Polyaniline nanoparticles magnetically coated Ti/Sb-SnO2 electrode as a flexible and efficient electrocatalyst for boosted electrooxidation of biorefractory wastewater.
In this paper, a novel electrode named 2.5D Ti/Sb-SnO2/PANI was developed by magnetically in-situ integration of adsorbent and electrocatalyst, where the green synthetic Fe3O4/polyaniline (PANI) nanoparticles with fair adsorption capability were used as auxiliary electrodes and coated on the surface of Ti/Sb-SnO2 main electrode, to enrich the pollutants in the vicinity of anode and therefore boost the electrochemical oxidation (EO) efficiency. Since the interchangeable auxiliary electrodes can endow the anode with adjustability and versatility, the effect of auxiliary electrodes on the surface structure and electrochemical properties of 2.5D Ti/Sb-SnO2/PANI were extensively investigated. Results showed that a tiny amount of Fe3O4/PANI auxiliary electrodes changed the solid-liquid interface, brought massive less acessible active sites and kept the similar electrode impedance and same EO capability of 2D Ti/Sb-SnO2. In terms of organic elimination and solution biodegradability enhancement, 2.5D Ti/Sb-SnO2/PANI showed a boosted 30%-60% EO efficiency on two typical biorefractory targets, i.e., Acid Red G and lignosulphonate. The specific effectiveness was dependent on the loading amount of magenetic PANI nanoparticles. The operating mechanism of the assembled 2.5D Ti/Sb-SnO2/PANI electrode was further proposed based on many details, as well as a design rule for developing novel electrodes with high efficient EO performance for wastewater treatment. Moreover, the assembled 2.5D electrode was proved to have good sustainability and recyclability, which shows a great potential in the practical applications.


Associations between social media use, fitness- and weight-related online content, and use of legal appearance- and performance-enhancing drugs and substances.
Prior research has documented the connection between social media use and engaging with fitspiration with body dissatisfaction, disordered eating behaviors, and various health risk behaviors (e.g., substance use). However, gaps remain in the knowledge base on whether social media use and engaging with fitness- and weight-related online content are associated with the use of legal appearance- and performance-enhancing drugs and substances (APEDS; e.g., whey protein), which was the aim of this study. Data from participants ages 16-30 years in Canadian Study of Adolescent Health Behaviors (N = 2731) were analyzed. Multiple modified Poisson regression analyses were conducted to determine the associations between hours per day of social media use and any engagement with fitness- and weight-related online content in the past 30 days and use of 10 different legal APEDS in the past 30 days. Greater time on social media was significantly associated with use of energy drinks and pre-workout drinks or powders in the past 30 days. Engaging with fitness- and weight-related online content was significantly associated with the use of caffeine, creatine monohydrate, pre-workout drinks or powders, probiotics, protein bars, and whey protein powders or shakes in the past 30 days. These findings expand prior research on the correlates of social media use and engagement with fitness- and weight-related online content among young people and have important implications for healthcare and public health professionals, as well as technology companies.


Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy.
Canine models for narcolepsy have mutations of the hypocretin receptor 2 gene, and preprohypocretin knockout murine lines exhibit narcoleptic-like behaviors. Human narcolepsy with cataplexy is associated with human leukocyte antigen DQB1*0602 and reduced hypocretin levels in cerebrospinal fluid, suggesting an autoimmune diathesis. We tested the hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have immunoglobulin (Ig)G reactive to human preprohypocretin and its cleavage products. Serum samples of 41 DQB1*0602-positive narcoleptic subjects with cataplexy and 55 control subjects were studied, as were 19 narcoleptic and 13 control samples of cerebrospinal fluid. We tested for IgG reactive to preprohypocretin and its major cleavage products (including hypocretin 1 and 2), using immunoprecipitation assays (IP), immunofluorescence microscopy (IF) of Chinese hamster ovarian cells expressing preprohypocretin, and Western blots. There was no evidence for IgG reactive to preprohypocretin or its cleavage products in CSF of subjects with narcolepsy as measured by IPs, Western blots, and IF. Although the IP with CSF and the C-terminal peptide showed significant differences by two methods of comparison, the control subjects had higher counts per minute than narcoleptic subjects, which was opposite to our hypothesis. The hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have IgG reactive to preprohypocretin or its cleavage products was not supported.


Atypical language in lesional and nonlesional complex partial epilepsy.
We investigated the relationship between partial epilepsy, MRI findings, and atypical language representation. A total of 102 patients (4 to 55 years) with left hemisphere epileptogenic zones were evaluated using three fMRI language tasks obtained at 1.5 or 3T with EPI BOLD techniques: verbal fluency, reading comprehension, and auditory comprehension. fMRI maps were visually interpreted at a standard threshold and rated as left or atypical language. Atypical language dominance occurred in 30 patients (29%) and varied with MRI type (p < 0.01). Atypical language representation occurred in 36% (13/36) with normal MRI, 21% (6/29) with mesial temporal sclerosis, 14% (4/28) with focal cortical lesions (dysplasia, tumor, vascular malformation), and all (6/6) with a history of stroke. Multivariate logistic regression analysis found handedness, seizure onset, and MRI type accounted for much of the variance in language activation patterns (chi(2) = 24.09, p < 0.01). Atypical language was more prevalent in patients with early seizure onset (43.2%, p < 0.05) and atypical handedness (60%, p < 0.01). None of the three clinical factors were correlated with each other (p > 0.40). Patients with atypical language had lower verbal abilities (F = 6.96, p = 0.01) and a trend toward lower nonverbal abilities (F = 3.58, p = 0.06). There were no differences in rates of atypical language across time, age groups, or MRI scanner. Early seizure onset and atypical handedness, as well as the location and nature of pathologic substrate, are important factors in language reorganization.


The effect of regadenoson-induced transient disruption of the blood-brain barrier on temozolomide delivery to normal rat brain.
The blood-brain barrier (BBB) significantly reduces the delivery of many systemically administered agents to the central nervous system. Although temozolomide is the only chemotherapy to improve survival in patients with glioblastoma, its concentration in brain is only 20 % of that in blood. Regadenoson, an FDA approved adenosine receptor agonist used for cardiac stress testing, transiently disrupts rodent BBB allowing high molecular weight dextran (70 kD) to enter the brain. This study was conducted to determine if regadenoson could facilitate entry of temozolomide into normal rodent brain. Temozolomide (50 mg/kg) was administered by oral gavage to non-tumor bearing F344 rats. Two-thirds of the animals received a single dose of intravenous regadenoson 60-90 min later. All animals were sacrificed 120 or 360 min after temozolomide administration. Brain and plasma temozolomide concentrations were determined using HPLC/MS/MS. Brain temozolomide concentrations were significantly higher at 120 min when it was given with regadenoson versus alone (8.1 ± 2.7 and 5.1 ± 3.5 µg/g, P < 0.05). A similar trend was noted in brain:plasma ratios (0.45 ± 0.08 and 0.29 ± 0.09, P < 0.05). Brain concentrations and brain:plasma ratios were not significantly different 360 min after temozolomide administration. No differences were seen in plasma temozolomide concentrations with or without regadenoson. These results suggest co-administration of regadenoson with temozolomide results in 60% higher temozolomide levels in normal brain without affecting plasma concentrations. This novel approach to increasing intracranial concentrations of systemically administered agents has potential to improve the efficacy of chemotherapy in neuro-oncologic disorders.


Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain.
Ketorolac tromethamine, a nonnarcotic, prostaglandin synthesis-inhibiting analgesic, was compared with morphine sulfate for relief of moderate to severe postoperative pain. The 155 patient participants received single intramuscular doses of either ketorolac, 10, 30, or 90 mg, or morphine, 6 or 12 mg, administered in a double-blind, randomized fashion. Pain scores (verbal and visual analog) were recorded at baseline and assessed at 30 minutes and then hourly to 6 hours. Pain relief was rated at the same times. Ketorolac, 90 and 30 mg, was rated significantly better than morphine, 6 mg, at each assessment interval after 1 hour. Ketorolac, 90 and 30 mg, was rated similarly to morphine, 12 mg, for the first 3 hours and better than morphine, 12 mg, 4 hours after injection. There were no serious side effects reported. The only side effect reported in more than 3% of patients was 8% somnolence with morphine. This study shows ketorolac to be a safe and effective analgesic for relief of postoperative pain.


GABA and glutamate receptors in the horizontal limb of diagonal band of Broca (hDB): effects on cardiovascular regulation.
The horizontal limb of diagonal band of Broca (hDB) is a part of the limbic system. It has been shown that microinjection of L-glutamate into the hDB elicited cardiovascular depressive responses in anesthetized rats and pressor effect in unanesthetized rats. But the role of glutamate receptor subtypes has not yet been investigated. In addition the role of the GABAergic system of the hDB in cardiovascular responses is not known. Therefore, we examined the cardiovascular responses elicited by glutamate and GABA receptors in the hDB by using their agonists and antagonists. Drugs (50 nl) were microinjected into the hDB of anaesthetized rats. Blood pressure and heart rate were recorded before and throughout each experiment. The average changes in the mean arterial pressure and heart rate at different intervals were compared both within each case group and between the case and control groups using repeated measures of ANOVA. Microinjection of GABA(A) receptor antagonist, bicuculline methiodide (BMI, 1 mM) increased both the mean arterial pressure and heart rate, and muscimole, a GABA(A) agonist (500 pmol) caused a significant decrease in the mean arterial pressure and heart rate. Microinjection of L-glutamate (0.25 M) into the hDB resulted in a maximum decrease of the mean arterial pressure of 24.4 +/- 3.7 mmHg and heart rate of 25.2 +/- 3.08 beats/min. Injection of AP5, an antagonist of glutamate NMDA receptor (1 and 2.5 mM), and CNQX, an antagonist of glutamate AMPA receptor (0.5 and 1 mM) caused small, nonsignificant changes of the heart rate and the blood pressure. Either AP5 or CNQX when coinjected with glutamate abolished the depressor effect of glutamate, suggesting that simultaneous activation of both glutamate receptors is necessary for the effect of glutamate to emerge. The depressor effect of the glutaminergic system of the hDB on the cardiovascular system was similar to the previous studies. For the first time, the effects of CNQX, AP5, BMI, and muscimole have been shown in this study.


[Intra-uterine insemination outcomes according to the serum AMH level on day 3].
The aim of this retrospective study was to compare the IUI outcomes according to serum antiMullerian hormone (AMH) levels on day 3 of cycle. Three hundred and sixteen patients undergoing their first IUI cycle after a serum AMH level test in our laboratory. These patients were less than 39 years of age and the number of motile spermatozoa inseminated (NMSI) was superior or equal to five millions. Patients were divided in three groups according to their serum AMH level: the group 1 with AMH level less than 1ng/ml, the group 2 with AMH level between 1 and 4.5ng/ml, and the group 3 with AMH level greater than 4.5ng/ml. clinical pregnancy rate and ongoing pregnancy rate per IUI cycle. No statistical difference has been observed on follicle stimulation, number of mature follicle, oestradiol level on day hCG, clinical pregnancy rate, spontaneous abortion. The ongoing pregnancy rate per IUI practised were respectively: 15.5% for AMH inferior to 1ng/ml versus 15.2% for AMH between 1 to 4.5ng/ml and versus 13.6% for AMH superior to 4.5ng/ml. AMH value does not seem to have an impact on the IUI outcomes and particularly on the pregnancy rates.


Postlabeling analysis of indigenous aromatic DNA adducts in mouse myocardium during aging.
The possible presence of aromatic chemicals covalently linked to DNA (aromatic adducts) was investigated in heart cells during aging of the C57BL/6Nia mouse. Heart DNAs were isolated from untreated mice of different ages and analyzed by 32P-postlabeling assays. To determine low levels of adducts, assays were carried out in which aromatic adducts were first isolated by phase transfer to 1-butanol, then labeled with excess, carrier-free [gamma-32P]ATP. This analysis showed that the number and frequency of aromatic adducts varied between DNA samples. Several adducts were present in all mouse DNA preparations and were more abundant in 32P-maps of senescent heart DNA. The results suggest that genomes of myocytes have a higher steady-state level of DNA damage in old animals which could adversely affect cell function.


Combined evaluation of CAC score and myocardial perfusion imaging in patients at risk of cardiovascular disease: where are we and what do the data say.
Advances in the prevention and treatment of cardiovascular disease (CVD) over the last decades have led to a marked reduction in mortality for CVD. Nevertheless, atherosclerosis leading to coronary artery disease and stroke remains one of the most common causes of death in the world. The usefulness of imaging tests in the early identification of disease led to identify subjects at major risk of poor outcomes, suggesting risk factor modification. The aim of this article is to analyze the state of art of combined imaging in patients at risk of CVD referred to MPI evaluation, to highlight the present and potential features able to provide incremental prognostic information to help clinicians in patient management and to reduce adverse events.


Impacts of iron on ultrastructural features of NCI-H295R cell line related to steroidogenesis.
The current study was intended to evaluate impacts of both iron (Fe) enrichment and overload (in the form of ferrous sulphate heptahydrate, FeSO4.7H2O) on ultrastructural characteristics of human adrenocarcinoma NCI-H295R cell line. Here, the NCI-H295R cells were treated with 0, 3.90, and 1000 µM FeSO4.7H2O, and consequently proceeded for purposes of ultrastructural studies. Micrographs taken under transmission electron microscope (TEM) were investigated from the qualitative and quantitative (unbiased stereological approaches) aspects, and obtained findings were compared among the three groups of the cells. The ultrastructural features related to the steroidogenic process were found to be similar between the untreated and both Fe-exposed cell populations, with conspicuous mitochondria with well-defined lamellar cristae (creating clusters of varying sizes in the regions of increased energy demands) and concentric whorls of smooth endoplasmic reticulum (SER) being the most noticeable characteristics. The precise estimates of the component (volume, surface) fractions of the nucleus, mitochondria, and lipid droplets (LDs), as well as of the nucleus/cytoplasm (N/C) ratio have revealed close similarities (P > 0.05) in all cell groups investigated. Nonetheless, the low concentration of FeSO4.7H2O exhibited beneficial action on ultrastructural organization of the NCI-H295R cells. In effect, these cells were distinguished by mitochondria with smoother surfaces and clearer outlines, higher density of thin, parallel lamellar cristae (deeply extending into the mitochondrial matrix), and more widespread distribution of fine SER tubules as compared to the control ones, all of them suggesting higher level of energy requirements and metabolic activity, and more intensive rate of steroidogenesis. Interestingly, no obvious ultrastructural modifications were observed in the NCI-H295R cells treated with high FeSO4.7H2O concentration. This finding can be linked to either an adaptive ultrastructural machinery of these cells to cope with the adverse effect of the element or to insufficient dose of FeSO4.7H2O (1000 µM) to induce ultrastructural signs of cytotoxicity. Purposefully, the results of the current study complement our previous paper dealing with impacts of FeSO4.7H2O on the NCI-H295R cell viability and steroidogenesis at the molecular level. Hence, they fill a knowledge gap considering structure-function coupling in this cellular model system upon the metal exposure. This integrated approach can enhance our understanding of the cellular responses to Fe enrichment and overload which can be helpful for individuals with reproductive health concerns.


Addressing influenza's underestimated burden - Iberian experts call to action.
Having a proper understanding of the impact of influenza is a fundamental step towards improved preventive action. This paper reviews findings from the Burden of Acute Respiratory Infections study on the burden of influenza in Iberia, and its potential underestimation, and proposes specific measures to lessen influenza's impact.


A ratchet-like apical constriction drives cell ingression during the mouse gastrulation EMT.
Epithelial-to-mesenchymal transition (EMT) is a fundamental process whereby epithelial cells acquire mesenchymal phenotypes and the ability to migrate. EMT is the hallmark of gastrulation, an evolutionarily conserved developmental process. In mammals, epiblast cells ingress at the primitive streak to form mesoderm. Cells ingress and exit the epiblast epithelial layer and the associated EMT is dynamically regulated and involves a stereotypical sequence of cell behaviors. 3D time-lapse imaging of gastrulating mouse embryos combined with cell and tissue scale data analyses revealed the asynchronous ingression of epiblast cells at the primitive streak. Ingressing cells constrict their apical surfaces in a pulsed ratchet-like fashion through asynchronous shrinkage of apical junctions. A quantitative analysis of the distribution of apical proteins revealed the anisotropic and reciprocal enrichment of members of the actomyosin network and Crumbs2 complexes, potential regulators of asynchronous shrinkage of cell junctions. Loss of function analyses demonstrated a requirement for Crumbs2 in myosin II localization and activity at apical junctions, and as a candidate regulator of actomyosin anisotropy.


Periodontopathogenic bacteria multiply in the environmental amoeba Acanthamoeba castellani.
Porphyromonas gingivalis and Prevotella intermedia are obligate anaerobe gram-negative periodontopathogenic bacteria. Free-living amoebae, such as Acanthamoeba spp., are well known as environmental hosts of several human pathogens, such as Franciscella tularensis, Chlamydia pneumoniae, Legionella pneumophila and Mycobacteria spp. This study tested the ability of P. gingivalis and P. intermedia to become internalized, to survive and replicate in Acanthamoeba castellani. Our results show for the first time that P. gingivalis and P. intermedia isolated from periodontitis patients are capable of infecting A. castellani cells in vitro and are able to survive and multiply intracellularly. From our experimental data it can be suggested that periodontopathogenic bacteria might be conditioned in the evolution by amoebae and free-living amoebae can act as an environmental reservoir for these pathogens.


Binding sites for corticotropin releasing factor in sensory areas of the rat hindbrain and spinal cord.
Binding sites of 125I-Tyr-O-ovine corticotropin releasing factor have been demonstrated in sensory areas of the rat hindbrain and spinal cord mainly in the posterior part of the nucleus tractus solitarii, the substantia gelatinosa nervi trigemini and the superficial layers of the spinal cord (laminae I and II). Specific binding was inhibited in the presence of unlabeled synthetic ovine or rat/human CRF indicating that the receptors recognize both forms of CRF.


Retrieval of Trophoblast Cells from the Cervical Canal: A Promising Non-invasive Method for Prenatal Diagnosis.
Extravillous trophoblasts (EVTs) cells have shown promise for their application in non-invasive prenatal diagnosis during the first trimester. The Trophoblast Retrieval and Isolation from the Cervix (TRIC) method allows for the isolation of homogeneous trophoblast cells from pregnant women as early as 5 weeks gestation. This study aimed to explore the potential value of extravillous trophoblast cells collected from the cervix, enriched, and purified using the TRIC method for first-trimester prenatal diagnosis. A prospective observational study was conducted, and we collected extravillous trophoblast cells from the cervixes of 100 pregnant women between 5-7 weeks gestation before an induced abortion. Subsequently, these cells underwent STR analysis and fluorescence in situ hybridization (FISH). Out of the 100 cases, trophoblast cells were successfully collected from 96 cases. Among them, STR analysis revealed maternal cell contamination in 13 cases. Gender determination using FISH showed 44 male cases (including one case with 47, XY, +21) and 39 female cases (including one case with 47, XXX). The results of the FISH examination of these 83 cases were in concordance with those of the villi FISH examination. The collection of fetal trophoblast cells from the cervix represents a feasible and non-invasive approach for first-trimester prenatal diagnosis. The TRIC method enables efficient enrichment and purification of trophoblast cells, which can be of significant benefit for subsequent diagnosis using the FISH method.


Allowance for effects of electrostatic repulsion on protein dimerization.
A simple procedure for assessing the extent of electrostatic effects on protein dimerization is described and illustrated by application to published results on the ionic strength dependence of the dimerization constant for alpha-chymotrypsin at pH 4 (Aune, K.C., Goldsmith, L.C. and Timasheff, S.N. (1971) Biochemistry 10, 1617-1622). From the analysis it is concluded that the inverse dependence of alpha-chymotrypsin dimerization upon ionic strength is predominantly a general electrostatic effect, rather than a consequence of repulsion between two specific charged residues on the adjacent monomers comprising dimer.


Abscisic acid is required for exodermal suberization to form a barrier to radial oxygen loss in the adventitious roots of rice (Oryza sativa).
To acclimate to waterlogged conditions, wetland plants form a barrier to radial oxygen loss (ROL) that can enhance oxygen transport to the root apex. We hypothesized that one or more hormones are involved in the induction of the barrier and searched for such hormones in rice. We previously identified 98 genes that were tissue-specifically upregulated during ROL barrier formation in rice. The RiceXPro database showed that most of these genes were highly enhanced by exogenous abscisic acid (ABA). We then examined the effect of ABA on ROL barrier formation by using an ABA biosynthesis inhibitor (fluridone, FLU), by applying exogenous ABA and by examining a mutant with a defective ABA biosynthesis gene (osaba1). FLU suppressed barrier formation in a stagnant solution that mimics waterlogged soil. Under aerobic conditions, rice does not naturally form a barrier, but 24 h of ABA treatment induced barrier formation. osaba1 did not form a barrier under stagnant conditions, but the application of ABA rescued the barrier. In parallel with ROL barrier formation, suberin lamellae formed in the exodermis. These findings strongly suggest that ABA is an inducer of suberin lamellae formation in the exodermis, resulting in an ROL barrier formation in rice.


Programmed death-ligand 1 expression and overall survival in Thai patients with gastric cancer.
Programmed death-ligand 1 (PD-L1) expression has now been implicated in gastric cancer (GC). This study was conducted to determine the impact of clinicopathological characteristics on PD-L1 expression and its association with survival in GC patients receiving standard-of-care. In total, 268 GC patients receiving upfront surgery were enrolled at Chiang Mai University Hospital. PD-L1 expression was assayed by immunohistochemistry staining using the Dako 22C3 pharmDx. The rates of PD-L1 positivity by combined positive score (CPS) at a cutoff value of 1 and 5 were 22% and 7%. PD-L1 positivity was significantly higher in patients younger than 55 than those older than 55 (32.6% vs. 16.5%, p = 0.003; 11.6% vs. 4.4%, p = 0.027). PD-L1 positivity was observed more frequently in GC with metastases than without (25.2% vs. 17.1%, p = 0.112; 7.2% vs. 6.7%, p = 0.673). Patients with PD-L1 positive had a significantly shorter median overall survival than those with PD-L1 negative (32.7 vs. 41.6 months, p = 0.042, 27.6 vs. 40.8 months, p = 0.038). In conclusion, PD-L1 expression has been associated with young age, short survival, and metastases, although unrelated to the tumor stage. For GC patients, PD-L1 testing is recommended, especially among young patients with metastases.


Metabolic and heart rate responses to hypoxia in early chicken embryos in the transition from diffusive to convective gas transport.
Measurements of normoxic, hypoxic (15% or 10% O₂) and post-hypoxic oxygen consumption (VO₂) were conducted in chicken embryos every other day between embryonic day 3 (E3) and day 19 (E19), out of a total embryogenic period of 20.5 days. The results indicated that, irrespective of age, hypoxia lowered VO₂ throughout embryogenesis without any contraction of an O₂ debt. Hypoxic hypometabolism was more prominent at E3 than at E5, probably because of the differences in O₂ sensitivity during the developmental transition from O₂ diffusion to O₂ convection forms of gas transport. Further measurements at these two ages with either progressively increasing hypoxia or a sudden drop to 8% O₂ indicated that, at E5, the less pronounced hypometabolism was accompanied by a greater drop in heart rate (HR) than at E3. It was postulated that a functional causative link existed between these two phenomena, the decrease in whole-embryo [Formula: see text] favouring O₂ availability to the heart. Indeed, when O₂ demands were decreased by cold exposure, the hypoxic effects on HR became similar between E3 and E5. We conclude that hypometabolism with no major reliance on anaerobic sources is the common response to hypoxia throughout embryogenesis. In the earliest phases of embryogenesis, when diffusion is the primary form of gas transport and despite the absence of neural regulation, the possibility of using some of the O₂ saved in favour of the heart adds further value to hypometabolism as a survival strategy against hypoxia.


Home Environmental Assessment Protocol-Revised Initial Psychometrics: A Pilot Study.
Efficient home assessments are needed for persons with dementia and their caregivers. Pilot studies to establish a content validity index (CVI), measure concurrent criterion validity, and examine test-retest reliability of the Home Environment Assessment Protocol-Revised (HEAP-R). Six experts reviewed the tool and scored content validity items. Twenty-one caregiver/person with dementia dyads engaged with HEAP and HEAP-R to examine concurrent criterion validity. Seventeen occupational therapists viewed 10 videos of home environments to examine reliability. The CVI score was .980. Concurrent criterion validity for domains: hazards (r =.792), adaptations (r = .742), clutter (r = .843), and comfort (r = .958). Test-retest reliability: hazards (r = .820), adaptations (r = .887), visual cues (r = .487), and clutter (r = .696). Pilot data suggest the HEAP-R has preliminary content and concurrent criterion validity and test-retest reliability. Robust psychometric analysis is needed prior to use in clinical practice.


The Alberta Neonatal Abstinence Syndrome Mother-Baby Care ImprovEmeNT (NASCENT) program: protocol for a stepped wedge cluster randomized trial of a hospital-level Neonatal Abstinence Syndrome rooming-in intervention.
Neonatal Abstinence Syndrome (NAS), a problem common in newborns exposed to substances in-utero, is an emerging health concern. In traditional models of care, infants with NAS are routinely separated from their mothers and admitted to the Neonatal Intensive Care Unit (NICU) with long, expensive length of stay (LOS). Research shows a rooming-in approach (keeping mothers and infants together in hospital) with referral support is a safe and effective model of care in managing NAS. The model's key components are facilitating 24-h care by mothers on post-partum or pediatric units with support for breastfeeding, transition home, and access to Opioid Dependency Programs (ODP). This study will implement the rooming-in approach at eight hospitals across one Canadian Province; support practice and culture shift; identify and test the essential elements for effective implementation; and assess the implementation's impact/outcomes. A stepped wedge cluster randomized trial will be used to evaluate the implementation of an evidence-based rooming-in approach in the postpartum period for infants born to mothers who report opioid use during pregnancy. Baseline data will be collected and compared to post-implementation data. Six-month assessment of maternal and child health and an economic evaluation of cost savings will be conducted. Additionally, barriers and facilitators of the rooming-in model of care within the unique context of each site and across sites will be explored pre-, during, and post-implementation using theory-informed surveys, interviews, and focus groups with care teams and parents. A formative evaluation will examine the complex contextual factors and conditions that influence readiness and sustainability and inform the design of tailored interventions to facilitate capacity building for effective implementation. The primary expected outcome is reduced NICU LOS. Secondary expected outcomes include decreased rates of pharmacological management of NAS and child apprehension, increased maternal ODP participation, and improved 6-month outcomes for mothers and infants. Moreover, the NASCENT program will generate the detailed, multi-site evidence needed to accelerate the uptake, scale, and spread of this evidence-based intervention throughout Alberta, leading to more appropriate and effective care and use of healthcare resources. ClinicalTrials.gov, NCT0522662. Registered February 4th, 2022.


Synthesis of 2-deoxy-2-fluoro-phosphatidylinositol-4,5-bisphosphate and analogues: probes and modulators of the mammalian PI-PLCS.
An approach to synthesis of 2-modified phosphatidylinositol-4,5-bisphosphates, which are substrate analogues useful as probes and modulators of the PI-PLC enzyme family, is described and illustrated for the dibutyl-2-deoxy-2-fluoro analogue, a probe designed for delineating substrate and PI-PLC interactions by X-ray crystallography.


Debio 0507 primarily forms diaminocyclohexane-Pt-d(GpG) and -d(ApG) DNA adducts in HCT116 cells.
To characterize the cellular action mechanism of Debio 0507, we compared the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human colon carcinoma cells by a combination of inductively coupled plasma mass spectrometry (ICP-MS) and ultraperformance liquid chromatography mass spectrometry (UPLC-MS/MS). HCT116 cells were treated with IC(50) doses of Debio 0507 or oxaliplatin for 3 days. Total cellular Pt-DNA adducts were determined by ICP-MS. The DNA was digested, and the major Pt-DNA adducts formed by both drugs were characterized by UPLC/MS/MS essentially as described previously for cisplatin (Baskerville-Abraham et al. in Chem Res Toxicol 22:905-912, 2009). The Pt level/deoxynucleotide was 7.4/10(4) for DNA from Debio 0507-treated cells and 5.5/10(4) for oxaliplatin-treated cells following a 3-day treatment at the IC(50) for each drug. UPLC-MS/MS in the positive ion mode confirmed the major Pt-DNA adducts formed by both drugs were dach-Pt-d(GpG) (904.2 m/z → 610 m/z and 904.2 m/z → 459 m/z) and dach-Pt-d(ApG) (888.2 m/z → 594 m/z and 888.2 m/z → 459 m/z). These data show that the major DNA adducts formed by Debio 0507 are the dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts and at equitoxic doses Debio 0507 and oxaliplatin form similar levels of dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts. This suggests that the action mechanisms of Debio 0507 and oxaliplatin are similar at a cellular level.


Influence of nanoporous titanium niobium alloy surfaces produced via hydrogen peroxide oxidative etching on the osteogenic differentiation of human mesenchymal stromal cells.
Titanium niobium alloys exhibit a lower stiffness compared to Ti6Al4V, the 'gold standard' for load-bearing bone implants. Thus, the critical mismatch in stiffness between the implant and adjacent bone tissue could be addressed with TiNb alloys and thereby reduce stress shielding, which can result in bone resorption and subsequent implant loosening; however, the cellular response on the specific material is crucial for sufficient osseointegration. We therefore hypothesize that the response of human mesenchymal stromal cells (hMSC) and osteoblast-like cells on Ti45Nb surfaces can be improved by a novel nanoporous surface structure. For this purpose, an etching technique using hydrogen peroxide electrolyte solution was applied to Ti45Nb. The treated surfaces were characterized using SEM, LSM, AFM, nanoindentation, and contact angle measurements. Cell culture experiments using hMCS and MG-63 were conducted. The H2O2 treatment resulted in surface nanopores, an increase in surface wettability and a reduction in surface hardness. The proliferation of MG-63 was enhanced on TiNb45 compared to Ti6Al4V. MG-63 focal adhesion complexes were detected on all Ti45Nb surfaces, whereas the nanostructures notably increased the cell area and decreased cell solidity, indicating stimulated cell spreading and pseudopodia formation. Alizarin red stainings indicated that the nanoporous surfaces stimulated the osteogenic differentiation of hMSC. It can be concluded that the proposed surface treatment could potentially help to stimulate the osseointegration behaviour of the advantageous low stiff Ti45Nb alloy.


Clinical management of hyperglycaemic patients receiving total parenteral nutrition.
We evaluated the course of total parenteral nutrition (TPN) therapy in patients with hyperglycaemia. We studied 1) incidence of hyperglycaemia, 2) amount of glucose and insulin provided and 3) incidence of metabolic problems in patients receiving TPN who required insulin to attain metabolic control. The group included 91 patients, 38 women (64 +/- 15 years) and 53 men (64 +/- 12 years), who developed glycaemia higher than 200 mg/dl. Nine patients had a previous diagnosis of IDDM, 36 NIDDM and 46 secondary hyperglycaemia.. Total caloric requirements were initially supplied at 132 +/- 20% the basal energy expenditure (Harris-Benedict formula), and 1.4 +/- 0.3 g/kg of amino-acids. Initially, TPN provided 150-200 g/day of glucose (2.1 mg/kg/min). Regular insulin was added to the bag. The annual incidence of hyperglycaemia was estimated to be 121 per 1000 patients. Mean insulin requirements were 50 U/day (25 to 150 U/day), 0.7 +/- 0.3 U/kg. Comparing with prehospitalization insulin dose, 22% needed similar doses, and 11% lower doses. IDDM patients needed 1.7 times their pre-admission dose (1-4.5 times). The ratio of insulin:glucose in TPN was 0.3 +/- 0.1 U/g (0.1-1.2 U/g). Patients with renal failure had similar insulin requirements (56 +/- 26 U/day) than patients with normal renal function (49 +/- 19 U/day). None of the patients developed glycemic complications. In conclusion, diabetic patients receiving TPN have an acceptable metabolic control if individualized prescriptions and supplemental insulin are used.


Vocational and psychosocial predictors of medical negligence claims among Australian doctors: a prospective cohort analysis of the MABEL survey.
To understand the association between medical negligence claims and doctors' sex, age, specialty, working hours, work location, personality, social supports, family circumstances, self-rated health, self-rated life satisfaction and presence of recent injury or illness. Prospective cohort study of Australian doctors. 12 134 doctors who completed the Medicine in Australia: Balancing Employment and Life survey between 2013 and 2019. Doctors named as a defendant in a medical negligence claim in the preceding 12 months. 649 (5.35%) doctors reported being named in a medical negligence claim during the study period. In addition to previously identified demographic factors (sex, age and specialty), we identified the following vocational and psychosocial risk factors for claims: working full time (OR=1.48, 95% CI 1.13 to 1.94) or overtime hours (OR 1.70, 95% CI 1.29 to 2.23), working in a regional centre (OR 1.69, 95% CI 1.37 to 2.08), increasing job demands (OR 1.16, 95% CI 1.04 to 1.30), low self-rated life satisfaction (OR 1.43, 95% CI 1.08 to 1.91) and recent serious personal injury or illness (OR 1.40, 95% CI 1.13 to 1.72). Having an agreeable personality was mildly protective (OR 0.91, 95% CI 0.83 to 1.00). When stratified according to sex, we found that working in a regional area, low self-rated life satisfaction and not achieving work-life balance predicted medical negligence claims in male, but not female, doctors. However, working more than part-time hours and having a recent personal injury or illness predicted medical negligence claims in female, but not male, doctors. Increasing age predicted claims more strongly in male doctors. Personality type predicted claims in both male and female doctors. Modifiable risk factors contribute to an increased risk of medical negligence claims among doctors in Australia. Creating more supportive work environments and targeting interventions that improve doctors' health and well-being could reduce the risk of medical negligence claims and contribute to improved patient safety.


DNA barcoding the Dioscorea in China, a vital group in the evolution of monocotyledon: use of matK gene for species discrimination.
Dioscorea is an important plant genus in terms of food supply and pharmaceutical applications. However, its classification and identification are controversial. DNA barcoding is a recent aid to taxonomic identification and uses a short standardized DNA region to discriminate plant species. In this study, the applicability of three candidate DNA barcodes (rbcL, matK, and psbA-trnH) to identify species within Dioscorea was tested. One-hundred and forty-eight individual plant samples of Dioscorea, encompassing 38 species, seven varieties and one subspecies, representing majority species distributed in China of this genus, were collected from its main distributing areas. Samples were assessed by PCR amplification, sequence quality, extent of specific genetic divergence, DNA barcoding gap, and the ability to discriminate between species. matK successfully identified 23.26% of all species, compared with 9.30% for rbcL and 11.63% for psbA-trnH. Therefore, matK is recommended as the best DNA barcoding candidate. We found that the combination of two or three loci achieved a higher success rate of species discrimination than one locus alone. However, experimental cost would be much higher if two or three loci, rather than a single locus, were assessed. We conclude that matK is a strong, although not perfect, candidate as a DNA barcode for Dioscorea identification. This assessment takes into account both its ability for species discrimination and the cost of experiments.


Successful treatment with injected hyaluronic acid in a patient with lip asymmetry after surgical correction of cleft lip.
Surgical repair of cleft lip, while correcting deformity and dysfunction, may leave residual cosmetic imperfections. The resultant asymmetry and low volume of the upper lip can be addressed surgically and via less invasive methods. We present the first reported use of injectable hyaluronic acid to correct the characteristic lip asymmetry and poor volume after surgical repair of a cleft lip. Using injectable hyaluronic acid, we treated the patient's upper lip to restore symmetry and achieve an augmented volume. We obtained a symmetric correction and aesthetically pleasing volume augmentation in the affected lip. These results lasted approximately 4 months. Using a temporary, alloplastic, injectable soft tissue filler such as hyaluronic acid satisfactorily achieves correction of asymmetry and low volume in a surgically repaired cleft lip. For patients who have endured multiple corrective surgeries, this is a novel and less invasive way to improve their cosmetic concerns.


Multiparametric MRI-Based Radiomics Signature with Machine Learning for Preoperative Prediction of Prognosis Stratification in Pediatric Medulloblastoma.
Despite advances in risk-stratified treatment strategies for children with medulloblastoma (MB), the prognosis for MB with short-term recurrence is extremely poor, and there is still a lack of evaluation of short-term recurrence risk or short-term survival. This study aimed to construct and validate a radiomics model for predicting the outcome of MB based on preoperative multiparametric magnetic resonance images (MRIs) and to provide an objective for clinical decision-making. The clinical and imaging data of 64 patients with MB admitted to Shenzhen Children's Hospital from December 2012 to December 2021 and confirmed by pathology were retrospectively collected. According to the 18-month progression-free survival, the cases were classified into a good prognosis group and a poor prognosis group, and all cases were divided into training group (70%) and validation group (30%) randomly. Radiomics features were extracted from MRI of each child. The consistency test, t-test, and the least absolute shrinkage and selection operator were used for feature selection. The support vector machine (SVM) and receiver operator characteristic were used to evaluate the distinguishing ability of the selected features to the prognostic groups. RAD score was calculated based on the selected features. The clinical characteristics and RAD score were included in the multivariate logistic regression, and prediction models were constructed by screening out independent influences. The radiomics nomogram was constructed, and its clinical significance was evaluated. A total of 1930 radiomic features were extracted from the images of each patient, and 11 features were included in the construction of radiomics score after selected. The area under the curve (AUC) values of the SVM model in the training and validation groups were 0.946 and 0.797, respectively. The radiomics nomogram was constructed based on the training cohort, and the AUC values in the training group and the validation group were 0.926 and 0.835, respectively. The results of clinical decision curve analysis showed that a good net benefit could be obtained from the nomogram. The radiomics nomogram established based on MRI can be used as a noninvasive predictive tool to evaluate the prognosis of children with MB, which is expected to help neurosurgeons better conduct preoperative planning and patient follow-up management.


[Light and electron microscopy studies of the development of Reissner's membrane in the cochlear duct of guinea pig fetuses].
Differentiation of the Reissner's membrane (membrana vestibularis) is described in precisely dated guinea pig fetuses. In newborn and adult animals, the Reissner's membrane consists of two layers of flat cells, an epithelial one and a mesenchymal one, separated by a basement membrane. The epithelial part develops from the initially simple columnar epithelium of the upper wall of the cochlear duct. The mesenchymal part arises from the embryonic connective tissue, which in early developmental stages occupies the space of the later scala vestibuli. The studies show that during fetal life, a mixture of the endolymph of the cochlear duct with the perilymph of the scala vestibuli is prevented by zonulae occludentes between the epithelial cells of Reissner's membrane. On the other hand, even at an early stage an exchange of material between the two fluids is to a small extent possible by means of cytopempsis through the cytoplasm of the epithelial cells.


Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease.
Alzheimer's disease (AD) is the most common cause of dementia. Neuritic amyloid plaques and concomitant chronic inflammation are prominent pathological features of AD. beta-amyloid peptide (Abeta), the major component of plaques, and advanced glycation end products (AGEs), post-translational protein modifications, are key activators of plaque-associated inflammation. Abeta, AGEs, S100b, and amphoterin bind to the receptor for AGEs (RAGE), which transmits the signal from RAGE via redox-sensitive pathways to nuclear factor kappa-B (NF-kappaB)-regulated cytokines. RAGE-mediated inflammation caused by glial cells and subsequent changes in neuronal glucose metabolism are likely to be important contributors to neurodegeneration in AD. As long as the neuronal damage is reversible, drugs interfering with the Abeta and AGE-RAGE pathways might be interesting novel therapeutics for the treatment of AD.


Enhanced biogas production from anaerobic codigestion of solid waste by sonolysis.
This paper examines the effectiveness of sonolysis in improving the anaerobic biodegradability of the organic fraction of municipal solid waste coming from mechanical selection, thus enhancing biogas production and energy recovery as well. Methane yield of solid organic material anaerobic digestion is significantly affected by substrate availability that was evaluated, in this investigation, through organic matter solubilisation tests carried out at different conditions of ultrasound treatment. Results show that sonolysis can significantly improve the solubilisation of organic solid waste, thus allowing higher biogas production from anaerobic treatment of sonicated substrates. After 45 days, the biogas produced during anaerobic codigestion tests for the sonicated mixture was 24% higher than untreated one. Therefore, these results can lay the basis for the development of technologies useful to produce high biogas quantities, in order to improve clean energy generation from biowaste.


Renal Involvement in a French Paediatric Cohort of Patients with Lysinuric Protein Intolerance.
Lysinuric protein intolerance (LPI) is a rare autosomal recessive metabolic disorder, caused by defective transport of cationic amino acids at the basolateral membrane of epithelial cells, typically in intestines and kidneys. The SLC7A7 gene, mutated in LPI patients, encodes the light subunit (y+LAT1) of a member of the heterodimeric amino acid transporter family.The diagnosis of LPI is difficult due to unspecific clinical features: protein intolerance, failure to thrive and vomiting after weaning. Later on, patients may present delayed growth osteoporosis, hepatosplenomegaly, muscle hypotonia and life-threatening complications such as alveolar proteinosis, haemophagocytic lymphohistiocytosis and macrophage activation syndrome. Renal involvement is also a serious complication with tubular and more rarely, glomerular lesions that may lead to end-stage kidney disease (ESKD). We report six cases of LPI followed in three different French paediatric centres who presented LPI-related nephropathy during childhood. Four of them developed chronic kidney disease during follow-up, including one with ESKD. Five developed chronic tubulopathies and one a chronic glomerulonephritis. A histological pattern of membranoproliferative glomerulonephritis was first associated with a polyclonal immunoglobulin deposition, treated by immunosuppressive therapy. He then required a second kidney biopsy after a relapse of the nephrotic syndrome; the immunoglobulin deposition was then monoclonal (IgG1 kappa). This is the first observation of an evolution from a polyclonal to a monotypic immune glomerulonephritis. Immune dysfunction potentially attributable to nitric oxide overproduction secondary to arginine intracellular trapping is a debated complication in LPI. Our results suggest all LPI patients should be monitored for renal disease regularly.


Competition in health care: it takes systems to pursue quality and efficiency.
Many stakeholders agree that the current model of U.S. health care competition is not working. Costs continue to rise at double-digit rates, and quality is far from optimal. One proposal for fixing health care markets is to eliminate provider networks and encourage informed, financially responsible consumers to choose the best provider for each condition. We argue that this "solution" will lead our health care markets toward even greater fragmentation and lack of coordination in the delivery system. Instead, we need markets that encourage integrated delivery systems, with incentives for teams of professionals to provide coordinated, efficient, evidence-based care, supported by state-of-the-art information technology.


Improving isobutanol production in metabolically engineered Escherichia coli by co-producing ethanol and modulation of pentose phosphate pathway.
Redox imbalance has been regarded as the key limitation for anaerobic isobutanol production in metabolically engineered Escherichia coli strains. In this work, the ethanol synthetic pathway was recruited to solve the NADH redundant problem while the pentose phosphate pathway was modulated to solve the NADPH deficient problem for anaerobic isobutanol production. Recruiting the ethanol synthetic pathway in strain AS108 decreased isobutanol yield from 0.66 to 0.29 mol/mol glucose. It was found that there was a negative correlation between aldehyde/alcohol dehydrogenase (AdhE) activity and isobutanol production. Decreasing AdhE activity increased isobutanol yield from 0.29 to 0.6 mol/mol. On the other hand, modulation of the glucose 6-phosphate dehydrogenase gene of the pentose phosphate pathway increased isobutanol yield from 0.29 to 0.41 mol/mol. Combination of these two strategies had a synergistic effect on improving isobutanol production. Isobutanol titer and yield of the best strain ZL021 were 53 mM and 0.74 mol/mol, which were 51 % and 12 % higher than the starting strain AS108, respectively. The total alcohol yield of strain ZL021 was 0.81 mol/mol, which was 23 % higher than strain AS108.


p-AKT/VPS4B regulates the small extracellular vesicle size in venous malformation endothelial cells.
Small extracellular vesicle (sEV)-mediated intercellular communication is increasingly the key for the understanding of venous malformations (VMs). This study aims to clarify the detailed changes of sEVs in VMs. Fifteen VM patients without treatment history and twelve healthy donors were enrolled in the study. sEVs were isolated from both fresh lesions and cell supernatant, and were examined by western blotting, nanoparticle tracking analysis and transmission electron microscopy. Western blot analysis, immunohistochemistry and immunofluorescence were adopted to screening candidate regulator of sEV size. Specific inhibitors and siRNA were employed to validate the role of dysregulated p-AKT/vacuolar protein sorting-associated protein 4B (VPS4B) signaling on the size of sEVs in endothelial cells. The size of sEVs derived from both VM lesion tissues and cell model was significantly increased. VPS4B, whose expression level was mostly significantly downregulated in VM endothelial cells, was responsible for the size change of sEVs. Targeting abnormal AKT activation corrected the size change of sEVs by recovering the expression level of VPS4B. Downregulated VPS4B in endothelial cells, resulted from abnormally activated AKT signaling, contributed to the increased size of sEVs in VMs.


Body mass and geographic distribution determined the evolution of the wing flight-feather molt strategy in the Neornithes lineage.
The evolutionary history of many organisms is characterized by major changes in morphology and distribution. Specifically, alterations of body mass and geographic distribution may profoundly influence organismal life-history traits. Here, we reconstructed the evolutionary history of flight-feather molt strategy using data from 1,808 Neornithes species. Our analysis suggests that the ancestral molt strategy of first-year birds was partial or entirely absent, and that complete wing flight-feather molt in first-year birds first evolved in the late Eocene and Oligocene (25-40 Ma), at least 30 Myr after birds first evolved. Complete flight-feather molt occurred mainly at equatorial latitudes and in relatively low body mass species, following a diversification of body mass within the lineage. We conclude that both body mass and geographic distribution shaped the evolution of molt strategies and propose that the evolutionary transition towards complete juvenile molt in the Neornithes is a novel, relatively late adaptation.


Pathological study of sternal osteomyelitis after median thoracotomy-a prospective cohort study.
Osteomyelitis of the sternum may arise either as a primary condition or secondary to median thoracotomy after cardiac surgery, with the latter being decidedly more frequent. Deep sternal wound infections appear as a complication of median thoracotomy in 0.2 to 4.4% of cases and may encompass the infection of the sternal bone. To date, there are no exhaustive histopathological studies of the sternal osteomyelitis. Our work group developed a surgical technique to remove the complete infected sternal bone in deep sternal wound infections. We therefore prospectively examined the en bloc resected sternal specimens. Seven standard histological sections were made from the two hemisternums. Forty-seven sternums could be investigated. The median age of the patients in the cohort was 66 (45-81) years and there were 10 females and 37 males. Two methods were developed to examine the histological findings, with one model dividing the results in inflammatory and non-inflammatory, while the second method using a score from 0 to 5 to describe more precisely the intensity of the bone inflammation. The results showed the presence of inflammation in 76.6 to 93.6% of the specimens, depending on the section. The left manubrial sections were more prone to inflammation, especially when the left mammary artery was harvested. No further risk factors proved to have a statistical significance. Our study proved that the deep sternal wound infection may cause a ubiquitous inflammation of the sternal bone. The harvest of the left mammary artery may worsen the extent and intensity of infection.


Development of an Adhesive Gel System for Changing the Structure and Properties of Its Adhesive Joint via Reactions with Amine Molecules after Adhesion.
Adhesive gel systems are attracting increasing interest from researchers to use gel materials for artificial biomaterials and engineering materials. Humans, among other living beings, eat foods, get nutrients from them, and use these nutrients to grow up day by day. The shapes and characteristics of their bodies change depending on the nutrients they get. This research develops an adhesive gel system that the chemical structure of the adhesive joint and their properties can be changed and regulated after adhesion, like the growth of living beings. The adhesive joint, which is constructed using a linear polymer comprising a cyclic trithiocarbonate monomer and acrylamide, developed in this research reacts with amines and forms chemical structures depending on amines. The differences in chemical structures endow the adhesive joint with the characteristics and properties that depend on the reaction of amines with the adhesive joint.


Genetic instability of BRCA1 gene at locus D17S855 is related to clinicopathological behaviors of gastric cancer from Chinese population.
To investigate genetic instability of gene BRCA1 at locus D17S855, and their relationship with clinicopathological characteristics of gastric cancer in Chinese population. Microsatellite instability (MSI) and loss of heterozygosity (LOH) of gene BRCA1 at locus D17S855 were compared between 37 samples of gastric cancer and corresponding non-cancerous gastric tissue. MSI at locus D17S855 was positive in 7 of 37 samples of gastric cancer (18.95%). MSI had a close relationship with TNM staging but no relation with lymph node metastasis, histological type or tumor differentiation. MSI positive frequency in TNM I + II (31.58%, 6/19) was much higher than that in TNM III + IV (5.56%, 1/18), (P < 0.05). LOH positive rate was 18.92% (7/37). LOH had no relationship to histological type, tumor differentiation or lymph node metastasis, but LOH positive rate in TNM III + IV was 33.33% (6/18), much higher than that in TNM I + II ( 5.26%, 1/19), (P < 0.05). BRCA1 protein was expressed in 14 of 37 samples of gastric cancer. The positive rates of BRCA1 protein in TNM I + II and TNM III + IV were 57.89% and 16.67%, respectively, (P < 0.05). The positive rate of BRCA1 protein was 77.78% in high differentiation samples, 30.77% in middle differentiation and 12.50% in lower differentiation samples, (P < 0.05). MSI of BRCA1 gene could be used as a molecular marker in early phases of sporadic gastric cancer in Chinese population. LOH occurs at later period of gastric cancer, therefore, it could be used as prognostic factor.


Taste responses to amino acids from facial nerve branches innervating oral and extra-oral taste buds in the channel catfish, Ictalurus punctatus.
Electrophysiological recordings were obtained from two branches of the facial nerve innervating oral and extra-oral taste receptive fields, respectively, in the channel catfish, Ictalurus punctatus. The results indicate that taste buds innervated by the ramus ophthalmicus superficialis (ros), innervating taste buds on the nasal barbel, and the ramus palatinus (rp), innervating taste buds on the anterior palate, have similar chemical specificities for amino acids. Among the amino acids tested, the most stimulatory compounds for both the ros and rp were L-alanine and L-arginine, having estimated electrophysiological thresholds of approximately 10(-9) M. Dose-response functions for amino acid stimuli recorded from both the ros and rp were power functions extending over 5 log units of stimulus concentrations. The general similarity in the nature of the taste input from spatially distinct gustatory areas supports a chemotactic role of the facial taste system in the channel catfish.


Vasospasm following transsphenoidal tumor removal associated with the arterial changes of oral contraception.
A case of fatal cerebral vasospasm after transsphenoidal removal of a pituitary macroadenoma with suprasellar extension is reported. On the second postoperative day the patient developed headache, lethargy, and cardiorespiratory arrest. Five days later, after recovery from this episode, she developed signs of involvement of the left hemisphere. At that time she demonstrated severe cerebral vasospasm, which was worse in the left supraclinoid segment of the internal carotid artery, and she died 19 days postoperatively. Postmortem examination showed left hemispheric and hypothalamic infarction with subsequent herniation. In addition, pathologic arterial changes usually related to use of oral contraceptives were present.


Clinical features of colorectal duplication in children: A study of 25 cases.
To describe the clinical features and surgical management of pediatric colorectal duplication. Twenty-five patients with colorectal duplication at Beijing Children's Hospital between January 2010 and December 2020 were reviewed. Colorectal duplications were divided into cystic, diverticular, tubular and mixed types according to shape. Of the patients, 64% were female, and 44% had accompanying malformations. Abnormal prenatal ultrasound findings (24%), abnormalities immediately found after birth (28%), and postnatal subjective symptoms (48%) were the main clinical presentations. Cystic lesions were observed in 16 patients (64%), including 12 in the colon and 4 in the rectum. Diverticular lesions were observed in 4 patients (16%), and all originated from the sigmoid colon. Among the 4 patients (16%) with tubular lesions, 3 involved the total colon, and the other originated from the splenic flexure to the proximal sigmoid colon. The patient with mixed duplication presented an intact enteric cyst within tubular duplication of the total colon. The mean age at surgery was 20 (0.3-130) months. Except for 4 total colon duplications, complete surgical resection of duplication lesions was performed in all patients. The "distal cross-section, mucosa stripping, and closure" procedure was performed in 3 patients with total colon duplication. Eighteen patients (72%) were followed up for a median time of 54.5 (5-129) months and recovered uneventfully. Owing to various clinical presentations, colorectal duplication requires careful preoperative differential diagnosis. Complete surgical resection is the preferred radical method for treating cystic, diverticular and short tubular colorectal duplications, except for total colon duplications. Level IV.


Severe involvement of the ambient gyrus in a case of dementia with argyrophilic grain disease.
We report here the severe involvement of the ambient gyrus in a case of argyrophilic grain (AG) dementia (AGD). The patient was a 78-year-old man who was first presented with prosopagnosia (agnosia of the face) at age 68, which was followed by progressive mental decline and the patient's death in a state of tetraplegia. The postmortem study showed severe atrophy of the medial temporal lobe with anterior gradient, most prominent in the ambient gyrus. Histologically, numerous AGs, pretangles and coiled bodies were detected by Gallyas-Braak (G-B) silver staining and also by immunostaining with various anti-tau antibodies in the affected area. Tau-immunoreactive ballooned neurons were also present. Neuronal loss and gliosis with laminar sponginess were evident in the ambient gyrus. Diffuse plaques were seen in the neocortex and frequently associated with clusters of AGs, which were morphologically distinct from neuritic plaques. Neurofibrillary tangles were localized in the entorhinal area. Vascular lesions were very scanty. Thus, this case fulfilled the morphological criteria of AGD. It is still unclear whether AG itself causes neuronal degeneration leading to dementia. The present case may reflect the importance of the ambient gyrus in the center of neuronal degeneration in AGD.


Certain plants are able to convert first stage larvae of the Green Peach Aphid into apterous larvae although the larger part of them would develop into alates if reared continuously on a holidic diet.This Apterousness Promoting Principle (ApP principle) has a greater effect on previously starved larvae and on those whose extremities were partly amputated. The ApP principle can be shown most clearly in young radish seedlings, as well as in other young plants if they are optimal hosts. It is reduced in old radish leaves and in plant species which are merely accepted by Myzus persicae for a longer time. The principle is also reduced by wilting, etiolation, or during and shortly following over-population of the young seedlings. By covering the cotyledons with a thin parafilm membrane or by washing them with water the ApP principle is partly eliminated. We suggest the ApP principle is largely coupled with "good" food, but an important component of it operates as a "token stimulus" perceived already in part on the plant surface. Hence the standard diet seems to offer "poor" nutrition. With further deterioration such as the omission of ascorbic acid or brief food deprivation the number of alates increases, whereas with extremely poor food (for example if the essential amino acid isoleucine is entirely omitted or if food is withheld for more than 18 h) this gives way to an increase in the formation of apterous larvae. A group effect may modify the reaction after brief omission of food: more of the larvae in groups develop into alates, single larvae more into apters.


Corneal endothelial changes after selective laser trabeculoplasty.
Whitish spots are sometimes noted in the corneal endothelium after selective laser trabeculoplasty. To evaluate the corneal endothelium after selective laser trabeculoplasty, corneal specular microscopy was performed. Prospective observational study in a private practice. Fifteen consecutive patients with open-angle glaucoma undergoing selective laser trabeculoplasty in February 2012 had their corneal endothelium examined with specular microscopy before and after treatment. Selective laser trabeculoplasty was done with 50 ± 5 shots to 180 degrees of meshwork using 0.3-0.9 mJ of power to achieve the reaction of a hint of microbubbles in 80% of laser shots. Corneal specular microscopy photographs (0.25 × 0.54 mm) were taken prior to, immediately after and 1 month after selective laser trabeculoplasty. These photographs were assessed and graded. Of the 15 patients, three showed numerous, four showed few and eight showed no increase of dark spots after selective laser trabeculoplasty. All the dark spots resolved by 1 month. The effect of selective laser trabeculoplasty on the corneal endothelium may be transient, and long-term effects are probably negligible in normal corneas. However, in compromised corneas and corneas with pigment deposits on endothelium, there may be a risk of corneal endothelial compromise, especially after repeated selective laser trabeculoplasty. Larger and longer term studies with histopathological evaluation would be useful to evaluate the effect of selective laser trabeculoplasty on normal and subnormal corneal endothelium. Until further studies are done, it would be wise to minimize the number and energy of laser shots.


Primary malignant gonadal mesotheliomas and asbestos.
The clinicopathological, immunohistochemical and aetiological aspects, with respect to asbestos, of seven primary gonadal mesotheliomas (three intratesticular, four ovarian) are described and compared. These tumours are extremely rare, poorly described and the knowledge of their natural history is very limited. The cases were collated from the UK Health and Safety Executive Mesothelioma Register over a 24-year period (1968-91). Primary mesotheliomas of the tunica vaginalis and ovary comprised 0. 09% (10 cases) and 0.03% (three cases) of mesothelioma deaths, respectively. No primary intratesticular (non-tunica vaginalis) malignant mesotheliomas have been described. In this study, we present seven (three intratesticular, four ovarian) primary malignant gonadal mesotheliomas. In both genders the tumours show a similar age distribution (with median onset in the sixth decade), a similar association with asbestos (in approximately 50% cases), a diverse histological spectrum (with predominantly tubulopapillary epithelial subtype tumours) and an immunophenotype that is comparable with malignant pleural and peritoneal mesothelioma. The clinical course appears variable (mean, 26 months; range, 9-50 months). All tumours in the study presented as localized masses and their prognosis appeared more favourable than that of diffuse pleural and peritoneal cases. An awareness of the existence of these rare forms of malignant mesothelioma is important to prevent misdiagnosis. Immunohistochemistry has an important role in confirmation of the diagnosis. The accurate diagnosis of primary gonadal mesothelioma has potentially important medicolegal compensation considerations as a significant proportion of these cases are associated with asbestos.


Organic solvent fractionation of acetosolv palm oil lignin: The role of its structure on the antioxidant activity.
Pressed palm oil mesocarp fibers (PPOMF) are by-products from oil palm industry and represents a potential source of lignocellulosic biomass. In order to add value to this agro-waste, dewaxed palm oil acetosolv lignin (DPOAL) was extracted under eco-friendly pulping method. The chemical composition and structural characteristics of DPOAL were investigated. The results showed elevated yield (48.5%) and high purity (94.3%), besides a moderate average molecular weight (1394 g mol-1) and narrow polydispersity index (1.88). Structural characterization via FT-IR, 1H13C HSQC and 31P NMR indicated that DPOAL was a typical HGS-type lignin. In addition, to increase the phenolic hydroxyl contents and improve DPOAL's antioxidant properties through a simple method, a fractionation process with methanol, ethanol and acetone was carried out, obtaining the methanol (MeOH-F), ethanol (EtOH-F) and acetone (ACT-F) soluble fractions. These were characterized by FT-IR, DSC, 1H13C HSQC and 31P NMR, which showed higher values of phenolic and aliphatic hydroxyls groups compared to DPOAL. The antioxidant activity was evaluated by the free radical scavenging activity of 2,2‑diphenyl‑1‑picrylhydrazyl radicals (DPPH·) and compared with commercial antioxidants, such as BHT and Irganox 1010. Interestingly, lignin samples had significantly lower IC50 values compared to commercial antioxidants, what suggests a great potential as novel natural antioxidant.


Endocrine mucin-producing sweat gland carcinoma of the eyelid.
An elderly woman was incidentally noted to have a nodular mass on the upper eyelid, whilst under investigation for cataracts. Punch biopsy of this presumed basal cell carcinoma revealed it to be endocrine mucin-producing sweat gland carcinoma (EMPSGC). The tumour extended to the deep dermal layer and comprised solid nests with foci of cystic and papillary change, and additional cytoplasmic and focal extracellular mucin deposits. Immunohistochemistry confirmed epithelial lineage and neuroendocrine differentiation, and adjacent tissue invasion. The tumour was excised completely with Mohs micrographic surgery with no recurrence after 8 months. EMPSGC is a low-grade sweat gland carcinoma with variable neuroendocrine differentiation, a solid, papillary, or cystic growth pattern, and a predilection for the eyelid of elderly women [Am J Surg Pathol 29:1330-1339, 2005]. There have been 54 previously documented cases of EMPSCG. We report an additional case and review the literature.


Brain activation during execution and motor imagery of novel and skilled sequential hand movements.
This experiment used functional magnetic resonance imaging (fMRI) to compare functional neuroanatomy associated with executed and imagined hand movements in novel and skilled learning phases. We hypothesized that 1 week of intensive physical practice would strengthen the motor representation of a hand motor sequence and increase the similarity of functional neuroanatomy associated with executed and imagined hand movements. During fMRI scanning, a right-hand self-paced button press sequence was executed and imagined before (NOVEL) and after (SKILLED) 1 week of intensive physical practice (n = 54; right-hand dominant). The mean execution rate was significantly faster in the SKILLED (3.8 Hz) than the NOVEL condition (2.5 Hz) (P < 0.001), but there was no difference in execution errors. Activation foci associated with execution and imagery was congruent in both the NOVEL and SKILLED conditions, though activation features were more similar in the SKILLED versus NOVEL phase. In the NOVEL phase, activations were more extensive during execution than imagery in primary and secondary cortical motor volumes and the cerebellum, while during imagery activations were greater in the striatum. In the SKILLED phase, activation features within these same volumes became increasingly similar for execution and imagery, though imagery more heavily activated premotor areas, inferior parietal lobe, and medial temporal lobe, while execution more heavily activated the precentral/postcentral gyri, striatum, and cerebellum. This experiment demonstrated congruent activation of the cortical and subcortical motor system during both novel and skilled learning phases, supporting the effectiveness of motor imagery-based mental practice techniques for both the acquisition of new skills and the rehearsal of skilled movements.


Coexpression network analysis associated with call of rice seedlings for encountering heat stress.
Coexpression network analysis is useful tool for identification of functional association of coexpressed genes. We developed a coexpression network of rice from heat stress transcriptome data. Global transcriptome of rice leaf tissues was performed by microarray at three time points--post 10 and 60 min heat stress at 42 °C and 30 min recovery at 26 °C following 60 min 42 °C heat stress to investigate specifically the early events in the heat stress and recovery response. The transcriptome profile was significantly modulated within 10 min of heat stress. Strikingly, the number of up-regulated genes was higher than the number of down-regulated genes in 10 min of heat stress. The enrichment of GO terms protein kinase activity/protein serine threonine kinase activity, response to heat and reactive oxygen species in up-regulated genes after 10 min signifies the role of signal transduction events and reactive oxygen species during early heat stress. The enrichment of transcription factor (TF) binding sites for heat shock factors, bZIPs and DREBs coupled with up-regulation of TFs of different families suggests that the heat stress response in rice involves integration of various regulatory networks. The interpretation of microarray data in the context of coexpression network analysis identified several functionally correlated genes consisting of previously documented heat upregulated genes as well as new genes that can be implicated in heat stress. Based on the findings on parallel analysis of growth of seedlings, associated changes in transcripts of selected Hsps, genome-wide microarray profiling and the coexpression network analysis, this study is a step forward in understanding heat response of rice, the world's most important food crop.


Chikungunya virus (CHIKV) inhibitors from natural sources: a medicinal chemistry perspective.
Chikungunya virus (CHIKV) is one of the re-emerging "neglected" tropical diseases whose recent outbreak affected not only Africa and South-East Asia but also several parts of America and Europe. To date, despite its serious nature, no antivirals or vaccines were developed in order to counter this resurgent infectious disease. The recent advancement in crystallography and availability of crystal structures of certain domains of CHIKV initiates the development of anti-CHIKV agents using structure-based drug design or synthetic medicinal chemistry approach. Despite the fact that almost 50% of the new chemical entities against several biological targets were either obtained from natural products or natural product analogues, a very humble effort was directed towards identification of novel CHIKV inhibitors from natural products. In this review, besides a brief overview on CHIKV as well as the nature as a source of medicines, we highlight the current progress and future steps towards the discovery of CHIKV inhibitors from natural products. This report could pave the road towards the design of novel semi-synthetic derivatives with enhanced anti-viral activities.


Coral reef carnivorous fish biomass relates to oceanographic features depending on habitat and prey preference.
Carnivorous fish are a key part of the Indonesian human population sustenance, and it is important to design marine protected areas that include environmental features that allow these species to thrive. Many studies report the role of coral cover and habitat complexity in determining fish distribution on coral reefs but broader environmental factors such as current velocity and productivity are less studied. Southern Indonesia is characterised by upwellings and strong currents, stemming from the tidal cycle and the Indonesian Throughflow. In this study we investigate how current velocity, chlorophyll-a (chl-a), sea surface height and temperature relate to the biomass of carnivorous fish, considering the influence of habitat complexity and coral cover. Data were collected by surveying seven sites around Nusa Penida MPA for a total of 97 h of observation. Serranids and Lutjanids showed higher dependency on coral cover than fish from family Lethrinidae, Carangidae and Scombridae for which current, sea surface height, chl-a, and temperature were more influential predictors. Considering the similar trophic ecology of these species, the different relationship with oceanographic factors is likely related to different body shapes, living, and feeding habits between fish families. Changes in sea surface temperature and current velocity induced by vertical mixing are affecting coral reef fisheries-targeted species distribution in Nusa Penida and investigating these relationships on a broader scale will better inform marine spatial planning decisions.


Valorisation of keratin waste: Controlled pretreatment enhances enzymatic production of antioxidant peptides.
Conversion of keratin waste to value-added products not only reduces waste volumes but also creates new revenue streams for the animal production industry. In the present study, combination of alkaline pretreatment of cattle hair with enzymatic hydrolysis was studied to produce keratin hydrolysates with relatively high antioxidant activities. Firstly, the effect of pretreatment conditions at a high solid/liquid mass ratio of 1:2 with different NaOH loadings and temperatures was studied. Increasing NaOH concentration from 1.0% to 2.5% and temperature from room temperature to 110 °C increased hair hydrolysis by keratinase and protein recovery in hydrolysates. Mild pretreatment with 1.5% NaOH at 70 °C for 30 min led to a protein recovery of 30% in the enzymatic hydrolysate. The resulting hydrolysate showed a high antioxidant activity, scavenging 69% of the ABTS radical with a low EC50 of 0.8 mg/mL. Severe pretreatment with 2.5% NaOH at 110 °C for 30 min resulted in a higher protein recovery of 45%, but a lower ABTS radical scavenging activity of 56% and a higher EC50 of 1.3 mg/mL. The reduced antioxidant activity was attributed to the reduced proportion of small peptides (<3 kDa) and the increased extent of amino acid chemical modification. This study demonstrated that controlling alkali pretreatment conditions could lead to the production of enzymatic hydrolysates with higher antioxidant activities for potential value-adding applications. The information generated from this study will aid scale-up and commercialisation of processes with optimised antioxidant peptide production.


Adenosine prevents isoprenaline-induced cardiac contractile and electrophysiological dysfunction.
Excessive levels of catecholamines are believed to contribute to cardiac dysfunction in a variety of disease states, including myocardial infarction and heart failure, and are particularly implicated in stress-induced cardiomyopathy, an increasingly recognized cardiomyopathy associated with significant morbidity and mortality. We have previously shown that a high dose of isoprenaline induces reversible regional dysfunction of the left ventricle in mice. We now hypothesize that adenosine can prevent cardiac dysfunction in this mouse model of stress-induced cardiomyopathy. Hundred male C57BL/6 mice were injected with 400mg/kg isoprenaline and then randomized to either 400mg/kg adenosine or saline. Cardiac function was evaluated by echocardiography at baseline and 2, 24, 48, 72, 96 and 120 min post isoprenaline. Myocardial fibrosis was quantified after 10 days. Intracellular lipid accumulation was quantified after 2 and 24h. Electrophysiological parameters and degree of lipid accumulation were evaluated in cultured HL1 cardiomyocytes. Two hours post isoprenaline treatment, echocardiographic parameters of global and posterior wall regional function were significantly better in adenosine-treated mice (P<0.05). This difference persisted at 24h, but saline-treated mice gradually recovered over the next 96 h. Intracellular lipid accumulation was also significantly lower in adenosine mice. We found no sign of fibrosis in the adenosine mice, whereas the extent of fibrosis in isoprenaline mice was 1.3% (P<0.05). Furthermore, adenosine-treated HL1 cells showed preserved electrophysiological function and displayed less severe intracellular lipid accumulation in response to isoprenaline. In conclusion, adenosine attenuates isoprenaline-induced cardiac dysfunction in mice and cells.


Differential sensitivity of the yeast Lon protease Pim1p to impaired mitochondrial respiration.
Mitochondria are essential organelles whose proteome is well protected by regulated protein degradation and quality control. While the ubiquitin-proteasome system can monitor mitochondrial proteins that reside at the mitochondrial outer membrane or are not successfully imported, resident proteases generally act on proteins within mitochondria. Herein, we assess the degradative pathways for mutant forms of three mitochondrial matrix proteins (mas1-1HA, mas2-11HA, and tim44-8HA) in Saccharomyces cerevisiae. The degradation of these proteins is strongly impaired by loss of either the matrix AAA-ATPase (m-AAA) (Afg3p/Yta12p) or Lon (Pim1p) protease. We determine that these mutant proteins are all bona fide Pim1p substrates whose degradation is also blocked in respiratory-deficient "petite" yeast cells, such as in cells lacking m-AAA protease subunits. In contrast, matrix proteins that are substrates of the m-AAA protease are not affected by loss of respiration. The failure to efficiently remove Pim1p substrates in petite cells has no evident relationship to Pim1p maturation, localization, or assembly. However, Pim1p's autoproteolysis is intact, and its overexpression restores substrate degradation, indicating that Pim1p retains some functionality in petite cells. Interestingly, chemical perturbation of mitochondria with oligomycin similarly prevents degradation of Pim1p substrates. Our results demonstrate that Pim1p activity is highly sensitive to mitochondrial perturbations such as loss of respiration or drug treatment in a manner that we do not observe with other proteases.


Metabolic Reprogramming toward Aerobic Glycolysis and the Gut Microbiota Involved in the Brain Amyloid Pathology.
Alzheimer's disease (AD) is characterized by the formation of senile plaques consisting of fibrillated amyloid-β (Aβ), dystrophic neurites, and the neurofibrillary tangles of tau. The oligomers/fibrillar Aβ damages the neurons or initiates an intracellular signaling cascade for neuronal cell death leading to Aβ toxicity. The Aβ is a 4 kDa molecular weight peptide originating from the C-terminal region of the amyloid precursor protein via proteolytic cleavage. Apart from the typical AD hallmarks, certain deficits in metabolic alterations have been identified. This study describes the emerging features of AD from the aspect of metabolic reprogramming in the main pathway of carbohydrate metabolism in the human brain. Particularly, the neurons in patients with AD favor glycolysis despite a normal mitochondrial function indicating a Warburg-like effect. In addition, certain dietary patterns are well known for their properties in preventing AD. Among those, a ketogenic diet may substantially improve the symptoms of AD. An effective therapeutic method for the treatment, mitigation, and prevention of AD has not yet been established. Therefore, the researchers pursue the development and establishment of novel therapies effective in suppressing AD symptoms and the elucidation of their underlying protective mechanisms against neurodegeneration aiming for AD therapy in the near future.


Knowledge mapping and current trends of immunotherapy for prostate cancer: A bibliometric study.
Prostate cancer (PCa) is the second most common malignancy in men worldwide. Growing evidence substantiates the important role of immunotherapy in human tumors. Given that immunotherapy is often unsatisfactory on PCa, many studies have been conducted on PCa immunotherapy to improve treatment efficacy. However, no relevant bibliometric study of PCa immunotherapy has hitherto been reported. A bibliometric analysis was performed to evaluate the global scientific production of PCa immunotherapy research and characterize the development trends for future studies in this article. The publications related to PCa immunotherapy were extracted from the Web of Science Core Collection. The contribution and co-occurrence relationships of countries/regions, institutions, journals, references, authors, and keywords were assessed and visualized by VOSviewer and CiteSpace to identify research hotspots and potential future trends. A total of 3,583 publications related to PCa immunotherapy from 1999 to 2021 were collected. The results of annual publications and citations exhibited a steady increase over the past 22 years. The National Cancer Institute in the USA published far more papers during the study than any institute. Accordingly, the USA had the most publications (n = 1,954, 54.54%). Gulley, James L. had the most number of published papers, and Small, Eric J. was the most co-cited authors in this field. Cancer Immunology Immunotherapy was the most productive journal, with 145 publications on PCa immunotherapy. Keyword cluster and keyword burst analyses showed that research in PCa immunotherapy shifted from "t cell infiltration" and "sipuleucel t" to "immune checkpoint inhibitor", "CTLA-4", and "PD-L1 expression". PCa immunotherapy has attracted much attention, reflected by the increasing number of annual publications and citations. Much emphasis has been placed on exploring the complex immunogenicity and tumor microenvironment for PCa and identifying the patient population who can benefit from immunotherapy. Combining immune checkpoint inhibitors with other therapeutic options and cancer vaccines represents the future development trends in PCa immunotherapy.


The crucial role of Y109 and R162 as catalytic residues of nanoKAZ: insights from molecular docking, molecular dynamics simulation, and quantum chemical investigations.
nanoKAZ is a compact luciferase that exhibits intense blue light emission when it catalyzes the substrate Furimazine (FMZ) as a luciferin, making it an excellent candidate as a reporter protein. However, the specific catalytic residues and mechanism of nanoKAZ have not been revealed. Recently, the structure of nanoKAZ was determined, and it was observed that the luminescent properties changed when FMZ analogs with naphthalene replacing benzene were used. It is speculated that the substituted naphthalene may influence the interaction between the catalytic residues and luciferins, thereby affecting the energy of the emitted light signal. Therefore, the primary objective of this study is to analyze and compare the molecular recognition between nanoKAZ and FMZ along with its four activity-altered naphthalene analogs, with aiming to identify the catalytic residues. Molecular docking was employed to construct all nanoKAZ-luciferin models, followed by a 500 ns molecular dynamics simulation. The simulation trajectory was subjected to MM/PBSA analysis to identify crucial residues that contribute significantly to luciferin binding. In the result, two polar residues Y109, and R162 were identified as active residues as their notable contributions to the binding energy. Subsequently, an oxygen molecule was introduced into the local region of the nanoKAZ-FMZ complex and followed with quantum chemical calculations (semiempirical and DFT methods were used) to investigate the catalysis details. The results illustrated the involvement of Y109 and R162 in the oxygenation of FMZ, leading to the formation of dioxetanone, which has been suggested as an important intermediate in the oxidation process among various luciferins sharing the same functional group as FMZ.


Reaction electronic flux and its role in DNA intramolecular proton transfers.
Proton transfer reactions present a key step in many biological and chemical processes. Here, we focused on the electronic changes in the proton transfer reactions of the four DNA bases. In combination with the previous structural analysis the reaction electronic flux together with local descriptors as the Hirshfeld-I charges allow us to identify chemical events and rationalize the underlying reaction mechanism. Our results show that imine-enamine in adenine and citosyne, and keto-enol tautomerizations in thymine and guanine have different reaction mechanisms. The former involve net structural rearrangements driven by favoured electrostatic interactions between the proton and the acceptor atom whereas the keto-enol tautomerizations require electronic changes reflected in the reaction electronic flux and changes in the NBO bond orders which favour the proton transfer reaction.


An emergency department-based program to change attitudes of youth toward violence.
Interpersonal violence continues to be a problem in the United States with a recurrence rate for repeat violence of 6 to 44%, with a 5-year mortality of 20%. This study describes the attitudinal changes of youth enrolled in a program to reduce violence risk. Patients aged 10 to 24 years at a community, teaching Level 1 trauma center who were victims of interpersonal violence (excluding child abuse, sexual assault, and domestic violence) were randomly enrolled in the study. The control group was simply provided a list of available services, whereas the treatment group received an assessment and case management for 6 months. The study examined the change in attitude and behavior of the youths in the treatment and control groups over time, using a combination of chi-square and ANCOVA. A total of 188 victims, 96 subjects in the treatment group and the 92 in the control group, had an average age of 18.6 years and were mostly (82.5%) males. A majority were African-Americans (65.4%), followed by Hispanic (31.4%). There was no significant difference found in mother involvement, father involvement, mother support, father support, peer support or peer delinquency. There was a decrease in support from both parents over time, which was not affected by the program. There was a decrease in peer delinquency for both the treatment group (67 to.41) and the control group (63 to.50). The results of this study demonstrate a lack of attitudinal changes. This may be attributed to limitations of study design and an inherent difficulty in dealing with high-risk inner city youth.


Regulation of alpha subunit synthesis by gonadal steroid feedback in the sheep anterior pituitary.
Cell-free translations of ovine pituitary RNA were used to examine the amount of alpha subunit synthesized in the presence and absence of physiological levels of gonadal steroids. Two animal groups were used: 1) no feedback-castrate ewes exhibiting high serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and 2) negative feedback-castrate ewes treated with estradiol and progesterone which suppressed LH and FSH secretion. Cytoplasmic RNA was extracted from the pituitaries, translated in a wheat germ cell-free system, and alpha subunit identified by specific immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gels. Low amounts of alpha subunit (0.06% of total incorporated trichloroacetic acid-insoluble cpm) were seen in steroid-treated castrate ewes which also exhibited low serum LH and FSH concentrations. The amount of alpha translated by pituitary RNA from untreated castrates was significantly higher than those amounts from the steroid-treated castrates (p less than 0.02). The decreased amount of translated alpha subunit in steroid-treated castrates was probably not due to unique in vitro translation properties since the isotope incorporated/microgram of RNA and the amount of translated growth hormone and prolactin were similar for all RNAs. The results obtained from this animal model system suggest that the chronic negative feedback action of gonadal steroids on the gonadotropic hormones is effected, in part, via inhibition of synthesis of the alpha subunit of LH and FSH.


The association between the parenting stress of the mother and the incidence of allergic rhinitis in their children.
The prevalence of allergic rhinitis and the social burden related to the management of allergic rhinitis have persistently increased. There are many studies investigating the association between the allergic diseases of children and the stress of their parent. However, the relationship between parenting stress and the incidence of allergic rhinitis among children requires further investigation. We aimed to investigate the significance of parenting stress for mothers with children treated for allergic rhinitis. The mothers of 250 children in the second and third grade of elementary school were involved in this study. The Parenting Stress Index-Short Form (PSI-SF) was used to measure parenting stress. Additionally, the monthly household income, treatment history for allergic diseases (atopic dermatitis, asthma, and allergic rhinitis) during the past 12 months, and maternal education status were investigated using the questionnaire. Parenting stress index score was significantly higher among the mothers of children treated for allergic rhinitis (76.41 ± 9.35) compared with the parents of children without treatment history for allergic rhinitis (70.06 ± 13.74). Nonetheless, there were no significant differences between the cases of children with atopic dermatitis and those with asthma. We analyzed the association between allergic rhinitis and parenting stress adjusted for the monthly household income, and maternal education status, and showed that a treatment history of allergic rhinitis was significantly associated with parenting stress (coefficient 7.477, 95% interval 1.703-13.252; p = 0.011). Treatment of the children for allergic rhinitis significantly affects the parenting stress of their mother. We recommend that mothers with children with allergic rhinitis should receive appropriate counseling about parenting stress.


Exposure of chick embryos to cadmium changes the extra-embryonic vascular branching pattern and alters expression of VEGF-A and VEGF-R2.
Cadmium (Cd) has several industrial applications, and is found in tobacco products, a notable source of human exposure. Vascular endothelial cells are key targets of Cd toxicity. Here, we aim to quantify the alteration to vascular branching pattern following Cd exposure in the chick extra-embryonic membrane (EEM) using fractal analysis, and explore molecular cues to angiogenesis such as VEGF-A and VEGF-R2 expression following Cd treatment. Chicken embryos were incubated for 60 h to Hamburger-Hamilton developmental stage 16-17, then explanted and treated with 50 μL of 50 μmol cadmium acetate (CdAc) or an equivalent volume of equimolar sodium acetate (NaAc). Images of embryos and their area vasculosa (AV) were captured and analyzed at 4 different time points (4, 8, 24 and 48 h) following treatment. Vascular branching in the AV was quantified using its fractal dimension (Df), estimated using a box counting method. Gallinaceous VEGF ELISA was used to measure the VEGF-A concentration in the EEM following treatment, with determination of the relative expression of VEGF-A and VEGF-R2 using quantitative real-time RT-PCR. Vascular branching increased monotonically in the control group at all time points. The anti-angiogenic effect of Cd exposure on the AV was reflected by a significant reduction in Df when compared with controls. Df was more markedly reduced in cultures with abnormal embryos. The expression of VEGF-A protein, and VEGF-A and VEGF-R2 mRNA were reduced in Cd-exposed EEMs. Both molecules contribute to growth, vessel sprouting and branching processes, which supports our findings using fractal analysis.


Middle cerebral artery velocity dynamic response profile during exercise is attenuated following multiple ischemic strokes: a case report.
Blood flow regulation is impaired in people with stroke. However, the time course of change in middle cerebral artery velocity (MCAv) following repeated stroke at rest and during exercise remains unknown. In this case study, we provide novel characterization of the dynamic kinetic MCAv response profile to moderate-intensity exercise before and after repeated ischemic MCA stroke. The initial stroke occurred in the left MCA. At 3 months poststroke, left MCAv amplitude (Amp) was ~50% lower than the right. At the 6-month follow-up visit, MCAv Amp declined in both MCA with the left MCAv Amp ~50% lower than the right MCAv Amp. Following a second right MCA stroke, we report further decline in Amp for the left MCA. At the 3- and 6-month visit following the second stroke, the left MCAv Amp declined further (~10%). The right MCAv Amp dramatically decreased by 81.3% when compared to the initial study visit. The MCAv kinetic analysis revealed a marked impairment in the cerebrovascular response to exercise following stroke. We discuss potential pathophysiological mechanisms contributing to poststroke cerebrovascular dysfunction and the need to test therapeutic interventions (such as exercise) that might attenuate cerebrovascular decline in people following stroke.