Valvular and Mural Endocardiosis in Aging Zebrafish (Danio rerio).
Endocardiosis or myxomatous degeneration of the cardiac valves is a well-described age-related change in humans and dogs. Lesions consist of polypoid nodular proliferations of loose extracellular matrix and valvular interstitial cells, most commonly affecting the mitral valve. This entity has not been previously described in fish. Herein we report the appearance, location, and occurrence of valvular and mural endocardiosis in a retrospective survey of aging laboratory zebrafish. Endocardiosis was present in 59 of 777 fish (7.59%), most commonly affecting the sinoatrial (34 fish; 57.6%) and atrioventricular (33 fish; 55.9%) valves. Lesions were more common in fish raised in recirculating water systems and fed commercial diets (52/230 fish; 22.6%) versus flow-through systems with fish fed semi-purified diets (4/234; 1.71%). Lesions were overrepresented in fish heterozygous for a mutant smoothened allele (34/61 fish, 55.7% vs 17/168, 10.1% wild type). There was no association between endocardiosis and intestinal carcinoids. Valvular endocardiosis is a significant age- and husbandry-related background finding in zebrafish and should be considered in the design and interpretation of research studies.


Purification of viral genome-linked protein VPg from potato virus A-infected plants reveals several post-translationally modified forms of the protein.
In order to be able to analyse post-translational modifications and protein interactions of viral genome-linked protein VPg taking place during potato virus A (PVA) infection, an affinity tag-based purification system was developed by inserting a sequence encoding a six-histidine and haemagglutinin (HisHA) tag to the 3' end of the VPg coding sequence within the infectious cDNA clone of PVA. The engineered virus was fully functional and the HisHA tag-encoding sequence remained stable in the PVA genome throughout the infection process. Purification under denaturing conditions resulted in a protein sample that contained multiple VPg and NIa forms carrying post-translational modifications that altered their isoelectric points. Non-modified tagged VPg (pI 8) was a minor product in the protein sample derived from total leaf proteins, but when the replication-associated membranes were used as starting material, its relative amount increased. Further characterization demonstrated that some of the PVA VPg isoforms were modified by multiple phosphorylation events. Purity of the proteins derived from the native purifications with either of the tags was evaluated. A clearly purer VPg sample was obtained by performing tandem affinity purification utilizing both tags sequentially. NIb, CI and HC-Pro co-purified in an affinity-tagged VPg-dependent manner, indicating that the system was able to isolate protein complexes operating during PVA infection.


Evolutionary repair of HIV type 1 gp41 with a kink in the N-terminal helix leads to restoration of the six-helix bundle structure.
The HIV-1 envelope glycoprotein complex (Env) can be stabilized by the introduction of a disulfide bond between the gp120 and gp41 subunits. The resulting protein is monomeric, but trimerization can be improved by the introduction of a single helix-breaking residue at the conserved Ile559 site in the N-terminal heptad repeat region of gp41. To provide more insight into how such a substitution in gp41 affects Env structure and function, we evaluated the effect on the wild-type Env in the context of replicating virus. The Ile559Gly and Ile559Pro mutations adversely affect Env biosynthesis and Env incorporation into virions. Biophysical studies show that the Ile559Pro mutation essentially disrupts the folding of a recombinant gp41 ectodomain core into a six-helix bundle structure. Viruses containing the Ile559Gly and Ile559Pro substitutions replicate poorly, but an evolutionary route is described that restores replication competence. In the escape virus, which contains a Pro559Leu first-site pseudoreversion, the local helical structure and, as a consequence, Env biosynthesis and function are restored.


The Duty to Rescue and Investigators' Obligations.
We examine current applications of the moral duty to rescue to justify clinical investigators' duties of ancillary care and standard of care to subjects in resource-poor settings. These applications fail to explain why investigators possess obligations to research participants, in particular, and not to people in need, in general. Further, these applications fail to recognize the normative significance of the institutional role of the investigators. We offer a positive account of the duty to rescue for investigators as institutional agents, with duties to populations rather than merely individuals.


The status of drug resistance and ampC gene expression in Enterobacter cloacae.
To investigate the status of the drug resistance and the ampC gene expression of Enterobacter cloacae. Disk diffusion tests were made for detecting the susceptibility of antimicrobial agents against Enterobacter cloacae. AmpC gene was amplified by polymerase chain reaction (PCR) and verified by DNA sequencing. AmpC gene expression was analyzed according to antimicrobial agent sensitive phenotype. The sensitivity rates of 144 strains to imipenam, cefepime and cefoperazone/sulbactam were 98.61%, 65.97% and 63.89%, respectively. The sensitivity rates of 144 strains to other antimicrobial agents were lower. Among the 144 strains 120 were found to be positive by PCR for ampC. The PCR product showed high homology to the GenBank ampC sequence. Stably derepressed strains, hyperinducible strains and unexpressing or lower level expressing strains accounted for 30.0% (36/120), 37.5% (45/120), and 32.5% (39/120), respectively. Fifty-six out of 120 strains (46.67%) also produced extended spectrum beta-lactamases (ESBLs). The hyperinducible strains were highly sensitive to all the antimicrobial agents except amoxicillin/clavulanic acid and cefuroxime, while the stably derepressed strains were only sensitive to imipenam and cefepime. However, sensitivity to cefepime decreased if the strains also produced ESBLs. The drug resistant status of Enterobacter cloacae is severe. Clearing out the expressive status of ampC gene will be helpful in selection of antimicrobial agents in the treatment of clinical infection.


Afterimage induced neural activity during emotional face perception.
The N170 response differs when positive versus negative facial expressions are viewed. This neural response could be associated with the perception of emotions, or some feature of the stimulus. We used an aftereffect paradigm to clarify. Consistent with previous reports of emotional aftereffects, a neutral face was more likely to be described as happy following a sad face adaptation, and more likely to be described as sad following a happy face adaptation. In addition, similar to previous observations with actual emotional faces, we found differences in the latency of the N170 elicited by the neutral face following sad versus happy face adaptation, demonstrating that the emotion-specific effect on the N170 emerges even when emotion expressions are perceptually different but physically identical. The re-entry of emotional information from other brain regions may be driving the emotional aftereffects and the N170 latency differences.


Calcitonin is a competitive inhibitor of the hydrosmotic effect of oxytocin in toad bladder.
The effects of calcitonin (CT) on the water transfer in the toad (Bufo arenarum) urinary bladder, an epithelial barrier commonly employed as a model of the mammalian nephron, were studied. The net transmembrane water flux was measured at minute intervals, while the endogenous adenosine 3',5'-cyclic monophosphate (cAMP) levels were determined in isolated epithelial cells. It was observed that 1) CT, up to 10(-6) M, did not have any effect on water permeability. 2) Preincubation with CT, between 10(-7) and 10(-8) M, inhibited the hydrosmotic response to a supramaximal dose of oxytocin (OXT; 2 x 10(-8) M), used here as an antidiuretic hormone (ADH) analogue. This inhibition was reversible and concentration related. Nevertheless, although the magnitude of the response was reduced, its time course of evolution did not change. 3) When CT was added on the previously developed response to OXT, inhibition was also dose dependent with a time course not distinguishable from hormonal washout. 4) CT, up to 10(-6) M, did not modify the hydrosmotic response to 8-bromo cAMP, a potent analogue of the ADH second messenger. 5) CT and OXT increased the intracellular cAMP levels, but both effects were not cumulative. The increase induced by CT plus OXT was significantly lower than the one elicited by OXT alone. It is concluded that CT is a competitive inhibitor to the hydrosmotic effect of OXT in toad urinary bladder. Its action must be located prior to cAMP formation.


Effect of Machine Learning on Dispatcher Recognition of Out-of-Hospital Cardiac Arrest During Calls to Emergency Medical Services: A Randomized Clinical Trial.
Emergency medical dispatchers fail to identify approximately 25% of cases of out-of-hospital cardiac arrest (OHCA), resulting in lost opportunities to save lives by initiating cardiopulmonary resuscitation. To examine how a machine learning model trained to identify OHCA and alert dispatchers during emergency calls affected OHCA recognition and response. This double-masked, 2-group, randomized clinical trial analyzed all calls to emergency number 112 (equivalent to 911) in Denmark. Calls were processed by a machine learning model using speech recognition software. The machine learning model assessed ongoing calls, and calls in which the model identified OHCA were randomized. The trial was performed at Copenhagen Emergency Medical Services, Denmark, between September 1, 2018, and December 31, 2019. Dispatchers in the intervention group were alerted when the machine learning model identified out-of-hospital cardiac arrest, and those in the control group followed normal protocols without alert. The primary end point was the rate of dispatcher recognition of subsequently confirmed OHCA. A total of 169 049 emergency calls were examined, of which the machine learning model identified 5242 as suspected OHCA. Calls were randomized to control (2661 [50.8%]) or intervention (2581 [49.2%]) groups. Of these, 336 (12.6%) and 318 (12.3%), respectively, had confirmed OHCA. The mean (SD) age among of these 654 patients was 70 (16.1) years, and 419 of 627 patients (67.8%) with known gender were men. Dispatchers in the intervention group recognized 296 confirmed OHCA cases (93.1%) with machine learning assistance compared with 304 confirmed OHCA cases (90.5%) using standard protocols without machine learning assistance (P = .15). Machine learning alerts alone had a significantly higher sensitivity than dispatchers without alerts for confirmed OHCA (85.0% vs 77.5%; P < .001) but lower specificity (97.4% vs 99.6%; P < .001) and positive predictive value (17.8% vs 55.8%; P < .001). This randomized clinical trial did not find any significant improvement in dispatchers' ability to recognize cardiac arrest when supported by machine learning even though artificial intelligence did surpass human recognition. ClinicalTrials.gov Identifier: NCT04219306.


Perivascular extension of microwave ablation zone: demonstrated using an ex vivo porcine perfusion liver model<sup/>.
Microwave ablation (MWA) has been proposed to suffer less from the heat sink effect compared to radiofrequency ablation but has been reported to cause extension of the ablation zone along intrahepatic vessels in clinical practice. To study this effect in detail, eight fresh porcine livers were perfused in an ex vivo organ perfusion system. Livers were perfused with oxygenated, O-positive human blood at 37 °C. Perfusion was discontinued immediately before ablation in the non-perfused group (n = 4) whilst in the perfused group (n = 4) perfusion was maintained during MWA (140 W X 2 min). Large intrahepatic vessels (> 6 mm) were avoided using ultrasound. MWA zones were bisected within 30 min of perfusion termination and sections were fixed in formalin and stained with H&E and NADH to assess cell viability. Magnetic resonance imaging (MRI) was performed on two livers (one perfused, one non-perfused) to provide imaging correlation before sectioning. Twenty-one out of a total of 30 MW ablation zones (70%) showed extension of the ablation zone along a vessel. There was no statistically significant difference (p = 1) in the incidence of ablation zone extension between perfused (9/13, 69%) and non-perfused organs (12/17, 71%). MRI also demonstrated ablation zone extension along blood vessels correlating with macroscopy in two livers. NADH staining also confirmed extension of the ablation zone. Liver MWA appears to be commonly associated with propagated thermal injury along adjacent vessels and occurs independent of active blood flow. In order to avoid possible complications through non-target tissue injury, this effect requires further investigation.


Lin28 and let-7: roles and regulation in liver diseases.
The diagnosis and treatment of liver disease remain a major health concern worldwide because of the diverse etiologies of this disease. For this reason, new therapeutic targets are greatly needed to halt the progression of this damaging disease. Upon initiation of liver injury by viral infection, autoimmune disease or toxin, and/or hepatitis, chronic disease may develop, which can progress to cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma, liver failure, or death. The Lin28/lethal-7 (let-7) molecular switch has emerged as a central regulator of multiorgan injuries and cancer development. Lin28 is a stem cell marker vital to initiation or maintenance of a stem cell phenotype. Lin28 has not been extensively studied in the liver, despite its ability to induce tissue regeneration via reprogramming of oxidative enzymes in other tissues and its involvement with numerous upstream regulators and downstream targets in liver disease. Theoretically, overexpression of Lin28 in certain forms of liver disease could be a potential treatment that aids in liver regeneration. Alternatively, Lin28 has been implicated numerous times in the progression of diverse cancer types and is associated with increased severity of disease. In this case, Lin28 could be a potential inhibitory target to prevent malignant transformation in the liver. This review seeks to characterize the role of Lin28 in liver disease.


Quantitative Evaluation of Rehabilitation Effect on Peripheral Circulation of Diabetic Foot.
Diabetes may cause different foot problems, which could easily lead to infection, ulcers, and increasing risk of amputation due to nerve or vascular injury. In order to reduce the risk of amputation, Buerger's exercise is frequently used for rehabilitation to improve the blood circulation in lower limbs. However, it is difficult to evaluate the rehabilitation efficiency with Buerger's exercise objectively. In this study, a novel non-invasively optical system is developed to non-invasively monitor the change of the foot blood circulation before and after long-term Buerger's exercise. Radial basis function neural network is also used for classifying the healthy and diabetic groups from the change of relative total hemoglobin (HbT) concentration and tissue oxygen saturation (StO2) and providing an index to evaluate the rehabilitation efficiency with Buerger's exercise. Finally, the experimental results show that the relative HbT concentration and StO2 in lower limbs corresponding to different groups are significantly different and could be used as the factors for the classification of healthy subjects and diabetic foot patients. Moreover, the tendency of the relative HbT concentration and StO2 rise after the long-term rehabilitation with Buerger's exercise.


The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ.
Microenvironmental and molecular factors mediating the progression of Breast Ductal Carcinoma In Situ (DCIS) are not well understood, impeding the development of prevention strategies and the safe testing of treatment de-escalation. We addressed methodological barriers and characterized the mutational, transcriptional, histological, and microenvironmental landscape across 85 multiple microdissected regions from 39 cases. Most somatic alterations, including whole-genome duplications, were clonal, but genetic divergence increased with physical distance. Phenotypic and subtype heterogeneity was frequently associated with underlying genetic heterogeneity and regions with low-risk features preceded those with high-risk features according to the inferred phylogeny. B- and T-lymphocytes spatial analysis identified three immune states, including an epithelial excluded state located preferentially at DCIS regions, and characterized by histological and molecular features of immune escape, independently from molecular subtypes. Such breast pre-cancer atlas with uniquely integrated observations will help scope future expansion studies and build finer models of outcomes and progression risk.


Environment-dependent costs and benefits of recombination in independently evolved populations of Escherichia coli.
Understanding of the causes by which reproductive isolation arises remains limited. We examine the role of adaptation in driving reproductive isolation among 12 Escherichia coli populations evolved in two different environments. We found that, regardless of whether parents were selected in the same or different environments, the average fitness of recombinants was lower than the expected, consistent with a prevailing influence of incompatibility between independently accumulated mutations. Exceptions to this pattern occurred among recombinants of some parents evolved in different environments. These recombinants were less fit than expected in the selective environment of one parent, but more fit than expected in the selective environment of the other parent. Our results indicate that both parallel and divergent adaptation can quickly lead to intrinsic genetic barriers contributing to the initial stages of speciation and show that these barriers can be complex, for example, depending on the environment in which recombinant offspring are tested.


Sleep lab adaptation in children with attention-deficit/hyperactivity disorder and typically developing children.
Objectives. Research has shown inconsistencies across studies examining sleep problems in children with attention-deficit/hyperactivity disorder (ADHD). It is possible that these inconsistencies are due to sleep lab adaptation. The goal of the current study was to investigate the possibility that children with ADHD adapt differently to the sleep lab than do typically developing (TD) children. Patients and Methods. Actigraphy variables were compared between home and the sleep lab. Sleep lab adaptation reports from the parent and child were compared between children with ADHD (n = 25) and TD children (n = 25). Results. Based on actigraphy, both groups had reduced sleep duration and reduced wake after sleep onset in the sleep lab compared to home. The only interaction effect was that TD children had increased sleep efficiency in the sleep lab compared to home. Conclusions. The results of this study do not support the hypothesis that children with ADHD adjust to the sleep lab differently than their typically developing peers. However, both groups of children did sleep differently in the sleep lab compared to home, and this needs to be considered when generalizing research findings from a sleep lab environment to children's sleep in general.


Organizing multiple femtosecond filaments in air.
We show that it is possible to organize regular filamentation patterns in air by imposing either strong field gradients or phase distortions in the input-beam profile of an intense femtosecond laser pulse. A comparison between experiments and 3+1 dimensional numerical simulations confirms this concept and shows for the first time that a control of the transport of high intensities over long distances may be achieved by forcing this well ordered propagation regime. In this case, deterministic effects prevail in multiple femtosecond filamentation, and no transition to the optical turbulence regime is obtained [Phys. Rev. Lett. 83, 2938 (1999)]].


Mitochondrial ATP synthase is a target for TNBS-induced protein carbonylation in XS-106 dendritic cells.
ROS are produced in dendritic cells (DCs) during antigen presentation in contact hypersensitivity (CHS). As a result, ROS cause a number of nonenzymatic protein modifications, including carbonylation, which is the most widely used marker of oxidative stress. 2,4,6-Trinitrobenzene sulfonic acid (TNBS) is a well-characterized contact allergen that results in the formation of ROS. However, proteins that are carbonylated in DCs in response to TNBS have not been identified. To study ROS-dependent protein carbonylation in response to TNBS, we used the well-established mouse DC line, XS-106. We focused on the effects of TNBS on oxidation by examining selected oxidative markers. We identified TNBS-induced ROS and myeloperoxidase (MPO) proteins and demonstrated that the increase in ROS resulted in IL-12 production. The increase in oxidation was further confirmed by an oxidation-dependent increase in protein modifications, such as carbonylation. In fact, TNBS strongly induced carbonylation of mitochondrial adenosine triphosphate (ATP) synthase in XS-106 DCs, as determined by MALDI-TOF analysis and 2-D Western blotting. ROS production and protein carbonylation were confirmed in human monocyte-derived DCs (Mo-DCs). Furthermore, glutathione (GSH) decreased ROS and protein carbonylation in Mo-DCs. Carbonylation of ATP synthase in DCs may contribute to the pathophysiology of CHS.


BEFORE OCEAN ACIDIFICATION: CALCIFIER CHEMISTRY LESSONS(1).
Ocean Acidification (OA) has been an important research topic for a decade. Scientists have focused on how the predicted 56% decline in the seawater carbonate ion () concentration will dramatically impair the ability of calcifiers, ranging from coccolithophores to shellfish, to form calcium carbonate (CaCO3 ) structures, and the implications of the reduced carbonate saturation state (Ω) for increased dissolution of such structures. However, many published OA studies have overlooked a fundamental issue: most calcifying organisms do not rely on carbonate from seawater to calcify; they use either bicarbonate () or metabolically-produced CO2 . The ability of important primary (corals, coralline seaweeds, and coccolithophores) and secondary (mollusks) producers to modify their local carbonate chemistry suggests that the primary threat to them from OA is by dissolution rather than impaired calcification. Here, we draw on calcification research from an era before OA and combine it with recent studies that question the source of the carbonate ion, to provide new insights into how OA might affect calcifying organisms. Organismal modification of local carbonate chemistry may enable some calcifiers to successfully form calcareous structures despite OA.


Changes in access to structural social capital and its influence on self-rated health over time for middle-aged men and women: a longitudinal study from northern Sweden.
Until recently, most studies on social capital and health have been cross-sectional making it difficult to draw causal conclusions. This longitudinal study used data from 33,621 individuals (15,822 men and 17,799 women) from the Västerbotten Intervention Program, to analyse how changes in access to individual social capital influence self-rated health (SRH) over time. Two forms of structural social capital, i.e. informal socializing and social participation, were measured. Age, sex, education, marital status, smoking, snuff, physical activity, alcohol consumption, high blood pressure, and body mass index were analysed as potential confounders. The association between changes in access to structural social capital and SRH in the follow-up was adjusted for SRH at baseline, as well as for changes in the socio-demographic and health-risk variables over time. The results support that changes in access to structural social capital over time impact on SRH. Remaining with no/low level of informal socializing over time increased the odds ratio for poor SRH for both men and women (OR of 1.45; 95%CI = 1.22-1.73 among men and OR of 1.56; 95%CI = 1.33-1.84 among women). Remaining with no/low levels of social participation was also detrimental to SRH in men and women (OR 1.14; 95%CI = 1.03-1.26 among men and OR 1.18; 95%CI = 1.08-1.29 among women). A decrease in informal socializing over time was associated with poor SRH for women and men (OR of 1.35; 95%CI = 1.16-1.58 among men and OR of 1.57; 95%CI = 1.36-1.82 among women). A loss of social participation had a negative effect on SRH among men and women (OR of 1.16; 95%CI = 1.03-1.30 among men and OR of 1.15; 95%CI = 1.04-1.27 among women). Gaining access to social participation was harmful for SRH for women (OR 1.17; 95%CI = 1.05-1.31). Structural social capital has complex and gendered effects on SRH and interventions aiming to use social capital for health promotion purposes require an awareness of its gendered nature.


Feasibility of Booster Vaccination in High-Risk Populations for Controlling Coronavirus Variants - China, 2021.
Vaccination booster shots are completely necessary for controlling breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China. The study aims to estimate effectiveness of booster vaccines for high-risk populations (HRPs). A vaccinated Susceptible-Exposed-Symptomatic-Asymptomatic-Recovered/Removed (SEIAR) model was developed to simulate scenarios of effective reproduction number (R eff ) from 4 to 6. Total number of infectious and asymptomatic cases were used to evaluated vaccination effectiveness. Our model showed that we could not prevent outbreaks when covering 80% of HRPs with booster unless R eff =4.0 or the booster vaccine had efficacy against infectivity and susceptibility of more than 90%. The results were consistent when the outcome index was confirmed cases or asymptomatic cases. An ideal coronavirus disease 2019 (COVID-19) booster vaccination strategy for HRPs would be expected to reach the initial goal to control the transmission of the Delta variant in China. Accordingly, the recommendation for the COVID-19 booster vaccine should be implemented in HRPs who are already vaccinated and could prevent transmission to other groups.


Systematic review on daily vitamin B12 losses and bioavailability for deriving recommendations on vitamin B12 intake with the factorial approach.
To systematically review the literature on daily losses and bioavailability of vitamin B12. These estimates could be used for deriving recommendations on vitamin B12 intake for adults and elderly. We identified publications on daily vitamin B12 losses (July 2011) and publications on the bioavailability of vitamin B12 from foods or diets (June 2010) in MEDLINE, EMBASE and the Cochrane Library. A pooled analysis of five studies (52 subjects) showed that 0.13 ± 0.03% of the total body store is lost per day. Absorption of vitamin B12 ranged from 4.5 (dose of 38 µg from consumption of liver) to 83% (dose of 3.0 µg from consumption of mutton meat). Data from eight studies including 83 subjects suggested that the amount of vitamin B12 absorbed from food (Ai) increased with increasing doses of vitamin B12 (Di) as described by the equation: ln(Ai) = 0.7694 * ln(Di) - 0.9614. Daily vitamin B12 losses in apparently healthy adults and elderly probably range from 1.4 to 5.1 µg. Vitamin B12 intakes needed to compensate for these losses seem to range from 3.8 to 20.7 µg. More evidence is needed on the relationships between biochemical markers of vitamin B12 status, vitamin B12 body store and long-term health outcomes to evaluate whether current recommendations on vitamin B12 intake (1.4-3 µg) need to be changed.


Cooperative hand movements: task-dependent modulation of ipsi- and contralateral cortical control.
Cooperative hand movements are known to be controlled by a task-specific neural coupling associated with an involvement of the respective ipsilateral hemispheres. The aim of this study was to explore in how far this neural control applies to and is modulated during various, fine and gross, cooperative hand movements required during activities of daily living. Somatosensory evoked potentials and contralateral electromyographic reflex responses to unilateral ulnar nerve stimulation were simultaneously recorded in healthy participants during three different cooperative hand movement tasks and a resting condition. Amplitude ratio (ipsi-/contralateral) of the somatosensory evoked potentials, which is a measure for the involvement of the ipsilateral hemisphere in movement control, was higher in all three movement tasks compared to resting. This ratio was highest during the fine cooperative movement studied here. Contralateral reflex responses, as a measure for the functional coupling of the arms, were elicited following stimulation of both arms during gross cooperative movements. However, such a response could only be elicited in the dominant arm during fine movement. It is concluded that the neural coupling and thus enhancement of ipsilateral cortical control is preserved through different cooperative hand movement tasks, independently whether fine or gross motor tasks are performed. However, modulation of cortical control can be observed as ipsilateral cortical control is stronger during fine movements and functional coupling of the arms more focused to the dominant hand compared to gross cooperative tasks.


The effect of nitric oxide synthase blockade and indomethacin on gastric emptying and gastric contractility.
The aim of the present study was to investigate the effect of nitric oxide (NO) synthase inhibition on gastric emptying rate in conscious rats and on gastric muscle contractility. The involvement of NO was also investigated in indometacin-induced (25 mg/kg, s.c.) changes in gastric emptying rate and smooth muscle contractility. L-NAME (NG-nitro-L-arginine methyl ester; 10 mg/kg, i.v.) inhibited the gastric emptying rate compared to controls and this effect was abolished by L-arginine (300 mg/kg, i.v.). Similarly, indometacin treatment led to a significant delay of gastric emptying rate with respect to vehicle-treated rats. Gastric longitudinal and circular muscle strips of L-NAME or indometacin-treated rats showed a reduction in contractile responses to carbachol. The results demonstrate that NO synthase blockade and indometacin treatment delay gastric emptying in conscious rats, concomitant with reduced responsiveness to carbachol, in vitro.


[Children with AIDS. Treatment plan and procedure of care].
The authors discuss treatment provided to children suffering from Acquired Immunodeficiency Syndrome (AIDS) and to their families. By means of checking the nursing files for hospitalized children, the authors observe alterations and omissions which are common to other diseases, plus those which are specifically related to this disease: psychosocial problems. A treatment plan and an assistance procedure are drawn up. In these, the role the family plays to support the patient as well as that of the multidisciplinary team are emphasized.


Group A Streptococcal Sepsis.
The fulminant nature of group A streptococcal sepsis poses impressive challenges from diagnostic and therapeutic perspectives. Most patients are seen early in the course of infection by primary care providers or emergency department physicians and sent home, only to return in 12 to 24 hours with fully developed group A streptococcal sepsis. Early diagnosis is imperative, but the clinician must have a high index of suspicion. Often, the diagnosis is established only after aggressive interventional management has begun. This review emphasizes salient clinical features and provides general recommendations for critical care management.


Gene expression effects of lithium and valproic acid in a serotonergic cell line.
Valproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. However, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log2 fold change ≥ 1.0; i.e., odds ratio of ≥2, at false discovery rate <5%), but only two genes ( Dynlrb2 and Cdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria. Both of these genes were also regulated by VPA. Many of the differentially expressed genes had functions of potential relevance to mood disorders or their treatment, such as several serpin family genes (including neuroserpin), Nts (neurotensin), Maob (monoamine oxidase B), and Ap2b1, which is important for synaptic vesicle function. Pathway analysis revealed significant enrichment of Gene Ontology terms such as extracellular matrix remodeling, cell adhesion, and chemotaxis. This study in a cell line derived from the raphe nucleus has identified a range of genes and pathways that provide novel insights into potential therapeutic actions of the commonly used mood stabilizer drugs.


Nutritional lipidomics: molecular metabolism, analytics, and diagnostics.
The field of lipidomics is providing nutritional science a more comprehensive view of lipid intermediates. Lipidomics research takes advantage of the increase in accuracy and sensitivity of mass detection of MS with new bioinformatics toolsets to characterize the structures and abundances of complex lipids. Yet, translating lipidomics to practice via nutritional interventions is still in its infancy. No single instrumentation platform is able to solve the varying analytical challenges of the different molecular lipid species. Biochemical pathways of lipid metabolism remain incomplete and the tools to map lipid compositional data to pathways are still being assembled. Biology itself is dauntingly complex and simply separating biological structures remains a key challenge to lipidomics. Nonetheless, the strategy of combining tandem analytical methods to perform the sensitive, high-throughput, quantitative, and comprehensive analysis of lipid metabolites of very large numbers of molecules is poised to drive the field forward rapidly. Among the next steps for nutrition to understand the changes in structures, compositions, and function of lipid biomolecules in response to diet is to describe their distribution within discrete functional compartments lipoproteins. Additionally, lipidomics must tackle the task of assigning the functions of lipids as signaling molecules, nutrient sensors, and intermediates of metabolic pathways.


The tryptophan derivative 6-formylindolo[3,2-b]carbazole, FICZ, a dynamic mediator of endogenous aryl hydrocarbon receptor signaling, balances cell growth and differentiation.
The aryl hydrocarbon receptor (AHR) is not essential to survival, but does act as a key regulator of many normal physiological events. The role of this receptor in toxicological processes has been studied extensively, primarily employing the high-affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, regulation of physiological responses by endogenous AHR ligands remains to be elucidated. Here, we review developments in this field, with a focus on 6-formylindolo[3,2-b]carbazole (FICZ), the endogenous ligand with the highest affinity to the receptor reported to date. The binding of FICZ to different isoforms of the AHR seems to be evolutionarily well conserved and there is a feedback loop that controls AHR activity through metabolic degradation of FICZ via the highly inducible cytochrome P450 1A1. Several investigations provide strong evidence that FICZ plays a critical role in normal physiological processes and can ameliorate immune diseases with remarkable efficiency. Low levels of FICZ are pro-inflammatory, providing resistance to pathogenic bacteria, stimulating the anti-tumor functions, and promoting the differentiation of cancer cells by repressing genes in cancer stem cells. In contrast, at high concentrations FICZ behaves in a manner similar to TCDD, exhibiting toxicity toward fish and bird embryos, immune suppression, and activation of cancer progression. The findings are indicative of a dual role for endogenously activated AHR in barrier tissues, aiding clearance of infections and suppressing immunity to terminate a vicious cycle that might otherwise lead to disease. There is not much support for the AHR ligand-specific immune responses proposed, the differences between FICZ and TCDD in this context appear to be explained by the rapid metabolism of FICZ.


A prospective blinded randomized trial comparing oral sodium phosphate and polyethylene glycol solutions for bowel preparation prior to barium enema.
A prospective blinded randomized trial to compare oral sodium phosphate (NaP) solution with polyethylene glycol (PEG) preparations as bowel preparation prior to barium enema examination. One hundred and ten patients consented to take part and each patient was randomly assigned to receive either NaP (Oral Fleet Prep) or PEG (Lyteprep). The barium enemas were reviewed by two radiologists blinded to the type of bowel preparation the patient had received. The colon was divided into six segments and each segment was assessed for the amount of stool and water present, the adequacy of coating, the ability to exclude inflammatory bowel disease and the presence of polyps. A score of 0-3 (failure to good) was assigned per segment on each of these criteria. The average individual score for the NaP group was 89.2. The average individual score for the PEG group was 88.81. No significant difference was found in the quality of bowel cleansing between the two agents. In particular there was no significant difference in the scores for water retention (two-tailed P = 0.748) and the difference for the quality of coating was considered not quite significant (two-tailed P = 0.0818). Oral sodium phosphate cleans the colon as well as polyethylene glycol solutions. The use of NaP will result in significant cost savings and improved patient compliance.


Screening for autism in infants and preschool children with developmental delay.
This study aimed to identify emotional and behavioural problems specific to young children with autism using the Developmental Behaviour Checklist (DBC-P) and thus evaluate the efficacy of this checklist as a screening tool for autism in children with developmental delay aged 18-48 months. Subjects were 60 children with autism and developmental delay and 60 children with developmental delay without autism. Features were identified which differentiated the children with autism from those with developmental delay without autism. Analyses revealed that a 17-item version of the DBC-P performed well as a screening tool for autism, with an 'area under the curve' of 0.874, sensitivity of 0.8750, and specificity of 0.6909. The DBC-P offers a potential simple and inexpensive method of screening at risk populations of preschool children with developmental delay for autism, thus facilitating timely referral to scarce specialist autism diagnostic services.


Morphological and chemical characteristics of airborne tungsten particles of Fallon, Nevada.
Morphological and chemical characteristics were determined for airborne tungsten particles in Fallon, Nevada, a town that is distinguishable environmentally by elevated airborne tungsten and cobalt. From samples of airborne dust collected previously at six different places in Fallon, tungsten-rich dust particles were isolated and analyzed with automated electron microprobe and wavelength-dispersive spectrometry. Representative W particles were further analyzed using transmission electron microscopy. Morphologically, Fallon W particles are angular and small, with minimum and maximum sizes of < or = 1 microm and 5.9 microm in diameter, respectively. The number and size of tungsten-rich particles decrease in Fallon with distance from a hard-metal facility located near the center of town. Chemically, Fallon airborne W particles include mixtures of tungsten with cobalt plus other metals such as chromium, iron, and copper. No W-rich particles were identifiable as CaWO4 (scheelite) or MnWO4 (huebnerite). From d-spacings, Fallon particles are most consistent with identification as tungsten carbide. Based on these multiple lines of evidence, airborne W particles in Fallon are anthropogenic in origin, not natural. The hard-metal facility in Fallon processes finely powdered W and W-Co, and further investigation using tracer particles is recommended to definitively identify the source of Fallon's airborne tungsten.


Monteggia type I equivalent lesion: diaphyseal ulna and proximal radius fracture with a posterior elbow dislocation in a child.
A rare type I equivalent Monteggia lesion in a child, diaphyseal ulna and proximal radius fracture with a posterior elbow dislocation, is described, as well as the probable mechanism of injury. An excellent result was obtained with nonoperative treatment.


Nighttime Walking with Music: Does Music Mediate the Influence of Personal Distress on Perceived Safety?
There is growing interest in identifying the environmental factors that contribute to individuals' perceptions of safety and sense of well-being in public spaces. As such, this study examined how music listening during nighttime walking influenced female university students' psychological state and perceptions of their campus. A total of 178 female university students with a mean age of 23.0 years participated in this study. One group of 78 students listened to prerecorded music while walking across their campus at night, while the other 100 students did not listen to music during nighttime walking. Immediately following their nighttime walking, participants were asked to rate their psychological state, perceptions on the safety of their campus, and the music (only for the music-listening group). For the non-music-listening group, significant correlations were found between the perceived safety of the campus and psychological states (both anxiety and psychological distress); the correlations were not significant in the music-listening group. The results indicate that music can mediate psychological states, supporting the proactive use of music as a psychological resource for coping with their perceptions of adverse environments. Given the limitations of this preliminary study, further studies with controlled music listening conditions, type of music, and environmental issues are suggested.


Prostanoids attenuate pial arteriolar dilation induced by cortical spreading depression in rabbits.
The role of prostanoids in mediating cerebrovascular responses to cortical spreading depression (CSD) was examined in anesthetized rabbits. CSD was elicited by KCl microinjection, and its propagation was monitored electrophysiologically. Pial arterial diameter was determined using a closed cranial window and intravital microscopy, and regional cerebral blood flow (rCBF) was determined using laser flowmetry. Levels of peri-arachnoid cerebrospinal fluid prostanoids were determined by radioimmunoassay. CSF increased pial arteriolar diameter 62% and rCBF 354% over the baseline levels. Locations of propagating CSD, dilating pial arteriole, and increased rCBF were always closely associated spatiotemporally. Cerebrospinal fluid prostanoid levels increased during single CSD-induced arteriolar dilation, and they were further augmented during multiple CSDs. Indomethacin enhanced both CSD-induced vasodilation (88%) and rCBF increase (580%), but it decreased the cerebrospinal fluid levels of prostanoids below the baseline levels and prevented their increase during CSD-induced vasodilation. These results indicate that prostanoids are synthesized from neurons or glial cells and/or the brain vessels and, as the net result, counteract pial arteriolar dilation and rCBF increase during CSD. In addition, they support the hypothesis that the vasodilation is caused primarily by neurogenic factors associated with CSD.


The use of nouns and verbs by children with Down syndrome in two different situations.
To verify the use of nouns and verbs by children with Down syndrome and to compare this use between conditions of interaction with the mother and the Speech-language pathologist (SLP). Participants were 21 children aged between 5 and 11 years, divided into three groups, according to chronological and mental age as established by the results of the Primary Tests of Nonverbal Intelligence. The speech sample was obtained through free interaction situations that were videotaped during session of 30 minutes and transcribed in specific protocols. The first 100 utterances from the first five minutes were used. The interval between each situation ranged from 7 to 15 days. T-test and analysis of variance were used for statistical analysis and the significance level adopted was of 5%. More verbs than nouns were used in both conditions; however, a higher number of nouns were observed during the interaction with the SLP. The between-group comparison in the interaction with the SLP shows significant differences for verbs and nouns, but during the interaction with the mother, there was tendency for difference only for the verbs. The data indicate the growing development on using of nouns and verbs according to the increase of age. There was a higher use of verbs when compared with nouns mainly in the condition of interaction with the SLP.


The Combination of Whole Cell Lipidomics Analysis and Single Cell Confocal Imaging of Fluidity and Micropolarity Provides Insight into Stress-Induced Lipid Turnover in Subcellular Organelles of Pancreatic Beta Cells.
Modern omics techniques reveal molecular structures and cellular networks of tissues and cells in unprecedented detail. Recent advances in single cell analysis have further revolutionized all disciplines in cellular and molecular biology. These methods have also been employed in current investigations on the structure and function of insulin secreting beta cells under normal and pathological conditions that lead to an impaired glucose tolerance and type 2 diabetes. Proteomic and transcriptomic analyses have pointed to significant alterations in protein expression and function in beta cells exposed to diabetes like conditions (e.g., high glucose and/or saturated fatty acids levels). These nutritional overload stressful conditions are often defined as glucolipotoxic due to the progressive damage they cause to the cells. Our recent studies on the rat insulinoma-derived INS-1E beta cell line point to differential effects of such conditions in the phospholipid bilayers in beta cells. This review focuses on confocal microscopy-based detection of these profound alterations in the plasma membrane and membranes of insulin granules and lipid droplets in single beta cells under such nutritional load conditions.


The creative evolution of scientific paradigms: Vernon Lee and the debate over the hereditary transmission of acquired characters.
By the end of the nineteenth century, evolution through natural selection had been widely accepted, but the means by which innate or acquired characteristics were transmitted from parent to offspring remained hotly contested. As the literary career of Vernon Lee makes evident, discussion of the validity of newly espoused theories was not limited to science. This essay explores Lee's lifelong engagement with emerging and often unproven ideas in heredity and evolutionary science by arguing, first, that rather than a unidirectional flow of ideas from experimental science to literature and the social sciences, there was instead a productive and creative trafficking between these fields; and, second, that despite Lee's early rejection of Lamarckism, she continued to utilize superseded paradigms to inform her writing in a number of fields outside evolutionary biology.


Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis.
Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human plasma. The purpose of this study was to examine the relationship between plasma ADMA and atherosclerosis in humans. Subjects (n=116; age, 52+/-1 years; male:female ratio, 100:16) underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and duplex scanning of the carotid arteries. These individuals had no symptoms of coronary or peripheral artery disease and were taking no medications. Univariate and multivariate analyses revealed that plasma levels of ADMA were positively correlated with age (P<0.0001), mean arterial pressure (P<0.0001), and Sigma glucose (an index of glucose tolerance) (P=0.0006). Most intriguingly, stepwise regression analysis revealed that plasma ADMA levels were significantly correlated to the intima-media thickness of the carotid artery (as measured by high-resolution ultrasonography). This study reveals that plasma ADMA levels are positively correlated with risk factors for atherosclerosis. Furthermore, plasma ADMA level is significantly correlated with carotid intima-media thickness. Our results suggest that this endogenous antagonist of NO synthase may be a marker of atherosclerosis.


Tracing mercury contamination from the Idrija mining region (Slovenia) to the Gulf of Trieste using Hg isotope ratio measurements.
To demonstrate the power of precise isotope ratio measurements of Hg in environmental samples and, more particularly, to test the use of stable isotopes as distinct tracers of the contamination source, we investigated a well-documented system, the Hg mining region near Idrija, Slovenia. Sediments alongside the Idrijca River, the Soca/Isonzo River, and in the Gulf of Trieste were analyzed to determine the variation in Hg isotopic composition versus distance from the source. Similar Hg isotopic signatures were observed among samples collected from the rivers Idrijca, Soca/Isonzo, and around the river mouth in the Gulf of Trieste, suggesting that sediments throughout the watershed of the Soca/Isonzo River to the Gulf of Trieste are dominated by Hg exported from the headwaters of the Idrijca River. Only locations on the southern part of the gulf, outside the river plume, showed lower values of the isotopic composition comparable to the Hg isotopic signature of Adriatic Sea sediments. Using a simple binary mixing-model, we could demonstrate that all samples investigated in this study were a result of variable proportions of Hg originating from the Idrija region (progressively decreasing from >90% in the northern partto <50% in the southern gulf) and from the Adriatic Sea. These results are, so far, the first evidence that tracking of mercury sources in natural systems using mercury stable isotope ratios is feasible.


Barriers and enablers to the implementation of multidisciplinary team meetings: a qualitative study using the theoretical domains framework.
Evidence-based clinical practice guidelines recommend discussion by a multidisciplinary team (MDT) to review and plan the management of patients for a variety of cancers. However, not all patients diagnosed with cancer are presented at an MDT. (1) To identify the factors (barriers and enablers) influencing presentation of all patients to, and the perceived value of, MDT meetings in the management of patients with pancreatic cancer and; (2) to identify potential interventions that could overcome modifiable barriers and enhance enablers using the theoretical domains framework (TDF). Semistructured interviews were conducted with radiologists, surgeons, medical and radiation oncologists, gastroenterologists, palliative care specialists and nurse specialists based in New South Wales and Victoria, Australia. Interviews were conducted either in person or via videoconferencing. All interviews were recorded, transcribed verbatim, deidentified and data were thematically coded according to the 12 domains explored within the TDF. Common belief statements were generated to compare the variation between participant responses. In total, 29 specialists were interviewed over a 4-month period. Twenty-two themes and 40 belief statements relevant to all the TDF domains were generated. Key enablers influencing MDT practices included a strong organisational focus (social/professional role and identity), beliefs about the benefits of an MDT discussion (beliefs about consequences), the use of technology, for example, videoconferencing (environmental context and resources), the motivation to provide good quality care (motivation and goals) and collegiality (social influences). Barriers included: absence of palliative care representation (skills), the number of MDT meetings (environmental context and resources), the cumulative cost of staff time (beliefs about consequences), the lack of capacity to discuss all patients within the allotted time (beliefs about capabilities) and reduced confidence to participate in discussions (social influences). The internal and external organisational structures surrounding MDT meetings ideally need to be strengthened with the development of agreed evidence-based protocols and referral pathways, a focus on resource allocation and capabilities, and a culture that fosters widespread collaboration for all stages of pancreatic cancer.


Advanced portable remote monitoring system for the regulation of treadmill running exercises.
This study aims to develop an advanced portable remote monitoring system to supervise high intensity treadmill exercises. The supervisory level of the developed hierarchical system is implemented on a portable monitoring device (iPhone/iPad) as a client application, while the real-time control of treadmill exercises is accomplished by using an on-line adaptive neural network control scheme in a local computer system. During training or rehabilitation exercises, the intensity (measured by heart rate) is regulated by simultaneously manipulating both treadmill speed and gradient. In order to achieve adaptive tracking performance, a neural network controller has been designed and implemented. Six real-time experiments have been conducted to test the performance of the developed monitoring system. Experimental results obtained in real-time with heart-rate set-point varying from 145 bpm to 180 bmp, demonstrate that the proposed system can quickly and accurately regulate exercise intensity of treadmill running exercises with desired performance (no overshoot, settling time Ts ≤ 100 s). Subjects aged from 29 to 38 years old participated in different set-point experiments to confirm the system's adaptability to inter- and intra-model uncertainty. The desired system performance under external disturbances has also been confirmed in a final real-time experiment demonstrating a user carrying the 10 kg bag then removing it during the exercise. In contrast with conventional control approaches, the proposed adaptive controller achieves better heart rate tracking performance under inter- and intra-model uncertainty and external disturbances. The developed system can automatically adapt to various individual exercisers and a range of exercise intensity.


Gap junction dysfunction reduces acetaminophen hepatotoxicity with impact on apoptotic signaling and connexin 43 protein induction in rat.
Acetaminophen (APAP) is a widely used antipyretic and analgesic agent. However, overdosing and sometimes even a recommended dose can lead to serious and conceivably fatal liver toxicity. Therefore, it is important to clarify understand mechanisms of hepatotoxicity induced by APAP. Gap junctions, formed by connexin, have important roles in maintenance of tissue homeostasis and control of cell growth and differentiation. In the liver, Cx32 is a major gap junction protein whose expression is known to gradually decrease with chronic liver disease progression. In the present study, acute hepatotoxic effects of APAP were found to be reduced in Cx32 dominant negative transgenic rats lacking normal gap junctional intercellular communication in the liver. In littermate wild-type rats, the injured centrilobular hepatocytes were positive for TUNEL staining and featured elevated expre ssion of cleaved caspase-3 and Cx43, which is not expressed in normal hepatocytes. These results suggest that APAP hepatotoxicity involves apoptosis, and induction of Cx43 expression may play an important role in the apoptotic signaling. Moreover, gap junctional functions of Cx32 can play important roles in removing damaged hepatocytes by apoptosis for liver tissue homeostasis.


A method for prioritization of areas for pesticides surveillance on surface waters: a study in Minas Gerais, Brazil.
The occurrence of pesticides in drinking water is a matter of growing concern in several parts of the world, mainly in developing countries, due the possible adverse effects on human health. Pesticides applied in the agriculture are an important source of contamination and are rarely monitored in surface water in developing countries, either by water supply operators or health authorities, often not accomplishing the legal issues regarding the quality control of raw waters. The paper discusses a method for prioritization of surveillance actions of pesticides in surface waters, through multicriteria analysis. Five criteria were defined and a range of weight was established for each criterion. For validation of the method, it was applied in five sub-basins of Grande River Basin - MG. This application allowed ordering priority sub-basins for pesticides surveillance, suggesting two sub-basins as priorities. The validation performed enabled the evaluation and adjustment of the method, mainly regarding the availability of information. The method showed a practical alternative for the environmental surveillance, targeting priority areas. Moreover, its structure allows the application in other different areas and for other pollutants.


The tissue cage model in the distribution of antibacterial agents.
Developments in the measurement of interstitial tissue fluid using the tissue cage model are described. The design and physical characteristics of tissue cages are examined and evidence is presented to show that the fluid contained within these cages is representative of interstitial tissue fluid. The distribution of a variety of antibacterial agents into tissue cage fluid is examined and shows that this technique is a reliable experimental model for the study of drug distribution. The results also show that some antibacterial agents may never, normally, distribute into the tissue fluid and that the use of tissue homogenates, especially the kidney, is unreliable as a guide to the tissue concentration of a drug.


Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease.
Alzheimer's disease (AD) is a severe age-related neurodegenerative disorder characterized by accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic and neuronal loss, and cognitive decline. Several genes have been implicated in AD, but chromatin state alterations during neurodegeneration remain uncharacterized. Here we profile transcriptional and chromatin state dynamics across early and late pathology in the hippocampus of an inducible mouse model of AD-like neurodegeneration. We find a coordinated downregulation of synaptic plasticity genes and regulatory regions, and upregulation of immune response genes and regulatory regions, which are targeted by factors that belong to the ETS family of transcriptional regulators, including PU.1. Human regions orthologous to increasing-level enhancers show immune-cell-specific enhancer signatures as well as immune cell expression quantitative trait loci, while decreasing-level enhancer orthologues show fetal-brain-specific enhancer activity. Notably, AD-associated genetic variants are specifically enriched in increasing-level enhancer orthologues, implicating immune processes in AD predisposition. Indeed, increasing enhancers overlap known AD loci lacking protein-altering variants, and implicate additional loci that do not reach genome-wide significance. Our results reveal new insights into the mechanisms of neurodegeneration and establish the mouse as a useful model for functional studies of AD regulatory regions.


Preinjury psychiatric status, injury severity, and postdeployment posttraumatic stress disorder.
Physical injury has been associated with the development of posttraumatic stress disorder (PTSD). Previous studies have retrospectively examined the relationship of preinjury psychiatric status and postinjury PTSD with conflicting results, but no prospective studies regarding this subject have been conducted, to our knowledge. To prospectively assess the relationship of predeployment psychiatric status and injury severity with postdeployment PTSD. Prospective, longitudinal study. United States military personnel deployed in support of the conflicts in Iraq and Afghanistan. United States service member participants in the Millennium Cohort Study who completed a baseline questionnaire (from July 1, 2001, through June 30, 2003) and at least 1 follow-up questionnaire (from June 1, 2004, through February 14, 2006, and from May 15, 2007, through December 31, 2008) and who were deployed in the intervening period. Self-reported health information was used to prospectively examine the relationship between baseline psychiatric status and follow-up PTSD in injured and uninjured deployed individuals. A positive screening result using the PTSD Checklist-Civilian Version. Of 22 630 eligible participants, 1840 (8.1%) screened positive for PTSD at follow-up, and 183 (0.8%) sustained a deployment-related physical injury that was documented in the Joint Theater Trauma Registry or the Navy-Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database. The odds of screening positive for PTSD symptoms were 2.52 (95% confidence interval, 2.01-3.16) times greater in those with 1 or more defined baseline mental health disorder and 16.1% (odds ratio, 1.16; 95% confidence interval, 1.01-1.34) greater for every 3-unit increase in the Injury Severity Score. Irrespective of injury severity, self-reported preinjury psychiatric status was significantly associated with PTSD at follow-up. Baseline psychiatric status and deployment-related physical injuries were associated with screening positive for postdeployment PTSD. More vulnerable members of the deployed population might be identified and benefit from interventions targeted to prevent or to ensure early identification and treatment of postdeployment PTSD.


Surgical site infection after penetrating abdominal trauma with bowel involvement: a comparison between HIV-seropositive and seronegative patients.
The influence of HIV-infection on surgical site infection (SSI) after surgery for penetrating abdominal trauma is not investigated and therefore not as yet elucidated. This prospective study was performed with the aim to compare the SSI rate in human immunodeficiency virus (HIV)-seropositive and HIV-negative patients and to identify other risk factors for this abdominal wound complication. 98 patients who underwent small or large bowel resection and subsequent anastomosis due to penetrating abdominal trauma were included in the study. Injury related factors as well as demographical and physiological parameters, including HIV-status were analysed and superficial and deep SSI incidence rates were evaluated. Of the 98 patients, 23 patients (23%) were HIV-seropositive. The overall superficial SSI rate was 45% and the deep SSI rate was 15%. No significant difference in SSI (superficial or deep) in the HIV-seropositive and -negative group was demonstrated (superficial SSI HIV-pos vs HIV-neg: 61% vs 40%; p=0.172, deep SSI 22% vs 13%, p=0.276). Multivariate analysis identified five independent risk factors for SSI: postoperative CD4 count < 250 cells/μl, postoperative albumin < 30 g/L, relook operation, anastomotic leak and colonic anastomosis. HIV-infection is not an independent risk factor for developing SSI after penetrating abdominal trauma. Low postoperative CD4 count, irrespective of HIV status, low postoperative albumin, relook operation, anastomotic leak and colonic anastomosis are predictors for SSI irrespective of the HIV-serostatus. These factors should be considered in unison during the decision-making process of abdominal wound closure; planned secondary wound treatment or immediate application of negative pressure dressings in patients with a high-risk profile may decrease the hospital stay and the financial burden on the health care system.


Light-induced systemic regulation of photosynthesis in primary and trifoliate leaves of Phaseolus vulgaris: effects of photosynthetic photon flux density (PPFD) versus spectrum.
The objectives of this work using Phaseolus vulgaris were to examine whether the light spectrum incident on mature primary leaves (PLs) is related to leaf-to-leaf systemic regulation of developing trifoliate leaves (TLs) in photosynthetic characteristics, and to investigate the relative importance of spectrum and photosynthetic photon flux density (PPFD) in light-induced systemic regulation. Systemic regulation was induced by altering PPFD and the spectrum of light incident on PLs using a shading treatment and lighting treatments including either white, blue, green or red light-emitting diodes (LEDs). Photosynthetic characteristics were evaluated by measuring the light-limited and light-saturated net photosynthetic rates and the amounts of nitrogen (N), chlorophyll (Chl) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 220.127.116.11). Shading treatment on PLs decreased the amounts of N, Chl and Rubisco of TLs and tended to decrease the photosynthetic rates. However, we observed no systemic effects induced by the light spectrum on PLs in this study, except that a higher amount of Rubisco of TLs was observed when the PLs were irradiated with blue LEDs. Our results imply that photoreceptors in mature leaves have little influence on photosynthetic rates and amounts of N and Chl of developing leaves through systemic regulation, although the possibility of the action of blue light irradiation on the amount of Rubisco cannot be ruled out. Based on these results, we concluded that the light spectrum incident on mature leaves has little systemic effect on developing leaves in terms of photosynthetic characteristics and that the light-induced systemic regulation was largely accounted for by PPFD.


Inorganic micelles as efficient and recyclable micellar catalysts.
An "inorganic micelle" structure that has a hydrophilic cavity and hydrophobic surface has been synthesized. The inorganic micelles possess large surface area and controllable hydrophobic/hydrophilic interface. It shows high catalytic efficiency and great recyclability in the bromination of alcohols. This work suggests that inorganic micelles may be suitable for selective organic syntheses as well as industrial applications and demonstrates the value of translating nanostructure design from organic to inorganic.


Tackling non-metastatic castration-resistant prostate cancer: special considerations in treatment.
Prostate cancer (PCa) is currently the second most common cancer affecting men worldwide. Metastatic castration-resistant prostate cancer (mCRPC) is the incurable form of PCa, carrying the poorest prognosis, and can develop from non-metastatic CRPC (M0 CRPC). CRPC is defined as progression of the disease with castrate level testosterone levels, achieved with primary androgen deprivation therapy (ADT). M0 CRPC is a highly heterogeneous disease process lacking clear standard of care therapies. Areas covered: In this review, a broad literature search was undertaken to explore data available for therapeutic options and guidelines in the management of M0 CRPC. Expert commentary: While there are compelling data for various therapeutics for the treatment of M0 CRPC, no clear standard of care is apparent at this time. Furthermore, technological advances in imaging may have a significant impact on this future of this disease state.


An intervention programme to establish regular toothbrushing: understanding parents' beliefs and motivating children.
To determine the benefit of twice daily toothbrushing on newly erupted first permanent molars. To investigate, through the Health Belief Model, how parents' beliefs influence the likelihood of their children brushing twice a day. To identify aspects of a toothbrushing intervention programme that can be used in general dental practice. Randomised controlled trial. Schools in deprived communities in Scotland. 461, 5-year-old children. Supervised toothbrushing on school-days with a 1,000 ppm chalk-based fluoride toothpaste for two years. A school and home-based incentive scheme including toothbrushing charts, 6-monthly dental examinations and parental questionnaires. Caries increment and twice daily toothbrushing. In the control group, children who brushed once a day or less had 64% more caries than those who brushed at least twice a day (P = 0.001). In the intervention group this difference in caries was reduced to 16% (P > 0.05). The most significant parental belief explaining variation in twice-daily brushing was whether parents feel strongly that there is time to check their child's toothbrushing (P = 0.0001). The odds of these parents reporting that their child brushes twice daily are nearly three times greater. 95% of parents felt that toothbrushing charts would be a good way for dentists in practice to encourage children to brush regularly. The benefit of twice daily toothbrushing on caries development in newly erupted first permanent molar teeth is around 50% compared to brushing once a day or less. Parents' beliefs do influence the likelihood of their children brushing twice a day. Key parts of the intervention programme can be used when children attend general dental practice and would be welcomed by parents.


[Role of the adenylate cyclase system in utilization of succinate by the frog gastric mucosa].
Interrelationship between the adenylate cyclase system state and utilization of succinate as a substrate of oxidation in mechanisms of HCl secretion by isolated gastric mucosa of frog Rana esculenta was studied. The inhibition of the protein synthesis by cycloheximide rendered gastric mucosa insensitive to the activation of HCl secretion by histamine and succinate. A similar effect was exerted by cimetidine, a blocking agent for H2-receptors. The blockade could be prevented with dibutyryl-cAMP. The seasonal dependence of activation of HCl secretion by specific and unspecific modifiers was discovered. The data obtained show the necessity of preliminary activation of adenylate cyclase and accumulation of limiting content of cAMP for the utilization of succinate in reactions of generation and transport of H+ by acid-producing cells of isolated gastric mucosa in frog.


Effect of anticoagulants on binding and neutralization of lipopolysaccharide by the peptide immunoglobulin conjugate CAP18(106-138)-immunoglobulin G in whole blood.
The 18-kDa cationic protein CAP18 is an antimicrobial protein isolated from rabbit granulocytes that binds lipopolysaccharide (LPS) and inhibits many of its biological activities. We covalently coupled a synthetic peptide representing amino acids 106 to 138 of CAP18 to human immunoglobulin G (IgG) by using the heterobifunctional linker N-succinimidyl-3-(2-pyridyidithio)propionate. The ability of CAP18(106-138)-IgG to bind and neutralize LPS in whole blood in the presence and absence of anticoagulants was studied. Both CAP18(106-138) and CAP18(106-138)-IgG significantly suppressed LPS-induced tumor necrosis factor (TNF) production in whole blood in the absence of anticoagulants. EDTA potentiated the ability of CAP18(106-138) and CAP18(106-138)-IgG to decrease LPS-induced TNF production in a dose-dependent manner. In contrast, heparin inhibited the ability of CAP18(106-138) and CAP18(106-138)-IgG to suppress LPS-induced TNF production. EDTA also enhanced LPS capture in a fluid-phase binding assay that utilizes magnetic anti-IgG beads to capture CAP18(106-138)-IgG (and bound [3H]LPS) in whole blood. In contrast, heparin inhibited the binding dose dependently. We conclude that CAP18(106-138)-IgG binds to and neutralizes LPS in whole blood in the absence of anticoagulants. Further studies of its protective efficacy in animal models are warranted. Caution should be used in interpreting assays that measure the binding and neutralization of LPS in whole blood in the presence of calcium-binding anticoagulants or heparin.


Validation of the Missouri Osteochondral Allograft Preservation System for the Maintenance of Osteochondral Allograft Quality During Prolonged Storage.
Fresh osteochondral allografts (OCAs) are limited in availability. The Missouri Osteochondral Allograft Preservation System (MOPS) has been reported to effectively preserve OCAs twice as long as current tissue bank protocols in preclinical studies. The viable chondrocyte density (VCD) in OCAs preserved for up to 70 days using the MOPS will not be significantly different from day 0, and the VCD in MOPS-preserved OCAs will be significantly higher than for standard tissue bank preservation. Media changes during preservation will significantly improve the VCD. Controlled laboratory study. Femoral condyles harvested from qualified donors (n = 12) were quartered (n = 48), assigned to 1 of 4 treatment groups (tissue bank protocol at 4°C or MOPS at 25°C, with or without media changes), and preserved for 0, 28, 56, or 70 days and assessed for the VCD and histopathological characteristics. In addition, osteochondral explants were created from the femoral condyles of 12 donors (n = 36 explants), assigned to the same groups and time points, and tested for biomechanical properties. MOPS-preserved OCAs maintained the day 0 VCD through 56 days. OCAs stored using current tissue bank protocols had a significantly lower VCD compared with day 0 and the MOPS by day 28. OCA histological and biomechanical properties did not significantly change from day 0 for any group. The MOPS preserved essential OCA viability and quality at significantly higher levels than current tissue bank protocols for at least 56 days after procurement. Improving the viability and duration of OCA preservation provides potential benefits to tissue banks, donor families, surgeons, and patients with respect to tissue use, financial costs, and outcomes.


PRDM16 Is a Compact Myocardium-Enriched Transcription Factor Required to Maintain Compact Myocardial Cardiomyocyte Identity in Left Ventricle.
Left ventricular noncompaction cardiomyopathy (LVNC) was discovered half a century ago as a cardiomyopathy with excessive trabeculation and a thin ventricular wall. In the decades since, numerous studies have demonstrated that LVNC primarily has an effect on left ventricles (LVs) and is often associated with LV dilation and dysfunction. However, in part because of the lack of suitable mouse models that faithfully mirror the selective LV vulnerability in patients, mechanisms underlying the susceptibility of LVs to dilation and dysfunction in LVNC remain unknown. Genetic studies have revealed that deletions and mutations in PRDM16 (PR domain-containing 16) cause LVNC, but previous conditional Prdm16 knockout mouse models do not mirror the LVNC phenotype in patients, and the underlying molecular mechanisms by which PRDM16 deficiency causes LVNC are still unclear. Prdm16 cardiomyocyte-specific knockout (Prdm16cKO) mice were generated and analyzed for cardiac phenotypes. RNA sequencing and chromatin immunoprecipitation deep sequencing were performed to identify direct transcriptional targets of PRDM16 in cardiomyocytes. Single-cell RNA sequencing in combination with spatial transcriptomics was used to determine cardiomyocyte identity at the single-cell level. Cardiomyocyte-specific ablation of Prdm16 in mice caused LV-specific dilation and dysfunction, as well as biventricular noncompaction, which fully recapitulated LVNC in patients. PRDM16 functioned mechanistically as a compact myocardium-enriched transcription factor that activated compact myocardial genes while repressing trabecular myocardial genes in LV compact myocardium. Consequently, Prdm16cKO LV compact myocardial cardiomyocytes shifted from their normal transcriptomic identity to a transcriptional signature resembling trabecular myocardial cardiomyocytes or neurons. Chamber-specific transcriptional regulation by PRDM16 was attributable in part to its cooperation with LV-enriched transcription factors Tbx5 and Hand1. These results demonstrate that disruption of proper specification of compact cardiomyocytes may play a key role in the pathogenesis of LVNC. They also shed light on underlying mechanisms of the LV-restricted transcriptional program governing LV chamber growth and maturation, providing a tangible explanation for the susceptibility of LV in a subset of LVNC cardiomyopathies.


Aneurysmoraphy or bypass? Surgical strategy for large M1 bifurcation aneurysm involving two branches based on vessel wall high-resolution MRI and intraoperative angiography.
Middle cerebral artery (MCA) M1 bifurcation aneurysms are common because of hemodynamic. For regular-shaped and small aneurysms, direct clipping is optimal. Aneurysmoraphy or bypass blood flow reconstruction are most commonly used in large aneurysm clipping. Based on preoperative vessel wall high-resolution magnetic resonance imaging (VW-HRMRI) and intraoperative angiography, an appropriate surgery strategy could be decided. We report a case of large MCA M1 bifurcation aneurysm aneurysmoraphy according to preoperative VW-HRMRI. Intraoperative digital subtraction angiography (DSA) showed an aneurysm neck remnant, and we adjusted clips according to intraoperative DSA. This patient recovered well with a modified Rankin scale of 0 at discharge. This case demonstrates that preoperative VWHRMRI could supply more aneurysm characteristics for direct aneurysmoraphy. Intraoperative DSA effectively reduces the possibility of aneurysm remnant.


The movement patterns used to rise from a supine position by children with developmental delay and age-related differences in these.
The purposes of this study were to determine (1) movement patterns and strategies of children with mild to moderate developmental delay (DD) used to rise up and how they differ from those used by age-matched children with typical development (TD), (2) whether the movement patterns differ with age in children with DD, and (3) to determine the developmental sequences for the UE, AX and LE in children with DD and whether they are different from those used by children with TD. Sixty six children with TD and 31 children with DD aged two to six years were recruited. Peabody Developmental Motor Scale II (PDMS-2) was used to determine the motor performance level. The participants were recorded during rising for at least five repetitions. Two trained pediatric physical therapists viewed each video recording and classified the movement patterns of the upper extremities (UE), trunk/axial (AX) and lower extremities (LE) regions using descriptive categories developed by previous researchers. The DD and TD groups were further divided into four subgroups each using a one-year interval. The percentage of occurrence of the each UE, AX and LE movement was determined and compared across subgroups, and between each age-matched pair of TD and DD groups. The results demonstrated that the participants in the TD group clearly followed the proposed developmental sequence and the children with DD followed the developmental sequences but with different maturation speeds and greater variability, especially at the age of three to five years. The most common movement patterns used by the children in each of the DD subgroups were at least one developmental categorical pattern behind those used by the age-matched children with TD before five years old, except for the LE region. In the DD group, the movement patterns had moderate to high correlation with the child's motor performance level, indicating that the children with better motor performances used more developmentally advanced patterns in comparison with those with lower scores. However, besides motor maturity, numerous other intrinsic/extrinsic factors may affect the child's performance of this task. The information obtained in this study would assist therapists when working with the children with DD, so that they can provide individualized treatment rather than guiding all such children toward a single, mature pattern.


Symptoms are highly prevalent among HIV outpatients and associated with poor adherence and unprotected sexual intercourse.
There is a paucity of data reporting the prevalence and burden of pain and symptoms among HIV patients in the era of antiretroviral therapy (ART). This study aimed to measure symptom prevalence and determine associations with key variables: demographics, treatment status, adherence and risk behaviours. Cross-sectional self-completion questionnaire in five HIV outpatient clinics in London and the south east UK. Consecutive patients were invited to participate, responding to clinical and behavioural variables including the memorial symptom assessment schedule (short form). Four multivariable models examined the relationship between dependent variables of psychological, physical, global symptom burden scores, the number of symptoms and key independent variables. 778 patients participated; response rate 77% of all patients approached. Both physical and psychological symptoms were highly prevalent: in the previous 7 days, 70.8% experienced lack of energy, 69.9% worry, 53.6% diarrhoea, 53.5% sexual dysfunction and 53.2% pain. In multivariable analysis, both unprotected sexual intercourse with a partner of unknown status, and poorer ART treatment adherence were significantly and independently associated with psychological symptom burden. Lower educational achievement was significantly associated with increasing physical, psychological and global symptom burden and with higher number of symptoms. Being on ART was not associated with any symptom distress measure. In the era of treatment, patients continue to experience high prevalence and burden of psychological and physical symptoms, which are not associated with treatment status. Attention to these distressing problems is essential and may enhance quality of life and adherence and minimise risk behaviour. Symptoms are highly prevalent among HIV outpatients and associated with poor adherence and unprotected sexual intercourse.


Poliomyelitis in intraspinally inoculated poliovirus receptor transgenic mice.
Mice transgenic with the human poliovirus receptor gene develop clinical signs and neuropathology similar to those of human poliomyelitis when neurovirulent polioviruses are inoculated into the central nervous system (CNS). Factors contributing to disease severity and the frequencies of paralysis and mortality include the poliovirus strain, dose, and gender of the mouse inoculated. The more neurovirulent the virus, as defined by monkey challenge results, the higher the rate of paralysis, mortality, and severity of disease. Also, the time to disease onset is shorter for more neurovirulent viruses. Male mice are more susceptible to polioviruses than females. TGM-PRG-3 mice have a 10-fold higher transgene copy number and produce 3-fold more receptor RNA and protein levels in the CNS than TGM-PRG-1 mice. CNS inoculations with type III polioviruses differing in relative neurovirulence show that these mouse lines are similar in disease frequency and severity, demonstrating that differences in receptor gene dosage and concomitant receptor abundance do not affect susceptibility to infection. However, there is a difference in the rate of accumulation of clinical signs. The time to onset of disease is shorter for TGM-PRG-3 than TGM-PRG-1 mice. Thus, receptor dosage affects the rate of appearance of poliomyelitis in these mice.


Evaluation of the psychometric properties of the Barthel Index in an Italian ischemic stroke population in the acute phase: a cross-sectional study.
The objective of this study was to assess and validate the psychometric properties of the Italian culturally adapted Barthel Index (IcaBI) in a cohort of people with ischemic stroke. The validation process was conducted in an Italian cohort of 99 stroke inpatients to whom the IcaBI was administered in order to test its structural validity, and inter-and intrarater reliability. The internal consistency (Cronbach's alpha) was 0.901. Factor analysis revealed a two-factor structure. The interclass correlation coefficient 3,1 (ICC) for intra-rater reliability was estimated at 0.987 (95% CI: 0.975-0.993), while the ICC for inter-rater reliability was 0.909 (95% CI: 0.852-0.948). This study demonstrates the psychometric properties of the IcaBI in an Italian stroke population, and therefore shows that the scale can be considered a valid and reliable assessment tool for measuring functional disability in Italian acute ischemic stroke survivors.


[Effect of glucocorticoids on activity of soluble and membrane-bound forms of carboxypeptidase H in vivo].
Inhibition of soluble and membrane-bound carboxypeptidase H in rat hypothalamus, striatum and pituitary gland by hydrocortisone and dexamethasone treatment in vivo has been established. Differences in the dynamics of change in the activity were determined by the action of hydrocortisone and dexamethasone. Differences of the dynamics of change in soluble and membrane-bound carboxypeptidase H activity were also observed. Possible causes of these differences are discussed.


Oral nickel tolerance: Fas ligand-expressing invariant NK T cells promote tolerance induction by eliciting apoptotic death of antigen-carrying, effete B cells.
Whereas oral nickel administration to C57BL/6 mice (Ni(high) mice) renders the animals tolerant to immunization with NiCl2 combined with H2O2 as adjuvant, as determined by ear-swelling assay, it fails to tolerize Jalpha18-/- mice, which lack invariant NKT (iNKT) cells. Our previous work also showed that Ni(high) splenic B cells can adoptively transfer the nickel tolerance to untreated (Ni(low)) recipients, but not to Jalpha18-/- recipients. In this study, we report that oral nickel administration increased the nickel content of splenic Ni(high) B cells and up-regulated their Fas expression while down-regulating expression of bcl-2 and Bcl-xL, thus giving rise to an Ag-carrying, apoptosis-prone B cell phenotype. Although oral nickel up-regulated Fas expression on B cells of both wild-type Ni(high) and Jalpha18-/- Ni(high) mice, only the former showed a reduced number of total B cells in spleen when compared with untreated, syngeneic mice, indicating that iNKT cells are involved in B cell homeostasis by eliciting apoptosis of effete B cells. Upon transfer of Ni(high) B cells, an infectious spread of nickel tolerance ensues, provided the recipients are immunized with NiCl2/H2O2. As a consequence of immunization, Fas ligand-positive (FasL+) iNKT cells appeared in the spleen and apparently elicited apoptosis of Ni(high) B cells. The apoptotic Ni(high) B cells were taken up by splenic dendritic cells, which thereby became tolerogenic for nickel-reactive Ni(low) T cells. In conclusion, FasL+ iNKT cells may act as ready-to-kill sentinels of innate immunity, but at the same time assist in tolerance induction by eliciting Fas/FasL-mediated apoptosis of effete, Ag-containing B cells.


The atypical sphingolipid SPB 18:1(14Z);O2 is a biomarker for DEGS1 related hypomyelinating leukodystrophy.
Sphingolipids (SL) represent a structurally diverse class of lipids that are central to cellular physiology and neuronal development and function. Defects in the sphingolipid metabolism are typically associated with nervous system disorders. The C4-dihydroceramide desaturase (DEGS1) catalyzes the conversion of dihydroceramide to ceramide, the final step in the SL de-novo synthesis. Loss of function mutations in DEGS1 cause a hypomyelinating leukodystrophy, which is associated with increased plasma dihydrosphingolipids (dhSL) and with the formation of an atypical SPB 18:1(14Z);O2 metabolite. Here, we characterize two novel DEGS1 variants of unknown significance (VUS), provide a structural model with a predicted substrate binding site, and propose a regulatory link between DEGS1 and fatty acid desaturase 3 (FADS3). Both VUS involve single amino acid substitutions near the C-terminus within conserved regions of the enzyme. Patient 1 (p.R311K variant) shows severe progressive tetraspasticity, intellectual disability, and epilepsy in combination with brain magnetic resonance imaging (MRI) findings, typical for DEGS1-related leukodystrophy. Patient 2 (p.G270E variant) presents with delayed psychomotor development, oculomotor apraxia, and a normal brain MRI. Plasma from the p.R311K carrier showed a significantly elevated dhSL species and the presence of SPB 18:1(14Z);O2, while the plasma SL profile for the p.G270E variant was not altered. This suggests the p.R331K variant is pathogenic, while the p.G270E appears benign. As an increase in dihydroSL species is also seen in other pathological disorders of the SL metabolism, the SPB 18:1(14Z);O2 seems to be a more specific biomarker to discriminate between pathogenic and benign DEGS1 variants.


Purification and characterization of thermophilin T, a novel bacteriocin produced by Streptococcus thermophilus ACA-DC 0040.
ACA-DC 0040 produced an antimicrobial agent, which was named thermophilin T, active against several lactic acid bacteria strains of different species and food spoilage bacteria, such as Clostridium sporogenes C22/10 and Cl. tyrobutyricum NCDO-1754. The crude antimicrobial compound is sensitive to proteolytic enzymes and alpha-amylase, heat-stable (100 degrees C for 30 min), resistant to pH exposure at pH 1-12 and demonstrates a bactericidal mode of action against the sensitive strain Lactococcus cremoris CNRZ-117. The production of bacteriocin was optimized approximately 10-fold in an aerobic fermenter held at constant pH 5.8 and 6.2. Ultrafiltration experiments with culture supernatant fluids containing the bacteriocin, and further estimation of molecular weight with gel filtration chromatography, revealed that bacteriocin in the native form has a molecular weight in excess of 300 kDa. SDS-gel electrophoresis of partially purified thermophilin T showed that bacteriocin activity was associated with a protein band of approximately 2.5 kDa molecular mass.


A Quasiclassical Trajectory Study of the Reaction of H Atoms with O2((1)Δg).
The kinetic and dynamic characteristics of the reaction of H atoms with electronically excited O2 were studied using the quasiclassical trajectory (QCT) method and the potential energy surface of Li et al. ( J. Chem. Phys. 2010 , 133 , 144306 - 144314 ). The reaction takes place via a deep potential well that can be entered by climbing a barrier in the reactant valley and can be left without a barrier on the product side. In this reaction, the basic assumptions of statistical rate theories are not fulfilled: (i) 80% of the trajectories cross the barrier region twice and are nonreactive; (ii) the energy is not equilibrated in the HO2 potential well. The QCT cross sections agree well with those from the existing exact quantum-mechanical data and extend them to vib-rotationally excited reactants. The thermal rate coefficients agree well with measurements of pure reactive quenching of O2((1)Δg) and are lower than those involving both reactive and electronic quenching. The temperature dependence is described as k2 = 5.81 × 10(-16) T(1.45) exp(-2270/T) cm(3) molecule(-1) s(-1). On the basis of a comparison of the QCT data with the two kinds of experiments, we estimate that electronic quenching is faster than reaction by a factor of about 10 at low and 2 at high flame temperatures.


Quantitative Aspects of Single Molecule Microscopy.
Single molecule microscopy is a relatively new optical microscopy technique that allows the detection of individual molecules such as proteins in a cellular context. This technique has generated significant interest among biologists, biophysicists and biochemists, as it holds the promise to provide novel insights into subcellular processes and structures that otherwise cannot be gained through traditional experimental approaches. Single molecule experiments place stringent demands on experimental and algorithmic tools due to the low signal levels and the presence of significant extraneous noise sources. Consequently, this has necessitated the use of advanced statistical signal and image processing techniques for the design and analysis of single molecule experiments. In this tutorial paper, we provide an overview of single molecule microscopy from early works to current applications and challenges. Specific emphasis will be on the quantitative aspects of this imaging modality, in particular single molecule localization and resolvability, which will be discussed from an information theoretic perspective. We review the stochastic framework for image formation, different types of estimation techniques and expressions for the Fisher information matrix. We also discuss several open problems in the field that demand highly non-trivial signal processing algorithms.


Lifetime discrimination burden, racial discrimination, and subclinical cerebrovascular disease among African Americans.
Explore interactive relations of lifetime discrimination burden and racial discrimination-chronic stressors among African Americans (AAs)-and age with MRI-assessed white matter lesion volume (WMLV), a prognostic indicator of poor clinical brain health outcomes. AAs (N = 71; 60.6% female, mean age = 50) participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study underwent quantitative magnetic resonance imaging coded for WMLV. Participants self-reported lifetime discrimination burden and racial discrimination approximately 5 years earlier. Multivariable regression models assessed interactions of linear and quadratic effects of discrimination and age with WMLV adjusted for sex and socioeconomic status. Findings revealed significant interactive relations of age and (a) quadratic, lifetime discrimination burden, B = .05, p = .014, ηpartial2 = .092, and (b) quadratic, racial discrimination, B = .03, p = .001, ηpartial2 = .155, with WMLV. Among older AA, increases in lifetime discrimination burden and racial discrimination were associated with increases in WMLV (ps < .03); in younger AA, decreasing levels of racial discrimination were related to increases in WMLV (p = .006). Among older AA, as lifetime discrimination burden and racial discrimination increased, so did WMLV. However, in younger AA, decreases in racial discrimination were associated with increased WMLV. Elucidation of complex mechanistic underpinnings, including potentially differential impacts of the acknowledgment versus suppression or underreporting of discriminatory experiences, among AA of different age cohorts, is critical to understanding the present pattern of findings. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Organ identity genes and modified patterns of flower development in Gerbera hybrida (Asteraceae)
We have used Gerbera hybrida (the cultivated ornamental, gerera) to investigate the molecular basis of flower development in Asteraceae, a family of flowering plants that have heteromorphic flowers and specialized floral organs. Flowers of the same genotype may differ in a number of parameters, including sex expression, symmetry, sympetaly and pigmentation. In order to study the role of organ identity determination in these phenomena we isolated and functionally analysed six MADS box genes from gerbera; these were shown by phylogenetic analysis to be orthologous to well characterized regulatory genes described from Arabidopsis and Antirrhinum. Expression analysis suggests that the two gerbera agamous orthologues, the globosa orthologue and one of the deficiens orthologues may have functional equivalency to their counterparts, participating in the C and B functions, respectively. However, the function of a second deficiens orthologue appears unrelated to the B function, and that of a squamosa orthologue seems distinct from squamosa as well as from the A function. The induction patterns of gerbera MADS box genes conform spatiotemporally to the multi-flowered, head-like inflorescence typical of Asteraceae. Furthermore, gerbera plants transgenic for the newly isolated MADS box genes shed light onto the mechanistic basis for some floral characteristics that are typical for Asteraceae. We can conclude, therefore, that the pappus bristles are sepals highly modified for seed dispersal, and that organ abortion in the female marginal flowers is dependent upon organ identity and not organ position when position is homeotically altered.