Atypical chemokine receptor 4 shapes activated B cell fate.
Activated B cells can initially differentiate into three functionally distinct fates-early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells-by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell-intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate.


Identifying Recent Cholera Infections Using a Multiplex Bead Serological Assay.
Estimates of incidence based on medically attended cholera can be severely biased. Vibrio cholerae O1 leaves a lasting antibody signal and recent advances showed that these can be used to estimate infection incidence rates from cross-sectional serologic data. Current laboratory methods are resource intensive and challenging to standardize across laboratories. A multiplex bead assay (MBA) could efficiently expand the breadth of measured antibody responses and improve seroincidence accuracy. We tested 305 serum samples from confirmed cholera cases (4 to 1083 d postinfection) and uninfected contacts in Bangladesh using an MBA (IgG/IgA/IgM for 7 Vibrio cholerae O1-specific antigens) as well as traditional vibriocidal and enzyme-linked immunosorbent assays (2 antigens, IgG, and IgA). While postinfection vibriocidal responses were larger than other markers, several MBA-measured antibodies demonstrated robust responses with similar half-lives. Random forest models combining all MBA antibody measures allowed for accurate identification of recent cholera infections (e.g., past 200 days) including a cross-validated area under the curve (cvAUC200) of 92%, with simpler 3 IgG antibody models having similar accuracy. Across infection windows between 45 and 300 days, the accuracy of models trained on MBA measurements was non-inferior to models based on traditional assays. Our results illustrated a scalable cholera serosurveillance tool that can be incorporated into multipathogen serosurveillance platforms. IMPORTANCE Reliable estimates of cholera incidence are challenged by poor clinical surveillance and health-seeking behavior biases. We showed that cross-sectional serologic profiles measured with a high-throughput multiplex bead assay can lead to accurate identification of those infected with pandemic Vibrio cholerae O1, thus allowing for estimates of seroincidence. This provides a new avenue for understanding the epidemiology of cholera, identifying priority areas for cholera prevention/control investments, and tracking progress in the global fight against this ancient disease.


Equivalent circuit modeling and vibrometry measurements of the Nigerian-origin Udu Utar drum.
The Udu drum, sometimes called the water pot drum, is a traditional Nigerian instrument. Musicians who play the Udu exploit its aerophone and idiophone resonances. This paper will discuss an electrical equivalent circuit model for the Udu Utar, a modern innovation of the traditional Udu, to predict the low frequency aerophone resonances and will also present scanning laser vibrometer measurements to determine the mode shapes of the dominant idiophone resonances. These analyses not only provide an understanding of the unique sound of the Udu instrument but may also be used by instrument designers to create instruments with resonance frequencies at traditional musical intervals for the various tones produced and to create musical harmonic ratios. The information, specifically the laser vibrometry measurements, may also be useful to musicians in knowing the best places to strike the Udu to excite musical tones.


Cardiotonic agents. 2. (Imidazolyl)aroylimidazolones, highly potent and selective positive inotropic agents.
A series of 4-alkyl-1,3-dihydro-5-[(1H-imidazolyl)benzoyl]-2H-imidazol-2-ones 9 was synthesized and evaluated in vitro for positive inotropic and cyclic AMP phosphodiesterase inhibitory activity. A wide range of inotropic and enzyme-inhibitory potencies was observed, substitution on the imidazolyl moiety being the major determinant of activity. The 4-ethyl-5-[4-(1H-imidazol-1-yl)benzoyl] congener 9g exhibited the highest potency in vitro. Incorporation of a methyl group at the imidazolyl 2-position gave 9h, which was less potent but remarkably selective in vivo for positive inotropic effects over heart rate and hypotensive effects.


Home care utilization by congestive heart failure patients: a pilot study.
Home health care costs have increased more than any other health care service covered by Medicare, and new methods of payment by Medicare are being introduced. A prospective payment system would replace the per visit rate now paid to home care agencies by Medicare. In order to remain viable under a new payment system, home health care agencies will need to be efficient in the delivery of home care services and still demonstrate effective patient care. The intent of this descriptive study was to determine norms of resource utilization for the congestive heart failure (CHF) patients admitted and discharged from a not-for-profit home health agency (HHA). Forty agency records were retrospectively reviewed using the Resource Utilization Inventory to collect the characteristics and resource utilization of the sample group. The CHF patients were older than most home care clients and had chronic health problems. Because of these chronic health problems, over half of the study population had caregivers so that the clients could remain in their own homes. Most clients clearly demonstrated the need for skilled nursing or home health aide visits after being hospitalized for an acute CHF episode. Less than half of the study group were discharged form the HHA as improved, and frequently were discharged to another healthcare facility. These results provide a beginning direction for profiling the CHF patient's consumption of resources for setting prospective reimbursement rates.


Size effects in the magnetic anisotropy of embedded cobalt nanoparticles: from shape to surface.
Strong size-dependent variations of the magnetic anisotropy of embedded cobalt clusters are evidenced quantitatively by combining magnetic experiments and advanced data treatment. The obtained values are discussed in the frame of two theoretical models that demonstrate the decisive role of the shape in larger nanoparticles and the predominant role of the surface anisotropy in clusters below 3 nm diameter.


Phosphate Ion Functionalization of Perovskite Surfaces for Enhanced Oxygen Evolution Reaction.
Recent findings revealed that surface oxygen can participate in the oxygen evolution reaction (OER) for the most active catalysts, which eventually triggers a new mechanism for which the deprotonation of surface intermediates limits the OER activity. We propose in this work a "dual strategy" in which tuning the electronic properties of the oxide, such as La1-xSrxCoO3-δ, can be dissociated from the use of surface functionalization with phosphate ion groups (Pi) that enhances the interfacial proton transfer. Results show that the Pi functionalized La0.5Sr0.5CoO3-δ gives rise to a significant enhancement of the OER activity when compared to La0.5Sr0.5CoO3-δ and LaCoO3. We further demonstrate that the Pi surface functionalization selectivity enhances the activity when the OER kinetics is limited by the proton transfer. Finally, this work suggests that tuning the catalytic activity by such a "dual approach" may be a new and largely unexplored avenue for the design of novel high-performance catalysts.


Characterization of an Infectious Bronchitis Virus Isolated from Commercial Layers Suffering from False Layer Syndrome.
Infectious bronchitis virus (IBV) is a gammacoronavirus that primarily induces an upper respiratory disease in chickens, also affecting the urogenital tract and occasionally leading to a condition called false layer syndrome (FLS), where sexually mature hens ovulate normally but are unable to lay eggs. Here, we describe an outbreak of FLS in Arizona from which an IBV variant that is nearly 90% homologous to DMV/1639 using the Spike subunit 1 gene, named AZ/FLS/17, was isolated and used in challenge experiments. Three-day-old specific-pathogen-free chicks were challenged with AZ/FLS/17 or M41 in high and low doses, and the disease outcomes were compared. Overall, no differences in microscopic lesions or viral loads in the reproductive tract were detected between AZ/FLS/17- and M41-infected birds. To minimize the losses linked to FLS in the problematic flocks, an updated live-attenuated IBV vaccine protocol including the use of the Ma5 strain at the hatchery was implemented, resulting in a drastic reduction of false layers in the subsequent flocks. To monitor the circulation of wild-type and vaccine strains in this population, a molecular surveillance study was performed. Samples were collected at 1, 7, 14, and 21 days of age, and from laying hens at 30 and 36 wk. In older birds, the IBV strains detected were more diverse than at 1 and 7 days of age. Nevertheless, live vaccine combinations are still widely used to decrease the losses caused by FLS in commercial egg laying flocks worldwide.


[Let's save our nurses and doctors!].
Several studies have shown that healthcare service is a dangerous workplace, but the reasons have been remained unexplained. The aim of the authors was to obtain data on the health condition of health care professionals and identify the underlying risk factors for the increased morbidity. Health care data obtained from 276 bedside nurses in 2004 and 1250 hospital employees in 2009 were analysed. In addition, the fate of department directors of Szent György University Hospital in Székesfehérvár between 1979 and 2010 was recorded and the data were compared to those obtained from a smaller hospital in Budapest during the same time period. The body mass index of bedside nurses between the age of 30-35 years reached the upper limit of normal (which occurred 5-10 years earlier as compared to the average population) and then it increased continuously above the average value. In hospital employees the increase of body mass index was accompanied by an increase in the frequency of chronic diseases such as hypertension, allergy, thyroid dysfunction, rheumatologic diseases, diabetes, peptic ulcer, cancer and depression. When the cause of death of the department directors who died between 1979 and 2010 was analyzed the authors found that cancer death occurred in 77% and 82% of department directors in Székesfehérvár and Budapest hospitals, respectively, while cancer death rate in 2011 was 25.4% in Hungary. The authors propose that continuous psychological stress, night shifts, nonstop standby and surcharge may all suppress the activity of the immune system. This proposal seems to be supported by novel psycho-neuro-immunological research data. The solution could be early prevention using stress control.


Tropical diabetes hand syndrome with autoamputation of the digits: case report and review of literature.
The tropical diabetes hand syndrome is a complication affecting patients with diabetes mellitus in the tropics, and consists of localized cellulitis, swelling and ulceration of the hands which may progress to fulminant sepsis and gangrene of the whole limb. It is associated with a poor outcome. We report a 32 year old woman with tropical diabetes hand infection with autoamputation of the digits, review the relevant literature, and highlight the need for prevention and early hospital presentation in diabetics with hand infection, in order to prevent potentially crippling or fatal complications.


Influence of ozone treatment on functional and rheological characteristics of food products: an updated review.
In this milieu, ozone technology has emerged as an avant-garde non-thermal mode of disinfection with potential applications in the food industry. This eco-friendly technology has a comprehendible adeptness in replacing alternative chemical sanitizers and is recognized as a generally safe disinfectant for fruits and vegetables. Several researchers have been focusing on the biochemical impacts of ozone on different quantitative and qualitative aspects of fruits and vegetables. A collection of those works is presented in this review highlighting the effect of ozone on the functional, antioxidant, and rheological properties of food. This can be a benevolent tool for discovering the processing states of ozone applications and ensuing influence on safety and quality attributes of previously studied foods and opening further research areas. It extends shelf life and never leaves any harmful residues on the product since it decomposes to form oxygen. It was seen that the impact on a specific property of food was dependent on the ozone concentration and treatment time, and the adverse effects of ozone exposure can be alleviated once the processing conditions are optimized. The present review can be used as a baseline for designing different food processing operations involving ozone.


Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease.
Adult hippocampal neurogenesis is strongly impaired in Alzheimer's disease (AD). In several mouse models of AD, it was shown that adult-born neurons exhibit reduced survival and altered synaptic integration due to a severe lack of dendritic spines. In the present work, using the APPxPS1 mouse model of AD, we reveal that this reduced number of spines is concomitant of a marked deficit in their neuronal mitochondrial content. Remarkably, we show that targeting the overexpression of the pro-neural transcription factor Neurod1 into APPxPS1 adult-born neurons restores not only their dendritic spine density, but also their mitochondrial content and the proportion of spines associated with mitochondria. Using primary neurons, a bona fide model of neuronal maturation, we identified that increases of mitochondrial respiration accompany the stimulating effect of Neurod1 overexpression on dendritic growth and spine formation. Reciprocally, pharmacologically impairing mitochondria prevented Neurod1-dependent trophic effects. Thus, since overexpression of Neurod1 into new neurons of APPxPS1 mice rescues spatial memory, our present data suggest that manipulating the mitochondrial system of adult-born hippocampal neurons provides neuronal plasticity to the AD brain. These findings open new avenues for far-reaching therapeutic implications towards neurodegenerative diseases associated with cognitive impairment.


Nitroxergic nerves mediate vagally induced relaxation in the isolated stomach of the guinea pig.
Here we show that the relaxation induced by stimulation of the vagus nerve in the presence of cholinergic (muscarinic) and adrenergic blockade in the isolated stomach of the guinea pig is mediated by nitric oxide (NO). This is substantiated by inhibition of vagal relaxation by NG-monomethyl-L-arginine, an inhibitor of NO synthesis. The effect of NG-monomethyl-L-arginine was partially reversed by coincubation with L-arginine but not with D-arginine. NO activates soluble guanylate cyclase, and relaxation of the stomach induced by vagal stimulation was prevented by an inhibitor of soluble guanylate cyclase, methylene blue, further supporting our conclusions. The relaxant effect of vagal stimulation was also ablated by hexamethonium, an inhibitor of ganglionic nicotinic receptors, thereby showing that ganglionic transmission did not rely on NO, through its release from preganglionic neurons. However, hexamethonium did not inhibit the gastric relaxation brought about by increasing the intragastric pressure, which is also mediated by NO as previously described by us. The selective inhibition by hexamethonium of only the vagally mediated relaxation but not of the pressure-induced relaxation of the stomach indicates the existence of at least two separate neuronal pathways able to generate NO and bring about gastric accommodation of food or fluid.


Testing vs. Believing Hypotheses: Magical Ideation in the Judgement of Contingencies.
This paper examines the idea that an important dimension of human cognition is the amount of objective evidence required for perception of meaningful patterns. At the clinical extreme of this dimension are patients with hallucinations and delusions who experience perception with no external evidence and see connections between objectively unrelated events. Also, normal individuals exhibit considerable variation along this continuum. The theory proposed here predicts that normal subjects with low evidential criteria will be more likely to accept causal explanations, not only for everyday ''paranormal'' coincidences, but also for random contingencies in a laboratory experiment. This prediction was confirmed when 40 students completed a differential reinforcement of low rates (DRL) task designed to induce superstitious behaviour and were then questioned about their hypotheses concerning the contingencies for successful performance. Participants scoring high on the Magical Ideation scale (indicating greater belief in paranormal phenomena) tested fewer hypotheses during the task, and they ended up believing in more hypotheses regarding illusory contingencies than did their low-scoring peers. We proposed that a continuum of hypothesis-testing behaviour underlies the schizotypy continuum, with ''positive'' schizotypal traits reflecting a Type I error bias and ''negative'' traits a Type II error bias. Differential activation patterns within frontal-limbic networks are tentatively suggested as a physiological correlate of the behavioural continuum.


6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol: a promising new anticancer compound.
The 7-nitro-2,1,3-nitrobenzoxadiazole (NBD) derivatives are a series of compounds containing the NBD scaffold that are not glutathione (GSH) peptidomimetics, and result in a strong inhibition of glutathione S-transferases (GSTs). Growing evidences highlight their pivotal roles and outstanding anticancer activity in different tumor models. In particular, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) is extensively studied, which is a very efficient inhibitor of GSTP1-1. It triggers apoptosis in several tumor cell lines and this cytotoxic activity is observed at micro and submicromolar concentrations. Importantly, studies have shown that NBDHEX acts as an anticancer drug by inhibiting GSTs catalytic activity, avoiding inconvenience of the inhibitor extrusion from the cell by specific pumps and disrupting the interaction between the GSTP1-1 and key signaling effectors. Additionally, some researchers also have discovered that NBDHEX can act as late-phase autophagy inhibitor, which opens new opportunities to fully exploit its therapeutic potential. In this review, we summarize the advantages, anticancer mechanisms, and analogs of this compound, which will establish the basis on the usage of NBDHEX in clinical applications in future.


A probabilistic atlas of finger dominance in the primary somatosensory cortex.
With the advent of ultra-high field (7T), high spatial resolution functional MRI (fMRI) has allowed the differentiation of the cortical representations of each of the digits at an individual-subject level in human primary somatosensory cortex (S1). Here we generate a probabilistic atlas of the contralateral SI representations of the digits of both the left and right hand in a group of 22 right-handed individuals. The atlas is generated in both volume and surface standardised spaces from somatotopic maps obtained by delivering vibrotactile stimulation to each distal phalangeal digit using a travelling wave paradigm. Metrics quantify the likelihood of a given position being assigned to a digit (full probability map) and the most probable digit for a given spatial location (maximum probability map). The atlas is validated using a leave-one-out cross validation procedure. Anatomical variance across the somatotopic map is also assessed to investigate whether the functional variability across subjects is coupled to structural differences. This probabilistic atlas quantifies the variability in digit representations in healthy subjects, finding some quantifiable separability between digits 2, 3 and 4, a complex overlapping relationship between digits 1 and 2, and little agreement of digit 5 across subjects. The atlas and constituent subject maps are available online for use as a reference in future neuroimaging studies.


Butyrylcholinesterase and cognitive function.
Butyrylcholinesterase (BuChE) is expressed in brain structures involved in cognition, but the effect of selective BuChE inhibitors on human cognitive function is unknown. We report a patient whose cognitive function deteriorated following a reduction and improved following reinstitution of ethopropazine, a selective BuChE inhibitor. We suggest that, because neurons expressing BuChE may be involved in cognition, there is merit to further evaluation of selective BuChE inhibitors in treating cognitive dysfunction.


Improving the safety of resuscitative endovascular balloon occlusion of the aorta - Compliant versus semi-compliant balloon systems.
Resuscitative endovascular balloon occlusion of the aorta is an alternative to resuscitative thoracotomy in non-compressible torso haemorrhage. Low-profile, compliant balloon catheter systems have been developed, which can be deployed without the need for fluoroscopy. However, concern exists for over inflation and aortic injury, especially as compliant balloon material can stretch reducing syringe feedback and limiting the effectiveness of a safety valve. An alternative material would be a semi-compliant balloon material, but its performance is unknown. The aim of this study was to compare the inflation characteristics of compliant versus semi-compliant balloon systems and to determine whether a pressure relief safety valve can be practically applied to a semi-compliant balloon catheter as a safety device. This was an ex vivo study using porcine segments of thoracic aorta. The study consisted of two phases. The first phase involved intermittent inflation of six compliant balloon and six semi-compliant balloon balloons until balloon or aortic rupture. In the second phase, six semi-compliant balloons with the pressure-relief valve set at 0.45 atmospheres were inflated in the aortas until the valve release, followed by injection with additional 30 mL. Data including pressure, volume, balloon working length, diameter and circumferential stretch ratio were collected. At failure, mean balloon volume was almost double in compliant balloon group vs semi-compliant balloon group - 49.83 mL (±23.25) and 25.16 mL (±8.93), respectively (p = 0.004), with 36% increase in working length in the compliant balloon group - 81.17 mm (±19.11) vs 59.49 (±4.86) for semi-compliant balloon (p = 0.023). When plotted, the relationship pattern between volume and pressure fit a linear model for the compliant balloon, and a quadratic model for the semi-compliant balloon. Following attempted over inflation with the pressure valve, there was no change in parameters before and after attempted over inflation. The inflation profile differs between balloon designs. In contrast to semi-compliant balloons, compliant balloons will accommodate more volume to mitigate increase in pressure. This does not completely eliminate the risk of over inflation. The inflation characteristics of the semi-compliant balloon permit pairing it with a safety valve, which could lead to a development of a safer balloon technology in the future.


Diffuse peritoneal seeding in immunoblastic lymphosarcoma.
The authors report a case of immunoblastic lymphosarcoma of B cells with an unusual presentation. Laparotomy on a 67-year-old women with an abdominal mass revealed extensive peritoneal seeding resembling carcinomatosis. At autopsy, immunoblastic lymphosarcoma, probably originating in the bowel wall, was found. It was studied by light, immunofluorescent and electron microscopy. Histologic examination showed monomorphic proliferation of malignant immunoblasts with plasmacytoid features. Immunofluorescent microscopy was positive for intracytoplasmic IgG, IgA, kappa and lambda light chains. The presence of diffuse peritoneal seeding in patients with malignant lymphomas is not well documented. The clinical and pathologic features of this entity and its relation to Mediterranean lymphoma are discussed.


Alpha 1-adrenoceptor blockade and/or 5-HT1A agonism during treadmill exercise in dogs.
1. The hypotensive effects of alpha 1-adrenergic blockade and/or stimulation of central nervous 5-HT1A receptors were studied using drugs with different affinity for central nervous 5-HT1A and peripheral alpha 1-adrenoceptors. Urapidil, 5-methylurapidil, flesinoxan and 8-OH-DPAT were compared under states of different activation of the autonomic nervous system, i.e. at rest and during graded treadmill exercise. 2. The rank order of hypotensive potency as derived from the most extensive decrease in resting diastolic arterial blood pressure was urapidil greater than 5-methylurapidil greater than flesinoxan much greater than 8-OH-DPAT. 3. The reflex increase in heart rate due to the decrease in arterial blood pressure at rest was suppressed after 0.1 mumol kg-1 flesinoxan. 4. The reflex increase in heart rate due to the decrease in arterial blood pressure at rest was less accentuated after high doses of urapidil and 5-methylurapidil. 5. During exercise both 5HT1A receptor agonists, flesinoxan and 8-OH-DPAT, decreased sympathetic tone. 6. The combined effects of alpha 1-adrenoceptor blockade and 5-HT1A receptor stimulation (urapidil and 5-methylurapidil) result in distinct decreases in blood pressure and slight suppression of reflex tachycardia at rest after high doses. Stimulation of 5-HT1A receptors alone (flesinoxan) suppresses reflex tachycardia by modulation of baroreceptor reflex and at high dose also diminishes exercise-induced increase in sympathetic tone.


Segregation of a novel FBN1 gene mutation, G1796E, with kyphoscoliosis and radiographic evidence of vertebral dysplasia in three generations.
Skeletal and spinal radiographic findings are described in five individuals of a three-generation kindred with kyphoscoliosis. The affected individuals have a novel FBN1 gene mutation, G1796E. To our knowledge, this is the first report of a family with an FBN1 gene mutation cosegregating with an unusual autosomal dominant progressive kyphoscoliosis of variable severity, together with radiological abnormalities of the spine, and some skeletal but no ocular or cardiac manifestations of Marfan syndrome. This previously undescribed phenotype represents yet another in the widening spectrum of fibrillinopathies caused by an FBN1 gene mutation.


SNAPPI-DB: a database and API of Structures, iNterfaces and Alignments for Protein-Protein Interactions.
SNAPPI-DB, a high performance database of Structures, iNterfaces and Alignments of Protein-Protein Interactions, and its associated Java Application Programming Interface (API) is described. SNAPPI-DB contains structural data, down to the level of atom co-ordinates, for each structure in the Protein Data Bank (PDB) together with associated data including SCOP, CATH, Pfam, SWISSPROT, InterPro, GO terms, Protein Quaternary Structures (PQS) and secondary structure information. Domain-domain interactions are stored for multiple domain definitions and are classified by their Superfamily/Family pair and interaction interface. Each set of classified domain-domain interactions has an associated multiple structure alignment for each partner. The API facilitates data access via PDB entries, domains and domain-domain interactions. Rapid development, fast database access and the ability to perform advanced queries without the requirement for complex SQL statements are provided via an object oriented database and the Java Data Objects (JDO) API. SNAPPI-DB contains many features which are not available in other databases of structural protein-protein interactions. It has been applied in three studies on the properties of protein-protein interactions and is currently being employed to train a protein-protein interaction predictor and a functional residue predictor. The database, API and manual are available for download at: http://www.compbio.dundee.ac.uk/SNAPPI/downloads.jsp.


Evaluation of bioprosthetic mitral valve failure.
Porcine bioprosthetic heart valves have been in use for the past 13 years. Although they are superior to mechanical valves in several clinical situations, their long-term durability remains in question. The slight increase in failure rate of the bioprosthetic valve starting about six years after implantation mandates close follow-up of these patients. Since primary care physicians often provide most of the medical care to patients who have undergone heart valve replacement, it is important that they recognize the signs of bioprosthetic valve failure.


Improved antimicrobial activities of synthetic-hybrid bacteriocins designed from enterocin E50-52 and pediocin PA-1.
Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics.


Chiral polychlorinated biphenyls (PCBs) in bioaccumulation, maternal transfer, and embryo development of chicken.
Polychlorinated biphenyls (PCBs) and enantiomer fractions (EFs) of PCB enantiomers (PCBs 95, 132, 135, and 149) were investigated in soil and chicken feed, chicken (Gallus domesticus) tissues, eggs on 0, 7, and 14 days after the onset of incubation, and newborn chick tissues. The EF values of PCBs 95, 132, and 149 changed significantly from soil to chicken tissues, and the values in the liver exhibited the highest deviation from the racemic ratio, indicating enantiomer-selective metabolism in hens. Congeners, which are highly resistant to degradation, such as PCBs 138, 153, and 180, exhibited the highest maternal transfer potentials when muscle and liver were used to assess the maternal transfer. However, uniform transfer ratios were observed for most of the PCB congeners when visceral fat was used. The EFs of chiral PCBs in eggs either did not match with muscle or with liver or were similar to those in visceral fat. These results indicate that hens mainly mobilized visceral fat for egg formation and PCBs were deposited in eggs by associating with these lipid materials. Further enantiomeric enrichment of PCBs 95, 132, and 149 occurred in the newborn chick tissues. However, an opposite enantioselectivity for PCB 135 in newborn chicks was observed. These results indicate that the potential toxicity of PCB enantiomers to newborn chicks may be different from that of adults.


Top-Down Proteomics and Farm Animal and Aquatic Sciences.
Proteomics is a field of growing importance in animal and aquatic sciences. Similar to other proteomic approaches, top-down proteomics is slowly making its way within the vast array of proteomic approaches that researchers have access to. This opinion and mini-review article is dedicated to top-down proteomics and how its use can be of importance to animal and aquatic sciences. Herein, we include an overview of the principles of top-down proteomics and how it differs regarding other more commonly used proteomic methods, especially bottom-up proteomics. In addition, we provide relevant sections on how the approach was or can be used as a research tool and conclude with our opinions of future use in animal and aquatic sciences.


Cortical Excitability and Agressive Behavior in Post-Traumatic Stress Disorder.
Hyperarousal and alertness play an important role in the clinical presentation of Post-traumatic stress disorder (PTSD). Strenuous effort has been made to shed light on the mechanisms that cause these symptoms of patients. Based on the claim that there is a relationship between some subtypes of hyperarousal symptoms and aggression in patients with PTSD, we aimed to examine the relationship between electrophysiological measurements that was measured through transcranial magnetic stimulation (TMS) and aggression scale scores of PTSD patients in this study. The study included 37 patients with a diagnosis of PTSD according to DSM-IV criteria and 25 healthy volunteers. Electrophysiological measurements of participants were made with TMS. The Buss Perry Aggression Questionnaires was administered to patients and control group. In the patient group, a positive correlation was found between scores of aggression and arousal symptoms. Motor excitability threshold, one of TMS measurements, which is a sign of cortical excitability, was significantly lower in the patient group than the control group. There was a negative correlation between aggression scale scores and the parameters of motor excitability threshold and cortical silent period which both shows cortical excitability of the patients. We concluded that there was an increase in cortical excitability in PTSD patients and we suggest that this increase might be associated with hyperarousal symptoms and aggressive behavior.


Ganglioneuroma presenting with differentiated skeletal metastases. Report of a case.
The authors report the case of a child with retroperitoneal ganglioneuroma and cytodifferentiated skeletal metastases. The primary tumor was surgically resected, and the child is alive and well 2 years later without additional therapy. This rarely documented phenomenon can be explained by spontaneous cytomaturation within both primary and metastatic tumor.


Clinical evaluation of coverage of open wounds: Polyglycolic acid sheet with fibrin glue spray vs split thickness skin.
This study aimed to evaluate the coverage of oral wounds using either a polyglycolic acid (PGA) sheet or split-thickness skin grafting (STSG). A total of 119 cases of wound coverage using a PGA sheet and fibrin glue spray as well as 132 cases of wound coverage cases using STSG were reviewed retrospectively. The site of the excision area, perioperative conditions, and postoperative functional problems were evaluated. The PGA group had significantly shorter operation time, earlier start of oral intake, and shorter hospitalization than the STSG group. If the PGA sheet over the wound with exposed bone could be protected by a surgical sprint, oral food intake could be started on the day after surgery at the earliest. When the size of the wound in the buccal excisional area was classified into two groups (<6 or ≥6 cm2), mouth opening in the STSG group was significantly larger at 3 months postoperatively. When the size of the wound in the tongue and floor of mouth was classified into two groups (<12 or ≥12 cm2), the STSG group had a significantly higher score in postoperative speech intelligibility. Selection of a PGA sheet or STSG based on the consideration of defect size, tumor location, patients' local and general condition and tolerance for surgery could reduce the patients' postsurgical dysfunctional problems.


Photoelectrochemical properties of N/C-codoped TiO2 film electrodes prepared by reactive DC magnetron sputtering.
This paper aims to characterize the photoelectrochemical properties of the visible-light enabling titanium dioxide (TiO2) film electrodes prepared by codoping nitrogen (N) and a presputtered carbon film (C-film) onto indium tin oxide (ITO) glass substrates using a direct current (DC) magnetron sputtering technique. To improve its photoelectrochemical properties, different amount of C-doping sources, 2 h and 4 h C-film, are chose to prepare the N/C-codoped TiO2 film electrodes. Under visible-light (420 < lambda < 610 nm) illumination, a remarkable photocurrent density of 22 microA/cm2 is obtained for the N/C-TiO2 film electrode prepared with a 4 h C-film (NC(4)-T) at an applied potential of +1.2 V versus SCE. Under ultraviolet (lambda approximately 365 nm) illumination, the NC(4)-T film electrode also exhibits the highest photocurrent density of 0.23 mA/cm2 among all samples tested. A more negative flat band potential of NC(4)-T film electrode is attributed to the synergistic effect of N/C codoping. The XRD spectrum of the NC(4)-T film electrode shows mainly the well-crystallized anatase TiO2 phase and an extremely intense (211) plane. Thus, photoelectrochemical activity of the NC(4)-T film electrode can be ascribed to the well-crystallized columnar crystals with pores at its grain boundary, open surface morphology, which are revealed by SEM and TEM images, and a more negative flat band potential. The visible-light induced activity is mostly enhanced as a result of the synergistic effects of N/C-codoping into the TiO2 crystals. A potential application to photocatalytic splitting of water for hydrogen evolution using solar light is practically possible.


Long COVID Through a Public Health Lens: An Umbrella Review.
Objectives: To synthesize existing evidence on prevalence as well as clinical and socio-economic aspects of Long COVID. Methods: An umbrella review of reviews and a targeted evidence synthesis of their primary studies, including searches in four electronic databases, reference lists of included reviews, as well as related article lists of relevant publications. Results: Synthesis included 23 reviews and 102 primary studies. Prevalence estimates ranged from 7.5% to 41% in non-hospitalized adults, 2.3%-53% in mixed adult samples, 37.6% in hospitalized adults, and 2%-3.5% in primarily non-hospitalized children. Preliminary evidence suggests that female sex, age, comorbidities, the severity of acute disease, and obesity are associated with Long COVID. Almost 50% of primary studies reported some degree of Long COVID-related social and family-life impairment, long absence periods off work, adjusted workloads, and loss of employment. Conclusion: Long COVID will likely have a substantial public health impact. Current evidence is still heterogeneous and incomplete. To fully understand Long COVID, well-designed prospective studies with representative samples will be essential.


Effect of cultivation conditions on β-estradiol removal in laboratory and pilot-plant photobioreactors by an algal-bacterial consortium treating urban wastewater.
The use of microalgal consortia for urban wastewater treatment is an increasing trend, as it allows simultaneous nutrient removal and biomass production. Emerging contaminants proposed for the list of priority substances such as the hormone 17β-estradiol are commonly found in urban wastewater, and their removal using algal monocultures has been accomplished. Due to the inherent potential of algae-based systems, this study aimed to assess the capability of native photobioreactor biomass to remove 17β-estradiol under indoor and outdoor conditions. At the same time, the microbial community changes in regular and bioaugmented operations with Scenedesmus were assessed. The results show that almost complete removal (>93.75%) of the hormone 17β-estradiol can be attained in the system under favourable seasonal conditions, although these conditions greatly influence biomass concentrations and microbial diversity. Even under the harsh conditions of low temperatures and solar irradiation, the established consortium removed more than 50% of the pollutant in 24 h. While species from genus Chlorella were stable during the entire operation, the microbial diversity analysis revealed that assorted and evenly distributed populations stimulate the removal rates. Bioaugmentation assays proved that the input of additional biomass results in higher overall removal and decreases the yield per mg of biomass.


Ferrokinetics is associated with the left ventricular mass index in patients with chronic kidney disease.
Background Patients with chronic kidney disease (CKD) often have the complication of anaemia. Usage of an erythropoietin-stimulating agent accelerates iron deficiency because it promotes iron utilization. Recently, iron administration was reported to be effective for patients with cardiac failure. We examined the association between ferrokinetics and cardiac function in patients with CKD. Methods In this cross-sectional study, we examined 558 patients (424 men and 134 women; mean age, 68.9 ± 13.1 years) with CKD who were admitted to our hospital. We assessed cardiac function by ultrasonography and ferrokinetics through transferrin saturation (TSAT) and ferritin levels. Results The primary diseases of CKD were nephrosclerosis (n = 247), diabetic nephropathy (n = 154), chronic glomerulonephritis (n = 73), and others. The mean estimated glomerular filtration rate was 16.9 ± 9.3 mL/min/1.7 m2, and the haemoglobin (Hb) level was 11.0 ± 1.7 g/dL. The median of TSAT was 28.05%, and patients were divided into two groups: below (L-Ts) and above (H-Ts) the median. The median of ferritin was 122 ng/mL, and patients were divided into two groups: below (L-f) and above (H-f) the median. We categorized four groups as H-Ts + H-F, H-Ts + L-F, L-Ts + H-F, and L-Ts + L-F. The Hb levels were 11.1 ± 1.8, 11.3 ± 1.4, 10.9 ± 1.6, and 10.8 ± 1.5 g/dL, respectively, and there was no difference between groups. However, the left ventricular mass indices (LVMIs) were 122.6 ± 46.6, 110.8 ± 32.0, 118.3 ± 36.0, 126.7 ± 46.9, respectively (P = 0.0291). This tendency was stronger in patients without cardiovascular events. Conclusion In patients with CKD, there is an association between ferrokinetics and LVMI. We have to be mindful not only of anaemia but also of ferrokinetics.


Phosphorus magnetic resonance spectroscopy of partially blocked muscle glycolysis. An in vivo study of phosphoglycerate mutase deficiency.
In vivo phosphorus magnetic resonance spectroscopy was used to evaluate the changes in muscle bioenergetics in a patient with a partial glycolytic block. Phosphoglycerate mutase-deficient muscle showed the following evidence: Abnormal accumulation of sugar phosphates does occur, even when 6% enzyme activity is present. The elimination of sugar phosphates was faster than in complete glycolytic blocks. Mild intracellular acidosis occurred during ischemic exercise. The energy state was slightly low at rest but not during exercise. Postexercise recovery was mildly slowed. These findings suggest that phosphorus magnetic resonance spectroscopy can detect partial defects, as well as full glycolytic blocks, in muscle metabolism.


Macular choroidal neovascularization in myopic eyes after phakic intraocular lens implantation.
To analyze the development and characteristics of choroidal neovascularization in highly myopic patients corrected by the implantation of phakic intraocular lenses (PIOLs). This retrospective, noncomparative interventional case series studied the development of choroidal neovascularization in 522 consecutive highly myopic eyes (spherical equivalent refraction >-6.00 diopters [D] and/or axial length >26 mm) (323 patients) corrected by the implantation of PIOLs, the treatment performed, and the results obtained. Parameters evaluated were best spectacle-corrected visual acuity (BSCVA) before and after treatment of choroidal neovascularization, and the interval between refractive surgery and the development of choroidal neovascularization. Follow-up ranged from 12 to 145 months (mean: 60.4 +/- 39.1 months). In 12 (2.29%) eyes, choroidal neovascularization developed after PIOL implantation at a mean interval time of 33.7 +/- 29.6 months (range: 1 to 87 months). Using Kaplan-Meier analysis, the risk of choroidal neovascularization in patients with high myopia corrected by PIOL implantation was 0.57% at 5 months, 0.81% at 18 months, 1.31% at 24 months, and 3.72% at 87 to 145 months. No statistically significant differences were found between patients with and without choroidal neovascularization in the following parameters: axial length (P=.826), age (P=.296), initial BSCVA (P=.085), spherical equivalent refraction (P=.663), and follow-up (P=.955). Phakic intraocular lens implantation for the correction of high myopia does not play a role in the development of choroidal neovascularization.


Improvement of Electrical Characteristics and Stability of Amorphous Indium Gallium Zinc Oxide Thin Film Transistors Using Nitrocellulose Passivation Layer.
In this research, nitrocellulose is proposed as a new material for the passivation layers of amorphous indium gallium zinc oxide thin film transistors (a-IGZO TFTs). The a-IGZO TFTs with nitrocellulose passivation layers (NC-PVLs) demonstrate improved electrical characteristics and stability. The a-IGZO TFTs with NC-PVLs exhibit improvements in field-effect mobility (μFE) from 11.72 ± 1.14 to 20.68 ± 1.94 cm2/(V s), threshold voltage (Vth) from 1.85 ± 1.19 to 0.56 ± 0.35 V, and on/off current ratio (Ion/off) from (5.31 ± 2.19) × 107 to (4.79 ± 1.54) × 108 compared to a-IGZO TFTs without PVLs, respectively. The Vth shifts of a-IGZO TFTs without PVLs, with poly(methyl methacrylate) (PMMA) PVLs, and with NC-PVLs under positive bias stress (PBS) test for 10,000 s represented 5.08, 3.94, and 2.35 V, respectively. These improvements were induced by nitrogen diffusion from NC-PVLs to a-IGZO TFTs. The lone-pair electrons of diffused nitrogen attract weakly bonded oxygen serving as defect sites in a-IGZO TFTs. Consequently, the electrical characteristics are improved by an increase of carrier concentration in a-IGZO TFTs, and a decrease of defects in the back channel layer. Also, NC-PVLs have an excellent property as a barrier against ambient gases. Therefore, the NC-PVL is a promising passivation layer for next-generation display devices that simultaneously can improve electrical characteristics and stability against ambient gases.


Novel spiral mapping catheter facilitates observation of the time-to-pulmonary vein isolation during cryoballoon ablation.
Observation of the time-to-pulmonary vein isolation (TTI) by a spiral mapping catheter has emerged as a valuable procedural parameter in cryoballoon pulmonary vein isolation (PVI). The 1st generation spiral mapping catheter (Achieve, SMC1) has been available as an 8-polar catheter with a distal loop diameter of 15 or 20 mm. The novel spiral mapping catheter (Achieve Advance, SMC2) was designed as a true guidewire and is available, in addition to the sizes of the SMC1, as a 10-polar mapping catheter with a distal loop diameter of 25 mm. Whether these novel features of SMC2 influence procedural characteristics of Cryo-PVI in comparison to SMC1 has not been reported. In this prospective cohort study 158 patients (age 65.1 ± 12.4 years, female 39%, paroxysmal AF 60%) undergoing PVI with the 2nd generation cryoballoon were included. SMC1 was used in 57 patients (36%), whereas 101 patients (64%) underwent Cryo-PVI with the SMC2. All PVs (623/623, 100%) were isolated successfully. Mean procedure duration was 72.0 ± 18.9 min in the SMC1 group and 74.4 ± 19.1 min in the SMC2 group (p = 0.432). Mean fluoroscopy time was also not different between both study groups (SMC1 15.7 ± 6.6 min, SMC2 15.7 ± 7.3 min, p = 0.593). TTI was observed in 68.6% of pulmonary veins in the SMC1 group, whereas TTI observation rate was 82.6% in the SMC2 group (p < 0.001). Number of freezes (5.5 ± 1.5 vs. 6.5 ± 1.9; p = 0.001) and total freeze duration (14.1 ± 4.5 vs. 17.6 ± 5.6; p < 0.001) were increased in the SMC2 group. SMC2 significantly increases TTI observation rate during Cryo-PVI. Procedure duration and fluoroscopy time are similar and number of freezes and total freeze duration are increased compared to PVI with SMC1 due to decreased stability and maneuverability of SMC2.


Efficacy of non-steroidal anti-inflammatory drugs for low back pain: a systematic review of randomised clinical trials.
To assess the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) for low back pain. Computer aided search of published randomised clinical trials and assessment of the methods of the studies. 26 randomised clinical trials evaluating NSAIDs for low back pain were identified. Score for quality (maximum = 100 points) of the methods based on four categories: study population; interventions; effect measurement; data presentation and analysis. Determination of success rate per study group and evaluation of different contrasts. Statistical pooling of placebo controlled trials in similar patient groups and using similar outcome measures. The methods scores of the trials ranged from 27 to 83 points. NSAIDs were compared with placebo treatment in 10 studies. The pooled odds ratio in four trials comparing NSAIDs with placebo after one week was 0.53 (95% confidence intervals 0.32 to 0.89) using the fixed effect model, indicating a significant effect in favour of NSAIDs compared with placebo. In nine studies NSAIDs were compared with other (drug) therapies. Of these, only two studies reported better results of NSAIDs compared with paracetamol with and without dextropropoxyphene. In the other trials NSAIDs were not better than the reference treatment. In 11 studies different NSAIDs were compared, of which seven studies reported no differences in effect. There are flaws in the design of most studies. The pooled odds ratio must be interpreted with caution because the trials at issue, including the high quality trials, did not use identical outcome measures. The results of the 26 randomised trials that have been carried out to date, suggest that NSAIDs might be effective for short-term symptomatic relief in patients with uncomplicated low back pain, but are less effective or ineffective in patients with low back pain with sciatica and patients with sciatica with nerve root symptoms.


Loss of imprinting and cancer.
Imprinting is defined as the parental allele-specific expression of a very limited set of genes (about 50-80). This regulation depends upon an epigenetic marking of parental alleles during gametogenesis. Monoallelic expression ensures that the levels of the proteins encoded by imprinted genes, important factors of embryonic growth, placental growth or adult metabolism, are assured. Without precise control of their expression, developmental abnormalities result, as is shown by a number of hereditary over-growth syndromes, including Beckwith-Wiedemann syndrome. The regulation of imprinted genes is largely dependent on methylation marks, which are laid down during embryological development of germ cells. Once in place, the methylation status of precise chromosomal regions, Imprinting Control Regions (ICRs), is read by either of two mechanisms, chromatin barrier formation or untranslated RNAs, thereby ensuring that only the maternal or paternal allele is expressed. Each imprinted gene is classified as maternal or paternal according to the expressed allele. The stability of the marked regions in somatic cells is maintained through each cellular replication by a methylation enzyme complex containing Dnmt1. Although the major reading mechanisms of imprinted status are known, chromatin boundary formation by CTCF and untranslated RNAs, the molecules elaborating the initial ICR methylation, are just being uncovered. Mis-regulation of imprinted gene expression (loss of imprinting [LOI]) is seen frequently and precociously in a large variety of human tumours, making LOI a potentially valuable tool for both diagnosis and treatment. In fact, LOI is presently considered the most abundant and most precocious alteration in cancer. The present review proposes a mechanism responsible for LOI, as well as its eventual value in tumour diagnosis and prognosis.


Tuning the conductance of dirac fermions on the surface of a topological insulator.
We study the transport properties of the Dirac fermions with a Fermi velocity v{F} on the surface of a topological insulator across a ferromagnetic strip providing an exchange field J over a region of width d. We show that the conductance of such a junction, in the clean limit and at low temperature, changes from oscillatory to a monotonically decreasing function of d beyond a critical J. This leads to the possible realization of a magnetic switch using these junctions. We also study the conductance of these Dirac fermions across a potential barrier of width d and potential V0 in the presence of such a ferromagnetic strip and show that beyond a critical J, the criteria of conductance maxima changes from chi=eV{0}d/variant Planck's over v{F}=npi to chi=(n+1/2)pi for integer n. We point out that these novel phenomena have no analogs in graphene and suggest experiments which can probe them.


Identification of the gene for disaggregatase from Methanosarcina mazei.
The gene sequences encoding disaggregatase (Dag), the enzyme responsible for dispersion of cell aggregates of Methanosarcina mazei to single cells, were determined for three strains of M. mazei (S-6(T), LYC and TMA). The dag genes of the three strains were 3234 bp in length and had almost the same sequences with 97% amino acid sequence identities. Dag was predicted to comprise 1077 amino acid residues and to have a molecular mass of 120 kDa containing three repeats of the DNRLRE domain in the C terminus, which is specific to the genus Methanosarcina and may be responsible for structural organization and cell wall function. Recombinant Dag was overexpressed in Escherichia coli and preparations of the expressed protein exhibited enzymatic activity. The RT-PCR analysis showed that dag was transcribed to mRNA in M. mazei LYC and indicated that the gene was expressed in vivo. This is the first time the gene involved in the morphological change of Methanosarcina spp. from aggregate to single cells has been identified.


Achieving uterine auto-transplantation in a sheep model using iliac vessel anastomosis: a short-term viability study.
To investigate, develop and evaluate anatomical, surgical and anastomotic aspects necessary for a successful uterine transplant in a large-animal model. Sheep model; longitudinal study involving five ewes. Royal Veterinary College, London, UK. Five ewes of proven fertility. The uterine allograft along with the internal iliacs, and uterine arterial and venous tree all intact were harvested en bloc. An end-to-side anastomosis was performed between the external iliac vessels and the internal iliac vessels of the graft using 6-0 polypropylene. Successful reperfusion of the graft was initially judged by the color shift of the uterus during reperfusion. Blood flow past the venous and arterial anastomotic sites was also ensured by visual inspection, together with pulse oximetry and multispectral imaging. Operative details (retrieval, ischemic, clamping, reperfusion and recipient hysterectomy duration); physiological profiles; gross morphology and histopathology. Five autotransplants were performed. One procedure was abandoned because of the inappropriate size of sheep model. Another procedure was halted because the animal suffered from respiratory failure in the immediate intra-operative period. Three transplants were completed. In those, at least two of four possible anastomoses were finished and the grafted uteri demonstrated immediate perfusion and appropriate viability 45 min post-operatively. Internal to external iliac vessel anastomoses are an acceptable surgical technique that should be applied in a human model to ensure adequate subsequent uterine perfusion.


Magnesium and immune function: an overview.
Mg participates in immune responses in numerous ways: as a cofactor for immunoglobulin synthesis, C'3 convertase, immune cell adherence, antibody-dependent cytolysis, IgM lymphocyte binding, macrophage response to lymphokines, T helper-B cell adherence, binding of substance P to lymphoblasts and antigen binding to macrophage RNA. Mg deficiency in rodents impairs IgG synthesis and cell-mediated immunity; complications include thymus atrophy, elevated IgE, hypereosinophilia, histaminosis and lymphoma. Immunologic sequelae of Mg deficiency in humans are subtle and may be affected by genetic control of blood cell Mg concentration. Abnormal C' activation, excess antibody production and susceptibility to allergy and to chronic fungal and viral infections have been reported. Mg appears to play a protective role in acute allergic reactions.


Determination of environmental persistence and thermogravimetric analysis of paper artificially aged by photoirradiation.
Fabriano paper was aged by irradiation with ultraviolet light (k=310) in a veterometer for 300 hours. At fixed time intervals, samples of the paper under test were analysed by titanium dioxide photosensor to determine electrochemically the "environmental persistence" index, by a suitable conductimeter method, to determine the specific conductivity variation and by thermogravimetry to determine the moisture content, the onset temperature of the cellulose degradation process and the value of the activation energy of the same process. The behaviour of these different types of indicators displayed approximately monotonous trends as a function of time.


Psychosocial issues of AIDS in the nursing care of homosexual men and their significant others.
The psychosocial issues of homosexual men with AIDS and their significant others pose a profound nursing care challenge. The nurse's knowledge and sensitivity to these issues is necessary to meet the challenge of this patient group. Unique aspects of AIDS such as youth, stigma, contagiousness and sexual transmission, combined with neurologic complications, resultant anxiety and depression, and drug and alcohol use present a complicated array of needs to be addressed by the nurse. Crisis and existential theory frameworks are useful to apply to the nursing process when caring for patients facing a life-threatening illness. Goals such as maintenance of psychological well-being and the promotion of psychological growth can occur as the nurse assists the patient and his significant others to confront existential concerns. These concerns include death, meaning, freedom, and isolation. Providing nursing care for this patient population also has an impact on the nurse as he or she confronts mortality and sexuality. This calls for the nurse to examine his/her values and attitudes in order to provide optimal nursing care. In caring for homosexual men with AIDS and their significant others, the nurse is likely to experience personal growth. As the nurse assists the patient and his loved ones to live as they confront potential death, the nurse often gains an added appreciation of life.


Rituximab: modes of action, remaining dispute and future perspective.
Less than two decades ago, immunotherapy joined chemotherapy and radiotherapy as an effective approach for the treatment of cancer. The anti-CD20 monoclonal antibody, rituximab, is now used to treat almost all types of non-Hodgkin's B-cell lymphomas, and it could be useful in the treatment of other diseases with B-cell involvement. Upon binding, rituximab induces death of the target cells. It seems to act not only by activating immune system defense mechanisms such as complement-dependent and antibody-dependent cellular cytotoxicity, but also by inducing direct cell death. In this paper, we review current knowledge on rituximab mechanisms of action, with particular attention to its direct effects, and also highlight potential future avenues of research.


Nod factors and a diffusible factor from arbuscular mycorrhizal fungi stimulate lateral root formation in Medicago truncatula via the DMI1/DMI2 signalling pathway.
Legumes form two different types of intracellular root symbioses, with fungi and bacteria, resulting in arbuscular mycorrhiza and nitrogen-fixing nodules, respectively. Rhizobial signalling molecules, called Nod factors, play a key role in establishing the rhizobium-legume association and genes have been identified in Medicago truncatula that control a Nod factor signalling pathway leading to nodulation. Three of these genes, the so-called DMI1, DMI2 and DMI3 genes, are also required for formation of mycorrhiza, indicating that the symbiotic pathways activated by both the bacterial and the fungal symbionts share common steps. To analyse possible cross-talk between these pathways we have studied the effect of treatment with Nod factors on mycorrhization in M. truncatula. We show that Nod factors increase mycorrhizal colonization and stimulate lateral root formation. The stimulation of lateral root formation by Nod factors requires both the same structural features of Nod factors and the same plant genes (NFP, DMI1, DMI2, DMI3 and NSP1) that are required for other Nod factor-induced symbiotic responses such as early nodulin gene induction and cortical cell division. A diffusible factor from arbuscular mycorrhizal fungi was also found to stimulate lateral root formation, while three root pathogens did not have the same effect. Lateral root formation induced by fungal signal(s) was found to require the DMI1 and DMI2 genes, but not DMI3. The idea that this diffusible fungal factor might correspond to a previously hypothesized mycorrhizal signal, the 'Myc factor', is discussed.


Current epidemiological trend of tuberculosis in Japan.
To observe the recent epidemiological trend of tuberculosis and to determine the factors related to the deteriorating trend in incidence and mortality rates in Japan. Descriptive analyses of tuberculosis notification rates and mortality rates by age, sex, year and birth-cohort. The decline in the tuberculosis notification rate has started slowing down since around 1980. Among the cohorts born before 1950, the trend of notification rate by age has levelled off since around 1980. The reduction in the tuberculosis mortality rate has also recently begun to slow down, but later and to a lesser extent than that of the notification rate. Although deaths due to tuberculosis occur mostly among the elderly, the rate of decline in mortality among middle-aged males has slowed down recently. The trend in the mortality rate of birth-cohorts has recently shown an upward trend with age. A major cause of the current stagnation of the decline in notification rates is the increase in the elderly population with a high prevalence of tuberculosis infection in the past, who are more likely to develop the disease as they approach biological senescence. Other possible causes are a gradual shift of the tuberculosis problem to socio-economically deprived segments of the urban population, and behavioural changes causing delay in case-finding.


Health care reform in the 1990s: an analysis of the problems and three proposals.
National health care reform is arguably the most important domestic policy issue of the 1990s and certainly is one of the most difficult and pressing of current social issues. It also is clear that health care reform is as much a political as it is a public policy issue. This article evaluates three health care reform proposals by members of the U.S. Congress--one single-payer model and two "play or pay" models--to analyze how well they responded to the underlying crisis in the American health care system. Specific criteria for evaluating health care reform proposals are delineated, and an evaluation of the competing models is provided.


Nhs: network-based hierarchical segmentation for cryo-electron microscopy density maps.
Cryo-electron microscopy (cryo-EM) experiments yield low-resolution (3-30 Å) 3D-density maps of macromolecules. These density maps are segmented to identify structurally distinct proteins, protein domains, and subunits. Such partitioning aids the inference of protein motions and guides fitting of high-resolution atomistic structures. Cryo-EM density map segmentation has traditionally required tedious and subjective manual partitioning or semisupervised computational methods, whereas validation of resulting segmentations has remained an open problem in this field. We introduce a network-based hierarchical segmentation (Nhs) method, that provides a multi-scale partitioning, reflecting local and global clustering, while requiring no user input. This approach models each map as a graph, where map voxels constitute nodes and weighted edges connect neighboring voxels. Nhs initiates Markov diffusion (or random walk) on the weighted graph. As Markov probabilities homogenize through diffusion, an intrinsic segmentation emerges. We validate the segmentations with ground-truth maps based on atomistic models. When implemented on density maps in the 2010 Cryo-EM Modeling Challenge, Nhs efficiently and objectively partitions macromolecules into structurally and functionally relevant subregions at multiple scales.


[Modeling of the mechanism of interactions of oligonucleotides with 3'-end of the yeast tRNA(Phe)].
Three dimensional atomic models of complexes between 10-, 15-mer long oligonucleotides and east tRNAPhe have been calculated. It has been found that the fast-forming primary complexes are the major groove complexes with the coaxial acceptor- and T-steams of the tRNA(Phe). Oligonucleotide forms a triplex of the recombinant R-triplex type. The long steams allow to make a "strong complexes" whith oligonucleotide, which delivers its 3'-end nucleotides to the vicinity of the T-loop, adjacent to the steam. These nucleotides destabilize the loop structure and initiate conformational rearrangement with a local destruction of the tRNA(Phe) and formation of the final tRNA(Phe)-oligonucleotide complementary complex. The primary complex formation and following destruction of the tRNA(Phe) constitutes the mechanism of the 'molecular wedge'. The effective anticense oligonucleotide should consist of the three segments: 1--complex initiator, 2--complex formative, 3--loop destructor an have to be complementary to the tRNA structure element of [(free end)/loop-steam-loop].


Determinants of early-onset cardiovascular disease: a case-control study of young myocardial infarction patients.
The present case-control investigation was undertaken with the aim of thoroughly assessing the risk profile of young coronary patients and to correlate it with their endothelium-dependent vasodilation and with the presence of atherosclerotic lesions. Forty-eight subjects (age < 41 years) diagnosed with myocardial infarction were screened. They were matched 1:1, for age and sex, with controls. We evaluated the serum total, HDL-, and LDL-cholesterol, triacylglycerols, fibrinogen, homocysteine, folic acid, vitamin B12, vitamin E, antioxidant capacity, and uric acid levels, and we also analyzed the patients for the presence of Helicobacter pylori and of methylenetetrahydrofolate reductase and cystathionine beta-synthase genetic mutations. Post-ischemic vasodilation of the brachial artery was evaluated and the intima-media thickness of the carotid arteries was measured at echo-Doppler. A statistical modeling selection between block variables revealed that smoking, the apoepsilon genotype, dyslipidemia, fibrinogen, vitamin E concentrations, and intima-media thickness were important predictors of cardiovascular disease, with an accuracy of 91.7%. On the basis of these results, we believe that acute coronary events in young subjects should be followed by a screening of their siblings, as they might be at higher risk for cardiovascular disease.


Ageing: from inflammation to cancer.
Ageing is the major risk factor for cancer development. Hallmark of the ageing process is represented by inflammaging, which is a chronic and systemic low-grade inflammatory process. Inflammation is also a hallmark of cancer and is widely recognized to influence all cancer stages from cell transformation to metastasis. Therefore, inflammaging may represent the biological phenomena able to couple ageing process with cancer development. Here we review the molecular and cellular pathway involved in age-related chronic inflammation along with its potential triggers and their connection with cancer development.


UK doctors awareness and use of specified electronic evidence-based medicine resources.
There is an increasing emphasis placed on evidence-based medicine, and the use of relevant resources. The aim of this study is to evaluate UK doctor's awareness and use of specified evidence-based medicine (EBM) electronic resources. Respondents were invited to complete an online questionnaire and 636 were completed. The most frequently used EBM resources available via the National Library for Health were the most established and well-known resources, namely, Medline/PubMed. The top three resources not freely available via the National Library for Health were general non-specialist specific resources. Over three-quarters of the respondents had not heard of the American resources and resources that had only ever been electronic were not widely known or used by the respondents. The introduction of new electronic resources to doctors must involve more than simply promoting the URL/web location. In fact, the development of a comprehensive list of resources highlighting their strengths (and weaknesses) may be beneficial for busy doctors.


Analysis of brain activity during clenching by fMRI.
It has been considered difficult to obtain satisfactory functional magnetic resonance images (fMRI) during jaw movements because the head motion during jaw movements makes artefacts on the images. To avoid these artefacts, we chose clenching task and larger pixels to allow some head motion of the subjects. Further the study discarded all data from subjects whom the head was evaluated to move more than 0.3 mm. The study examined 10 healthy right-handed volunteers with echo-planar magnetic resonance (MR) imaging and functional MR signal intensity changes could be obtained in all subjects. However, in the analysis of each pixel of individuals, three different types of pixels were established. It was determined that the pixels that synchronized positively with the task on/off and where signal intensity increase was below 10% expressed the real brain activity. Pixels showing the real brain activity were found in the sensory, motor and pre-motor cortexes in both hemispheres in all subjects, and also in the insula region of two subjects. No pixels were found in the striatum and supplementary motor areas. From the above careful consideration and individual analysis of each pixel, it was concluded that brain activity during the clenching task could be obtained by fMRI.


Mucogingival grafting procedures--an update.
Gingival recession is the exposure of the root surface due to the apical migration of the gingival margin. It is a common feature in the general population and can often lead the patient to seek treatment. Mucogingival therapy may be required to prevent further recession, correct aesthetic problems, aid plaque control and reduce dentine hypersensitivity. There are several different mucogingival treatment approaches which usually involve the manipulation of the patient's tissues to augment the gingivae and cover the exposed root. This article reviews the management procedures that are indicated for the treatment of gingival recession. To make the dental practitioner aware of the different surgical modalities available for the treatment of gingival recession and improve his/her ability to identify patients who might benefit from them.


SIDS-protective infant care practices among Auckland, New Zealand mothers.
To survey the knowledge and implementation of sudden infant death syndrome (SIDS)-protective infant care practices in mothers of infants aged less than 4 months. A postal survey was carried out of knowledge of SIDS risk factors and infant care practices of 200 mothers with infants aged 6-8 weeks and 3-4 months. Mothers who could cite supine sleeping as protective comprised 84%, while 73% knew that smoking was a risk factor. Fewer knew that room sharing, keeping the face clear of bedding, and avoiding bed sharing and overheating are also protective. Fifty-four percent of the infants usually room-share with a parent, while 39% both room-share and sleep in their own bed. Sixteen percent usually co-slept for part or all of the night. Nearly one-third used pacifiers. Mothers who smoked during pregnancy comprised 8%, while 7% had smoked in the last 24 hours. Most infants (97%) had been breastfed at some time. Maternal education of the benefits of supine sleeping, not smoking, and breastfeeding appear well understood by these mothers. However, more education is needed about other SIDS-protective behaviours such as keeping the face clear and sleeping the infant in their own bed in the parents' room.


Nuclear magnetic resonance studies of amino acids and proteins. Deuterium nuclear magnetic resonance relaxation of deuteriomethyl-labeled amino acids in crystals and in Halobacterium halobium and Escherichia coli cell membranes.
We have obtained deuterium (2H) Fourier transform nuclear magnetic resonance (NMR) spectra of zwitterionic L-[beta-2H3]alanine, DL-[gamma-2H6]valine, DL-[beta, gamma-2H4]threonine, L-[delta-2H3]leucine, and L-[alpha, beta, gamma, gamma', delta-2H10]isoleucine in the crystalline solid state and have determined the deuteriomethyl group spin-lattice relaxation rates as a function of temperature. The results yield the Arrhenius activation energies (delta E) for methyl rotation, and through use of a suitable mathematical model, rotational correlation times, tau c. For alanine, valine, threonine, leucine, and isoleucine at 37 degrees C, tau c and delta E values are 780, 100, 40, 38, and 18 ps and 22, 14.0, 17.6, 15.5, and 8.6 kJ, respectively. For L-[beta-2H3]alanine in the zwitterionic lattice, a spin-lattice relaxation time (T1) minimum of 2.1 +/- 0.3 ms is observed (at 0 degree C), in excellent agreement with the 1.92-ms prediction of the mathematical model. Similar tau c and delta E measurements are reported for bacteriorhodopsin in the purple membrane of Halobacterium halobium R1 and for Escherichia coli cell membranes. Overall, our results demonstrate a great similarity between the dynamics in amino acid crystals and in membrane proteins. However, threonine exhibits a nonlinear Arrhenius behavior in bacteriorhodopsin, and in the valine-, leucine-, and isoleucine-labeled membrane samples at higher temperatures (approximately greater than 37 degrees C), there is evidence of an additional slow side-chain motion. The lipid phase state in E. coli does not appear to influence, on the average, the dynamics of the valine side chains. These results indicate that the sensitivity of the deuterium NMR technique is now adequate to study in moderate detail the dynamics of most types of amino acids in a membrane protein and that adequate sensitivity, in some instances, should be available for the study of individual amino acids in suitably labeled membrane proteins.


IL-22 Is Deleterious along with IL-17 in Allergic Asthma but Is Not Detrimental in the Comorbidity Asthma and Acute Pneumonia.
There is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. To investigate the role of IL-22, we used IL-22 deficient mice (IL-22 KO) sensitized and challenged with ovalbumin (OVA) and compared with wild type (WT) animals exposed to OVA. IL-22 KO animals exposed to OVA showed a decreased number and frequency of eosinophils, IL-5 and IL-13 in the airways, reduced mucus production and pulmonary inflammation. In addition, IL-22 KO animals exhibited a decreased percentage and number of lung CD11c+CD11b+ cells and increased apoptosis of eosinophils. Th17 cell transfer generated from IL-22 KO to animals previously sensitized and challenged with OVA caused a reduction in eosinophil frequency and number in the airways compared to animals transferred with Th17 cells generated from WT mice. Therefore, IL-22 is deleterious with concomitant secretion of IL-17. Our findings show a pro-inflammatory role for IL-22, confirmed in a model of allergen-free and allergen-specific immunotherapy. Moreover, during the comorbidity asthma and pneumonia that induces neutrophil inflammation, IL-22 was not detrimental. Our results show that targeting IL-22 would negatively affect the survival of eosinophils, reduce the expansion or migration of CD11c+CD11b+ cells, and negatively regulate allergic asthma.


Chemical quenching of singlet oxygen by betanin.
Betanin is the best known natural dye belonging to the betacyanin family. In this work, efficient singlet oxygen quenching by betanin in deuterated water with the rate constant 1.20 ± 0.15 × 10(8) M(-1) s(-1) is reported, deduced from the (1)O2 phosphorescence decays measured as a function of betanin concentration. The quenching occurs by a chemical mechanism, as confirmed by the analysis of the transient absorption kinetics at the probe λ ∼ 535 nm, by comparison of the initial triplet signal amplitude of perinaphthenone acting as the (1)O2 photosensitizer with the final bleaching signal of betanin. The main betanin oxidation product is 2-decarboxy-2,3-dehydrobetanin, with its formation observed as the transient absorption signal at λ ∼ 445 nm. LC-MS/MS analysis of the photolyzed solutions supports the product identification as 2-decarboxy-2,3-dehydrobetanin, based on the molecular ion [M](+) observed at m/z 505. Isobetanin also undergoes a similar photooxidation reaction.


Electrolytes and clinical outcomes in patients with acute ischemic stroke or transient ischemic attack.
Abnormal electrolytes were closely related to the prognosis of various diseases, the prognostic role of electrolytes in stroke has not been investigated well. We aimed to investigate the association between electrolytes and clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Data were recruited from the China National Stroke Registry III study. Patients were classified into three groups according to tertiles and the normal range of each electrolyte. Multivariable logistic and Cox proportional hazards regressions were adopted to explore the associations of electrolytes with poor functional outcomes [modified Rankin Scale (mRS) 3-6/2-6] and all-cause death at 3 months and 1 year. A total of 10,299 eligible patients were enrolled. After adjusted for confounding factors, the first tertile electrolytes were associated with increased risk of poor functional outcome (mRS score 3-6) at 1 year, the adjusted odds ratios (95% confidence intervals) were 1.33 (1.14-1.55) for potassium, 1.41 (1.20-1.60) for sodium, 1.27 (1.08-1.48) for chloride, compared with the second tertile. Similar results were found when poor functional outcome was defined as mRS score 2-6 and all-cause death. However, almost no significant association was present of calcium with these outcomes. All results were consistent when each electrolyte was classified into three groups according to the normal range and the outcomes timepoint was set at 3 months. Lower levels of potassium, sodium, chloride but not calcium were associated with higher risk of poor functional outcomes and death in patients with AIS or TIA.


Ethnic and religious discrimination: the multifaceted role of religiosity and collective self-esteem.
This study analyses the roles of collective self-esteem and religiosity in the relationship between discrimination and psychological distress among a sample of 432 recent immigrants from Haiti and Arab countries living in Montreal, Quebec. Collective self-esteem (CSE), religiosity, discriminatory experiences, and psychological symptoms of depression and anxiety were assessed. Regression analyses revealed direct negative effects of discrimination, CSE, and religiosity on psychological distress for the entire sample. CSE, however, also appeared to moderate the effects of discrimination on psychological distress. Participants with higher CSE reported lower levels of anxiety and depression as a result of discrimination compared to those who expressed lower CSE levels. The results suggest that the relationship between CSE, discrimination, and psychological distress must be reexamined in light of recent sociopolitical changes and the upsurge in ethnic and religious tensions following the war on terror.


Suicidal behaviour among alcohol-dependent Danes attending outpatient treatment.
The association between alcohol dependence and suicidal behaviour is well established and patients with suicidal behaviour in treatment for alcohol dependence present a considerable challenge for clinical services. The aim of this study is to identify risk factors for suicide attempts and to evaluate the outcome of treatment in patients in treatment for alcohol dependence. Semi-structured, detailed interviews were administered at baseline and at three sequential follow-up interviews with a large sample of 1692 patients at an outpatient treatment centre in the county of Funen in Denmark. Characteristics of, predictors for and outcome among suicidal patients were studied. Alcohol-dependent patients with a history of suicide attempts were found to constitute a highly selected group in alcohol abuse treatment as they often had a more severe course of alcohol dependence, were unemployed, younger, were more often lowly educated, and had more physical and psychiatric problems. Traumatic childhood experience related to physical or sexual abuse was found as a major predictor for suicidal behaviour among alcohol-dependent patients. We found no significant difference in the effect of treatment in patients with and without suicidal behaviour. These results support the hypothesis that alcohol-dependent patients with a history of suicide attempts are a selected group in respect to a number of demographical and psychosocial factors, but we found no difference in the outcome of treatment. This may imply that suicidal patients in treatment for alcohol abuse are treated effectively within the present treatment settings.


Role of the M3 muscarinic acetylcholine receptor in beta-cell function and glucose homeostasis.
The release of insufficient amounts of insulin in the presence of elevated blood glucose levels is one of the key features of type 2 diabetes. Various lines of evidence indicate that acetylcholine (ACh), the major neurotransmitter of the parasympathetic nervous system, can enhance glucose-stimulated insulin secretion from pancreatic beta-cells. Studies with isolated islets prepared from whole body M(3) muscarinic ACh receptor knockout mice showed that cholinergic amplification of glucose-dependent insulin secretion is exclusively mediated by the M(3) muscarinic receptor subtype. To investigate the physiological relevance of this muscarinic pathway, we used Cre/loxP technology to generate mutant mice that lack M(3) receptors only in pancreatic beta-cells. These mutant mice displayed impaired glucose tolerance and significantly reduced insulin secretion. In contrast, transgenic mice overexpressing M(3) receptors in pancreatic beta-cells showed a pronounced increase in glucose tolerance and insulin secretion and were resistant to diet-induced glucose intolerance and hyperglycaemia. These findings indicate that beta-cell M(3) muscarinic receptors are essential for maintaining proper insulin secretion and glucose homeostasis. Moreover, our data suggest that enhancing signalling through beta-cell M(3) muscarinic receptors may represent a new avenue in the treatment of glucose intolerance and type 2 diabetes.


[Analysis of risk factors of recurrence of hepatocellular carcinoma after control of surgical-risk-factors].
R0 resection, Pringle maneuver, intraoperative massive blood loss and perioperative blood transfusion have been definitely recognized to be surgery-related risk factors of recurrence of hepatocellular carcinoma (HCC) in recent years. The aim of this study was to investigate the post-operative risk factors of recurrence of HCC after control of the above mentioned risk factors. 288 consecutive HCC patients underwent hepatectomy with selective regional vascular occlusion by the same surgical team. All patients had R0 resection, less than 800 ml blood loss and had no perioperative blood transfusion. The clinical and pathological factors were retrospectively analyzed. The total 1-year, 3-year and 5-year disease-free survival rate (DFS) was 74.9%, 49.3% and 34.3%, respectively. Univariate analysis showed that serum gamma-glutamyl-transferase rise >55 U/L, AFP > 400 ng/ml, tumor diameter >5 cm, multi-focal lesions, satellite nodules, poor differentiation, microvascular invasion, envelope invasion, postoperative liver insufficiency, preoperative TACE and postoperative TACE were significantly associated with poor DFS. Multivariate Cox analyses revealed that tumor size, satellite nodules, poor differentiation, microvascular invasion and postoperative liver insufficiency were independent prognostic predictors associated with shorter DFS. According to the results of multivariate Cox analysis of 158 cases with at least one risk factor selected from the whole group, further analysis demonstrated that perioperative TACE was not significantly associated with the median DFS (P > 0.05 for all). Selective regional vascular occlusion may effectively control the surgiury-related risk factors of recurrence of HCC. Tumor features are the main affecting factors of DFS. Preoperative or postoperative TACE do not benefit patients who received curative resection.


The economic impact of educational training assessed by the Handling Questionnaire with three inhalation devices in asthma and Chronic Obstructive Pulmonary Disease patients.
The usability of inhalation devices depends on several factors, eg, the drug to inhale, device handling, and patients' training. Usability is then presumed to have economic consequences. To assess and compare the cost of patients' training for proper usability of Breezhaler and Genuair (both dry powder inhalers) and Respimat (a soft mist inhaler) in asthma and chronic obstructive pulmonary disease (COPD) outpatients. The acceptance and handling of the three devices were investigated by means of the Handling Questionnaire. The time spent in specific training for ensuring a proper actuation and the corresponding costs were also calculated. Linear and logistic regressions were used in order to investigate the factors influencing proper handling of the devices. A significance level of P<0.05 was accepted. According to both the patients' and the nurse's judgments, Genuair and Respimat were perceived as the easiest devices to use, while Breezhaler required the highest number of attempts for achieving the first proper actuation (2.6 vs 1.6; P<0.0001). The total training cost per patient (including the nurse's time for demonstration and that for attending the patients' maneuvers) was €1.38±€1.21. Breezhaler was found to be the most expensive as the cost per patient was €2.35±€1.26, which was three to four times higher than that of Genuair and Respimat (both devices involved a cost of <€1 per patient, with negligible differences between each other). Asthma and COPD patients showed a similar trend, with better outcomes reported for asthma patients probably due to lower age. Substantial differences were found to exist in patients' acceptability and handling of the three devices. The economic impact of specific training was also different and strictly related to the comprehension of the procedure for actuation of each device. Respimat as a soft mist inhaler and Genuair as an metered-dose inhaler proved to be the most convenient in economic terms also.


Effect of excessive dietary vitamin E on the chick.
Day-old male broiler chicks were fed a broiler ration for five weeks to which was added one of the following levels of dl-alpha tocopheryl acetate; 0; 2,000; 4,000; 8,000; 16,000; 32,000, and 64,000 I.U./kg. The chicks fed diets containing 4,000 I.U./kg. or more of vitamin E showed decreased pigmentation in their beaks, feet and shanks, and liver as a percent of body weight was significantly increased. Feeding at least 8,000 I.U./kg of the vitamin significantly reduced chick body weight and resulted in waxy appearing feathers. Dietary inclusion of 16,000 I.U./kg. or more of vitamin E significantly increased feather, spleen, liver, and plasma vitamin E content.


Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus.
Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and functionality. Here, we discuss the differences in clinical outcome and immune response following influenza and RSV. Specifically, we focus on differences in their recognition by innate immunity; the strategies used by each virus to evade these early immune responses; and effects across the innate-adaptive interface that may prevent long-lived memory generation. Thus, by comparing these globally important pathogens, we highlight mechanisms by which optimal antiviral immunity may be better induced and discuss the potential for these insights to inform novel vaccines.


Comparison of umbilical artery Doppler and non-stress test in assessment of fetal well-being in gestational diabetes mellitus: A prospective cohort study.
Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy and is related to poor perinatal outcomes. Reduction of neonatal complications of GDM is feasible by assessment of fetal well-being. Both fetal Doppler and NST are used for the screening of high-risk pregnancies. We aimed to compare the non-stress test (NST) and umbilical artery (UA) Doppler assessments for evaluation of the adverse perinatal outcomes in GDM. We conducted a prospective cohort study on 50 pregnant women with GDM in Jame Zanan Hospital, Tehran, Iran, from Oct 2014 to Sep 2015. A convenient sampling method was used for patient recruitment. Inclusion criteria were women with GDM, singleton pregnancies, and gestational age>32 weeks who had neither medical conditions nor fetal anomalies. Adverse perinatal outcomes were defined as Apgar scores at 1-min and 5-min <7, hypoglycemia (blood glucose <45 mg/dl), neonatal acidosis (PH<7.2), hypocalcemia (Ca<8 mg/dl), admission to the NICU for more than 24 hours, and perinatal death. Statistical analyses were performed with SPSS version 16 using Chi-square, Fisher's exact test, and independent-samples t-test. The significance level was considered at 0.05. Totally, 22% and 12% of women had an abnormal UA Doppler and a non-reactive NST respectively. Poor outcomes were detected in 13 women. The most frequent poor outcomes were hypoglycemia (n=9), Apgar 1-min <7 (n=8), neonate admitted in NICU (n=6), and respiratory distress syndrome (n=6). Poor outcome was more prevalent in women with non-reactive NST (p<0.001), abnormal UA Doppler (p=0.033), and those with infant birth weight >4000 gram (p=0.033). Sensitivity and specificity of the NST in predicting different poor outcomes were 76.9% and 97.3% respectively. Sensitivity and specificity of UA Doppler in predicting different poor outcomes were 30.8% and 94.6% respectively. NST is a better predictor of adverse perinatal outcomes in GDM patients.


Determinants of excellent/good self-rated health among HIV positive individuals in South Africa: evidence from a 2012 nationally representative household survey.
In South Africa, HIV is increasingly becoming a chronic disease as a result of advances in HIV treatment and prevention in the last three decades. This has changed the perception from a life threating to a potentially manageable disease. However, little is known about self-perceived health status of HIV-infected individuals. Self-rated health (SRH) has been shown to be a sensitive indicator of health-relatedchanges directly linked to HIV, but can also be influenced by differences in social and material conditions. The aim of this paper was to identify determinants of excellent/good SRH among HIV-infected individuals using socio-demographic, life style and health related data. The study used data from the nationally representative 2012 South African population-based household survey on HIV prevalence, incidence and behaviour conducted using multi-stage stratified cluster sampling design. Bivariate and multivariate logistic regression models were used to identify determinants of SRH among HIV-infected individuals. Out of a total of 2632 HIV positive participants 74.1% (95% CI: 68.4-74.2) reported excellent/good SRH. Increased likelihood of reporting excellent/good SRH was significantly associated with being Black African [OR= 1.97 (95%CI: 1.12-3.46), p = 0.019] and belonging to least poor household [OR= 3.13 (95%CI: 1.26-7.78), p = 0.014]. Decreased likelihood of reporting excellent/good SRH was significantly associated with those aged 25 to 34 years [OR= 0.49 (95% CI: 0.31-0.78), p = 0.003], 35 to 44 years[OR= 0.27 (95% CI: 0.17-0.44), p < 0.001], 45 to 54 years [OR= 0.20 (95% CI: 0.12-0.34), p < 0.001], and those 55 years and older [OR= 0.15 (95% CI: 0.09-0.26), p < 0.001], hospitalization in the past twelve months [OR= 0.40 (95% CI: 0.26-0.60), p < 0.001]. To have positive health effects and improve the perceived health status for PLWH social interventions should seek to enhance to support for the elderly HIV-positive individuals, and address the challenge of socio-economic inequalities and underlying comorbid conditions resulting in hospitalization.


[Experimental study of peripheral nerve expansion with a tissue expander].
If a peripheral nerve could be elongated by a tissue expander (TE) without apparent damage, the length gained could be used to overcome a nerve gap without recourse to nerve graft. An experimental study was made to investigate whether this method for repairing a nerve gap is feasible. The tissue expander was designed by the authors and the median nerve of rabbits were stretched with TE at the rate of about 1 mm/day. The results showed that when the elongation rate was 18.4%, the motor nerve conduction velocity (MCV) was 67.8% and the myelinated nerve fibres (MNF) was 82.9% of the control nerves. In a further study nerve grafting and nerve expansion for repairing segmental nerve loss were compared with 10 mm defects. 4 months later the MCV, MNF, isometric contraction force (ICF) and muscle wet weight (MWW) were not significantly different between the 2 techniques. But with the 15 mm defects, elongated nerve were inferior to the nerve grafting method.