Postoperative Transfusions after Administration of Delayed Cold-stored Platelets versus Room Temperature Platelets in Cardiac Surgery: A Retrospective Cohort Study.
Delayed cold storage of room temperature platelets may extend shelf life from 5 to 14 days. The study hypothesized that the use of delayed cold-stored platelets in cardiac surgery would be associated with decreased postoperative platelet count increments but similar transfusion and clinical outcomes compared to room temperature-stored platelets. This is an observational cohort study of adults transfused with platelets intraoperatively during elective cardiac surgery between April 2020 and May 2021. Intraoperative platelets were either room temperature-stored or delayed cold-stored based on blood bank availability rather than clinical features or provider preference. Differences in transfusion and clinical outcomes, including a primary outcome of allogenic transfusion exposure in the first 24 h postoperatively, were compared between groups. A total of 713 patient encounters were included: 529 (74%) room temperature-stored platelets and 184 (26%) delayed cold-stored platelets. Median (interquartile range) intraoperative platelet volumes were 1 (1 to 2) units in both groups. Patients receiving delayed cold-stored platelets had higher odds of allogeneic transfusion in the first 24 h postoperatively (81 of 184 [44%] vs. 169 of 529 [32%]; adjusted odds ratio, 1.65; 95% CI, 1.13 to 2.39; P = 0.009), including both erythrocytes (65 of 184 [35%] vs. 135 of 529 [26%]; adjusted odds ratio, 1.54; 95% CI, 1.03 to 2.29; P = 0.035) and platelets (48 of 184 [26%] vs. 79 of 529 [15%]; adjusted odds ratio, 1.91; 95% CI, 1.22 to 2.99; P = 0.005). There was no difference in the number of units administered postoperatively among those transfused. Platelet counts were modestly lower in the delayed cold-stored platelet group (-9 × 109/l; 95% CI, -16 to -3]) through the first 3 days postoperatively. There were no significant differences in reoperation for bleeding, postoperative chest tube output, or clinical outcomes. In adults undergoing cardiac surgery, delayed cold-stored platelets were associated with higher postoperative transfusion utilization and lower platelet counts compared to room temperature-stored platelets without differences in clinical outcomes. The use of delayed cold-stored platelets in this setting may offer a viable alternative when facing critical platelet inventories but is not recommended as a primary transfusion approach.


[Patient support in pharmaceutical practice: Update on formalised care plans].
The evolution of patient management has led the pharmacist to change gear and get closer to the patient. To better ensure these missions, several educational and support programs have emerged: "Advice", "consultations" and "pharmaceutical interviews", "shared medication report" or "therapeutic patient education", all these programs are intended "guarantee the best conditions for initiation, monitoring and compliance as well as evaluation of treatment", taking into account the wishes and needs of patients. Although these programs have similarities, there are significant differences (i.e. regulatory, functional, organisational, educational). The aim here is to clarify the various support programs in order to better know their fields of application and put them into practice.


The effect of benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) treatment on regulation of reactive oxygen species metabolism involved in wound healing of potato tubers during postharvest.
Benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) can improve wound healing of potato tubers; however, how the chemical regulates reactive oxygen species (ROS) generation and scavenging during wound healing is not completely understood. BTH at 100 mg·L-1 regulated changes in ROS generation and scavenging in healing tissues of potato tubers. A higher H2O2 content was presented in healing tissues of potato tubers, while cell membrane permeability and malondialdehyde content declined due to BTH treatment. Additionally, the activities and transcript level of enzymes related with ROS generation, including NADPH oxidase, peroxidase and polyamine oxidase, as well as enzymes involved in ROS scavenging, such as superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase, were significantly enhanced by BTH treatment. It is suggested that ROS metabolism might play a crucial role in wound healing of potato tubers mediated by BTH during postharvest.


Current concepts in pathophysiology and diagnosis of compartment syndromes.
A compartment syndrome is a neurovascular compromise resulting from an increased local tissue pressure. Compartment syndromes can have many etiologies and may arise in any area of the body that has little or no capacity for tissue expansion. The sequelae are severe in the absence of immediate diagnosis and treatment. The diagnosis is usually a clinical one but compartment pressure measurements are often helpful. Many methods of treatment have been investigated, but definitive treatment consists of immediate removal of the constricting force, most often accomplished with surgical fasciotomy.


Structure-activity relationships in the acronycine and benzo[b]acronycine series: role of the pyran ring.
In order to explore the structure-activity relationships in the acronycine series, simplified analogues of cis-1,2-diacetoxy-1,2-dihydroacronycine and cis-1,2-diacetoxy-1,2-dihydrobenzo[b]acronycine (S23906-1, under clinical trials) lacking the fused pyran ring, but possessing an acetoxymethyl leaving group at position 4 were prepared. These new analogues only displayed marginal antiproliferative activity compared to the parent compounds. The presence of the angularly fused dimethylpyran ring appears as an indispensable structural requirement to observe significant cytotoxic activity in this series.


Low expression of the K280N TNNT2 mutation is sufficient to increase basal myofilament activation in human hypertrophy cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder with patients typically showing heterozygous inheritance of a pathogenic variant in a gene encoding a contractile protein. Here, we study the contractile effects of a rare homozygous mutation using explanted tissue and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to gain insight into how the balance between mutant and WT protein expression affects cardiomyocyte function. Force measurements were performed in cardiomyocytes isolated from a HCM patient carrying a homozygous troponin T mutation (cTnT-K280N) and healthy donors. To discriminate between mutation-mediated and phosphorylation-related effects on Ca2+-sensitivity, cardiomyocytes were treated with alkaline phosphatase (AP) or protein kinase A (PKA). Troponin exchange experiments characterized the relation between mutant levels and myofilament function. To define mutation-mediated effects on Ca2+-dynamics we used CRISPR/Cas9 to generate hiPSC-CMs harbouring heterozygous and homozygous TnT-K280N mutations. Ca2+-transient and cell shortening experiments compared these lines against isogenic controls. Myofilament Ca2+-sensitivity was higher in homozygous cTnT-K280N cardiomyocytes and was not corrected by AP- and PKA-treatment. In cTnT-K280N cells exchanged with cTnT-WT, a low level (14%) of cTnT-K280N mutation elevated Ca2+-sensitivity. Similarly, exchange of donor cells with 45 ± 2% cTnT-K280N increased Ca2+-sensitivity and was not corrected by PKA. cTnT-K280N hiPSC-CMs show elevated diastolic Ca2+ and increases in cell shortening. Impaired cardiomyocyte relaxation was only evident in homozygous cTnT-K280N hiPSC-CMs. The cTnT-K280N mutation increases myofilament Ca2+-sensitivity, elevates diastolic Ca2+, enhances contractility and impairs cellular relaxation. A low level (14%) of the cTnT-K280N sensitizes myofilaments to Ca2+, a universal finding of human HCM.


Lack of gender difference in acetazolamide-induced cerebral vasomotor reactivity in patients suffering from type-1 diabetes mellitus.
The aim of the present work was to investigate the impact of gender on resting cerebral blood flow velocity and cerebrovascular reserve capacity among diabetic patients. Middle cerebral artery mean blood flow velocity (MCAV) was measured in 72 patients suffering from type 1 diabetes mellitus at rest and 5, 10, 15 and 20 min after intravenous administration of 1 g acetazolamide. Cerebrovascular reserve was calculated as the maximal percent increase in MCAV after acetazolamide. Resting MCAV and cerebrovascular reserve capacity were compared between males and females. Resting cerebral blood flow velocity was higher in diabetic females than in males (men, 55.0+/-17.0 cm/s; women, 64.4+/-12.6 cm/s, p=0.0094). Cerebrovascular reserve capacity was similar in diabetic women and men (men, 44.0%+/-18.6%; women, 52.6%+/-32.9%, p=0.17). Comparing MCAV and cerebrovascular reserve capacity among the diabetic subgroups with disease duration < or = 10 years and >10 years, we did not detect any differences between women and men. Duration of diabetes was an important factor in determining cerebrovascular reserve capacity in both sexes: long-term diabetic women and men showed lower CRC values than diabetics with < or = 10 years disease duration. Cerebrovascular reserve capacity is similar in diabetic women and men. Taking into consideration that cerebrovascular reserve is normally higher among women, our finding indicates a relatively more serious worsening of cerebral vasodilatory responses in women suffering from type 1 diabetes.


Apomorphine-like effect of an aminotetralin on the linguomandibular reflex of the cat.
Low doses of 5,6-dihydroxy-2-dimethylaminotetralin (M-7) produced inhibition of the linguomandibular reflex in the cat. This inhibition was similar to that produced by apomorphine and was blocked by haloperidol, bulbocapnine or chlorpromazine. M-7 also had a brief but marked hypertensive effect. Gradual bradycardia also developed. These results indicate that M-7 inhibits the linguomandibular reflex by interaction at dopamine receptors, or 'apomorphine' receptors.


Cyclopentane-based human NK1 antagonists. Part 2: development of potent, orally active, water-soluble derivatives.
The synthesis and optimization of a cyclopentane-based hNK1 antagonist scaffold 3, having four chiral centers, will be discussed in the context of its enhanced water solubility properties relative to the marketed anti-emetic hNK1 antagonist EMEND (Aprepitant). Sub-nanomolar hNK1 binding was achieved and oral activity comparable to Aprepitant in two in vivo models will be described.


Food-dependent exercise-induced anaphylaxis: influence of concurrent aspirin administration on skin testing and provocation.
Provocation tests in patients with food-dependent exercise-induced anaphylaxis (FDEIA) are often negative, even after a sufficient quantity of the implicated food and exercise have been taken. To investigate the effect of aspirin in provocation tests and in skin prick testing (SPT) of patients with FDEIA. Gluten as a major allergen in wheat-dependent FDEIA was also investigated. Provocation tests and SPT with suspected foods were performed in 12 patients with FDEIA. Provocation tests were performed with combinations of foods, exercise and aspirin. Detection of gluten-specific IgE was also performed by the CAP System FEIA radioallergosorbent test, SPT and a histamine release test. The SPT reaction was enhanced by pretreatment with oral aspirin in five of eight (62.5) patients. Aspirin facilitated provocation in five of seven (71%) patients tested. Ingestion of wheat and aspirin without exercise provoked symptoms in two patients. Aspirin provoked symptoms even with a small amount of wheat and exercise in one patient. Only the combination of aspirin, wheat and exercise provoked anaphylaxis in one patient. Specific IgE, SPT and/or the histamine release test with gluten were positive in nine of 11 patients with wheat-dependent FDEIA. Aspirin enhances symptoms of FDEIA, and prior ingestion of aspirin under controlled conditions can be used to confirm FDEIA. In practice, such patients should avoid aspirin ingestion. Gluten appears to be the major allergen in these patients with wheat-dependent FDEIA.


Optimization of municipal solid waste management in Port Said - Egypt.
Optimization of solid waste management systems using operational research methodologies has not yet been applied in any Egyptian governorate. In this paper, a proposed model for a municipal solid waste management system in Port Said, Egypt is presented. It includes the use of the concept of collection stations, which have not yet been used in Egypt. Mixed integer programming is used to model the proposed system and its solution is performed using MPL software V4.2. The results show that the best model would include 27 collection stations of 15-ton daily capacity and 2 collection stations of 10 ton daily capacity. Any transfer of waste between the collection station and the landfill should not occur. Moreover, the flow of the district waste should not be confined to the district collection stations. The cost of the objective function for this solution is 10,122 LE/day (equivalent to 1716 US dollars). After further calculations, the profit generated by the proposed model is 49,655.8 LE/day (equivalent to 8418.23 US dollars).


Pulmonary hypertension and persistent fetal circulation in the newborn.
Despite these infants' very significant medical instabilities, which require vigorous therapeutic intervention, we have seen a population of infants with little in the way of persistent residual problems. Although many of their pulmonary complications persist after hospital discharge, most resolve within the first year of life. In addition, there are few neurodevelopmental disabilities encountered in such a high-risk population of children.


Coccidia (Protozoa: Eimeridae) of the herbivorous mole-rat, Spalax leucodon Nordmann.
A survey of 96 herbivorous mole-rats, Spalax leucodon Nordmann, in Lalahan district of Ankara, Turkey, revealed the presence of 6 new species of coccidia. The species found, the shape and average length-width dimensions (in micrometers) of their oocysts, and the numbers of animals from which they were isolated were as follow: Eimeria lalahanensis sp. n., subspherical to ellipsoidal (20.3 X 12.5), from 10; Eimeria tuzdili sp. n., spherical to subspherical with radially striated oocyst wall, (20.5 X 16.5), from 3; Eimeria spalacis sp. n., ellipsoidal to cylindrical (16.3 X 9.8), from 90; Eimeria elliptica sp. n., ellipsoidal (14.3 X 10.1), from 8; Eimeria turkmenica sp. n., ellipsoidal (11.3 X 8.9), from 1; Isospora anatolicum sp. n., spherical (7.6 X 5.1), from 1 animal. The overall infection rate for 96 examined herbivorous mole-rats was 100%.


Pediatric stress echocardiography.
Traditional health evaluations are performed while the patient is at rest. Stress echocardiography extends these examinations by providing data in a physiologic setting more closely mimicking the typically active state of children. The test represents a fusion of the fields of two-dimensional echocardiography and cardiovascular stress testing and can be used to assess myocardial perfusion in patients with suspected coronary artery pathology or to evaluate cardiac gradients or functional reserve in patients with noncoronary artery pathology. Testing should be performed with a trained sonographer and attending physician and in collaboration with adult cardiology colleagues. Stress can be administered to the patient through either exercise or pharmacologic agents. Echocardiography is used to assess regional wall motion abnormalities when evaluating myocardial perfusion or gradients and/or function when assessing the patient without coronary artery issues. Conditions with potential coronary artery pathology for which stress echocardiography is appropriate include Kawasaki disease, transplant graft vasculopathy, arterial switch operation for transposition of the great arteries, anomalous coronary artery origins or courses, pulmonary atresia with intact ventricular septum, hyperlipidemia, insulin-dependent diabetes mellitus, and supravalvar aortic stenosis. Stress echocardiography can also be helpful in determining the behavior during activity of gradients in conditions such as hypertrophic cardiomyopathy or aortic and pulmonic stenosis, of cardiac pressures in pulmonary hypertension and of ventricular function in conditions such as dilated cardiomyopathy or mitral and aortic regurgitation.


Primary structure and organization of the gene for a procaryotic, cell envelope-located serine proteinase.
We have determined the complete nucleotide sequence of the gene for the cell envelope-located proteinase of Lactococcus lactis SK11. The gene contains a very AT-rich promoter region followed by the coding sequence of a protein of 1962 amino acids. Comparison of the NH2-terminal amino acid sequence of the mature proteinase and the expected primary translation product of the proteinase gene indicates that the enzyme is probably synthesized as a pre-pro-protein. This is confirmed by expression studies of the proteinase gene in Escherichia coli. The amino acid sequence of the proteinase shows significant homology to a number of serine proteinases of the subtilisin family. Compared with the related proteinase of L. lactis Wg2, the proteinase of L. lactis SK11 contains a 60-amino acids duplication and a total of 44-amino acid substitutions, some of which may account for the different cleavage specificity of both enzymes. Furthermore, a region was identified in the Lactococcus proteinase, which shows homology to the membrane-anchoring domains of a number of proteins from other Gram-positive bacteria.


Diet diversity and clutch size of aquatic and terrestrial salamanders.
Terrestrial species of salamanders generally have a higher diversity of prey in their stomachs and produce smaller and less frequent clutches than do species living in wetter habitats. This may be a consequence of differences in prey availability in the two types of habitats. Prey frequently fluctuate in availability in terrestrial areas as a result of fluctuations in rainfall and the inability of salamanders to forage efficiently during dry periods; the salamanders respond with a generalist diet and relatively K-selected reproductive tactics. In wetter habitats, prey fluctuations are probably dampened due to more constant conditions of moisture; salamanders respond with a more specialized diet and relatively r-selected reproductive tactics.


Scorpions, spiders and solpugids: predation and competition among distantly related taxa.
Scorpions, spiders and solpugids are generalist predators on the same types of arthropod prey. However, these potential competitors also frequently eat one another (=intraguild predation). In a 29 mo. experiment, >6,000 scorpions were removed from 300 (10x10m) quadrats. Significantly more spiders (but not solpugids) occurred in removal versus control quadrats. Two alternate hypotheses potentially explain this result: exploitation competition for jointly exploited prey or intraguild predation. There was no evidence of exploitation competition: no differences existed between removal and control quadrats in prey abundance or spider size and reproductive characteristics. It appears that the release from predation pressure in areas from which scorpions were removed produced the observed increase in spider abundance. Current ecological theory does not fully apply to situations whereby species at the same trophic level interact as both predators and potential competitors.


Properties and antimicrobial activity of wheat-straw nanocellulose-arabinoxylan acetate composite films incorporated with silver nanoparticles.
In the current study, the novel eco-friendly and biodegradable nanocomposite films (NC-AXAc) were prepared from wheat-straw NC and AXAc with improved functional properties. NC derived from wheat-straw cellulose has a fibre-like structure with mean-particle size in the 340-520 nm range. AX derived AXAc was prepared with Degree of Substitution (DS) in the range of 1.85-1.89. Furthermore, to enhance antimicrobial properties, AgNPs were prepared via the reduction method using NaBH4 and added into the concentration of 4 × 10-4M into the emulsion forming composite films. The silver nanoparticles (AgNPs) incorporated in the composite exhibited an average size of 40-70 nm and a surface plasmon resonance (SPR) absorption peak at 395 nm. The high-resolution XPS spectrum of the Ag element showed that the two peaks at around 374.2 eV (Ag3d3/2) and 368.2 eV (Ag3d5/2) clearly revealed the metallic Ag existence in composite films. SEM analysis revealed the coarse and heterogeneous morphology of AgNPs incorporated films. The AgNPs incorporated composites exhibited good mechanical, thermal stability, and antimicrobial activity. The results suggested that AgNPs incorporated NC-AXAc composites could be used as a potential biodegradable antimicrobial nanocomposite in active food packaging systems for shelf-life extension of perishable commodities.


Isolation and structure elucidation of isoaltenuene, a new metabolite ofAlternaria alternata.
Isoaltenuene, a previously unknownAlternaria metabolite has been isolated from a rice culture ofAlternaria alternata and purified by semipreparative HPLC. The assigned structure, elucidated by UV, IR, MS, and NMR spectroscopy, was 2', 3', 4', 5'-tetrahydro-3, 4'β, 5'α-trihydroxy-5-methoxy-2'α-methyldibenzo (α)-pyrone and corresponded to a diasteroisomer of altenuene with inverted configuration at C-2'. Isoaltenuene showed a minor phytotoxic activity on tomato leaves at level of 20 μg/spot and no antifungal activity onGeotrichum candidum (up to 20 μg/disk).


Obstetric paralysis: anterior arthroscopic release of the shoulder and transfer of the latissimus dorsi using a homologous graft.
Description of a new surgical technique for treating the shoulders of patients with sequelae of obstetric paralysis. Preliminary analysis on the results obtained from this technique. Five consecutive patients underwent the proposed surgical procedure, consisting of arthroscopic anterior joint release followed by transfer of the latissimus dorsi tendon (elongated and reinforced with a homologous tendon graft) to the posterosuperior portion of the greater tubercle, using a single deltopectoral approach. All the patients were reevaluated after a minimum postoperative period of twelve months. The functional assessment was based on the range of motion and the modified Mallet classification system. Statistical analyses were not possible because of the small sample. Overall, passive and active lateral rotations increased, while medial rotation decreased. The other movements (elevation, capacity to place a hand in the mouth and capacity to place a hand behind the neck) had less consistent evolution. The mean modified Mallet score improved by 4.2 points (from 11.4 to 15.6). The latissimus dorsi tendon can be transferred to the posterosuperior portion of the greater tubercle through a single deltopectoral approach when elongated and reinforced with a homologous tendinous graft.


Mesenchymal stem cells: In vivo therapeutic application ameliorates carbon tetrachloride induced liver fibrosis in rats.
Egypt has the highest prevalence of hepatitis C virus in the world with infection rate up to 60%, for which liver fibrosis or hepatic carcinoma is the final outcome. Stem cell therapy provides a new hope for hepatic repair instead of traditional treatment, liver transplantation, as it is safer, gives long term engraftment and avoid expensive immunosuppressive drugs and unexpected hazardous effects. This work aimed at determining the therapeutic potential of mesenchymal stem cells (MSC) in hepatic repair as a new line of therapy for liver fibrosis. 33 female albino rats were divided into three groups: Group I: 10 rats injected subcutaneously with olive oil, Group II: 13 rats injected with carbon tetrachloride (CCl4) and Group III: 10 rats injected with CCl4 then bone marrow derived MSC from male rats. Blood and liver tissue samples were taken from all rats for biochemical and histological study. Liver functions for group II rats showed significant deterioration in response to CCl4 in addition to significant histological changes in liver lobules and portal areas. Those parameters tend to be normal in MSC-treated group. Group III rats revealed normalized liver function and histological picture. Meanwhile, most of the pathological lesions were still detected in rats of second group. Undifferentiated MSCs have the ability to ameliorate CCl4 induced liver injury in albino rats in terms of liver functions and histological features. So, stem cell therapy can be considered clinically to offer a hope for patients suffering from liver fibrosis.


Behavioral and electrophysiological (ECoG) effects of haplophyllum robustum and TRPA1 antagonist in adult male wistar rats.
This article aimed to investigate the effects of Haplophyllum robustum hydroalcoholic extract on animals' behavioral and electrocorticographic changes. This plant is mainly found in Turkey, Iran, and Central Asia, and is reported to have convulsive effects. In this article, we worked on the effects of its hydroalcoholic extract on electrocorticography (ECoG), along with changes induced by intracerebroventricular administration of GABAA antagonists. Furthermore, the effects of low doses of this extract on behavioral depression were examined. Four animal sets were used to compare ECoG in Wistar rats. A group of negative control, a group of positive control (PTZ), and two groups received an injection of plant extract (500 mg/kg, ip), with or without administration of Diazepam (5 mg/kg). Also, three sets were applied to compare receiving and not receiving intracerebroventricular (icv) injection of Transient receptor potential ankyrin 1 antagonist (HC-030031) (2 μg/kg) on plant-induced seizure delay and animal death. Two groups of control and a group with plant extract together with TRPA1 antagonist were administrated. Furthermore, in the present study, the forced swimming test (FST) was used as a model of depression. The behaviors of animals in three groups of negative control and positive control (Fluoxetine) and plant extract (200 mg/kg, ip) were compared. According to the ECoG, high doses of extract of plants led to seizures similar to PTZ, which were then reduced by diazepam injection. At this dose, injection of TRPA1 antagonist did not significantly delay the onset of seizures or the death of the animals. Further, a subconvulsive dose of hydroalcoholic plant extracts was equally effective in treating depression as Fluoxetine injections.


Potential immunologic targets for treating fibrosis in systemic sclerosis: a review focused on leukocytes and cytokines.
Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. Although the pathogenesis remains unclear, a variety of cells contribute to the fibrotic process via interactions with each other and production of various cytokines. Recent literature related to the immunologic pathogenesis and future strategies for treating the fibrosis of SSc are discussed and, especially, this literature-based review that includes the authors' perspective, focused on leukocytes and cytokines. A PubMed search for articles published between January 2005 and January 2012 was conducted using the following keywords: systemic sclerosis, leukocyte, cytokine, growth factor, and chemokine. The reference lists of identified articles were searched for further articles. Targeting profibrogenic cytokines, including transforming growth factor-β, is still a very active area of research in SSc and most cellular studies have focused on the roles of fibroblasts in SSc. However, a growing number of recent studies indicate a role for B cells in the development of SSc and other autoimmune diseases such as systemic lupus erythematosus. Therefore, B-cell-targeted therapies, including currently available monoclonal antibodies against CD19, CD20, CD22, and B-cell-activating factor, belonging to the tumor necrosis factor family represent possible treatment options. Furthermore, the modulation of T-cell costimulatory molecules such as a recombinant fusion protein of cytotoxic T-lymphocyte antigen-4 may be as effective in SSc as it is in treating other autoimmune diseases. Approaches to antagonize interleukin (IL)-1, IL-6, or IL-17A signaling may also be attractive. This review describes recent advances in the treatment of fibrosis in SSc patients focused on immunologic strategies, such as leukocyte- or cytokine-targeted therapies.


Aconitine linoleate, a natural lipo-diterpenoid alkaloid, stimulates anti-proliferative activity reversing doxorubicin resistance in MCF-7/ADR breast cancer cells as a selective topoisomerase IIα inhibitor.
Aconitine linoleate (1) is a lipo-diterpenoid alkaloid, isolated from Aconitum sinchiangense W. T. Wang. The study aimed at investigating the anti-proliferative efficacy and the underlying mechanisms of 1 against MCF-7 and MCF-7/ADR cells, as well as obvious the safety evaluation in vivo. The cytotoxic activities of 1 were measured in vitro. Also, we investigated the latent mechanism of 1 by cell cycle analysis in MCF-7/ADR cells and topo I and topo IIα inhibition assay. Molecular docking is done by Discovery Studio 3.5 and Autodock vina 1.1.2. Finally, the acute toxicity of 1 was detected on mice. 1 exhibited significant antitumor activity against both MCF-7 and MCF-7/ADR cells, with IC50 values of 7.58 and 7.02 μM, which is 2.38 times and 5.05 times more active, respectively than etoposide in both cell lines, and being 9.63 times more active than Adriamycin in MCF-7/ADR cell lines. The molecular docking and the topo inhibition test found that it is a selective inhibitor of topoisomerase IIα. Moreover, activation of the damage response pathway of the DNA leads to cell cycle arrest at the G0G1 phase. Furthermore, the in vivo acute toxicity of 1 in mice displayed lower toxicity than aconitine, with LD50 of 2.2 × 105 nmol/kg and only slight pathological changes in liver and lung tissue, 489 times safer than aconitine. In conclusion, compared with aconitine, 1 has more significant anti-proliferative activity against MCF-7 and MCF-7/ADR cells and greatly reduces in vivo toxicity, which suggests this kind of lipo-alkaloids is powerful and promising antitumor compounds for breast cancer.


The role of ventromedial and dorsolateral prefrontal cortex in attention and interpretation biases in individuals with general anxiety disorder (GAD): A tDCS study.
and purpose of the study: Individuals with general anxiety disorder (GAD) have deficits in emotional and cognitive processing, including cognitive bias, which plays a causal role in anxiety. Hyperactivity of the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) is assumed to be involved in cognitive bias. We aimed to explore the causal contribution of the dorsolateral and ventromedial prefrontal cortices (dlPFC, vmPFC) on cognitive bias via non-invasive brain stimulation, and expected a bias-reducing effect of cortical activity enhancement over these areas in GAD, with a larger contribution of the vmPFC to perceptual, and of the dlPFC to interpretation bias. The study was conducted in a randomized, single-blinded, and complete crossover design. Thirty-four adults with GAD, received transcranial direct current stimulation (tDCS) in 5 separate sessions (1.5 mA, 20 min) with the following electrode montages: anodal dlPFC/cathodal vmPFC, anodal vmPFC/cathodal dlPFC, anodal dlPFC/cathodal right shoulder, anodal vmPFC/cathodal left shoulder, and sham stimulation. During stimulation, in each session, participants performed the Dot-Probe and Reading Mind from Eyes tests to measure attention and interpretation biases. A significant effect of stimulation condition on attention and interpretation biases was observed. Anodal vmPFC and dlPFC stimulation coupled with an extracranial cathodal electrode reduced attention bias to threat-related stimuli in the dot-probe test. Furthermore, anodal dlPFC/cathodal vmPFC stimulation reduced negative interpretation bias in reading from eyes test. As suggested by the results of this study, both dlPFC and vmPFC are involved in cognitive bias in GAD, but with partially different roles. Anodal stimulation over the right vmPFC and the left dlPFC reduced attention bias, supporting the relevance of these areas for attention bias. For interpretation bias, the significant effect of anodal dlPFC/cathodal vmPFC stimulation, but only trendwise effect of anodal tDCS over the dlPFC combined with an extracephalic return electrode is in accordance with a predominant effect of the dlPFC on interpretation bias, but does not rule out an additional minor involvement of the vmPFC. Based on these results, a new model is suggested for the neural underpinnings of anxiety symptoms.


Underwater CAM photosynthesis elucidated by Isoetes genome.
To conserve water in arid environments, numerous plant lineages have independently evolved Crassulacean Acid Metabolism (CAM). Interestingly, Isoetes, an aquatic lycophyte, can also perform CAM as an adaptation to low CO2 availability underwater. However, little is known about the evolution of CAM in aquatic plants and the lack of genomic data has hindered comparison between aquatic and terrestrial CAM. Here, we investigate underwater CAM in Isoetes taiwanensis by generating a high-quality genome assembly and RNA-seq time course. Despite broad similarities between CAM in Isoetes and terrestrial angiosperms, we identify several key differences. Notably, Isoetes may have recruited the lesser-known 'bacterial-type' PEPC, along with the 'plant-type' exclusively used in other CAM and C4 plants for carboxylation of PEP. Furthermore, we find that circadian control of key CAM pathway genes has diverged considerably in Isoetes relative to flowering plants. This suggests the existence of more evolutionary paths to CAM than previously recognized.


Submucosal choledochal emphysema after transduodenal sphincteroplasty.
The widespread use of sphincteroplasty in the treatment of benign biliary obstruction requires that those physicians who must treat the complications associated with sphincteroplasty recognize the potential diagnostic pitfalls that may delay appropriate treatment. A case demonstrating one such potential pitfall is presented.


The scale of demographic heterogeneity in a population of Peromyscus leucopus.
The patterns of spatial heterogeneity in density and demography were studied in a population of Peromyscus leucopus inhabiting a deciduous forest in west-central Indiana. A series of 9 live-trapping grids sampled densities from 3 spatial scales: 3 ha, 80 ha and 350 km2. We found high levels of variation within all three spatial scales. There was as much variation within a single, large grid as within the entire Sugar Creek Valley (350 km2). The patterns of density variation were not temporally stable and thus represent variation in demographic processes rather than simply differences in habitat quality. We suggest that the Sugar Creek Valley represents a metapopulation of Peromyscus leucopus composed of a number of temporally unstable subpopulations. This structure provides considerable demographic variation that dispersing animals can exploit.


Studies on the prevalence of renal disease and hypertension in relation to schistosomiasis. III. Proteinuria, haematuria, pyuria and bacteriuria in the rural community of Nigeria.
Midstream specimen of urine was collected from the total population of two rural communities in the immediate environs of Ibadan. One has a higher and the other a low endemicity of urinary schistosomiasis. Proteinuria, haematuria, pyuria and bacteriuria were found to be significantly more frequent in the area of high than low endemicity.


Applications of metabolomics for understanding the action of peroxisome proliferator-activated receptors (PPARs) in diabetes, obesity and cancer.
The peroxisome proliferator-activated receptors (PPARs) are a set of three nuclear hormone receptors that together play a key role in regulating metabolism, particularly the switch between the fed and fasted state and the metabolic pathways involving fatty-acid oxidation and lipid metabolism. In addition, they have a number of important developmental and regulatory roles outside metabolism. The PPARs are also potent targets for treating type II diabetes, dyslipidemia and obesity, although a number of individual agonists have also been linked to unwanted side effects, and there is a complex relationship between the PPARs and the development of cancer. This review examines the part that metabolomics, including lipidomics, has played in elucidating the roles PPARs have in regulating systemic metabolism, as well as their role in aspects of drug-induced cancer and xenobiotic metabolism. These studies have defined the role PPARδ plays in regulating fatty-acid oxidation in adipose tissue and the interaction between aging and PPARα in the liver. The potential translational benefits of these approaches include widening the role of PPAR agonists and improved monitoring of drug efficacy.


Enantiomeric quantification of (S)-(+)-methamphetamine in urine by an immunoaffinity column and liquid chromatography-electrospray-mass spectrometry.
A method using an immunoaffinity column (IAC) and liquid chromatography-electrospray ionization mass spectrometry (LC/MS) for on-line detecting the presence of MA in the effluent was developed for the quantitative and enantiomeric determination of (S)-(+)-methamphetamine (d-MA) in urine. The IAC was made in our laboratory and utilized in the LC/MS to simultaneously extract and separate enantiomers of MA from urine samples. An aqueous ammonium acetate buffer was used as the mobile phase. Urine samples were spiked with racemic deuterated methamphetamine (MA-d14) as internal standard (IS), filtered through a membrane, and injected into the LC/MS without any further pre-treatment. Protonated molecular ion of MA and MA-d(14) (m/z 150 and 164) were isolated and further fragmented, the respective product ions, m/z 119 and 130, were collected for quantitative determination. This is an improvement of our previous method (A.C. Lua, Tsong-Yung Chou, J. Chromatogr. A 967 (2002) 191). In the previous method, MA was separated with HPLC, the efflux was fractionated and each fraction was either determined with an immunoassay or GC/MS. Monitoring of MA in the efflux is tedious and time consuming. Urine samples spiked with different concentrations of d-MA were measured by this method. A linear relationship exists in the 150-1050 ng/mL range, and the detection limit (defined as signal-to-noise ratio 3) of d-MA was determined to be 18 ng/mL. The linearity of the method for d-MA can be described by the equation (Y=1.415 x 10(-3)X+0.034, correlation coefficient: r2=0.999). Within run, accuracy and precision (n=6, relative error: -7.2 to +4.0% and relative standard deviation: 3.8-9.3%) of the method are fairly good.


Conventional computerized tomography of the heart.
Ungated cardio-CT provides good morphologic information in the case of congenital heart disease, volume or pressure loading, left ventricular aneurysm, tumours, thrombi, cardiac calcifications and pericardial diseases. It allows qualitative assessments of myocardial thickness and perfusion of coronary bypass grafts. ECG-gated cardio-CT allows a quantitative assessment of systolic and diastolic myocardial thickness, volume calculation of cardiac cavities and evaluation of functional parameters. The correlation of the calculated left ventricular ejection fraction comparing laevocardiography and ECG-gated cardio-CT was poor (r = 0.7) mainly due to the comparable poor time resolution on the side of cardio-CT (approximately 0.1s). The quantitative analysis of regional wall motion based on cardio-CT showed for the diagnosis of pathologic wall motion a specificity of 80.5%, sensitivity of 73.9% and accuracy of 75.7%. Side effects must be taken into account following the injection of 200-250 ml hyperosmolar contrast medium during 5-10 minutes which causes intravascular fluid retention and cardiac volume loading. Patients prone to cardiac decompensation should be excluded from cardio-CT examinations.


Effect of Ti on the Structure and Mechanical Properties of TixZr2.5-xTa Alloys.
To determine the effects of Ti and mixing entropy (ΔSmix) on the structure and mechanical proper-ties of Zr-Ta alloys and then find a new potential energetic structural material with good me-chanical properties and more reactive elements, TixZr2.5-xTa (x = 0, 0.5, 1.0, 1.5, 2.0) alloys were investigated. The XRD experimental results showed that the phase transformation of TixZr2.5-xTa nonequal-ratio ternary alloys depended not on the value of ΔSmix, but on the amount of Ti atoms. With the addition of Ti, the content of the HCP phase decreased gradually. SEM analyses revealed that dendrite morphology and component segregation increasingly developed and then weakened gradually. When x increases to 2.0, TixZr2.5-xTa with the best mechanical properties can be ob-tained. The yield strength, compressive strength and fracture strain of Ti2.0Zr0.5Ta reached 883 MPa, 1568 MPa and 34.58%, respectively. The dependence of the phase transformation and me-chanical properties confirms that improving the properties of Zr-Ta alloys by doping Ti is feasible.


The myofibroblastic component of rubeosis iridis.
Nineteen blind eyes enucleated for painful angle closure-glaucoma secondary to iris neovascularization (rubeosis iridis) were examined by scanning electron microscopy and correlative light and transmission electron microscopy. Fresh and deparaffinized tissue from patients with diabetes mellitus, central retinal vein occlusion, and retinoblastoma were studied. Scanning electron microscopy revealed extensive peripheral anterior synechia formation and flattening and effacement of the anterior iridic surface by a confluent fibrovascular membrane. New vessels on the anterior iris uniformly were hidden beneath a clinically inapparent, superficial layer of myofibroblasts, ie, fibroblastic cells with smooth muscle differentiation. Myofibroblasts may provide the motive force for synechial closure and ectropion iridis in neovascular glaucoma.


Short-term regulation of carnitine palmitoyltransferase activity in isolated rat hepatocytes.
An assay procedure for carnitine palmitoyltransferase is described which allows rapid measurement of the overt activity of this enzyme in isolated rat hepatocytes. In a one-step procedure digitonin permeabilizes the plasma membrane and at the same time carnitine palmitoyltransferase activity is measured. The use of the present procedure shows that carnitine palmitoyltransferase activity is regulated on the short term by different types of agonists. Thus, insulin, epidermal growth factor, vasopressin and the phorbol ester PMA inhibit carnitine palmitoyltransferase activity, whereas glucagon treatment renders the enzyme more active. These changes in enzyme activity coincide with corresponding changes in the rate of fatty acid oxidation.


Differences between high and low performers in face recognition in electrophysiological correlates of face familiarity and distance-to-norm.
Valentine's influential norm-based multidimensional face-space model (nMDFS) predicts that perceived distinctiveness of a face increases with its distance to the norm. Occipito-temporal event-related potentials (ERPs) have been recently shown to respond selectively to variations in distance-to-norm (P200) or familiarity (N250, late negativity), respectively (Wuttke & Schweinberger, 2019). Despite growing evidence on interindividual differences in face perception skills at the behavioral level, little research has focused on their electrophysiological correlates. To reveal potential interindividual differences in face spaces, we contrasted high and low performers in face recognition in regards to distance-to-norm (P200) and familiarity (N250). We replicated both the P200 distance-to-norm and the N250 familiarity effect. Importantly, we observed: i) reduced responses in low compared to high performers of face recognition, especially in terms of smaller distance-to-norm effects in the P200, possibly indicating less 'expanded' face spaces in low compared to high performers; ii) increased N250 responses to familiar original faces in high performers, suggesting more robust face identity representations. In summary, these findings suggest the contribution of both early norm-based face coding and robust face representations to individual face recognition skills, and indicate that ERPs can offer a promising route to understand individual differences in face perception and their neurocognitive correlates.


Computational Modeling of Environmental Co-exposure on Oil-Derived Hydrocarbon Overload by Using Substrate-Specific Transport Protein (TodX) with Graphene Nanostructures.
Bioremediation is a biotechnology field that uses living organisms to remove contaminants from soil and water; therefore, they could be used to treat oil spills from the environment. Herein, we present a new mechanistic approach combining Molecular Docking Simulation and Density Functional Theory to modeling the bioremediation-based nanointeractions of a heterogeneous mixture of oil-derived hydrocarbons by using pristine and oxidized graphene nanostructures and the substrate-specific transport protein (TodX) from Pseudomonas putida. The theoretical evidences pointing that the binding interactions are mainly based on noncovalent bonds characteristic of physical adsorption mechanism mimicking the "Trojan-horse effect". These results open new horizons to improve bioremediation strategies in over-saturation conditions against oil-spills and expanding the use of nanotechnologies in the context of environmental modeling health and safety.


Novel bisthiolane polysulfides from lachrymatory factor synthase-suppressed onion and their in vitro cyclooxygenase-1 inhibitory activity.
Two novel bisthiolane polysulfides (compounds 1 and 2), trivially named thiolanotrisulfide and thiolanotetrasulfide, were isolated from a reaction model of tearless onion (in which lachrymatory factor synthase is suppressed), and the presence of another novel bisthiolane polysulfide (3), trivially named thiolanopentasulfide, was confirmed. On the basis of spectroscopic and mass spectrometric analyses, it was found that these bisthiolane polysulfides were bis(5-hydroxy-3,4-dimethylthiolan-2-yl)-tri/tetra/pentasulfide with the general formulas of C12H22O2S5 (tri-), C12H22O2S6 (tetra-) and C12H22O2S7 (penta-), and they were confirmed to exist in authentic tearless onion juice. Thiolanotrisulfide (1) and thiolanotetrasulfide (2) inhibited cyclooxygenase-1 activity with IC50 values of 720 ± 78 and 464 ± 48 μM respectively, compared with 3282 ± 188 μM for aspirin.


Effect of temperature and nutrients on the growth and development of seedlings of an invasive plant.
Plant species distributions are determined by the response of populations to regional climates; however, little is known about how alien plants that arrive in central Europe from climatically warmer regions cope with the temperature conditions at the early stage of population development. Ambrosia artemisiifolia (common ragweed) is an invasive annual plant causing considerable health and economic problems in Europe. Although climate-based models predict that the whole of the Czech Republic is climatically suitable for this species, it is confined to the warmest regions. To determine the factors possibly responsible for its restricted occurrence, we investigated the effects of temperature and nutrient availability on its seedlings. The plants were cultivated at one of seven temperature regimes ranging from 10 to 34 °C, combined with three nutrient levels. The data on the rate of leaf development were used to calculate the lower developmental threshold (LDT, the temperature, in °C, below which development ceases), the sum of effective temperatures (SET, the amount of heat needed to complete a developmental stage measured in degree days above LDT) and width of the thermal window. The rate of development decreased with decrease in temperature and nutrient supply. Besides this, the decrease in the availability of nutrients resulted in decreased LDT, increased SET and wider thermal window. The dependence of LDT and SET on the availability of nutrients contradicts the concept that thermal constants do not vary. Our results highlight temperature as the main determinant of common ragweed's distribution and identify nutrient availability as a factor that results in the realized niche being smaller than the fundamental niche; both of these need to be taken into account when predicting the future spread of A. artemisiifolia.


Austin Powers' Steamroller: Lessons Learned to Benefit Patients with Congenital Heart Disease.
A structural crisis is brewing in advanced care for patients with congenital heart disease (CHD)-specifically, single-ventricle patients palliated by the Fontan procedure. The largest study evaluating management practices in pediatric cardiac teams found that 93% of providers believe that after the Fontan procedure, patients "will eventually have signs/symptoms of heart failure (HF) and will need a heart transplant (HT) at some point in their lives."1 Despite this, the majority either disagreed about (45%) or were undecided about (24%) "whether routine evaluation by a HF/HT cardiologist is needed." This may be, in part, attributable to the lack of an HF/HT subspecialty in the American College of Pediatrics, but these findings highlight a concerning disconnect in the minds of providers caring for patients undergoing the Fontan procedure, for whom the providers' preparation seems incongruous in terms of the anticipated endpoint. This disconnect would likely be even worse had the survey been conducted in adult providers, given that the providers of care for adults with congenital heart disease (ACHD) have limited required HF/HT training, and adult HF/HT cardiologists have little required training in CHD.


Testing anxious depression as a predictor and moderator of symptom improvement in major depressive disorder during treatment with escitalopram.
The purpose of this analysis was to explore the potential role of anxious MDD as a treatment predictor and moderator in major depressive disorder (MDD) using a large escitalopram clinical trial dataset. Individual patient-level data from 13 double-blinded, randomized, controlled trials in patients with MDD were pooled. Both univariate, last observation carried forward (LOCF) analyses and repeated measurements analyses without imputation (MMRM) were carried out for change in symptom scores, response and remission rates. Of 3,919 patients, 48.0% were classified as having anxious MDD depression (HAMD) somatization/anxiety subscale score ≥7 at baseline. Patients with anxious MDD were less likely to report symptom improvement on some outcome measures than patients without anxious MDD (predictor analysis). Specifically, the difference in response rates for patients with vs. patients without anxious MDD according to the MADRS (55.6% vs. 57.7%, respectively) was not statistically different. However, the difference in remission rates for patients with versus without anxious MDD according to the MADRS (37.6% vs. 44.1%, respectively) was statistically significant. Escitalopram was more effective than placebo, and as effective as the SSRIs and SNRIs, in the treatment of anxious MDD. The present analysis provides some evidence that the presence of an anxious MDD subtype is a predictor of poor response. There was no difference in the response to treatment of patients with or without anxious MDD to escitalopram, SSRIs, or SNRIs. The present analysis did not support the notion that SNRIs are more effective than escitalopram in the treatment of anxious MDD, nor was there evidence to support treatment moderating effects for anxious MDD.


Comparison of standard versus orthogonal ECG leads for T-wave alternans identification.
T-wave alternans (TWA), an electrophysiologic phenomenon associated with ventricular arrhythmias, is usually detected from selected ECG leads. TWA amplitude measured in the 12-standard and the 3-orthogonal (vectorcardiographic) leads were compared here to identify which lead system yields a more adequate detection of TWA as a noninvasive marker for cardiac vulnerability to ventricular arrhythmias. Our adaptive match filter (AMF) was applied to exercise ECG tracings from 58 patients with an implanted cardiac defibrillator, 29 of which had ventricular tachycardia or fibrillation during follow-up (cases), while the remaining 29 were used as controls. Two kinds of TWA indexes were considered, the single-lead indexes, defined as the mean TWA amplitude over each lead (MTWAA), and lead-system indexes, defined as the mean and the maximum MTWAA values over the standard leads and over the orthogonal leads. Significantly (P < 0.05) higher TWA in the cases versus controls was identified only occasionally by the single-lead indexes (odds ratio: 1.0-9.9, sensitivity: 24-76%, specificity: 76-86%), and consistently by the lead-system indexes (odds ratio: 4.5-8.3, sensitivity: 57-72%, specificity: 76%). The latter indexes also showed a significant correlation (0.65-0.83) between standard and orthogonal leads. Hence, when using the AMF, TWA should be detected in all leads of a system to compute the lead-system indexes, which provide a more reliable TWA identification than single-lead indexes, and a better discrimination of patients at increased risk of cardiac instability. The standard and the orthogonal leads can be considered equivalent for TWA identification, so that TWA analysis can be limited to one-lead system.


The impact of seasonal variations in DOC arising from a moorland peat catchment on coagulation with iron and aluminium salts.
Natural organic matter (NOM) is one of the main sources of environmental pollution to drinking water supplies in much of the UK and the US. Whilst traditional treatment with trivalent coagulants has proven a successful strategy in the past, operational problems are now being reported during periods of elevated organic levels in the water. Characterisation of the pollutants in terms of polarity, molecular weight and charge, provides a method to understand the impact of the observed temporal and spatial variations in terms of a mechanistic parameter relevant to the treatment processes. Results from this study demonstrate that it is not simply the increased organic concentration, but also the change in NOM composition and character, which influences the impact on the treatment processes. Consequently, monitoring of these parameters provides an insight into how to manage the impact caused by environmental changes to the catchments.


Effects of milnacipran and paroxetine on overactive bladder due to neurologic diseases: a urodynamic assessment.
To determine the effects of milnacipran hydrochloride, a serotonin-norepinephrine reuptake inhibitor (SNRI), or paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on overactive bladder (OAB) in neurologic diseases, given by objective measures of urodynamic studies. This is a prospective open trial, and we enrolled 24 patients (16 men, 8 women; mean age, 63.9 years) with OAB in a neurology clinic. They were randomly allocated into two groups: the milnacipran group (11 patients), and paroxetine group (13 patients). We started with 100 mg/day of milnacipran or 40 mg/day of paroxetine. Before and 3 months after the treatment, we performed a urinary questionnaire and urodynamic studies. Milnacipran reduced daytime urinary frequency (average, from 9.4 to 7.1 times, p < 0.001), improved the quality of life index (p = 0.023), and increased bladder capacity (average, from 289 to 377 ml, p = 0.009) as shown in urodynamic studies. No such changes were noted in the other categories of the lower urinary tract symptoms questionnaire or urodynamic studies, or in the paroxetine group. One male patient complained of mild voiding difficulty. Other adverse effects were not seen during the observation period. Milnacipran, an SNRI, increased bladder capacity as shown in urodynamic studies, and thereby ameliorated OAB in patients with neurologic diseases without serious adverse effects.


Fluconazole prophylaxis is associated with a decreased rate of coagulase-negative Staphylococcal infections in a subset of extremely low birth weight neonates.
Fluconazole prophylaxis is being used efficaciously in the neonatal intensive care unit (NICU) for fungal prophylaxis in very low birth weight and extremely low birth weight (ELBW) neonates. Little is known about the effect of fluconazole prophylaxis on bacterial infections. The purpose of this study was to examine that issue in a subset of ELBW, those weighing ≤900 g at birth. This is a retrospective study conducted in a level III NICU at state-designated children hospital in New Jersey (USA). We examined the data from our records of neonates ≤ 900 g birth weight during the period March 1, 2007-February 28, 2011. Inclusion in the study was all infants ≤ 900 g before (n = 67) and after (n = 81) the institution of fluconazole prophylaxis. Fluconazole prophylaxis was accompanied by a significant decrease in both the rate and number of days of bacterial infections as well as co-infections. We found that the incidence of coagulase-negative Staphylococcus (CONS) decreased from 46.2 to 24.7 % (OR 2.63; 95 % CI 1.31-5.27). Similarly, days of infection also decreased significantly (p < 0.0001). These data suggest that fluconazole prophylaxis may be associated with a reduction in CONS infections in that subset of ELBW neonates.


Outpatient cervical ripening with prostaglandin E2 gel in uncomplicated postdate pregnancies.
A double-blind, placebo-controlled, prospective investigation was undertaken to determine whether the outpatient administration of prostaglandin E2 gel was helpful for ripening the cervix in postdate pregnancies. One hundred eighteen women with an uncomplicated pregnancy at or beyond 42 weeks' gestation with an unripe cervix (Bishop score less than or equal to 5) were randomly administered a single dose of gel containing either 2.5 mg prostaglandin E2 (n = 55) or a placebo (n = 63) before induction of labor with Pitocin. No side effects were detected in these healthy mothers and fetuses. A distinct change in Bishop score after 12 hours occurred more often in the prostaglandin E2 than in the placebo group (42% versus 6%, p less than 0.0001). Forty-four women (80%) who had received prostaglandin E2 were admitted in early labor; they required little or no oxytocin for augmentation. The duration of labor and maximum dose of oxytocin infused were significantly decreased in the prostaglandin E2 group, and forceps delivery or primary cesarean sections were performed less often when prostaglandin E2 was used (24% versus 44%, p less than 0.05). The outpatient administration of a single dose of prostaglandin E2 gel is safe in the uncomplicated postdate pregnancy and was found to significantly change the unripe cervix, enhance the onset of labor, minimize the need for oxytocin administration, and encourage a spontaneous vaginal delivery.


Emotional experience and metacognition among people with schizophrenia: Analysis of session by session and outcome of metacognitive-oriented psychotherapy.
Research suggests that in-session emotional experiences in psychotherapy promote both session and treatment outcomes across different clinical samples and treatment approaches. However, little is known about how this notion applies to clients with schizophrenia, who experience particular deficits related to emotional experience. To explore this question, we investigated the association between clients' emotional experience and their session outcome evaluations and metacognitive growth in a metacognitively-oriented treatment, Metacognitive Reflection and Insight Therapy (MERIT). MERIT is a recovery-oriented treatment approach for psychosis that focuses on recapturing a coherent sense of self and personal agency by enhancing metacognitive capacity. Five-hundred-and-sixty-three sessions of 37 clients with schizophrenia who took part in an ongoing MERIT trial were analyzed. The Emotional Experience Self-Report (EE-SR) and Outcome Rating Scale (ORS) were collected on a session-by-session basis. Levels of metacognition ware assessed pre- and post-treatment using the Metacognitive Assessment Scale-Abbreviated (MAS-A) coding system. We used multilevel modeling to test our session-level predictions, and linear regression analysis for treatment-level predictions. Greater emotional experience, expression, and regulation within a session were associated with better session outcome. Regarding treatment level, greater emotional experience was associated with improvement in metacognitive mastery. Our findings reveal that experiencing emotions in MERIT has significant implications for clients' subjective well-being during therapy sessions and for their ability to respond to psychological challenges using metacognitive knowledge. These findings lend weight to the idea that emotional experience is a key mechanism of change in metacognitive therapy for schizophrenia.


The enhanced activity of Pt-Ce nanoalloy for oxygen electroreduction.
The widespread use of low-temperature polymer electrolyte membrane fuel cells for clean energy source require significant reductions in the amount of expensive electrocatalyst Pt for the oxygen reduction reaction (ORR). Pt based binary alloys are promising materials for more active and stable electrocatalysts. In this paper, we studied Pt-Ce nanoalloy, which was prepared by hydrogen reduction techniques as ORR electrocatalysts. Among all PtCe alloy catalysts, the PtCe/C-800 ℃ shows superior ORR activity, stability and durability compared to commercial Pt/C. The results presented in this paper will provide the future perspectives to research based on Pt-RE (RE = Ce, Dy, Gd, Er, Sm, and La) alloy as an novel electrocatalyst for various electrocatalytic reactions.


Oscyp71Z2 involves diterpenoid phytoalexin biosynthesis that contributes to bacterial blight resistance in rice.
Bacterial blight is one of the most destructive rice diseases, which caused by Xoo, and results in yield losses, endangering worldwide food security. Diterpenoid phytoalexins, a type of antimicrobials produced in rice, are critical for resistance to fungal and bacterial pathogens. This article reports the characterization of the cytochrome P450 gene Oscyp71Z2, which belongs to the CYP71Z subfamily. Overexpression of Oscyp71Z2 in rice enhanced resistance to Xoo at the booting stage. The accumulation of phytoalexins was rapidly and strongly induced in Oscyp71Z2-overexpressing plants, and the transcript levels of genes related to the phytoalexin biosynthesis pathway were elevated. The H₂O₂ concentration in Oscyp71Z2-overexpressing plants was reduced in accordance with the increase in ROS-scavenging ability due to the induction of SOD as well as POD and CAT activation. We also showed that suppression of Oscyp71Z2 had no significantly effect on disease resistance to Xoo in rice. These results demonstrated that Oscyp71Z2 plays an important role in bacterial blight resistance by regulating the diterpenoid phytoalexin biosynthesis and H₂O₂ generation.


Nurses' uniform color and feelings/emotions in school-aged children receiving health care.
Children may fear nurses wearing white uniforms. When emotions and uniform color were studied in 233 children, many positive emotions were most often associated with blue, bold pink-patterned, or yellow-patterned tops (all p ≤ .002). Negative emotions were not associated with uniform top colors (all p < .001). However, after excluding "uniform color does not matter," 8 negative emotions were most often associated with white uniform color (p < .001-.04), and 2 others were most often associated with the yellow-patterned top. Bold pink-patterned and solid blue uniform tops were preferred. In conclusion, children's emotions were associated with nurse uniform color.


IDE (rs6583817) polymorphism and type 2 diabetes differentially modify executive function in older adults.
We tested independent and interactive contributions of a recently noted and promising insulin degrading enzyme polymorphism (IDE; rs6583817) and type 2 diabetes (T2D) to executive function performance, concurrently and longitudinally. Regarding normal neurocognitive decline and Alzheimer's disease, T2D is a known risk factor and this IDE variant might contribute risk or risk reduction via the minor (A) or major (G) allele. We compared normal aging and T2D groups (baseline n = 574; ages 53-95 years) over 2 longitudinal waves (mean interval = 4.4 years). We used confirmatory factor analysis, latent growth curve modeling, and path analysis. A confirmed single-factor model of 4 executive function tasks established the cognitive phenotype. This IDE variant predicted concurrent group differences and differential change in cognitive performance. Furthermore, the IDE major allele reduced risk of cognitive decline. T2D predicted performance only concurrently. Both IDE and T2D are associated with executive function levels in older adults, but only IDE moderated 2-wave change. Previously linked to Alzheimer's disease, this IDE variant should be further explored for its potential influence on cognitive phenotypes of normal aging.


The Clinical and Morphologic Features Related to Aneurysm Wall Enhancement and Enhancement Pattern in Patients with Anterior Circulation Aneurysms.
Aneurysm wall enhancement (AWE) may predict rupture-prone intracranial aneurysms (IAs). However, the clinical and morphologic risk factors related to AWE have not been well described. Furthermore, the risk factors related to enhancement patterns have never been studied, especially in patients with anterior circulation aneurysms. Therefore, we aimed to investigate the risk factors related to wall enhancement and the enhancement patterns in anterior circulation unruptured aneurysms. One hundred patients (median age, 59 years; 68% female) with 113 anterior circulation unruptured aneurysms were included in this prospective study. Clinical and morphologic risk factors related to wall enhancement and circumferential enhancement were analyzed using univariate and multivariate analyses. There were 33 symptomatic unruptured IAs (29.2%) and 50 IAs with AWE (44.2%) (partial [n = 16] and circumferential [n = 34]). Univariate analysis showed that symptomatic IAs and morphologic factors (irregular shape, size, width, dome depth, size ratio, aspect ratio, and bottleneck) correlated with wall enhancement. Furthermore, female sex, blood parameters (cholesterol and low-density lipoprotein), and morphologic factors (size and dome depth) correlated with wall enhancement patterns (P <0.05). Multivariate analysis showed that size was the most important factor in wall enhancement (P = 0.06; odds ratio, 3.758) and a trend for symptomatic IAs (P = 0.033; odds ratio, 2.426). Female sex was the most important factor in circumferential enhancement (P = 0.017; odds ratio, 7.276). AWE was strongly associated with aneurysm size and was observed more frequently in symptomatic unruptured IAs. Sex hormones and atherosclerotic factors may be involved in circumferential enhancement. However, further studies should be performed to investigate the pathologic mechanisms for pattern of enhancement.


[The relationship between the amount of blood that mosquitoes engorge and their infectivity with the causative agent of malaria].
The infection of mosquitoes with malaria plasmodia was found to be affected by relative (to full portion) blood amount of the infected donor, which they suck out, i.e. to what extent the engorged portion approximates to the limiting one when mosquitoes cease bloodsucking. The facts obtained show that the survival of plasmodia in a mosquito (most likely, the passing of ookinetes into the outer side of the mid-gut) is associated with the degree of its stretching during bloodsucking. The limit stretching may be also attained during feeding up on a healthy donor.


The role of oxygen therapy in the healing of experimental skin wounds and colonic anastomosis.
A number of experimental studies have indicated that wound healing is adversely affected by hypoxia, and it has been suggested that healing can be improved by increasing inspired oxygen tensions. However, this hypothesis is based on observations on simulated wounds or tissue implants in experimental animals, and the clinical relevance of these observations is uncertain. The effects of oxygen therapy on the healing of skin wounds and colonic anastomoses were examined in rats. Sutured skin incisions and normal and ischaemic colonic anastomoses were studied in control animals breathing air and in test animals breathing 50 per cent oxygen. Wound healing was assessed by measurements of wound breaking strength, colonic bursting wall tension and wound collagen after 7 days' treatment with oxygen. There was no significant difference in the measurements in skin wounds or colonic anastomoses in test and control animals, and there was a similar incidence of anastomotic dehiscence in the ischaemic colon of test animals and controls. Oxygen therapy had no apparent effect on wound healing in this study, and it was concluded that further studies are required to determine whether or not there is a rational basis for the clinical use of oxygen therapy to help wound healing.


Clinical Signs and Diagnosis of the Canine Primary Glaucomas.
The diagnosis of glaucoma is highly dependent on a working understanding of the clinical signs and available diagnostic procedures. Clinical signs may be attributable to increased intraocular pressure and/or complex alterations in the physiology or molecular biology of the anterior segment, retinal ganglion cells, and optic nerve. Many diagnostic procedures seek to more fully characterize these alterations and to identify which clinical features increase the risk of overt primary angle closure glaucoma (PACG) occurring. Considerable progress has been made in identifying the anatomic features that predispose an eye to PACG, and in elucidating the role of reverse pupillary block.


A study of the evoked electromyography of the superior orbicularis oris muscle in man.
A study was made of the impulse conduction speed by moving recording electrodes at 5 mm intervals, successively, after stimulating facial nerves on one side in normal subjects. The findings showed that the speed of the potentials was fast and the amplitude was large, up to a distance of 0.5 cm across the midline. This makes us believe that there is an intermingling, of approximately one cm, of the left and right superior orbicularis oris muscles. Evoked potentials were recorded up to 1.5 to 2.5 cm across the midline--but as the speed reduced abruptly and the amplitude became small, we believe these potentials were conveyed by volume conductors. Six patients with facial palsy were studied, but in none were these findings indicating any reinnervation from the normal side. However, the conduction speed was delayed in them (as compared to normal subjects).


[An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis].
A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.


Outcomes for Angioplasty and Bypass Lower Limb Revascularisation Procedures for Limb Salvage in England: Findings From the Getting It Right First Time Programme.
The aim of this study was to investigate outcomes for lower limb revascularisation for limb salvage within the National Health Service (NHS) in England. This was a retrospective observational study of administrative data. Data were extracted from the Hospital Episodes Statistics database for England. Data were included for a seven year period (1 April 2011-31 March 2018 inclusive) for all patients aged ≥ 18 years receiving surgery for peripheral arterial occlusive disease. Data were extracted for patient age, sex and frailty level, the NHS trusts undertaking the procedure, the technique used (angioplasty, bypass, endarterectomy, or hybrid), the mode of admission (elective or emergency), the surgical speciality, the financial year of admission, length of hospital stay during the procedure, subsequent emergency re-admission, revascularisation procedures within 30 days and subsequent amputation and mortality within one year and within five years. The primary outcome was one year amputation free survival. For analysis, data were separated into diabetic and non-diabetic patients. Multilevel modelling was used to adjust for hierarchy and observed confounding when investigating outcomes. Data were available for 98 109 procedures across 124 hospital trusts. For non-diabetic patients (odds ratio 1.142, 95% confidence interval 1.068-1.222), one year amputation free survival was higher for angioplasty than for bypass. For diabetic patients, there was no difference in the primary outcome. One year amputation rates, 30 day emergency re-admission rates, and length of stay were all lower for angioplasty, and 30 day revascularisation rates were lower for bypass for both diabetic and non-diabetic patients. Outcomes were generally better for angioplasty than for bypass surgery for lower limb revascularisation for both diabetic and non-diabetic patients. The findings should be interpreted with caution given the likely different clinical presentations of those selected for each procedure. Future clinical trials may provide more definitive data.


Risk of early anticoagulation in patients with small deep infarcts possibly caused by cardiogenic emboli.
From a prospective registry of 103 stroke patients on early anticoagulation for cardiac embolus we selected 23 patients with a small deep infarct. We studied the incidence of hemorrhagic infarction on CT, and the risk of early anticoagulation. We found no hemorrhagic infarction on CT in any case, and no bleeding complications during the three week observation period. Obviously, early anticoagulation can be started safely in patients with a small deep infarct possibly caused by cardiac embolism.


Down-regulation of microRNA-146a in the early stage of liver ischemia-reperfusion injury.
MicroRNAs (miRNAs), 21-23-nucleotide noncoding RNAs, act as regulators of gene expression transcriptionally. MicroRNA-146a(miR-146a) has been demonstrated to be one of the key molecules in oncogenesis and inflammatory responses. Few data describe the expression of miR-146a in liver ischemia-reperfusion (IR) injury. The present study sought to explore the relationship of miR-146a to Toll-like receptor 4 (TLR4) signaling pathways in a rat model of warm IR injury. The expression of miR-146a was detected by real-time reverse-transcriptase polymerase chain reaction using a partial warm hepatic IR injury model. The expression of TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6), and interleukin-1 receptor-associated kinase (IRAK 1) protein was assessed by Western blotting as well as the signaling pathways induced by TLR4. The expression of hepatic miR-146a was down-regulated in IR injury during the 24 hours after reperfusion, reaching the lowest level at 6 hours after reperfusion. Increases in TLR4, TRAF6, and IRAK1 were accompanied by decreased miR-146a during the 24 hours after reperfusion, peaking at 6 hours. Immunohistochemistry showed cytoplasmic expression of cells positive for TLR4, and nuclear expression of cells positive for nuclear factor κB p65 and c-jun to be increased among IR groups after reperfusion. miR-146a was down-regulated in the early stage of liver IR injury.


Analysis of glycated amino acids by high-performance liquid chromatography of phenylthiocarbamyl derivatives.
A method has been developed for the analysis of hexitolamino acids formed by acid-catalyzed hydrolysis of nonenzymatically glycated proteins that have been treated with sodium borohydride. The hexitolamino acids are converted into phenylthiocarbamyl (PTC) derivatives which are analyzed by reverse-phase HPLC. The PTC derivatives of N alpha-hexitolamino acids behave like lactones, migrating on the column more slowly than the corresponding PTC-amino acids. The PTC derivatives of N epsilon-glucitol- and N epsilon-mannitol-lysine are probably free acids, since they migrate faster than PTC-lysine. The method, which can be used to determine the degree of glycation of N-terminal and lysyl residues, has been applied successfully to human hemoglobin, serum albumin, and ocular lens proteins.


Evaluation of the electrophoretic behaviour of opioid peptides Separation by capillary electrophoresis-electrospray ionization mass spectrometry.
A general equation established in a previous study was used to model the electrophoretic mobility of a series of opioid peptides as a function of pH of the separation electrolyte. The concordance between the predicted and the experimental electrophoretic mobilities was excellent and the optimum pH for the separation of the modelled compounds could be predicted from a limited amount of experimental data. The equations were also useful for the accurate determination of the ionization constants of the polyprotic analytes. It was also demonstrated that if ionization constant values are known, the CE separations of the studied peptides can easily be predicted taking into account the classical semiempirical relationships between electrophoretic mobility and charge-to-mass ratio (m(e) versus q/M(alpha)). The separations simulated considering the accurate charge-to-mass ratios of each peptide at a certain pH value were in good agreement with the experimental results. Once an optimum separation pH value and a running buffer compatible with electrospray mass spectrometry (ESI) detection were selected, a method for the separation and characterization of this series of analytes by capillary electrophoresis-electrospray ionization mass spectrometry (CE-ESI-MS) was established using a commercial sheath-flow interface. Method validation was performed in order to prove the suitability of the proposed method for quantitative analysis. Thus, quality parameters, such as repeatability, reproducibility, limits of detection and linearity were determined.


[Comparative study of lipid A from pertussis microbes differing in the toxicity of their O-antigens. I. Chemical composition and stability of the bond between lipid A and the specific polysaccharide in B. pertussis lipopolysaccharide].
Data presented in this work indicated that antigens, contrastive by toxicity, obtained by Boiven's method and O'Neill and Tood's method from two strains of Bordetella pertussis differed by stability of lipid A binding with the specific polysaccharide. The influence of duration of the lipopolysaccharide hydrolysis on the fatty acid content in lipid A, and of heptose in the specific polysaccharide was demonstrated. Lipid A fatty acid composition was studied. It is supposed that bound fatty acids are presented as C14 and C19--C22. There was a correlation between the antigen toxicity and the stability of lipid A bond with the specific polysaccharide. Stability of the lipopolysaccharide complex bond depended on heptose and lipid A content and on the composition and the amount of fatty acids in the lipid A preparations.


CSF and serum interferon in multiple sclerosis: longitudinal study.
We studied interferon (IFN) in the serum and CSF of 31 patients with multiple sclerosis. The sensitive IFN bioassay required only small volumes and detected IFN levels as low as 0.5 international units/ml (CSF) or 4 international units/ml (serum) of IFN. Two hundred twenty-eight paired CSF/serum samples were tested, and no IFN was found.


Chemoselective heterocyclization and pharmacological activities of new heterocycles--a review. Part V-Synthesis of biocidal 4-thiazolidinones derivatives.
4-Thiazolidinones have been reported to possess biological activity especially fungicidal activity. With an intention to prepare some more 4-thiazolidinones as drugs for anti HIV and anticancer activity, we have synthesized some more 4-thiazolidinones by the action of mercaptoacetic acid on Schiff's base and/or heterocyclization of N-substituted thioureas with monochloracetic acid. Characterization of 4-thiazolidinone was deduced upon elemental and spectral analysis.


Managerial leadership is associated with employee stress, health, and sickness absence independently of the demand-control-support model.
Research on health effects of managerial leadership has only taken established work environment factors into account to a limited extent. We therefore investigated the associations between a measure of Attentive Managerial Leadership (AML), and perceived stress, age-relative self-rated health, and sickness absence due to overstrain/fatigue, adjusting for the dimensions of the Demand-Control-Support model. Blue- and white-collar workers from Finland, Germany and Sweden employed in a multi-national forest industry company (N=12,622). Cross-sectional data on leadership and health from a company-wide survey analysed with logistic regression in different subgroups. AML was associated with perceived stress, age-relative self-rated health, and sickness absence due to overstrain/fatigue after controlling for the Demand-Control-Support model. Lack of AML was significantly associated with a high stress level in all subgroups (OR=1.68-2.67). Associations with age-relative self-rated health and sickness absence due to overstrain/fatigue were weaker, but still significant, and in the expected direction for several of the subgroups studied, suggesting an association between lack of AML and negative health consequences. The study indicates that managerial leadership is associated with employee stress, health, and sickness absence independently of the Demand-Control-Support model and should be considered in future studies of health consequences for employees, and in work environment interventions.


Diagnostic molecular markers in thyroid cancer.
The use of molecular assays to analyze clinical tissues in the diagnosis and management of thyroid cancer, similar to other tumors, will likely allow for more accurate characterization of the aggressiveness of individual tumors and may allow for the early diagnosis of recurrence. The application of these methods to thyroid nodules and nodal metastases is less encumbered by difficulties arising from amplification of transcripts in non-thyroid cells. For these tissues, these assays are likely to be used clinically in the near-future. New data arising from cDNA arrays identifying novel markers of malignancy or tumor aggressiveness make this a growing area of interest. The use of molecular assays in diagnosing distant metastases is more problematic due to issues with ectopic expression of either full length or splice variants of genes thought to be thyroid-specific. Assay quantitation is a complex problem owing to variability in the level of expression of "housekeeping" genes and the variety of phlebotomy and RT-PCR methods reported. Additional research in this area is clearly required before a recommendation can be given regarding clinically applicability of these tests.


Comparing 2 methods of emergent zipper release.
There are several types of emergent zipper release methods described. The standard method can be difficult. The purpose of this study is to determine if an alternate method of zipper release can be easier to accomplish. Subjects were provided with zippers and were taught 2 methods of emergent zipper release using a standard method (cutting the median bar of the actuator) and an alternate method (cutting the closed teeth of the zipper). The elapsed times to successful zipper release for both methods were measured. Mean zipper release times were faster for the alternate method (10.5 seconds) compared with the standard method (75.8 seconds) ( P < .001). The alternate method of zipper release is faster and easier than the standard method of zipper release; however, the optimal procedure is also dependent on the location of the entrapped tissue relative to the zipper actuator and the type of zipper.


Novel automated assay for the quality control of mexiletine hydrochloride formulations using sequential injection and on-line dilution.
The first automated method for the determination of mexiletine hydrochloride - an antiarrhythmic agent - is reported. The method is based on the reaction of the analyte with o-phthalaldehyde (OPA) in the presence of sulfite in basic medium using a sequential injection (SI) manifold. The reaction product was monitored spectrofluorimetrically (lambda(ex)=350 nm/lambda(em)=446 nm). A simple and effective on-line dilution approach was adopted in order to expand the linearity and apply the method to assay, dosage uniformity and dissolution tests with minimum sample preparation. Chemical (pH, amount concentrations of OPA and sulfite) and instrumental variables (temperature, flow rate, injection volumes, etc.) that affected the determination were studied. The developed assay was validated in terms of linearity, range, limits of detection (LOD=3.4 mg L(-1)) and quantitation (LOQ=10 mg L(-1)), accuracy, precision (R.S.D.<3.4%) and selectivity. The method was applied successfully to the quality control of a mexiletine-containing formulation. The results were in good agreement with the US pharmacopoeia HPLC method.


Methylglyoxal causes swelling and activation of a volume-sensitive anion conductance in rat pancreatic beta-cells.
Membrane potential and whole-cell current were studied in rat pancreatic beta-cells using the 'perforated patch' technique and cell volume measured by a video-imaging method. Exposure of beta-cells to the alpha-ketoaldehyde methylglyoxal (1 mM) resulted in depolarization and electrical activity. In cells voltage-clamped at -70 mV, this effect was accompanied by the development of inward current noise. In voltage-pulse experiments, methylglyoxal activated an outwardly rectifying conductance which was virtually identical to the volume-sensitive anion conductance previously described in these cells. Two inhibitors of this conductance, 4,4'-dithiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), also inhibited the depolarization and inward current evoked by methylglyoxal. Methylglyoxal increased beta-cell volume to a relative value of 1.33 after 10 min with a gradual return towards basal levels following withdrawal of the alpha-ketoaldehyde. None of the effects of methylglyoxal was observed in response to t-butylglyoxal which, unlike methylglyoxal, is a poor substrate for the glyoxalase pathway. Methylglyoxal had no apparent effect on beta-cell K+ channel activity. It is suggested that the metabolism of methylglyoxal to D-lactate causes beta-cell swelling and activation of the volume-sensitive anion channel, leading to depolarization. These findings could be relevant to the stimulatory action of D-glucose, the metabolism of which generates significant quantities of L-lactate.


Triple procedure for pseudophakic bullous keratopathy in complicated cataract surgery: Glued IOL with single-pass four-throw pupilloplasty with pre-Descemet's endothelial keratoplasty.
Pseudophakic bullous keratopathy is a major deterrent to visual recovery after a complicated cataract surgery. Decentered intraocular lenses (IOLs) incite chronic inflammation that often leads to bullous keratopathy. The triple procedure of glued IOL allows secondary IOL fixation along with single-pass four-throw pupilloplasty that prevents the slippage of air into the vitreous cavity and maintains air tamponade followed by pre-Descemet's endothelial keratoplasty that supplants the endothelial layer, thereby retaining its functionality.


Short-term Outcomes of Transanal Hemorrhoidal Dearterialization With Mucopexy Versus Vessel-Sealing Device Hemorrhoidectomy for Grade III to IV Hemorrhoids: A Prospective Randomized Multicenter Trial.
Transanal hemorrhoidal dearterialization with mucopexy and vessel-sealing device hemorrhoidectomy seem to reduce postoperative pain compared with classic excisional hemorrhoidectomy, but whether one of them is superior remains unclear. We compared transanal hemorrhoidal dearterialization with mucopexy and vessel-sealing device hemorrhoidectomy. This was a multicenter, randomized controlled trial. The study was conducted at 6 Spanish centers. Patients aged ≥18 years with grade III to IV hemorrhoids were included. Patients were randomly assigned to transanal hemorrhoidal dearterialization with mucopexy (n = 39) or vessel-sealing device hemorrhoidectomy (n = 41). Primary outcome was the mean postoperative number of days in which patients needed nonsteroidal anti-inflammatory drugs. Secondary outcomes were postoperative pain, 30-day morbidity, patient satisfaction, Vaizey score, hemorrhoid symptoms score, return to work, and quality of life. More patients were still taking analgesia in the vessel-sealing device hemorrhoidectomy group during the second postoperative week compared with the transanal hemorrhoidal dearterialization with mucopexy group (87.8% vs 53.8%; p = 0.002). For the transanal hemorrhoidal dearterialization with mucopexy group, analgesia consumption continued until day 10.1 (mean; SD = 7.22 d), whereas in the vessel-sealing device hemorrhoidectomy group it continued until day 15.2 (mean; SD = 8.70 d; p = 0.006). The mean daily average pain was similar during the first (p = 0.900) and second postoperative weeks (p = 0.265). Mean operative time was higher for the transanal hemorrhoidal dearterialization with mucopexy group versus the vessel-sealing device hemorrhoidectomy group (45 min; range, 40-60 vs 20 min; range, 15-41 min; p < 0.001). Postoperative complications rate, use of laxatives, patient satisfaction, Vaizey score, hemorrhoids symptoms score, return to work, and quality of life at 1 month after surgery were similar between groups. The main limitation of this study was that the 2 groups did not contain equal numbers of grade III and IV hemorrhoids. Transanal hemorrhoidal dearterialization with mucopexy is associated with a shorter need for postoperative analgesia compared with vessel-sealing device hemorrhoidectomy. See Video Abstract at http://links.lww.com/DCR/A915. clinicaltrials.gov identifier: NCT02654249.


Rapid development of band keratopathy in dry eyes.
In three patients, calcium deposits rapidly developed within the superficial corneal stroma. All eyes had severe desiccation, a bacterial corneal ulcer, and frequent instillation of an artificial tear preparation. Calcium deposition within the ulcer base occurred within two to three weeks.


Lead exposure and its association with cardiovascular disease and diabetic kidney disease in middle-aged and elderly diabetic patients.
Previous studies have suggested that a high blood lead level (BLL) is associated with cardiovascular outcomes and impaired renal function in the general population; however, studies investigating the effect of a high BLL on diabetic vascular complications have been limited. We aimed to investigate whether a higher BLL is associated with cardiovascular disease (CVD) and diabetic kidney disease (DKD). We analyzed 4234 individuals out of 4813 diabetic participants enrolled from seven communities in China in 2018 in this cross-sectional study. Macrovascular measurements, including assessment of common carotid artery (CCA) plaques and their diameters, were performed with ultrasound. CVD was defined as a composite measure including a previous diagnosis of coronary heart disease, myocardial infarction, or stroke. The definition of DKD was an albumin to creatinine ratio (ACR) ≥30 mg/g or an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2. Linear and logistic regression analyses were used to measure the associations. The median age and BLL of the participants were 67 years (interquartile range, 62-72 years) and 26 μg/L (interquartile range, 18-36 μg/L). Compared with the first quartile, the odds ratio (OR) (95% CI) of CCA plaques ranging from none to bilateral in the ordinal logistic regression analysis associated with BLL was 1.53 (1.29, 1.82) in the fourth BLL quartile (P for trend <0.01), and the odds of having CVD was significantly increased by 44% for participants in the fourth quartile (1.44 (1.17, 1.76)) (P for trend <0.01). The odds of DKD in the fourth BLL quartile increased by 36% (1.36 (1.06, 1.74)) compared with that in the first quartile (P for trend <0.05). These associations were adjusted for potential confounders. A high BLL may be a potential risk factor for CVD and DKD in middle-aged and elderly diabetic adults.


Bermuda grass latent virus in Australia: genome sequence, sequence variation, and new hosts.
Bermuda grass latent virus (BGLV; genus Panicovirus) is identified for the first time in Australia and in only the second country after the USA. A full-length genome sequence was obtained, which has 97% nucleotide sequence identity to that of the species exemplar isolate. Surveys for BGLV, utilising a newly designed universal panicovirus RT-PCR assay for diagnosis, demonstrated widespread infection by this virus in a broad variety of Bermuda grass cultivars (Cynodon dactylon and C. dactylon × C. transvaalensis) grown in both New South Wales and Queensland. The virus was also detected in Rhodes grass (Chloris gayana) and Kikuyu grass (Cenchrus clandestinus), which are both important pasture grasses in subtropical Australia, and the latter is also grown as turf. Furthermore, the Rhodes grass plant, which had strong mosaic symptoms, was also infected with sugarcane mosaic virus, warranting further investigations as to whether synergistic interactions occur between these two viruses.


Super-resolved FT-IR spectroscopy: Strategies, challenges, and opportunities for membrane biophysics.
Direct correlation of molecular conformation with local structure is critical to studies of protein- and peptide-membrane interactions, particularly in the context of membrane-facilitated aggregation, and disruption or disordering. Infrared spectroscopy has long been a mainstay for determining molecular conformation, following folding dynamics, and characterizing reactions. While tremendous advances have been made in improving the spectral and temporal resolution of infrared spectroscopy, it has only been with the introduction of scanned-probe techniques that exploit the raster-scanning tip as either a source, scattering tool, or measurement probe that researchers have been able to obtain sub-diffraction limit IR spectra. This review will examine the history of correlated scanned-probe IR spectroscopies, from their inception to their use in studies of molecular aggregates, membrane domains, and cellular structures. The challenges and opportunities that these platforms present for examining dynamic phenomena will be discussed. This article is part of a Special Issue entitled: FTIR in membrane proteins and peptide studies.


Effect of long-term yoga training on autonomic function among the healthy adults.
Autonomic dysfunction is one of the major complications in noncommunicable diseases, and there are studies to prove yoga practice improves cardiac autonomic function. So, this present study was done to compare the autonomic functions among yoga practitioners and nonyoga practitioners. This cross-sectional comparative study was initiated among 68 healthy volunteers of both sexes, after recruiting them based on inclusion and exclusion criteria in the age group of 17-30 yrs. The autonomic reactivity tests like resting heart rate, response of heart rate to standing, Valsalva maneuver, and response of heart rate to deep breathing, response of BP to standing, and sustained hand-grip were done. In the autonomic reactivity test, resting heart rate (80.92 ± 11.76 vs 69.24 ± 10.64) and sustained handgrip (16.30 ± 4.53 vs 10.20 ± 3.67) significantly decreased (P < 0.05) in the participants of the yoga group compared to control group. Deep breathing test, Valsalva maneuver, 30:15 ratio in lying to standing, and BP response to standing test did not show any significant difference between the groups (P > 0.05). The present study revealed diminished sympathetic activity and improved parasympathetic activity among the regular yoga practicing participants. It can be practiced regularly to reduce stress and prevent lifestyle-associated disorders in the future.