination of EB and p-chloromercuribenzoate inhibitions, indicated that the dye interacts with ATPase at sites other than the catalytic ones. No correlation was found between the in vitro inhibition of ATPase and EB effect on parasite growth.


Spatial re-organization of myogenic regulatory sequences temporally controls gene expression.
During skeletal muscle differentiation, the activation of some tissue-specific genes occurs immediately while others are delayed. The molecular basis controlling temporal gene regulation is poorly understood. We show that the regulatory sequences, but not other regions of genes expressed at late times of myogenesis, are in close physical proximity in differentiating embryonic tissue and in differentiating culture cells, despite these genes being located on different chromosomes. Formation of these inter-chromosomal interactions requires the lineage-determinant MyoD and functional Brg1, the ATPase subunit of SWI/SNF chromatin remodeling enzymes. Ectopic expression of myogenin and a specific Mef2 isoform induced myogenic differentiation without activating endogenous MyoD expression. Under these conditions, the regulatory sequences of late gene loci were not in close proximity, and these genes were prematurely activated. The data indicate that the spatial organization of late genes contributes to temporal regulation of myogenic transcription by restricting late gene expression during the early stages of myogenesis.


Family eczema-history in 2-year-olds with eczema; a prospective, population-based study. The PACT-study, Norway.
A maternal line of inheritance regarding eczema has been described in several studies, whereas others find associations to both a maternal as well as a paternal line of inheritance. When studying family history of eczema symptoms, cohort studies including siblings are rare. Time point for assessing family eczema-history could be of importance when studying the associations between family eczema-history and children with eczema, as parents with unaffected children may not recall mild symptoms in other siblings or their own disease history. We therefore aimed to study the associations between reported eczema in mother, father and siblings and reported eczema in index child where information on family history was collected at two different ages of index child. Parents/children participating in The Prevention of Allergy among Children in Trondheim (PACT) study were given questionnaires on reported eczema symptoms in mother, father and siblings at 6 weeks and 1 year. When index child was 2 years of age, a detailed questionnaire on different health issues with emphasize on different allergy related disorders were filled in. Both maternal and paternal reports on eczema were significantly associated with eczema in index child. Reporting family eczema-history at 1 year (N = 3087), "eczema sibling only" [adjusted odds ratio (aOR) = 3.13 (2.27-4.33)] as well as all other family-groups containing siblings with eczema were strongly associated with eczema 2 years. When family eczema-history was reported at 6 weeks (N = 2657), reporting of "eczema sibling only" was not associated to reported eczema at 2 years in index child [aOR = 1.31 (0.77-2.23)]. Having sibling(s) with eczema strengthened the associations between maternal and paternal reports on eczema with eczema in index child only when exposure was reported at 1 year. These findings indicate that results from questionnaires-based studies of family eczema-history depend on whether or not index child has yet developed eczema.


Contrasting diversity patterns of crenarchaeal, bacterial and fungal soil communities in an alpine landscape.
The advent of molecular techniques in microbial ecology has aroused interest in gaining an understanding about the spatial distribution of regional pools of soil microbes and the main drivers responsible of these spatial patterns. Here, we assessed the distribution of crenarcheal, bacterial and fungal communities in an alpine landscape displaying high turnover in plant species over short distances. Our aim is to determine the relative contribution of plant species composition, environmental conditions, and geographic isolation on microbial community distribution. Eleven types of habitats that best represent the landscape heterogeneity were investigated. Crenarchaeal, bacterial and fungal communities were described by means of Single Strand Conformation Polymorphism. Relationships between microbial beta diversity patterns were examined by using Bray-Curtis dissimilarities and Principal Coordinate Analyses. Distance-based redundancy analyses and variation partitioning were used to estimate the relative contributions of different drivers on microbial beta diversity. Microbial communities tended to be habitat-specific and did not display significant spatial autocorrelation. Microbial beta diversity correlated with soil pH. Fungal beta-diversity was mainly related to soil organic matter. Though the effect of plant species composition was significant for all microbial groups, it was much stronger for Fungi. In contrast, geographic distances did not have any effect on microbial beta diversity. Microbial communities exhibit non-random spatial patterns of diversity in alpine landscapes. Crenarcheal, bacterial and fungal community turnover is high and associated with plant species composition through different set of soil variables, but is not caused by geographical isolation.


Distribution of occlusal traits in a sample of 1337 children aged 15--18 residing in upstate New York.
Preliminary findings on the distribution of occlusal traits (COCSTOC-MOT) have been presented as measured on 1337 orthodontic models. These models were made from a sample representing more than 400 000 children ages 15 to 18 in Upstate New York (all of New York State with the exception of New York City). Some of the findings for occlusal traits in this survey are comparable to those from a representative sample of younger children representing the US population ages 6--11 years. For comparable traits differences between the findings in New York State and for the United States were: Openbite--1 per cent higher in the US sample. Overjet 6 mm or more--5.7 per cent higher in the US sample. Neutro-occlusion--7 per cent more in the US sample. Disto-occlusion--8 per cent more in the US sample. Mesio-occlusion--8 per cent more in the US sample. Differences in findings between these surveys are assumed to be largely due to the fact that the current survey measured occlusal traits in the permanent dentition; whereas, the US survey measured those traits in the mixed dentition. Some of the traits found in the mixed dentition are believed to be self-correcting. Statistically determined means and medians for some of the occlusal traits of COCSTOC indicate that there is considerable variation from ideal occlusion found in a large population.


Carbohydrate intake reduces fat oxidation during exercise in obese boys.
The recent surge in childhood obesity has renewed interest in studying exercise as a therapeutic means of metabolizing fat. However, carbohydrate (CHO) intake attenuates whole body fat oxidation during exercise in healthy children and may suppress fat metabolism in obese youth. To determine the impact of CHO intake on substrate utilization during submaximal exercise in obese boys, seven obese boys (mean age: 11.4 ± 1.0 year; % body fat: 35.8 ± 3.9%) performed 60 min of exercise at an intensity that approximated maximal fat oxidation. A CHO drink (CARB) or a placebo drink (CONT) was consumed in a double-blinded, counterbalanced manner. Rates of total fat, total CHO, and exogenous CHO (CHO(exo)) oxidation were calculated for the last 20 min of exercise. During CONT, fat oxidation rate was 3.9 ± 2.4 mg × kg fat-free mass (FFM)(-1 )× min(-1), representing 43.1 ± 22.9% of total energy expenditure (EE). During CARB, fat oxidation was lowered (p = 0.02) to 1.7 ± 0.6 mg × kg FFM(-1 )× min(-1), contributing to 19.8 ± 4.9% EE. Total CHO oxidation rate was 17.2 ± 3.1 mg × kg FFM(-1 )× min(-1) and 13.2 ± 6.1 mg × kg FFM(-1) × min(-1) during CARB and CONT, respectively (p = 0.06). In CARB, CHO(exo) oxidation contributed to 23.3 ± 4.2% of total EE. CHO intake markedly suppresses fat oxidation during exercise in obese boys.


Economic violence against women: A case in Turkey.
The aim of this study was to determine the factors affecting the exposure of women in the 15-59 age group in Turkey to economic violence by their husbands/partners. The micro data set of the National Research on Domestic Violence against Women in Turkey, which was conducted by the Hacettepe University Institute of Population Studies, was employed in this study. The factors affecting women's exposure to economic violence were determined using the binary logistic regression analysis. In the study, women in the 15-24, 25-34 and 35-44 age group had a higher ratio of exposure to economic violence compared to the reference group. Women who graduated from elementary school, secondary school, and high school had a higher ratio of exposure to economic violence compared to those who have never gone to school. Women's exposure to physical, sexual and verbal violence was also important factor affecting women's exposure to economic violence. The results obtained in this study are important in that they can be a source of information for establishing policies and programs to prevent violence against women. This study can also be a significant guide in determining priority areas for the resolution of economic violence against women.


Glucose indices as inflammatory markers in children with acute surgical abdomen: a cross-sectional study.
Glycaemic dysregulation potentiates the pro-inflammatory response and increases oxidative injury; therefore, preoperative hyperglycaemia is linked to increased mortalities. In addition, inflammation is accompanied by higher glycated haemoglobin (HbA1c) levels, and the relationship between this and random blood sugar (RBS) could be non-linear. This is a cross-sectional study. Non-diabetic paediatric patients with acute surgical abdomen, presenting to the emergency surgical services were enrolled, over a period of 6 months. They were all screened for their random blood sugar and HbA1c levels. Fifty-three cases were studied. The prevalence of glycaemic dysregulation in the enrolled children was high. Abnormal HbA1c was observed in 66% of the study group. Stress hyperglycaemia was observed in 60% of the enrolled children. There was a significant correlation (r = 0.770, p-value: < 0.001) between RBS and the total leucocytic count (TLC). The TLC cutoff value for predicting stress hyperglycaemia was 13,595 cells/mm3. The cutoff value of RBS for predicting leukocytosis was 111.5 mg/dl. Median RBS level was significantly higher in complicated appendicitis (169.5 mg/dl), compared to uncomplicated appendicitis (118.0 mg/dl). HbA1c and RBS could be used as inflammatory markers for surgical acute abdomen and its degree of severity, respectively. HbA1c rises in a considerable number of cases with surgical acute abdomen, irrespective of the disease stage. However, as the disease progresses, the random blood sugar rises due to stress hyperglycaemia, thus becoming a surrogate inflammatory marker.


Left-Right and Upper-Lower Light Sensitivity Asymmetry in Visual Field Defects Caused by Pituitary Adenoma: A Retrospective Observational Study.
The purpose of this study was to quantitatively investigate light sensitivity asymmetry both between left and right eyes and between upper and lower quadrant in the 30-degree visual field of patients with visual field defects caused by pituitary adenoma. Preoperative Humphrey 30-2 perimetry results were reviewed retrospectively using the charts of 28 pituitary adenoma patients who underwent surgery. Inter-eye light sensitivity comparisons of the temporal and nasal hemifields between the left and right eyes were conducted in each patient to study left-right asymmetry. Upper-lower asymmetry was investigated by comparing the frequency of severe scotoma (light sensitivity 5 dB or less) in the upper and lower visual field quadrants in the temporal and nasal hemifields. Left-right asymmetry was demonstrated in 61% of cases in the temporal hemifield and in 57% of cases in the nasal hemifield. Severe scotoma test points were investigated in the worse eye of each patient and were more frequent in the superotemporal quadrant of the visual field compared with the inferotemporal quadrant (P = 0.00029) and in the inferonasal quadrant compared to the superonasal quadrant (P = 0.00268). Asymmetric visual field defects between left and right eyes are common in patients with pituitary adenoma. Severe scotoma is more frequent in the upper quadrant of the temporal hemifield and in the lower quadrant of the nasal hemifield.


Rectal bioavailability of delta-9-tetrahydrocannabinol from the hemisuccinate ester in monkeys.
Oral administration of delta-9-tetrahydrocannabinal (delta 9-THC) was shown to result in low and erratic bioavailability, while the drug showed no bioavailability from various suppository formulations. delta 9-THC-Hemisuccinate was formulated as a prodrug for delta 9-THC in suppositories using Witepsol H15 base. The bioavailability of delta 9-THC from this formulation was evaluated in monkeys. The plasma levels of delta 9-THC and its metabolite 11-nor-delta 9-THC-9-COOH were determined using GC/MS analysis. The calculated bioavailability of delta 9-THC from this formulation was found to be 13.5%. Non-compartmental analysis of the plasma concentration data using statistical moments showed the mean residence time (MRT) for delta 9-THC in the body to be 3 h following iv administration of delta 9-THC or its hemisuccinate ester (3.4 and 2.7 h, respectively), as compared with 5.8 h following rectal administration of the delta 9-THC hemisuccinate. The observed rectal bioavailability of delta 9-THC from suppositories containing the hemisuccinate ester as a prodrug is of significant importance in developing an alternative approach to oral administration of the drug.


Inhibition of both sclerostin and DKK1 results in novel skull findings in the rat and non-human primate that is not observed with inhibition of sclerostin alone.
Sclerostin is an extracellular inhibitor of canonical Wnt signaling that inhibits bone formation and stimulates bone resorption. Anti-sclerostin antibodies (Scl-Ab) have been developed as bone-building agents. DKK1, another extracellular inhibitor of the pathway, is upregulated in osteocytes in response to sclerostin inhibition. To further enhance bone-forming effects, a bispecific antibody inhibiting both sclerostin and DKK1 was created (AMG 147). In nonclinical safety studies, AMG 147 resulted in novel skull findings. In the rat, there was increased thickness of skull bones of neural crest origin due to increased subperiosteal compact lamellar and intramembranous woven bone. Externally, subperiosteal fibroblastic/osteoblastic stromal cell proliferation with woven bone and hemorrhage was also observed. Scl-Ab alone resulted in increased skull thickness in the rat, like AMG 147, but without the stromal cell proliferation/woven bone formation. In contrast to embryonic flat bone development, intramembranous bone formed similar to plexiform bone. In the monkey, AMG 147 resulted in macroscopic skull thickening due to a diffuse increase in appositional lamellar bone and increased intramembranous bone on both periosteal surfaces of all skull bones. These data demonstrate that dual inhibition of sclerostin and DDK1 results in unique effects on the skull not observed with sclerostin inhibition alone.


[Pharmacy compounding of medicinal shampoos: an update].
Delivery of magistral (extemporaneous) preparations must comply with quality standards, as described in the "Guide to Good Officinal Pharmaceutical Practice" and the pharmacy's Quality Manual (Royal Decree of 21 January 2009). In this study, the shampoo Simplex Herdewijn, prepared with Texapon NSO, is compared with commercially available basic shampoos (Shampoo Fagron and Shampoo Simplex Conforma) with respect to its composition as well as its physicochemical properties. These basic shampoos were used to develop medicinal shampoos. The active compounds of these shampoos were: 0.5% hexachlorophene, 1% ichtammol, 1% cade oil or 2% liquor carbonis detergens. The necessary concentration of Cetomacrogol 1000, required to solubilise the active compounds was determined, as well as the amount of sodium chloride needed to adjust the viscosity of the shampoo. The viscosity of the basic and medicinal shampoos was determined by means of rheograms and by calculating their apparent viscosity. Additionally, a number of fundamental aspects of the formulation of shampoos are discussed in this paper. The results can be useful to pharmacists as guidelines for the preparation of medicinal shampoos. Beside patient instruction and pharmaceutical care, the intrinsic quality of magistral preparations is a prerequisite for therapeutic activity.


Antiprotozoal Effect of Artemisia indica Extracts and Essential Oil.
Diverse solvent extracts of Artemisia indica leaves originating from the West Bengal region (India) were assessed for the content of artemisinin and characteristic Artemisia polymethoxyflavonoids, namely eupatin (1), casticin (2), chrysoplenetin (3), cirsilineol (4), chrysophenol-D (5), and artemetin (6). HPLC-DAD and HPLC-MS were used to investigate the extracts macerated by solvents of increasing polarity, i.e., petroleum ether, n-hexane, dichloromethane, acetone, MeOH, or EtOH (either 96, 80, or 60 % v/v), and hot water. Artemisinin was absent in all extracts. The acetone and EtOH extracts comprised the highest levels of polymethoxyflavonoids, whereas no flavonoid could be detected in the infusion. None of the remaining extracts contained chryosphenol-D (5) or artemetin (6), while chrysoplenetin (3) was found in all extracts. The essential oil of the plant was also obtained by hydrodistillation and analysed by gas chromatography and gas chromatography-mass spectrometry simultaneously. Of the 92 compounds detected in the oil, camphor (13.0 %) and caryophyllene oxide (10.87 %) were the major components. All solvent extracts and the volatile oil showed in vitro antimalarial activity, plus a potential malaria prophylactic effect by inhibiting at least two recombinant plasmodial fatty acid biosynthesis (PfFAS-II) enzymes. Except for the infusion, all extracts were also active against other parasitic protozoa and displayed low cytotoxicity against mammalian cells. This is the first detailed study investigating both artemisinin and polymethoxyflavonoid content as well as in vitro malaria prophylactic and detailed antiprotozoal potential of A. indica extracts against a panel of protozoan parasites. This is also the first report of antiparasitic activity of the essential oil of the plant.


Chemical signals in insects and other arthropods: from molecular structure to physiological functions.
Chemical communication is virtually universal among terrestrial and aquatic organisms. Chemical signals control the interactions of cells and organs (hormones) as well as the intra- (pheromones) and interspecific (allelochemicals) relationships between animals. The review considers three examples for chemical communication in insects and other arthropods on different hierarchic levels of biological organization, from the intraindividual level, where hormones control development and reproduction of the animals, to the interspecific level, where semiochemicals function as defense agents against predators or may be used for finding and recognizing food resources. Knowledge of the function of these systems and of the molecular structures of the chemical compounds involved may provide the basis for highly selective techniques of pest control.


Student evaluation: a performance indicator of quality in nurse education.
This study, which forms part of a doctoral thesis, is derived from the increasing demand for economic models of nurse education as a process within a wider economic agenda which converts inputs (e.g. training costs) into outputs (e.g. registered nurses). In such a climate the pursuance and determination of quality in nurse education should be of fundamental concern to the nursing profession. The development of models for evaluation and measurement of quality must take due cognisance of the stakeholders' interests and concerns, and student nurses, as the consumers of nurse education, must be regarded as major stakeholders. This paper describes the use of the course experience questionnaire, an instrument designed to investigate the students' perspective on teaching and learning. The study incorporates a comparative analysis between Project 2000 students in Northern Ireland and students in the apprenticeship programme in the Republic of Ireland, from general, psychiatric, sick children's and mental handicap nursing. This comparative analysis does provide the nursing profession with a level of feedback on which to make decisions in the interest of quality. Nurse teachers should examine potential reasons why their programmes are poorly or highly rated and the actions that may be required to remedy imperfections on the one hand and the actions that may be taken to promote excellence on the other. As nurse education continues to forge links with universities, nurse teachers, by adopting student evaluation as a performance indicator, can maximize an essential element in the web of public accountability.


Prescription trends and the selection of initial oral antidiabetic agents for patients with newly diagnosed type 2 diabetes: a nationwide study.
The aim of this study was to examine the characteristics of patients, physicians, and medical facilities, and their association with prescriptions that do not include metformin as the initial oral antidiabetic agent. Observational, cross-sectional study. Patients with incident type 2 diabetes between January 1, 2006, and December 31, 2010, were identified from the Taiwan National Insurance Research Database. We describe trends in the initial prescription of antidiabetic medications that do not contain metformin during the study period. A multivariable logistic model and a multilevel linear model were used in the analysis of factors at a range of levels (patient, physician, and medical facility), which may be associated with the selection of oral antidiabetic drugs. During the study period, the proportion of prescriptions that did not include metformin declined from 43.8% to 26.2%. Male patients were more likely to obtain non-metformin prescriptions (adjusted odds ratio [OR]: 1.15; 95% confidence interval [CI]: 1.08-1.23), and the likelihood that a patient would be prescribed a non-metformin prescription increased with age. Physicians aged ≥35 years and those with specialties other than endocrinology tended to prescribe non-metformin prescriptions. Metformin was less commonly prescribed in for-profit hospitals (adjusted OR: 1.34, 95% CI: 1.11-1.61) and hospitals in smaller cities (adjusted OR: 1.28, 95% CI: 1.05-1.57) and rural areas (adjusted OR: 1.83, 95% CI: 1.32-2.54). Disparities continue to exist in clinical practice with regard to the treatment of diabetes. These inequalities appear to be linked to a variety of factors related to patients, physicians, and medical facilities. Further study will be required to understand the effects of continuing medical education in enhancing adherence to clinical guidelines.


Microbial variome database: point mutations, adaptive or not, in bacterial core genomes.
Analysis of genetic differences (gene presence/absence and nucleotide polymorphisms) among strains of a bacterial species is crucial to understanding molecular mechanisms of bacterial pathogenesis and selecting targets for novel antibacterial therapeutics. However, lack of genome-wide association studies on large and epidemiologically well-defined strain collections from the same species makes it difficult to identify the genes under positive selection and define adaptive polymorphisms in those genes. To address this need and to overcome existing limitations, we propose to create a "microbial variome"--a species-specific resource database of genomic variations based on molecular evolutionary analysis. Here, we present prototype variome databases of Escherichia coli and Salmonella enterica subspecies enterica (http://depts.washington.edu/sokurel/variome, last accessed March 26, 2013). The prototypes currently include the point mutations data of core protein-coding genes from completely sequenced genomes of 22 E. coli and 17 S. enterica strains. These publicly available databases allow for single- and multiple-field sorting, filtering, and searching of the gene variability data and the potential adaptive significance. Such resource databases would immensely help experimental research, clinical diagnostics, epidemiology, and environmental control of human pathogens.


[Liver transplantation for metabolic liver disease in adulthood].
The clinical presentation of metabolic liver disease is highly variable, covering acute liver failure, liver cirrhosis, hepatic cancer and various extrahepatic manifestations. Both natural course and prognosis after liver transplantation are substantially influenced by extrahepatic manifestations. In many types of metabolic liver disease, timely diagnosis allows for successful medical treatment. However, progressive liver failure and severe extrahepatic damage can be the indication for liver transplantation. In general, standard transplantation criteria also apply for metabolic liver disease. They have to be modified by disease-specific criteria, and extrahepatic damage may necessitate multiorgan transplantation. The overall prognosis after liver transplantation for metabolic liver disease is favorable. Furthermore, several metabolic defects are phenotypically cured by liver transplantation. Alternative treatments like hepatocyte transplantation or gene therapy are still in the experimental stage.


Etiology and Risk Factors for Mortality in an Adult Community-acquired Pneumonia Cohort in Malawi.
Rationale: In the context of rapid antiretroviral therapy rollout and an increasing burden of noncommunicable diseases, there are few contemporary data describing the etiology and outcome of community-acquired pneumonia (CAP) in sub-Saharan Africa.Objectives: To describe the current etiology of CAP in Malawi and identify risk factors for mortality.Methods: We conducted a prospective observational study of adults hospitalized with CAP to a teaching hospital in Blantyre, Malawi. Etiology was defined by blood culture, Streptococcus pneumoniae urinary antigen detection, sputum mycobacterial culture and Xpert MTB/RIF, and nasopharyngeal aspirate multiplex PCR.Measurements and Main Results: In 459 patients (285 [62.1%] males; median age, 34.7 [interquartile range, 29.4-41.9] yr), 30-day mortality was 14.6% (64/439) and associated with male sex (adjusted odds ratio, 2.60 [95% confidence interval, 1.17-5.78]), symptom duration greater than 7 days (2.78 [1.40-5.54]), tachycardia (2.99 [1.48-6.06]), hypoxemia (4.40 [2.03-9.51]), and inability to stand (3.59 [1.72-7.50]). HIV was common (355/453; 78.4%), frequently newly diagnosed (124/355; 34.9%), but not associated with mortality. S. pneumoniae (98/458; 21.4%) and Mycobacterium tuberculosis (75/326; 23.0%) were the most frequently identified pathogens. Viral infection occurred in 32.6% (148/454) with influenza (40/454; 8.8%) most common. Bacterial-viral coinfection occurred in 9.1% (28/307). Detection of M. tuberculosis was associated with mortality (adjusted odds ratio, 2.44 [1.19-5.01]).Conclusions: In the antiretroviral therapy era, CAP in Malawi remains predominantly HIV associated, with a large proportion attributable to potentially vaccine-preventable pathogens. Strategies to increase early detection and treatment of tuberculosis and improve supportive care, in particular the correction of hypoxemia, should be evaluated in clinical trials to address CAP-associated mortality.


Self-care strategies for symptom management in patients with chronic heart failure.
The troublesome symptoms experienced by patients with chronic heart failure are associated with diminished quality of life, frequent hospitalizations, and mortality. To describe the symptoms experienced by patients with heart failure, to detail the self-care strategies used by these patients in managing their symptoms, and to categorize the self-care strategies. Six focus groups were used with 23 patients who had heart failure, along with six focus groups with 18 family members of the patients. Data analysis was performed by transcription of audiotape recordings of the group sessions and review of field notes. The patients reported a large number of troublesome symptoms, many consistent with past empirical findings, but some not reported in previous studies. Self-care strategies to manage the symptoms clustered into 11 categories. Results from this study provided direction for future studies to (a) identify the prevalence, severity, and etiologies of the commonly reported symptoms, particularly cognitive impairment, loss of balance, and depression; (b) evaluate the emotions reported by women with heart failure; and (c) test the strategies as part of an intervention program to improve symptom management in patients with heart failure.


Fecal metabolome of the Hadza hunter-gatherers: a host-microbiome integrative view.
The recent characterization of the gut microbiome of traditional rural and foraging societies allowed us to appreciate the essential co-adaptive role of the microbiome in complementing our physiology, opening up significant questions on how the microbiota changes that have occurred in industrialized urban populations may have altered the microbiota-host co-metabolic network, contributing to the growing list of Western diseases. Here, we applied a targeted metabolomics approach to profile the fecal metabolome of the Hadza of Tanzania, one of the world's few remaining foraging populations, and compared them to the profiles of urban living Italians, as representative of people in the post-industrialized West. Data analysis shows that during the rainy season, when the diet is primarily plant-based, Hadza are characterized by a distinctive enrichment in hexoses, glycerophospholipids, sphingolipids, and acylcarnitines, while deplete in the most common natural amino acids and derivatives. Complementary to the documented unique metagenomic features of their gut microbiome, our findings on the Hadza metabolome lend support to the notion of an alternate microbiome configuration befitting of a nomadic forager lifestyle, which helps maintain metabolic homeostasis through an overall scarcity of inflammatory factors, which are instead highly represented in the Italian metabolome.


Establishment and characterization of immortalized Gli-null mouse embryonic fibroblast cell lines.
Hedgehog (Hh) signaling is a conserved morphogenetic pathway which plays critical roles in embryonic development, with emerging evidence also supporting a role in healing and repair processes and tumorigenesis. The Gli family of transcription factors (Gli1, 2 and 3) mediate the Hedgehog morphogenetic signal by regulating the expression of downstream target genes. We previously characterized the individual and cooperative roles of the Gli proteins in Hh target gene regulation using a battery of primary embryonic fibroblasts from Gli null mice. Here, we describe the establishment of spontaneously immortalized mouse embryonic fibroblast (iMEF) cell lines lacking single and multiple Gli genes. These non-clonal cell lines recapitulate the unique ligand mediated transcriptional response of primary MEFs. While loss of Gli1 had no effect on target gene induction, Gli2 null cells demonstrated reduced target gene induction while Gli3 null cells exhibited elevated basal and ligand-induced expression. Target gene response in Gli1-/-2-/-iMEFs was severely reduced while Gli2-/-3-/-iMEFs were incapable of ligand-induced transcriptional response. However, we found that both Gli1-/-2-/- and Gli2-/-3-/-iMEFs exhibited robust leukotriene synthesis-dependent migration responses to Hh ligand, demonstrating that this response is not transcriptionally-dependent. This study provides fundamental characterizations of the transcriptional and non-transcriptional Hh responsiveness of a battery of Gli-null iMEFs. Moving forward, these cell lines should prove a valuable tool set to study the unique functional regulation of the Gli proteins in a Hh-responsive cell-type.


Opioid Use Increases the Rate of Pseudarthrosis and Revision Surgery in Patients Undergoing Anterior Cervical Discectomy and Fusion.
Retrospective Cohort. To (1) quantify the risk opioids impart on pseudarthrosis development, (2) analyze the effect of pseudarthrosis on clinical outcomes, and (3) identify if the amount of opioids prescribed are predictive of pseudarthrosis revision. Patients who underwent ACDF at a single institution between 2017-2019 were retrospectively identified. Postoperative dynamic cervical spine radiographs were reviewed to assess fusion status. Logistic regression models measured the effect of morphine milligram equivalents (MME) prescribed on the likelihood of pseudarthrosis development. Receiver operating characteristic (ROC) curves were generated to predict the probability of surgical revision based on MME prescribed. Of 298 included patients, an average of 2.01 ± 0.82 levels were included in the construct and 121 (40.9%) patients were diagnosed with a pseudarthrosis. However, only 14 (4.7%) required a pseudarthrosis revision. Patients requiring pseudarthrosis revision had worse one-year postoperative Δ PCS-12 (-1.70 vs. 7.58, P = 0.004), Δ NDI (3.33 vs. -15.26, P = 0.002), and Δ VAS Arm (2.33 vs. -2.48, P = .047). Multivariate logistic regression analyses found the three-month postoperative (OR=1.00, P = .010), one-year postoperative (OR=1.001, P = 0.025), and combined pre- and postoperative MME (OR=1.000, P = .035) increased the risk of pseudarthrosis. ROC analysis identified cutoff values to predict pseudarthrosis revision at 90.00 (area under the curve (AUC): 0.693, confidence interval (CI): 0.554-0.832), 132.86 (0.710, CI: 0.589-0.840), 224.76 (0.687, CI: 0.558-0.817) and 285.00 (0.711, CI: 0.585-0.837) MME in the preoperative, three-month postoperative, one-year postoperative, and combined pre-and postoperative period. Increased prescription of opioid medications following ACDF procedures may increase the risk of pseudarthrosis development and revision surgery. Therapeutic Level III.


Biomarkers in precision therapy in colorectal cancer.
Colorectal cancer (CRC) is the most commonly diagnosed cancer in Europe. Because CRC is also a major cause of cancer-related deaths worldwide, a lot of research has been focused on the discovery and development of biomarkers to improve the diagnostic process and to predict treatment outcomes. Up till now only a few biomarkers are recommended by expert panels. Current TNM criteria, however, cause substantial under- and overtreatment of CRC patients. Consequently, there is a growing need for new and efficient biomarkers to ensure optimal treatment allocation. An ideal biomarker should be easily translated into clinical practice, to identify patients who can be spared from treatment or benefit from therapy, ultimately resulting in precision medicine in the future. In this review we aim to provide an overview of a number of frequently studied biomarkers in CRC and, at the same time, we will emphasize the challenges and controversies that withhold the clinical introduction of these biomarkers. We will discuss both prognostic and predictive markers of chemotherapy, aspirin therapy as well as overall therapy toxicity. Currently, only mutant KRAS, mutant BRAF, MSI and the Oncotype DX® Colon Cancer Assay are used in clinical practice. Other biomarker studies showed insufficient evidence to be introduced into clinical practice. Divergent patient selection criteria, absence of validation studies and a large number of single biomarker studies are possibly responsible. We therefore recommend that future studies focus on combining key markers, rather than analysing single markers, standardizing study protocols, and validate the results in independent study cohorts, followed by prospective clinical trials.


Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance.
Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance.


The outbreak of COVID-19: An overview.
In late December 2019, a previous unidentified coronavirus, currently named as the 2019 novel coronavirus#, emerged from Wuhan, China, and resulted in a formidable outbreak in many cities in China and expanded globally, including Thailand, Republic of Korea, Japan, United States, Philippines, Viet Nam, and our country (as of 2/6/2020 at least 25 countries). The disease is officially named as Coronavirus Disease-2019 (COVID-19, by WHO on February 11, 2020). It is also named as Severe Pneumonia with Novel Pathogens on January 15, 2019 by the Taiwan CDC, the Ministry of Health and is a notifiable communicable disease of the fifth category. COVID-19 is a potential zoonotic disease with low to moderate (estimated 2%-5%) mortality rate. Person-to-person transmission may occur through droplet or contact transmission and if there is a lack of stringent infection control or if no proper personal protective equipment available, it may jeopardize the first-line healthcare workers. Currently, there is no definite treatment for COVID-19 although some drugs are under investigation. To promptly identify patients and prevent further spreading, physicians should be aware of the travel or contact history of the patient with compatible symptoms.


A comparative investigation of methods for protein immobilization on self-assembled monolayers using glutaraldehyde, carbodiimide, and anhydride reagents.
Three different approaches to the immobilization of proteins at surfaces have been compared. All rely on the creation of surface groups that bind primary amines on lysine residues. Carboxylic acid terminated self-assembled monolayers (SAMs) have been activated using a water soluble carbodiimide to yield an active ester functionalized surface and with trifluoroacetic anhydride to yield a surface anhydride, and amine terminated SAMs have been activated using glutaraldehyde. Although the degree of surface derivatization by n-alkylamines was greater using the carbodiimide and anhydride methods under anhydrous conditions, the glutaraldehyde activation of amine terminated SAMs yielded significantly greater attachment of streptavidin than is achieved using either of the other methods. This is attributed to the susceptibility to hydrolysis of the active species formed by activation of the carboxylic acid terminated monolayers. Patterned protein structures may be formed by using both glutaraldehyde activation of amine terminated thiols and carbodiimide activation of carboxylic acid terminated thiols, in conjunction with selective photo-oxidation of oligo(ethylene glycol) terminated SAMs.


The influence of everyday events on prospective timing "in the moment".
We conducted two experiments to investigate how the eventfulness of everyday experiences influences people's prospective timing ability. Specifically, we investigated whether events contained within movies of everyday activities serve as markers of time, as predicted by Event Segmentation Theory, or whether events pull attention away from the primary timing task, as predicted by the Attentional Gate theory. In the two experiments reported here, we asked participants to reproduce a previously learned 30-s target duration while watching a movie that contained eventful and uneventful intervals. In Experiment 2, reproduction also occurred during "blank movies" while watching a fixation. In both experiments, participants made shorter and more variable reproductions while simultaneously watching eventful as compared to uneventful movie intervals. Moreover, in Experiment 2, the longest reproductions were produced when participants had to watch the blank movies, which contained no events. These results support Event Segmentation Theory and demonstrate that the elapsing events during prospective temporal reproduction appear to serve as markers of temporal duration rather than distracting from the timing task.


High-accuracy theoretical thermochemistry of atmospherically important sulfur-containing molecules.
In this study, several sulfur-containing molecules with atmospherical importance were investigated by means of high-accuracy quantum chemical calculations including: HSO, HOS, HOSO2, HSNO, SH, CH2SO, CH2SH, S2COH, and SCSOH. After identifying the stable conformers of the molecules, a coupled-cluster-based composite model chemistry, which includes contributions up to quadruple excitations as well as corrections beyond the nonrelativistic and Born–Oppenheimer approximations, was applied to calculate the corresponding heat of formation (Δ(f)H(0)° and Δ(f)H(298)°) and entropy (S(298)°) values. In most of the cases, this study delivers more reliable estimates for the investigated thermodynamic properties than those reported in previous investigations. Our data also suggest that the experimental heats of formation associated with the HSO molecule are very likely to belong to its structural isomer, HOS. It is also confirmed by the calculated thermodynamic properties including standard reaction entropies, enthalpies, and equilibrium constants that, in the reaction CS2 + OH CS2OH, the SCSOH structural isomer is produced. It is also noted that the currently accepted Δ(f)H(0)°(S(gas)) = 274.73 ± 0.3 kJ/mol value is in need of revision, and based on a recent measurement, which is also confirmed by our computations, it is advised to update it to Δ(f)H(0)°(S(gas)) = 277.25 ± 0.3 kJ/mol.


Mapping vegetation species succession in a mountainous grassland ecosystem using Landsat, ASTER MI, and Sentinel-2 data.
Vegetation species succession and composition are significant factors determining the rate of ecosystem biodiversity recovery after being disturbed and subsequently vital for sustainable and effective natural resource management and biodiversity. The succession and composition of grasslands ecosystems worldwide have significantly been affected by accelerated environmental changes due to natural and anthropogenic activities. Therefore, understanding spatial data on the succession of grassland vegetation species and communities through mapping and monitoring is essential to gain knowledge on the ecosystem and other ecosystem services. This study used a random forest machine learning classifier on the Google Earth Engine platform to classify grass vegetation species with Landsat 7 ETM+ and ASTER multispectral imager (MI) data resampled with the current Sentinel-2 MSI data to map and estimate the changes in vegetation species succession. The results indicate that ASTER MI has the least accuracy of 72%, Landsat 7 ETM+ 84%, and Sentinel-2 had the highest of 87%. The result also shows that other species had replaced four dominant grass species totaling about 49 km2 throughout the study.


Does green finance reduce environmental pollution?-a study based on China's provincial panel data.
As a bridge between economy and ecology, green finance is vital in improving environmental quality and promoting sustainable development. Based on the building of an environmental pollution index system, this paper constructs the [Formula: see text] model to deeply explore the specific impact of green finance on environmental pollution using China's provincial panel data from 2007 to 2020. This paper constructs an intermediary model to test the impact mechanism of green finance on reducing environmental pollution and discusses the regional heterogeneity of green finance in reducing environmental pollution. The results show that (1) green finance can significantly reduce environmental pollution, among which green credit has a pronounced effect on reducing environmental pollution, green investment has a relatively small effect, and green securities have not significant effect. (2) Green finance has the best inhibitory effect on solid pollution, less inhibitory effect on air pollution, and no significant improvement effect on water pollution. (3) Green technology innovation, industrial structure upgrading, and environmental regulation play an intermediary role in the process of green finance reducing environmental pollution and improving environmental quality. (4) The effect of green finance in the eastern and carbon emission pilot areas is significantly better than in the central and western regions and non-carbon emission pilot areas respectively. According to the research results of this paper, suggestions are put forward to promote the development of green finance, which is of great significance to reducing environmental pollution and achieving sustainable development goals.


Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc-.
Transport of system xc- is an exchange agency with high specificity for anionic form of cystine and glutamate. The protein mediating this transport is a disulfide-linked heterodimer of a light chain named xCT and a heavy chain previously known as 4F2hc. We have isolated two cDNAs encoding xCT from the human cDNA library. One clone coded for a protein of 501 amino acids with 12 putative transmembrane domains. When functionally expressed in Xenopus oocytes together with the human 4F2hc, human xCT induced the transport activity whose characteristics are similar to those of system xc-. Another clone seemed to contain a partial human xCT and a long 3' untranslated region. The human xCT gene was localized at chromosome 4q28-31. Analysis of the 5'-flanking region of the human xCT gene revealed several sites for potentially binding of transcriptional factors, including NF-E2 and AP-1. Transport of cystine via system xc- has been known as a regulatory factor for the intracellular glutathione level, and its transport activity is induced in response to the oxygen tension in culture. Northern blot analysis demonstrated that the expression of both xCT and 4F2hc was significantly enhanced by oxygen. The results suggest that oxygen regulates the activity of system xc- by modulating the expression of both xCT and 4F2hc mRNAs.


Cherry angioma: A case-control study.
Cherry angiomas (CAs) are very common asymptomatic vascular skin lesions. There are only a few studies on CAs in the literature and those assessing risk factors of CAs are scarce. The aim of our study was to determine risk factors for the development of CAs. A case-control study was conducted at a tertiary care center in Riyadh, Saudi Arabia. Patients underwent a full-body examination for CAs. Demographics and other data including medical history and medications were extracted from electronic medical records. A total of three hundred patients were enrolled: one hundred cases with at least five CAs and two hundred controls without CAs. Bivariate analysis identified benign prostatic hyperplasia (odds ratio [OR]: = 2.591), malignancy (OR = 2.567), tamsulosin (OR = 3.171), and clopidogrel (OR = 0.321) as statistically significant associations. After multivariate logistic regression analysis, only tamsulosin (OR = 3.475, P = 0.009) and clopidogrel (OR = 0.281, P = 0.028) were found to be independent risk factors for CAs. Malignancies tended to be more associated with CAs, but this did not reach statistical significance (P = 0.07). Tamsulosin is a possible risk factor for the development of CAs. Clopidogrel seems to have a protective role preventing the development of CAs.


Maternal Inflammatory Bowel Disease During Pregnancy is Not a Risk Factor for Long-term Morbidity of the Offspring.
To investigate whether offspring of women suffering from inflammatory bowel disease [IBD] during their pregnancy are at an increased risk for long-term paediatric morbidity. In this population-based cohort study, we investigated the incidence of long-term [up to the age of 18 years] hospitalizations due to cardiovascular, endocrine, neurological, haematological, respiratory, gastrointestinal, and urinary paediatric morbidities of offspring of mothers affected by IBD during their pregnancy. Deliveries occurred between the years 1991 and 2014 in a regional tertiary medical centre. Newborns with congenital malformations as well as multiple pregnancies were excluded from the study. During the study period, 255 352 deliveries met the inclusion criteria; 278 offspring were born to mothers with IBD. During the follow-up period, children born to mothers with IBD did not have an increased risk for long-term [up to the age of 18 years] morbidity compared with the control group. Maternal IBD during pregnancy is not a risk factor for long-term paediatric morbidity of the offspring.