Immediate & Short Term Outcome of Using Single Bolus Eptifibatide in Percutaneous Coronary Intervention: A Randomized Control Study.
The purpose of this study was to assess the immediate and short term outcome of single bolus dose of eptifibatide in elective percutaneous coronary intervention (PCI). We enrolled 146 patients who underwent elective PCI from May 2013 to May 2014 in University Cardiac Centre, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Among 146 patients, seventy four patients received single bolus dose of eptifibatide (10 mg intra coronary single bolus dose) just after crossing the lesion were selected as case. The other 72 patients, who did not receive eptifibatide, were selected as control. All patients of both the groups were treated with aspirin, clopidogrel before and after the procedure and all received a single bolus dose of Clopidogrel (300mg) before the procedure. All patient received weight adjusted doses of heparin during and after the procedure. The outcome measures were 24-hours and 30-day morbidity (complications or adverse events) and mortality. The patients of eptifibatide group experienced significantly lower incidence of QMI lesions and complete absence of NQMI lesion in 24 hours of PCI as compared to 5.6% and 6.9% of the lesions respectively in their control counterparts (p=0.027 and p=0.025 respectively). However, the incidence of bleeding and target vessel revascularization (TVR) were no different between the groups (p=0.255 and p=0.117). There was no incidence of TVR at all in the eptifibatide group as opposed to 5.6% in the control group in 30 days following stenting (p=0.017). Single bolus dose of eptifibatite reduces the Major adverse cardiac events as immediate and short term outcome in elective percutaneous coronary intervention.


Closed mitral valvotomy.
The results of closed mitral valvotomy operations in 359 patients operated on from August 1957 to October 1974 were assessed at July 1975. About 60% of the patients were in good health. These results suggest that there is still a place for closed mitral valvotomy in carefully selected cases.


Protein quality control at the inner nuclear membrane.
The nuclear envelope is a double membrane that separates the nucleus from the cytoplasm. The inner nuclear membrane (INM) functions in essential nuclear processes including chromatin organization and regulation of gene expression. The outer nuclear membrane is continuous with the endoplasmic reticulum and is the site of membrane protein synthesis. Protein homeostasis in this compartment is ensured by endoplasmic-reticulum-associated protein degradation (ERAD) pathways that in yeast involve the integral membrane E3 ubiquitin ligases Hrd1 and Doa10 operating with the E2 ubiquitin-conjugating enzymes Ubc6 and Ubc7 (refs 2, 3). However, little is known about protein quality control at the INM. Here we describe a protein degradation pathway at the INM in yeast (Saccharomyces cerevisiae) mediated by the Asi complex consisting of the RING domain proteins Asi1 and Asi3 (ref. 4). We report that the Asi complex functions together with the ubiquitin-conjugating enzymes Ubc6 and Ubc7 to degrade soluble and integral membrane proteins. Genetic evidence suggests that the Asi ubiquitin ligase defines a pathway distinct from, but complementary to, ERAD. Using unbiased screening with a novel genome-wide yeast library based on a tandem fluorescent protein timer, we identify more than 50 substrates of the Asi, Hrd1 and Doa10 E3 ubiquitin ligases. We show that the Asi ubiquitin ligase is involved in degradation of mislocalized integral membrane proteins, thus acting to maintain and safeguard the identity of the INM.


Analysis of the pharmaceuticals market and its technological development in Turkey.
The objectives of this study were to analyze the current structure of the Turkish pharmaceuticals market to explain the latest developments and to offer some insight into the likely policy issues that this sector will face. Systematic searches of the relevant Turkish and English research literature were made, using electronic databases in addition to written reports. The pharmaceutical industry in Turkey currently has eighty-seven manufacturing firms, eleven raw material manufacturers and thirty-eight importing firms. These add up to a total of 136 firms, 35 of which are driven by foreign capital, with 8 of these foreign-run firms having their own plants in Turkey. The industry employs approximately 19,000 personnel. In terms of growth, the value of pharmaceutical products in Turkey recently has exceeded that in Europe. In addition, per capita drug consumption levels are quite low compared with the Organisation for Economic Co-operation and Development and European Union countries. Major international players in the medical equipment and pharmaceutical products sector have also been opening offices in Turkey to reap the benefits of this rapidly evolving market. The pharmaceutical industry in Turkey is quite advanced and diverse, with high quality, generic pharmaceutical products being manufactured as well as poor quality copies that have not been appropriately tested in terms of bioequivalence and bioavailability. The country faces a low level of drug consumption due to economic and cultural constraints compared with Western countries. Governmental control and regulations are key issues because the majority of drug purchases (70-80 percent) throughout the country are currently reimbursable through public sector agencies such as the Pension Fund and the Social Insurance Organization.


Assessing social cognition and pragmatic language in adolescents with traumatic brain injuries.
Traumatic brain injuries (TBI) in children and adolescents can impair social cognition and communication skills but there are few assessment tools suitable for adolescents. The Awareness of Social Inference Test (TASIT) uses professionally enacted audiovisual vignettes of everyday conversational exchanges and is a valid measure of social perception disorders in adults. This study examined its utility for assessing impairments in social cognition in a group of 16 adolescents with TBI, compared to a group of 16 typically developing (TD) adolescents. Adolescents with TBI were, on average, no different to their TD peers on TASIT 1 (emotion recognition) and TASIT 3 (recognizing lies and sarcasm when provided with additional cues) but performed more poorly on TASIT 2 which required them to interpret sarcastic and sincere conversational exchanges with few cues other than the demeanor of the speakers. Within the TBI group, poor performance on TASIT correlated to both relative and self-reported communication difficulties at home. It also correlated with IQ, face recognition and severity of injury as indexed by duration of post-traumatic amnesia. Overall, this study suggests TASIT is a valid measure for adolescents although it raised questions as to how effective normative data is for comparing performance in social cognition during childhood and adolescence.


The ABC transporters MDR1 and MRP2: multiple functions in disposition of xenobiotics and drug resistance.
ATP-binding cassette (ABC) transporters comprise one of the largest membrane bound protein families. They are involved in transport of numerous compounds. These proteins transport substrates against a concentration gradient with ATP hydrolysis as a driving force across the membrane. Mammalian ABC proteins have important physiological, pharmacological and toxicological functions including the transport of lipids, bile salts, drugs, toxic and environmental agents. The efflux pumps serve both as natural defense mechanisms and influence the bioavailability and disposition of drugs. In general terms, the transporters remove xenobiotics from the cellular environment. For example, in cancer cells, over expression of these molecules may confer to multidrug resistance against cytostatic drugs. In addition, based on diverse structural characteristics and a broad substrate specifity, ABC transport proteins alter the intracellular concentration of a variety of therapeutically used compounds and toxicologically relevant agents. We review the function of the human multidrug resistance protein MDR1, (P-glycoprotein, ABCB1) and the multidrug resistance protein MRP2 (ABCC2). We focus on four topics namely 1) structure and physiological functions of these transporters, 2) substrates e.g., drugs, xenotoxins, and environmental toxicants including their conjugates, 3) drug-drug interactions, and the role of chemosensitizers which may be able to reverse drug resistance, and 4) pharmacologically and toxicologically relevant genetic polymorphisms in transport proteins and their clinical implications.


Radiographic temporal subtraction analysis can detect finger joint space narrowing progression in rheumatoid arthritis with clinical low disease activity.
Background Recent papers suggest that finger joints with positive synovial vascularity (SV) assessed by ultrasonography under clinical low disease activity (CLDA) in rheumatoid arthritis (RA) patients may cause joint space narrowing (JSN) progression. Purpose To investigate the performance of a computer-based method by directly comparing with the conventional scoring method in terms of the detectability of JSN progression in hand radiography of RA patients with CLDA. Material and Methods Fifteen RA patients (13 women, 2 men) with long-term sustained CLDA of >2 years were included. Radiological progression of finger joints was measured or scored using the computer-based method which can detect JSN progression between two radiographic images as the joint space difference index (JSDI), as well as the Genant-modified Sharp score (GSS). We also quantitatively assessed SV of these joints using ultrasonography. Results Out of 270 joints, we targeted 259 finger joints after excluding nine damaged joints (four ankylosis, three complete luxation, and two subluxation) and two improved joints according to the GSS results. The JSDI of finger joints with JSN progression was significantly higher than those without JSN progression ( P = 0.018). The JSDI of finger joints with ultrasonographic SV was significantly higher than those without ultrasonographic SV ( P = 0.004). Progression in JSDI showed stronger associations with ultrasonographic SV than progression in GSS (odds ratio [95% confidence interval]: 7.19 [3.37-15.36] versus 5.84 [2.76-12.33]). Conclusion The computer-based method was comparable to the conventional scoring method regarding the detectability of JSN progression in RA patients with CLDA.


Pulmonary sequestration.
31 surgically treated cases of pulmonary sequestration are reported. There were 23 of intralobar and 8 of extralobar type, 23 were on the left and 8 on the right. All but three had symptoms most of them pointing to a respiratory tract infection. Six patients had pneumonia, five haemoptyses, three patients pleurisy and two patients empyema before the operation. In addition to chest x-ray, aortogram appeared to be the most valuable tool in providing the accurate diagnosis preoperatively. Most of the cases were treated by lobectomy, in 7 cases by sequestrectomy and in 2 cases by pneumonectomy. One of the patients died from pulmonary infarction due to anomalous ipsilateral pulmonary venous draingae and ligation of the veins by oversight during right lower lobectomy. The rest of the patients recovered uneventfully. On microscopical examination of the specimens a case of aspergillosis was noted, which has not been described previously in the literature in association of pulmonary sequestration. In one case acid-fast bacteria were found in the necrotic mass of the cavities in the sequestration.


[Effect of Electroacupuncture on Learning-memory Ability in Rats with Hypoxic-ischemic Encephalopathy].
To observe the effect of electroacupuncture (EA) on changes of learning-memory ability, psychomotor coordination and anxiety-like behavior of cerebral hypoxic-ischemia (CHI) young rats, so as to explore its protective effect on neurons under hypoxic-ischemic conditions. SD rats (aged 7 days) were randomly divided into sham operation (sham, n=12), model (n=11), and EA groups (n=12). In addition, 6 young rats in each group were used for observing the number of dendritic spines after Golgi staining. The CHI model was established by ligation of the left common carotid artery combined with hypoxia in a closed transparent vessel. EA was applied to "Baihui" (GV 20)and "Dazhui" (GV 14) for 20 min, once every other day, for 28 days. The rats' behavior changes were assessed by using rotarod performance (for psychomotor coordination), elevated plus maze (anxiety-like behavior) tests and Morris water maze (learning-memory ability) tests, separately. After modeling, the average escape latency and average escape distance of location navigation test within 70 seconds were significantly increased (P<0.05), and the average times and average duration of safe-platform quadrant crossing of spacial probing test were markedly reduced relevant to the sham group (P<0.05). After EA treatment, CHI-induced increases of escape latency and escape distance, and the decreased times and duration of platform quadrant crossing were significantly reversed (P<0.05). No significant differences were found among the three groups in the falling latency of rotarod performance test, and in the time of opening and closing arms of elevated plus maze tests (P>0.05). The density of dendritic spines was significantly lo-wer in the model group than in the sham group (P <0.05), and notably higher in the EA group than in the model group (P<0.05). EA can improve the learning-memory ability of CHI young rats, which may be related to its effect in protecting the dendritic spines of CA 1 region of hippocampus from injury.


Characterization of atherosclerosis plaques by measuring both backscattering and attenuation coefficients in optical coherence tomography.
Intravascular optical coherence tomography (OCT) has been proven a powerful diagnostic tool for cardiovascular diseases. However, the optical mechanism for the qualitative observations are still absent. We address the fundamental issues that underlie the tissue characterization of OCT images obtained from coronary arteries. For this, we investigate both the attenuation and the backscattering properties of different plaque components of postmortem human cadaver coronary arteries. The artery samples are examined both from lumen surface using a catheter and from transversely cut surface using an OCT microscope, where OCT images could be matched to histology exactly. Light backscattering coefficient microb and attenuation coefficients microt are determined for three basic plaque types based on a single-scattering physical model: calcification (microb=4.9+/-1.5 mm(-1), microt=5.7+/-1.4 mm(-1)), fibers (microb=18.4+/-6.4 mm(-1), microt=6.4+/-1.2 mm(-1)), and lipid pool (microb=28.1+/-8.9 mm(-1), microt=13.7+/-4.5 mm(-1)). Our results not only explain the origins of many qualitative OCT features, but also show that combination of backscattering and attenuation coefficient measurements can be used for contrast enhancing and better tissue characterization.


A Data Augmentation Method for Prohibited Item X-Ray Pseudocolor Images in X-Ray Security Inspection Based on Wasserstein Generative Adversarial Network and Spatial-and-Channel Attention Block.
For public security and crime prevention, the detection of prohibited items in X-ray security inspection based on deep learning has attracted widespread attention. However, the pseudocolor image dataset is scarce due to security, which brings an enormous challenge to the detection of prohibited items in X-ray security inspection. In this paper, a data augmentation method for prohibited item X-ray pseudocolor images in X-ray security inspection is proposed. Firstly, we design a framework of our method to achieve the dataset augmentation using the datasets with and without prohibited items. Secondly, in the framework, we design a spatial-and-channel attention block and a new base block to compose our X-ray Wasserstein generative adversarial network model with gradient penalty. The model directly generates high-quality dual-energy X-ray data instead of pseudocolor images. Thirdly, we design a composite strategy to composite the generated and real dual-energy X-ray data with background data into a new X-ray pseudocolor image, which can simulate the real overlapping relationship among items. Finally, two object detection models with and without our data augmentation method are applied to verify the effectiveness of our method. The experimental results demonstrate that our method can achieve the data augmentation for prohibited item X-ray pseudocolor images in X-ray security inspection effectively.


Use of corticosteroids and other adjunct therapies for acute bacterial meningitis in adults.
Acute bacterial meningitis is associated with high morbidity and mortality despite the availability of effective antibiotics. The inflammatory response induced by bacterial products in the subarachnoid space is responsible for neuronal injury. The use of adjuvant therapy in acute bacterial meningitis draws its rationale from the notion of arresting the inflammatory cascade at an early stage of the disease to improve clinical outcome. Corticosteroids have been studied extensively in these patients and seems effective in selective groups of patients, particularly those with pneumococcal meningitis. Glycerol appears harmful in adults with acute bacterial meningitis. Experimental models suggest promising role of newer anti-inflammatory drugs such as antioxidants, inhibitors of Tumor Necrosis Factor-α, poly-ADP-ribose inhibitors, caspase inhibitors, brain-derived neurotrophic factor etc.; however clinical trials are still lacking for these novel potential targets in acute bacterial meningitis. This review focuses on corticosteroids with comments on the role of other potential adjuvant therapy in adults with acute bacterial meningitis.


Rethinking the network determinants of motor disability in Parkinson's disease.
For roughly the last 30 years, the notion that striatal dopamine (DA) depletion was the critical determinant of network pathophysiology underlying the motor symptoms of Parkinson's disease (PD) has dominated the field. While the basal ganglia circuit model underpinning this hypothesis has been of great heuristic value, the hypothesis itself has never been directly tested. Moreover, studies in the last couple of decades have made it clear that the network model underlying this hypothesis fails to incorporate key features of the basal ganglia, including the fact that DA acts throughout the basal ganglia, not just in the striatum. Underscoring this point, recent work using a progressive mouse model of PD has shown that striatal DA depletion alone is not sufficient to induce parkinsonism and that restoration of extra-striatal DA signaling attenuates parkinsonian motor deficits once they appear. Given the broad array of discoveries in the field, it is time for a new model of the network determinants of motor disability in PD.


Neonatal macrocephaly: cerebral primitive neuroectodermal tumor or neuroblastoma as an infrequent cause--a case report and review of the literature.
We report a male term newborn presenting with a congenital macrocephaly 3.5 standard deviations above the median, with a wide and tense anterior fontanel, splayed calvarial sutures, and muscular hypotonia. Antenatal head circumferences were repeatedly below the median. A postnatal head ultrasound showed a large right intracerebral mass with right lateral ventricle compression, right temporal horn dilation, and right frontal horn enlargement with lateral displacement. Additional imaging by computed tomography scan and magnetic resonance imaging was performed. A decompression was performed and histology, immunohistochemistry, and molecular biology supported the diagnosis of a primitive neuroectodermal tumor. A MYCN gene amplification assay remained negative. The incidence of neonatal brain tumors is between 1.4 and 4.1/100,000 live births. Their most common presentation is macrocephaly, hydrocephalus, stillbirth, or diagnosis by pre- or postnatal imaging. Although hydrocephaly and intra- or extracranial hemorrhage are the most frequent causes of congenital macrocephaly, this should be initially investigated by head ultrasound. A suspected malignancy will be confirmed by histopathology, immunohistochemistry, and molecular biology.


Low doses of ethanolic extract of Boldo (Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro.
Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo (Peumus boldus), known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin's cytotoxicity without affecting its anticancer potential. The cytotoxicity of Boldo extract (BE) and cisplatin, administered alone and in combination, was determined in three cancer cell lines (A549, HeLa, and HepG2) and in normal liver cells (WRL-68). Drug-DNA interaction, DNA damage, cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP, ΔΨ) were also studied. Hepatotoxicity and antioxidant activity levels were determined by alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and glutathione assays in mice. The cytotoxicity of related proteins was tested by Western blotting. Co-administration of BE and cisplatin increased viability of normal cells, but had no effect on the viability of cancer cells. Boldo protected liver from damage and normalized different antioxidant enzyme levels in vivo and also reduced ROS and re-polarized MMP in vitro. Bax and cytochrome c translocation was reduced with caspase 3 down-regulation. Further, a drug-DNA interaction study revealed that BE reduced cisplatin's DNA-binding capacity, resulting in a reduction in DNA damage. Results indicated that a low dose of BE could be used beneficially in combination with cisplatin to reduce its toxicity without hampering cisplatin's anticancer effect. These findings signify a potential future use of BE in cancer therapy.


An assessment of clinical performance measures for pediatric emergency physicians.
The objectives were to evaluate clinical performance measures used for pediatric emergency medicine (PEM) physicians for reliability, correlation with one another, and relationship with clinical experience. This retrospective cohort study collected performance data for PEM physicians working at an urban children's hospital emergency department (ED) for each of 7 consecutive 6-month periods. Low correlations were seen between patients per hour or admission rate and 72-hour revisit rates. No significant association existed between level of experience and any performance measure. Physician treatment times appeared to be most reliable, and revisit rates were least reliable. Increase in number of patients seen per hour or lower admission rates in the ED are not significantly associated with an increase in revisit rates. Provider experience did not affect performance measures. Physician treatment time, patients per hour, admission rate, and charges per hour are reliable measures to assess the clinical performance of PEM physicians working at a single center.


A new sucrosephenylpropanoid ester from Polygonum pubescens Blume.
The present study investigated the chemical constituents of aerial part of Polygonum pubescens Blume. Twenty-two compounds 1-22 were obtained from petroleum ether and ethyl acetate extracts of aerial part of P. pubescens, including a new phenylpropanoide esters 1 and 21 known compounds. The structures were determined on the basis of spectroscopic and chemical methods. Sixteen compounds were assessed for their cytotoxic and anti-inflammatory activities. Several compounds showed effects on different targets.


Electronic Rearrangement in Molecular Plasmons: An Electron Density and Electrostatic Potential-Based Study.
Plasmonic modes in single-molecule systems have been previously identified by scaling two-electron interactions in calculating excitation energies. Analysis of transition dipole moments for states of polyacenes based on configuration interaction is another method for characterising molecular plasmons. The principal features in the electronic absorption spectra of polyacenes are a low-intensity, lower-in-energy peak and a high-intensity, higher-in-energy peak. From calculations using time-dependent density functional theory with the B3LYP/cc-pVTZ basis set, both these peaks are found to result from the same set of electronic transitions, that is, HOMO-n to LUMO and HOMO to LUMO+n, where n varies as the number of fused rings increases. In this work, the excited states of polyacenes, naphthalene through pentacene, are analysed using electron densities and molecular electrostatic potential (MESP) topography. Compared to other excited states the bright and dark plasmonic states involve the least electron rearrangement. Quantitatively, the MESP topography indicates that the variance in MESP values and the displacement in MESP minima positions, calculated with respect to the ground state, are lowest for plasmonic states. The excited-state electronic density profiles and electrostatic potential topographies suggest the least electron rearrangement for the plasmonic states. Conversely, high electron rearrangement characterises a single-particle excitation. The molecular plasmon can be called an excited state most similar to the ground state in terms of one-electron properties. This is found to be true for silver (Ag6 ) and sodium (Na8 ) linear chains as well.


Proteinuria in Children: Evaluation and Differential Diagnosis.
Although proteinuria is usually benign in the form of transient or orthostatic proteinuria, persistent proteinuria may be associated with more serious renal diseases. Proteinuria may be an independent risk factor for the progression of chronic kidney disease in children. Mechanisms of proteinuria can be categorized as glomerular, tubular, secretory, or overflow. A history, a physical examination, and laboratory tests help determine the cause. Transient (functional) proteinuria is temporary. It can occur with fever, exercise, stress, or cold exposure, and it resolves when the inciting factor is removed. Orthostatic proteinuria is the most common type in children, especially in adolescent males. It is a benign condition without clinical significance. Persistent proteinuria can be glomerular or tubulointerstitial in origin. The urine dipstick test is the most widely used screening method. Although a 24-hour urine protein excretion test is usually recommended for quantitation of the amount of protein excreted in the urine, it may be impractical in children. A spot, first-morning urine test for a protein-to-creatinine or protein-to-osmolality ratio is a reliable substitute. Treatment of proteinuria should be directed at the underlying cause. Patients with active urinary sediments, hematuria, hypertension, hypocomplementemia, renal insufficiency with depressed glomerular filtration rate, or signs and symptoms suggestive of vasculitic disease may require referral to a pediatric nephrologist and a renal biopsy.


Role of delayed nuclear envelope breakdown and mitosis in Wolbachia-induced cytoplasmic incompatibility.
The bacterium Wolbachia manipulates reproduction in millions of insects worldwide; the most common effect is cytoplasmic incompatibility (CI). We found that CI resulted from delayed nuclear envelope breakdown of the male pronucleus in Nasonia vitripennis. This caused asynchrony between the male and female pronuclei and, ultimately, loss of paternal chromosomes at the first mitosis. When Wolbachia were present in the egg, synchrony was restored, which explains suppression of CI in these crosses. These results suggest that Wolbachia target cell cycle regulatory proteins. A striking consequence of CI is that it alters the normal pattern of reciprocal centrosome inheritance in Nasonia.


Graduate medical education and the law.
The law can become involved in graduate medical education in several contexts: (a) when applicants are denied admission to residency programs; (b) when residents are dismissed from programs; and (c) when residents, hospitals sponsoring residency programs, or attending physicians are sued for malpractice. A knowledge of the rights and responsibilities of residents, hospitals, and attending physicians is crucial if they are to avoid unnecessary litigation. The authors here review the law in this area and recommend guidelines to be followed by those areas of graduate medical education.


Attitudes about vaccines to prevent Ebola virus disease in Guinea at the end of a large Ebola epidemic: Results of a national household survey.
In 2014-2016, an Ebola epidemic devastated Guinea; more than 3800 cases and 2500 deaths were reported to the World Health Organization. In August 2015, as the epidemic waned and clinical trials of an experimental, Ebola vaccine continued in Guinea and neighboring Sierra Leone, we conducted a national household survey about Ebola-related knowledge, attitudes, and practices (KAP) and opinions about "hypothetical" Ebola vaccines. Using cluster-randomized sampling, we selected participants aged 15+ years old in Guinea's 8 administrative regions, which had varied cumulative case counts. The questionnaire assessed socio-demographic characteristics, experiences during the epidemic, Ebola-related KAP, and Ebola vaccine attitudes. To assess the potential for Ebola vaccine introduction in Guinea, we examined the association between vaccine attitudes and participants' characteristics using categorical and multivariable analyses. Of 6699 persons invited to participate, 94% responded to at least 1 Ebola vaccine question. Most agreed that vaccines were needed to fight the epidemic (85.8%) and that their family would accept safe, effective Ebola vaccines if they became available in Guinea (84.2%). These measures of interest and acceptability were significantly more common among participants who were male, wealthier, more educated, and lived with young children who had received routine vaccines. Interest and acceptability were also significantly higher among participants who understood Ebola transmission modes, had witnessed Ebola response teams, knew Ebola-affected persons, believed Ebola was not always fatal, and would access Ebola treatment centers. In multivariable analyses of the majority of participants living with young children, interest and acceptability were significantly higher among those living with vaccinated children than among those living with unvaccinated children. The high acceptability of hypothetical vaccines indicates strong potential for introducing Ebola vaccines across Guinea. Strategies to build public confidence in use of Ebola vaccines should highlight any similarities with safe, effective vaccines routinely used in Guinea.


Synthesis of Zeolitic Mo-Doped Vanadotungstates and Their Catalytic Activity for Low-Temperature NH3-SCR.
Mo was successfully introduced into a vanadotungstate (VT-1), which is a crystalline microporous zeolitic transition-metal oxide based on cubane clusters [W4O16]8- and VO2+ linkers (MoxW4-x. x: number of Mo in VT-1 unit cell determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES)). It was confirmed that W in the cubane units was substituted by Mo. The resulting materials showed higher microporosity compared with VT-1. The surface area and the micropore volume increased to 296 m2·g-1 and 0.097 cm3·g-1, respectively, for Mo0.6W3.4 compared with the those values for VT-1 (249 m2·g-1 and 0.078 cm3·g-1, respectively). The introduction of Mo changed the acid properties including the acid amount (VT-1: 1.06 mmol g-1, Mo0.6W3.4: 2.18 mmol·g-1) and its strength because of the changes of the chemical bonding in the framework structure. MoxW4-x showed substantial catalytic activity for the selective catalytic reduction of NO with NH3 (NH3-selective catalytic reduction (SCR)) at a temperature as low as 150 °C.


Draft Genome Sequence of Erwinia billingiae OSU19-1, Isolated from a Pear Tree Canker.
Plant-associated Erwinia include pathogenic and nonpathogenic species. We report the 5.6-Mb genome sequence of Erwinia billingiae OSU19-1, isolated from a canker on a pear tree inoculated with Erwinia amylovora. OSU19-1 and a closely related European isolate, E. billingiae Eb661(T), share many similarities including 40 kb of plasmid sequence.


Potassium transport systems in the moss Physcomitrella patens: pphak1 plants reveal the complexity of potassium uptake.
Potassium uptake is one of the most basic processes of plant physiology. However, a comprehensive description is lacking. At a cellular level fungi have provided a helpful but imperfect plant model, which we aim to improve using Physcomitrella patens. Blast searches in expressed sequence tag databases demonstrated that Physcomitrella expresses the same families of K(+) and Na(+) transport systems as flowering plants. We cloned two inward rectifier channels, PpAKT1-2, and four HAK-type transporters (PpHAK1-4). In both types of transport system, phylogenetic analyses revealed that despite their high sequence conservation they could not be included in Arabidopsis or rice (Oryza sativa) clusters. Both inward rectifier channels and one HAK transporter (PpHAK1) were expressed in yeast. PpAKT1 and activated mutants of PpAKT2 and PpHAK1 showed clear functions that were similar to those of homologous systems of flowering plants. A pphak1 null mutant line of Physcomitrella failed to deplete K(+) below 10 mum. Moreover, in a non-K(+)-limiting medium in which wild-type plants grew only as protonema, pphak1-1 plants produced leafy gametophores and contained 60% more K(+). We found that Physcomitrella takes up K(+) through several systems. PpHAK1 is the dominant system in plants that underwent K(+) starvation for long periods but an as-yet unidentified system, which is non-selective for K(+), Rb(+), and Cs(+), dominates in many other conditions. Finally, we discuss that, similar to PpHAK1, one of the functions of AtHAK5 may be to control cellular K(+) content and that a non-selective as-yet unidentified system also exists in Arabidopsis.


The Hippocampus Contributes to Temporal Discounting When Delays and Rewards Are Experienced in the Moment.
Temporal discounting (TD) represents the mental devaluation of rewards that are available after a delay. Whether the hippocampus is critical for TD remains unclear, with marked discrepancies between animal and human studies: although animals with discrete hippocampal lesions display impaired TD, human participants with similar lesions show intact performance on classic intertemporal choice tasks. A candidate explanation for this discrepancy is that delays and rewards are experienced in the moment in animal studies but tend to be hypothetical in human studies. We tested this hypothesis by examining the performance of amnesic participants with hippocampal lesions (one female, six males) on a novel experiential intertemporal choice task that used interesting photographs occluded by thick lines as rewards (Patt et al., 2021). Using a logistic function to model indifference points data, we compared performance to that on a classic intertemporal choice task with hypothetical outcomes. Participants with hippocampal lesions displayed impaired patterns of choices in the experiential task but not in the hypothetical task. Specifically, hippocampal lesions were associated with decreased amplitude of the delay-reward trade-off, with persistent choice of the delayed option despite delay increase. These results help explain previous discrepancies across animal and human studies, indicating that the hippocampus plays a critical role in temporal discounting when the outcomes of decisions are experienced in the moment, but not necessarily when they are hypothetical.SIGNIFICANCE STATEMENT Impaired temporal discounting (TD) has been related to maladaptive behaviors, including substance dependence and nonadherence to medical treatment. There is consensus that TD recruits the brain valuation network but whether the hippocampal memory system is additionally recruited remains unclear. This study examined TD in hippocampal amnesia, providing a unique opportunity to explore the role of the hippocampus in cognition. Whereas most human studies have used hypothetical outcomes, this study used a novel experiential task with real-time delays and rewards. Results demonstrated hippocampal involvement in the experiential task, but not in a classic hypothetical task administered for comparison. These findings elucidate previous discrepancies between animal and human TD studies. This reconciliation is critical as animals serve as models of human neurocognition.


[Effect of interferonogenic molecular complex of yeast RNA--tilorone on DNA, RNA and protein synthesis in vitro].
In the experiments in vitro using the primary mononuclear cells (MNC) culture of the human peripheral blood the influence of interferonogenic yeast RNA-tilorone molecular complex on the DNA, RNA and protein synthesis was studied. The complex was shown to inhibit the insertion of 3H-thymidine, 3H-uridine and 3H-leucine into DNA, RNA and protein of MNC total pool (by 13, 1 and 40% respectively); that was practically conformed with this synthesis inhibition upon to a natural origin polynucleotide interferon inducers--lariphan (9, 0 and 57% respectively) and ridostin (9, 0 and 56% respectively) action, and at the same time rather less than poly(I)-poly(C) (14, 5 and 62% respectively). In the case of preliminary cell stimulation by the mitogen PHA the complex revealed comitogenic action at a concentration 25 micrograms/ml, that corresponded to optimal for interferonogenesis; the increase of the doses till 100-1000 micrograms/ml lead to in the reversal effect. To proceed from mutual relation between interferonogen preparations influence on the mentioned synthesis and their cytotoxicity the conclusion was about made the complex promising usage as an interferon inducer both in vitro and in vivo conditions.


[Epileptic seizure-like effect of Sophora alkaloid sophoridine on experimental animals].
To investigate the epileptic seizure-like effect of Sophora alkaloid sophoridine on electroencepholography (EEG) and its possible characteristic and the mechanism of the seizure-like effect. Chronic electron implantation was employed for the intracranial electroencepholography (IEEG) recording in rat, and the traditional anti-seizure drugs were for the mechanism study in mice. Compared with the medial perforant path (PP) area and the temporal cortex (TC), the granule cells in hippocampus dentate gyrus (DG) area is more sensitive in the kindling effect by sc sophoridine. Under-threshold hypnotic dosage of diazepam and the hypnotic dosage of pentobarbital sodium can block the sophoridine kinded seizure in mice, but the phenytoin sodium can not block the seizure, also the dosage of it can block the maximal electroconvulsive shock (MES) seizure. Sophoridine-induced synchronous oscillations in the hippocampus could elicit the generation and development of seizure. And the hippocampus might play the crucial role and be the original part of the seizure. Sophoridine kinded seizure might belong to clonic seizures, and the diazepam is the ideal agent for the treatment.


On the use of T7 RNA polymerase transcripts for physical investigation.
A few years ago we made some observations which raised questions about the accuracy with which T7 RNA polymerase transcribes templates in vitro, and the suitability of its in vitro products for biophysical study (1). The experiments described below demonstrate that there is no reason for concern; the products of T7 RNA polymerase transcription in vitro are as suitable for biophysical characterization as RNAs synthesized in vivo. It is likely that aggregation involving the transcribed portions of the T7 RNA polymerase promoter caused our initial observations.


Evaluating everyday explanations.
People frequently rely on explanations provided by others to understand complex phenomena. A fair amount of attention has been devoted to the study of scientific explanation, and less on understanding how people evaluate naturalistic, everyday explanations. Using a corpus of diverse explanations from Reddit's "Explain Like I'm Five" and other online sources, we assessed how well a variety of explanatory criteria predict judgments of explanation quality. We find that while some criteria previously identified as explanatory virtues do predict explanation quality in naturalistic settings, other criteria, such as simplicity, do not. Notably, we find that people have a preference for complex explanations that invoke more causal mechanisms to explain an effect. We propose that this preference for complexity is driven by a desire to identify enough causes to make the effect seem inevitable.


Intravenous infusion of xenon-containing liposomes generates rapid antidepressant-like effects.
Similar to ketamine, xenon gas acts as a glutamatergic N-methyl-d-aspartate receptor antagonist, but devoid of propensity to cause untoward effects. Herein, we loaded xenon gas into a liposomal carrier called xenon-containing liposomes (Xe-liposome) for systemic delivery, and investigated its effect as an antidepressant and also analyzed synaptic biomarkers including brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), mammalian target of rapamycin (mTOR), protein kinase C (PKC) and extracellular signal-regulated kinase-1/2 (ERK1/2) in blood and brain. Xe-liposomes (15 μl/mg) were prepared by a pressurized freeze-thaw method, and injected via the lateral tail vein (0.6 mL/rat) in male Wistar rats. The uncaging of xenon gas from circulating Xe-liposome was facilitated by continuous ultrasound application externally on the neck over the internal common carotid artery. One-hour after Xe-liposome infusion, animals were assessed for depression-like behaviors using a forced swimming test (FST), and spontaneous locomotor activity. Blood, as well as frontal cortex and hippocampal samples were obtained for immunoblotting and/or enzyme-linked immune sorbent assays. Acute intravenous infusion of Xe-liposome, at 6 mg/kg, showed an increase in swimming time in the FST (p < 0.006), indicating antidepressant-like phenotypes. Higher doses of Xe-liposomes (9 mg/kg) failed to improve swimming duration. This behavioral discrepancy was not associated with locomotion aberrations, as gross activity of rats remained similar for both doses. In biochemical analyses of frontal cortex, protein levels of BDNF increased by 64%, and enhanced phosphorylation of AKT (43%) and mTOR (93%) was observed at the 6 mg/kg dose level of Xe-liposomes, while these biomarkers and phosphorylated PKC and ERK1/2 levels remained unchanged at the higher dose. Moreover, Xe-liposomal treatment did not change the plasma and protein levels of BDNF, and phosphorylated AKT, mTOR, PKC and ERK1/2 hippocampal expressions. Xe-liposomes mediate a rapid antidepressant-like effect through activation of AKT/mTOR/BDNF signaling pathway.


Histamine inhibits immunoglobulin production via histamine H2 receptors without affecting cell growth in human B cells.
The effect of histamine upon immunoglobulin (Ig) production and proliferation in human B cells was studied. Histamine inhibited Ig production by the human B cell lines IM-9 and CBL in a dose-dependent fashion during 4 days of culture. As little as 10(-5) M was inhibitory. In contrast, proliferation was not affected. Inhibition by histamine was blocked by histamine H2 antagonist, cimetidine, but not by histamine H1 antagonist, diphenhydramine. Moreover, histamine H2 agonist dimaprit inhibited Ig production from B cell lines in a dose-dependent manner, and as little as 10(-8) M was inhibitory. Histamine also inhibited IgM and IgG production by peripheral and tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I and IL-2 without affecting proliferation. This inhibition was also blocked by cimetidine. These results indicate that histamine has a direct inhibitory effect on B cells via histamine H2 receptors, and acts as an immunoregulatory factor.


Association between symptoms of allergic rhinitis with decreased general health-related quality of life.
The impact of specific allergic rhinitis symptoms on patient quality of life (QOL) is currently unknown. In this study, we sought to determine the association between nasal and extranasal symptoms of allergic rhinitis with general health-related QOL. A total of 150 participants with ages > 18 years and persistent allergic rhinitis were prospectively recruited for this cross-sectional study. General health-related QOL was measured by using the visual analog scale (VAS) from the five-dimension EuroQol QOL survey (EQ-5D). The severity of nasal and extranasal symptoms was measured by using the 22-item Sino-Nasal Outcome Test (SNOT-22). The severity of nasal obstruction was measured by using the Nasal Obstruction Severity Evaluation (NOSE) scale. Each participant also completed a Rhinitis Control Assessment Test (RCAT). The total SNOT-22 score was significantly correlated with RCAT (r = -0.68 [95% confidence interval {CI}, -0.75 to -0.58]; p < 0.001) and EQ-5D VAS (r = -0.44 [95% CI, -0.56 to -0.30]; p < 0.001). Of the 22 symptoms assessed on the SNOT-22, sleep-related symptoms, and otologic symptoms were associated with the greatest decrease in general health-related QOL. Nasal symptoms were least associated with general health-related QOL. The symptom of nasal obstruction was not at all associated with general health-related QOL (p = 0.267). We confirmed this finding by showing no significant correlation between the NOSE score and EQ-5D VAS (r = -0.05 [95% CI, -0.21 to 0.12]; p = 0.582). Sleep and otologic symptoms were associated with the greatest negative impact on QOL in adults with persistent allergic rhinitis and should be routinely assessed in their clinical evaluation.


Interaction between the substrate and probe in liquid metal Ga: experimental and theoretical analysis.
Interaction between two bodies in a liquid metal is an important topic for development of metallic products with high performance. We conducted atomic force microscopy measurements and achieved the interaction between the substrate and the probe in liquid Ga of an opaque and highly viscous liquid. The interaction cannot be accessed with the normal atomic force microscopy, electron microscopy, and beam reflectometry. We performed a theoretical calculation using statistical mechanics of simple liquids by mixing an experimentally derived quantum effect. From both experiment and theory, we found an unusual behaviour in the interaction between the solvophobic substances, which has never been reported in water and ionic liquids. Shapes of the interaction curves between several solvophobic and solvophilic pairs in liquid Ga are also studied.


Inhibition of peptidoglycan hydrolase activity in vivo and in vitro by energy uncouplers in Escherichia coli.
The effects of energy uncouplers on in vivo and in vitro peptidoglycan hydrolase activities in Escherichia coli were determined. Sodium azide, potassium cyanide, and carbonyl cyanide m-chlorophenylhydrazone all inhibited ampicillin-induced lysis of exponential phase cultures, even when they were added to lysis-committed cultures. These energy uncouplers also inhibited the solubilization of radiolabeled peptidoglycan by bacterial suspensions that had been treated with 5% trichloroacetic acid by the method of Hartmann et al.3 to activate the peptidoglycan hydrolases. Therefore, the in vivo and in vitro activities of peptidoglycan hydrolases in E. coli are dependent on membrane energization.


Appearance of aseptic vascular grafts after endovascular aortic repair on [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography.
Diagnosis of prosthetic vascular graft infection with [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) allows for early detection of functional changes associated with infection, based on increased glucose utilization by activated macrophages and granulocytes. Aseptic vascular grafts, like all foreign bodies, can stimulate an inflammatory response, which can present as increased activity on 18F-FDG PET/CT. Consequently, distinguishing aseptic inflammation from graft infection, though important, can be difficult. In the case of endovascular aneurysm repair (EVAR), a minimally invasive procedure involving the transfemoral insertion of an endoprosthetic stent graft, the normal postoperative appearance of these grafts on 18F-FDG PET/CT can vary over time, potentially confounding study interpretation. To investigate the visual, semiquantitative, and temporal characteristics of aseptic vascular grafts in patients status post EVAR. In this observational retrospective cohort study, patients with history of EVAR who underwent 18F-FDG PET/CT for indications other than infection were identified retrospectively. All patients were asymptomatic for graft infection - no abdominal pain, fever of unknown origin, sepsis, or leukocytosis - at the time of imaging and for ≥ 2 mo after each PET/CT. Imaging studies such as CT for each patient were also reviewed, and any patients with suspected or confirmed vascular graft infection were excluded. One hundred two scans performed on 43 patients (34 males; 9 females; age = 77 ± 8 years at the time of the final PET/CT) were retrospectively reviewed. All 43 patients had an abdominal aortic (AA) vascular graft, 40 patients had a right iliac (RI) limb graft, and 41 patients had a left iliac (LI) limb graft. Twenty-two patients had 1 PET/CT and 21 patients had from 2 to 9 PET/CTs. Grafts were imaged between 2 mo to 168 mo (about 14 years) post placement. Eight grafts were imaged within 6 mo of placement, including three that were imaged within three months of placement. The mean interval between graft placement and PET/CT for all 102 scans was 51 ± 39 mo. PET/CT data was reconstructed with region-of-interest analysis of proximal, mid and distal portions of the grafts and background ascending aorta. Maximum standardized uptake value (SUVmax) was recorded for each region. SUVmax-to-background uptake ratios (URs) were calculated. Visual assessment was performed using a 2-pattern grading scale: Diffuse (homogeneous uptake less than liver uptake) and focal (one or more areas of focal uptake in any part of the graft). Statistical analysis was performed. In total, there were 306 AA grafts, 285 LI grafts, 282 RI grafts, and 306 ascending aorta background SUVmax measurements. For all 102 scans, mean SUVmax values for AA grafts were 2.8-3.0 along proximal, mid, and distal segments. Mean SUVmax values for LI grafts and RI grafts were 2.7-2.8. Mean SUVmax values for background were 2.5 ± 0.5. Mean URs were 1.1-1.2. Visual analysis of the scans reflected results of quantitative analysis. On visual inspection, 98% revealed diffuse, homogeneous 18F-FDG uptake less than liver. Graft URs and visual pattern categories were significantly associated for AA graft URs (F-ratio = 21.5, P < 0.001), LI graft URs (F-ratio = 20.4, P < 0.001), and RI graft URs (F-ratio = 30.4, P < 0.001). Thus, visual patterns of 18F-FDG uptake corresponded statistically significantly to semiquantitative URs. The age of grafts showing focal patterns was greater than grafts showing diffuse patterns, 87 ± 89 vs 50 ± 37 mo, respectively (P = 0.02). URs were significantly associated with graft age for AA grafts (r = 0.19, P = 0.001). URs were also significantly associated with graft age for LI grafts (r = 0.25, P < 0.0001), and RI grafts (r = 0.31, P < 0.001). Quartiles of similar numbers of graft (n = 25-27) grouped by graft age indicated that URs were significantly higher for 4th quartile vs 2nd quartile URs (F-ratio = 19.5, P < 0.001). When evaluating URs, graft SUVmax values within 10%-20% of the ascending aorta SUVmax is evident in aseptic grafts, except for grafts in the oldest quartiles. In this study, grafts in the oldest quartiles (> 7 years post EVAR) showed SUVmax up to 30% higher than the ascending aorta SUVmax. Characteristics of an aseptic vascular stent graft in the aorta and iliac vessels on 18F-FDG PET/CT include graft SUVmax values within 10%-20% of the ascending aorta background SUVmax. The SUVmax of older aseptic grafts can be as much as 30% above background. The visual uptake pattern of diffuse, homogeneous uptake less than liver was seen in 98% of aseptic vascular grafts, making this pattern particularly reassuring for clinicians.


Analysis of DNA Methylation by Pyrosequencing.
Pyrosequencing is a technique that uses a sequencing-by-synthesis system which is designed to quantify single-nucleotide polymorphisms (SNPs). Artificial C/T SNP creation via bisulfite modification permits measurement of DNA methylation locally and globally in real time. Alteration in DNA methylation has been implicated in aging, as well as aging-related conditions such as cancer, as well as cardiovascular, neurodegenerative, and autoimmune diseases. Considering its ubiquitous presence in divergent clinical pathologies, quantitative analysis of DNA CpG methylation both globally and at individual genes helps to elucidate the regulation of genes involved in pathophysiological conditions. The ability to detect and quantify the methylation pattern of DNA has the potential to serve as an early detection marker and potential drug target for several diseases. Here, we provide a detailed technical protocol for pyrosequencing supplemented by critical information about assay design and nuances of the system that provides a strong foundation for beginners in the field.


Histamine-stimulated cytokine secretion from human conjunctival epithelial cells: inhibition by the histamine H1 antagonist emedastine.
The present studies demonstrate that histamine induces the secretion of IL-6, IL-8 and GM-CSF from human conjunctival epithelial cells in a dose- and time-dependent manner. The histamine antagonists emedastine (H1), ranitidine (H2) and thioperamide (H3) were evaluated for their ability to inhibit secretion of these cytokines. Emedastine potently inhibited histamine-induced IL-6, IL-8 and GM-CSF secretion with mean IC50 values of 2.23, 3.42 and 1.50 nM, respectively. Ranitidine and thioperamide failed to inhibit cytokine secretion over a wide dose range. These data suggest that mast cell derived histamine may stimulate inflammatory cytokine production in allergic conjunctivitis via activation of epithelial cell H1 receptors. The histamine H1 antagonist emedastine potently inhibits this response.


Developments in the molecular biology of DYT1 dystonia.
The identification of a mutation of the DYT1 gene as a cause of inherited dystonia has led to many insights regarding the genetics of this disorder. In addition, there is a rapidly expanding list of inherited dystonia syndromes, the genes for some of which have been identified or localized. The DYT1 mutation has been found in a variety of ethnic groups, and it may result in a range of phenotypes. To date, studies of torsinA, the protein product of the DYT1 gene, have not revealed its function, although its widespread distribution throughout the central nervous system suggests a universal role. TorsinA has structural homology to heat shock and chaperone proteins. Evidence from studies in cell cultures and Caenorhabditis elegans, and the presence of torsinA in inclusion bodies in several neurodegenerative diseases may be indicative of a function of this nature. Preliminary studies in humans with DYT1 dystonia and in DYT1 transgenic mice suggest disruption of the dopaminergic nigrostriatal system. A functional interference with neuronal signal processing induced by mutation of torsinA is consistent with current hypotheses regarding impairment of the center-surround mechanism in the striatum.


Novel pharmacological therapies for the treatment of bronchial asthma.
Asthma has long been recognized as a chronic inflammatory disease of the airways, often in response to inhaled allergens prompting inappropriate activation of the immune response involving a range of cells including mast cells, Th2 lymphocytes and eosinophils alongside a wide range of inflammatory mediators. First-line therapy for treatment of persistent asthma involves the use of inhaled corticosteroids (ICS) in combination with inhaled β<inf>2</inf>-agonists enabling both the control of the underlying airways inflammation and a reduction of airway hyperresponsiveness. However, many patients remain symptomatic despite high-dose therapy. Therefore, there is a continued unmet clinical need to develop specifically new anti-inflammatory therapies for patients with asthma, either as an add-on therapy to ICS or as replacement monotherapies. The success of fixed dose combination inhalers containing both a bronchodilator and an anti-inflammatory drug has also led to the development of "bifunctional" drugs which are molecules specifically designed to have two distinct pharmacological actions based on distinct pharmacophores. In this review we will discuss these different pharmacological approaches under development for the treatment of bronchial asthma and the available preclinical and clinical data.


Ionic Liquids as Biocompatible Antibacterial Agents: A Case Study on Structure-Related Bioactivity on Escherichia coli.
The potential of ionic liquids (ILs) to be used as antimicrobial agents for biomedical applications has been hindered by the fact that most of them are cytotoxic toward mammalian cells. Understanding the mechanism of bacterial and mammalian cellular damage of ILs is key to their safety design. In this work, we evaluate the antimicrobial activity and mode of action of several ILs with varying anions and cations toward the clinically relevant Gram-negative Escherichia coli. Langmuir monolayer technique was used to evaluate if the IL's mode of action was related to the bacterial cell membrane interaction for an effective E. coli killing. 1-Decyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide [DMIM][TFSI] and trihexyltetradecyl phosphonium bis(trifluoromethylsulfonyl) imide [P6,6,6,14][TFSI] were surface-active and induced bacterial cell lysis, through a membrane-disruption phenomenon on bacteria, in a mechanism that was clearly related to the long alkyl chains of the cation. 1-Ethyl-3-methylimidazolium hydrogen sulfate [EMIM][HSO4] was highly antimicrobial toward E. coli and found suitable for biological applications since it was harmless to mammalian cells at most of the tested concentrations. The results suggest that the imidazolium cation of the ILs is mostly responsible not only for their antimicrobial activity but also for their cytotoxicity, and the inclusion of different anions may tailor the ILs' biocompatibility without losing the capacity to kill bacteria, as is the case of [EMIM][HSO4]. Importantly, this IL was found to be highly antimicrobial even when incorporated in a polymeric matrix.


To total amount of activity….. and beyond: perspectives on measuring physical behavior.
The aim of this paper is to describe and discuss some perspectives on definitions, constructs, and outcome parameters of physical behavior. The paper focuses on the following constructs: Physical activity and active lifestyle vs. sedentary behavior and sedentary lifestyle; Amount of physical activity vs. amount of walking; Detailed body posture and movement data vs. overall physical activity data; Behavioral context of activities; Quantity vs. quality; Physical behavior vs. physiological response. Subsequently, the following outcome parameters provided by data reduction procedures are discussed: Distribution of length of bouts; Variability in bout length; Time window; Intensity and intensity threshold. The overview indicates that physical behavior is a multi-dimensional construct, and it stresses the importance and relevance of constructs and parameters other than total amount of physical activity. It is concluded that the challenge for the future will be to determine which parameters are most relevant, valid and responsive. This is a matter for physical behavior researchers to consider, that is critical to multi-disciplinary collaboration.


Relationship between Blurring and Refocus Flip Angle in 3D-double Inversion Recovery MRI.
It is important to optimize imaging parameters in 3D-double inversion recovery (DIR) magnetic resonance imaging (MRI) for detecting cortical micro lesions. However, inadequate parameters markedly raise blurring in 3DDIR MRI. The purpose of this study was to evaluate the relationship between the blurring and refocus flip angle (RFA) in 3D-DIR MRI. White matter attenuated inversion recovery (WAIR) images as a test sample were obtained by 1.5T MRI with various RFA settings (30°, 40°, 60°, 100°, 140°, 180°, and variable refocus flip angle (VRFA)). Optimal RFA was evaluated using Scheffé's method (Nakaya changing method) by five observers. The results of average preferences indicated that RFA settings of under the 60° of RFA or VRFA suppressed the blurring in 3DDIR MRI. The yard sticks of RFAs of 30° and 40° were significantly higher than the yard sticks of other RFAs (p<0.01). For detecting cortical microlesions, it is very important to obtain WAIR images with no blurring. Using low RFA or VRFA didn't cause significant differences of signal intensity between high-frequency region and low-frequency region in k-space of 3D-DIR MRI. Therefore, it is recommended to set lower RFA (under 60° or VRFA) for suppressing blur in 3D-DIR MRI.


Neuromodulatory Effects of Auditory Training and Hearing Aid Use on Audiovisual Speech Perception in Elderly Individuals.
Although audiovisual (AV) training has been shown to improve overall speech perception in hearing-impaired listeners, there has been a lack of direct brain imaging data to help elucidate the neural networks and neural plasticity associated with hearing aid (HA) use and auditory training targeting speechreading. For this purpose, the current clinical case study reports functional magnetic resonance imaging (fMRI) data from two hearing-impaired patients who were first-time HA users. During the study period, both patients used HAs for 8 weeks; only one received a training program named ReadMyQuipsTM (RMQ) targeting speechreading during the second half of the study period for 4 weeks. Identical fMRI tests were administered at pre-fitting and at the end of the 8 weeks. Regions of interest (ROI) including auditory cortex and visual cortex for uni-sensory processing, and superior temporal sulcus (STS) for AV integration, were identified for each person through independent functional localizer task. The results showed experience-dependent changes involving ROIs of auditory cortex, STS and functional connectivity between uni-sensory ROIs and STS from pretest to posttest in both cases. These data provide initial evidence for the malleable experience-driven cortical functionality for AV speech perception in elderly hearing-impaired people and call for further studies with a much larger subject sample and systematic control to fill in the knowledge gap to understand brain plasticity associated with auditory rehabilitation in the aging population.


Localization of arylsulphatase A and B activities in rat kidney.
Very high arylsulphatase activity has been detected in rat kidney. It is the highest in renal cortex (19 U/g tissue), 3-30 times higher than in other rat organs. Histochemically, arylsulphatase B (N-acetylgalactosamine-4-sulphate sulphatase) activity is localized in large lysosomes of proximal convoluted tubules, where it accounts for over 90% of total arylsulphatase activity. This suggests that the enzyme plays an important role in the degradation of endocytosed sulphated oligosaccharides.


Pediatric posttraumatic orbital subperiosteal hematoma.
To report five children with posttraumatic orbital subperiosteal hematoma. In this study, five cases with posttraumatic orbital subperiosteal hematoma were studied and reviewed along with similar cases in a systematic literature review. The mean age of our patients was 9.40 ± 3.51 years, ranging from 4 to 13 years, and all were male. Mechanisms of injuries were blunt trauma, falling from a building, car accident, and falling from a bicycle. All patients had unilateral involvement. Treatment options included needle aspiration, surgical drainage, and observation for spontaneous resolution. Except for one patient, positive outcomes were achieved. The most common location for posttraumatic orbital subperiosteal hematoma is the superior orbital wall. Traumatic optic neuropathy and permanent visual loss are uncommon. Observation, surgical drainage, and aspiration are common treatment options.


LOW FREQUENCY OF t HAPLOTYPES IN NATURAL POPULATIONS OF HOUSE MICE (MUS MUSCULUS DOMESTICUS).
t haplotypes are a naturally occurring, autosomal, meiotic-drive system found on chromosome 17 of the house mouse. They show non-Mendelian transmission from heterozygous +/t males, such that 90% or more of the male's offspring inherit the t-bearing chromosome. Although they are expected to become rapidly fixed, surveys of natural populations typically report low overall frequencies of only ~15-25% +/t heterozygotes. Generally, such studies of t haplotypes in wild populations have sampled only small numbers of individuals due to the need to genotype mice by breeding, thus we have conducted a large survey of wild mice, Mus musculus domesticus, using DNA markers to examine the frequency and distribution of t haplotypes in natural populations. The overall frequency of +/t heterozygotes from our entire sample was 0.062, which is much lower than all previous estimates of t haplotype frequency. t haplotypes were patchily distributed and rare, and were present in only 46% of the populations we sampled. There were no significant sex-specific differences in the frequency of t haplotypes. Our data suggest that the frequency of +/t heterozygotes in independent populations varies with respect to population size and stability: t haplotypes were at low frequency in all large, relatively persistent populations, whereas they were at more variable, and often higher, frequencies in small, temporally unstable populations. The extinction and recolonization of many of the smaller populations may contribute to the greater variation in t haplotype frequency observed, and small populations may be important reservoirs of t haplotypes in the wild. The highest frequencies of t haplotypes were obtained from populations with semilethal, or complementing lethal, t haplotypes, where t/t homozygous mice were present.


Mice deficient in Ext2 lack heparan sulfate and develop exostoses.
Hereditary multiple exostoses (HME) is a genetically heterogeneous human disease characterized by the development of bony outgrowths near the ends of long bones. HME results from mutations in EXT1 and EXT2, genes that encode glycosyltransferases that synthesize heparan sulfate chains. To study the relationship of the disease to mutations in these genes, we generated Ext2-null mice by gene targeting. Homozygous mutant embryos developed normally until embryonic day 6.0, when they became growth arrested and failed to gastrulate, pointing to the early essential role for heparan sulfate in developing embryos. Heterozygotes had a normal lifespan and were fertile; however, analysis of their skeletons showed that about one-third of the animals formed one or more ectopic bone growths (exostoses). Significantly, all of the mice showed multiple abnormalities in cartilage differentiation, including disorganization of chondrocytes in long bones and premature hypertrophy in costochondral cartilage. These changes were not attributable to a defect in hedgehog signaling, suggesting that they arise from deficiencies in other heparan sulfate-dependent pathways. The finding that haploinsufficiency triggers abnormal cartilage differentiation gives insight into the complex molecular mechanisms underlying the development of exostoses.


[The application of superselective embolization of renal vessels in case of bleeding after percutaneous nephro- lithotomy].
Bleeding, injures to surrounding organs and pleura are serious complications of percutaneous nephrolithotripsy. The inefficiency of hemostatic therapy is an indication for superselective embolization of the renal vessels. This technique demonstrates the high efficiency in case of postoperative bleeding. To develop a treatment algorithm and to evaluate an efficiency of superselective embolization of the renal vessels, based on the results of treatment of postoperative complications, which are associated with bleeding. A retrospective analysis of 1375 patients treated from January 2011 to December 2018 for large (over 1.5 cm) and staghorn renal stones was performed. A number of patients had various complications in the early postoperative period, which were graded according to the Clavien-Dindo classification, including bleeding due to intraoperative damage to renal vessels, which required additional interventions. The treatment strategy was based on the assessment of volume and severity of blood loss as well as the hemodynamic stability. Based on the severity of bleeding and hemodynamic stability, the treatment algorithm was developed. The analysis of the results of superselective embolization of renal arteries demonstrates the high effectiveness of this technique in case of postoperative bleeding. Superselective embolization is an effective method of hemostasis in case of postoperative bleeding. The proposed algorithm allows for early coordination of therapeutic measures depending on the severity of bleeding and the patients condition in order to evaluate the risk of continued bleeding and the determine the optimal treatment strategy.


Carbachol desensitizes pancreatic enzyme secretion by downregulation of receptors.
First incubating guinea pig pancreatic acini with carbachol reduced the subsequent stimulation of amylase release caused by carbachol, cholecystokinin octapeptide (CCK-8), and bombesin but not that caused by vasoactive intestinal peptide, substance P, 8-bromoadenosine 3',5'-cyclic monophosphate, A23187, or 12-O-tetradecanoylphorbol-13-acetate. Carbachol also reduced the subsequent binding of N-[3H]methylscopolamine, 125I-CCK-8, and 125I-[Tyr4]bombesin. Pancreatic acini possess a high-affinity class of cholinergic receptors and a low-affinity cholinergic receptors appears to produce the reduction in carbachol-stimulated amylase release and binding of N-[3H]methylscopolamine. First incubating acini with carbachol caused a complete loss of high-affinity cholinergic receptors with no change in the number or affinity of low-affinity cholinergic receptors. Carbachol occupation of low-affinity cholinergic receptors appears to produce the reduction in CCK-8- and bombesin-stimulated amylase release and in binding of 125I-CCK-8 and 125I-[Tyr4]bombesin. Acini possess two classes of CCK receptors. One class has a high affinity for CCK-8; the other class has a low affinity for CCK-8. First incubating acini with carbachol caused a 60% decrease in the number of high-affinity CCK receptors with no change in the number of low-affinity receptors or the affinities of either class of receptors for CCK-8. Acini possess a single class of bombesin receptors, and first incubating acini with carbachol caused a 40% decrease in the number of bombesin receptors with no change in their affinity for bombesin. 12-O-tetradecanoyl phorbol-13-acetate reproduced the action of carbachol on binding of N-[3H]methylscopolamine and 125I-CCK-8 but not on binding of 125I-[Tyr4]bombesin, suggesting that carbachol activation of protein kinase C may in some way mediate the effect of carbachol on receptors for carbachol and those for CCK but not that on receptors for bombesin.


Socioeconomic Inequalities in Psychological Distress among Urban Adults: The Moderating Role of Neighborhood Social Cohesion.
Various studies have reported socioeconomic inequalities in mental health among urban residents. This study aimed at investigating whether neighborhood social cohesion influences the associations between socio-economic factors and psychological distress. Cross-sectional questionnaire study on a random sample of 18,173 residents aged 16 years and older from 211 neighborhoods in the four largest cities in the Netherlands. Psychological distress was the dependent variable (scale range 10-50). Neighborhood social cohesion was measured by five statements and aggregated to the neighborhood level using ecometrics methodology. Multilevel linear regression analyses were used to investigate cross-level interactions, adjusted for neighborhood deprivation, between individual characteristics and social cohesion with psychological distress. The mean level of psychological distress among urban residents was 17.2. Recipients of disability, social assistance or unemployment benefits reported higher psychological distress (β = 5.6, 95%CI 5.2 to 5.9) than those in paid employment. Persons with some or great financial difficulties reported higher psychological distress (β = 3.4, 95%CI 3.2 to 3.6) than those with little or no financial problems. Socio-demographic factors were also associated with psychological distress, albeit with much lower influence. Living in a neighborhood with high social cohesion instead of low social cohesion was associated with a lower psychological distress of 22% among recipients of disability, social assistance or unemployment benefits and of 13% among citizens with financial difficulties. Residing in socially cohesive neighborhoods may reduce the influence of lack of paid employment and financial difficulties on psychological distress among urban adults. Urban policies aimed at improving neighborhood social cohesion may contribute to decreasing socio-economic inequalities in mental health.


[Characterization methods of flowability of traditional Chinese medicine powders].
To characterize the flowability of traditional Chinese medicine (TCM) powders by using appropriate methods. With highly flowable direct compression excipients and Chinese traditional medicine powder as raw materials, the flowability of material powders is determined by the Carr method and the Jenike method. The Carr method and the Jenike method for the determination of the flowability of Chinese herb extract powder and direct-pressing excipients have no obvious difference. But the flowability of Chinese herb extract powder is not as good as direct compression excipients. From the characterization results of both methods, we can find that the Carr method better reflects the actual flowability of TCM extracts, while the Jenike method can be used for guiding the design of the hopper device.


Genetic background differences and nonassociative effects in mouse trace fear conditioning.
Fear conditioning, including variants such as delay and trace conditioning that depend on different neural systems, is widely used to behaviorally characterize genetically altered mice. We present data from three strains of mice, C57/BL6 (C57), 129/SvlmJ (129), and a hybrid strain of the two (F(1) hybrids), trained on various versions of a trace fear-conditioning protocol. The initial version was taken from the literature but included unpaired control groups to assess nonassociative effects on test performance. We observed high levels of nonassociative freezing in both contextual and cued test conditions. In particular, nonassociative freezing in unpaired control groups was equivalent to freezing shown by paired groups in the tests for trace conditioning. A number of pilot studies resulted in a new protocol that yielded strong context conditioning and low levels of nonassociative freezing in all mouse strains. During the trace-CS test in this protocol, freezing in unpaired controls remained low in all strains, and both the C57s and F(1) hybrids showed reliable associative trace fear conditioning. Trace conditioning, however, was not obtained in the 129 mice. Our findings indicate that caution is warranted in interpreting mouse fear-conditioning studies that lack control conditions to address nonassociative effects. They also reveal a final set of parameters that are important for minimizing such nonassociative effects and demonstrate strain differences across performance in mouse contextual and trace fear conditioning.


Pancreatic cancer presenting as a Sister Mary Joseph's nodule: case report and update of the literature.
Cutaneous metastasis of an occult malignancy to the umbilicus has come to be known as a Sister Mary Joseph's nodule (SMJN). More than 400 cases of this well-described clinical presentation of advanced gastrointestinal and gynecologic cancers have been reported. Pancreatic cancer presenting as a SMJN is a rare phenomenon. In most series, the pancreas is the source of a SMJN in 7% to 9% of cases. We report a case of pancreatic adenocarcinoma in which the initial presenting sign was a SMJN. We also reviewed the published literature from the last 100 years on this phenomenon by conducting a detailed PubMed search. Including this case, we identified 57 cases of SMJN originating from the pancreas. The clinical patient characteristics with regard to age, male-female ratio, race, and prognosis of these cases were similar to that of pancreatic cancer in general. In contrast, 91% of these cases originated in the tail and body of the pancreas rather than the head of the pancreas. This case emphasizes that pancreatic cancer should be considered in the differential diagnosis of umbilical metastasis.


Which dietary reference intake is best suited to serve as the basis for nutrition labeling for daily values?
The U.S. Food and Drug Administration is currently reviewing regulations on nutrition labeling to better address current health issues as well as updating nutrient daily values (DVs), most of which are still based on recommended dietary allowances (RDAs) established in 1968. In 2003 the Committee on Use of Dietary Reference Intakes in Nutrition Labeling of the Institute of Medicine recommended that the DVs be based on the estimated average requirement (EAR) rather than the RDA and that a population-weighted mean of EARs be used. The rationale given is that the EAR is the best statistical approximation of the nutrient requirement for any one individual in the population, and its use would result in a food appearing more nutritious, as it would provide a greater percentage of the DV if the DV were a smaller amount. Concerns about these recommendations focus on the appropriate role of the Nutrition Facts panel, 1 of the 3 major public nutrition education tools in the United States (along with MyPyramid and Dietary Guidelines for Americans). Providing a benchmark or standard that knowingly has only a 50% chance of meeting a consuming individual's requirement is not appropriate. The DV on a Nutrition Facts panel should provide useful guidance to the individual about how a serving will assist in meeting that person's goal for consumption, and thus it should be based on the RDA or adequate intake, rather than the EAR, and be derived from the highest recommended intake, as has been the practice since 1973.


At the crossway of ER-stress and proinflammatory responses.
Immune cells detect specific microbes or damage to tissue integrity in order to initiate efficient immune responses. Abnormal accumulation of proteins in the endoplasmic reticulum (ER) can be seen as a sign of cellular malfunction and stress that triggers a collection of conserved emergency rescue programs. These different signaling cascades, which favor ER proteostasis and promote cell survival, are collectively known as the unfolded protein response (UPR). In recent years, a synergy between the UPR and inflammatory cytokine production has been unraveled, with different branches of the UPR entering in a cross-talk with specialized microbe sensing pathways, which turns on or amplify inflammatory cytokines production. Complementary to this synergetic activity, UPR induction alone, can itself be seen as a danger signal, and triggers directly or indirectly inflammation in different cellular and pathological models, this independently of the presence of pathogens. Here, we discuss recent advances on the nature of these cross-talks and how innate immunity, metabolism dysregulation, and ER-signaling pathways intersect in specialized immune cells, such as dendritic cells (DCs), and contribute to the pathogenesis of inflammatory diseases.


Risk Compensation Following Medical Male Circumcision: Results from a 1-Year Prospective Cohort Study of Young School-Going Men in KwaZulu-Natal, South Africa.
This study sought to assess risk compensation following voluntary medical male circumcision of young school-going men. Risk compensation is defined as an inadvertent increase in sexual risk behaviors and a corresponding decrease in self-perceived risk for contracting HIV following the application of a risk reduction technology. This study documented the sexual practices of circumcised (n = 485) and uncircumcised (n = 496) young men in 42 secondary schools at three time points (baseline and 6 and 12 months) in a sub-district of KwaZulu-Natal, South Africa. Study participants were aged from 16 to 24 years old. At the end of the study period, there was no significant difference between the two cohorts concerning learners' perceptions of being at risk of contracting HIV (interaction effect: b = -0.12, p = 0.40). There was also no significant difference in the number of sexual partners in the previous month (interaction effect: b = -0.23, p = 0.15). The proportion of learners who have never used a condom decreased significantly over time (time effect: b = -0.27, p = 0.01), and there was no difference between the circumcised and uncircumcised learners (interaction effect: b = -0.09, p = 0.91). Risk compensation, as evidenced in this study over a 1-year period, was not associated with undergoing voluntary medical male circumcision (VMMC) in our sample of young school-going men. However, it is of concern that at the end of this study, less than half of the sexually active sample in a high-HIV-prevalence community used condoms consistently in the previous month (39% for both study cohorts). The latter underscores the need to view VMMC as a potential entry point for planned HIV and sexuality education interventions targeting young men in this community.


Cultured mucosal cell sheet with a double layer of keratinocytes and fibroblasts on a collagen membrane.
The aim of this study was to develop a novel cultured mucosal membrane that was facile to prepare and easy to handle, and that could be applied to mucosal defects in the oral cavity. Human oral keratinocytes and fibroblasts were prepared from the oral mucosa. We made the following two types of cultured mucosal cell sheets: a monolayer sheet of keratinocytes cultured on a collagen membrane (K-S) and a double-layered sheet of keratinocytes and fibroblasts on a collagen membrane (KF-S). A collagen membrane was used as a control. Each type of sheet was transplanted onto dorsal skin defects of nude mice. The wound area was measured for the assessment of wound contraction and a specimen was harvested for histologic evaluation 1 week and 4 weeks after grafting. Wound contraction was minimal with KF-S grafts. Although histologic examination showed normal differentiation of the epithelium in all graft types, the involucrin expression pattern of KFS was most similar to that of normal epithelium. These results indicate that a double-layered sheet of keratinocytes and fibroblasts cultured on a collagen membrane may facilitate epithelial healing and prevent wound contraction.


Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male db/db Mice.
Angiotensin-converting enzyme 2 (ACE2) gene therapy aimed at counteracting pancreatic ACE2 depletion improves glucose regulation in two diabetic mouse models: db/db mice and angiotensin II-infused mice. A disintegrin and metalloproteinase 17 (ADAM17) can cause shedding of ACE2 from the cell membrane. The aim of our studies was to determine whether ADAM17 depletes ACE2 levels in pancreatic islets and β-cells. Dynamics of ADAM17-mediated ACE2 shedding were investigated in 832/13 insulinoma cells. Within a wide range of ACE2 expression levels, including the level observed in mouse pancreatic islets, overexpression of ADAM17 increases shed ACE2 and decreases cellular ACE2 levels. We provide a mathematical description of shed and cellular ACE2 activities as a function of the ADAM17 activity. The effect of ADAM17 on the cellular ACE2 content was relatively modest with an absolute control strength value less than 0.25 and approaching 0 at low ADAM17 activities. Although we found that ADAM17 and ACE2 are both expressed in pancreatic islets, the β-cell is not the major cell type expressing ACE2 in islets. During diabetes progression in 8-, 12-, and 15-week-old db/db mice, ACE2 mRNA and ACE2 activity levels in pancreatic islets were not decreased over time nor significantly decreased compared with nondiabetic db/m mice. Levels of ADAM17 mRNA and ADAM17 activity were also not significantly changed. Inhibiting basal ADAM17 activity in mouse islets failed to affect ACE2 levels. We conclude that whereas ADAM17 has the ability to shed ACE2, ADAM17 does not deplete ACE2 from pancreatic islets in diabetic db/db mice.


[Analysis of the system of evaluation of a medical career in Chile].
For the purpose of measuring the extent to which the modern university accomplishes its purposes, the authors have devised an evaluation methodology inspired by the work of the most modern international specialists in the subject. They have applied their methodology first to the system for evaluating medical programs in general and then to a specific medical program regarded as representative of medical training in Chile. Surveys of faculty and students led them to the conclusion that in actual evaluative practice there have been wide deviations from the ideal model, and that the evaluation system could be improved to become an essential component of the process of informing and training the student and to provide feedback to th teaching-learning process.


Influence of isolate pathogenicity on the aerosol transmission of Porcine reproductive and respiratory syndrome virus.
The objectives of this study were to evaluate the role of isolate pathogenicity in the aerosol transmission of Porcine reproductive and respiratory syndrome virus (PRRSV) and to determine whether PRRSV could be detected in air samples. To assess transmission, we exposed naive recipient pigs to aerosols from pigs inoculated with PRRSV MN-30100, an isolate of low pathogenicity, or MN-184, a highly pathogenic isolate. Blood samples and nasal-swab samples were collected from the inoculated pigs during the exposure period and tested for the presence of PRRSV RNA by quantitative (real-time) reverse-transcriptase polymerase chain reaction (RT-PCR); the amount of RNA was expressed as the median tissue culture dose per milliliter (TCID50/mL). The recipient pigs were clinically evaluated for 14 d after exposure and tested on days 7 and 14 by qualitative RT-PCR and enzyme-linked immunosorbent assay (ELISA). To prove the presence of PRRSV in aerosols, air samples were collected from each recipient-pig chamber by means of an air sampler. The PRRSV RNA concentrations were significantly higher (P = 0.01) in the blood samples from the pigs infected with PRRSV MN-184 than in the blood samples from those infected with PRRSV MN-30100; however, the concentrations in the nasal-swab samples were not significantly different (P = 0.26). Recipient pigs exposed to aerosols from pigs infected with PRRSV MN-184 became infected, whereas those exposed to aerosols from pigs infected with PRRSV MN-30100 did not; the difference in transmission rate was significant at P = 0.04. We detected PRRSV MN-184 RNA but not PRRSV MN-30100 RNA in air samples by PCR. Under the conditions of this study, PRRSV isolate pathogenicity may influence aerosol transmission of the virus.


Elective Endovascular Aneurysm Repair (EVAR) for the Treatment of Infrarenal Abdominal Aortic Aneurysms of 5.0-5.5 cm: Differences between Men and Women.
There is significant debate regarding the existence of sex-related differences in the presentation, treatment, and outcomes of men versus women affected by abdominal aortic aneurysm (AAA). The purpose of this study is to compare endovascular aneurysm repair (EVAR) of infrarenal AAAs with the current sex-neutral 5.0-5.5 cm-diameter threshold for intervention between the two sexes. Retrospective review of consecutive cases from a single teaching institution over a period of five years of patients who had undergone elective EVAR for AAAs between 5.0 and 5.5 cm in diameter. Outcomes of interest were compared according to sex. Ninety-four patients were included in the analysis, with a higher prevalence of men (53%). Females were older at the time of repair, 78 ± 5.1 years, versus 71.7 ± 7 years (p < 0.01), and had higher incidence of underlying comorbidities, namely, arrhythmia, chronic kidney disease, and previous carotid revascularization. Women had higher incidence of immediate systemic complications (p = 0.021), post-operative AMI (p = 0.001), arrhythmia (p = 0.006), pulmonary oedema (p < 0.001), and persistent renal dysfunction (p = 0.029). Multivariate analysis for post-operative factors associated to mortality and adjusted for sex confirmed that AMI (p = 0.015), arrhythmia (p = 0.049), pulmonary oedema (p = 0.015), persistent renal dysfunction (p < 0.001), cerebral ischemia (p < 0.001), arterial embolism of lower limbs (p < 0.001), and deep-vein thrombosis of lower limbs (p < 0.001) were associated to higher EVAR-related mortality; a higher incidence of post-operative AMI (p = 0.014), pulmonary edema (p = 0.034), and arterial embolism of lower limbs (p = 0.046) were associated to higher 30-days mortality. In females there was also a higher rate of suprarenal fixation (p = 0.026), insertion outside the instruction for use (p = 0.035), and a more hostile neck anatomy with different proximal aortic diameter (p < 0.001) and angle (p = 0.003). A similar threshold of size of AAA for elective surgery for both males and females might not be appropriate for surgical intervention, as females tend to have worse outcomes. Further population-based studies are needed to guide on sex-related differences and intervention on AAA.


Stage 1 hypertension defined by the 2017 American College of Cardiology/American Heart Association guideline and risk of adverse birth outcomes in Eastern China.
The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommended a lower threshold (130/80 mmHg) for hypertension in nonpregnant adults. However, the influence of this guideline in Chinese pregnant women is not well characterized. Data of 32 742 and 14 479 mothers who had blood pressure (BP) less than 130/80 mmHg and no proteinuria before 20 gestational weeks and delivered live singletons between 1 January 2014 and 30 November 2019 were extracted from Taizhou and Taicang register-based cohorts, respectively. The average measured BP in the third trimester was obtained and categorized according to the 2017 ACC/AHA guideline. The association between BP and risk of adverse birth outcomes was assessed by multivariate logistic regression analysis. In the third trimester, 331 (1.01%) and 378 (2.61%) women had mean BP at least 140/90 mmHg, but 2435 (7.44%) and 1054 (7.28%) had stage 1 hypertension (130-139/80-89 mmHg) in Taizhou and Taicang, respectively. Significant associations between stage 1 hypertension and small for gestational age [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.14-1.52] and low birth weight (OR = 1.81, 95% CI = 1.46-2.25) were observed in the Taizhou population. Consistent results were also shown in the Taicang population [OR (95% CI), of 1.46 (1.18-1.79) and 1.50 (1.07-2.11), respectively]. Stage 1 hypertension in the third trimester defined by the 2017 ACC/AHA guideline was associated with an increased risk for adverse birth outcomes in Eastern Chinese pregnant women, suggesting that this guideline may improve the detection of high BP and surveillance of adverse neonatal outcomes in China.


Startle Seizures and Diffuse Leukoencephalopathy After Resolution of Herpes Simplex Virus 1 Encephalitis in a Child.
We describe a unique clinical presentation of a child after the acute phase of herpes simplex virus 1 (HSV1) encephalitis. A 17-month-old boy first presented with HSV1 encephalitis and was promptly treated with antiviral medication. Seven months later, he was re-admitted for startle seizures. Magnetic Resonance Imaging of the brain showed diffuse confluent leukoencephalopathy. This constellation of symptoms has not been previously reported in HSV1 encephalitis. In conclusion, we showed that brain injury due to HSV1 encephalitis can be associated with the development of startle seizures and diffuse white matter injury in the post-acute phase.


Perioperative Complications in Patients With Sleep Apnea Undergoing Total Joint Arthroplasty.
This study aims to evaluate the effect of sleep apnea (SA) on perioperative complications after total joint arthroplasty (TJA) and whether the type of anesthesia influences these complications. Using the ninth and tenth revisions of the International Classification of Diseases, coding systems, we queried our institutional TJA database from January 2005 to June 2016 to identify patients with SA who underwent TJA. These patients were matched in a 1:3 ratio based on age, gender, type of surgery, and comorbidities to patients who underwent TJA but were not coded for SA. Perioperative complications were identified using the same coding systems. Multivariate analysis was used to test if SA is an independent predictor of perioperative complications and if type of anesthesia can affect these complications. A total of 1246 patients with SA were matched to 3738 patients without SA. Pulmonary complications occurred more frequently in patients with SA (1.7% vs 0.6%; P < .001), confirmed using multivariate analysis (odds ratio = 2.91; 95% confidence interval, 1.58-5.36; P = .001). Use of general anesthesia increased risk of all but central nervous system complications and mortality (odds ratio = 15.88; 95% confidence interval, 3.93-64.07; P < .001) regardless of SA status compared with regional anesthesia. Rates of pulmonary and gastrointestinal complications, acute anemia, and mortality were lower in SA patients when regional anesthesia was used (P < .05). SA increases risk of postoperative pulmonary complications. The use of regional anesthesia may reduce risk of pulmonary complications and mortality in SA patients undergoing TJA.


microRNA-29b: an emerging player in human cancer.
MicroRNAs (miRNAs) are ubiquitously expressed small, non-coding RNAs that negatively regulate gene expression at a post transcriptional/translational level. They have emerging as playing crucial roles in cancer at all stages ranging from initiation to metastasis. As a tumor suppressor miRNA, aberrant expression of microRNA-29b (miR-29b) has been detected in various types of cancer, and its disturbance is related with tumor development and progression. In this review, we summarize the latest findings with regard to the tumor suppressor signature of miR-29b and its regulatory mechanisms. Our review highlights the diverse relationships between miR-29b and its target genes in malignant tumors.


Elevated sensitivity to cardiac ischemia in proteinuric rats is independent of adverse cardiac remodeling.
Chronic renal dysfunction severely increases cardiovascular risk. Adverse cardiac remodeling is suggested to play a major role as predisposition for increased cardiac ischemic vulnerability. The aim of the present study was to examine the role of adverse cardiac remodeling in cardiac sensitivity to acute ischemia/reperfusion damage in a rat model for renal dysfunction. Munich Wistar Fromter (MWF) rats, developing spontaneous progressive renal dysfunction and mild hypertension, were compared to healthy Wistar rats, and to nonproteinuric spontaneously hypertensive rats (SHRs). In MWF rats, renal dysfunction and mild hypertension were confirmed. Hearts were analyzed for adverse cardiac remodeling, including myocyte hypertrophy, capillary density, and interstitial fibrosis, by histology. In parallel, sensitivity to cardiac ischemia/reperfusion damage was obtained from infarct size measured after 30-min coronary artery occlusion, followed by 24 h of reperfusion. Infarcts were larger in MWF rats [56 ± 3% of risk area (P = 0.04)], but at a similar extent in SHRs [52 ± 4% (P = 0.16)], when compared to Wistar rats (45 ± 4%). However, whereas SHRs showed pronounced adverse cardiac remodeling, MWF rats did not: no left ventricular hypertrophy (myocyte size MWF rats +29%; SHRs +72%), no lower capillary density (MWF rats +34%; SHRs -13%), and no interstitial fibrosis (MWF rats -16%; SHRs +70%). Data indicate that chronic renal dysfunction in MWF rats is associated with elevated cardiac sensitivity to acute ischemia/reperfusion damage, as reflected by larger infarcts. Comparing results to SHRs suggests that this higher susceptibility could not be attributed to hypertension or adverse cardiac remodeling.


Atomic Scale Dynamics Drive Brain-like Avalanches in Percolating Nanostructured Networks.
Self-assembled networks of nanoparticles and nanowires have recently emerged as promising systems for brain-like computation. Here, we focus on percolating networks of nanoparticles which exhibit brain-like dynamics. We use a combination of experiments and simulations to show that the brain-like network dynamics emerge from atomic-scale switching dynamics inside tunnel gaps that are distributed throughout the network. The atomic-scale dynamics emulate leaky integrate and fire (LIF) mechanisms in biological neurons, leading to the generation of critical avalanches of signals. These avalanches are quantitatively the same as those observed in cortical tissue and are signatures of the correlations that are required for computation. We show that the avalanches are associated with dynamical restructuring of the networks which self-tune to balanced states consistent with self-organized criticality. Our simulations allow visualization of the network states and detailed mechanisms of signal propagation.