Effects of fasting on the distribution of cytoplasmic and nuclear oestrogen receptors in rat liver, uterus, pituitary and hypothalamus before and after exogenous oestrogen administration.
The accumulation of oestrogen receptors in the liver cell nuclei of intact female rats 45 min after administration of 100 micrograms 17 alpha-ethynyloestradiol-17 beta i.p., decreased progressively during a 72-h fast from 2550 +/- 860 to 257 +/- 67 fmol/mg DNA, a level not significantly different from that in uninjected animals. Cytoplasmic oestrogen receptor concentrations also decreased, but only to about 60% of the original level (from 84.1 +/- 27.5 to 50.3 +/- 2.09 fmol/mg protein during the fast). Similar differences were found when these parameters were examined in normally fed and 72-h-fasted ovariectomized rats. On the other hand these parameters were unaffected in uterus, pituitary and hypothalamus. Uterine cytoplasmic receptor concentrations remained at about 500 fmol/mg protein during the fasting period, those in the pituitary and hypothalamus at about 230 and 30 fmol/mg protein, respectively. Nor was in vivo translocation in these organs affected by fasting. Regardless of nutritional status, the nuclear oestrogen receptor concentrations in uterus rose from about 500 to 2000 fmol/mg DNA after ethynyloestradiol administration, those in the pituitary and hypothalamus from approximately 250 to 2000 and from 250 to 500 fmol/mg DNA respectively.


Etiology of otitis media with effusion: antihistamines--decongestants.
In an attempt to find a causative factor for the increased incidence of otitis media with effusion, a detailed study of 50 cases was conducted. This study included 50 cases of nonpurulent otitis media with effusion requiring ventilating tubes without tonsilloadenoid pathology. A study of these cases revealed an interesting pattern which suggests that antihistamines and decongestants may be causative or precipitating factors in the etiology of otitis media with effusion. A pilot study on the effects of these drugs on mucociliary activity was conducted and revealed further evidence that antihistamines and decongestants interfere with normal mucociliary activity which probably is a factor in abnormal Eustachian tube physiology.


[The importance and role of laparoscopic appendectomy].
Inspite of earlier beginning the laparoscopic appendectomy is in the shadow of laparoscopic cholecystectomy. In connection with laparoscopic appendectomy some problems are discussed--his significance or substantiality, techniques, advantages or disadvantages in contrast to classical appendectomy. The authors discussed these questions on the base of their own experiences with 56 laparoscopic appendectomies. These were done from 21. October 1992 to 7. February 1994. Known advantages of laparoscopic procedures are expressed--shorter hospital stay after the operation (in average 2.3 days), better view in the operating field with possibility of the treatment of gynecological pathology. Technical aspects are also discussed. The equipment with staplers according their opinion is needed. The time of the operations--average 44 minutes--is acceptable. The complication and conversion rate, which were noted in 3.6% resp. 5.3%, is quite good. There is a possibility to lower these numbers with increasing experience. The possibility for training in the laparoscopic field is great opportunity especially for young surgeons. In the end there is stated, that the authors consider laparoscopic appendectomy as an important step to the advanced procedures. The broad acceptance is recommended.


Risks and Rewards of Bariatric Surgery in Advanced Chronic Liver Diseases.
The burden of obesity and metabolic syndrome has determined a sharp increase in bariatric surgery (BS) procedures, which lead to marked weight loss, improved metabolic syndrome, reduced cardiovascular risk, and even improvement in nonalcoholic steatohepatitis (NASH). Despite these promising results, BS in patients with chronic liver disease can rarely lead to worsening of liver function, progression to cirrhosis and its complications, and even liver transplantation. On the other hand, since obesity in patients with cirrhosis is a major cofactor for progression to a decompensated stage of the disease and a risk factor for hepatocellular carcinoma, BS has been used to achieve weight loss in this population. In this review, we critically analyze the existing data on outcomes of BS in patients with cirrhosis and the possible mechanisms leading to fibrosis progression and worsening liver function in patients undergoing BS. Finally, we propose a set of measures that could be taken to improve the multidisciplinary management of liver disease in patients undergoing BS, including early recognition of malnutrition and alcohol misuse.


Rictor/mTORC2 loss in osteoblasts impairs bone mass and strength.
Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase conserved through evolution that coordinates extra cellular signals associated with cell growth. Main functions of mTOR present in the form of two complexes, namely mTORC1 and mTORC2, which are distinct in their unique components, raptor and rictor. In the current study, using a Cre/loxp system, we found an anabolic effect of mTORC2 signaling on skeleton. Osteoblast differentiation was reduced, with down-regulation of mTORC2 signaling activity in primary cultures of osteoblasts that did not contain rictor. Mice with a specific deletion of rictor in mature osteoblasts showed a significant reduction in lean mass and bone mineral density by dual energy x-ray absorptiometry analysis. Micro-computed tomography, histomorphometric, and molecular biological analyses revealed a marked impairment of the cortical bone mass and microarchitecture, as well as minor changes in trabecular bone, of the Rictorob(-/-) mice. Cortical bone mass and thickness of the femoral mid-shaft were dramatically reduced, with unusual increases in porosity and marrow area in Rictorob(-/-) mice. Thinner trabeculae were found in the L4 vertebrae with relatively normal structural indices of trabecular numbers and separation. A lower rate of bone turnover was observed, as the consequence of the decreased individual osteoblast activity and bone resorption. Furthermore, these changes were associated with significantly decreased bone biomechanical properties. In conclusion, expression of rictor in osteoblasts is essential for the maintenance of normal bone remodeling and microarchitecture, especially for the maintenance of the cortical bone.


Mitochondrial dynamics in the heart as a novel therapeutic target for cardioprotection.
Traditionally, mitochondria have been regarded solely as energy generators for cells; however, accumulating data have demonstrated that these complex organelles play a variety of roles within the cardiomyocyte that extend beyond this classic function. Mitochondrial dynamics involves mitochondrial movements and morphologic alterations by tethering, fusion, and fission, which depend on cellular energy requirements and metabolic status. Many studies have indicated that mitochondrial dynamics may be a fundamental component of the maintenance of normal cellular homeostasis and cardiac function. Mitochondrial dynamics is controlled by the protein machinery responsible for mitochondrial fusion and fission, but cardiomyocytes are densely packed as part of an intricate cytoarchitecture for efficient and imbalanced contraction; thus, mitochondrial dynamics in the adult heart are restricted and occur more slowly than in other organs. Cardiac mitochondrial dynamics is important for cardiac physiology in diseased conditions such as ischemia-reperfusion (IR) injury. Changes in mitochondrial morphology through modulation of the expression of proteins regulating mitochondrial dynamics demonstrates the beneficial effects on cardiac performance after IR injury. Thus, accurately defining the roles of mitochondrial dynamics in the adult heart can guide the identification and development of novel therapeutic targets for cardioprotection. Further studies should be performed to establish the exact mechanisms of mitochondrial dynamics.


[Surgery of infected hand injuries in Bács-Kiskun County].
The therapy of the diseases of the infected hand belongs to the most difficult tasks of the hand surgery. In the county Bács-Kiskun we have reached important results during the last two decades, described in this paper, together with the Hand Surgery Work Groups of the Accident Departments of Kecskemét (County Hospital), Baja and Kiskunhalas.


Melilotus indicus extract induces apoptosis in hepatocellular carcinoma cells via a mechanism involving mitochondria-mediated pathways.
Melilotus indicus, is a traditional medicine used as analgesic and emollient. Although Melilotus indicus extract (MIE) has recently been shown to suppress growth of several tumor cell lines, information regarding its antitumor mechanism is completely unknown. Here, we report the mechanism underlying the effects of MIE on human hepatocellular carcinoma cells, specifically HepG2, and SNU-182 cells. Methanolic MIE impaired the proliferation, and induced cell death in both HepG2 and SNU-182 cells but not in normal hepatic L-02 cells. Mechanistically, flow cytometric analysis revealed that MIE induces apoptosis in HepG2, and SNU-182 cells. However, MIE-induced apoptosis were not affected by a pan caspase inhibitor z-VAD-fmk as well as MIE did not stimulate caspase activation. Furthermore we found that MIE-induced apoptosis could be attributed to a mechanism involving mitochondria-mediated pathways evidenced by decrease in the mitochondrial membrane potential (ΔΨm), increase in the Bax/Bcl-2 ratio, and translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus. Suppression in AIF expression by siRNA reduced MIE-induced apoptosis which suggested the dependency of MIE on AIF to induce apoptosis in hepatocellular carcinoma cells. To the best of our knowledge this is the first report elucidating the anticancer mechanism of MIE. Our findings suggested that MIE might be a good extract for developing anticancer drugs for human hepatocellular carcinoma treatment.


Neurobiological mechanisms of panic anxiety: biochemical and behavioral correlates of yohimbine-induced panic attacks.
The effects of yohimbine, an alpha 2-adrenergic receptor antagonist, on anxiety, blood pressure, heart rate, and plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and cortisol were determined in 20 healthy subjects and 68 patients who had agoraphobia with panic attacks or panic disorder. Yohimbine produced panic attacks meeting DSM-III criteria in 37 patients and one healthy subject. The patients reporting yohimbine-induced panic attacks had significantly larger increases in plasma MHPG, cortisol, systolic blood pressure, and heart rate than the healthy subjects. These findings support the hypothesis relating high noradrenergic neuronal activity to the pathophysiology of panic attacks in a subgroup of panic disorder patients.


Targeted deletion of Kcne3 impairs skeletal muscle function in mice.
KCNE3 (MiRP2) forms heteromeric voltage-gated K+ channels with the skeletal muscle-expressed KCNC4 (Kv3.4) α subunit. KCNE3 was the first reported skeletal muscle K+ channel disease gene, but the requirement for KCNE3 in skeletal muscle has been questioned. Here, we confirmed KCNE3 transcript and protein expression in mouse skeletal muscle using Kcne3-/- tissue as a negative control. Whole-transcript microarray analysis (770,317 probes, interrogating 28,853 transcripts) findings were consistent with Kcne3 deletion increasing gastrocnemius oxidative metabolic gene expression and the proportion of type IIa fast-twitch oxidative muscle fibers, which was verified using immunofluorescence. The down-regulated transcript set overlapped with muscle unloading gene expression profiles (≥1.5-fold change; P < 0.05). Gastrocnemius K+ channel α subunit remodeling arising from Kcne3 deletion was highly specific, involving just 3 of 69 α subunit genes probed: known KCNE3 partners KCNC4 and KCNH2 (mERG) were down-regulated, and KCNK4 (TRAAK) was up-regulated (P < 0.05). Functionally, Kcne3-/- mice exhibited abnormal hind-limb clasping upon tail suspension (63% of Kcne3-/- mice ≥10-mo-old vs. 0% age-matched Kcne3+/+ littermates). Whereas 5 of 5 Kcne3+/+ mice exhibited the typical biphasic decline in contractile force with repetitive stimuli of hind-limb muscle, both in vivo and in vitro, this was absent in 6 of 6 Kcne3-/- mice tested. Finally, myoblasts isolated from Kcne3-/- mice exhibit faster-inactivating and smaller sustained outward currents than those from Kcne3+/+ mice. Thus, Kcne3 deletion impairs skeletal muscle function in mice.-King, E. C., Patel, V., Anand, M., Zhao, X., Crump, S. M., Hu, Z., Weisleder, N., Abbott, G. W. Targeted deletion of Kcne3 impairs skeletal muscle function in mice.


Breathheld autocalibrated phase-contrast imaging.
To compare generalized autocalibrating partially parallel acquisitions (GRAPPA), modified sensitivity encoding (mSENSE), and SENSE in phase-contrast magnetic resonance imaging (PC-MRI) applications. Aliasing of the torso can occur in PC-MRI applications. If the data are further undersampled for parallel imaging, SENSE can be problematic in correctly unaliasing signals due to coil sensitivity maps that do not match that of the aliased volume. Here, a method for estimating coil sensitivities in flow applications is described. Normal volunteers (n = 5) were scanned on a 1.5 T MRI scanner and underwent PC-MRI scans using GRAPPA, mSENSE, SENSE, and conventional PC-MRI acquisitions. Peak velocity and flow through the aorta and pulmonary artery were evaluated. Bland-Altman statistics for flow in the aorta and pulmonary artery acquired with mSENSE and GRAPPA methods (R = 2 and R = 3 cases) have comparable mean differences to flow acquired with conventional PC-MRI. GRAPPA and mSENSE PC-MRI have more robust measurements than SENSE when there is aliasing artifact caused by insufficient coil sensitivity maps. For peak velocity, there are no considerable differences among the mSENSE, GRAPPA, and SENSE reconstructions and are comparable to conventional PC-MRI. Flow measurements of images reconstructed with autocalibration techniques have comparable agreement with conventional PC-MRI and provide robust measurements in the presence of wraparound.


Clinical outcomes and dislocation rates after hip reconstruction using the Bioball system.
Instability accounts for 1/3 of revision total hip arthroplasty (rTHA) performed in the UK. Removal of well-fixed femoral stems in rTHA is challenging with a risk of blood loss and iatrogenic damage to the femur. The Bioball universal adaptor (BUA), a modular head neck extension adaptor, provides a mechanism for optimisation of femoral offset, leg length and femoral anteversion. This can avoid the need for femoral stem revision in selected cases.The aim of this study is to present the clinical results and rate of instability following revision with this BUA at a minimum of 2 years follow-up. A review of our prospectively collected database was performed. All patients treated with the Bioball device were included. Clinical and radiologic review were performed pre- and post-surgery. Specific enquiry for instability was made. The Oxford Hip Score (OHS), EuroQol (EQ-5D) score and WOMAC scores were calculated pre-and post-operatively. Complications were recorded. 32 rTHA procedures were performed using the Bioball device between 2013 and 2016. 4 patients did not wish to complete post-operative questionnaires. 2 patients (2/28, 7%) complained of recurrent dislocations following their rTHA procedure. 1 patient complained of instability but no dislocation. The median pre-operative EQ-5D was 0.195 (range -0.07-0.85), OHS was 20 (range 5-43) and WOMAC was 29.8 (range 15.5-52.3). The median EQ-5D was 0.85 (range 0.59-1), OHS was 39 (range 21-48) and WOMAC was 91.1 (range 44.5-99.2) at final follow-up. There were significant improvements in the EQ-5D (p = 0.0009), OHS (p = 0.0004) and WOMAC (p = 0.0001). The BUA is associated with significant functional improvement and relatively low dislocation rates in revision THA. It is a viable option for use in the revision setting.


Kaistia granuli sp. nov., isolated from anaerobic granules in an upflow anaerobic sludge blanket reactor.
A Gram-negative, chemo-organotrophic, non-motile, non-spore-forming, rod-shaped bacterium (designated strain Ko04(T)) was isolated from anaerobic granules in an upflow anaerobic sludge blanket reactor, and was investigated using a polyphasic taxonomic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain Ko04(T) belongs to the order Rhizobiales in the Alphaproteobacteria. Comparative 16S rRNA gene sequence analysis showed that strain Ko04(T) was most closely related to Kaistia adipata (97.5 %) and that sequence similarities with other species of Rhizobiales with validly published names were less than 92.5 %. The predominant ubiquinone was Q-10 and the major fatty acids were C(18 : 1)omega7c/omega9t/omega12t, C(19 : 0 )cyclo omega8c and C(18 : 0). The G+C content of the genomic DNA of strain Ko04(T) was 67.8 mol%. The level of DNA-DNA relatedness with K. adipata Chj404(T) was 15 %. The results of the genotypic analyses in combination with chemotaxonomic and physiological data demonstrated that strain Ko04(T) represents a novel species within the genus Kaistia, for which the name Kaistia granuli sp. nov. is proposed. The type strain is Ko04(T) (=KCTC 12575(T)=LMG 23410(T)).


Dual antibacterial activities of a chitosan-modified upconversion photodynamic therapy system against drug-resistant bacteria in deep tissue.
Photodynamic therapy (PDT) has recently been proposed as an innovative approach to combat multi-drug resistant (MDR) bacteria. To improve the penetration depth of current PDT, a core-shell upconversion nanoparticle (UCNP) based PDT system, composed of a cationic N-octyl chitosan (OC) coated UCNP loaded with the photosensitizer zinc phthalocyanine (OC-UCNP-ZnPc), was constructed to enhance the antibacterial efficacy against MDR bacteria in deep tissue. The core-shell UCNPs displayed a higher upconversion fluorescence efficiency compared to the inner UCNP core. Dual antibacterial activities induced by chitosan and PDT-induced ROS were demonstrated, independent of the bacterial species. In particular, these nanoconstructs exhibited excellent antibacterial effects on the MDR bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and β-lactamase-producing Escherichia coli. In vivo antibacterial therapy for murine MRSA-infected abscesses in the deep tissue (1 cm) strongly confirmed the outstanding anti-MRSA efficacy of OC-UCNP-ZnPc. Our results indicated that the OC-UCNP-ZnPc based PDT system triggered by deep-penetrating NIR light has a prominent antibacterial effect on MDR bacteria, which could be a promising strategy for deep-tissue infections.


Microtubule search-and-capture model evaluates the effect of chromosomal volume conservation on spindle assembly during mitosis.
Variation in the chromosome numbers can arise from the erroneous mitosis or fusion and fission of chromosomes. While the mitotic errors lead to an increase or decrease in the overall chromosomal substance in the daughter cells, fission and fusion keep this conserved. Variations in chromosome numbers are assumed to be a crucial driver of speciation. For example, the members of the muntjac species are known to have very different karyotypes with the chromosome numbers varying from 2n=70+3B in the brown brocket deer to 2n=46 in the Chinese muntjac and 2n=6/7 in the Indian muntjac. The chromosomal content in the nucleus of these closely related mammals is roughly the same and various chromosome fusion and fission pathways have been suggested as the evolution process of these karyotypes. Similar trends can also be found in lepidoptera and yeast species which show a wide variation of chromosome numbers. The effect of chromosome number variation on the spindle assembly time and accuracy is still not properly addressed. We computationally investigate the effect of conservation of the total chromosomal substance on the spindle assembly during prometaphase. Our results suggest that chromosomal fusion pathways aid the microtubule-driven search and capture of the kinetochore in cells with monocentric chromosomes. We further report a comparative analysis of the site and percentage of amphitelic captures, dependence on cell shape, and position of the kinetochore in respect to chromosomal volume partitioning.


Propagation of cortical spreading depolarization in the human cortex after malignant stroke.
To investigate hemodynamic response pattern and spatiotemporal propagation of cortical spreading depolarization in the peri-infarct region of malignant hemispheric stroke. In this prospective observational case study we used intraoperative laser speckle technology to measure cerebral blood flow in patients with malignant hemispheric stroke. Additionally, postoperative occurrence of cortical spreading depolarization was monitored using a subdural recording strip for electrocorticography and infarct progression was assessed by serial MRI. In 7 of 20 patients, 19 blood flow changes typical of cortical spreading depolarizations occurred during a 20-minute period. Thirteen events were characterized by increase, 2 by biphasic response, and 4 by decrease of blood flow. Propagation velocity ranged from 1.7 to 9.2 mm/min and propagation area from 0.1 to 4.8 cm(2). Intrinsic optical signal alterations preceded and low-frequency vascular fluctuations were suppressed during the hemodynamic responses. A mean number of 56 ± 82 cortical spreading depolarizations per patient was recorded and a mean infarct progression of 30 ± 13 cm(3) was detected in 5 of 7 patients. We visualize the spatiotemporal propagation of spreading depolarizations in the human cerebral cortex intraoperatively. In patients with focal ischemia, multiple cortical spreading depolarizations with either hyperemic or hypoemic flow responses occurred. Our data suggest that, in patients with focal ischemia, cortical spreading depolarizations are associated with both unfavorable and protective hemodynamic responses.


Management of stress urinary incontinence.
Although there is renewed interest in conservative therapies for stress urinary incontinence, such as pelvic floor exercises, electrical stimulation, and duloxetine therapy, surgery remains the primary choice in managing this condition. Surgical options include paravaginal defect repair, the Marshall-Marchetti-Krantz procedure, open and laparoscopic Burch urethropexy, and pubovaginal sling procedures. There is a growing trend in the United States toward use of the pubovaginal sling procedure as the primary operation for urinary incontinence due to less invasive techniques. Studies comparing the pubovaginal sling with open urethropexy have shown similar short-term cure rates. More large prospective, randomized studies are needed to assess long-term rates.


Interaction between rocuronium bromide and some drugs used during anaesthesia.
In cats anaesthetized with i.p. chloralose and pentobarbitone, neuromuscular blockade produced by various doses of rocuronium was measured and dose response curves constructed in the presence of halothane, enflurane, nitrous oxide, propofol, alfentanil, thiopentone, ketamine, diazepam, chlorpromazine, morphine or streptomycin. In general, when a shift in the dose response curve was produced, it was a parallel shift to the left, indicating potentiation. Both halothane and enflurane produced a left shift and a small increase in the time from maximum block to 90% recovery. Nitrous oxide had no effect on the depth of block but delayed recovery. Thiopentone and ketamine potentiated the blocking effect of rocuronium but propofol and alfentanil had no effect. Chlorpromazine and morphine caused potentiation which took 1-1.5 h to develop. Streptomycin had a potentiating effect in four cats but not in two others. Diazepam displaced the dose-response curve to the right in four cats. Prior treatment with suxamethonium had no effect.


The role of goal-related autonomy: A self-determination theory analysis of perfectionism, poor goal progress, and depressive symptoms.
Adopting a self-determination theory perspective, this 3-wave longitudinal study explores the role of perfectionism in goal pursuit and the experience of depressive symptoms. The findings highlight the role of goal-related autonomy in mediating the opposite effects of self-critical and personal standards perfectionism on goal progress and depressive symptoms over the course of an academic year. The results suggest a way of understanding the pathway to depressive symptoms and poor goal progress in perfectionists. They point to a number of implications for clinical practice when working with self-critical perfectionists. Specifically, they indicate that interventions aimed at promoting autonomous motivation, may not only bolster goal progress but also act as a protective factor against depressive symptoms. Together, the results indicate that autonomous motivation is central to goal progress and suggest that low goal-related autonomy can be linked to negative outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Vitamin D Trajectories and Cardiometabolic Risk Factors During Childhood: A Large Population-Based Prospective Cohort Study.
Vitamin D has been indicated to play an important role in the optimal function of the cardiovascular system. However, with limited evidence, it remains unclear whether vitamin D status transition during childhood would affect cardiometabolic risk factors. Thus, we aimed to identify the associations of the longitudinal trajectory of vitamin D status with cardiometabolic risk factors in children. A total of 10,482 participants with complete follow-up records from a large population-based prospective cohort study were included in this analysis. The 25-hydroxyvitamin D [25(OH)D] concentrations, blood pressure, blood lipids, and fasting blood glucose were determined. Vitamin D deficiency was defined as serum 25(OH)D concentrations below 30 nmol/L according to the Institute of Medicine recommendations. Based on the vitamin D status at baseline and follow-up, we identified four possible trajectories: (1) persistent non-deficiency (reference); (2) baseline non-deficiency to follow-up deficiency; (3) baseline deficiency to follow-up non-deficiency; (4) persistent deficiency. The relationships between cardiometabolic risk factors and vitamin D trajectories were evaluated using adjusted risk ratios (RRs). Overall, 35.1 and 24.2% of participants had vitamin D deficiency at the baseline and follow-up, respectively, and 15.1% were under the condition of persistent vitamin D deficiency. Compared to children with persistent non-deficiency, those who shifted from non-deficiency at baseline to deficiency at follow-up had a 2.09-fold (95% CI: 1.36, 3.23) increased risk of high triglyceride (TG). Besides, children with altered vitamin D status from deficiency to non-deficiency during follow-up were still at a significantly higher risk of high total cholesterol (TC) than the reference group [RR (95% CI): 1.39 (1.04, 1.86)]. Finally, children with persistent vitamin D deficiency were at the highest risks of high TC [RR (95% CI): 1.61 (1.18, 2.19), P trend < 0.001], high low-density lipoprotein cholesterol (LDL-C) [RR (95% CI): 1.53 (1.04, 2.27), P trend = 0.046], and high TG [RR (95% CI): 1.96 (1.34, 2.87), P trend = 0.003]. Our results suggest that persistent vitamin D deficiency might increase the risk of dyslipidemia in children, and vitamin D deficiency could have has short- and long-term effects on TG and TC, respectively.


Investigating the relationship between specific negative symptoms and metacognitive functioning in psychosis: A systematic review.
Disrupted metacognition is implicated in development and maintenance of negative symptoms, but more fine-grained analyses would inform precise treatment targeting for individual negative symptoms. This systematic review identifies and examines datasets that test whether specific metacognitive capacities distinctly influence negative symptoms. PsycINFO, EMBASE, Medline and Cochrane Library databases plus hand searching of relevant articles, journals and grey literature identified quantitative research investigating negative symptoms and metacognition in adults aged 16+ with psychosis. Authors of included articles were contacted to identify unique datasets and missing information. Data were extracted for a risk of bias assessment using the Quality in Prognostic Studies tool. 85 published reports met criteria and are estimated to reflect 32 distinct datasets and 1623 unique participants. The data indicated uncertainty about the relationship between summed scores of negative symptoms and domains of metacognition, with significant findings indicating correlation coefficients from 0.88 to -0.23. Only eight studies investigated the relationship between metacognition and individual negative symptoms, with mixed findings. Studies were mostly moderate-to-low risk of bias. The relationship between negative symptoms and metacognition is rarely the focus of studies reviewed here, and negative symptom scores are often summed. This approach may obscure relationships between metacognitive domains and individual negative symptoms which may be important for understanding how negative symptoms are developed and maintained. Methodological challenges around overlapping participants, variation in aggregation of negative symptom items and types of analyses used, make a strong case for use of Individual Participant Data Meta-Analysis to further elucidate these relationships.


Chemoselective Lewis pair polymerization of renewable multivinyl-functionalized γ-butyrolactones.
Multivinyl-functionalized γ-butyrolactones, γ-vinyl-γ-methyl-α-methylene-γ-butyrolactone (γVMMBL) and γ-allyl-γ-methyl-α-methylene-γ-butyrolactone (γAMMBL), have been synthesized from biorenewable ethyl levulinate and effectively polymerized by Lewis pairs consisting of an organic N-heterocyclic carbene Lewis base and a strong organo-Lewis acid E(C6F5)3 (E = Al, B). This Lewis pair polymerization is quantitatively chemoselective, proceeds exclusively via polyaddition across the conjugated α-methylene double bond without participation of the γ-vinyl or γ-allyl double bond, and produces high-molecular-weight functionalized polymers with unimodal molecular-weight distributions. The Al-based Lewis pair produces a polymer with approximately 5.5 times higher molecular weight than that produced by the B-based Lewis pair. The resulting vinyl-functionalized polymers are soluble in common organic solvents and stable at room temperature, and can be thermally cured into crosslinked materials.This article is part of the themed issue 'Frustrated Lewis pair chemistry'.


Patient with Crouzon Syndrome Treated with Modified Le Fort III Osteotomy without Previous Orthodontic Treatment: Case Report and a Review of the Literature.
Crouzon syndrome is the most common type of craniofacial dysostosis anomaly which presents a great challenge for clinicians since birth. Multiple synostoses in the sutures of the cranial base in this syndrome result in the hypoplasia of the midface, shallow orbits, a short nasal dorsum, maxillary hypoplasia, and, in severe cases, obstruction of the upper airways. Apart from esthetic and functional problems, these patients suffer from various psychological problems which mandate correction of midface deformities at younger ages. The aim of this report is to describe the case of a 26-year-old female patient with Crouzon syndrome displaying severe midface hypoplasia and proptosis with no history of orthodontic treatment, who was treated with modified Le Fort III osteotomy with a coronal and intraoral approach without periocular incisions.


Risk of exposure of surgical personnel to patients' blood during surgery at San Francisco General Hospital.
We undertook an observational study of 1307 consecutive surgical procedures at San Francisco General Hospital to record descriptions of intraoperative exposures to blood and other body fluids, determine the factors predictive of these exposures, and identify interventions that might reduce their frequency. During a two-month period, circulating nurses took note of parenteral and cutaneous exposures to blood and recorded information about all procedures. In a follow-up validation study, 50 additional procedures were observed by the study investigators to determine the accuracy of the data collected by the nurses. A total of 960 gloves used by surgical personnel during the validation study were examined to determine the perforation rate. Accidental exposure to blood (parenteral or cutaneous) occurred during 84 procedures (6.4 percent; 95 percent confidence interval, 5.1 to 7.8 percent). Parenteral exposure occurred in 1.7 percent. The risk of exposure was highest when the procedures lasted more than three hours, when blood loss exceeded 300 ml, and when major vascular and intraabdominal gynecologic surgery was involved. Neither knowledge of diagnosed human immunodeficiency virus (HIV) infection nor awareness of a patient's high-risk status for such infection influenced the rate of exposure. Double gloving prevented perforations of the inner glove and cutaneous exposures of the hand. We conclude that all surgical personnel are at risk for intraoperative exposure to blood. Our data support the practice of double gloving and the increased use of water-proof garments and face shields to prevent mucocutaneous exposures to blood. No evidence was found to suggest that preoperative testing for HIV infection would reduce the frequency of accidental exposures to blood.


A multi-task deep learning model for the classification of Age-related Macular Degeneration.
Age-related Macular Degeneration (AMD) is a leading cause of blindness. Although the Age-Related Eye Disease Study group previously developed a 9-step AMD severity scale for manual classification of AMD severity from color fundus images, manual grading of images is time-consuming and expensive. Built on our previous work DeepSeeNet, we developed a novel deep learning model for automated classification of images into the 9-step scale. Instead of predicting the 9-step score directly, our approach simulates the reading center grading process. It first detects four AMD characteristics (drusen area, geographic atrophy, increased pigment, and depigmentation), then combines these to derive the overall 9-step score. Importantly, we applied multi-task learning techniques, which allowed us to train classification of the four characteristics in parallel, share representation, and prevent overfitting. Evaluation on two image datasets showed that the accuracy of the model exceeded the current state-of-the-art model by > 10%. Availability: https://github.com/ncbi-nlp/DeepSeeNet.


Localization of enterobacterial common antigen: Proteus mirabilis and its various L-forms.
An investigation of Proteus mirabilis wild-type strains and their various derived L-forms shows that the enterobacterial common antigen (ECA) is localized in the outer membrane of the cell envelope of these strains. In strains where the outer membrane is lacking (stable protoplast L-forms) or where its amount is reduced (spheroplast UL19) no ECA or only reduced amounts of it are detected by serological tests or by ferritin-labeling techniques.


Treatment foster care services: a research agenda for child welfare.
Treatment foster care is a recent and rapidly expanding multisystem service. This article summarizes the empirical literature on treatment foster care and offers suggestions for future research directions. Results from program evaluations and experimental research suggest that treatment foster care is an effective alternative to residential treatment for seriously troubled and troubling children. The research has lacked rigorous controls regarding the populations served, however, as well as the critical components of interventions used in treatment foster care that produce positive results for the children. Integration with pertinent research findings from other disciplines is also necessary because of the multisystemic needs of the diverse population of children served in treatment foster care.


Therapies for Tau-associated neurodegenerative disorders: targeting molecules, synapses, and cells.
Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders (Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating (1) the broad class of chemicals termed "small molecules"; (2) adaptive immunity through both passive and active antibody treatments; (3) innate immunity with an emphasis on microglial modulation; (4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.


Recombinant adenovirus as a methodology for exploration of physiologic functions of growth factor pathways.
The use of recombinant adenoviruses (Ad) to express secreted antagonists of growth factors represents a powerful strategy for studying physiologic functions of growth factor pathways in experimental animals. Indeed, a single adenoviral injection can produce characteristic high-level and persistent plasma expression of soluble receptor ectodomains or secreted protein antagonists, allowing highly stringent conditional inactivation of target pathways in vivo. In this review, we describe our experience using recombinant Ad to inactivate growth factor pathways in vivo and discuss their advantages and limitations. Using our studies on vascular endothelial growth factor and Wnt systems as examples, we further describe how recombinant Ad can unveil previously unknown physiological roles of signaling pathways. Finally, we discuss the potential physiological and therapeutic relevance of our findings.


Haemodynamic assessment of fetal heart arrhythmias.
The effects of fetal heart arrhythmias were examined serially in two pregnancies by three non-invasive methods: fetal ECG, fetal phonocardiography and ultrasonic measurement of fetal blood flow. In a case of supraventricular arrhythmia, there was evidence suggesting that the stroke volume varied with ventricular filling according to the Frank-Starling law. In a case of total atrioventricular block the mean blood flow in the fetal descending aorta and in the umbilical vein was within the normal range. Blood flow velocity in the inferior vena cava of the fetus reflected atrial contractions. In the phonocardiogram, a phenomenon similar to 'bruit de canon' was found. Both pregnancies had good outcomes and subsequent development of the infants was normal except for the persisting dysrhythmias. The two cases exemplify how fetal heart function can be assessed in utero.


Orientin alleviates cognitive deficits and oxidative stress in Aβ1-42-induced mouse model of Alzheimer's disease.
β-Amyloid (Aβ)-mediated neurotoxicity plays a critical role in the pathogenesis of Alzheimer's disease (AD), possibly including Aβ-induced mitochondrial dysfunction and oxidative stress. Previous studies have demonstrated that orientin (Ori) possesses antioxidation capabilities in vitro. Therefore, current study is to demonstrate that Ori can activate Nrf2/HO-1 signaling and alleviate apoptosis induced by Aβ1-42, and ameliorate cognitive deficits in AD mice. AD models were made by injecting Aβ1-42 into the bilateral hippocampus of mice. The mice were randomly assigned to three groups: the normal mice and Aβ1-42-induced AD mice with saline, and Aβ1-42-induced AD mice with Ori (5mg/kg), and were injected intraperitoneally once a day for 15 days. After the Morris Water Maze (MWM) test, mice were sacrificed and brains were harvested for biochemical analysis. Results indicated that Ori could ameliorate cognitive deficits in AD mice. Levels of oxidative stress, indicated by production of reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), 4-hydroxy-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), were significantly decreased after Ori treatment. In addition, the current study showed that Ori could attenuate mitochondrial dysfunction induced by Aβ1-42, and subsequently inhibited the mitochondrial apoptotic pathway. Ori induced the nuclear translocation of Nrf2, which enhanced the expression of HO-1 and activation of the redox signaling pathway. Ori might alleviate cognitive deficits and oxidative stress in AD mice, which might be a potential therapeutic drug for AD.


Comparing EEG, its time-derivative and their joint use as features in a BCI for 2-D pointer control.
Efficient and accurate classification of event related potentials is a core task in brain-computer interfaces (BCI). This is normally obtained by first extracting features from the voltage amplitudes recorded via EEG at different channels and then feeding them into a classifier. In this paper we evaluate the relative benefits of using the first order temporal derivatives of the EEG signals, not the EEG signals themselves, as inputs to the BCI: an area that has not been thoroughly examined. Specifically, we compare the classification performance of features extracted from the first derivative, with those derived from the amplitude, as well as their combination using data from a P300-based BCI mouse. Features were selected based on the absolute difference of medians of the target and non-target classes. Classification was carried out by an ensemble of linear support vector machines which were optimised using the mutual information criterion. Comparisons were based on the area under the receiver operating characteristics. The Mann-Whitney one-tailed test was used to study significance. Results show that EEG amplitudes are outperformed by both the first derivative and the combined feature vector and that derivatives are better than the combined vector.


Pre-meiotic transformation of germplasm-related structures during male gamete differentiation in Xenopus laevis.
To highlight the ultrastructural features of transformation occurring with germplasm-related structures (GPRS), the spermatogenic cells of Xenopus laevis were studied by transmission electron microscopy and quantitative analysis. It was determined that in spermatogonia and spermatocytes, the compact germinal granules underwent fragmentation into particles comparable with inter-mitochondrial cement (IMC). Fragments of IMC agglutinated some cell mitochondria and resulted in the creation of mitochondrial clusters. Clustered mitochondria responded with loss of their membranes that occurred by the twisting of membranous protrusions around themselves until multi-layered membranes were formed. The mitochondrial affinity of multi-layered membranes was proven by an immunopositive test for mitochondrial dihydrolipoamide acetyltransferase. As a consequence of mitochondrial membrane twisting, the naked mitochondrial cores appeared and presumably underwent dispersion, which is the terminal stage of GPRS transformation. As no GPRS were observed in spermatids and sperm, it was assumed that these structures are functionally assigned to early stages of meiotic differentiation.


Evaluation of poor left ventricle: multislice computer tomography in the assessment of myocardial viability.
The evaluation of left ventricular function and viability is critical in patients with suspected or documented ischemic heart disease. Recently, cardiac multislice computed tomography (MSCT) has emerged as a powerful modality for cardiac imaging. In addition to coronary artery assessment, contrast enhanced MSCT can provide reliable information about myocardial function, perfusion and viability. This review will focus on the pathophysiological mechanisms and clinical applications of contrast enhanced myocardial function and viability MSCT imaging.


Localized co-delivery of CNTF and FK506 using a thermosensitive hydrogel for retina ganglion cells protection after traumatic optic nerve injury.
Following the traumatic axonal injury in the optic nerve, the failure of retrograde axonal transport to continuously supply neurotrophins from the brain to retina results in deprivation of neurotrophins in retinal ganglion cells (RGCs), which in turn can modulate the fate of RGCs toward apoptosis and thereby impede axon regeneration. In this study, a ciliary neurotrophic factor (CNTF) loaded thermo-sensitive hydrogel was designed and developed as a localized drug depot to restore neurotrophins supply following axon injury. Besides, following traumatic axon injury, overactive immune responses cause neurotoxicity and induce scar formation which together constitutes the major hindrances for axon regeneration. Thus, the FK506, a hydrophobic macrolide immunosuppressant, was co-loaded into the hydrogel after encapsulating it into a polymeric micelle. The materials can undergo sol-to-gel transition within minutes under a physiological pH of 37 °C. The release of drugs from the hydrogel exhibited a sustainable profile in vitro. The optic nerve was exposed by surgical procedure and the animal model was prepared by crushing the nerve with a reverse clamp. For the localized delivery to the optic nerve, a pre-hydrogel liquid containing chitosan, FK506 (in micelle), CNTF, and the gelling agent was directly smeared on the injured site, which gelled under physiological condition. This co-delivery system exhibited in vivo RGCs protective effect against the adverse effects caused by traumatic optic nerve injury, indicating the potential of this drug delivery system for effective optic nerve repair and this strategy may provide promising platforms for localized drug delivery in various other therapies.


Long-term follow-up study of 10 adolescent patients with sleep-wake schedule disorders.
Therapeutic trials for sleep-wake schedule disorders have been described, but a long-term follow-up of adolescents with such disorders have not previously been reported. We investigated 10 adolescents with sleep-wake schedule disorders who had formerly received intensive treatment. The investigation was carried out with detailed questionnaires about current sleep conditions and social state. The follow-ups were obtained from 1.2 to 11.2 years after the initial treatment. Three cases have remitted, and six have improved in illness severity. All patients showed improvement in social adaptation. Improvement in the social adaptation level was greater than improvement in the illness severity level. More cases should be studied to learn what factors influence the prognosis of these disorders.


EBV-miR-BART10-3p facilitates epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma by targeting BTRC.
Epstein-Barr virus (EBV) infection is closely associated with tumorigenesis and development of nasopharyngeal carcinoma (NPC), but the underlying molecular mechanisms remain poorly understood. It has been recently reported that EBV encodes 44 mature miRNAs, some of which were found to promote tumor development by targeting virus-infected host genes or self-viral genes. However, few targets of EBV encoded-miRNAs that are related to NPC development have been identified to date. In this study, we revealed that in NPC cells, EBV-miR-BART10-3p directly targets BTRC gene that encodes βTrCP (beta-transducin repeat containing E3 ubiquitin protein ligase). We found that EBV-miR-BART10-3p expression in clinical samples from a cohort of 106 NPC patients negatively correlated with BTRC expression levels. Over-expression of EBV-miR-BART10-3p and down-regulation of BTRC were associated with poor prognosis in NPC patients. EBV-miR-BART10-3p promoted the invasion and migration cabilities of NPC cells through the targeting of BTRC and regulation of the expression of the downstream substrates β-catenin and Snail. As a result, EBV-miR-BART10-3p facilitated epithelial-mesenchymal transition of NPC. Our study presents an unreported mechanism underlying EBV infection in NPC carcinogenesis, and provides a potential novel biomarker for NPC diagnosis, treatment and prognosis.


WHO Class of Obesity Influences Functional Recovery Post-TKA.
No study in the literature has compared early functional recovery following total knee arthroplasty (TKA) in the obese with the nonobese using World Health Organization (WHO) classes of obesity. Our aim was to compare functional scores and flexion post-TKA in each class of obesity as per WHO classification against a matched control group of nonobese patients. Records of 885 consecutive primary TKA patients (919 knees) operated by a single surgeon were reviewed. The first 35 knees in each class I, class II and class III obesity group during the study period were then matched with a similar number of knees in nonobese TKA patients during the same period. Functional scores recorded pre- and postoperatively at 3 months and 1 year were Western Ontario and McMaster Osteoarthritis Index (WOMAC), Short-Form Health Survey (SF-12) score, and Knee Society Score (KSS). There was no difference in any parameter between the class I obese and matched nonobese at any assessment point. In the class II obese, as compared to the nonobese, there was no difference in any parameter preoperatively and 3 months postoperatively. However, 1 year postoperatively, the SF-12 physical subscore was lower in the class II obese than the nonobese (44.7 vs. 48.6, p = 0.047) and the WOMAC score was significantly higher (15.8 vs. 9.7, p = 0.04). In the class III obese, the WOMAC score was significantly higher than the nonobese (58.1 vs. 44.3, p < 0.001 preoperatively; 15.7 vs. 8.1, p = 0.005 at 1 year) and KSS was significantly lower (83.5 vs. 96.5, p = 0.049 preoperatively; 172 vs. 185; p = 0.003 at 1 year). Knee flexion was significantly lower in the class III obese than the nonobese (95 vs. 113; p < 0.001 preoperatively; 120 vs. 127; p = 0.002 at 1 year). The class I obese can expect good early and late functional recovery as the nonobese. The class II obese can expect comparable early functional recovery as the nonobese but their late function may be lesser. The class III obese would have poorer functional scores and lesser knee flexion postoperatively compared to the nonobese. However, compared to their own preoperative status, there is definite improvement in function and knee flexion.


["Chronic ileo-colic intussusception without abdominal symptoms" (authors transl)].
A chronic ileo-colic intussusception of an 8 1/2 year old boy did not cause any abdominal complaints. There was a hypochromic anaemia with iron deficiency; occult blood was found in the stoll. Radiographically the lumen within the intussusceptum was extremely narrowed. Following surgery the anaemia disappeared.


Detrimental effects of Bartonella henselae are counteracted by L-arginine and nitric oxide in human endothelial progenitor cells.
The recruitment of circulating endothelial progenitor cells (EPCs) might have a beneficial effect on the clinical course of several diseases. Endothelial damage and detachment of endothelial cells are known to occur in infection, tissue ischemia, and sepsis. These detrimental effects in EPCs are unknown. Here we elucidated whether human EPCs internalize Bartonella henselae constituting a circulating niche of the pathogen. B. henselae invades EPCs as shown by gentamicin protection assays and transmission electron microscopy (TEM). Dil-Ac-LDL/lectin double immunostaining and fluorescence-activated cell sorting (FACS) analysis of EPCs revealed EPC bioactivity after infection with B. henselae. Nitric oxide (NO) and its precursor l-arginine (l-arg) exert a plethora of beneficial effects on vascular function and modulation of immune response. Therefore, we tested also the hypothesis that l-arg (1-30 mM) would affect the infection of B. henselae or tumor necrosis factor (TNF) in EPCs. Our data provide evidence that l-arg counteracts detrimental effects induced by TNF or Bartonella infections via NO (confirmed by DETA-NO and L-NMMA experiments) and by modulation of p38 kinase phosphorylation. Microarray analysis indicated several genes involved in immune response were differentially expressed in Bartonella-infected EPCs, whereas these genes returned in steady state when cells were exposed to sustained doses of l-arg. This mechanism may have broad therapeutic applications in tissue ischemia, angiogenesis, immune response, and sepsis.


Respiratory support strategies in the prevention and treatment of bronchopulmonary dysplasia.
Neonates who are born preterm frequently have inadequate lung development to support independent breathing and will need respiratory support. The underdeveloped lung is also particularly susceptible to lung injury, especially during the first weeks of life. Consequently, respiratory support strategies in the early stages of premature lung disease focus on minimizing alveolar damage. As infants grow and lung disease progresses, it becomes necessary to shift respiratory support to a strategy targeting the often severe pulmonary heterogeneity and obstructive respiratory physiology. With appropriate management, time, and growth, even those children with the most extreme prematurity and severe lung disease can be expected to wean from respiratory support.


Effects of plant genotype and growth stage on the betaproteobacterial communities associated with different potato cultivars in two fields.
Bacterial communities in the rhizosphere are dynamic and susceptible to changes in plant conditions. Among the bacteria, the betaproteobacteria play key roles in nutrient cycling and plant growth promotion, and hence the dynamics of their community structures in the rhizosphere should be investigated. Here, the effects of plant cultivar, growth stage, and soil type on the communities associated with potato cultivars Aveka, Aventra, Karnico, Modena, Premiere, and Désirée were assessed for two different fields containing sandy soil with either a high or low organic compound content. Thus, bacterial and betaproteobacterial PCR-denaturing gradient gel electrophoresis analyses were performed to analyze the effects of plant cultivar and growth on the rhizosphere community structure. The analyses showed that in both fields all cultivars had a rhizosphere effect on the total bacterial and betaproteobacterial communities. In addition, the plant growth stage strongly affected the betaproteobacterial communities in both fields. Moreover, the community structures were affected by cultivar, and cultivars differed in physiology, as reflected in their growth rates, root development, and estimated tuber starch contents. Analyses of betaproteobacterial clone libraries constructed for two selected cultivars (one cultivar that produced low-starch-content tubers and one cultivar that produced high-starch-content tubers), as well as bulk soil, revealed that the rhizospheres of the two cultivars selected for specific bacteria, including plant-growth-promoting bacteria, such as Variovorax and Achromobacter spp. In addition, quantitative PCR-based quantification of the Variovorax paradoxus-specific functional gene asfA (involved in desulfonation) indicated that there were clear potato rhizosphere effects on the abundance of this gene. Interestingly, both cultivar type and plant growth stage affected the community under some circumstances.


Inhibitory effects of vancomycin and fosfomycin on methicillin-resistant Staphylococcus aureus from antibiotic-impregnated articulating cement spacers.
Vancomycin and fosfomycin are antibiotics commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. This study compares the in vitro inhibitory effects against MRSA of articulating cement spacers impregnated with either vancomycin or fosfomycin. Vancomycin-impregnated articulating cement spacers and fosfomycin-impregnated articulating cement spacers were immersed in sterile phosphate-buffered saline (PBS) solutions and then incubated. Samples were collected for bioactivity evaluation. The aliquots were tested for MRSA inhibition with the disc diffusion method, and the inhibition zone diameters were measured. The inhibition zone differences were evaluated using the Wilcoxon Rank Sum Test. The vancomycin group had significantly larger inhibition zones than the fosfomycin group from day three through to completion of the fourth week of incubation (p < 0.001). The vancomycin group exhibited a MRSA inhibition zone up to four weeks but the fosfomycin group showed an inhibition zone for only three days and after that did not show the the potential to inhibit MRSA. This in vitro study found that the inhibitory effect of vancomycin-impregnated articulating cement spacers against MRSA outperformed fosfomycin-impregnated articulating cement spacers. Further comparing our results to other published reports suggests there might be a limitation of the disc diffusion bioassay to show a large inhibitory zone in a high concentration of a highly soluble antibiotic.Cite this article: V. Yuenyongviwat, N. Ingviya, P. Pathaburee, B. Tangtrakulwanich. Inhibitory effects of vancomycin and fosfomycin on methicillin-resistant Staphylococcus aureus from antibiotic-impregnated articulating cement spacers. Bone Joint Res 2017;6:132-136. DOI: 10.1302/2046-3758.63.2000639.


A flow cytometric assessment of the lymphocyte immunophenotypes in dogs naturally infected with Babesia rossi.
Immunity to Babesia infection requires both innate and acquired responses, including cell mediated- and humoral responses. The aims of this study were to investigate the variation in selected peripheral blood lymphocyte phenotypes in dogs with virulent babesiosis at presentation and over time after treatment, and to determine whether these were correlated with the severity of clinical signs. Forty-four dogs naturally infected with B. rossi were studied and 5 healthy dogs were included as controls. Blood samples were collected from the jugular vein at admission, prior to any treatment, and at 24h and 48-72h. Leukocytes were incubated with canine specific, fluorochrome conjugated anti-CD3, anti-CD4, anti-CD8, and anti-B cell markers. Babesia-infected dogs were divided into complicated or uncomplicated groups on clinical grounds and in-house laboratory assays. The percentage CD3+ lymphocytes in the complicated group was lower compared to the controls (P=0.014) and uncomplicated group (P=0.007). The percentage CD4+ T lymphocytes in the complicated group was lower compared to the controls (P=0.027) and uncomplicated group (P=0.014). Both the complicated as well as the uncomplicated groups expressed a lower percentage CD8+ T lymphocytes compared to the control group (P<0.001 and P=0.005, respectively). The percentage B lymphocytes was higher in the complicated group at 48-72h. These findings could indicate the presence of a functional immune suppression secondary to increased apoptosis or redistribution of effector lymphocytes and/or a combination of other immune modulatory mechanisms induced by B. rossi infection.


Investigation of timing of surgery and other factors possibly influencing outcome in dogs with acute thoracolumbar disc extrusion: a retrospective study of 1501 cases.
Intervertebral disc extrusions in the thoracolumbar region are a common spinal neurologic disorder in dogs and usually considered a neurological emergency. Several factors, like timing of surgery, have previously been analysed in order to determine the effect on outcome and time of recovery. Most studies have investigated one defined population of dogs and the influence of a single factor on the overall outcome. In this retrospective study, a large cohort of dogs and the influence of one or combinations of several factors on outcome and time of recovery were analysed. The bivariate analysis demonstrated a significant association between the following variables and the time of recovery: the time span between the onset of clinical signs and surgery (Cramers Phi [Formula: see text] = 0.14; P = 0.003), the grade of severity ([Formula: see text] = 0.23; P < 0.001) and the implementation of physical rehabilitation ([Formula: see text] = 0.2; P < 0.001). However, the analysis of a multivariable regression model demonstrated that a significant correlation only exists between the time span between the onset of clinical signs and surgery and the overall outcome (P = 0.007), as well as between the grade of severity and the time of recovery (P < 0.001). The percentage of dogs with lacking deep pain perception (DPP) that had to be euthanised due to their neurological condition, decreased from 20.0 to 2.9% when physical rehabilitation was implemented. Additionally, the proportion of dogs (same group) that improved to reach an ambulatory status increased from 80.0 to 91.4%. The results of the bivariate analysis demonstrated several correlations between some variables and overall outcome or time of recovery, whereas the multivariable regression model demonstrated only two associations. The time span between the onset of clinical signs and surgery was significantly associated with the overall outcome. We therefore suggest that a surgical intervention should be performed without unreasonable delay. Due to the correlation between the grade of severity and time of recovery, owners of dogs with more severe neurological deficits prior to surgery should be informed about the presumably prolonged time of recovery.


No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults.
Object-location memory (OLM) is known to decline with normal aging, a process accelerated in pathological conditions like mild cognitive impairment (MCI). In order to maintain cognitive health and to delay the transition from healthy to pathological conditions, novel strategies are being explored. Tentative evidence suggests that combining cognitive training and anodal transcranial direct current stimulation (atDCS), both reported to induce small and often inconsistent behavioral improvements, could generate larger or more consistent improvements or both, compared to each intervention alone. Here, we explored the combined efficacy of these techniques on OLM. In a subject-blind sham-controlled cross-over design 32 healthy older adults underwent a 3-day visuospatial training paired with either anodal (20 min) or sham (30 s) atDCS (1 mA, temporoparietal). Subjects were asked to learn the correct object-location pairings on a street map, shown over five learning blocks on each training day. Acquisition performance was assessed by accuracy on a given learning block in terms of percentage of correct responses. Training success (performance on last training day) and delayed memory after 1-month were analyzed by mixed model analysis and were controlled for gender, age, education, sequence of stimulation and baseline performance. Exploratory analysis of atDCS effects on within-session (online) and between-session (offline) memory performance were conducted. Moreover, transfer effects on similar trained (visuospatial) and less similar (visuo-constructive, verbal) untrained memory tasks were explored, both immediately after training, and on follow-up. We found that atDCS paired with OLM-training did not enhance success in training or performance in 1-month delayed memory or transfer tasks. In sum, this study did not support the notion that the combined atDCS-training approach improves immediate or delayed OLM in older adults. However, specifics of the experimental design, and a non-optimal timing of atDCS between sessions might have masked beneficial effects and should be more systematically addressed in future studies.


Biotechnology to harness the benefits of dietary phenolics; focus on Lamiaceae.
Phytochemicals from herbs and fermented legumes are excellent dietary sources of phenolic metabolites. These phenolics have importance not only as food preservatives but increasingly have therapeutic and pharmaceutical applications. The long-term research objecitves of the food biotechnology program at the University of Massachusetts are to elucidate the molecular and physiological mechanisms associated with synthesis of important health-related, therapeutic phenolic metabolites in food-related plants and fermented plant foods. Current efforts focus on elucidation of the role of the proline-linked pentose phosphate pathway in regulating the synthesis of anti-inflammatory compound, rosmarinic acid (RA). Specific aims of the current research efforts are: (i) To develop novel tissue culture-based selection techniques to isolate high RA-producing, shoot-based clonal lines from genetically heterogeneous, cross-pollinating species in the family Lamiaceae; (ii) To target genetically uniform, regenerated shoot-based clonal lines for: (a) preliminary characterization of key enzymes associated with the pentose phosphate pathway and linked to RA synthesis; (b) development of genetic transformation techniques for subsequent engineering of metabolic pathways associated with RA synthesis. These research objectives have substantial implications for harnessing the genetic and biochemical potential of genetically heterogeneous, food-related medicinal plant species. The success of this research also provides novel methods and strategies to gain access to metabolic pathways of pharmaceutically important metabolites from ginger, curcuma, chili peppers, melon or other food-related species with novel phenolics.


Pancreatic Cancer Progression in a Patient With Lynch Syndrome Receiving Immunotherapy: A Cautionary Tale.
Pancreatic ductal adenocarcinomas (PDACs) with DNA mismatch repair deficiency (MMRd) respond preferentially to immune checkpoint inhibitors (ICIs). However, a subset of MMRd PDACs does not respond to these agents. This report describes a patient with PDAC who experienced rapid disease progression suggestive of hyperprogressive disease. The case involved a 63-year-old man carrying a pathogenic germline PMS2 mutation who developed metastatic PDAC. His tumor showed isolated loss of PMS2 expression by immunohistochemistry (IHC). He was treated with pembrolizumab, but his disease rapidly progressed. Whole-genome and transcriptome sequencing of a liver metastasis biopsy, acquired at disease progression, showed a retained wild-type PMS2 allele and hallmarks of microsatellite stability, including low tumor mutational burden and low MSIsensor score. PCR-based microsatellite instability (MSI) testing of the treatment-naïve tumor showed microsatellite stability. The ICI-treated tumor had a lower density of CD8+ T-cell infiltration than the treatment-naïve tumor, which is contrary to the expected evolution with ICI responsiveness. Through this case and a review of the literature, we highlight the low penetrance of PMS2 germline mutations in PDAC and discuss pitfalls in ascertaining MMRd and MSI based on IHC testing alone. An orthogonal confirmatory assay is warranted in the presence of uncommon immunophenotypes, such as isolated PMS2 loss, to optimize selection of patients with PDAC for immunotherapy.


Contrasting Photochromic and Acidochromic Behaviors of Pyridyl- and Pyrimidylethynylated Mono- and Bis-Benzopyrans.
Investigation of photochromic and acidochromic behaviors of a set of pyridyl- and pyrimidylethynylated mono- and bis-benzopyrans reveals an intriguing influence of the N-heteroaryl ring on spectrokinetic properties of the photogenerated o-quinonoid colored reactive intermediates. While the absorption maxima of the pyridylethynylated bis-benzopyran and its photogenerated o-quinonoid colored species undergo bathochromic shifts by ca. 40 and 22 nm, respectively, in the presence of an acid (e.g., trifluoroacetic acid (TFA)), the same remain unaffected for the analogous pyrimidylethynylated bis-benzopyran and its photogenerated o-quinonoid colored species under similar conditions. Modification of the photochromic behavior of these benzopyrans and, hence, spectrokinetic properties of their photogenerated o-quinonoid species in the presence of H+ is a consequence of relative proton affinities of N-heteroaryl rings, i.e., pyridyl/pyrimidyl, and the resonance effects relayed through the ethynyl spacers in a push-pull π-delocalized-type skeleton; the mesomeric effects operate in a contrasting manner depending on the N-heteroaryl ring in the absence and in the presence of an acid. These molecular systems offer a unique opportunity to modulate both photochromic and acidochromic properties of benzopyrans and their photogenerated colored o-quinonoid intermediates by leveraging N-heteroaromatic rings.


Expression of vascular endothelial growth factor, fibroblast growth factor, and lactate dehydrogenase by human peritoneal mesothelial cells in solutions with lactate or bicarbonate or both.
In patients on long-term continuous ambulatory peritoneal dialysis, the efficiency of dialysis declines because of peritoneal neovascularization and loss of peritoneal mesothelial cells. In this study, we investigated the influence of lactate and bicarbonate in peritoneal dialysis fluid on such changes of the peritoneum. We studied the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which induce peritoneal neovascularization, by human peritoneal mesothelial cells (HPMCs) cultured with lactate or bicarbonate or both. Lactate dehydrogenase (LDH) was also measured to assess cell necrosis. Levels of VEGF, bFGF, and LDH in the culture supernatant showed a significant decrease after incubation of HPMCs with 15 mEq/L lactate plus 25 mEq/L bicarbonate, or with 40 mEq/L bicarbonate, as compared with incubation with 40 mEq/L lactate. Levels of VEGF and bFGF showed a concentration-dependent decrease when the cells were incubated with lactate or bicarbonate; a concentration-dependent increase of LDH was simultaneously observed. These results suggest that dialysis fluid containing 40 mEq/L bicarbonate is superior to fluid containing 40 mEq/L lactate with regard to its influence on the production of VEGF and bFGF although lactate and bicarbonate are both toxic for HPMCs.


Synthesis and hypolipidemic activity of diesters of arylnaphthalene lignan and their heteroaromatic analogs.
A series of diesters of arylnaphthalene lignan and their heteroaromatic analogs were synthesized and evaluated for hypolipidemic activity. The disasters with modifications at C-3 showed excellent hypocholesterolemic and high-density lipoprotein (HDL) cholesterol-elevating activities. Structure-activity analysis indicated that the 2-pyridylmethyl ester 5l has the optimum activity.


Treatment of Acute Type A Aortic Dissection Involving Upper Extremity Reperfusion Injury.
A 70-year-old man underwent emergent primary central repair for acute type A aortic dissection (AAAD) with right upper extremity ischemia. Ascending aorta and hemi-arch replacement concomitant with additional right upper peripheral bypass was performed for persistent right upper arm ischemia. The early reperfusion injury (RI) of the right upper extremity was defined the next day, and managed by continuous hemodialysis (CHD) and infusion therapy, resulting in the arm being salvaged. This is an extremely rare adverse phenomenon, and we herein described its successful treatment with perioperative intensive management following central repair of AAAD.


Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity.
Aggressive posterior retinopathy of prematurity (formerly known as fulminate/type II/rush disease) occurs in zone 1 or posterior zone 2. Treatment involves extensive near confluent laser ablation of a large area of avascular retina. Anterior segment ischemia is a rare complication that can occur due to injury to the long posterior ciliary arteries in the horizontal meridians during aggressive posterior laser treatment. The outcome of this rare complication is very poor. This case describes a favorable outcome of intravitreal injection of bevacizumab (Avastin) in a case of anterior segment ischemia.


The associations between THBD c.1418C>T polymorphism and lower extremity deep vein thrombosis or endothelial progenitor cell.
Studies have shown that the thrombomodulin gene (THBD) c.1418C>T polymorphism is associated with a variety of cardiovascular diseases. However, the study of THBD c.1418C>T polymorphism in deep vein thrombosis (DVT) is rare. This study aimed to reveal the correlation between the THBD c.1418C>T mutation and the occurrence of DVT, and to reveal partial molecular mechanism of endothelial progenitor cells (EPCs) participating in the onset of DVT. Whole blood samples of patients with lower extremity DVT (N.=100) and normal volunteers (N.=100) were collected to analyze the distribution of genotype of THBD c.1418C>T polymorphism using PCR and DNA sequencing. The pCMV6-entry vectors containing wild-type (WT) or mutated THBD cDNA (p. Ala473Val) were transfected into bone marrow derived EPCs. And the successful transfection of recombinant THBD and the stable expression of p. Ala473Val variant were determined by ELISA, respectively. Wound healing assay and Transwell migration assay were used to determine the migration ability of EPCs, and the cell angiogenesis ability was determined by tube formation assay. Western blotting was used to detect the expression level of related proteins. The frequencies of CC, CT and TT genotypes were 56%, 36%, 8% in patients with lower extremity DVT and 72%, 25%, 3% in controls group, respectively, and THBD c.1418C>T polymorphism was related with increased risk of DVT, especially in women. High level of p. Ala473Val variant inhibited the EPCs migration, the p. Ala473Val variant significantly decreased the activation of protein C and the expressions of VEGFRs and MMP1, MMP2, MMP3. Furthermore, p. Ala473Val variant also weaken the angiogenesis of EPCs and decreased the expression level of VE-cadherin, Flk-1, eNOS, and TIE-2. THBD c.1418C>T polymorphism is related with the lower extremity DVT, this may partially because of the inhibition of migration and angiogenesis of EPCs.


Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle.
Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. Although many skeletal muscle proteins are O-GlcNAcylated, the modification has not been extensively studied in this tissue, especially in the context of exercise. This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. DEM and exercise both reduced intracellular glutathione and increased O-GlcNAc. DEM upregulated OGT protein expression. The effects of the interventions were significant 4 h after exercise (P < 0.05). The changes in the mRNA levels of O-GlcNAc enzymes were different in the two muscles, potentially resulting from different rates of oxidative stress and metabolic demands between the muscle types. These findings indicate that oxidative environment promotes O-GlcNAcylation in skeletal muscle and suggest an interrelationship between cellular redox state and O-GlcNAc protein modification. This could represent one mechanism underlying cellular adaptation to oxidative stress and health benefits of exercise.


Development of a culturally tailored genetic counseling booklet about hereditary breast and ovarian cancer for Black women.
Printed educational materials (PEM) can serve as important tools to enhance and reinforce information presented during genetic counseling (GC) for BRCA1/2 testing, yet few such materials have been specifically developed for the Black community. The goal of the current study was to develop a BRCA1/2 genetic education booklet for Black women at increased risk for hereditary breast and ovarian cancer (HBOC). Investigators identified available PEM about BRCA1/2 targeted toward Blacks. To obtain possible perspectives of the target population regarding modified and newly developed materials, a Community Advisory Panel (CAP) comprising breast cancer survivors, advocates, and community leaders was convened. While the CAP felt PEM were an important adjunct to GC, the panel recommended developing materials that were more personalized and relevant to Black women. A 12-page booklet that follows the flow of a standard GC session was developed; it includes a limited amount of technical information, incorporates familiar terms and images to describe key concepts, and contains vignettes and photographs of Black women. Upon review of the newly developed booklet, CAP members agreed their input had been well implemented, and only had minor suggestions. The booklet is currently being used in a population-based study of BRCA1/2 mutations among Black women diagnosed with early-onset breast cancer. Involving members of the target community is critical to the development of culturally tailored PEM. Further evaluation of the utility of our booklet in increasing awareness and understanding of HBOC and promoting informed decision-making regarding genetic testing and medical management among Black women is needed.


Detachable Trap Preconcentrator with a Gas Chromatograph-Mass Spectrometer for the Analysis of Trace Halogenated Greenhouse Gases.
A detachable trap preconcentrator coupled with a gas chromatograph-mass spectrometer (GC-MS) was developed for measuring trace amounts of anthropogenic halogenated greenhouse gases such as hydrofluorocarbons (HFCs) and nitrogen trifluoride (NF3). Hayesep D cooled to -135 °C was used as an adsorbent for preconcentrating the target analytes. A differential trapping method was applied to remove major interfering substances such as CO2, N2, and O2 in order to ensure sufficient sampling volume of secondary injection trap. This was accomplished without using any CO2-removal agent such as molecular sieve adsorbents. Consequently, the temperature of the primary transfer trap was set to -75 °C for selective desorption of a significant amount of CO2 that could be vented out. In the meantime, the major components of air, e.g., N2 and O2, were vented out before transferring the analytes to the secondary injection trap, in order to protect the gas plumbing from pressure shock induced by rapid temperature ramping over 100 °C/min in the secondary trap. When the traps were heated, linear motion was operated to detach them from the copper baseplate on the freezer, thereby restricting heat transfer to the freezer and maintaining the freezer close to the background temperature of -135 °C. This trap design is a key improvement to address the insufficient cooling capacity of the employed freezer, allowing sensitive detection of trace halogenated greenhouse gases in GC-MS. NF3 and various HFCs at ambient levels were quantitatively and qualitatively measured with a precision of 0.35% at rates below 45 min/cycle. In particular, the limit of detection for NF3 was evaluated to be 0.2 pmol/mol, with linear responses at ambient concentration.


Reduction of leukocyte-derived H2S linked to abnormal glycolipid metabolism in hypertensive subjects.
We deduced that leukocyte-derived H2S would also play a pivotal role regarding nutrition homeostasis in hypertensive subjects. Plasma was obtained from patients with hypertension (n = 151) as well as control (n = 41). Leukocyte-derived H2S speed was determined, and biochemical indices of glucose and lipid metabolism were measured. Western blot analyses of CSE were also performed. Inflammation factors were measured. Leukocyte-derived H2S is produced at a significantly lower rate in overweight or obese patients (p < 0.05). There is a significant negative correlation between H2S and the levels of HOMA-RI and insulin in overweight patients and has a positive relationship with HDL-C only in overweight hypertensive patients (p < 0.05). Patients with high insulin levels showed down-regulation of CSE (p < 0.05). The levels of IL-10 decreased in both the obese and the overweight which showed significant relationship with all metabolism parameters such as HDL-C(r = 0.176, p = 0.031), insulin (r = -0.181, p = 0.027), HOMA-IR (r = -0.166, p = 0.045), and H2S speed (r = 0.995, p = 0.001). Linear regression analysis showed that insulin levels will increase (β = -1.685, p = 0.041) with the slower speed of H2S. Leukocyte-derived H2S production varied according to the nutritional status of hypertensive subjects, and the H2S/IL-10 signaling pathway may be the junction point among hypertension, disturbance of nutritional status, and inflammation.


Bottom-up formation of endohedral mono-metallofullerenes is directed by charge transfer.
An understanding of chemical formation mechanisms is essential to achieve effective yields and targeted products. One of the most challenging endeavors is synthesis of molecular nanocarbon. Endohedral metallofullerenes are of particular interest because of their unique properties that offer promise in a variety of applications. Nevertheless, the mechanism of formation from metal-doped graphite has largely eluded experimental study, because harsh synthetic methods are required to obtain them. Here we report bottom-up formation of mono-metallofullerenes under core synthesis conditions. Charge transfer is a principal factor that guides formation, discovered by study of metallofullerene formation with virtually all available elements of the periodic table. These results could enable production strategies that overcome long-standing problems that hinder current and future applications of metallofullerenes.


The tumor suppressor gene lkb1 is essential for glucose homeostasis during zebrafish early development.
The liver kinase B1 (LKB1) is encoded by tumor suppressor gene STK11, which is mutated in Peutz-Jeghers syndrome patients. Lkb1 plays indispensable roles in energy homeostasis. However, how Lkb1 regulates energy homeostasis in vivo remains to be fully understood. We found that inactivation of zebrafish Lkb1 upregulates pyruvate dehydrogenase kinase 2 expression and inactivates pyruvate dehydrogenase complex by increasing phosphorylation of pyruvate dehydrogenase. As a result, glycolysis is significantly enhanced as indicated by increased lactate production, which resembles the Warburg effect in cancer cells. Inhibition of Pdk2 in lkb1 mutants with dichloroacetate, a promising anticancer drug, rescued the lactate production to wild-type level, suggesting the lkb1 mutant may be used to screen compounds targeting aerobic glycolysis in cancer therapy.


Association Between DRD2 and DRD4 Polymorphisms and Eating Disorders in an Italian Population.
Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are the three most common eating disorders (EDs). Their etiopathogenesis is multifactorial where both the environmental and genetic factors contribute to the disease outcome and severity. Several polymorphisms in genes involved in the dopaminergic pathways seem to be relevant in the susceptibility to EDs, but their role has not been fully elucidated yet. In this study, we have analyzed the association between selected common polymorphisms in the DRD2 and DRD4 genes in a large cohort of Italian patients affected by AN (n = 332), BN (n = 122), and BED (n = 132) compared to healthy controls (CTRs) (n = 172). Allelic and genotypic frequencies have been also correlated with the main psychopathological and clinical comorbidities often observed in patients. Our results showed significant associations of the DRD2-rs6277 single nucleotide polymorphism (SNP) with AN and BN, of the DRD4-rs936461 SNP with BN and BED and of DRD4 120-bp tandem repeat (TR) polymorphism (SS plus LS genotypes) with BED susceptibility. Moreover, genotyping of DRD4 48-bp variable number TR (VNTR) identified the presence of ≥7R alleles as risk factors to develop each type of EDs. The study also showed that ED subjects with a history of drugs abuse were characterized by a significantly higher frequency of the DRD4 rs1800955 TT genotype and DRD4 120-bp TR short-allele. Our findings suggest that specific combinations of variants in the DRD2 and DRD4 genes are predisposing factors not only for EDs but also for some psychopathological features often coupled specifically to AN, BN, and BED. Further functional research studies are needed to better clarify the complex role of these proteins and to develop novel therapeutic compounds based on dopamine modulation.


Molecular energy and electron transfer assemblies made of self-organized lipid-porphyrin bilayer vesicles.
Novel molecular energy and electron transfer assemblies in vesicular form, which are made of self-organized amphiphilic porphyrins bearing phospholipid-like substituents (lipid-porphyrins), have been photochemically characterized. Tetraphenylporphyrin (TPP) derivatives with four dialkylphosphocholine groups [free-base (1 a), Zn(2+) complex (1 b), and Fe(3+) complex (1 c)] are spontaneously associated in water to form spherical unilamellar vesicles with a diameter of 100-150 nm. Exciton calculations based on the bilayered sheet model of 1 b, which has a porphyrin packing similar to that seen in the triclinic unit cell of the Zn(2+)TPP crystals, reproduced the Soret band bathochromic shift appearing in the aqueous solution of 1 b well. The UV/Vis absorption spectrum of the 1 a/1 b hybrid vesicles (molar ratio: 1/1) showed no electronic interaction between the two porphyrin chromophores in the ground state, but efficient intermolecular singlet-singlet energy transfer took place from the excited 1 b donors to the 1 a acceptor within the vesicle. Near-field scanning optical microspectroscopy of the 1 a/1 b vesicles on a graphite surface also showed only free-base porphyrin fluorescence. The efficiency of the energy transfer was 0.81 and the rate constant was 3.1 x 10(9) s(-1). On the other hand, protoporphyrin IX bearing two alkylphosphocholine propionates (2) was incorporated into the 1 a or 1 c bilayer vesicles (ca. 100 nm phi, molar ratio: 1 a/2 or 1 c/2=10). The UV/Vis absorption spectrum showed that 2 was successfully anchored into the fluid alkylene region of the membrane without stacking. Photoirradiation (lambda(ex): 390 nm) of the 1 c/2 vesicles in the presence of triethanolamine led a vectorial electron transfer from the outer aqueous phase to the membrane center, which allowed reduction of the ferric ion of the Fe(3+)TPP platform.


Pharmacokinetics of minocycline and vancomycin in rabbits.
The pharmacokinetic disposition of minocycline and vancomycin was studied in New Zealand White rabbits before initiating an experimental staphylococcal endocarditis protocol. Minocycline was administered in a multiple-dose regimen of 3 mg/kg i.v. every 12 h, 3 mg/kg i.v. every 8 h, and 6 mg/kg i.v. every 8 h. Vancomycin was given in a similar fashion using regimens of 75 mg/kg i.v. every 12 h and 50 mg/kg i.v. every 8 h. Multiple serum samples were obtained after the fifth dose and drug concentrations were analyzed by microbiologic assay. The pharmacokinetic parameters for each of the drug regimens were calculated using a two-compartment model by nonlinear least-squares regression. No statistically significant differences were noted in the volume of distribution or the half-life of the individual dosing regimens for either agent. As a result of this study, it appears that a minocycline regimen of 6 mg/kg i.v. every 8 h and a vancomycin regimen of 50 mg/kg i.v. every 8 h are appropriate dosing schemes for a comparative study of these agents in rabbits.


Prevalence of leptospirosis among dogs and rodents and their possible role in human leptospirosis from Mumbai, India.
A total of 100 blood and 18 urine samples of rodents and suspected dogs were collected from Mumbai, India during 2006-2008. In order to determine the role of animals in transmission of the disease to humans, all the samples were screened retrospectively by real-time polymerase chain reaction for leptospiral DNA and antibodies were detected using microscopic agglutination test. Leptopsiral DNA was detected from two blood and five urine samples from rodents. Of a total of 71 rodent and dog samples investigated for anti-Leptospira antibodies, 14 (19.7%) were positive. Pyrogenes was the predominant serovar found in 100.0% (7/7) and 85.7% (6/7) from suspected canine cases and rodents, respectively; followed by Icterohemorrhagiae, which was found in one rodent sample 14.28% (1/7). The study proves that there is high prevalence of leptospirosis in rodents and dogs in this region, which proves possible role of these animals in transmission of leptospires to humans. Hence it is imperative to necessary control measures to prevent human leptospirosis.


Personalized Low-Energy Defibrillation Through Feedback Based Resynchronization Therapy.
Defibrillation shocks may cause AV node burnout, scar formation, and pain. In this study, we present a real-time feedback-based control of ventricular fibrillation (VF) with a series of low-energy shocks using ventricular electrical activity as the feedback input. Isolated rabbit hearts were Langendorff perfused and stained with a fluorescent Vm dye. The ventricular activity was measured with a pair of photodiodes, and processed with a feedback controller to calculate defibrillation shock parameters in real-time. Shock timing was based on desynchronized activation of the left and right ventricles during VF, and the strength was proportional to the amplitude difference of the photodiode signals. Shocks were delivered with a custom-developed arbitrary waveform trans-conductance amplifier. Feedback based resynchronization therapy converts VT to MT before sinus rhythm is restored with a reduction of defibrillation energy, compared to a single biphasic shock. Feedback based resynchronization therapy is based on real-time sensing of ventricular activity, while a series of low-energy shocks are delivered, reducing the risk of associated side effects.


A review of the changes to the licensing of influenza vaccines in Europe.
In 2014, the European Committee for Medicinal Products for Human Use (CHMP) published a draft regulatory guideline for the evaluation of influenza vaccines. Following a public consultation round, the final guidance will be published in the near future. Here, we highlight the main changes in the clinical section in this guideline and discuss the background to these changes and whether the new consolidated guidance document can be expected to achieve a better understanding of the performance of seasonal, zoonotic and pandemic influenza vaccines during the regulatory licensing process. The new influenza guideline reflects a changed approach to the regulatory assessment of influenza vaccines, resulting in the abolition of serological criteria, known as the CHMP criteria, which have been the mainstay for evaluating the influenza vaccine immunogenicity for several decades. The new guideline adopts a more diversified approach to the measurement and reporting of the immune response to influenza vaccines and sets a requirement to conduct clinical outcome trials in young children. Importantly, more emphasis is placed on the post-licensure monitoring of the benefit risk of influenza vaccines, including a request for continuous monitoring of efficacy and enhanced safety surveillance. Despite the improvements these new requirements will expectedly bring to the regulatory assessment of influenza vaccines, major challenges remain which cannot be overcome by new guidance alone. Ongoing initiatives in which academia, manufacturers, public health institutes and regulators work together to address these challenges are central to the development of robust tools to evaluate and monitor performance of influenza vaccines in the future.


Bioinformatics Analysis of Proteome Changes in Calu-3 Cell Infected by Influenza A Virus (H5N1).
This paper aimed to identify the differentially expressed proteins (DEPs) in Calu-3 cells infected by influenza A virus (IAV) subtype H5N1. We downloaded proteome data (BTO: 0000762) from the Proteomics Identifications database and identified the DEPs in the IAV-infected Calu-3 cells. Then we constructed a protein-protein interaction network and a transcriptional regulatory network of the proteins. Finally, we performed gene ontology (GO) analysis to study the IAV infection at a functional level. A total of 4 protein groups between the normal cells and the Calu-3 cells infected by IAV, severe acute respiratory syndrome or swine influenza were identified. In the networks, we found 5 significant proteins including FAN, CPSF2, AGO1, AGO2 and PAX5. In addition, we demonstrated those proteins were associated with GO terms such as phosphate metabolic process, calcium ion transport, cell division and regulation of cell motion. STAT1, NS2, CD5, NCKX6 and PDGFB were significant DEPs in these GO terms. By referring to the previous studies, we suggest that proteins including FAN, CPSF2, AGO1, AGO2, PAX5, STAT1 and PDGFB can be used as therapeutic targets of IAV infection.


Electronic structures and chemical bonding in diatomic ScX to ZnX (X = S, Se, Te).
Bond distances, vibrational frequencies, electron affinities, ionization potentials, dissociation energies, and dipole moments of the title molecules in neutral, positively, and negatively charged ions were studied using density functional method. Ground electronic state was assigned for each molecule. The bonding patterns were analyzed and compared with both the available data and across the series. It was found that, besides ionic component, covalent bonds are formed between the metal s, d orbitals, and the p orbital of S, Se, and Te. For neutral and cationic molecules, the covalent character increases from ScX to CrX and from FeX to CuX with an exception of decrease at MnX and ZnX, while for anionic molecules, the trend is not obvious. For both neutral and charged molecules, the sulfides have the shortest bond distance and largest vibrational frequency, while tellurides have the largest bond distance and smallest vibrational frequency. For neutral and anionic molecules, the dissociation energy of sulfides is the largest, that of tellurides is the smallest, while this only remains true for cationic molecules from ScX(+) to FeX(+).


Early changes in the immune microenvironment of oral potentially malignant disorders reveal an unexpected association of M2 macrophages with oral cancer free survival.
Understanding the dynamics of the immune microenvironment is critical to the development of immuno-based strategies for the prevention of oral potentially malignant disorders transformation to oral squamous cell carcinoma (OSCC). We used laser capture microdissection and RNA-sequencing to profile the expression of 13 matched pairs of epithelial versus stromal compartments from normal mucosa, hyperplasia, dysplasia, and invasive tumors in the 4-nitroquinolein (4-NQO) murine model of oral carcinogenesis. Genes differentially expressed at each step of transformation were defined. Immune cell deconvolution and enrichment scores of various biological processes including immune-related ones were computed. Immunohistochemistry was also performed to characterize the immune infiltrates by T-cells (T-cells CD3+, helper CD4+, cytotoxic CD8+, regulatory FoxP3+), B-cells (B220+), and macrophages (M1 iNOS+, M2 CD163+) at each histological step. Enrichment of three independent M2 macrophages signatures were computed in 86 oral leukoplakia with available clinical outcome. Most gene expression changes were observed in the stromal compartment and related to immune biological processes. Immune cell deconvolution identified infiltration by the macrophage population as the most important quantitatively especially at the stage of dysplasia. In 86 patients with oral leukoplakia, three M2 macrophages signatures were independently associated with improved oral cancer-free survival. This study provides a better understanding of the dynamics of the immune microenvironment during oral carcinogenesis and highlights an unexpected association of M2 macrophages gene expression signatures with oral cancer free survival in patients with oral leukoplakia.