Compressibility of aqueous solutions of nonelectrolytes: an equilibrium model.
In this paper the parabolic-shaped dependences of compressibility kappa(S) of a nonelectrolyte in water solvent on concentration are explained and described semiquantitatively in terms of hydrate formation equilibrium reaction. It was demonstrated that only two fitted parameters, the hydration number n(h) and the formation constant of the hydrate K, are sufficient to reproduce satisfactorily the experimental data, in particular the characteristic minimums of kappa(S) versus composition observed at low contents of solutes.


Analysis of monohydroxyeicosatetraenoic acids and F2-isoprostanes as markers of lipid peroxidation in rat brain mitochondria.
We have introduced two specific techniques for the quantitative measurement of monohydroxyeicosatetraenoic acids (HETEs) and F2-isoprostanes by gas chromatography-mass spectrometry/negative ion chemical ionization (GC-MS/NICI) to study lipid peroxidation in isolated rat brain mitochondria by iron/ascorbate. The analysis of HETEs involved hydrogenation, solid phase extraction on a C18-cartridge, formation of pentafluorobenzyl bromide and trimethylsilyl ether derivatives. In the case of F2-isoprostanes, the analytical procedure was similar to that of HETEs except that the hydrogenation step was omitted. We found that HETE content (sum of 5-, 8-12-, and 15-isomers) in freshly prepared rat brain mitochondria was 220 +/- 40pmol/mg protein. The corresponding content for the F2-isoprostane, 8-iso-PGF2alpha, was 0.21 +/-+/- 0.10 pmol/mg protein. HETEs and 8-iso-PGF2alpha were predominantly present in the esterified form. The content of both HETEs and 8-iso-PGF2alpha were increased in presence of iron/ascorbate as oxidation system. After 30 min incubation with Fe2+ ascorbate, the content of HETE isomers was increased about 6-fold compared with baseline levels whereas that for 8-iso-PGF2alpha was elevated 100-fold. Formation of HETEs and F2-isoprostanes corresponded to the consumption of arachidonic acid (AA) and alpha-tocopherol, respectively. There were almost no changes in the content of free (non-esterified) HETEs and 8-iso-PGF2alpha during the course of iron/ascorbate induced oxidation of the brain mitochondria. Our data provide the first direct evidence for the presence of HETEs and F2-isoprostanes in freshly isolated rat brain mitochondria and that esterified HETEs and 8-iso-PGF2alpha are predominantly generated during iron/ascorbate induced lipid peroxidation. Sensitive quantification of these products of non-enzymatic lipid peroxidation as indicators of oxidant injury opens new areas of investigation regarding the role of free radicals in the pathogenesis of human diseases. In addition, HETEs and F2-isoprostanes may be important mediators for mitochondrial functions.


Joint deconvolution and classification with applications to passive acoustic underwater multipath.
This paper addresses the problem of classifying signals that have been corrupted by noise and unknown linear time-invariant (LTI) filtering such as multipath, given labeled uncorrupted training signals. A maximum a posteriori approach to the deconvolution and classification is considered, which produces estimates of the desired signal, the unknown channel, and the class label. For cases in which only a class label is needed, the classification accuracy can be improved by not committing to an estimate of the channel or signal. A variant of the quadratic discriminant analysis (QDA) classifier is proposed that probabilistically accounts for the unknown LTI filtering, and which avoids deconvolution. The proposed QDA classifier can work either directly on the signal or on features whose transformation by LTI filtering can be analyzed; as an example a classifier for subband-power features is derived. Results on simulated data and real Bowhead whale vocalizations show that jointly considering deconvolution with classification can dramatically improve classification performance over traditional methods over a range of signal-to-noise ratios.


Triphenylethylene antiestrogen-binding sites in cockerel liver nuclei: evidence for an endogenous ligand.
Salt extracts of purified nuclei from cockerel liver contain a limited number of sites that bind triphenylethylene nonsteroidal antiestrogens with high affinity and specificity. The assay of the [3H]tamoxifen (3H-labeled 1-[4-(2-dimethylaminoethyoxy)phenyl] 1,2-diphenylbut-1-(Z)ene)-binding sites is optimally achieved by preincubation of the salt extracts with charcoal-dextran suspension; a 4- to 8-fold increase in activity over that obtained with nontreated extracts is found. This suggests that the binding sites are occupied in vivo by an unknown endogenous ligand. The equilibrium dissociation constant for [3H]tamoxifen binding is 4.76 +/- 1.8 nM, and the binding site concentration is 1.7 +/- 0.7 fmol/microgram DNA. The concentration of high affinity estrogen-binding sites in the same extracts is almost 30-fold less (0.06 +/- 0.01 fmol/micrograms DNA). The relative binding affinities of various antiestrogens for the nuclear antiestrogen-binding sites (with tamoxifen arbitrarily set at 100%) are as follows: nafoxidine (1-[2-(p-[3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl]phenoxy)ethyl] pyrrolidine hydrochloride); 126%) greater than tamoxifen (100%) greater than N-des-methyltamoxifen (16%) greater than CI-628 (alpha-[p-[2-(1-pyrrolidine)ethyoxy]phenyl] 4-methoxy-alpha'-nitrostilbene; 14%) greater than 4-hydroxytamoxifen (7%). Estrogens (17 beta-estradiol, estriol, estrone, and diethylstilbestrol) and several other steroids (cholesterol, dihydrotestosterone, pregnenolone, progesterone, and hydrocortisone) show little or no affinity for binding to the nuclear sites (relative binding affinity, less than 0.5%). However, ether extracts of cockerel serum or liver nuclei contain a substance(s) that competitively inhibits [3H]tamoxifen binding to the nuclear antiestrogen-binding sites. The ether-soluble material does not compete for [3H]estradiol binding to the salt-soluble nuclear estrogen receptor. These studies suggest that cockerel serum and liver nuclei contain a natural compound which competes with the triphenylethylenes at the antiestrogen-binding site and may occupy the nuclear binding sites in vivo.


[Opposition to organ donation in France: marker of a growing social divide?].
Over the past 20 years in France, whereas medical treatments have been advancing, information campaigns on organ donation have multiplied and the Agence de la Biomédecine has been effectively supervising transplant procedures, the donor waiting list has continued to grow. Is this trend linked to a social issue or is it because the law is now unsuitable? The present article examines this question, based on the experience of the President of the Greffe de vie (Graft for Life) Foundation who, for last 7 years, has been trying to increase awareness of organ donation in France.


In silico analysis of mutations occurring in the protein N-acetylgalactosamine-6-sulfatase (GALNS) and causing mucopolysaccharidosis IVA.
The goals were to analyze and characterize the secondary structure, regions of intrinsic disorder and physicochemical characteristics of three classes of mutations described in the enzyme N-acetylgalactosamine-6-sulfatase that cause mucopolysaccharidosis IVA: missense mutations, insertions and deletions. All mutations were compared to wild-type enzyme, and the results showed that with 25 of 129 missense mutations secondary structure was maintained and that 104 mutations showed minor changes, such as an increase or decrease in the size of the elements. The secondary structure of all insertions and deletions introduced important changes, such as increase in the number and size of elements. The results obtained from intrinsic disorder analysis revealed that missense mutations caused no alterations. However, the insertions and deletions led to major regions of intrinsic disorder. The physicochemical characteristics of the amino acids found in missense mutations revealed unchanged characteristics in 32 of the 129 mutations. However, the remainder had changes that could lead to a modification of tertiary structure. The results proved that it was feasible and necessary to obtain the three-dimensional structure of the enzyme with its mutants to better understand the change in function.


Molybdenum impregnated g-C3N4 nanotubes as potentially active photocatalyst for renewable energy applications.
Molybdenum (Mo) impregnated g-C3N4 (Mo-CN) nanotubes are fabricated via a thermal/hydrothermal process to augment photoelectrochemical properties during solar-driven water-splitting (SDWS) reactions. Graphitic-C3N4 is an attractive material for photocatalysis because of its suitable band energy, high thermal and chemical stability. The FE-SEM and HR-TEM comprehend the nanotube-like morphology of Mo-CN. The spectroscopic characterization revealed bandgap energy of 2.63 eV with high visible-light activity. The x-ray diffraction of pristine g-C3N4 and Mo-CN nanotubes discloses the formation of triazine-based nanocrystalline g-C3N4, which remains stable during hydrothermal impregnation of Mo. Furthermore, Mo-CN nanotubes possess high sp2-hybridized nitrogen content, and metallic/oxidized Mo nanoparticles (in a ratio of 1:2) are impregnated into g-C3N4. The XPS analysis confirms C, N, and Mo for known atomic and oxidation states in Mo-CN. Furthermore, high photocurrent efficiency (~ 5.5 mA/cm2) is observed from 5%-Mo-CN nanotubes. That displays efficient SDWS by 5%-Mo-CN nanotubes than other counterparts. Impedance spectroscopy illustrated the lowest charge transfer resistance (Rct) of 5%-Mo-CN nanotubes, which further confirms the fast electron transfer kinetics and efficient charge separation resulting in high photocurrent generation. Hence, 5%Mo-CN composite nanotubes can serve as a potential photocatalytic material for viable solar-driven water splitting.


Identification of the Klambothrips myopori (Thysanoptera: Phlaeothripidae) Predator Complex in California.
To identify the predator complex of the invasive thrips, Klambothrips myopori, on its ornamental host plant Myoporum laetum, field surveys were conducted at three sites in southern California over the period of 1 y. Five insect orders and five spider families were represented in the survey. Although the most abundant groups differed among collection sites, syrphid larvae, anthocorids, Chrysoperla spp., Franklinothrips orizabensis Johansen (Thysanoptera: Aeolothripidae), and one spider family (Salticidae) were all collected at each site. Based on the field surveys, Orius spp. and Chrysoperla spp. were identified as possible key natural enemies of K. myopori. Laboratory studies were then conducted to determine the consumption rates of Orius insidiosus Say (Hemiptera: Anthocoridae) and Chrysoperla rufilabris Burmeister (Neuroptera: Chrysopidae) at constant densities of K. myopori and to define the functional responses of the predators. Both predators consumed more second-instar larvae than other prey stages. Orius insidious displayed a type II functional response, while C. rufilabris displayed both type II and type III depending on prey stage. Generally speaking, O. insidiosus and C. rufilabris consumed a higher proportion of prey at lower pest densities, implying that in an augmentative control program using these commercially available natural enemies, predators could be released early in the year when host plants begin to flush and thrips populations are low to suppress population growth.


A novel role for epidermal growth factor receptor tyrosine kinase and its downstream endoplasmic reticulum stress in cardiac damage and microvascular dysfunction in type 1 diabetes mellitus.
Epidermal growth factor receptor tyrosine kinase (EGFRtk) and endoplasmic reticulum (ER) stress are important factors in cardiovascular complications. Understanding whether enhanced EGFRtk activity and ER stress induction are involved in cardiac damage, and microvascular dysfunction in type 1 diabetes mellitus is an important question that has remained unanswered. Cardiac fibrosis and microvascular function were determined in C57BL/6J mice injected with streptozotocin only or in combination with EGFRtk inhibitor (AG1478), ER stress inhibitor (Tudca), or insulin for 2 weeks. In diabetic mice, we observed an increase in EGFRtk phosphorylation and ER stress marker expression (CHOP, ATF4, ATF6, and phosphorylated-eIF2α) in heart and mesenteric resistance arteries, which were reduced with AG1478, Tudca, and insulin. Cardiac fibrosis, enhanced collagen type I, and plasminogen activator inhibitor 1 were decreased with AG1478, Tudca, and insulin treatments. The impaired endothelium-dependent relaxation and -independent relaxation responses were also restored after treatments. The inhibition of NO synthesis reduced endothelium-dependent relaxation in control and treated streptozotocin mice, whereas the inhibition of NADPH oxidase improved endothelium-dependent relaxation only in streptozotocin mice. Moreover, in mesenteric resistance arteries, the mRNA levels of Nox2 and Nox4 and the NADPH oxidase activity were augmented in streptozotocin mice and reduced with treatments. This study unveiled novel roles for enhanced EGFRtk phosphorylation and its downstream ER stress in cardiac fibrosis and microvascular endothelial dysfunction in type 1 diabetes mellitus.


Arginine side-chain modification that occurs during copper-catalysed azide-alkyne click reactions resembles an advanced glycation end product.
Dehydroascorbate is a by-product of copper-catalysed azide-alkyne click (CuAAC) reactions and also forms advanced glycation end products (AGEs) in tissues undergoing oxidative stress. Here we isolate and characterize an arginine-dehydroascorbate adduct formed during CuAAC reactions, investigate strategies for preventing its formation, and propose its biological relevance as an AGE.


Race/ethnicity and response to blood pressure lowering treatment after intracerebral hemorrhage.
It is unknown if race/ethnicity modifies the response to blood pressure (BP) lowering treatment after intracerebral hemorrhage (ICH). We aimed to examine the race/ethnicity differences in the response to BP lowering treatment after ICH. This is a post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial. The primary outcome is good outcome, defined as 90-day modified Rankin Scale 0-3. The primary predictor is race/ethnicity for which we included non-Hispanic categories of White, Black, Asian, and the category of Hispanic. We fit adjusted logistic regression models with the predictor of race/ethnicity and models with the interaction term of treatment*race/ethnicity. We included a total of 953 patients in our analysis (White = 213, Black = 112, Asian = 554, and Hispanic = 74). In the models with the interaction between race/ethnicity and treatment, we found that White patients assigned to the intensive treatment arm had lower predicted probability of good outcome than those assigned to the standard treatment arm (Model 1: 56.2% vs. 68.1%, p = .027; Model 2: 53.4% vs. 68.3%, p = .009). When divided into White and non-White groups, intensive treatment was associated with higher odds of serious adverse events in White group but not in the non-White group. In addition, there was an association between intensive treatment and higher risk of hematoma expansion in White patients and lower risk of hematoma expansion in non-White patients. In the ATACH-2, there was an interaction between race/ethnicity and response to BP lowering treatment after ICH, with White patients having an association between intensive blood pressure reduction and worse outcome.


Telemedicine: The Future of Global STEMI Care.
Telemedicine is an innovative tool in the setting of ST-elevation myocardial infarction (STEMI), because it addresses the greatest challenge-delivering optimal reperfusion therapies in a timely manner. Telemedicine targets delays related to geography, distance, and stated prehospital systems of care. Integration of telemedicine into prehospital STEMI management has been shown to yield cost-effective improvements in patient care. Despite socioeconomic constraints, a standard prehospital network based on telemedicine is globally feasible. This article proposes 2 models that enable the use of telemedicine in the STEMI management protocol.


Antibiotics for preventing recurrent urinary tract infection in non-pregnant women.
Urinary tract infection (UTI) is a common health care problem. Recurrent UTI (RUTI) in healthy non-pregnant women is defined as three or more episodes of UTI during a twelve month period. Long-term antibiotics have been proposed as a prevention strategy for RUTI. To determine the efficacy (during and after) and safety of prophylactic antibiotics used to prevent uncomplicated RUTI in adult non-pregnant women. We searched MEDLINE (1966-April 2004), EMBASE (1980-January 2003), Cochrane Central Register of Controlled Trials( in The Cochrane Library Issue 1, 2004) and reference lists of retrieved articles Any published randomised controlled trial where antibiotics were used as prophylactic therapy in RUTI. Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). Nineteen studies involving 1120 women were eligible for inclusion. Antibiotic versus antibiotic (10 trials, 430 women): During active prophylaxis the rate range of microbiological recurrence patient-year (MRPY) was 0 to 0.9 person-year in the antibiotic group against 0.8 to 3.6 with placebo. The RR of having one microbiological recurrence (MR) was 0.21 (95% CI 0.13 to 0.34), favouring antibiotic and the NNT was 1.85. For clinical recurrences (CRPY) the RR was 0.15 (95% CI 0.08 to 0.28). The NNT was 1.85. The RR of having one MR after prophylaxis was 0.82 (95% CI 0.44 to 1.53). The RR for severe side effects was 1.58 (95% CI 0.47 to 5.28) and for other side effects the RR was 1.78 (CI 1.06 to 3.00) favouring placebo. Side effects included vaginal and oral candidiasis and gastrointestinal symptoms. Antibiotic versus antibiotic (eight trials, 513 women): These trials were not pooled. Weekly pefloxacin was more effective than monthly. The RR for MR was 0.31(95% CI 0.19 to 0.52). There was no significant difference in MR between continuous daily and postcoital ciprofloxacin. Continuous antibiotic prophylaxis for 6-12 months reduced the rate of UTI during prophylaxis when compared to placebo. After prophylaxis two studies showed nodifference between groups. There were more adverse events in the antibiotic group. One RCT compared postcoital versus continuous daily ciprofloxacin and found no significant difference in rates of UTIs, suggesting that postcoital treatment could be offered to woman who have UTI associated with sexual intercourse.


The SlWRKY57-SlVQ21/SlVQ16 module regulates salt stress in tomato.
Salt stress is a major abiotic stress which severely hinders crop production. However, the regulatory network controlling tomato resistance to salt remains unclear. Here, we found that the tomato WRKY transcription factor WRKY57 acted as a negative regulator in salt stress response by directly attenuating the transcription of salt-responsive genes (SlRD29B and SlDREB2) and an ion homeostasis gene (SlSOS1). We further identified two VQ-motif containing proteins SlVQ16 and SlVQ21 as SlWRKY57-interacting proteins. SlVQ16 positively, while SlVQ21 negatively modulated tomato resistance to salt stress. SlVQ16 and SlVQ21 competitively interacted with SlWRKY57 and antagonistically regulated the transcriptional repression activity of SlWRKY57. Additionally, the SlWRKY57-SlVQ21/SlVQ16 module was involved in the pathway of phytohormone jasmonates (JAs) by interacting with JA repressors JA-ZIM domain (JAZ) proteins. These results provide new insights into how the SlWRKY57-SlVQ21/SlVQ16 module finely tunes tomato salt tolerance.


Comparative proteome analyses reveal that nitric oxide is an important signal molecule in the response of rice to aluminum toxicity.
Acidic soils inhibit crop yield and reduce grain quality. One of the major contributing factors to acidic soil is the presence of soluble aluminum (Al(3+)) ions, but the mechanisms underlying plant responses to Al(3+) toxicity remain elusive. Nitric oxide (NO) is an important messenger and participates in various plant physiological responses. Here, we demonstrate that Al(3+) induced an increase of NO in rice seedlings; adding exogenous NO alleviated the Al(3+) toxicity related to rice growth and photosynthetic capacity, effects that could be reversed by suppressing NO metabolism. Comparative proteomic analyses successfully identified 92 proteins that showed differential expression after Al(3+) or NO treatment. In particular, some of the proteins are involved in reactive oxygen species (ROS) and reactive nitrogen species (RNS) metabolism. Further analyses confirmed that NO treatment reduced Al(3+)-induced ROS and RNS toxicities by increasing the activities and protein expression of antioxidant enzymes, as well as S-nitrosoglutathione reductase (GSNOR). Suppressing GSNOR enzymatic activity aggravated Al(3+) damage to rice and increased the accumulation of RNS. NO treatment altered the expression of proteins associated with cell wall synthesis, cell division and cell structure, calcium signaling and defense responses. On the basis of these results, we propose that NO activates multiple pathways that enhance rice adaptation to Al(3+) toxicity. Such findings may be applicable to crop engineering to enhance yield and improve stress tolerance.


Development of a prediction model for head and neck volume reduction by clinical factors, dose-volume histogram parameters and radiomics in head and neck cancer†.
In external radiotherapy of head and neck (HN) cancers, the reduction of irradiation accuracy due to HN volume reduction often causes a problem. Adaptive radiotherapy (ART) can effectively solve this problem; however, its application to all cases is impractical because of cost and time. Therefore, finding priority cases is essential. This study aimed to predict patients with HN cancers are more likely to need ART based on a quantitative measure of large HN volume reduction and evaluate model accuracy. The study included 172 cases of patients with HN cancer who received external irradiation. The HN volume was calculated using cone-beam computed tomography (CT) for irradiation-guided radiotherapy for all treatment fractions and classified into two groups: cases with a large reduction in the HN volume and cases without a large reduction. Radiomic features were extracted from the primary gross tumor volume (GTV) and nodal GTV of the planning CT. To develop the prediction model, four feature selection methods and two machine-learning algorithms were tested. Predictive performance was evaluated by the area under the curve (AUC), accuracy, sensitivity and specificity. Predictive performance was the highest for the random forest, with an AUC of 0.662. Furthermore, its accuracy, sensitivity and specificity were 0.692, 0.700 and 0.813, respectively. Selected features included radiomic features of the primary GTV, human papillomavirus in oropharyngeal cancer and the implementation of chemotherapy; thus, these features might be related to HN volume change. Our model suggested the potential to predict ART requirements based on HN volume reduction .


LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds.
Recently, we reported a rare leukocyte adhesion deficiency (LAD) associated with severe defects in integrin activation by chemokine signals, despite normal ligand binding of leukocyte integrins.(1) We now report that the small GTPase, Rap1, a key regulator of inside-out integrin activation is abnormally regulated in LAD Epstein-Barr virus (EBV) lymphocyte cells. Both constitutive and chemokine-triggered activation of Rap1 were abolished in LAD lymphocytes despite normal chemokine signaling. Nevertheless, Rap1 expression and activation by phorbol esters were intact, ruling out an LAD defect in Rap1 guanosine triphosphate (GTP) loading. The very late antigen 4 (VLA-4) integrin abnormally tethered LAD EBV lymphocytes to its ligand vascular cell adhesion molecule 1 (VCAM-1) under shear flow due to impaired generation of high-avidity contacts despite normal ligand binding and intact avidity to surface-bound anti-VLA-4 monoclonal antibody (mAb). Thus, a defect in constitutive Rap1 activation results in an inability of ligand-occupied integrins to generate high-avidity binding to ligand under shear flow. This is a first report of an inherited Rap1 activation defect associated with a pathologic disorder in leukocyte integrin function, we herein term it "LAD-III."


Heart Rate Variability and Performance of Commercial Airline Pilots during Flight Simulations.
Pilots undergo a variety of stressors that may affect their performance during all phases of flight. Heart rate variability (HRV) has been considered as a reliable indicator of the parasympathetic and sympathetic activities of human autonomic nervous system, which can be used to characterize the sympathetic stress response of pilots during flight. In this study, thirty active commercial airline pilots were recruited to fly three flight segments in a Federal Aviation Administration (FAA)-certified A320 flight simulator with each segment at a different carbon dioxide (CO₂) concentration on the flight deck. The pilots performed a series of maneuvers of varying difficulty, and their performance was evaluated by FAA designated pilot examiners. The HRV metrics (SDNN, RMSSD and LF/HF ratio) of each pilot both before and during flight simulations were measured with a Movisens EcgMove3 sensor. The average SDNN, RMSSD and LF/HF ratio of the pilots during flight simulations were 34.1 ± 12.7 ms, 23.8 ± 10.2 ms and 5.7 ± 2.8 respectively. Decreased HRV was associated with aging, obesity and performing difficult maneuvers. Both CO₂ exposure and HRV had an independent effect on the pilot performance, while their interaction was not significant. The generalized additive mixed effect model results showed that a pilot performed better on a maneuver when his stress response was lower, as indicated by higher SDNN and RMSSD and lower LF/HF ratio. An interquartile range (IQR) increase in SDNN (21.97 ms) and RMSSD (16.00 ms) and an IQR decrease in LF/HF ratio (4.69) was associated with an increase in the odds of passing a maneuver by 37%, 22% and 20%, respectively.


Mobile Technologies for the Discovery, Analysis, and Engineering of the Global Microbiome.
The microbiome has been heralded as a gauge of and contributor to both human health and environmental conditions. Current challenges in probing, engineering, and harnessing the microbiome stem from its microscopic and nanoscopic nature, diversity and complexity of interactions among its members and hosts, as well as the spatiotemporal sampling and in situ measurement limitations induced by the restricted capabilities and norm of existing technologies, leaving some of the constituents of the microbiome unknown. To facilitate significant progress in the microbiome field, deeper understanding of the constituents' individual behavior, interactions with others, and biodiversity are needed. Also crucial is the generation of multimodal data from a variety of subjects and environments over time. Mobile imaging and sensing technologies, particularly through smartphone-based platforms, can potentially meet some of these needs in field-portable, cost-effective, and massively scalable manners by circumventing the need for bulky, expensive instrumentation. In this Perspective, we outline how mobile sensing and imaging technologies could lead the way to unprecedented insight into the microbiome, potentially shedding light on various microbiome-related mysteries of today, including the composition and function of human, animal, plant, and environmental microbiomes. Finally, we conclude with a look at the future, propose a computational microbiome engineering and optimization framework, and discuss its potential impact and applications.


MicroRNA-mediated down-regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg cells: a potential pathogenetic lesion in Hodgkin lymphomas.
PRDM1/Blimp-1, a master regulator in terminal B-cell differentiation, has been recently identified as a tumor suppressor target for mutational inactivation in diffuse large B-cell lymphomas of the activated B-cell type. Our studies here demonstrate that PRDM1/blimp-1 is also a target for microRNA (miRNA)-mediated down-regulation by miR-9 and let-7a in Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL). MiRNA expression profiling by direct miRNA cloning demonstrated that both of these miRNAs are among the most highly expressed in cultured HRS cells. These miRNAs functionally targeted specific binding sites in the 3' untranslated region of PRDM1/blimp-1 mRNA and repressed luciferase reporter activities through repression of translation. In addition, high levels of miR-9 and let-7a in HL cell lines correlated with low levels of PRDM1/Blimp-1. Similar to their in vitro counterparts, the majority of HRS cells in primary HL cases showed weak or no PRDM1/Blimp-1 expression. Over-expression of miR-9 or let-7a reduced PRDM1/Blimp-1 levels in U266 cells by 30% to 50%, whereas simultaneous inhibition of their activities in L428 cells resulted in an approximately 2.6-fold induction in PRDM1/Blimp-1. MiRNA-mediated down-regulation of PRDM1/Blimp-1 may contribute to the phenotype maintenance and pathogenesis of HRS cells by interfering with normal B-cell terminal differentiation, thus representing a novel molecular lesion, as well as a potential therapeutic target in HL.


Acute respiratory distress syndrome in pregnancy.
To summarize the pathophysiology and treatment of acute lung injury and acute respiratory distress syndrome (ARDS) during pregnancy. Review of select articles from MEDLINE, including published abstracts, case reports, observational studies, controlled trials, review articles, and institutional experience. ARDS occurs in pregnancy and may have unique causes. Despite extensive clinical research to improve the management of ARDS, mortality remains high, and few strategies have shown a mortality benefit. Furthermore, in most published studies, pregnancy is an exclusionary criterion, and thus, few treatments have been adequately evaluated in obstetric populations. The treatment of ARDS in pregnancy is extrapolated from studies performed in the general ARDS patient population, with consideration given to the normal physiologic changes of pregnancy. In general, the best support of the fetus is support of the mother. From the age of viability (24-26 wks at most institutions) until full term, decisions regarding delivery should be made based primarily on the standard obstetric indications. Little evidence exists regarding the management of ARDS specifically in pregnancy, and thus, treatment approaches must be drawn from studies performed in a general patient population. A multidisciplinary approach involving maternal-fetal medicine, neonatology, anesthesiology, and intensivist clinicians is essential to optimizing maternal and fetal outcomes.


Insights into the Fate and Removal of Antibiotics in Engineered Biological Treatment Systems: A Critical Review.
Antibiotics, the most frequently prescribed drugs of modern medicine, are extensively used for both human and veterinary applications. Antibiotics from different wastewater sources (e.g., municipal, hospitals, animal production, and pharmaceutical industries) ultimately are discharged into wastewater treatment plants. Sorption and biodegradation are the two major removal pathways of antibiotics during biological wastewater treatment processes. This review provides the fundamental insights into sorption mechanisms and biodegradation pathways of different classes of antibiotics with diverse physical-chemical attributes. Important factors affecting sorption and biodegradation behavior of antibiotics are also highlighted. Furthermore, this review also sheds light on the critical role of extracellular polymeric substances on antibiotics adsorption and their removal in engineered biological wastewater treatment systems. Despite major advancements, engineered biological wastewater treatment systems are only moderately effective (48-77%) in the removal of antibiotics. In this review, we systematically summarize the behavior and removal of different antibiotics in various biological treatment systems with discussion on their removal efficiency, removal mechanisms, critical bioreactor operating conditions affecting antibiotics removal, and recent innovative advancements. Besides, relevant background information including antibiotics classification, physical-chemical properties, and their occurrence in the environment from different sources is also briefly covered. This review aims to advance our understanding of the fate of various classes of antibiotics in engineered biological wastewater treatment systems and outlines future research directions.


Medical and non-medical costs of Parkinson disease - comparison of Europe, USA, Asia an Australia.
At present different kinds of dementia impose a significant economic burden on the whole societies. Parkinsons disease is the second most common type of dementia. The purpose of this study is to analyze the costs of people suffering from Parkinsons disease in the context of public expenditure needs for the affected people. Firstly, the treatment costs and care in the selected European countries are analyzed, and secondly, these data are compared with the data from other countries and continents. The focus is not only on the developed economies where the issue of costs and PD already causes significant expenditure from public budgets, but also on the developing economies. The methods applied in this study include a method of literature search of available sources describing the costs of PD and a qualitative comparative analysis method. The findings show that the data from the European countries range between 1,949 € and 12,054 €. Comparable data are in the USA at 17,064 €, in Australia at 7,020 € and in Asia they range between 649 € and 9,544 €. These values are certainly connected not only with the available data, but also with the level and possibilities of healthcare services in these countries. In addition, GDP for these continents and countries was specified and the cost ratio of patient with respect to GHD per capita was described. This calculation provides an orientation relative indicator about the economic burden with respect to the countrys development. The results indicate that the most significant issues are diseases and treatment in the European countries in which their highest incidence is expected in future.Key words: Parkinsons disease costs health care analysis.


First-pass radionuclide angiography via pulmonary arterial catheters. A critical analysis of background components.
Residual background activity following first-pass radionuclide angiography was assessed in 44 patients after eliminating activity in the right heart, left lung, and most of the right lung. The ejection fraction (EF) was calculated in two ways: (a) assuming background activity was present only in the right heart and lungs, and (b) correcting for scattered radiation by placing a circular region of interest around the left ventricle. With the first method, contrast EF was significantly underestimated in both AP and RAO views. With the second method, correlation was close in both views and absolute values agreed well with contrast EF. These results indicate that there is a substantial and measurable background component, due mainly to Compton scatter, even when activity from the right heart and lungs is eliminated.


ObesiTV: how television is influencing the obesity epidemic.
Obesity is a major public health concern in the United States. Over the last several decades, the prevalence of obesity among both adults and children has grown at an alarming rate and is now reaching epidemic proportions. The increase in obesity has been associated with rises in a host of other chronic conditions including cardiovascular disease, type 2 diabetes, and some cancers. While the causes of obesity are multifaceted, there is growing evidence that television viewing is a major contributor. Results of numerous studies indicate a direct association between time spent watching television and body weight. Possible explanations for this relationship include: 1) watching television acts as a sedentary replacement for physical activity; 2) food advertisements for nutrient-poor, high-calorie foods stimulate food intake; and 3) television viewing is associated with "mindless" eating. In addition to decreasing physical activity and increasing the consumption of highly palatable foods, television viewing can also promote weight gain in indirect ways, such as through the use of targeted product placements in television shows; by influencing social perceptions of body image; and airing programs that portray cooking, eating and losing weight as entertainment. This paper will provide an interdisciplinary review of the direct and indirect ways in which television influences the obesity epidemic, and conclude with ways in which the negative impact of television on obesity could be reduced.


Comparing the effect of a leaflet and a movie in preventing tick bites and Lyme disease in The Netherlands.
Lyme disease (LD) has become the most common vector borne illness in the Northern hemisphere. Prevention relies predominantly on fostering protective behaviors (e.g., avoiding tick areas, using protective clothing and repellent, and doing routine tick checks post-exposure). The objective of this study was to evaluate the effectiveness (in terms of knowledge, perceived severity and susceptibility, self-efficacy, response efficacy, intention, and behavior over time) and appreciation of a leaflet and a movie as tools for informing the public in the Netherlands about ticks and LD protective behaviors. Participants (1,677 at t1 and 361 extra at t2) were members of a representative Internet panel (adults aged 18 years and above). A four group randomized controlled design was used to test the effect of an information leaflet and a movie (two intervention groups), compared to a control group and a follow-up only control group. Data were collected over two periods: July 15-29, 2013 (t1) and at follow-up 4 weeks later, August 16-31, 2013 (t2). Post-intervention results show all respondents in all groups possess good general basic knowledge of ticks and LD. Respondents in both the leaflet and movie groups knew more than respondents in the control group, and had greater awareness of best practices after a tick bite. Intention to perform protective behavior in future was stronger among respondents in the intervention groups. While respondents generally appreciated both the movie and the leaflet, they found the movie ran too long. Follow-up revealed no lasting positive effects from either the leaflet or the movie. Our results suggest that both the movie and the leaflet are valued and effective intervention tools for improving knowledge about tick bites and strengthening self-efficacy and intentions to perform protective behavior against ticks and LD . Achieving lasting effects, however, calls for more action.


Purification and characterization of an 'actomyosin' complex from Escherichia coli W3110.
An 'actomyosin' complex was purified from Escherichia coli W3110 using selective precipitation. The complex contains three major components of 19.5, 18.5 and 17 kDa. The 19.5- and 17-kDa proteins were purified by electroelution, peptide mapped and N-terminally sequenced. The structural gene for the 17-kDa protein was found to have been previously identified in an operon containing several other genes including the essential lpxA, lpxB and dnaE. The possible function of the 17-kDa protein and the other 'actomyosin' components is discussed.


Determinants of patient loyalty to healthcare providers: An integrative review.
Patient loyalty is key to business success for healthcare providers and also for patient health outcomes. This study aims to identify determinants influencing patient loyalty to healthcare providers and propose an integrative conceptual model of the influencing factors. PubMed, CINAHL, OVID, ProQuest and Elsevier Science Direct databases were searched. Publications about determinants of patient loyalty to health providers were screened, and 13 articles were included. Date of publication, location of the research, sample details, objectives and findings/conclusions were extracted for 13 articles. Thirteen studies explored eight determinants: satisfaction, quality, value, hospital brand image, trust, commitment, organizational citizenship behavior and customer complaints. The integrated conceptual model comprising all the determinants demonstrated the significant positive direct impact of quality on satisfaction and value, satisfaction on trust and commitment, trust on commitment and loyalty, and brand image on quality and loyalty. This review identifies and models the determinants of patient loyalty to healthcare providers. Further studies are needed to explore the influence of trust, commitment, and switching barriers on patient loyalty.


Clinical Exome Sequencing Enables Congenital Sialidosis Type II Diagnosis in Two Siblings Presenting with Unreported Clinical Features from a Rare Homozygous Sequence Variant p.(Tyr370Cys) in NEU1.
Sialidosis is a rare autosomal recessive disease that presents with progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by homozygous or compound heterozygous sequence variants in the neuraminidase 1 (NEU1) gene. These sequence variants can lead to sialidosis type I and II; the latter is the most severe and presents prenatally or at early age. However, sialidosis diagnosis is challenging, especially in those health systems with limited resources of developing countries. Consequently, it is necessary to dip into high-throughput molecular diagnostic tools to allow for an accurate diagnosis with better cost-effectiveness and turnaround time. We report a 4-member pedigree segregating an ultrarare missense variant, c.1109A>G; p.Tyr370Cys, in NEU1 as detected by whole-exome sequencing. Two short-lived siblings, who presented with previously unreported clinical features from such a homozygous sequence variant, were diagnosed with sialidosis type II. Additionally, we present a novel molecular model exhibiting the consequences of the variant in the sialidase-1 tridimensional structure. This study allowed us to provide a definitive diagnosis for our patients, increase our understanding of this pathogenic variant, and improve genetic counseling.


Spectrum of false positive 18F-sodium fluoride (NaF) bone PET/CT findings in Oncology imaging; A narrative pictorial review of cases from a single institution.
Fluorine-18-sodium fluoride (18F-NaF) is a positron emission tomography (PET) bone imaging agent mainly used for oncology staging but may also be used in the evaluation of benign bone and joint pathology conditions. Fluorine-18-NaF is an excellent bone-seeking agent with high bone uptake owing to favorable biodistribution with rapid single-pass extraction, limited plasma protein binding and prompt renal clearance. Fluorine-18-NaF PET/computed tomography (CT) is highly sensitive in identifying both sclerotic and lytic bone metastatic lesions. Occasionally 18F-NaF uptake in benign bone lesions can mimic malignantpathology. In these cases, the pattern of 18F-NaF uptake may elicit a specific diagnosis and correlation with clinical information and morphological information from correlative CT is essential for a correct diagnosis. In the present article, we present a series of clinical cases demonstrating examples of 18F-NaF uptake in benign lesions which can simulate malignant pathology in patients undergoing cancer staging.


Regulation of alpha 1b-adrenergic receptor gene expression in rat liver cell lines.
alpha 1b-Adrenergic receptor gene expression was investigated in two rat hepatic cell lines, Clone 9 and McA-RH7777 cells. By Northern blot analysis, Clone 9 cells expressed a 2.7 kb alpha 1b-adrenergic receptor gene transcript whereas two transcripts, 3.3 kb and 2.7 kb, were observed in total cellular RNA isolated from rat liver. A binding site for the alpha 1-adrenergic antagonist [3H]prazosin was observed in Clone 9 cell membrane preparations (Bmax = 47 +/- 7 fmol/mg protein and Kd = 0.11 +/- 0.02 nM, n = 5). In contrast, alpha 1b-adrenergic receptor gene transcripts could not be detected in total cellular RNA prepared from McA-RH7777 cells by either Northern blot analysis or ribonuclease protection assays. However, results from nuclear run-off assays indicated that the alpha 1b-adrenergic receptor gene was transcribed in McA-RH7777 cells and alpha 1b-adrenergic receptor gene transcripts were observed in McA-RH7777 cell nuclear RNA. These results suggest that alpha 1b-adrenergic receptor gene expression in liver may be regulated in part post-transcriptionally and that this level of regulation may be altered or disrupted in the Clone 9 and McA-RH7777 cell lines.


Aneurysms of the temporal bone.
Aneurysms of the internal carotid artery in the temporal bone are rare lesions which can present clinically as a growth in the middle ear cleft. Hemorrhage, occurring spontaneously or iatrogenically, is a primary concern. This study describes morphological and embryological characteristics of the internal carotid artery in relationship to the protympanum and temporal bone. Concepts of pathogenesis and pathology are discussed, with reference to the neurosurgical and otolaryngologic literature. Clinical characteristics, including methods of surgical repair, are presented using three illustrative case reports. Methods of surgical repair include: 1) reinforcement; 2) ligation; and 3) primary excision and reanastomosis.


Real-time PCR based on SYBR-Green I fluorescence: an alternative to the TaqMan assay for a relative quantification of gene rearrangements, gene amplifications and micro gene deletions.
Real-time PCR is increasingly being adopted for RNA quantification and genetic analysis. At present the most popular real-time PCR assay is based on the hybridisation of a dual-labelled probe to the PCR product, and the development of a signal by loss of fluorescence quenching as PCR degrades the probe. Though this so-called 'TaqMan' approach has proved easy to optimise in practice, the dual-labelled probes are relatively expensive. We have designed a new assay based on SYBR-Green I binding that is quick, reliable, easily optimised and compares well with the published assay. Here we demonstrate its general applicability by measuring copy number in three different genetic contexts; the quantification of a gene rearrangement (T-cell receptor excision circles (TREC) in peripheral blood mononuclear cells); the detection and quantification of GLI, MYC-C and MYC-N gene amplification in cell lines and cancer biopsies; and detection of deletions in the OPA1 gene in dominant optic atrophy. Our assay has important clinical applications, providing accurate diagnostic results in less time, from less biopsy material and at less cost than assays currently employed such as FISH or Southern blotting.


Seventh cervical rib associated with subclavian artery occlusion and multiple infarcts: case report.
A cervical rib, or supernumerary (extra) rib arising from the 7th cervical vertebra, is a congenital abnormality that occurs in less than 1% of the population. Clinically, it can cause obscure nervous or vascular symptoms and be difficult to diagnose. In this rare case, a 37-year-old woman developed a subclavian artery occlusion after undergoing a chiropractic manipulation for neck, shoulder, and arm pain. The occlusion led to multiple cerebellar infarcts, frontal subarachnoid hemorrhage, myocardial infarction, and right-hand vascular compromise. The patient was subsequently diagnosed with a 7th cervical rib, which likely caused compression of the subclavian artery after a hyperextension injury sustained during the chiropractic procedure. The departments of vascular surgery, neurosurgery, cardiology, and neurology collaborated to review all elements of the patient's diagnosis and care. After the patient was stabilized, she spent 6 weeks in acute inpatient rehabilitation; upon discharge, her symptoms were greatly improved but still present. Three months later, the patient underwent a subclavian-artery-to-axillary-artery bypass with resection of the left cervical rib. She tolerated surgery well with no complications. As a result of the devastating insults sustained secondary to the presence of the 7th cervical rib and her subclavian artery occlusion, this patient faced months of recovery. Treatment involved a structured interdisciplinary plan of care.


SubtiWiki 2.0--an integrated database for the model organism Bacillus subtilis.
To understand living cells, we need knowledge of each of their parts as well as about the interactions of these parts. To gain rapid and comprehensive access to this information, annotation databases are required. Here, we present SubtiWiki 2.0, the integrated database for the model bacterium Bacillus subtilis (http://subtiwiki.uni-goettingen.de/). SubtiWiki provides text-based access to published information about the genes and proteins of B. subtilis as well as presentations of metabolic and regulatory pathways. Moreover, manually curated protein-protein interactions diagrams are linked to the protein pages. Finally, expression data are shown with respect to gene expression under 104 different conditions as well as absolute protein quantification for cytoplasmic proteins. To facilitate the mobile use of SubtiWiki, we have now expanded it by Apps that are available for iOS and Android devices. Importantly, the App allows to link private notes and pictures to the gene/protein pages. Today, SubtiWiki has become one of the most complete collections of knowledge on a living organism in one single resource.


Sutureless Valves Reduce Hospital Costs Compared to Traditional Valves.
The study aim was to assess differences in clinical outcome, safety, and associated costs between sutureless and aortic isolated aortic valve replacement (AVR) with a standard bioprosthesis. A retrospective comparative study was conducted to investigate 65 patients, each of whom had undergone isolated AVR with a traditional aortic valve (T) or a Perceval S sutureless aortic prosthesis (P) between January 2010 and December 2012. Cost data were drawn from the proprietary cost accounting system of the hospital, excluding acquisition costs of the devices. A linear regression model was used to estimate the mean total costs difference between groups. The mean cardiopulmonary bypass time and aortic cross-clamp times in the T and P groups were 80 ± 41 min and 58 ± 26 min versus 38 ± 16 min and 26 ± 10 min, respectively (p <0.0001). The mean intensive care unit and ward stays in both groups were 4.2 ± 5.9 and 11.9 ± 6.5 days versus 3.8 ± 4.7 and 10 ± 4.5 days, respectively (p = 0.68 and p = 0.05). The mean costs savings for group P compared to group T were €3,801 (p = 0.13), mainly driven by hospital stay costs. Savings between the P and T groups increased with age: €4,992 in patients aged 70-79 years and €9,326 in those aged 80+ years, and with risk (€4,296 for high-risk patients). Sutureless aortic valves present shorter procedural times and lower hospital costs compared to traditional valves, with higher cost savings at increased patient age and risk. Sutureless aortic valves seem to be cost-effective in patients undergoing AVR.


From Antarctica to the subtropics: Contrasted geographical concentrations of selenium, mercury, and persistent organic pollutants in skua chicks (Catharacta spp.).
Seabirds integrate bioaccumulative contaminants via food intake and have revealed geographical trends of contamination in a variety of ecosystems. Pre-fledging seabird chicks are particularly interesting as bioindicators of chemical contamination, because concentrations in their tissues reflect primarily dietary sources from the local environment. Here we measured 14 trace elements and 18 persistent organic pollutants (POPs) in blood of chicks of skuas that breed in four sites encompassing a large latitudinal range within the southern Indian Ocean, from Antarctica (Adélie Land, south polar skua Catharacta maccormicki), through subantarctic areas (Crozet and Kerguelen Islands, brown skua C. lonnbergi), to the subtropics (Amsterdam Island, C. lonnbergi). Stables isotopes of carbon (δ13C, feeding habitat) and nitrogen (δ15N, trophic position) were also measured to control for the influence of feeding habits on contaminant burdens. Concentrations of mercury (Hg) and selenium (Se) were very high at all the four sites, with Amsterdam birds having the highest concentrations ever reported in chicks worldwide (4.0 ± 0.8 and 646 ± 123 μg g-1 dry weight, respectively). Blood Hg concentrations showed a clear latitudinal pattern, increasing from chicks in Antarctica to chicks in the subantarctic and subtropical islands. Interestingly, blood Se concentrations showed similar between-population differences to Hg, suggesting its involvement in protective mechanisms against Hg toxicity. Chicks' POPs pattern was largely dominated by organochlorine pesticides, in particular DDT metabolites and hexachlorobenzene (HCB). Skua chicks from subantarctic islands presented high concentrations and diversity of POPs. By contrast, chicks from the Antarctic site overall had the lowest concentrations and diversity of both metallic and organic contaminants, with the exception of HCB and arsenic. Skua populations from these sites, being naturally exposed to different quantities of contaminants, are potentially good models for testing toxic effects in developing chicks in the wild.


Epidemiology in Malta from routine health information.
To estimate the prevalence of diabetes in the Maltese Islands from data regarding drug consumption, and to assess the prescribing habits and management attitudes of local doctors. The prescribed average daily dose of each type of anti-diabetic drug was calculated from random representative samples of patients (total 1,444) attending the Health Department's primary and secondary health centres as well as of patients seeing their private practitioners. This constituted circa 16% of the total estimated number of diabetics on drug therapy in Malta. The quantities of drugs consumed were obtained both from Government and private industry sources, whilst relevant data on therapy modalities, including proportions of patients on a combination of anti-diabetic preparations, were obtained from records held at the Dept. of Health. Applying the appropriate formulae (as proposed by Eurodiab. subarea C 1989 programme) the global prevalence of diabetes worked out to be 5.22%, an underestimate of circa 12% of the figure extrapolated from the recent population based epidemiological studies. Overall 51% of cases were treated with 'diet only', whilst less than 10% of subjects were managed with insulin. Compared to patients attending the better staffed and equipped health centres, those seeing their private physicians were proportionately less frequently put on insulin (5.7% vs 11.7%), and were prescribed a slightly higher mean daily dose (1.7 vs. 1.4 tab) of glibenclamide suggesting the need of better education of the patient (and probably also of the physician). This type of study proved to be relatively simple and inexpensive to perform. Although it cannot replace epidemiological field surveys it can still give a reasonably fair (albeit with limitations) estimate of diabetes prevalence in a population. Moreover it permits an important insight into local public health indicating ways to improve diabetes care.


Kinetic modeling of methyl butanoate in shock tube.
An increased necessity for energy independence and heightened concern about the effects of rising carbon dioxide levels have intensified the search for renewable fuels that could reduce our current consumption of petrol and diesel. One such fuel is biodiesel, which consists of the methyl esters of fatty acids. Methyl butanoate (MB) contains the essential chemical structure of the long-chain fatty acids and a shorter, but similar, alkyl chain. This paper reports on a detailed kinetic mechanism for MB that is assembled using theoretical approaches. Thirteen pathways that include fuel decomposition, isomerization, and propagation steps were computed using ab initio calculations [J. Org. Chem. 2008, 73, 94]. Rate constants from first principles for important reactions in CO(2) formation, namely CH(3)OCO=CH(3) + CO(2) (R1) and CH(3)OCO=CH(3)O + CO (R2) reactions, are computed at high levels of theory and implemented in the mechanism. Using the G3B3 potential energy surface together with the B3LYP/6-31G(d) gradient, Hessian and geometries, the rate constants for reactions R1 and R2 are calculated using the Rice-Ramsperger-Kassel-Marcus theory with corrections from treatments for tunneling, hindered rotation, and variational effects. The calculated rate constants of reaction R1 differ from the data present in the literature by at most 20%, while those of reaction R2 are about a factor of 4 lower than the available values. The new kinetic model derived from ab initio simulations is combined with the kinetic mechanism presented by Fisher et al. [Proc. Combust. Inst. 2000, 28, 1579] together with the addition of the newly found six-centered unimolecular elimination reaction that yields ethylene and methyl acetate, MB = C(2)H(4) + CH(3)COOCH(3). This latter pathway requires the inclusion of the CH(3)COOCH(3) decomposition model suggested by Westbrook et al. [Proc. Combust. Inst. 2008, accepted]. The newly composed kinetic mechanism for MB is used to study the CO(2) formation during the pyrolysis of MB as well as to investigate the autoignition of MB in a shock tube reactor at different temperatures and pressures. The computed results agree very well with experimental data present in the literature. Sensitivity and flux (rate-of-production) analyses are carried out for the CO(2) formation with the new MB mechanism, together with available reaction mechanisms, to assess the importance of various kinetic pathways for each regime. With the new mechanism, the flux analyses for the formation of C(2)H species, one of the most important species for ignition delay time, are also presented at different conditions. In addition to giving a better chemical insight of the pyrolysis/oxidation of MB, the results suggest ways to improve the mechanism's capability to predict CO(2) formation and ignition delay times in pyrolysis and oxidation conditions.


A 4-AP-sensitive current is enhanced by chronic carbon monoxide exposure in coronary artery myocytes.
A physiological role of carbon monoxide has been suggested for coronary myocytes; however, direct evidence is lacking. The objective of this study was to test the effect of chronic carbon monoxide exposure on the K(+) currents of the coronary myocytes. The effect of 3-wk chronic exposure to carbon monoxide was assessed on K(+) currents in isolated rat left coronary myocytes by the use of the patch-clamp technique in the whole cell configuration. Moreover, membrane potential studies were performed on coronary artery rings using intracellular microelectrodes, and coronary blood flow in isolated heart preparation was recorded. Carbon monoxide did not change the amplitude of global whole cell K(+) current, but it did increase the component sensitive to 1 mM 4-aminopyridine. Carbon monoxide exposure hyperpolarized coronary artery segments by approximately 10 mV and, therefore, increased their sensitivity to 4-aminopyridine. This effect was associated with an enhancement of coronary blood flow. We conclude that chronic carbon monoxide increases a 4-aminopyridine-sensitive current in isolated coronary myocytes. This mechanism could, in part, contribute to hyperpolarization and to increased coronary blood flow observed with carbon monoxide.


Bioprinting of Cartilage and Skin Tissue Analogs Utilizing a Novel Passive Mixing Unit Technique for Bioink Precellularization.
Bioprinting is a powerful technique for the rapid and reproducible fabrication of constructs for tissue engineering applications. In this study, both cartilage and skin analogs were fabricated after bioink pre-cellularization utilizing a novel passive mixing unit technique. This technique was developed with the aim to simplify the steps involved in the mixing of a cell suspension into a highly viscous bioink. The resolution of filaments deposited through bioprinting necessitates the assurance of uniformity in cell distribution prior to printing to avoid the deposition of regions without cells or retention of large cell clumps that can clog the needle. We demonstrate the ability to rapidly blend a cell suspension with a bioink prior to bioprinting of both cartilage and skin analogs. Both tissue analogs could be cultured for up to 4 weeks. Histological analysis demonstrated both cell viability and deposition of tissue specific extracellular matrix (ECM) markers such as glycosaminoglycans (GAGs) and collagen I respectively.


Value of routine diagnostic criteria of bullous pemphigoid.
The clinical, histologic, and direct (DIF) and indirect (IIF) immunofluorescence findings are used in a critical, although arbitrary, manner in the routine diagnostic process of bullous pemphigoid (BP). Our purpose was to estimate their relative value. In the present retrospective study, a follow-up of at least 18 months was used as a prerequisite for the final diagnosis of BP (63 patients) and controls (n=159). The clinical, histologic, DIF, and IIF diagnostic criteria of BP were found to vary independently of each other. Positive DIF was the most sensitive (90.5%) typical for BP histology and positive IIF were the most specific (99%). Immunopathologic tests were the most valuable, especially in the atypical varieties of BP. Nearly 25% of patients in this group would have been misdiagnosed if IF tests had not been performed. Atypical cases (40%) seemed to represent a clinical continuum over the whole spectrum of the disease. Patients with exclusively immunoglobulin G (IgG) and C3 basal membrane zone (BMZ) deposits were significantly more often seropositive than the rest of the DIF-positive cases; however, the class of BMZ immunoreactants varied according to the site of biopsy. C3 was almost invariably deposited at the BMZ of DIF-positive patients. When Igs were also present, they were only exceptionally (5% of cases) of greater fluorescence intensity than C3. The combination of clinical data plus one positive immunopathologic test provide the best combination of sensitivity and specificity (98%), and seem to be most appropriate in defining patient populations for study purposes. The relationship between the classes of immunoreactants should be better evaluated with reference to the site of skin biopsy. It may be suggested, however, that the likelihood of BP existence is very low when in vivo C3 is absent or of lower intensity of fluorescence than the concomitant Ig(s).


Comparison of the activity of Rapitard and Actraphane insulins.
This study examined the activity of two intermediate acting premixed insulins, Rapitard and Actraphane, in non diabetic individuals using the euglycaemic clamp technique. Rapitard, a mixture of 25% soluble porcine insulin and 75% bovine insulin crystals was compared to porcine Actraphane, a mixture of 30% soluble and 70% isophane insulins. Glucose requirements and serum insulin levels were monitored over a 12 h period. The mean (+/- SEM) total glucose requirements were higher following administration of Actraphane (246.7 +/- 37.2 g) compared to Rapitard (188.7 +/- 15.4 g) but this difference did not reach statistical significance. Following injection of Actraphane significantly higher glucose infusion rates for the half hour periods from 240, 270, 300, 330 and 420 min and serum insulins at 180, 210, 240, 270, 300, 330, 360 and 480 min were observed compared to Rapitard. These differences are likely to be of clinical relevance and should be considered when changing a diabetic subject from Rapitard to Actraphane insulins.


A two-year pollen and spore survey of Southeast Florida.
A two-year pollen survey of southeast Florida revealed significant airborne pollen and spores. Ragweed, grass, tree pollen and mold spores were identified. Pollen and mold spores were found to be present in lower quantities than in the temperate regions but for more prolonged periods of time.


Aortic root rupture during balloon-expandable transcatheter aortic valve replacement in a patient without recognized risk factors for aortic root rupture: a case report.
Aortic root rupture is a severe complication of balloon-expandable transcatheter aortic valve replacement (TAVR). Although previous studies have revealed several risk factors for this complication, predicting this complication is occasionally difficult. A 78-year-old male patient underwent TAVR via a transfemoral approach using a 29-mm balloon-expandable valve. No recognized risk factors for aortic root rupture existed in pre-procedural multi-detector computed tomography (MDCT) analysis. However, after the valve deployment, sudden haemodynamic collapse occurred. Transoesophageal echocardiography revealed pericardial effusion, which led to an immediate diagnosis of cardiac tamponade following aortic root rupture. Following pericardial drainage via a subxiphoid approach, the haemodynamics were immediately stabilized. After 10 days of close observation, the patient was discharged on Day 39 without additional problems. He was still alive at the 6-month follow-up without sequelae. Established risk factors for aortic root rupture include >20% area oversizing, bicuspid aortic valve, small annulus (<20 mm), shallow sinus of Valsalva (SOV) compared with the aortic annulus, and massive annular or subannular calcification. Our patient did not have any of the recognized risk factors for aortic root rupture, suggesting the existence of other factors. Pre-procedural MDCT showed a flat calcification orthogonal to the aortic root wall, and post-procedural MDCT revealed that this calcification penetrated the SOV with extravasation. Thus, we suggest that a flat calcification orthogonal to the aortic root wall might be an additional risk factor for aortic root rupture.


FDA-Approved Pharmacotherapy for Weight Loss Over the Last Decade.
Obesity is a recently defined illness whose diagnosis and treatment continue to be stigmatized. Currently, due to lifestyle changes brought on by technological advancements and the wide availability and affordability of high-calorie foods, millions of people around the world suffer from obesity and/or its sequelae. Finding adequate prevention and treatment options would therefore lead to massive improvements in the duration and quality of life of affected individuals. In this review, we searched the PubMed database for studies exploring the safety and efficacy of the five medications currently approved by the FDA for the treatment of obesity. We included only studies pertaining to adult patients that have been published between 2012 and 2022. We found evidence that all the drugs analyzed such as orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, and semaglutide appear to be effective in inducing weight loss, with the suggestion that semaglutide may have superior efficacy. However, a massive obstacle in developing treatment guidelines remains the lack of prolonged studies monitoring the long-term safety and efficacy of obesity medications. Nevertheless, in patients at risk of complications from obesity, the benefits of losing fat mass may outweigh the potential side effects associated with these medications and clinicians should prescribe whichever of the FDA-approved pharmacotherapy they deem most appropriate for the patient's specific set of circumstances.


Safety and efficacy of hematopoietic and mesanchymal stem cell therapy for treatment of T1DM: a systematic review and meta-analysis protocol.
Insulin standard treatment of T1DM cannot cure the patients as different chronic complications occurred subsequently. Investigations on a curative treatment in T1DM propose cell replacement or maintenance instead of exogenous insulin therapy, but different dimensions of this novel treatment are not clarified. We will include all clinical trials which have evaluated the efficacy MSC or HSC transplantation in T1DM treatment; electronically search bibliographic databases, country registration data banks, and gray literatures; and hand-search two key journals, two experts' article, and references of the included articles with no language restriction. Primary outcome is the extent of reduction in insulin requirement and secondary outcomes are safety of MSC and HSC therapy, effect of this therapy on diabetic parameters, effect of the rout of transplantation and origin of the MSC or HSC on efficacy of treatment, studies heterogeneity and potential reasons of it. Heterogeneity and its severity will be calculated with Q Cochrane test, P value, and I2 index. STATA software version 12 will be used for meta-analysis. PROSPERO Registration number: CRD42016047176. We will publish the systematic review in a peer review journal; as it presents an analysis of published literature, the study does not require ethical approval. This systematic review and meta-analysis will investigate the efficacy of MSC and HSC transplantation in T1DM treatment with no language restriction. Also we will evaluate gray literatures after hand searching. This protocol is prepared according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Two reviewers will evaluate screened full texts, extract data, and asses risk of bias of eligible primary studies independently. As there is the possibility that we miss some unpublished primary studies due to negative results, we will use funnel plot to detect this and correct it with fill and trim method.


European economies in terms of energy dependence.
The sustainable development and energy security are currently the priority challenges for the European Union countries. The sustainable and stable development of European economies is closely dependent on the stable access to energy resources. The constant increase of the demand for electricity requires long-term planning of the common European policy. The aim of the article is to analyse the fuel and energy resources situation of the member states with regard to their energy balances and with the determination of their import dependence in relation to fossil fuels, such as: coal, oil and natural gas. Based on the collected statistical data the analysis of clusters was presented in order to separate homogenous subsets, that is groups of the European Union Member States. The squared Euclidean distance has been adopted as the measure of similarities of the member states in the clusters, and the k-means algorithm has been used as the method of grouping. As a result of the analysis seven clusters were selected-groups of homogenous countries in terms of the import dependence due to the major energy resources (oil, natural gas and coal). The results of the paper can constitute bases for shaping the appropriate long-term common energy policy for the listed potential groups of countries. Statistical data were collected based on the Eurostat publication.


Performance comparison of new Veris and Xpert random access HIV-1 RNA quantification assays.
Recent systems for Human Immunodeficiency Virus 1 (HIV-1) viral load (VL) monitoring allow one-by-one analysis and fast turn-around-time for results. VL measurement on two rapid recently commercialized systems, GeneXpert (Cepheid) and Veris (Beckman Coulter) was compared to classical methods. Plasma specimen from HIV-1 (group M) positive patients (n = 129) initially quantified with Abbott RealTime HIV-1 and Generic HIV-VL Biocentric assays were retrospectively tested with GeneXpert and Veris. Valid results on all techniques were obtained for 116/129 specimens composed of 89 Abbott quantifiable VL (38 B, 51 non-B subtypes) [range: 2.09-7.20 log cp/mL] and 27 plasma (9 B, 18 non-B) with Abbott-VL below the limit of quantification (LLQ). All techniques showed good correlation and agreement with a lowest Spearman correlation coefficient of 0.86. Compared to Abbott, the mean bias was 0.35 (95% CI: 0.25-0.45), 0.44 (0.36-0.53) and - 0.04 (- 0.13-0.05) for Biocentric, Beckman and Cepheid, respectively. A difference over 0.5 log cp/mL between VL-quantification of the same sample was observed for 19, 9 and 6 samples with Biocentric, Beckman and Cepheid, respectively. No influence of HIV-1 subtypes on VL was identified. Among 29 samples below LLQ on Abbott, only one was detected and quantified with the Veris assay (38 cp/mL), none with Cepheid. Both random access systems from Cepheid and Beckman appear well designed for quantifying plasma HIV-1 VL, are easy to handle, fast and fully automated. The slight observed differences suggest to follow the current guidelines recommending the use of the same technique over time for patient viral load monitoring.


The major tegument structural protein VP22 targets areas of dispersed nucleolin and marginalized chromatin during productive herpes simplex virus 1 infection.
The herpes simplex virus (HSV) major tegument structural protein VP22 resides in multiple subcellular regions during productive infection. During an analysis of the molecular determinants of these localizations, we observed that a transfected fusion of the C-terminal portion of VP22, containing its pat4 nuclear localization signal, with GFP lacked nucleolar sparing compared to GFP alone. Thus, the initial goal was to determine whether VP22 associates with nucleoli. Using an optimized indirect immunofluorescence system to visualize nucleolin and viral proteins, we observed that VP22 present in VP22-expressing Vero (V49) cells "surrounded" nucleolin. These two initial findings implied that VP22 might associate directly with nucleoli. We next analyzed HSV-infected cells and observed that at late times, anti-nucleolin immune reactivity was dispersed throughout the nuclei while it retained uniform, circular staining in mock-infected cells. Time course infection experiments indicated that nucleolin initiated its transition from uniform to dispersed structures between 2 and 4 hpi. Comparison of Hoechst stained nuclei showed bright anti-nucleolin staining localized to regions of marginalized chromatin. These effects required de novo infected cell protein synthesis. A portion of VP22 detected in nuclei at 4 and 6 hpi localized to these areas of altered nucleolin and marginalized chromatin. VP22 was excluded from viral replication compartments containing the viral regulatory protein ICP22. Finally, altered nucleolin and marginalized chromatin were detected with a VP22-null virus, indicating that VP22 was not responsible for these nuclear architecture alterations. Thus, we conclude that nuclear VP22 targets unique subnuclear structures early (<6hpi) during herpes simplex virus 1 (HSV-1) infection.


Insight into the Mechanism of Improved Interfacial Properties between Electrodes and Electrolyte in the Graphite/LiNi0.6Mn0.2Co0.2O2 Cell via Incorporation of 4-Propyl-[1,3,2]dioxathiolane-2,2-dioxide (PDTD).
4-Propyl-[1,3,2]dioxathiolane-2,2-dioxide (PDTD) has been investigated as an electrolyte additive for the graphite/LiNi0.6Mn0.2Co0.2O2 pouch cell. A significant improvement on the initial Coulombic efficiency and cycling stability has been achieved by incorporating 1.0 wt % PDTD additive. Specifically, initial Coulombic efficiency increased from 83.7% (baseline) to 87.8% (w/w, 1.0 wt % PDTD), and from 75.7% to 83.7% for capacity retention after 500 cycles upon cycling at room temperature. Improvements in the interfacial properties between cathode and electrolyte as well as between anode and electrolyte through incorporation of 1.0 wt % PDTD are believed to account for the observed enhanced cell performance. Insight into the mechanism of improved interfacial properties between electrodes and electrolyte in the graphite/LiNi0.6Mn0.2Co0.2O2 system has been addressed with a combination of theoretical computation and experimental techniques, including electrochemical methods and spectroscopic characterization.


Adenoviruses in oncology: a viable option?
The feasibility of using adenoviruses for gene therapy has been under close scrutiny recently, as it has become clear that significant toxicity can result from the strong immune response created by intravenous administration of large doses of first generation adenovirus vectors. This suggests that other vectors could be more useful for treatment of metabolic and hereditary disease, where widespread transduction is often necessary for effective gene replacement, and the viability of target cells is important. However, promising recent results in human cancer trials have confirmed that adenoviruses can be very useful in oncology. For cancer treatment, the unparalleled transduction efficacy of adenovirus in dividing and dormant cells is a major benefit. As the goal in cancer gene therapy is to kill infected tumour cells, long-term transgene expression is not necessary. In addition, the immune response generated against infected cells could be useful for eradicating uninfected tumour. Importantly, more than 670 cancer patients have been treated with adenovirus intratumorally, intra-arterially, intraperitoneally and intravenously with very manageable adverse effects and no unexpected severe or lethal toxicity. Currently, the most promising approaches are based on replication-competent agents that allow efficient tumour penetration because of their capacity for tissue-specific replication. In addition to transcriptional control, it is becoming clear that targeting is necessary for efficient tumour transduction and less infection of normal tissues. Exciting results are anticipated when the first selectively replicating targeted adenoviruses go to clinical trials. In conclusion, intense gene therapy and virological research have suggested that while other vectors could be more useful for treatment of hereditary disease, adenoviruses are highly promising and safe agents for oncology, as suggested in a number of early phase clinical trials.


Evaluation of B-mode ultrasound as a means of improving radium dosimetry in the treatment of gynecologic cancer.
The radiation dose to the base of the bladder and anterior rectal wall during radium applications for gynecologic cancer is a function of the distances between the source and the bladder and rectum. Precise measurement of these distances depends on a number of factors and cannot be obtained with current radiographic localization techniques. B-mode ultrasound is useful as a means of supplementing available information. While it is not necessarily more accurate than standard radiographs, it offers a three-dimensional appreciation of pelvic anatomy and does appear to be more accurate than transverse axial tomography.


Investigation into the hypogonadism of the obese mouse (genotype ob/ob).
Features of the reproductive axis in the genetically hypogonadal, obese mouse (genotype, ob/ob) were examined at 5-8 months of age and compared with those of wild-type litter mates. Hypothalamic concentrations of dopamine and 5-hydroxytryptamine were normal. Those of 5-hydroxyindoleacetic acid, noradrenaline and LH-RH were raised. LH-RH was biologically active. Pituitary concentration of LH was normal, but that of FSH was raised. Serum concentrations of LH and FSH, compared with those of wild-type animals, were normal and low, respectively. Gonad and accessory sex organs weights were reduced. These findings suggest that the release of FSH but not LH is defective in the ob/ob mouse. Preliminary in-vitro experiments indicated that the pituitary gland responded normally or even supernormally towards LH-RH in its release of LH. The defect in the reproductive axis of the obese mouse may be due to inadequate release of LH-RH although an insensitivity of the pituitary gland towards LH-RH in its release of FSH cannot be excluded.


Effectiveness and Adherence Rate of S-flurbiprofen Plaster for the Pain Management of Patients With Moderate and End-Stage Knee Osteoarthritis.
S-flurbiprofen plaster (SFPP) is highly skin permeable and represents a new conservative treatment for knee osteoarthritis (KOA) that can attain considerably higher concentrations in the synovium than topical flurbiprofen. To date, no study has investigated the efficacy and adherence rate of SFPP in patients with end-stage KOA. This study aimed to compare the effectiveness and adherence rate of SFPP for pain management in patients with moderate and end-stage KOA. This retrospective study included a total of 118 patients with KOA (Kellgren-Lawrence classification grades II (n = 29), III (n = 32), and IV (n = 57)). The difference in SFPP use rate, adverse drug reactions rate, whether 50% pain relief occurred, and the percentage of patients who underwent surgical treatment were calculated. The overall SFPP use rate at one year was 61.0% (88.1% at less than one month, 79.7% at three months, and 61.0% at six months), with no significant differences among Kellgren-Lawrence grade II, III, and IV groups (p = 0.538). Adverse drug reactions such as skin rash (n = 23), skin irritation (n = 8), and gastrointestinal disorders (n = 2) were observed. The one-year SFPP use rate was significantly lower in patients in whom these side effects occurred but did not decrease in patients in whom only a skin rash occurred. Overall, 19 patients underwent surgery after discontinuation of SFPP use. Surgery was statistically selected more by the "over 71 years of age" group (p = 0.038) and the "ineffective" group (p = 0.007). SFPP exerts a comparable therapeutic effect even in end-stage KOA and may be an effective treatment option. Even if patients have end-stage KOA, there are cases in which the patient's background does not allow for surgery positively, such as high perioperative risk or desire for conservative treatment. In such cases, SFPP may be an effective treatment option worth trying.


A new virus found in garlic virus complex is a member of possible novel genus of the family Betaflexiviridae (order Tymovirales).
Plant vegetative propagation strategies for agricultural crops cause the accumulation of viruses, resulting in the formation of virus complexes or communities. The cultivation of garlic is based on vegetative propagation and more than 13 virus species from the genera Potyvirus, Allexivirus and Carlavirus have been reported. Aiming for an unbiased identification of viruses from a garlic germplasm collection in Brazil, total RNA from eight garlic cultivars was sequenced by high-throughput sequencing (HTS) technology. Although most viruses found in this study were previously reported, one of them did not belong to any known genera. This putative new virus was found in seven out of eight garlic cultivars and phylogenetic data positioned it as representative of an independent evolutionary lineage within family Betaflexiviridae. This virus has been tentatively named garlic yellow mosaic-associated virus (GYMaV), sharing highest nucleotide identities with African oil palm ringspot virus (genus Robigovirus) and potato virus T (genus Tepovirus) for the replicase gene, and with viruses classified within genus Foveavirus for the coat protein gene. Due to its high frequency in garlic cultivars, GYMaV should be considered in upcoming surveys of pathogens in this crop and in the development of virus-free garlic plants.


Outcome of inappropriate initial antimicrobial treatment in patients with methicillin-resistant Staphylococcus aureus bacteraemia.
To determine the impact of delayed treatment of methicillin-resistant Staphylococcus aureus bacteraemia (MRSA bacteraemia) on mortality. We used two different and complementary approaches: a retrospective cohort study and a matched case-control study. Of the total of all patients with S. aureus bacteraemia in a tertiary hospital over a 4 year period, 127 patients with MRSA bacteraemia were enrolled in the cohort study. The cases for the case-control study were defined as patients who received appropriate empirical treatment for MRSA bacteraemia; the controls, who were patients who received inappropriate empirical treatment for MRSA bacteraemia, were selected according to the matching variables of age, sex, severity of underlying illness, classification of main underlying disease and prior hospital stay. On the 14-point matching scale that was used to select the best controls, the average score (+/-S.D.) of the 30 controls was 11.2 (+/-2.0). In the cohort study, the difference in S. aureus bacteraemia-related mortality between appropriate (30%, 9/30) and inappropriate (39%, 38/97) empirical treatment was not significant (P=0.36). In addition, multivariate analysis did not indicate that inappropriate empirical treatment was associated with mortality when independent predictors for mortality were considered (adjusted OR 1.1, 95% CI 0.4-3.1). In the case-control study, S. aureus bacteraemia-related mortality in case patients was 30% (9/30) and in control patients 33% (10/30) (P>0.99, McNemar's test). In four of the nine discordant pairs, the case patients died whereas the control patients lived. Our data suggest that an initial delay of 2 days in the use of appropriate antibiotics, especially of vancomycin or other glycopeptides, before the preliminary microbiological report may not adversely affect the outcome in patients with MRSA bacteraemia.


The use of non-invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance.
Clarithromycin resistance of Helicobacter pylori (H. pylori) represents a major challenge in eradication therapy. In this study, we assessed if non-invasive stool tests can be used to verify successful H. pylori eradication and determine clarithromycin resistance. In this prospective study, patients undergoing urea breath testing (UBT) for confirmation of H. pylori eradication were asked to collect the stool as both a dry fecal sample and fecal immunochemical test (FIT). Stool H. pylori antigen testing (SAT) was performed on these samples and assessed for its accuracy in eradication verification. Type and duration of antibiotic treatment were retrospectively collected from patient records and compared with clarithromycin resistance determined by PCR of stool samples. H. pylori eradication information was available for a total of 145 patients (42.7% male, median age: 51.2). Successful eradication was achieved in 68.1% of patients. SAT on FIT samples had similar accuracy for eradication assessment compared to dry fecal samples, 72.1% [95% CI 61.4-81.2] versus 72.2% [95% CI 60.9-81.7]. Clarithromycin resistance rate was 13.4%. H. pylori antigen testing on FIT stool samples to verify H. pylori eradication is feasible and has similar accuracy as H. pylori antigen testing on dry stool samples. Dry stool, but not FIT, was suitable for non-invasive identification of H. pylori clarithromycin resistance by rt-PCR personalizing antibiotic treatment strategies without the need for invasive diagnostics is desirable, as the cure rate of first-line empirical H. pylori treatment remains low.


Contribution of endocytic motifs in the cytoplasmic tail of herpes simplex virus type 1 glycoprotein B to virus replication and cell-cell fusion.
The use of endocytic pathways by viral glycoproteins is thought to play various functions during viral infection. We previously showed in transfection assays that herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) is transported from the cell surface back to the trans-Golgi network (TGN) and that two motifs of gB cytoplasmic tail, YTQV and LL, function distinctly in this process. To investigate the role of each of these gB trafficking signals in HSV-1 infection, we constructed recombinant viruses in which each motif was rendered nonfunctional by alanine mutagenesis. In infected cells, wild-type gB was internalized from the cell surface and concentrated in the TGN. Disruption of YTQV abolished internalization of gB during infection, whereas disruption of LL induced accumulation of internalized gB in early recycling endosomes and impaired its return to the TGN. The growth of both recombinants was moderately diminished. Moreover, the fusion phenotype of cells infected with the gB recombinants differed from that of cells infected with the wild-type virus. Cells infected with the YTQV-mutated virus displayed reduced cell-cell fusion, whereas giant syncytia were observed in cells infected with the LL-mutated virus. Furthermore, blocking gB internalization or impairing gB recycling to the cell surface, using drugs or a transdominant negative form of Rab11, significantly reduced cell-cell fusion. These results favor a role for endocytosis in virus replication and suggest that gB intracellular trafficking is involved in the regulation of cell-cell fusion.


Benefits of maggot debridement therapy on leg ulcers: a literature review.
Maggot debridement therapy (MDT) is an effective method for debriding wounds such as leg ulcers, supporting the concept of wound bed preparation ( Dumville et al, 2009 ; Soares et al, 2009 ; Mudge et al, 2014 ). New evidence is emerging to suggest that maggots might contribute to wound healing in other ways. For example, the reduction of biofilms and disinfection of wounds ( Van Der Plas et al, 2008 ; Brown et al, 2012 ; Pritchard and Brown, 2015 ) plus regulation of protease levels ( Chambers et al, 2003 ; Van Der Plas et al, 2009a ; Van Der Plas et al, 2009b ). This review will discuss research exploring new benefits of maggots in the management of individuals with chronic leg ulcers.


Decreasing gender differences in "avoidable" mortality in Sweden.
"Avoidable" mortality, that is mortality from conditions amenable to healthcare intervention, is commonly studied as an indicator of the outcome of healthcare. The objective of this study was to analyse gender equity in avoidable mortality trends in Sweden from 1971 to 1996. The underlying cause of death was analysed for all deaths in the Swedish population in the age group 0-69 years during the period 1971-96. On the basis of those used in international studies, 18 indicators of avoidable mortality were identified. The conditions were divided into two groups: those mainly indicating an outcome of medical care and those mainly reflecting the effect of health policy. Age-standardized death rates were calculated for each indicator of avoidable mortality and for total mortality broken down by sex. Gender differences in death rates were studied. The annual trends in death rates were analysed using regression models. For total mortality the death rates were 80% higher for males than for females. The largest gender differences were found among those conditions mainly reflecting the effects of health policy. For most medical care indicators the gender differences were fairly small. For several avoidable causes of death the gender differences decreased considerably and for some causes of death the differences were eliminated. The avoidable mortality method seems to be useful in continuous epidemiological surveillance of the equity in healthcare. The comparatively low gender differences for avoidable death indicators as well as the decrease in these differences indicate decreasing gender inequity in health.


Lactational response of dairy cows to oral administration of L-tyrosine.
Tyrosine was administered to lactating cows to determine if the lack of response to canola meal treated with formaldehyde could be due to failure to increase uptake of tyrosine. Disappearance of free tyrosine from nylon bags suspended in the rumen of a fistulated steer was 27.4% after 12 h. Oral administration of tyrosine to sheep increased the free tyrosine concentration of duodenal fluid but did not affect tyrosin concentration in blood plasma. Tyrosine (50 g/cow per day) was fed to six lactating Holsteins in a switchback design. Milk yield was increased by 1.0 kg/day. In a second trial with a switchback design, tyrosine was fed to 12 lactating cows that were consuming diets containing formaldehyde-treated canola meal. Supplementing tyrosine to the formaldehyde-treated diet increased milk production by 1.6 kg/day, but adding tyrosine to the untreated diet did not affect milk yield. Results suggest that availability of tyrosine can limit milk production in some circumstances and that the lack of response to canola meal treated with formaldehyde may be partly due to failure to increase the uptake of tyrosine.


The effect of single set resistance training on strength and functional fitness in pulmonary rehabilitation patients.
The primary goal of pulmonary rehabilitation (PR) is for patients to achieve and maintain their maximum level of independence and functioning in the community. Traditional PR uses a predominantly aerobic/endurance approach to rehabilitation with little or no inclusion of exercises to increase strength. Few studies have investigated the impact of resistance training on PR despite growing evidence supporting its efficacy to improve physical function (functional fitness) in both healthy individuals and those with chronic disease. The purpose of this study was to investigate the effect of single-set resistance training on strength and functional fitness outcomes in PR patients. Twenty PR patients, 60 to 81 years old, were randomly assigned to an 8-week endurance-based PR program (ET) or an ET plus resistance training program (RT). Strength increased in RT (P < .05) and decreased in ET for both upper and lower body. Functional fitness improved (P < .05) in 5 of 7 tests for RT compared with 2 tests for ET. Single set RT can elicit significant improvements in both strength and functional fitness, which is not obtained by traditional PR alone. Our results are comparable to other studies with similar outcomes using multiple-set RT protocols. These findings may have important implications for program design, application, and adherence in PR.


Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states.
The hypothalamic paraventricular nucleus (PVN) is a unique and important brain region involved in the control of cardiovascular, neuroendocrine, and other physiological functions pertinent to homeostasis. The PVN is a major source of excitatory drive to the spinal sympathetic outflow via both direct and indirect projections. In this review, we discuss the role of the PVN in the regulation of sympathetic output in normal physiological conditions and in hypertension. In normal healthy animals, the PVN presympathetic neurons do not appear to have a major role in sustaining resting sympathetic vasomotor activity or in regulating sympathetic responses to short-term homeostatic challenges such as acute hypotension or hypoxia. Their role is, however, much more significant during longer-term challenges, such as sustained water deprivation, chronic intermittent hypoxia, and pregnancy. The PVN also appears to have a major role in generating the increased sympathetic vasomotor activity that is characteristic of multiple forms of hypertension. Recent studies in the spontaneously hypertensive rat model have shown that impaired inhibitory and enhanced excitatory synaptic inputs to PVN presympathetic neurons are the basis for the heightened sympathetic outflow in hypertension. We discuss the molecular mechanisms underlying the presynaptic and postsynaptic alterations in GABAergic and glutamatergic inputs to PVN presympathetic neurons in hypertension. In addition, we discuss the ability of exercise training to correct sympathetic hyperactivity by restoring blood-brain barrier integrity, reducing angiotensin II availability, and decreasing oxidative stress and inflammation in the PVN.


Complete sequence of an immunoglobulin mRNA using specific priming and the dideoxynucleotide method of RNA sequencing.
The complete sequence of the mouse immunoglobulin kappa light chain MOPC 21 messenger RNA has been determined using a chain termination method and chemically synthesised deoxyoligonucleotides to initiate the synthesis of a DNA molecule complementary to the mRNA template. Five such oligonucleotide primers have been used for the sequence analysis of this messenger RNA. The approach is excellent for comparative studies of mouse k-chain mRNAs because they can be made on impure mRNA preparations. The MOPC 21 light chain mRNA is 943 nucleotides in length excluding the poly(A) region. An unexpected finding was that there are only three bases in the 5' non-coding region and its significance in terms of ribosome binding is discussed; 87 code for the precursor or leader sequence of the protein, 642 for the mature protein and 211 for the 3' non-coding region. The codons for the precursor region allows the previously undetermined amino acid sequence to be predicted. In common with other precursor regions a high proportion of the predicted amino acids are hydrophobic.


WZY-321, a novel evodiamine analog, inhibits glioma cell growth in an autophagy-associated manner.
Glioblastoma is one of the most aggressive types of brain tumor. The median survival rate of patients with glioblastoma (World Health Organization grade IV) is <15 months. Therefore, there is an urgent requirement for the development of novel and efficient therapeutic agents against glioma. In previous studies, WZY-321 (10-hydroxy-1-methyl-8,13b-dihydro-5H,7H-benzo[e]benzofuro[2',3':3,4]pyrido[2,1-b][1,3]oxazin-5-one), a novel evodiamine (Evo) analog, was reported to exhibit enhanced pharmacological properties and improved cytotoxicity against a number of human cancer cell lines compared with Evo. In the current study, the anti-proliferative effect of WZY-321 on SHG-44 and SWO-38 glioma cells was further studied, and its mechanism of action investigated. The results indicated that WZY-321 inhibited the proliferation of SHG-44 cells in a dose- and time-dependent manner by enhancing cellular apoptosis and inducing cell cycle arrest at the G2-M phase. Treatment of glioma cells with WZY-321 concomitantly increased the expression levels of microtubule associated protein 1 light chain 3α and Beclin1, indicating enhanced autophagy. Overall, the results of the present study revealed the anti-proliferative potential of WZY-321 in glioma cells, thus providing a possible autophagy-based therapeutic strategy for the treatment of glioblastoma.