Flaxseed meal and oat hulls supplementation modulates growth performance, blood lipids, intestinal fermentation, bile acids, and neutral sterols in growing pigs fed corn-soybean meal-based diets.
The present study was conducted to determine the effect of flaxseed meal and oat hulls supplementation on growth performance, apparent total tract digestibility (ATTD) of fat, serum lipids, and concentrations of VFA, bile acids (BA), and neutral sterols (NS) in digesta and feces in growing pigs. Forty-eight Genesus [(Duroc boar × Yorkshire-Landrace sows] barrows (25.0 ± 0.32 kg initial BW) were housed in pairs. Pigs were assigned to 1 of the 3 corn-soybean meal-based diets-a basal corn-soybean meal-containing diet (control), a flaxseed meal-containing diet (FM), or an oat hulls-containing diet (OH)-in a completely randomized design. All diets were formulated to be isoenergetic and to contain similar standardized ileal digestible AA contents and meet other nutrient requirements for growing pigs. The experiment lasted for 28 d. Average daily feed intake; ADG; G:F; ATTD of fat, serum lipids, and digesta; and fecal VFA, BA, and NS concentrations were determined. Pigs fed the control or OH had greater final BW ( < 0.001), ADFI ( = 0.005), and ADG ( < 0.001) than FM-fed pigs. The ATTD of fat in the FM was lowest at 70.1% followed by 79.2% in OH and was greatest at 92.4% in the control ( = 0.020). Total serum cholesterol content was 2.25 and 1.99 mmol/L and lower ( < 0.001) in pigs fed FM and OH, respectively, than the 2.36 mmol/L in pigs fed the control. Pigs fed the FM and OH had greater ileal and cecal total VFA ( < 0.001), ileal deoxycholic acid ( < 0.01), and cecal ( < 0.001) and fecal cholesterol ( = 0.002) concentrations than those fed the control. Pigs fed the FM excreted more fecal lithocholic acid ( = 0.002) and ursodeoxycholic acid ( = 0.001) compared with those that consumed the control and OH. The concentrations of coprostanol in cecal digesta ( < 0.001) and feces ( = 0.011) were higher in pigs fed the FM and OH than in pigs fed the control. In conclusion, feeding flaxseed meal and oat hulls induced intestinal fermentation; however, the former depressed growth performance whereas the latter did not have any effect. Addition of flaxseed meal and oat hulls in growing pig diets reduced fat digestibility and serum cholesterol and stimulated malabsorption of primary BA and excretion of secondary BA and NS.


Cell hybridization and cell agglutination. II. Enhancement of cell hybridization by polycations.
An efficient technique for hybridization of mammalian cells was developed by combining agglutination by pretreatment with polycations, such as polyarginine, and conventional polyethylene glycol(PEG)-mediated cell fusion. Polyarginine and subsequent PEG treatment resulted in markedly decreased viability in the treated cells, but addition of polyvinyl pyrrolidone or glycerol to the polyarginine prevented this cytotoxicity. Polyarginine was much more effective than polylysine or polyornithine in inducing hybridization. Other polycations, including polybrene and protamine but not DEAE-dextran, were also active in inducing hybridization. The condition of the cells at the time of polycation treatment was an important factor in the enhancement of hybridization. The condition of the cells at the time of polycation treatment was an important factor in the enhancement of hybridization. The enhancement of hybridization of cells in monolayer incubated for 2 h was much higher than that of cells incubated for 24 h. These findings suggest that polycations do not necessarily operate by agglutinating cells. The mechanism of polycation-enhanced cell hybridization is discussed.


Predictive value of several signs of infection as surrogate markers for mortality in a neutropenic guinea pig model of Pseudomonas aeruginosa sepsis.
Infected, neutropenic animals are used as experimental models to evaluate the relative efficacies of antimicrobial agents and host-pathogen-antibiotic interactions. In the past, these models used death as the study end point. Because of the concern about use of death as an end point, we evaluated the accuracy with which various signs of infection predicted mortality in a neutropenic guinea pig model of treated and untreated Pseudomonas aeruginosa sepsis. The potential surrogate markers studied included ruffled fur, respiratory distress, diarrhea, hunched posture, lethargy, abnormal neurologic movements (twitching, paralysis of a limb), inappetence for > 48 h, the inability to ambulate, and the inability of a supine animal to stand. In addition, we evaluated whether percentage of weight loss or change in daily food and water consumption were predictive of mortality. Animals were inspected for these signs at least every 4 h during the day and every 8 h in the evening. In treated and untreated animals, 100% of subjects that were unable to ambulate or to rise from the supine position died (positive predictive value for death was 100% for either sign). Guinea pigs that could not rise from a supine position expired between 1 and 8 h after this sign was observed. Those that could not ambulate died between 4 and 40 h after that sign was observed. In treated and untreated animals, none of the survivors manifested either sign of disease (100% specificity for each sign). However, 59% of untreated and 69% of treated animals that were ambulatory were found dead at the next observation period, underscoring the rapidity with which this infection progresses to death when it enters its final stage. No other signs of infection distinguished animals that survived or died. Thus, the inability of neutropenic, infected guinea pigs to rise from a supine position and the inability to ambulate were the only signs that accurately predicted death and, therefore, are the only signs that can be used as surrogates for death in this experimental model of P. aeruginosa sepsis.


Developing a pig model for crypt fenestration-induced localized hypoplastic enamel defects in humans.
Hypoplastic pits on human deciduous canine teeth are attributed to nutritionally induced thinning of the crypt wall prior to eruption, exposing ameloblasts to unspecified physical trauma through the fenestration. Traditionally known as localized hypoplasia of the primary canine (LHPC), this little-understood condition is reported in fields ranging from public health to bioarchaeology. We propose the defect be termed a 'crypt fenestration hypoplastic enamel defect' (CFED) to reflect that an analogous lesion is created postnatally on maxillary molars of pigs. Pigs are accepted as a suitable proxy for many studies in human biology. We compare fenestration defects and CFEDs between 50 Sick Pen pigs, who died naturally, and 20 Controls. Observations were made of the presence, number and size of fenestrations in molar crypts. CFEDs were counted on erupted deciduous last molars and permanent first molars. Signs of being underweight and cranio-dental infection at death were recorded. Sick pen pigs show significantly more fenestrations at death and CFEDs acquired before death. These conditions co-occur with infection and poor growth. The deep fibers of temporalis muscle lie adjacent to the crypt wall of maxillary molars. We propose that contraction of this muscle during suckling and chewing creates large compressive forces against fenestrated bony surfaces sufficient to have physiological consequences for physically unprotected ameloblasts. While we conclude that a pig model is appropriate to study fenestration-induced enamel defects, this naturalistic experiment leaves unresolved whether osteopenia in pigs, and by extension in human infants, is due to disease and/or malnutrition.


A novel NDUFA1 mutation leads to a progressive mitochondrial complex I-specific neurodegenerative disease.
Mitochondrial diseases have been shown to result from mutations in mitochondrial genes located in either the nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Mitochondrial OXPHOS complex I has 45 subunits encoded by 38 nuclear and 7 mitochondrial genes. Two male patients in a putative X-linked pedigree exhibiting a progressive neurodegenerative disorder and a severe muscle complex I enzyme defect were analyzed for mutations in the 38 nDNA and seven mtDNA encoded complex I subunits. The nDNA X-linked NDUFA1 gene (MWFE polypeptide) was discovered to harbor a novel missense mutation which changed a highly conserved glycine at position 32 to an arginine, shown to segregate with the disease. When this mutation was introduced into a NDUFA1 null hamster cell line, a substantial decrease in the complex I assembly and activity was observed. When the mtDNA of the patient was analyzed, potentially relevant missense mutations were observed in the complex I genes. Transmitochondrial cybrids containing the patient's mtDNA resulted in a mild complex I deficiency. Interestingly enough, the nDNA encoded MWFE polypeptide has been shown to interact with various mtDNA encoded complex I subunits. Therefore, we hypothesize that the novel G32R mutation in NDUFA1 is causing complex I deficiency either by itself or in synergy with additional mtDNA variants.


Effects of anthropogenic light on species and ecosystems.
Anthropogenic light is ubiquitous in areas where humans are present and is showing a progressive increase worldwide. This has far-reaching consequences for most species and their ecosystems. The effects of anthropogenic light on natural ecosystems are highly variable and complex. Many species suffer from adverse effects and often respond in a highly specific manner. Ostensibly surveyable effects such as attraction and deterrence become complicated because these can depend on the type of behavior and specific locations. Here, we considered how solutions and new technologies could reduce the adverse effects of anthropogenic light. A simple solution to reducing and mitigating the ecological effects of anthropogenic light seems unattainable, because frugal lighting practices and turning off lights may be necessary to eliminate them.


Significant inter-annual fluctuation in CO2 and CH4 diffusive fluxes from subtropical aquaculture ponds: Implications for climate change and carbon emission evaluations.
Aquaculture ponds are potential hotspots for carbon cycling and emission of greenhouse gases (GHGs) like CO2 and CH4, but they are often poorly assessed in the global GHG budget. This study determined the temporal variations of CO2 and CH4 concentrations and diffusive fluxes and their environmental drivers in coastal aquaculture ponds in southeastern China over a five-year period (2017-2021). The findings indicated that CH4 flux from aquaculture ponds fluctuated markedly year-to-year, and CO2 flux varied between positive and negative between years. The coefficient of inter-annual variation of CO2 and CH4 diffusive fluxes was 168% and 127%, respectively, highlighting the importance of long-term observations to improve GHG assessment from aquaculture ponds. In addition to chlorophyll-a and dissolved oxygen as the common environmental drivers, CO2 was further regulated by total dissolved phosphorus and CH4 by dissolved organic carbon. Feed conversion ratio correlated positively with both CO2 and CH4 concentrations and fluxes, showing that unconsumed feeds fueled microbial GHG production. A linear regression based on binned (averaged) monthly CO2 diffusive flux data, calculated from CO2 concentrations, can be used to estimate CH4 diffusive flux with a fair degree of confidence (r2 = 0.66; p < 0.001). This algorithm provides a simple and practical way to assess the total carbon diffusive flux from aquaculture ponds. Overall, this study provides new insights into mitigating the carbon footprint of aquaculture production and assessing the impact of aquaculture ponds on the regional and global scales.


Tissue heart valve mineralization: Review of calcification mechanisms and strategies for prevention.
Attempts to replace diseased human valves with prostheses began more than 30 yrs ago. Heart valve prostheses can be broadly classified into mechanical prostheses (made out of non-biological materials) and bioprostheses made out of biological tissue. Biological valves are made from animal tissue bovine pericardium and porcine valves. The use of these tissues became commercially available after the introduction of the glutaraldehyde (GA) fixation technique. GA reacts with tissue proteins to form inter- and intramolecular crosslinks, resulting in improved durability. The advantage of bioprostheses compared with mechanical valves is the freedom from thromboembolism; and therefore, the avoidance of long-term anticoagulation therapy. These prostheses are preferable in elderly people and in patients who do not tolerate anticoagulants. However, tissular calcification and primary tissue failure (caused by the mechanical stress) are the main unresolved problems. The causes of calcification are numerous and, to date, a satisfactory solution to this question has not been found, although chemical treatments with metal cations, diphosphonates and treatments eliminating phospholipids have proved to mitigate calcification. In addition, alterna-tive approaches to GA chemical treatment fixation are being proposed to provide the tissue with greater resistance to this process. Studies are under way using polyepoxy compounds, derivates of amino oleic acid (AOA), agents such as diphenylphosphorylazide, carbodiimide, amino acids etc. Further improvements in fixation techniques, as well as in bioprosthesis design (stentless valves) are being made to improve the durability and functional characteristics of bioprosthetic heart valves. The development of a biomaterial capable of withstanding calcification and mechanical stress, while being as durable as mechanical prostheses, would convert the bioprostheses into the replacement of choice by eliminating the need for anticoagulation therapy.


Cell trajectory modeling identifies a primitive trophoblast state defined by BCAM enrichment.
In early placental development, progenitor cytotrophoblasts (CTB) differentiate along one of two cellular trajectories: the villous or extravillous pathways. CTB committed to the villous pathway fuse with neighboring CTB to form the outer multinucleated syncytiotrophoblast (SCT), whereas CTB committed to the extravillous pathway differentiate into invasive extravillous trophoblasts (EVT). Unfortunately, little is known about the processes controlling human CTB progenitor maintenance and differentiation. To address this, we established a single cell RNA sequencing (scRNA-seq) dataset from first trimester placentas to identify cell states important in trophoblast progenitor establishment, renewal and differentiation. Multiple distinct trophoblast states were identified, representing progenitor CTB, column CTB, SCT precursors and EVT. Lineage trajectory analysis identified a progenitor origin that was reproduced in human trophoblast stem cell organoids. Heightened expression of basal cell adhesion molecule (BCAM) defined this primitive state, where BCAM enrichment or gene silencing resulted in enhanced or diminished organoid growth, respectively. Together, this work describes at high-resolution trophoblast heterogeneity within the first trimester, resolves gene networks within human CTB progenitors and identifies BCAM as a primitive progenitor marker and possible regulator.


Thyroid endocrine disruption and external body morphology of Zebrafish.
This study examined the effects thyroid-active compounds during early development on body morphology of Zebrafish (Danio rerio). Three-day postfertilization (dpf) larvae were exposed to goitrogen [methimazole (MZ, 0.15mM)], combination of MZ (0.15mM) and thyroxine (T4, 2nM), T4 (2nM), or control (reconstituted water) treatments until 33dpf and subsequently maintained in reconstituted water until 45dpf. Samples were taken at 33 and 45dpf for multivariate analysis of geometric distances between selected homologous landmarks placed on digital images of fish, and for histological assessment of thyrocytes. Body mass, standard length, and pectoral fin length were separately measured on remaining fish at 45dpf. Histological analysis confirmed the hypothyroid effect (increased thyrocyte height) of MZ and rescue effect of T4 co-administration. Geometric distance analysis showed that pectoral and pelvic fins shifted backward along the rostrocaudal axis under hypothyroid conditions at 45dpf and that T4 co-treatment prevented this shift. Pectoral fin length at 45dpf was reduced by exposure to MZ and rescued by co-administration of T4, but it was not associated with standard length. Methimazole caused a reduction in body mass and length at 45dpf that could not be rescued by T4 co-administration, and non-thyroidal effects of MZ on body shape were also recognized at 33 and 45dpf. Alterations in the length and position of paired fins caused by exposure to thyroid-disrupting chemicals during early development, as shown here for Zebrafish, could affect physical aspects of locomotion and consequently other important organismal functions such as foraging, predator avoidance, and ultimately survival and recruitment into the adult population. Results of this study also suggest the need to include rescue treatments in endocrine disruption studies that rely on goitrogens as reference for thyroid-mediated effects.


[Hemodynamics of erection: current pharmacological findings].
Over twenty drugs were injected into the corpora cavernosa. Pharmacologically these drugs come under seven therapeutic categories. Two types of pharmacodynamics explain the mode of action of these agents on the erectile tissues. The discovery of these drugs can be added to the array of investigations and actions normally used to study and remedy the problems of organic impotence, as well as a new test which may provide a therapeutic base for vascular rehabilitation and, in some cases, a substrate for a pharmacological prosthesis.


Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells.
This study evaluated to what extent presentation of exogenously acquired self-Ags via MHC class I molecules on DC might contribute to the activation of self-reactive CTL and subsequent development of autoimmune disease. We show here by using the rat insulin promotor lymphocytic choriomeningitis virus glycoprotein model of autoimmune diabetes that the activation of self-reactive CTL by DC after uptake of exogenous Ag is very limited, first by the short half-life of MHC class I-associated peptides on DC in vitro and in vivo, and second by the rather inefficient MHC class I presentation of cell-associated self-Ags by DC. These two mechanisms are probably crucial in establishing high thresholds for the induction of self-reactive CTL that prevent autoimmune sequelae after release of sequestered and previously immunologically ignored tissue Ags.


Histopathological features with angiographic correlates of internal carotid artery pseudo-occlusion: impact of plaque compositions. Clinical article.
This study describes clinicopathological characteristics of pseudo-occlusion of the internal carotid artery with regard to its possible mechanisms. The authors retrospectively reviewed 17 patients with pseudo-occlusion and 23 with high-grade stenosis (North American Symptomatic Carotid Endarterectomy Trial criteria ≥ 90%, but no collapsed distal internal carotid artery) who underwent carotid endarterectomy. Atherosclerotic risk factors, clinical presentation, angiographic findings, and histological features of plaque obtained from the carotid endarterectomy were investigated and comparisons were made between groups. Plaques obtained in the pseudo-occlusion group were significantly more fibrous and less atheromatous than those in the high-grade stenosis group. Old, organized thrombi were more frequently found in pseudo-occlusion group plaques than in high-grade stenosis group plaques. Plaques acquired in the pseudo-occlusion group had 2 different histological features: the presence or absence of the original lumen. The pseudo-occlusion plaques with total occlusion and recanalization (8 patients) were composed of thrombotic total occlusion with lumen recanalization by large neovascular channels, whereas those with severe stenosis (9 patients) were fibrous or fibroatheromatous and had severe stenosis of the original lumen. In patients with pseudo-occlusion and total occlusion and recanalization, the authors observed a significantly higher incidence of transient ischemic attack and anterior communicating artery-posterior communicating artery collateral flow than those with high-grade stenosis and pseudo-occlusion with severe stenosis. Plaques of the pseudo-occlusion group were more fibrous than those of the high-grade stenosis group and had 2 different histological features: pseudo-occlusion with total occlusion and recanalization or pseudoocclusion with severe stenosis. This difference in plaque histology may be related to the clinical features of pseudoocclusion, such as symptoms and collateral flow patterns.


Myocardial strain is associated with adverse cardiac events in patients treated with chimeric antigen receptor (CAR) T-cell therapy.
Cardiovascular events, including heart failure and arrhythmias, following chimeric antigen receptor (CAR) T-cell therapy are increasingly recognized. Although global longitudinal strain (GLS) has demonstrated prognostic utility for other cancer therapy-related cardiac dysfunction, less is known regarding the association of GLS with adverse cardiac events following CAR T-cell therapy. To determine the association of baseline GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy. Patients who had an echocardiogram within 6 months prior to receiving CAR T-cell therapy were retrospectively identified. Clinical data and cardiac events were collected via chart review. Echocardiograms were analyzed offline for GLS, left ventricular ejection fraction, and Doppler parameters. Multivariable logistic regression was used to determine the association between adverse cardiovascular events and echocardiographic parameters. Among 75 CAR T-cell therapy patients (mean age 63.9, 34.7% female), nine patients (12%) experienced cardiac events (CEs) including cardiovascular death, new/worsening heart failure, and new/worsening arrhythmia within 1 year of treatment. In univariable models, higher baseline GLS (OR 0.78 [0.63, 0.96], p = .021) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.40 [1.08, 1.81], p = .012) was associated with a higher risk of CE. After adjusting for age and LDH, higher baseline GLS (OR 0.65 [0.48-0.88], p = <.01) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.56 [1.06, 2.29], p = .024) was associated with a higher risk of CE. Lower GLS and higher mitral E/e' on a baseline echocardiogram were associated with higher risk for CEs in patients receiving CAR T-cell therapy.


3D in vitro technology for drug discovery.
Three-dimensional (3D) in vitro systems that can mimic organ and tissue structure and function in vivo, will be of great benefit for a variety of biological applications from basic biology to toxicity testing and drug discovery. There have been several attempts to generate 3D tissue models but most of these models require costly equipment, and the most serious disadvantage in them is that they are too far from the mature human organs in vivo. Because of these problems, research and development in drug discovery, toxicity testing and biotech industries are highly expensive, and involve sacrifice of countless animals and it takes several years to bring a single drug/product to the market or to find the toxicity or otherwise of chemical entities. Our group has been actively working on several alternative models by merging biomaterials science, nanotechnology and biological principles to generate 3D in vitro living organs, to be called "Human Organs-on-Chip", to mimic natural organ/tissues, in order to reduce animal testing and clinical trials. We have fabricated a novel type of mechanically and biologically bio-mimicking collagen-based hydrogel that would provide for interconnected mini-wells in which 3D cell/organ culture of human samples in a manner similar to human organs with extracellular matrix (ECM) molecules would be possible. These products mimic the physical, chemical, and biological properties of natural organs and tissues at different scales. This paper will review the outcome of our several experiments so far in this direction and the future perspectives.


Nanoparticle induced cell magneto-rotation: monitoring morphology, stress and drug sensitivity of a suspended single cancer cell.
Single cell analysis has allowed critical discoveries in drug testing, immunobiology and stem cell research. In addition, a change from two to three dimensional growth conditions radically affects cell behavior. This already resulted in new observations on gene expression and communication networks and in better predictions of cell responses to their environment. However, it is still difficult to study the size and shape of single cells that are freely suspended, where morphological changes are highly significant. Described here is a new method for quantitative real time monitoring of cell size and morphology, on single live suspended cancer cells, unconfined in three dimensions. The precision is comparable to that of the best optical microscopes, but, in contrast, there is no need for confining the cell to the imaging plane. The here first introduced cell magnetorotation (CM) method is made possible by nanoparticle induced cell magnetization. By using a rotating magnetic field, the magnetically labeled cell is actively rotated, and the rotational period is measured in real-time. A change in morphology induces a change in the rotational period of the suspended cell (e.g. when the cell gets bigger it rotates slower). The ability to monitor, in real time, cell swelling or death, at the single cell level, is demonstrated. This method could thus be used for multiplexed real time single cell morphology analysis, with implications for drug testing, drug discovery, genomics and three-dimensional culturing.


Double-labelling immunohistochemical study of megakaryocytes in African swine fever.
Bone marrow samples from pigs infected with the highly virulent Malawi'83 or moderately virulent Dominican Republic (DR'78) isolates of African swine fever virus were studied by means of a double labelling immunohistochemical technique which stained the major structural protein VP73 of the virus and megakaryocytes simultaneously. In pigs infected with the highly virulent Malawi'83 isolate, 2.2 per cent of megakaryocytes were VP73+ five days after inoculation, and at six and seven days 2.5 and 9.5 per cent of megakaryocytes were VP73+. Some infected and uninfected megakaryocytes showed pyknosis and karyorrhexis, particularly at seven days after inoculation. However, in comparison with uninfected pigs, the number of megakaryocytes decreased only at seven days after inoculation. In pigs infected with the moderately virulent DR'78 isolate, only 0.2 per cent of megakaryocytes were VP73+ at eight days after inoculation. However, at eight, nine and 10 days after inoculation the total number of megakaryocytes was significantly lower (P < 0.01) than in control uninfected pigs, and the majority of the megakaryocytes showed signs of cell death such as pyknosis and karyorrhexis. The fact that this greater destruction of megakaryocytes was associated with the lower rate of infection of this cell type suggests that indirect damage to megakaryocytes is an additional mechanism of thrombocytopenia in acute and subacute African swine fever.


Sphingosine but not sphingosine-1-phosphate stimulates suicidal erythrocyte death.
Sphingosine kinase 1 phosphorylates sphingosine, which is converted to ceramide by ceramide synthetase. Ceramide triggers eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine (PS) exposure at the erythrocyte surface. Erythrocytes lack sphingosine phosphate-degrading enzymes and thus store large quantities of sphingosine phosphate. The present study explored the influence of sphingosine and sphingosine phosphate on eryptosis. [Ca(2+)](i), was estimated from Fluo3 fluorescence, cell volume from forward scatter and PS exposure from annexin V-binding in FACS analysis. Sphingosine (0.1 - 10 μM) but not sphingosine-1- phosphate (0.1 - 10 μM) increased [Ca(2+)](i), decreased cell volume and increased PS-exposure. The observations disclose sphingosine, but not sphingosine-1-phosphate, as a strong inducer of eryptosis.


Gastric involvement in progressive systemic sclerosis: electrogastrographic and sonographic findings.
To determine whether electrogastrography (EGG) can discern sonographically demonstrated motility disorders in patients with progressive systemic sclerosis (SSc) and to evaluate EGG as a possible diagnostic tool. Prospective study with control group and testing for reliability. 15 SSc patients [women aged 33-70 years (mean 53.3 years)] and 15 healthy volunteers. Bipolar cutaneous EGG was recorded to obtain the following parameters: period dominant frequency (PDF), percentage of gastric dysrhythmia and normogastria (defined as 2-4/min), period dominant power (PDP) and its change after a standardized meal of 500 kcal (2093 kJ), and instability coefficients of dominant frequency and power (DFIC, DPIC). Simultaneously, real-time sonography was performed in the aortomesenteric plane (3.5-MHz curved-array probe). In 10 patients and 13 control subjects, the distance from the anterior wall of the gastric antrum to the abdominal skin was measured. Three patients (20%) showed hypomotility of the gastric antrum sonographically. The percentage of bradygastria was significantly lower in these patients, but the PDF, DFIC and DPIC values were not significantly different. The distance between the cutaneous electrodes and the antrum bore a greater relationship to the PDP values than did the sonographically demonstrated number of gastric contractions. Although cutaneous EGG can be performed in SSc patients without apparent derangement in frequency and stability of the signal, it offers no advantage over sonography in diagnosis and follow-up.


Adoption of a managerial innovation: a study of physician impact analysis.
This article examines the adoption of physician impact analysis (PIA) among active treatment hospitals in Ontario, Canada. The influence of variables from three different levels of analysis (individual, organizational and contextual) were included as well as measures of key stakeholders' (Chief Executive Officer (CEO) and Medical Chief of Staff) assessments of the attributes of the innovation. A number of conclusions were drawn. First, by adding information about the perceived attributes of the innovation the model was able to account for a larger percentage of explained variance than has been seen in related work. Secondly, the adoption of PIA within a context of written guidelines agreed to by senior management, specifying process and structure concerns, is most likely in organizations which are large and where the CEO positively evaluates the innovation.


Perspectives in the development of hybrid bifunctional antitumour agents.
In spite of the development of a large number of novel target-specific antitumour agents, the single-agent therapy is in general not able to provide an effective durable control of the malignant process. The limited efficacy of the available agents (both conventional cytotoxic and novel target-specific) reflects not only the expression of defence mechanisms, but also the complexity of tumour cell alterations and the redundancy of survival pathways, thus resulting in tumour cell ability to survive under stress conditions. A well-established strategy to improve the efficacy of antitumour therapy is the rational design of drug combinations aimed at achieving synergistic effects and overcoming drug resistance. An alternative strategy could be the use of agents designed to inhibit simultaneously multiple cellular targets relevant to tumour growth/survival. Among these novel agents are hybrid bifunctional drugs, i.e. compounds resulting by conjugation of different drugs or containing the pharmocophores of different drugs. This strategy has been pursued using various conventional or target-specific agents (with DNA damaging agents and histone deacetylase inhibitors as the most exploited compounds). A critical overview of the most representative compounds is provided with emphasis on the HDAC inhibitor-based hybrid agents. In spite of some promising results, the actual pharmacological advantages of the hybrid agents remain to be defined. This commentary summarizes the recent advances in this field and highlights the pharmacological basis for a rational design of hybrid bifunctional agents.


The effect of trapidil on the reactive astrocytic proliferation following spinal cord trauma in rats: light and electron microscopic findings.
Platelet-derived growth factor (PDGF) released from platelets is one of the mitogens in serum, which plays a major role upon the cell biology, namely enhancing cell division and controlling of the maturation, especially upon the glial cell growth and its differentiation. Trapidil, which is an anti-PDGF agent, inhibits the effect of PDGF, especially the proliferative effects on the glial and tumoral cells in vitro. Previous studies suggested that the astrocytic proliferation stimulated by PDGF was inhibited by trapidil via the selective antagonism. Trapidil was not found to have a considerable effect on the prevention of nonpermissive astrocytes in this study. It should be theorized that trapidil, administered immediately even after the trauma, could not reach the injury site in effective measure because of secondary events such as edema and impairment of blood circulation. This suggestion should be another subject for studies concerning trapidil which is administered prior to the trauma.


Effectiveness of a breastfeeding promotion intervention model based on Society ecosystems Theory for maternal women: a study protocol of randomized controlled trial.
Breastfeeding is recognized internationally as the most scientific and effective way to feed infants and young children. According to the World Health Organization in 2022, the exclusive breastfeeding rate within 6 months is 34.1% in China, which is still far from the goal of "more than 60% exclusive breastfeeding rate of infants within 6 months" by 2030 required by China's State Council. It is necessary to promote breastfeeding and provide maternal breastfeeding guidance to increase exclusive breastfeeding. Factors influencing breastfeeding can be explained by the society ecosystems theory, distributed in macro, mezzo and micro systems. The interventions focused on breastfeeding promotion are mainly carried out in the health systems and services, home and family environment, community environment, work environment, policy environment or a combination of these facilities. But there is sparse research on integrating resources in the macro, mezzo and micro systems of maternal breastfeeding processes to promote breastfeeding behavior. A randomized controlled trial will test the effect of a breastfeeding promotion intervention model based on the society ecosystems theory versus usual prenatal and postnatal care on maternal and infant health and the exclusive breastfeeding rate at 6 months. The study is a single-blind, parallel design, randomized controlled trial with an intervention group (n = 109) and a control group (n = 109) that compares the effect of a breastfeeding promotion intervention model based on the society ecosystems theory with usual prenatal and postnatal care. The intervention covers macro- (policy, culture), mezzo- (family-hospital-community) and micro- (biological, psychological and social) systems of the maternal breastfeeding process. Infant feeding patterns, neonatal morbidity and physical and mental health of antenatal and postpartum women will be collected at baseline (28 to 35 weeks of gestation), 1-, 4-, and 6-month postpartum. This is a multifaceted, multifactorial, and multi-environmental breastfeeding promotion strategy to help mothers and their families learn breastfeeding knowledge and skills. The study provides a new modality for adding breastfeeding interventions to prenatal and postnatal care for healthcare providers in the hospital and the community. Chinese Clinical Trial Registry at www.chictr.org.cn , ChiCTR2300075795.


[Concurrent leishmaniasis and human immunodeficiency virus (HIV) infection: a study of four cases].
Few cases of concurrent leishmaniasis and HIV infection have been reported in Brazil, despite both infections being in expansion. Two cases of visceral leishmaniasis and two cases of mucocutaneous leishmaniasis are discussed. Disseminated skin and oral lesions were found in the patients with the cutaneous form of the disease. Prolonged fever, hepatosplenomegaly and pancytopenia were the main manifestations of the visceral form. The CD4 T lymphocyte count was low in all cases. Direct examination of bone marrow aspirate for leishmania and biopsy of cutaneous lesions are the techniques of choice to confirm diagnosis. Pentavalent antimonials and amphotericin B are preferred drugs for the treatment of leishmaniasis, including patients with AIDS. The authors recommend the inclusion of this parasitosis in the differential diagnosis of opportunistic diseases in patients with AIDS.


Design of a Multi-Feature Classification Scheme for Infant Epileptic Seizures.
Neonatal epileptic seizures take place in the early childhood years, accounting for a severe condition with several deaths and neurological problems in newborn neonates. Despite the early advancements on the diagnosis and/or treatment of this condition, as a major difficulty accounts the inability of the physicians to identify and characterize a seizure, as one a small percentage gets detected in neonatal intensive care units (NICU). An important step towards any kind of seizure classification is the detection and reduction of non-cerebral activity. Towards this direction, our multi-feature approach contains spectral and statistical characteristics of EEG signals of 79 infants with suspicion of seizure and assesses the performance of two classification algorithms iteratively. The trained models (Support Vector Machine (SVM) and Random Forest classifiers) yielded high classification performance (>80% and >85% respectively). A robust neonatal seizure classification scheme is thus proposed, along with nine high scoring spectrum and statistical features. The importance of embedding an artefact reduction approach is also discussed, since the complex artifacts spread throughout the signals have great impact on the accuracy of the algorithms. The nine extracted high scoring spectral and statistical features might be used as potential biomarkers for neonatal seizure prediction in a clinical setting.


Central nervous system reactions to histamine-2 receptor blockers.
To review the incidence, risk factors, pharmacology, and management of central nervous system reactions to histamine-2 receptor (H2) blockers. English-language articles were identified through a search of the MEDLINE and Current Contents data-bases. Bibliographies of retrieved articles were examined for relevant articles. Case reports submitted to the Food and Drug Administration through 19 September 1989 were obtained. Studies on the association between central nervous system toxicity (psychosis, agitation, hallucinations, delirium, mental status changes, disorientation, confusion, irritability, obtundation, or hostility) and H2 blockers were analyzed. All data on the incidence of and potential predisposing factors for central nervous system reactions to H2 blockers were analyzed. Limitations of the data are discussed. Central nervous system toxicities have been associated with all H2 blockers. These reactions generally occur during the first 2 weeks of therapy and resolve within 3 days of drug withdrawal. The estimated incidence of central nervous system reactions is 0.2% or less in outpatients and 1.6% to 80% in hospitalized patients. Cimetidine is most frequently associated with these reactions; however, no clear evidence exists that one H2 blocker is more likely than another to cause a reaction. Risk factors for central nervous system reactions have been proposed, but only advanced age has some, albeit limited, data to support it as a risk factor. Studies have only infrequently established causality and there have been difficulties in establishing risk factors for an relative incidences of a phenomenon that occurs infrequently in outpatients and that can be multifactorial in origin. All H2 blockers are associated with central nervous system reactions. There is no clear evidence of a higher rate of reactions with one H2 blocker compared with another.


Time and frequency domain analyses of heart rate variability in patients with epilepsy.
Heart rate variability (HRV) is a useful tool for the detection of sympathetic-parasympathetic balance of autonomic nervous system in patients at risk of sudden death (SD). SD is more common in patients with epilepsy and the exact mechanisms of SD are unknown. Autonomic nervous system involvement in patients with epilepsy has rarely been studied and has shown conflicting results. Our purpose was to determine if HRV showed any changes in patients with epilepsy in comparison with normal population. A short period analysis of HRV was performed for both the frequency and time domain in 43 epilepsy patients who had generalized tonic-clonic seizures (GTCS) and who were not taking any medications and also in 43 age and sex matched controls. In the time domain analysis, patients displayed higher SDNN (standard deviation of all R-R intervals), SDANN (standard deviation of mean NN intervals in 5 min recordings) and HRV triangular index than did healthy subjects (p < 0.0001). Patients tended to display higher pNN50 (number of R-R intervals differed by > 50 ms from adjacent interval divided by the total number of all R-R intervals) and RMSSD (root-mean-square of successive differences) values than did healthy subjects, but the differences were not statistically significant (p > 0.05). In the frequency domain analysis, the spectral measures of HRV showed a reduction of high frequency (HF) values (is a marker of parasympathetic activity) and an increase of low frequency (LF) values (is a measure of sympathetic activity); as a result, the ratio between low and high frequencies (LF/HF) was significantly increased (p < 0.0001, p < 0.0001 and p < 0.001, respectively). Our data suggests an increase in the sympathetic control of the heart rate in epilepsy patients who have GTCS. This increased sympathetic activity could play a key role in the development of ventricular tachyarrhythmias in patients with epilepsy and may be related to the higher incidence of sudden death in this disorder as compared to controls.


Evaluating the impact of trigeminal neuralgia.
Patients with idiopathic trigeminal neuralgia (TN) were categorised into 3 subtypes (n = 225). Group 1 (n = 155, 68.9%) had TN without concomitant pain, group 2 (n = 32, 14.2%) had TN with intermittent concomitant pain, and group 3 (n = 39, 16.9%) had TN with autonomic symptoms. We tested 2 hypotheses: (1) that different pain profiles would be associated with the different groups; (2) that the severe pain associated with TN would impact negatively on activities of daily living and thereby result in disability as defined by the World Health Organisation. A different pain profile was found across the groups. We obtained unequivocal evidence that TN causes disability with up to 45% of patients being absent from usual daily activities 15 days or more in the past 6 months. On the Hospital Anxiety and Depression Scale, 35.7% patients had mild-to-severe depression and over 50% were anxious. The Pain Catastrophizing Scale showed that 78% of patients had considerable negative thoughts with scores >20 and a mean score of 36.4. Prior to referral, only 54% had been prescribed carbamazepine while opioids had been prescribed in 14.6% of the patients. Prior to referral, over 80% had already been to 1 specialist centre which had not provided appropriate management. Patients with TN report varied characteristics but all result in some degree of psychosocial disability especially before adequate therapy is attained.


Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.
The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemiologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease.


Differential effects of aging on dendritic spines in visual cortex and prefrontal cortex of the rhesus monkey.
Aging decreases the density of spines and the proportion of thin spines in the non-human primate (NHP) dorsolateral prefrontal cortex (dlPFC). In this study, we used confocal imaging of dye-loaded neurons to expand upon previous results regarding the effects of aging on spine density and morphology in the NHP dlPFC and compared these results to the effects of aging on pyramidal neurons in the primary visual cortex (V1). We confirmed that spine density, and particularly the density of thin spines, decreased with age in the dlPFC of rhesus monkeys. Furthermore, the average head diameter of non-stubby spines in the dlPFC was a better predictor than chronological age of the number of trials required to reach criterion on both the delayed response test of visuospatial working memory and the delayed nonmatching-to-sample test of recognition memory. By contrast, total spine density was lower on neurons in V1 than in dlPFC, and neither total spine density, thin spine density, nor spine size in V1 was affected by aging. Our results highlight the importance and selective vulnerability of dlPFC thin spines for optimal prefrontal-mediated cognitive function. Understanding the nature of the selective vulnerability of dlPFC thin spines as compared to the resilience of thin spines in V1 may be a promising area of research in the quest to prevent or ameliorate age-related cognitive decline.


Impact of foot-and-mouth disease on milk production on a large-scale dairy farm in Kenya.
The economic impact of foot-and-mouth disease (FMD) has been poorly characterised particularly in endemic settings where such knowledge is important for decision-making on disease control with limited resources. In order to address this, a study was designed using individual animal data from a large-scale dairy farm in Kenya to estimate the impact of an FMD outbreak due to serotype SAT2 virus on milk yield. Daily milk yields from 218 mainly European-breed cattle that were lactating during the 29-day outbreak period were considered in the analysis. At the herd level, the average daily yields decreased from around 20 to 13kg per cow, recovering approximately 2 months after the commencement of the outbreak. Generalised estimating equations (GEE) and an autoregressive correlation matrix were used to compare yields of reported clinical FMD cases and non-cases. No difference was found between reported clinical and non-clinical cases suggesting inaccurate case recording, poor sensitivity of the case definition and subclinical infections being present. To further investigate the impact of FMD, yields were predicted for each individual animal based on historic data from the same herd using a similar GEE approach. For cattle lactating during the outbreak, comparisons were made between actual and predicted yields from the commencement of the outbreak to 305 days lactation using a linear regression model. Animals produced significantly less than predicted if in parity 2 or greater and between 0 and 50 days in milk (DIM) at the start of the outbreak period. The maximum effect was seen among animals in parity ≥4 and between 0 and 50 DIM at the start of the outbreak, producing on average 688.7kg (95%CI 395.5, 981.8) less milk than predicted for their remaining lactation, representing an average 15% reduction in the 305 day production for these animals. Generalisation of the results requires caution as the majority of Kenyan milk is produced in smallholder farms. However, such farms use similar genetics and feeding practices to the study farm, and such systems are increasingly important in the supply of milk globally. These results make an important and unique contribution to the evidence base on FMD impact among dairy cattle in an endemic setting.


Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.
The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.


Systemic lupus erythematosus: nurse and patient education.
Systemic lupus erythematosus (lupus) is an autoimmune disease in which the immune system attacks healthy cells, tissue and organs, including the skin, kidney, heart, lungs, brain, joints and blood vessels. Symptoms of lupus vary between patients. The most common symptoms include unexplained fever, skin rash, swollen or painful joints, fatigue and kidney problems. Lupus can be treated effectively, but there is presently no cure for the condition. People with lupus may experience periods of exacerbation of symptoms, which are termed 'flares', as well as periods of remission. Nurses need to have a good understanding of the disease to provide patients with appropriate support and advice about how to maintain wellbeing and lead active lives.


Computational studies on the resistance of penicillin-binding protein 2B (PBP2B) of wild-type and mutant strains of Streptococcus pneumoniae against β-lactam antibiotics.
Mutations within transpeptidase domain of penicillin-binding protein 2B of the strains of Streptococcus pneumoniae leads to resistance against β-lactam antibiotics. To uncover the important residues responsible for sensitivity and resistance, the recently determined three dimensional structures of penicillin-binding protein 2B of both wild-type R6 (sensitive) and mutant 5204 (resistant) strains along with the predicted structures of other mutant strains G54, Hungary19A-6 and SP195 were considered for the interaction study with β-lactam antibiotics using induced-fit docking of Schrödinger. Associated binding energies of the complexes and their intermolecular interactions in the binding site clearly show that the wild-type R6 as sensitive, mutant strains 5204 and G54 as highly resistant, and the mutant strains Hungary19A-6 and SP195 as intermediate resistant. The study also reveals that the mutant strains Hungary19A-6 and SP195 exhibit intermediate resistant because of the existence of mutations till the intermediate 538th and 516th positions, respectively, and not till the end of the C-terminus. Furthermore, our investigations show that if the mutations are extended till the end of the C terminus, then the antibiotic resistance of induced-mutated strains increases from intermediate to high as in the strains 5204 and G54. The binding patterns obtained in the study are useful in designing potential inhibitors against multidrug resistant S. pneumoniae.


A clinical, neurolinguistic, and radiological study of a Chinese follow-up case with primary progressive aphasia.
Primary progressive aphasia (PPA) is a progressive neurodegenerative disorder characterized by the deterioration of language functions. The Han language bears some unique features from the Latin languages; however, the features of PPA in the Han language-speaking population are not well understood. In this study, we performed a 3-year follow-up on a Han language-speaking PPA patient with corresponding changes in magnetic resonance imaging (MRI). During the early stage, linguistic analysis revealed several symptoms including difficulty with auditory comprehension, right-left disorientation, reading disorders, and agraphia, specifically the execution of serial oral instructions. This Chinese PPA patient presented with a reading disorder, but his word comprehension ability remained intact. There are two different possible modalities of incorrect writing in this case. The patient also presented with noun-verb double dissociation. The early-stage MRI showed atrophy of the left frontal lobe, which was most severe in the inferior frontal gyrus. Three years later, the patient was found to have progressive atrophy in the parietal, frontal, and temporal lobes, among which the frontal lobe remained the most severely affected region. The brain imaging of the Chinese-speaking PPA patient showed changes similar to those of a Latin language-speaking PPA patient. The prominent change was asymmetrical atrophy in the frontal and temporal lobes. This is the first report of noun-verb double dissociation existing in a Chinese-language speaking PPA patient. The dissociation may be related to an impaired function of the inferior frontal gyrus, which is likely associated with verb-naming in Chinese-speaking people. Several unique features were observed in this case, including impairment in writing ability.


Thyroid function in postmenopausal women with breast cancer on tamoxifen.
In 42 postmenopausal women with breast cancer, aged 48-85 years (mean age 62.4 years) serum thyroid hormone concentrations were measured before and after 6 months of tamoxifen therapy (20 mg daily). In particular triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroxine-binding globulin (TBG) and thyroid-stimulating hormone (TSH) concentrations before and 30 minutes after thyrotrophin-releasing hormone (TRH) administration (200 microg i.v.) were measured before and 6 months after tamoxifen therapy. T3 and T4 concentrations increased significantly (p<0.001 and p<0.05, respectively) whereas FT3 and FT4 remained unchanged (p>0.05), TBG increased significantly (p<0.001) and basal TSH concentrations as well as TSH response to TRH injection increased significantly (p<0.05) after tamoxifen therapy. It is concluded that tamoxifen administration changes thyroid hormone concentrations. However free thyroid hormone levels remain unchanged and the patients remain euthyroid after long-term tamoxifen therapy.


Reported speech in individuals with Down syndrome: First evidence.
Narratives are enriched by taking the perspective of the protagonists, which can be expressed using reported speech. Nevertheless, the use of reported speech is unaddressed internationally among individuals with Down syndrome. Narratives of 28 children and adolescents with Down syndrome were collected using a non-verbal picture book. Occurrence and forms of reported speech were analysed and compared to typically-developing children (TD; n = 33). Participants from both populations use reported speech in their narratives with a comparable proportion. Nevertheless, differences appear concerning forms of direct speech with persons with Down syndrome using more free direct speech than TD-children. The results suggest that children and adolescents are able to implement the use of reported speech regardless of their syntactic impairments. Concerning the occurring forms of direct speech, the results might point to cognitive impairments that manifest in limited consideration of the interlocutor's knowledge.


Frequency and severity of the symptoms of irritable bowel syndrome across the anxiety disorders and depression.
High rates of irritable bowel syndrome (IBS) symptoms have been reported in individuals diagnosed with anxiety and depressive disorders. However, most studies have investigated these relations in a single disorder, rather than a heterogeneous group of patients, thereby not allowing for comparisons across anxiety disorders and depression, or for considering the effects of comorbidity. Thus, the present study investigated the symptoms of IBS in a diverse group of patients (N=357) by administering questionnaires and a diagnostic interview. A high frequency of IBS symptoms was found in patients with panic disorder, generalized anxiety disorder, and major depressive disorder. However, the frequency of IBS symptoms in patients with social anxiety disorder, specific phobia, and obsessive-compulsive disorder was comparable to rates found in community samples. In addition, anxiety sensitivity and illness attitudes and intrusiveness were predictive of elevated IBS symptomatology. Together, these findings emphasize the role physiological symptoms of anxiety and worry in the co-occurrence of the anxiety disorders and IBS.


Christian and Political Conservatism Predict Opposition to Sexual and Gender Minority Rights through Support for Christian Hegemony.
Although significant strides have been made for sexual and gender minority (SGM) rights in the United States, there continues to be opposition to SGM rights from many conservative Christians and political conservatives. In this study, we investigate this opposition by examining support for Christian hegemony (i.e., the idea that Christianity should be the norm and Christians should be in power in the United States) and unawareness of Christian privilege (i.e., unearned advantages for Christians) as religiopolitical variables that help to explain the association between Christian and political conservatism and opposition to a host of SGM rights (same-sex marriage, same-sex adoption, nondiscrimination policies in jobs and housing for SGMs, and bills regarding transgender public bathroom use). Based on structural equation modeling analysis with heterosexual cisgender Christian (n = 688) and Areligious (n = 327) students, we demonstrate that support for Christian hegemony and unawareness of Christian privilege help to explain the association between Christian and political conservatism and opposition to SGM rights. These findings advance our understanding of a new type of religious-based variable focused on religious power and privilege to help understand conservative religious and political opposition to SGM rights. Limitations, implications, and directions for future research also are discussed.


Phthalate exposure and human semen parameters.
There is scientific and public concern about commonly used chemicals, including phthalates, that are associated with reproductive toxicity in laboratory animals and are hormonally active. People are exposed to phthalates through diet, consumer products and medical devices. The present study explored whether environmental levels of phthalates are associated with altered semen quality in humans. We recruited 168 men who were part of subfertile couples and who presented to the Massachusetts General Hospital andrology laboratory for semen analysis between January 2000 and April 2001. Semen parameters were dichotomized based on 1999 World Health Organization reference values for sperm concentration (< 20 million/ml) and motility (< 50% motile), as well as Tygerberg Strict criteria for morphology (< 4% normal). The comparison group was men for whom these semen parameters were all above the reference values. In urine, eight phthalate metabolites were measured with high-performance liquid chromatography and tandem mass spectrometry. Specific gravity-adjusted phthalate metabolite levels were categorized into tertiles. There was a dose-response relation between tertiles of mono-butyl phthalate and sperm motility (odds ratio per tertile = 1.0, 1.8, 3.0; P-value for trend = 0.02) and sperm concentration (1.0, 1.4, 3.3; P-value for trend = 0.07). In addition, there was a dose-response relation between tertiles of mono-benzyl phthalate and sperm concentration (1.0, 1.4, 5.5; P-value for trend = 0.02). There were dose-response relations for monobutyl phthalate and monobenzyl phthalate with one or more semen parameters, and suggestive evidence for monomethyl phthalate with sperm morphology. The lack of a relation for other phthalates may indicate a difference in spermatotoxicity among phthalates.


Synthesis of a new seleninic acid anhydride and mechanistic studies into its glutathione peroxidase activity.
Starting from low toxic salicyloylglycine, a new seleninic acid anhydride 7 that lacks SeN or SeO non-bonded interactions was synthesized. This compound exhibits a fourfold higher glutathione peroxidase-like (GPx-like) activity than ebselen and inhibits plant and mammalian 12/15-lipoxygenases at lower micromolar concentrations. Because of these pharmacological properties, 7 may constitute a new lead compound for the development of anti-inflammatory low-molecular-weight seleno-organic compounds. Analyzing the redox products of 7 with glutathione (GSH) and tBuOOH, we identified three potential catalytic cycles (A, B, C) of GPx-like activity that are interconnected by key metabolites. To study the relative contribution of these cycles to the catalytic activity, we prepared selected reaction intermediates and found that the activity of seleninic acid anhydride 7 and of the corresponding diselenide 11 and selenol 14 compounds were in the same range. In contrast, the GPx-like activity of monoselenide 9 was more than one order of magnitude lower. These data suggested that cycles A and B may constitute the major routes of GPx-like activity of 7, whereas cycle C may not significantly contribute to catalysis.


Ureteroarterial fistulas after radical pelvic surgery: pathogenesis, diagnosis, and therapeutic modalities.
Ureteroarterial fistulas (UAF) are a rare but potentially life-threatening complication of intra-abdominal malignancy, typically occurring after vascular or pelvic surgery. Patients with a history of radical pelvic surgery, chronic indwelling ureteral stents, and prior pelvic radiation appear to be at increased risk. The predisposing risk factors suggest that gynecological oncologists are the likely specialty to face this problem and should be familiar with the clinical presentation and etiology of UAF. We present two such cases to illustrate these salient points of clinical diagnosis and management.


The conduction system in double outlet right ventricle with subpulmonic ventricular septal defect and related hearts (the Taussig-Bing group).
The Taussig-Bind group of hearts is that group in which the aorta emerges completely from the right ventricle, unrelated to the position of the ventricular septal defect (VSD), while the pulmonary trunk emerges at varying degrees from the right ventricle related to the location of the VSD. Several types of surgical procedures involve the VSD in these hearts. The conduction systems in six of these hearts were therefore studied. The atrioventricular (A-V) bundle lies in the inferior (posterior) wall of the defect on the left side beneath the summit of the ventricular septum. In some cases, the bundle may be proximal to the defect, thus lying intramuscularly, and only the right and left bundle branches are related to the defect. The pattern od development of the atrioventricular (A-V) node, bundle and bundle branches is related primarily to the development of the endocardial cushions and posterior ventricular septum, and not to that of the absorption of the bulbus.


[C-H Functionalization by Transition-metal-catalyst or in Situ Generated Base].
Direct functionalization of the C-H bond is a highly attractive method because it does not require any pre-functionalized starting materials. Therefore this method can be adopted to attain the atom- and step-economic synthesis of organic compounds. We recently developed novel C-H functionalization reactions using two strategies. The first strategy is transition-metal catalyzed C-H functionalization, which comprises the copper-catalyzed oxidative C(sp3)-H functionalization of 2-alkyl-N-arylbenzamides for the synthesis of N-aryl-isoindolinones. This method can be applied to various substituted substrates and the synthesis of bioactive compounds, indoprofen and DWP205190. It provides an efficient approach toward the construction of isoindolinone skeletons. The second strategy is an in situ generated base-mediated C-H functionalization comprising the deprotonative silylation of C(sp)-H and C(sp2)-H bonds by the base generated in situ from trifluoromethyltrimethylsilane (CF3SiMe3) and its activator. In the C(sp)-H silylation of terminal alkynes, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) acts as both a solvent and activator; therefore no additional activator is required. Moreover, the preferential deprotonation of terminal alkynes using this system proceeds faster than the trifluoromethylation of ketones and esters.


Uncertainties of spectral in situ measurements in wastewater using different calibration approaches.
Three calibration methods were applied to UV/VIS spectra recorded in the influent of six wastewater treatment plants (WWTPs) to measure total COD (CODtot), filtered COD (CODfil), nitrate and nitrite nitrogen (NO(x)-N) and total suspended solids (TSS). It could be shown that a calibration of the sensor using data sets from four Swiss WWTPs leads to an improvement of the precision in comparison to the global calibration provided by the manufacturer. A calibration to the specific wastewater matrix always improves the results and gives the highest accuracy. For CODtot a mean coefficient of variation CVx of 12.5% could be reached, whereas for NOx-N only weak results were achieved (average CVx = 36%).


Interactions between physicians and pharmaceutical sales representatives in Saudi Arabia.
Interaction between physicians and pharmaceutical sales representative (PR) is a major component of the promotional activities by pharmaceutical companies. The lack of studies examining the magnitude of this interaction in Saudi Arabia is evident. The objective of this study is to estimate the magnitude and associated characteristics of physician-PR interaction. A cross-sectional study was conducted among physicians working in the different regions of Saudi Arabia between March and July of 2012. A cross-sectional study was undertaken between March and July of 2012 in the different regions of Saudi Arabia. A self-administrated questionnaire was developed and handed to all participants, both in paper and electronic formats. A total of 663 participants completed the questionnaire. The participation rate was 66.3% (663/1000). The majority of the participants (72.9%) reported interaction with PRs. This was lower among residents/interns compared to higher ranking employees (55.6% vs 83.6%, P < .001). Approximately half (48.3%) of the interactions occurred at a rate of more than once a month. A majority of the participants (72.1%) occasionally accepted gifts such as stationery (57%), drug samples (54%), meals (38%), and sponsorship of educational activities (30%). The following characteristics were independently associated with physician-PR interaction: non-Saudi nationals, a higher monthly income, Western medical education, working in a private hospital, being a specialist or registrar (rather than resident or intern), working on certain specialties (such as psychiatry and family medicine), and having limited number of patients with high socioeconomic status. Although lower than seen in many parts of the world, a high prevalence of physician-PR inter.action in Saudi hospitals is reported. Delineating associated characteristics may assist with future interventions. Further research should focus on ethical, clinical, prescription, and economic impact of interaction as well as determining the best strategy to reduce negative impact.


p53-Dependent anticancer effects of leptomycin B on lung adenocarcinoma.
Leptomycin B (LMB) and/or its derivatives are considered a novel class of cancer therapeutics through blocking chromosome maintenance region 1, which mediates p53 nuclear export. The objectives of the present study were to first evaluate the cytotoxic effects of LMB on a normal human lung epithelial cell line (BEAS-2B) and three human lung adenocarcinoma cell lines with various p53 status (wild type: A549, mutant: NCI-H522, and null: NCI-H358) and then to identify LMB-induced gene expression alterations in human p53 signaling pathway. Cells were treated with 0.01-100 nM LMB or 0.1% ethanol (vehicle control) for 4-72 h. Gene expression analyses using gene array for 84 genes involved in p53-mediated signaling pathways were performed in A549 and NCI-H358 after treatment with 20 nM LMB or vehicle control for 24 h. Cytotoxic results from MTS assays revealed a significant dose- and time-dependent effect of LMB on all cell lines. However, this effect was more pronounced in cancer cells than in normal cells, and cancer cells with p53 wild type tended to be less sensitive than those with p53 mutant or null. A total of 23 genes, predominantly involved in apoptosis and cell cycle/proliferation, were significantly altered in A549 after LMB treatment, while no strong modulating effects were observed in NCI-H358. The protein expression of two selected genes, p21 and survivin, was further confirmed by Western blots. Our results suggest that LMB has anti-cancer potential and provides a new regimen of individualized therapy for lung cancer treatment.


Extended Length of Stay After Lumbar Spine Surgery: Sick Patients, Postoperative Complications, or Practice Style Differences Among Hospitals and Physicians?
The degree to which extended length of stay (LOS) after surgery represents patient illness or postoperative complications is unknown. The aim of this study was to investigate the influence of postoperative complications and patient comorbidities on variance in extended length of hospital stay after lumbar spine surgery. Data from the American College of Surgeons National Surgical Quality Improvement Program were analyzed from January 1, 2008, through December 31, 2014. Study participants were 23,102 patients undergoing a 1-level or 2-level lumbar decompression and fusion procedure. Multivariable logistic regression analysis was used to determine the odds ratio for risk-adjusted extended length of hospital stay, defined as patients with a hospital stay greater than the 75th percentile (LOS >5 days) for the cohort. The primary outcome was the extent to which extended LOS represented preoperative patient illness or postoperative complications. Of 23,102 participants, 3794 (16.42%) had extended LOS. Most patients (2849 patients; 75.10%) with extended LOS did not have a documented postoperative complication. Only a minority of patients with extended LOS had a history of comorbidities known to influence outcomes in patients undergoing spine surgery, including diabetes (24%), chronic obstructive pulmonary disease (7%), congestive heart failure (0.69%), myocardial infarction (0.20%), acute renal failure (0.26%), and stroke (2.23%). This study suggests that much of the variation in LOS after lumbar spine surgery is not attributable to baseline patient illness or complications and most likely represents differences in practice style or surgeon preference.


Development of a Shock and Detonation Velocity Measurement System Using Chirped Fiber Bragg Gratings.
Dynamic measurements of shock and detonation velocities are performed using long chirped fiber Bragg gratings (CFBGs). Such thin probes, with a diameter of typically 125 µm or even 80 µm can be directly inserted into high-explosive (HE) samples or simply glued laterally. During the detonation, the width of the optical spectrum is continuously reduced by the propagation of the wave-front, which physically shortens the CFBG. The light power reflected back shows a ramp-down type signal, from which the wave-front position is obtained as a function of time, thus yielding a detonation velocity profile. A calibration procedure was developed, with the support of optical simulations, to cancel out the optical spectrum distortions from the different optical components and to determine the wavelength-position transfer function of the CFBG. The fitted slopes of the X-T diagram give steady detonation velocity values which are in very good agreement with the classical measurements obtained from discrete electrical shorting pins (ESP). The main parameters influencing the uncertainties on the steady detonation velocity value measured by CFBG are discussed. To conclude, different HE experimental configurations tested at CEA (Commissariat à l'Energie Atomique et aux Energies Alternatives) are presented: bare cylindrical sticks, wedges for shock-to-detonation transitions (SDT), spheres, a cast-cured stick around a CFBG, and a detonation wave-front profile configuration.


Revisiting the thermodynamic modelling of type I gas-hydroquinone clathrates.
Under specific pressure and temperature conditions, certain gaseous species can be engaged in a host lattice of hydroquinone molecules, forming a supramolecular entity called a gas hydroquinone clathrate. This study is devoted to the thermodynamic modelling of type I hydroquinone clathrates. The gases considered in this work are argon, krypton, xenon, methane, nitrogen, oxygen and hydrogen sulphide. The basic van der Waals and Platteeuw model, which is, for example, not able to predict well the phase equilibrium properties of such clathrates at high temperature, is modified and extended by considering first the solubility of the guest in solid HQ and then the mutual interactions between the gaseous molecules inside the clathrate structure (i.e. guest-guest interactions). Other improvements of the basic theory, such as the choice of the reference state, are proposed, and a unique set of thermodynamic parameters valid for all the studied guests are finally calculated. Very good agreement is obtained between the model predictions and the experimental data available in the literature. Our results clearly demonstrate that the highest level of theory is necessary to describe well both the triphasic equilibrium line (where the HQ clathrate, the native hydroquinone HQα and the gas coexist), the occupancy of the guest in the clathrate, and the intercalation enthalpy.


Psycho-education to enhance couples' transition to parenthood.
A substantial proportion of couples struggle to adapt to parenthood, feel stress in caring for their infant, and experience a significant decline in their couple relationship adjustment. Moreover, there is a substantial association between effective parenting of infants and sustaining a mutually satisfying couple relationship. This paper reviews randomized controlled trials of psycho-education to assist new parent couples with parenting and their couple relationship. The majority of programs target either the couple relationship or parenting, with few programs addressing both areas. The best outcomes seem to be achieved when programs are accessible by couples at home, when skill-training is provided, and possibly when programs target couples at high-risk of maladjustment to parenthood.


Non-breath-hold high b-value diffusion-weighted MRI with parallel imaging technique: apparent diffusion coefficient determination in normal abdominal organs.
To detect apparent diffusion coefficient (ADC) values in normal abdominal organs using non-breath-hold high b-value diffusion-weighted magnetic resonance imaging (DW-MRI) with a parallel imaging technique. A total of 50 patients with normal abdominal MRI findings were retrospectively enrolled. DW-MRI was performed with b-factors of 0, 500, and 1000 s/mm(2). Mean ADC measurements were calculated. There were statistically significant differences (P < 0.001) between the ADC values of four liver segments (left lobe lateral segment: 1.77 +/- 0.21 x10(-3) mm(2)/s, left lobe medial segment: 1.59 +/- 0.21 x 10(-3) mm(2)/s, right lobe anterior segment: 1.46 +/- 0.18 x 10(-3) mm(2)/ s, right lobe posterior segment: 1.34 +/- 0.20 x 10(-3) mm(2)/s). The ADC value for the left lobe lateral segment was significantly higher than the values for the other segments. The calculated ADC values for cortex and medulla of kidney were 2.08 +/- 0.22 x 10(-3) mm(2)/ s, 1.94 +/- 0.18 x 10(-3) mm(2)/s, respectively; (P < 0.001), for pancreas tail 1.59 +/- 0.38 x 10(-3) mm(2)/s, for pancreas body 1.68 +/- 0.26 x 10(-3) mm(2)/s, pancreas head 1.65 +/- 0.29 x 10(-3) mm(2)/s, stomach wall 1.84 +/- 0.22 x 10(-3) mm(2)/s, and spleen 1.28 +/- 0.38 x 10(-3) mm(2)/s. Knowledge of ADC values for normal abdominal organs will be required during quantitative evaluation of DW-MR images in diseases in accordance with the technique used. We believe that further studies investigating the effect of diseases on normal ADC values are necessary and would be helpful in quantitative DWI.


Development of mandibular, hyoid and hypobranchial muscles in the zebrafish: homologies and evolution of these muscles within bony fishes and tetrapods.
During vertebrate head evolution, muscle changes accompanied radical modification of the skeleton. Recent studies have suggested that muscles and their innervation evolve less rapidly than cartilage. The freshwater teleostean zebrafish (Danio rerio) is the most studied actinopterygian model organism, and is sometimes taken to represent osteichthyans as a whole, which include bony fishes and tetrapods. Most work concerning zebrafish cranial muscles has focused on larval stages. We set out to describe the later development of zebrafish head muscles and compare muscle homologies across the Osteichthyes. We describe one new muscle and show that the number of mandibular, hyoid and hypobranchial muscles found in four day-old zebrafish larvae is similar to that found in the adult. However, the overall configuration and/or the number of divisions of these muscles change during development. For example, the undivided adductor mandibulae of early larvae gives rise to the adductor mandibulae sections A0, A1-OST, A2 and Aomega, and the protractor hyoideus becomes divided into dorsal and ventral portions in adults. There is not always a correspondence between the ontogeny of these muscles in the zebrafish and their evolution within the Osteichthyes. All of the 13 mandibular, hyoid and hypobranchial muscles present in the adult zebrafish are found in at least some other living teleosts, and all except the protractor hyoideus are found in at least some extant non-teleost actinopterygians. Of these muscles, about a quarter (intermandibularis anterior, adductor mandibulae, sternohyoideus) are found in at least some living tetrapods, and a further quarter (levator arcus palatini, adductor arcus palatini, adductor operculi) in at least some extant sarcopterygian fish. Although the zebrafish occupies a rather derived phylogenetic position within actinopterygians and even within teleosts, with respect to the mandibular, hyoid and hypobranchial muscles it seems justified to consider it an appropriate representative of these two groups. Among these muscles, the three with clear homologues in tetrapods and the further three identified in sarcopterygian fish are particularly appropriate for comparisons of results between the actinopterygian zebrafish and the sarcopterygians.


Evaluation of education on the appropriate use of vitamin k in warfarin reversal in adult inpatients.
Vitamin K (phytonadione) is a commonly used first-line reversal agent for vitamin K antagonist (VKA) therapy in patients presenting with a supratherapeutic international normalized ratio (INR) with or without significant bleeding or in patients with a therapeutic INR in need of surgery. The purpose of this study was to determine the impact of education on the appropriate use of vitamin K for VKA reversal. Data were collected on patients admitted to a community teaching hospital during February 2010 (pre-education group). These data were analyzed to determine the most common guideline deviations in vitamin K use. Following this analysis, pharmacist education took place in the form of in-service presentations; a protocol, including a guideline-based dosing table, was developed to assist pharmacists in evaluating vitamin K therapy. Data were then collected on patients admitted during February 2011 (post-education group). Forty patients and 47 vitamin K administrations were included in the pre-education group, and 34 patients and 49 vitamin K administrations were included in the post-education group. The number of patients with appropriate vitamin K administrations improved after pharmacist education (25% pre-education vs 55.8% post-education; P = .01). Whereas 27.6% of individual vitamin K administrations were appropriate in the pre-education group, this increased to 63.2% in the post-education group (P = .04). Education techniques on the appropriate use of vitamin K for VKA reversal significantly improved compliance with standards of care for proper use of vitamin K. Additional education sessions are necessary to further increase compliance with standards of care and subsequently optimize patient care.


Neural evidence for defective top-down control of visual processing in Parkinson's and Alzheimer's disease.
We used a functional MRI paradigm involving conventional vs. unconventional views of objects to assess bottom-up vs. top-down visual processing in Parkinson's disease (PD) with normal cognition, PD with mild cognitive impairment (MCI), and MCI due to Alzheimer's disease (AD) as compared to healthy controls. We particularly aimed at determining whether the task discriminated between PD with and without MCI and between two MCI groups due to distinct pathologies (AD and PD). 116 right-handed subjects (21 MCI due to AD; 16 PD with normal cognition; 24 PD with MCI; 55 healthy controls) performed a visual object-matching task in a T MR scanner. T statistic maps were computed to contrast task-based activation during unconventional vs. conventional view conditions. One-way ANOVAs and post hoc tests were performed to assess differences across and between groups. Both MCI groups performed worse than controls in the unconventional views condition and showed reduced activation of right anterior cingulate cortex and right superior parietal lobule (PD with MCI), and right middle and inferior frontal gyri (MCI due to AD). Neural responses in cortical areas within the ventral and dorsal visual pathway appeared to be preserved in both MCI groups. Receiver operating characteristic analysis of MRI contrast in the right superior parietal lobule distinguished PD with and without MCI with 87.50% sensitivity and 86.98% specificity. Impaired recognition of objects presented in unconventional orientations in MCI due to PD and AD was associated with decreased activation of frontoparietal regions, consistent with defective top-down regulation of visual processing. Aberrant activation of superior parietal cortex may serve as an early imaging biomarker of impending cognitive impairment in PD.


A framework for integration of heterogeneous medical imaging networks.
Medical imaging is increasing its importance in matters of medical diagnosis and in treatment support. Much is due to computers that have revolutionized medical imaging not only in acquisition process but also in the way it is visualized, stored, exchanged and managed. Picture Archiving and Communication Systems (PACS) is an example of how medical imaging takes advantage of computers. To solve problems of interoperability of PACS and medical imaging equipment, the Digital Imaging and Communications in Medicine (DICOM) standard was defined and widely implemented in current solutions. More recently, the need to exchange medical data between distinct institutions resulted in Integrating the Healthcare Enterprise (IHE) initiative that contains a content profile especially conceived for medical imaging exchange: Cross Enterprise Document Sharing for imaging (XDS-i). Moreover, due to application requirements, many solutions developed private networks to support their services. For instance, some applications support enhanced query and retrieve over DICOM objects metadata. This paper proposes anintegration framework to medical imaging networks that provides protocols interoperability and data federation services. It is an extensible plugin system that supports standard approaches (DICOM and XDS-I), but is also capable of supporting private protocols. The framework is being used in the Dicoogle Open Source PACS.


Montelukast Has no Impact on the Systemic Production of TGFβ-1 in Patients with Nasal Polyposis Associated with Aspirin Intolerance.
Introduction Nasal polyposis is a disease characterized by a mechanical dysfunction of the nasal mucosa, closely related to the unique makeup of its extracellular matrix, which develops as the result of an anomalous tissue remodeling process. Transforming growth factor beta 1 (TGF-β1) is reduced not only in the nasal polypoid tissue, but also in the plasma of aspirin-intolerant patients. These patients exhibit an imbalance in the production of eicosanoids characterized by an increase in leukotrienes. Thus, it is important that the relationship between the production of leukotrienes and TGF-β1 be assessed. Objective To evaluate the effects of the cysteinyl leukotriene (CysLT) receptor antagonist montelukast on the systemic production of TGF-β1 in patients with nasal polyposis, with or without concomitant aspirin intolerance. Methods The sample comprised 48 individuals with diagnosis of nasal polyposis and 15 healthy controls for comparison of the baseline TGF-β1 levels in the peripheral blood and after treatment with CysLT receptor antagonist montelukast in the nasal-polyposis group. Results There was no difference in the change in TGF-β1 levels after the treatment with montelukast in the subgroup of patients with polyposis and asthma ( p = 0.82) and in the subgroup with polyposis, asthma, and aspirin intolerance ( p = 0.51). Conclusion we found no impact of the therapy with a leukotriene receptor blocker on the production of TGF-β1, making the antileukotriene therapy a highly questionable choice for the treatment of nasal polyposis, particularly from the standpoint of seeking to modify the remodeling process in this disease.


Multiple Chronic Conditions among Seriously Ill Adults Receiving Palliative Care.
The objective of this study was to characterize multiple chronic conditions (MCCs) among seriously ill adults receiving palliative care at the end of life. A latent class analysis was conducted to identify latent subgroups of seriously ill older adults based on a baseline Charlson comorbidity index (CCI) measurement, a measure of comorbidity burden, and mortality risk. The three latent subgroups were: (1) low to moderate CCI with MCC, (2) high CCI with MCC, and (3) high CCI and metastatic cancer. The "low to moderate CCI and MCC" subgroup included older adults with chronic obstructive pulmonary disease (COPD), cardiovascular disease, congestive heart failure, myocardial infarction, dementia, diabetes, and lymphoma. A "high CCI and MCC" subgroup included individuals with severe illness including liver or renal disease among other MCCs. A "high CCI and metastatic cancer" included all participants with metastatic cancer. This study sheds light on the MCC profile of seriously ill adults receiving palliative care.


The complete genome sequence of Colwellia sp. NB097-1 reveals evidence for the potential genetic basis for its adaptation to cold environment.
Colwellia sp. NB097-1, isolated from a marine sediment sample from the Bering Sea, is a psychrophilic bacterium whose optimal and maximal growth temperatures were 13 and 25°C, respectively. Here, we present the complete genome of Colwellia sp. NB097-1, which was 4,661,274bp in length with a GC content of 38.5%. The genome provided evidence for the potential genetic basis for its adaptation to a cold environment, such as producing compatible solutes and cold-shock proteins, increasing membrane fluidity and synthesizing glycogen. Some cold-adaptive proteases were also detected in the genome of Colwellia sp. NB097-1. Protease activity analysis further showed that extracellular proteases of Colwellia sp. NB097-1 remained active at low temperatures. The complete genome sequence may be helpful to reveal how this strain survives at low temperature and to find cold-adaptive proteases that may be useful to industry.


Identification and characterization of a new beta-casein variant in goat milk by high-performance liquid chromatography with electrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry.
A new variant of beta-casein was detected in the casein fraction obtained from milk of a goat belonging to an autochthonous breed of southern Italy, "Argentata dell'Etna". Reversed-phase high-performance liquid chromatography/electrospray ionization mass spectrometry (RP-HPLC/ESI-MS) analysis indicated that the new beta-casein variant, here named D, has a M(r) 15 Da higher than that of variant C previously described. The modification in the amino acid sequence responsible for the 15 Da difference in M(r) between variants C and D was determined by coupling trypsin digestion with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and RP-HPLC/ESI-MS, and it was demonstrated that it is due to the point mutation Val(207) --> Asn(207). The phosphorylation pattern of the new variant D was shown to be identical to that of variant C, as the protein shows two phosphorylation levels, 5 and 6P, occurring with comparable relative abundances. Ser35 was determined as one of the phosphorylation sites, whereas the others were probably analogous to those determined previously for the beta-Cn variant C, at Thr12 and Ser1517-19. The results reported here indicate that the combined use of RP-HPLC/ESI-MS, MALDI-TOFMS and MS/MS represents a powerful tool for the detection and characterization of minor components present in complex protein mixtures.


The Reach, Use, and Impact of a Free mHealth Mindfulness App in the General Population: Mobile Data Analysis.
As smartphones are now used by most Americans, it is increasingly possible for mental health mobile apps to be disseminated to the general public. However, little is known about how mobile mental health apps are used by the general population outside of a controlled research design. Our objective is to describe how the general population engages with Mindfulness Coach, an iOS- and Android-based app designed to deliver a mindfulness training course. Using anonymous download and analytics data, we characterized the reach, usage, retention, and impact of Mindfulness Coach. We included mobile analytics data from all unique downloads of Mindfulness Coach between August 1, 2018, and April 8, 2019 (N=104,067) as well as starred reviews from all Mindfulness Coach users who provided reviews of the app as of March 1, 2020. Mindfulness characteristics were measured by an in-app assessment using the Five-Facet Mindfulness Questionnaire-Short Form (FFMQ-SF). Users engaged, on average, in 4.3 visits to the app (SD 8.8; median 2; 90th percentile 8) and associated with an average total of 49.2 interactions with the app (ie, clicks within the app) (SD 113.8; median 19; 90th percentile 105). Users spent an average of 16.2 minutes (SD 63.1) engaged with the app over the full study time period. There were strong linear effects of app engagement on total FFMQ-SF scores. For example, FFMQ-SF scores were associated with more time spent engaged with the app (R2=.23; P<.001). Mindfulness Coach has been reviewed in the Google Play Store 3415 times, with an average rating of 4.7 out of 5 stars, and over 2000 times in the Apple App Store, with an average rating of 4.8 out of 5 stars. These findings suggest that Mindfulness Coach has achieved substantial and sustained reach in the general population; however, it was used less frequently by many downloaders than researchers and designers intended. There was a subpopulation of users who engaged in the app regularly over an extended period of time, and there was a clear relationship between app use and improvements in mindfulness. To strengthen Mindfulness Coach's public health impact, more research is needed to understand who is using the app and how, and to design strategies to increase user engagement in order for users to receive a larger dose of mindfulness treatment.


Clinicopathological features of genetically confirmed Danon disease.
Danon disease is due to primary deficiency of lysosome-associated membrane protein-2. To define the clinicopathologic features of Danon disease. The features of 20 affected men and 18 affected women in 13 families with genetically confirmed Danon disease were reviewed. All patients had cardiomyopathy, 18 of 20 male patients (90%) and 6 of 18 female patients (33%) had skeletal myopathy, and 14 of 20 male patients (70%) and one of 18 female patients (6%) had mental retardation. Men were affected before age 20 years whereas most affected women developed cardiomyopathy in adulthood. Muscle histology revealed basophilic vacuoles that contain acid phosphatase-positive material within membranes that lack lysosome-associated membrane protein-2. Heart transplantation is the most effective treatment for the otherwise lethal cardiomyopathy. Danon disease is an X-linked dominant multisystem disorder affecting predominantly cardiac and skeletal muscles.


Manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin acts as a pro-oxidant to inhibit electron transport chain proteins, modulate bioenergetics, and enhance the response to chemotherapy in lymphoma cells.
The manganese porphyrin, manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin (MnTE-2-PyP(5+)), acts as a pro-oxidant in the presence of intracellular H2O2. Mitochondria are the most prominent source of intracellular ROS and important regulators of the intrinsic apoptotic pathway. Due to the increased oxidants near and within the mitochondria, we hypothesized that the mitochondria are a target of the pro-oxidative activity of MnTE-2-PyP(5+) and that we could exploit this effect to enhance the chemotherapeutic response in lymphoma. In this study, we demonstrate that MnTE-2-PyP(5+) modulates the mitochondrial redox environment and sensitizes lymphoma cells to antilymphoma chemotherapeutics. MnTE-2-PyP(5+) increased dexamethasone-induced mitochondrial ROS and oxidation of the mitochondrial glutathione pool in lymphoma cells. The combination treatment induced glutathionylation of Complexes I, III, and IV in the electron transport chain, and decreased the activity of Complexes I and III, but not the activity of Complex IV. Treatment with the porphyrin and dexamethasone also decreased cellular ATP levels. Rho(0) malignant T-cells with impaired mitochondrial electron transport chain function were less sensitive to the combination treatment than wild-type cells. These findings suggest that mitochondria are important for the porphyrin's ability to enhance cell death. MnTE-2-PyP(5+) also augmented the effects of 2-deoxy-D-glucose (2DG), an antiglycolytic agent. In combination with 2DG, MnTE-2-PyP(5+) increased protein glutathionylation, decreased ATP levels more than 2DG treatment alone, and enhanced 2DG-induced cell death in primary B-ALL cells. MnTE-2-PyP(5+) did not enhance dexamethasone- or 2DG-induced cell death in normal cells. Our findings suggest that MnTE-2-PyP(5+) has potential as an adjuvant for the treatment of hematologic malignancies.