Superconducting filaments formed during nonvolatile resistance switching in electrodeposited δ-Bi(2)O(3).
We show that electrodeposited films of δ-Bi2O3 in a Pt/δ-Bi2O3/Au cell exhibit unipolar resistance switching. After being formed at a large electric field of 40 MV/m, the cell can be reversibly switched between a low resistance state (156 Ω) and a high resistance state (1.2 GΩ) by simply cycling between SET and RESET voltages of the same polarity. Because the high and low resistance states are persistent, the cell is a candidate for nonvolatile resistance random access memory (RRAM). A Bi nanofilament forms at the SET voltage, and it ruptures to form a 50 nm gap during the RESET step at a current density of 2 × 10(7) A/cm(2). The diameter of the Bi filament is a function of the compliance current, and can be tuned from 140 to 260 nm, but the current density in the RESET step is independent of the Bi diameter. An electromigration rupture mechanism is proposed. The Bi nanofilaments in the low resistance state are superconducting, with a Tc of 5.8 K and an Hc of 5 kOe. This is an unexpected result, because bulk Bi is not a superconductor.


Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells.
The gene encoding glutamic acid decarboxylase (GAD), the key enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid, is shown to be expressed in the testis of several different species. Nucleotide sequence analysis of a cDNA clone isolated from the human testis confirmed the presence of GAD mRNA in the testis. The major GAD mRNA in the testis was 2.5 kilobases. Smaller amounts of a 3.7-kilobase mRNA with the same size as GAD mRNA in the brain was also detected in the testis. In situ hybridization using a GAD-specific probe revealed GAD mRNA expressing spermatocytes and spermatids located in the middle part of rat seminiferous tubules. Studies on the ontogeny of GAD mRNA expression showed low levels of GAD mRNA in testes of prepubertal rats, with increasing levels as sexual maturation is reached, compatible with GAD mRNA expression in germ cells. In agreement with this, fractionation of cells from the rat seminiferous epithelium followed by Northern (RNA) blot analysis showed the highest levels of GAD mRNA associated with spermatocytes and spermatids. Evidence for the presence of GAD protein in the rat testis was obtained from the demonstration of GAD-like immunoreactivity in seminiferous tubules, predominantly at a position where spermatids and spermatozoa are found. Furthermore, GAD-like immunoreactivity was seen in the midpiece of ejaculated human spermatozoa, the part that is responsible for generating energy for spermatozoan motility.


The de novo design of α-helical peptides for supramolecular self-assembly.
One approach to designing de novo proteinaceous assemblies and materials is to develop simple, standardised building blocks and then to combine these symmetrically to construct more-complex higher-order structures. This has been done extensively using β-structured peptides to produce peptide fibres and hydrogels. Here, we focus on building with de novo α-helical peptides. Because of their self-contained, well-defined structures and clear sequence-to-structure relationships, α helices are highly programmable making them robust building blocks for biomolecular construction. The progress made with this approach over the past two decades is astonishing and has led to a variety of de novo assemblies, including discrete nanoscale objects, and fibrous, nanotube, sheet and colloidal materials. This body of work provides an exceptionally strong foundation for advancing the field beyond in vitro design and into in vivo applications including what we call protein design in cells.


Learning to use learning resources during medical school and residency.
This study (1) examined the natural history of learning to use learning resources by medical students and residents and (2) considered whether that history is consistent with the ways in which physicians approach their learning tasks. The authors conducted and analyzed thirty-two open-ended interviews of first-year and third-year medical students and first-year and senior residents in internal medicine, family medicine, or pediatrics. Learning to use learning resources occurs at the same time as learning done to address instructional and clinical problems that physicians-in-training face, with all kinds of learning following well-documented stages. Skills for using resources are developed gradually and by overcoming barriers such as time constraints and existing habits. Implications of the natural history of learning to use learning resources can be employed by librarians and medical teachers to facilitate self-directed learning for physicians-in-training. Specific recommendations are provided.


Triglyceride response to an intensive lifestyle intervention is enhanced in carriers of the GCKR Pro446Leu polymorphism.
Glucokinase regulatory protein (GCKR) regulates the trafficking and enzymatic activity of hepatic glucokinase, the rate-limiting enzyme in glycogen synthesis and glycolysis. The intronic single-nucleotide polymorphism (SNP) rs780094 (intron 16) and the missense SNP rs1260326 (P446L) in the GCKR gene are strongly associated with increased circulating triglyceride and C-reactive protein levels and, paradoxically, reductions in diabetes incidence, fasting glucose levels, and insulin resistance. OBJECTIVE, SETTING, AND PATIENTS: We sought to replicate these associations and evaluate interactions with lifestyle and metformin interventions in the multiethnic Diabetes Prevention Program (DPP). We genotyped the two GCKR SNP in 3346 DPP participants and evaluated association with progression to diabetes and both baseline levels and changes in triglycerides, homeostasis model assessment of insulin resistance (HOMA-IR), oral disposition index, and inflammatory markers along with their interactions with DPP interventions. GCKR variation did not predict development of type 2 diabetes. At baseline, the 446L allele was associated with higher triglyceride and C-reactive protein levels (both P < 0.0001) and lower fasting glucose (P = 0.001) and HOMA-IR (P = 0.06). The lifestyle intervention was associated with a decrease in magnitude of the effect of the 446L allele on triglyceride levels (interaction P = 0.04). Metformin was more effective in reducing HOMA-IR in carriers of the P446 allele (interaction P = 0.05). Intensive lifestyle intervention appears to partially mitigate the effect of the 446L allele on higher triglycerides, whereas the P446 allele appears to enhance responsiveness to the HOMA-IR-lowering effect of metformin.


Investigating eye movement acquisition and analysis technologies as a causal factor in differential prevalence of crossed and uncrossed fixation disparity during reading and dot scanning.
Previous studies examining binocular coordination during reading have reported conflicting results in terms of the nature of disparity (e.g. Kliegl, Nuthmann, & Engbert (Journal of Experimental Psychology General 135:12-35, 2006); Liversedge, White, Findlay, & Rayner (Vision Research 46:2363-2374, 2006). One potential cause of this inconsistency is differences in acquisition devices and associated analysis technologies. We tested this by directly comparing binocular eye movement recordings made using SR Research EyeLink 1000 and the Fourward Technologies Inc. DPI binocular eye-tracking systems. Participants read sentences or scanned horizontal rows of dot strings; for each participant, half the data were recorded with the EyeLink, and the other half with the DPIs. The viewing conditions in both testing laboratories were set to be very similar. Monocular calibrations were used. The majority of fixations recorded using either system were aligned, although data from the EyeLink system showed greater disparity magnitudes. Critically, for unaligned fixations, the data from both systems showed a majority of uncrossed fixations. These results suggest that variability in previous reports of binocular fixation alignment is attributable to the specific viewing conditions associated with a particular experiment (variables such as luminance and viewing distance), rather than acquisition and analysis software and hardware.


Application of pulsed radiofrequency currents to rat dorsal root ganglia modulates nerve injury-induced tactile allodynia.
Application of pulsed radiofrequency (PRF) currents to the dorsal root ganglia (DRG) has been reported to produce relief from certain pain states without causing thermal ablation. In this study, we examined the direct correlation between PRF application to DRG associated with spinal nerve injury and reversal of injury-induced behavioral hypersensitivity in a rat neuropathic pain model. Neuropathic lesioning was performed via left L5 spinal nerve ligation on male adult Sprague-Dawley rats. Once the injured rats had developed tactile allodynia, one group was then assigned to PRF treatment of the L5 DRG and another group was assigned to the sham treatment to the DRG. Behavioral testing was performed on both the control and treated paws using the von Frey filament test before the surgery and at indicated days. The resulting data were analyzed using a linear mixed model to assess the overall difference between the treatment groups and the overall difference among the study days. Cohen's d statistic was computed from paired difference-from-baseline scores for each of the 14 study days after treatment and these measures of effect size were then used to descriptively compare the recovery patterns over time for each study group. Spinal nerve injury resulted in the development of behavioral hypersensitivity to von Frey filament stimulation (allodynia) in the hindpaw of the left (injury) side. Mixed linear modeling showed a significant difference between the treatment groups (P = 0.0079) and a significant change of paw withdrawal threshold means over time (P = 0.0006) for all 12 animals. Evaluation of Cohen's d (effect size) revealed that the PRF-treated animals exhibited better recovery and recorded larger effect sizes than the sham-treated animals on 10 of the 14 post-PRF treatment days and exhibited moderate-to-strong effects posttreatment at days 8 to 10 and at and beyond day 32. Findings from this study support that PRF of the DRG causes reversal of nerve injury (spinal nerve ligation)-induced tactile allodynia in rats. This allodynia reversal indicates that nonablative PRF acting via modulation of the DRG can speed recovery in nerve injury-induced pain.


Evaluation of metal concentration and antioxidant activity of three edible mushrooms from Mugla, Turkey.
This study is designed for the determination of metal concentrations, antioxidant activity potentials and total phenolics of Amanita caesarea, Clitocybe geotropa and Leucoagaricus pudicus. Concentrations of four heavy metals (Pb, Cd, Cr, Ni) and five minor elements (Zn, Fe, Mn, Cu, Co) are determined. In the case of A. caesarea, Cr and Ni concentrations are found in a high level. Concentrations of the metals are found to be within safe limits for C. geotropa. In beta-carotene/linoleic acid test, L. pudicus showed the highest activity potential. In DPPH system, A. caesarea showed 79.4% scavenging ability. Additionally, reducing power and chelating capacity of the mushrooms increased with concentration. The strongest super-oxide anion scavenger was A. caesarea. In the case of total phenolics, L. pudicus found to have the highest content.


Inferring model parameters in network-based disease simulation.
Many models of infectious disease ignore the underlying contact structure through which the disease spreads. However, in order to evaluate the efficacy of certain disease control interventions, it may be important to include this network structure. We present a network modeling framework of the spread of disease and a methodology for inferring important model parameters, such as those governing network structure and network dynamics, from readily available data sources. This is a general and flexible framework with wide applicability to modeling the spread of disease through sexual or close contact networks. To illustrate, we apply this modeling framework to evaluate HIV control programs in sub-Saharan Africa, including programs aimed at concurrent partnership reduction, reductions in risky sexual behavior, and scale up of HIV treatment.


The dynamics of soybean leaf and shoot apical meristem transcriptome undergoing floral initiation process.
Flowering process governs seed set and thus affects agricultural productivity. Soybean, a major legume crop, requires short-day photoperiod conditions for flowering. While leaf-derived signal(s) are essential for the photoperiod-induced floral initiation process at the shoot apical meristem, molecular events associated with early floral transition stages in either leaves or shoot apical meristems are not well understood. To provide novel insights into the molecular basis of floral initiation, RNA-Seq was used to characterize the soybean transcriptome of leaf and micro-dissected shoot apical meristem at different time points after short-day treatment. Shoot apical meristem expressed a higher number of transcripts in comparison to that of leaf highlighting greater diversity and abundance of transcripts expressed in the shoot apical meristem. A total of 2951 shoot apical meristem and 13,609 leaf sequences with significant profile changes during the time course examined were identified. Most changes in mRNA level occurred after 1short-day treatment. Transcripts involved in mediating responses to stimulus including hormones or in various metabolic processes represent the top enriched GO functional category for the SAM and leaf dataset, respectively. Transcripts associated with protein degradation were also significantly changing in leaf and SAM implicating their involvement in triggering the developmental switch. RNA-Seq analysis of shoot apical meristem and leaf from soybean undergoing floral transition reveal major reprogramming events in leaves and the SAM that point toward hormones gibberellins (GA) and cytokinin as key regulators in the production of systemic flowering signal(s) in leaves. These hormones may form part of the systemic signals in addition to the established florigen, FLOWERING LOCUS T (FT). Further, evidence is emerging that the conversion of shoot apical meristem to inflorescence meristem is linked with the interplay of auxin, cytokinin and GA creating a low cytokinin and high GA environment.


Megaloblastic anaemia in a vegetarian Hindu community.
138 Indian patients with megaloblastic haemopoiesis were studied. All were lifelong vegetarians. The diagnosis was nutritional cobalamin deficiency in 95 and pernicious anaemia in 20; only 4 patients had folate deficiency. A third had intestinal malabsorption, 20 had features of osteomalacia, and 87 were iron deficient. Tuberculosis was diagnosed in 17. Cobalamin deficiency may have contributed to these complications via intestinal malabsorption and impaired bacterial killing of phagocytosed bacilli by cobalamin-deficient macrophages. The frequency of pernicious anaemia was the same in Indian subjects as in Caucasians.


[Results of pre-hospital cardiac resuscitation in the Reykjavik area 2004-2007].
In the Reykjavik area, a physician staffed ambulance -responded to cardiac arrests from 1982-2007. The aim of this study was to assess the outcome of attempted pre-hospital cardiac resuscitations in the period from 2004-2007 and compare to previous studies. All cases of attempted prehospital resuscitations in cardiac arrests of presumed cardiac etiology. Data was gathered according to the Utstein template. Of a total of 289 cases in cardiac arrest, resuscitation was attempted in 279 and 200 of those were presumed to have a cardiac etiology. Men were 76% of the patients and the average age was 67.7 years. Average response time was 6.3 min. One hundred and seven (54%) survived to hospital admission and 50 (25%) survived to discharge compared to 16-19% in previous studies (p=0.16). The presenting rhythm was ventricular fibrillation/ventricular tachycardia (VF/VT) in 50% of the cases, 30% was in asystole and 20% in pulseless electrical activity (PEA). Of those admitted to intensive care unit/ department and had ventricular fibrillation on the first rhythm strip 70% were discharged during 2004-2007 compared to 49% during 1999-2002 (p=0.01). Bystander CPR was provided in 62% of witnessed cases compared to 54% in a previous study (p=0.26). One hundred and twenty (60%) were witnessed cases of which 37 (31%) survived to hospital discharge compared to 5 (8%)of non witnessed cases (p<0.01). One in every four cardiac arrest patients in the Reykjavik area survives to discharge. This is similar to previous studies in the area (16-19%) and high compared to international studies 3-16%. Survival of those admitted to intensive care unit/ department and had ventricular fibrillation on the first rhythm strip was significantly higher compared to previous studies. Survival was found to be significantly higher if the cardiac arrest was witnessed.


Extracorporeal membrane oxygenation: a literature review.
Extracorporeal membrane oxygenation is a modality of extracorporeal life support that allows for temporary support in pulmonary and/or cardiac failure refractory to conventional therapy. Since the first descriptions of extracorporeal membrane oxygenation, significant improvements have occurred in the device and the management of patients and, consequently, in the outcomes of critically ill patients during extracorporeal membrane oxygenation. Many important studies about the use of extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome refractory to conventional clinical support, under in-hospital cardiac arrest and with cardiogenic refractory shock have been published in recent years. The objective of this literature review is to present the theoretical and practical aspects of extracorporeal membrane oxygenation support for respiratory and/or cardiac functions in critically ill patients.


Novel fabrication of gelatin-encapsulated copper nanoparticles using Aspergillus versicolor and their application in controlling of rotting plant pathogens.
The fabrication of copper nanoparticles (CuNPs) with smallest size and more stability, with potential effects in plant disease management, may need a modified protocol for green synthesis. In this study, we could biosynthesize stable CuNPs extracellularly by an eco-friendly route using A. versicolor. The biosynthesis of nanoparticles was confirmed by UV-visible spectroscopy, Fourier transform infrared (FTIR), transmission electron microscope (TEM) and dynamic light scattering (DLS) techniques. CuNPs have a size range of 23-82 nm with round to polygonal shape. Antifungal study showed that CuNPs have potential antifungal activity against rotting plant pathogens, where 3.2 and 2.8 µg ml-1 of nanoparticle solution totally inhibited the growth of both Fusarium oxysporum and Phytophthora parasitica, respectively. Damaged hyphae with limited deformed spores were detected through scanning electron microscope (SEM) analysis after the treatment of both pathogens with CuNPs. Between all tested polymers, gelatin-encapsulated nanoparticles were characterized 'by their smallest size, 7-33 nm, and regular spherical shape at all experimental conditions. After 6 months of storage, gelatin-CuNPs maintained full nanoscale and antifungal properties compared with uncoated particles which lost these properties after only 1 month. It is concluded that CuNPs can be biosynthesized by an eco-friendly cheap method using A. versicolor and can be preserved stably for a long time with the smallest size and full antifungal activity by their encapsulation with gelatin as a natural polymer. These nanoparticles can be used safely in the management of plant rotting fungi.


Core Genome Multilocus Sequence Typing and Prediction of Antimicrobial Susceptibility Using Whole-Genome Sequences of Escherichia coli Bloodstream Infection Isolates.
In total, 50 Escherichia coli bloodstream isolates from the clinical laboratory and 12 E. coli isolates referred for pulsed-field gel electrophoresis (PFGE) were sequenced, assessed for clonality using core genome multilocus sequence typing (cgMLST), and evaluated for genomic susceptibility predictions using ARESdb. Results of sequence typing using whole-genome sequencing (WGS)-based MLST and sequence type (ST)-specific PCR were identical. Overall categorical agreement between genotypic (ARESdb) and phenotypic susceptibility testing for 62 isolates and 11 antimicrobial agents was 91%. Among the referred isolates, high major error rates were found for ceftazidime, cefepime, and piperacillin-tazobactam.


Effect of prolonged uremia on insulin-like growth factor-I receptor autophosphorylation and tyrosine kinase activity in kidney and muscle.
Recently, based on a study in rats with chronic renal failure (CRF), it has been suggested that IGF-I resistance in uremia may be caused in part by defective IGF-I receptor autophosphorylation and tyrosine kinase activity. Thus if such a defect were to develop in prolonged acute renal failure (ARF), this may explain why IGF-I therapy, effective in rats, has failed to promote recovery from ARF in patients. Accordingly, we examined IGF-I receptor function in rats with uremia of increasing duration and in pair-fed sham-operated controls. After 6 days of prolonged ARF, kidney IGF-I receptor binding increased twofold, while IGF-I stimulated receptor phosphorylation and tyrosine kinase activity were unchanged. Muscle receptor binding, autophosphorylation and tyrosin kinase activity were similar to control values after 6 or even 21 days of uremia. Taking all these findings together it appears that IGF-I resistance in uremia cannot be attributed to a receptor defect. This in turn argues against altered receptor function as a cause of the failure of IGF-I to modify clinical ARF.


Prevalence and factors associated with use of herbal medicine among women attending an infertility clinic in Uganda.
Infertility is a public health problem associated with devastating psychosocial consequences. In countries where infertility care is difficult to access, women turn to herbal medicines to achieve parenthood. The aim of this study was to determine the prevalence and factors associated with herbal medicine use by women attending the infertility clinic. This was a cross-sectional study of 260 women attending the infertility clinic at Mulago hospital. The interviewer administered questionnaire comprised socio-demographic characteristics, infertility-related aspects and information on herbal medicine use. The main outcome measure was herbal medicines use for infertility treatment. Determinants of herbal medicine use were assessed using multivariable logistic regression. The majority (76.2%) of respondents had used herbal medicines for infertility treatment. The mean age of the participants was 28.3 years ± 5.5. Over 80% were married, 59.6% had secondary infertility and 2/3 of the married participants were in monogamous unions. In a multivariable model, the variables that were independently associated with increased use of herbal medicine among infertile patients were being married (OR 2.55, CI 1.24-5.24), never conceived (OR 4.08 CI 1.86-8.96) and infertility for less than 3 years (OR 3.52 CI 1.51-8.821). Factors that were associated with less use of herbal medicine among infertile women were being aged 30 years or less (OR 0.18 CI 0.07-0.46), primary and no education (OR 0.12 CI 0.05-0.46) and living with partner for less than three years (OR 0.39 CI 0.16-0.93). The prevalence of herbal medicine use among women attending the infertility clinic was 76.2%. Herbal medicine use was associated with the participants' age, level of education, marital status, infertility duration, nulliparity, and duration of marriage. Medical care was often delayed and the majority of the participants did not disclose use of herbal medicines to the attending physician. Health professionals should enquire about use of herbal medicines. This may help in educating the patients about the health risks of using herbal medicine and may reduce delays in seeking appropriate care. Collaboration of health professionals with herbal medicine practitioners would help identify the common herbal medicines used for infertility treatment, their potential benefits and harm.


Observation and modelling of clamshell droplets on vertical fibres subjected to gravitational and drag forces.
Extensive experimental investigation of the wetting processes of fibre-liquid systems during air filtration (when drag and gravitational forces are acting) has shown many important features, including droplet extension, oscillatory motion, and detachment of drops from fibres as airflow velocity increases, and also movement or flow of droplets along fibres. A detailed experimental study of the processes was conducted using stainless steel filter fibres and H2O aerosol, which coalesce on the fibre to form clamshell droplets. The droplets were predominantly observed in the Reynolds transition flow region, since this is the region where most of the above features occur. The droplet oscillation is believed to be induced by the onset of the transition from laminar to turbulent flow as the increasing droplet size increases Reynolds number for the flow around the droplet. Two-dimensional flow in this region is usually modelled using the classical Karman vortex street, however there exist no 3D equivalents. Therefore to model such oscillation it was necessary to create a new conceptual model to account for the forces both inducing and preventing such oscillation. The agreement between the model and experimental results is very good for both the radial and transverse oscillations.


Absorption of nitro-polycyclic aromatic hydrocarbons by biomembrane models: effect of the medium lipophilicity.
To demonstrate the relationship between the structure of nitro-polycyclic aromatic hydrocarbons and their effect on biomembranes, we have investigated the influence of three structurally different nitro-polycyclic aromatic hydrocarbons, 2-nitrofluorene, 2,7-dinitrofluorene and 3-nitrofluoranthene, on the thermotropic behavior of dimyristoylphosphatidylcholine multilamellar vesicles, used as biomembrane models, by means of differential scanning calorimetry. The obtained results indicate that the studied nitro-polycyclic aromatic hydrocarbons affected the thermotropic behavior of multilamellar vesicles to various extents, modifying the pretransition and the main phase transition peaks and shifting them to lower temperatures. The effect of the aqueous and lipophilic medium on the absorption process of these compounds by the biomembrane models has been also investigated revealing that the process is hindered by the aqueous medium but strongly allowed by the lipophilic medium.


The multiple roentgen manifestations of sclerosing mediastinitis.
Sclerosing mediastinitis is excessive production of fibrous tissue in the mediastinum. Its most common manifestations, widening of the mediastinum and superior vena caval obstruction, are the only roentgenographic findings generally recognized to be associated with this disease. Analysis of 29 cases of sclerosing mediastinitis and review of the literature reveal that compression of mediastinal organs by constricting bands of collagen may cause various roentgen manifestations including bronchial or tracheal obstruction leading to atelectasis or obstructive pneumonitis, pulmonary venous obstruction, pulmonary artery obstruction, esophageal obstruction and nerve entrapment. The most common abnormality seen on the chest roentgenogram, mediastinal widening, is usually superior and especially right paratracheal in location. Superior vena caval compression is smooth and tapered rather than irregular as in malignant disease. Pulmonary venous and arterial obstruction may cause cor pulmonale and death, although the other manifestations are usually not life-threatening. The most common causes of sclerosing mediastinitis are generally considered to be granulomatous diseases, especially histoplasmosis, although many other causes have also been suggested. The disease may be regarded as an inappropriate response to one of several stimuli.


Costs versus Coverage, Then and Now.
To expand coverage to those without it, Democrats in 2010 sacrificed cost control methods that might have helped those already insured. The law therefore did not offer most Americans what they wanted most. President Obama and those who thought like him convinced themselves the legislation would control costs by reforming how health care is organized, but any such effects have been both weak and unpopular. Now many commentators are accusing Democratic candidates of making the same mistake by prioritizing an ideological vision of "Medicare for All" over voters' worries about out-of-pocket costs. Yet Medicare for All, unlike less "radical" approaches, addresses those concerns directly. Unfortunately, neither elites (outside the industry!) nor voters seem to understand that, and it is politically risky because of the same fears about change, industry opposition, and distrust of government that inhibited more effective action a decade before.


Relationship of recipient age and development of chronic allograft failure.
The elderly are the fastest growing segment of the end stage renal disease (ERSD) population. Older renal transplant recipients experience fewer acute rejection episodes than do younger patients. Despite this, death censored graft survival is no better in these older transplant recipients than in younger recipients. We examined the United States Renal Data System (USRDS) database to determine whether recipient age itself has an independent effect on the development of chronic allograft failure (CAF). We analyzed 59,509 patients from the files of the USRDS. To determine whether age was an independent risk factor for CAF, the population was analyzed separately for Caucasians, African-Americans, and other ethnic groups. All renal transplant recipients from 1988 to 1997 were examined. Both univariate and multivariate analysis were performed using chronic allograft failure as the outcome of interest. Actuarial 8-year censored graft survival was significantly decreased in the older age groups 67% for ages 18-49 vs. 61.8% for ages 50-64 vs. 50.7% for ages 65+ (P<0.001). In the multivariate analysis, recipient age was a strong and independent risk factor for the development of chronic allograft failure in Caucasians (RR 1.29 for ages 50-64, RR 1.67 for ages older than 65). These findings were reinforced by an analysis that was restricted to living donor transplants without acute rejection. In Caucasians increased recipient age is an independent risk factor for the development of chronic renal allograft failure.


Multivessel Versus Culprit Vessel-Only Percutaneous Coronary Intervention Among Patients With Acute Myocardial Infarction: Insights From the TRANSLATE-ACS Observational Study.
Among patients with acute myocardial infarction (MI) who have multivessel disease, it is unclear if multivessel percutaneous coronary intervention (PCI) improves clinical and quality-of-life outcomes compared with culprit-only intervention. We sought to compare clinical and quality-of-life outcomes between multivessel and culprit-only PCI. Among 6061 patients with acute MI who have multivessel disease in the TRANSLATE-ACS (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study, we used inverse probability-weighted propensity adjustment to study the associations between multivessel and culprit-only intervention during the index PCI and major adverse cardiovascular events, unplanned all-cause readmission, and angina frequency at 6 weeks and 1 year. Multivessel PCI was performed in 1208 (20%) of patients with MI who had multivessel disease. Relative to the culprit-only intervention, patients receiving multivessel PCI were similarly aged and more likely to be seen with non-ST-segment elevation MI or cardiogenic shock. At 6 weeks, the initial multivessel PCI strategy was associated with lower major adverse cardiovascular events and unplanned readmission risks, whereas angina frequency was not significantly different between multivessel and culprit-only PCI. At 1 year, major adverse cardiovascular event risk was persistently lower in the multivessel PCI group (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72-0.99), whereas long-term readmission risk (adjusted hazard ratio, 0.94; 95% confidence interval, 0.84-1.04) and angina frequency were similar between groups (adjusted odds ratio, 1.01; 95% confidence interval, 0.82-1.24). Similar associations were seen when patients with ST-segment elevation MI and non-ST-segment elevation MI were examined separately. Among patients with acute MI who have multivessel disease, multivessel PCI was associated with lower risk of all-cause readmission at 6 weeks and lower risk of major adverse cardiovascular events at 6 weeks and 1 year. However, similar short- and long-term angina frequencies were noted.


Structure-function of the multifunctional Ca2+/calmodulin-dependent protein kinase II.
Ca2+/calmodulin (CaM)-dependent protein kinase (CaMKII) is a ubiquitous mediator of Ca2+-linked signalling that phosphorylates a wide range of substrates to co-ordinate and regulate Ca2+-mediated alterations in cellular function. The transmission of information by the kinase from extracellular stimuli and the intracellular Ca2+ rise is not passive. Rather, its multimeric structure and autoregulation enable this enzyme to participate actively in the sensitivity, timing and location of its action. CaMKII can: (i) be activated in a Ca2+-spike frequency-dependent manner; (ii) become independent of its initial Ca2+/CaM activators; and (iii) undergo a 'molecular switch-like' behaviour, which is crucial for certain forms of learning and memory. CaMKII is derived from a family of four homologous but distinct genes, with over 30 alternatively spliced isoforms described at present. These isoforms possess diverse developmental and anatomical expression patterns, as well as subcellular localization. Six independent catalytic/autoregulatory domains are connected by a narrow stalk-like appendage to each hexameric ring within the dodecameric structure. Ca2+/CaM binding activates the enzyme by disinhibiting the autoregulatory domain; this process initiates an intra-holoenzyme autophosphorylation reaction that induces complex changes in the enzyme's sensitivity to Ca2+/CaM, including the generation of Ca2+/CaM-independent (autonomous) activity and marked increase in affinity for CaM. The role of CaMKII in Ca2+ signal transduction is shaped by its autoregulation, isoenzymic type and subcellular localization. The molecular determinants and mechanisms producing these processes are discussed as they relate to the structure-function of this multifunctional protein kinase.


Exercise-induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work.
High work of breathing and exercise-induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise-induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing-related changes in quadriceps muscle fatigue. Reducing the work of breathing or eliminating exercise-induced arterial hypoxaemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8 male, 8 female) completed three constant load exercise tests over 4 days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso-time and iso-work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes, quadriceps force was equally reduced after the control trial (-27 ± 2% baseline) and was attenuated with hyperoxia and PAV (-18 ± 1 and -17 ± 2% baseline, P < 0.01, respectively), with no sex difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r2 = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative V̇O2 of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue.


Functional neuroimaging in early-onset anorexia nervosa.
Previous neuroimaging studies in early-onset anorexia nervosa provide evidence of limbic system dysfunction. The current study adds support to the possibility by revealing a significant association between unilateral reduction of blood flow in the temporal region and impaired visuospatial ability, impaired visual memory, and enhanced speed of information processing.


Renal Cancer in Recipients of Kidney Transplant.
The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48) recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66); 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17-73); 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days). Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.


Reconsidering Kantian arguments against organ selling.
Referring to Kant's arguments addressing the moral relationship between our bodies and ourselves is quite common in contemporary debate about organ selling, although he does not provide us with any specific arguments related to this debate. It is widely argued that the most promising way to show the moral impermissibility of organ selling is to mount an argument on Kantian grounds. This paper asks whether it is possible to argue coherently against organ selling in a Kantian framework. It will be shown that by mounting the argument on Kantian grounds no compelling argument can be given against sale of organs, either because the arguments apply to donation of organs, too, or the arguments are not convincing for other independent reasons. In the first section, it will be argued that donation and selling are not distinguishable in a Kantian framework, since the concern about commodification of the body and its parts shall be raised by both actions. In the second section, some contemporary accounts inspired by Kant will be presented and discussed separately. It will be argued that the reasons for promoting organ donation while arguing against selling clash with each other in an unconvincing way.


Adsorption and stability of streptavidin on cluster-assembled nanostructured TiOx films.
The study of the adsorption of proteins on nanostructured surfaces is of fundamental importance to understand and control cell-surface interactions and, notably, cell adhesion and proliferation; it can also play a strategic role in the design and fabrication of nanostructured devices for postgenomic and proteomic applications. We have recently demonstrated that cluster-assembled nanostructured TiO x films produced by supersonic cluster beam deposition possess excellent biocompatibility and that these films can be functionalized with streptavidin, allowing the immobilization of biotinylated retroviral particles and the realization of living-cell microarrays for phenotype screening. Here we present a multitechnique investigation of the adsorption mechanisms of streptavidin on cluster-assembled TiO x films. We show that this nanostructured surface provides an optimal balance between adsorption efficacy and protein functionality. By using low-resolution protein arrays, we demonstrate that a layer of adsorbed streptavidin can be stably maintained on a cluster-assembled TiO x surface under cell culture conditions and that streptavidin retains its biological activity in the adsorbed layer. The adsorption mechanisms are investigated by atomic force microscopy in force spectroscopy mode and by valence-band photoemission spectroscopy, highlighting the potential role of the interaction of the exposed carboxyl groups on streptavidin with the titanium atoms of the nanostructured surface.


Inward rectifier potassium channels. Cloning, expression and structure-function studies.
A PCR-based cloning strategy was used to identify novel subunits of the two-transmembrane domain inward rectifier potassium channel family from rat brain, heart, and skeletal muscle. When expressed in Xenopus oocytes, two of these clones (Kir4.1 and Kir2.3) gave rise to inwardly rectifying potassium currents. Two-electrode voltage clamp commands to potentials negative to EK evoked inward potassium-selective currents which rapidly reached a peak amplitude and then relaxed to a steady-state level. Differences in the extent of current relaxation, the degree of rectification, and the voltage-dependent block by external cesium were detected. Two other members of this family (Kir5.1 and Kir3.4) did not produce macroscopic currents, when expressed by themselves, yet both subunits modified the currents when coexpressed with other specific members of the Kir family. Expression of chimeric subunits between Kir4.1 and either Kir5.1 or Kir3.4 suggested that the transmembrane domains determine the specificity of subunit heteropolymerization, while the C-terminal domains contribute to alterations in activation kinetics and rectification. Expression of covalently linked subunits demonstrated that the relative subunit positions, as well as stoichiometry, affect heteromeric channel activity.


The structure of ribosomes as indicated by studies of tetramers from hypothermic chick embryos.
Ribosome tetramers induced in chick embryos by exposure to cold, and tetramers of large subunits derived from them, have been studied by electron microscopy and sucrose-density-gradient analysis. Individual ribosomes of the normal tetramer are elongated bean-shaped structures, 220-280A by 195A (1A=10(-1)nm) with a cleft in the outer edge which divides the two-dimensional image into two unequal ends. Most of the tetramers appear to attach to the surface of the electron-microscope grid by one preferred face. The subunits of the large-subunit tetramers have a round outline and no cleft. About 25% of the subunits of these tetramers have a line running radially across the particle. The dissociation of tetramers into large-subunit tetramers and small subunits has been shown to be reversible. Mixtures of these particles from sucrose-density-gradient fractions were reassociated to give a tetramer with the same sedimentation coefficient as the original tetramer and with the same structure as viewed in the electron microscope. The results indicate that the cleft is a property of the complete ribosome, and that it marks the position of the small subunit. The reversibility of the dissociation also strengthens the view that no change in the large subunit occurs during dissociation or reassociation, i.e. that the sites of interaction between ribosomes in both types of tetramer are the same. The conclusions affect the interpretation of electron-micrograph images and an anomaly in the relationship between the two types of tetramer is discussed.


IL-25 causes apoptosis of IL-25R-expressing breast cancer cells without toxicity to nonmalignant cells.
As cells differentiate into tissues, the microenvironment that surrounds these cells must cooperate so that properly organized, growth-controlled tissues are developed and maintained. We asked whether substances produced from this collaboration might thwart malignant cells if they arise in the vicinity of normal tissues. Here, we identified six factors secreted by nonmalignant mammary epithelial cells (MECs) differentiating in three-dimensional laminin-rich gels that exert cytotoxic activity on breast cancer cells. Among these, interleukin-25 (IL-25/IL-17E) had the highest anticancer activity without affecting nonmalignant MECs. Apoptotic activity of IL-25 was mediated by differential expression of its receptor, IL-25R, which was expressed in high amounts in tumors from patients with poor prognoses but was low in nonmalignant breast tissue. In response to IL-25, the IL-25R on the surface of breast cancer cells activated caspase-mediated apoptosis. Thus, the IL-25/IL-25R signaling pathway may serve as a new therapeutic target for advanced breast cancer.


Structural leitmotif and functional variations of the structural catalytic core in (chymo)trypsin-like serine/cysteine fold proteinases.
Proteinases with the (chymo)trypsin-like serine/cysteine fold comprise a large superfamily performing their function through the Acid - Base - Nucleophile catalytic triad. In our previous work (Denesyuk AI, Johnson MS, Salo-Ahen OMH, Uversky VN, Denessiouk K. Int J Biol Macromol. 2020;153:399-411), we described a universal three-dimensional (3D) structural motif, NBCZone, that contains eleven amino acids: dipeptide 42 T-43 T, pentapeptide 54 T-55 T-56 T-57 T(base)-58 T, tripeptide 195 T(nucleophile)-196 T-197 T and residue 213 T (T - numeration of amino acids in trypsin). The comparison of the NBCZones among the members of the (chymo)trypsin-like protease family suggested the existence of 15 distinct groups. Within each group, the NBCZones incorporate an identical set of conserved interactions and bonds. In the present work, the structural environment of the catalytic acid at the position 102 T and the fourth member of the "catalytic tetrad" at the position 214 T was analyzed in 169 3D structures of proteinases with the (chymo)trypsin-like serine/cysteine fold. We have identified a complete Structural Catalytic Core (SCC) consisting of two classes and four groups. The proteinases belonging to different classes and groups differ from each other by the nature of the interaction between their N- and C-terminal β-barrels. Comparative analysis of the 3CLpro(s) from SARS-CoV-2 and SARS-CoV, used as an example, showed that the amino acids at positions 103 T and 179 T affect the nature of the interaction of the "catalytic acid" core (102 T-Core, N-terminal β-barrel) with the "supplementary" core (S-Core, C-terminal β-barrel), which ultimately results in the modulation of the enzymatic activity. The reported analysis represents an important standalone contribution to the analysis and systematization of the 3D structures of (chymo)trypsin-like serine/cysteine fold proteinases. The use of the developed approach for the comparison of 3D structures will allow, in the event of the appearance of new representatives of a given fold in the PDB, to quickly determine their structural homologues with the identification of possible differences.


Primary brain tumors associated with cerebral aneurysm: report of three cases.
The primary brain tumors associated with cerebral aneurysms are rare in neurosurgical practice. The present article constitutes an evaluation of the management of coexistent primary brain tumor and cerebral aneurysm. A retrospective study of three cases of primary brain tumor with cerebral aneurysm was performed. We evaluated the complications and clinic outcomes by assessing the clinical and imaging findings. Case 1 presented with a subarachnoid hemorrhage from an aneurysm of the anterior communicating artery, with an incidental left frontal oligodendroglioma. Case 2 presented with chronic headache due to left frontal convexity meningioma, with proximal internal carotid artery aneurysm which was found incidentally during preoperative magnetic resonance angiography. Case 3 was admitted to our hospital complaining of headache, memory disturbance, and weakness in her left lower extremity. Magnetic resonance imaging revealed right frontal lymphoma and an unruptured aneurysm at the left middle cerebral artery. Preoperative magnetic resonance imaging revealed right frontal lymphoma and unruptured left middle cerebral artery. The frequency of primary brain tumor and cerebral aneurysm coexistence is increasing due to improvements in high-resolution imaging. In these complicated cases, the management will differ according to each pathology present, and this is an important problem for a neurosurgeon.


Comparative Transcriptome Profiling in a Segregating Peach Population with Contrasting Juiciness Phenotypes.
Cold storage of fruit is one of the methods most commonly employed to extend the postharvest lifespan of peaches ( Prunus persica (L.) Batsch). However, fruit quality in this species is affected negatively by mealiness, a physiological disorder triggered by chilling injury after long periods of exposure to low temperatures during storage and manifested mainly as a lack of juiciness, which ultimately modifies the organoleptic properties of peach fruit. The aim of this study was to identify molecular components and metabolic processes underlying mealiness in susceptible and nonsusceptible segregants. Transcriptome and qRT-PCR profiling were applied to individuals with contrasting juiciness phenotypes in a segregating F2 population. Our results suggest that mealiness is a multiscale phenomenon, because juicy and mealy fruit display distinctive reprogramming processes affecting translational machinery and lipid, sugar, and oxidative metabolism. The candidate genes identified may be useful tools for further crop improvement.


[Osteoma of the mastoid: apropos of 2 cases].
The authors report two cases of mastoid osteoma: it is a rare benign tumor attached to the cortex of the mastoid bone, approximatively fifty cases have been described in the english language literature and eight in the french literature. The clinical and radiological characteristics combined with histopathologic evidence demonstrate the diagnosis of mastoid osteoma, the most common type being the compact osteoma. Differential diagnosis should be considered with others benign bone-forming lesions (osteochondroma, chondroma, osteoblastoma, exostosis, fibrous dysplasia...) and with malignant lesions (osteosarcoma...). Surgical removal proposed for cosmetic deformity is a simple procedure for the vast majority of small osteomas. Early surgical intervention is recommended to avoid the evolution toward giant osteoma with potential risks of surgical complications.


Risk of stroke and heart failure attributable to atrial fibrillation in middle-aged and elderly people: Results from a five-year prospective cohort study of Japanese community dwellers.
The relative and absolute risks of stroke and heart failure attributable to atrial fibrillation (AF) have not been sufficiently examined. A prospective study of 23,731 community-dwelling Japanese individuals was conducted. Participants were divided into two groups based on the presence or absence of prevalent AF (n = 338 and n = 23,393, respectively). Excess events (EE) due to AF and relative risks (RRs) determined using the non-AF group as the reference for incident stroke and heart failure were estimated using Poisson regression stratified by age groups (middle-aged: 40-69 years old; elderly: 70 years of age or older) after adjustment for sex and age. There were 611 cases of stroke and 98 cases of heart failure during the observation period (131,088 person-years). AF contributed to a higher risk of stroke both in middle-aged individuals (EE 10.4 per 1000 person-years; RR 4.88; 95% confidence interval [CI], 2.88-8.29) and elderly individuals (EE 18.3 per 1000 person-years; RR 3.05; 95% CI, 2.05-4.54). AF also contributed to a higher risk of heart failure in middle-aged individuals (EE 3.7 per 1000 person-years; RR 8.18; 95% CI, 2.41-27.8) and elderly individuals (EE 15.4 per 1000 person-years; RR 7.82; 95% CI, 4.11-14.9). Results obtained from multivariate-adjusted analysis were similar (stroke: EE 8.9 per 1000 person-years; RR 4.40; 95% CI, 2.57-7.55 in middle-aged and EE 17.4 per 1000 person-years; RR 2.97; 95% CI, 1.99-4.43 in elderly individuals; heart failure: EE 3.1 per 1000 person-years; RR 7.22; 95% CI, 2.06-25.3 in middle-aged and EE 14.1 per 1000 person-years; RR 7.41; 95% CI, 3.86-14.2 in elderly individuals). AF increased the risk of stroke by the same magnitude as that reported previously in Western countries. AF increased the RR of heart failure more than that in Western populations.


What drives changes in institutionalised mental health care? A qualitative study of the perspectives of professional experts.
Since 1990, the provision of mental healthcare has changed substantially across Western Europe. There are fewer psychiatric hospital beds and more places in forensic psychiatric hospitals and residential facilities. However, little research has investigated the drivers behind these changes. This study explored qualitatively the perspectives of mental health professional experts on what has driven the changes in Western Europe. In-depth interviews were conducted with twenty-four mental health experts in England, Germany and Italy, who as professionals had personal experiences of the changes in their country. Interviewees were asked about drivers of changes in institutionalised mental health care from 1990 to 2010. The accounts were subjected to a thematic analysis. Four broad themes were revealed: the overall philosophy of de-institutionalisation, with the aim to overcome old-fashioned asylum style care; finances, with a pressure to limit expenditure and an interest of provider organisations to increase income; limitations of community mental health care in which most severely ill patients may be neglected; and emphasis on risk containment so that patients posing a risk may be cared for in institutions. Whilst all themes were mentioned in all three countries, there were also differences in emphasis and detail. Distinct factors appear to have influenced changes in mental health care. Their precise influence may vary from country to country, and they have to be considered in the context of each country. The drivers may be influenced by professional groups to some extent, but also depend on the overall interest and attitudes in the society at large.


Inequitable health service use in a Canadian paediatric population: A cross-sectional study of individual- and contextual-level factors.
Health service use may be influenced by multilevel predisposing, enabling, and need factors but is equitable when driven by need. The study's objectives were as follows: (a) to investigate residential context's effect on child health service use and (b) to examine inequity of child health service use by testing for effect measure modification of need factors. The sample of 1,451 children was from a prenatal cohort recruited from London, Ontario, between 2002 and 2004, with follow-up until children were toddler/preschooler-aged. Individual-level data were linked by residential address to neighbourhood contextual-level data sourced from Statistics Canada. Multilevel logistic regression modelled factors associated with child health service use. Interaction terms were included in the model to test for effect measure modification of need factors by predisposing and enabling factors. Contextual-level factors were not associated with child health service use. Maternal parity and nativity to Canada modified the effect of the need factor, paediatric health condition, on health service use. Health condition's effect was lowest in children of Canadian-born mothers with one child only (OR = 1.58, p = .04) and highest in children of Canadian-born mothers with three or more children (OR = 3.52, p < .01). Further, its effect was higher in children of Canadian-born mothers compared to children of mothers who migrated to Canada; however, odds ratios were not statistically significant for the latter. Results may inform future investigation of the potential inequity of health service use for subgroups of children whose mothers are of lower parity and not Canadian-born. An understanding of these inequities may inform future healthcare policy and care for paediatric populations.


Mucoid Pseudomonas aeruginosa in cystic fibrosis: characterization of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection.
A distinguishing feature of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients is their mucoid, exopolysaccharide alginate-overproducing phenotype. One mechanism of conversion to mucoidy is based on mutations in the algU mucABCD cluster, encoding the stress sigma factor AlgU and its regulators. However, conversion to mucoidy in laboratory strains can be achieved via mutations in other chromosomal sites. Here, we investigated mechanisms of the emergence of mucoid P. aeruginosa in CF by analyzing the status of mucA in a collection of mucoid P. aeruginosa isolates from 53 CF patients. This negative regulator of algU, when inactivated under laboratory conditions, causes conversion to mucoidy. The overall frequency of mucA alterations in mucoid CF isolates was 84%. Nucleotide sequence analyses revealed that the majority of the alterations caused premature termination of the mucA coding sequence. Comparison of paired nonmucoid and mucoid P. aeruginosa isolates from three CF patients indicated the presence of mucA mutations only in the mucoid strains. Interestingly, mucoid P. aeruginosa isolates from urinary tract infections also had mutations in the mucA gene. Clearance of CF isolates from the murine lung was investigated in an aerosol infection model with C57BL/6J, BALB/c, and DBA/2NHsd mice. Two CF strains, selected for further study based on the dependence of their alginate production on the concentration of salt in the medium, were used to examine the effects of mucoidy on pulmonary clearance. Statistically significant improvement in recovery from the murine lung of viable mucoid P. aeruginosa cells relative to the nonmucoid bacteria was observed in the majority of mouse strains tested. Collectively, the results reported here suggest that mucA is most likely the preferential site for conversion to mucoidy in CF and that alginate overproduction in mucA-mutant P. aeruginosa improves its resistance to the innate clearance mechanisms in the lung.


Serial cranial ultrasonography or early MRI for detecting preterm brain injury?
To investigate detection ability and feasibility of serial cranial ultrasonography (CUS) and early MRI in preterm brain injury. Prospective cohort study. Level III neonatal intensive care unit. 307 infants, born below 29 weeks of gestation. Serial CUS and MRI were performed according to standard clinical protocol. In case of instability, MRI was postponed or cancelled. Brain images were assessed by independent experts and compared between modalities. Presence of preterm brain injury on either CUS or MRI and discrepant imaging findings on CUS and MRI. Serial CUS was performed in all infants; early MRI was often postponed (n=59) or cancelled (n=126). Injury was found in 146 infants (47.6%). Clinical characteristics differed significantly between groups that were subdivided according to timing of MRI. 61 discrepant imaging findings were found. MRI was superior in identifying cerebellar haemorrhage; CUS in detection of acute intraventricular haemorrhage, perforator stroke and cerebral sinovenous thrombosis. Advanced serial CUS seems highly effective in diagnosing preterm brain injury, but may miss cerebellar abnormalities. Although MRI does identify these lesions, feasibility is limited. Improved safety, better availability and tailored procedures are essential for MRI to increase its value in clinical care.


ICD lead implantation following sharp cannulation of a blocked superior vena cava.
Blocked superior vena cava (SVC) presents a well-recognized problem for the implantation of device leads. Implantable cardioverter defibrillator (ICD) leads pose a greater challenge than the pacing leads by requiring an adequate shock vector for successful defibrillation. We present here a novel technique of opening the blocked SVC to facilitate ICD lead implantation through the upper venous system.


Grazing Soybean to Increase Voluntary Cow Traffic in a Pasture-based Automatic Milking System.
Pasture-based automatic milking systems (AMS) require cow traffic to enable cows to be milked. The interval between milkings can be manipulated by strategically allocating pasture. The current experiment investigated the effect of replacing an allocation of grazed pasture with grazed soybean (Glycine max) with the hypothesis that incorporating soybean would increase voluntary cow traffic and milk production. One hundred and eighty mixed age, primiparous and multiparous Holstein-Friesian/Illawarra cows were randomly assigned to two treatment groups (n = 90/group) with a 2×2 Latin square design. Each group was either offered treatments of kikuyu grass (Pennisetum clandestinum Hoach ex Chiov.) pasture (pasture) or soybean from 0900 h to 1500 h during the experimental period which consisted of 2 periods of 3 days following 5 days of training and adaptation in each period with groups crossing over treatments after the first period. The number of cows trafficking to each treatment was similar together with milk yield (mean ≈18 L/cow/d) in this experiment. For the cows that arrived at soybean or pasture there were significant differences in their behaviour and consequently the number of cows exiting each treatment paddock. There was greater cow traffic (more cows and sooner) exiting pasture allocations. Cows that arrived at soybean stayed on the allocation for 25% more time and ate more forage (8.5 kg/cow/d/allocation) relative to pasture (4.7 kg/cow/d/allocation). Pasture cows predominantly replaced eating time with rumination. These findings suggest that replacing pasture with alternative grazeable forages provides no additional incentive to increase voluntary cow traffic to an allocation of feed in AMS. This work highlights the opportunity to increase forage intakes in AMS through the incorporation of alternative forages.


Ciliary granule plaques: membrane-intercalated particle aggregates associated with Ca2+-binding sites in paramecium.
In Paramecium nine rectangular aggregates of membrane-intercalated particles surround the freeze-cleaved membrane of the ciliary base. These "ciliary granule plaques" occur independently of the "ciliary necklace" which is observed in a more basal position on some cilia. In each individual plaque the approximately 10 nm large granules are arranged in a square grid pattern: the granules of one plaque invariably form 3 vertical rows (number of horizontally arranged particles per row: Nh = 3) and 3-6 horizontal rows (mean value fos intrahepatic tributaries then can be approached under direct vision in a relatively bloodless field for safe, accurate liquation and/or reconstruction.


Potential opportunities and perils of imperfect dengue vaccines.
Dengue vaccine development efforts have focused on the development of tetravalent vaccines. However, a recent Phase IIb trial of a tetravalent vaccine indicates a protective effect against only 3 of the 4 serotypes. While vaccines effective against a subset of serotypes may reduce morbidity and mortality, particular profiles could result in an increased number of cases due to immune enhancement and other peculiarities of dengue epidemiology. Here, we use a compartmental transmission model to assess the impact of partially effective vaccines in a hyperendemic Thai population. Crucially, we evaluate the effects that certain serotype heterogeneities may have in the presence of mass-vaccination campaigns. In the majority of scenarios explored, partially effective vaccines lead to 50% or greater reductions in the number of cases. This is true even of vaccines that we would not expect to proceed to licensure due to poor or incomplete immune responses. Our results show that a partially effective vaccine can have significant impacts on serotype distribution and mean age of cases.


Bedside Ultrasonography for Early Diagnosis of Occult Radial Head Fractures in Emergency Room: A CT-Comparative Diagnostic Study.
Some of the Mason type I fractures cannot be detected on early radiographic images. These occult fractures are considered as a diagnostic challenge for physicians. Our aim was to determine the value of bedside ultrasonography for the detection of Mason I radial head fractures that are non-visible in early X-ray's. A prospective blind single-center diagnostic study was conducted (from June 2012 till May 2013) concerning 23 patients who were clinically suspicious of having a radial head fracture. These patients were evaluated with a bedside high frequency ultrasound in the Emergency Room (E.R.). The two sonographic criteria that were considered to be diagnostic for fracture were: a. effusion besides the radial head-neck and b. cortical discontinuity of the radial head or neck. All patients also underwent a Computed Tomography (CT) as the gold standard imaging modality for diagnosis of occult radial head fractures. Fifteen out of 23 patients were diagnosed with radial head fracture using both ultrasound and CT. On the other hand, there were three patients with negative ultrasound and positive CT, in addition two patients were found positive in the ultrasonographic exam, while this result was not confirmed by the CT scan. In comparison with CT, ultrasound exam appeared to have 83.3% sensitivity, 60% specificity, 88.2% positive prognostic value and 50% negative prognostic value (when at least one diagnostic sonographic criterion was positive). The accuracy of the sonographic study for the diagnosis of the aforementioned fractures was 78.2%. Effusion in contact with the radial neck was the most sensitive sonographic sign (14/15 of the true positive radial head ultrasounds). Bedside ultrasound in the E.R. was proven to be a sensitive tool for early (day-1) diagnosis of the occult radial head fractures. It could be used as an adjacent imaging modality in patients suspicious for radial head fracture, when the initial X-rays are negative. II.


Severity and Frequency of Menopausal Symptoms in Middle Aged Women, Rasht, Iran.
Menopause is a natural event in women's life. Some studies have shown that, these symptoms can lead to low quality of life. To identify the severity and frequency of menopausal symptoms in different stages of menopause, in a group of middle aged women. This cross-sectional study was conducted on 646 women aged 45-60 years in Rasht, Iran, who were included in the study by convenience sampling method. Menopause Rating Scale (MRS) was used to measure the severity of menopausal symptoms. Descriptive and analytical statistics by SPSS software version 19.0 was used for analysis. Mean age of women was 50.7± 4.65 years. About half of the participants (49.2%) were postmenopausal. The remaining 18.1% (n=117) and 32.7% (n=211) were perimenopausal and premenopausal, respectively. The score of physical domain for menopause symptoms was higher in postmenopausal women. Joint and muscle problems were the most frequent symptoms in post and perimenopausal women. Also, total score for menopausal symptoms was more in postmenopausal group than other groups (p<0.001). Severe symptoms were seen only in three post-menopausal women and 55.2% of them had mild to moderate symptoms. The menopause related symptoms differed based on the stage of menopause. Such studies are useful for creating awareness among women so that they can identify common menopausal symptoms and consequently may improve their quality of life.


Mobility of supercooled liquid toluene, ethylbenzene, and benzene near their glass transition temperatures investigated using inert gas permeation.
We investigate the mobility of supercooled liquid toluene, ethylbenzene, and benzene near their respective glass transition temperatures (Tg). The permeation rate of Ar, Kr, and Xe through the supercooled liquid created when initially amorphous overlayers are heated above their glass transition temperature is used to determine the diffusivity. Amorphous benzene crystallizes at temperatures well below its Tg, and as a result, the inert gas underlayer remains trapped until the onset of benzene desorption. In contrast, for toluene and ethylbenzene the onset of inert gas permeation is observed at temperatues near Tg. The inert gas desorption peak temperature as a function of the heating rate and overlayer thickness is used to quantify the diffusivity of supercooled liquid toluene and ethylbenzene from 115 to 135 K. In this temperature range, diffusivities are found to vary across 5 orders of magnitude (∼10(-14) to 10(-9) cm(2)/s). The diffusivity data are compared to viscosity measurements and reveal a breakdown in the Stokes-Einstein relationship at low temperatures. However, the data are well fit by the fractional Stokes-Einstein equation with an exponent of 0.66. Efforts to determine the diffusivity of a mixture of benzene and ethylbenzene are detailed, and the effect of mixing these materials on benzene crystallization is explored using infrared spectroscopy.


Identification of amino-acid substitutions in the proteolipid subunit of the ATP synthase from dicyclohexylcarbodiimide-resistant mutants of Escherichia coli.
The amino acid sequence of the proteolipid subunit of the ATP synthase was analyzed in six mutant strains from Escherichia coli K12, selected for their increased resistance towards the inhibitor N,N'-dicyclohexylcarbodiimide. All six inhibitor-resistant mutants were found to be altered at the same position of the proteolipid, namely at the isoleucine at residue 28. Two substitutions could be identified. In type I this residue was substituted by a valine resulting in a moderate decrease in sensitivity to dicyclohexylcarbodiimide. Type II contained a threonine residue at this position. Here a strong resistance was observed. These two amino acid substitutions did not influence functional properties of the ATPase complex. ATPase as well as ATP-dependent proton-translocating activities of mutant membranes were indistinguishable from the wild type. At elevated concentrations, dicyclohexylcarbodiimide still bound specifically to the aspartic acid at residue 61 of the mutant proteolipid as in the wild type, and thereby inhibited the activity of the ATPase complex. It is suggested that the residue 28 substituted in the resistant mutants interacts with dicyclohexylcarbodiimide during the reactions leading to the covalent attachment of the inhibitor to the aspartic acid at residue 61. This could indicate that these two residues are in close vicinity and would thus provide a first hint on the functional conformation of the proteolipid. Its polypeptide chain would have to fold back to bring together these two residues separated by a segment of 32 residues.


Rapid maxillary expansion effects on nocturnal enuresis in children: a follow-up study.
To assess the effects of 10-14 days of rapid maxillary expansion (RME) on nocturnal enuresis (NE) in children who have long-standing resistance to medical therapy and to evaluate the long-term success rate after 10 years. Twenty-three children with NE, aged 6-15 years old (mean age = 10), who wet their bed almost every night and had never been dry were referred from pediatric specialists. Mean RME was 6.5 mm (range = 5-8), but only 7 of the 23 patients had lateral crossbites. Rhinomanometric measurements were taken before and after RME, and patients were interviewed 10 years after treatment. Positive effects of RME were observed in nearly 50% of the patients within 1 month of treatment: six were completely dry and five had notable improvements. Relapse in the overexpanded arches to a normal transversal occlusion was noted within 1 year. No correlation was found between success and improved airways, familial heritage, school performance, or other social factors. Younger children responded better to the treatment. Results were stable at the 10-year follow-up, and no adverse reactions were reported. Orthodontic RME is a new option for treating children with NE who are resistant to medical therapy; the treatment has no adverse side effects.


Zinc signalling and subcellular distribution: emerging targets in type 2 diabetes.
A finely tuned subcellular distribution of zinc (Zn), through the coordinated action of Zn transporters (ZnTs) and metallothioneins (MTs), is crucial for optimal cell function. Dysfunctions of these proteins might act as key causative or promoting factors in several chronic pathologies. Evidence of their involvement in the pathogenesis of type 2 diabetes (DM2) is emerging. The association of single nucleotide polymorphisms in genes encoding ZnT-8 and MT with DM2 has drawn attention to the relevance of Zn homeostasis for insulin secretory capacity and responsiveness. Here, we propose that potential mechanisms leading to altered subcellular Zn distribution rather than deficiency might be important in DM2. Increasing knowledge of the mechanisms of Zn homeostasis and signalling should promote the development of targeted interventions with the potential to reduce the burden of disease.


A regret-induced status quo bias.
A suboptimal bias toward accepting the status quo option in decision-making is well established behaviorally, but the underlying neural mechanisms are less clear. Behavioral evidence suggests the emotion of regret is higher when errors arise from rejection rather than acceptance of a status quo option. Such asymmetry in the genesis of regret might drive the status quo bias on subsequent decisions, if indeed erroneous status quo rejections have a greater neuronal impact than erroneous status quo acceptances. To test this, we acquired human fMRI data during a difficult perceptual decision task that incorporated a trial-to-trial intrinsic status quo option, with explicit signaling of outcomes (error or correct). Behaviorally, experienced regret was higher after an erroneous status quo rejection compared with acceptance. Anterior insula and medial prefrontal cortex showed increased blood oxygenation level-dependent signal after such status quo rejection errors. In line with our hypothesis, a similar pattern of signal change predicted acceptance of the status quo on a subsequent trial. Thus, our data link a regret-induced status quo bias to error-related activity on the preceding trial.


Recovery of Recombinant Rotaviruses by Reverse Genetics.
Rotaviruses are the primary cause of severe gastroenteritis in infants and young children throughout the world. To combat rotavirus illness, several live oral vaccines have been developed, or are under development, that are formulated from attenuated human or human-animal reassortant strains of rotavirus. While the effectiveness of these vaccines is generally high in developed countries, the same vaccines are significantly less effective in many developing countries, where the need for rotavirus vaccines is greatest. Recently, reverse genetics systems have been developed that allow modification of the segmented double-stranded (ds)RNA genome of rotavirus, including reprogramming the genome to allow expression of additional proteins that may stimulate expanded neutralizing antibody responses in vaccinated children. The use of reverse genetics systems may not only lead to the development of more potent classes of vaccines but can be used to better explore the intricacies of rotavirus molecular biology and pathogenesis. In this article, we share protocols that can be used to generate recombinant rotaviruses, including modified strains that express foreign proteins.


Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a.
More than 1,200 mutations in neuronal voltage-gated sodium channel (VGSC) genes have been identified in patients with several epilepsy syndromes. A common feature of genetic epilepsies is variable expressivity among individuals with the same mutation. The Scn2a(Q54) transgenic mouse model has a mutation in Scn2a that results in spontaneous epilepsy. Scn2a(Q54) phenotype severity varies depending on the genetic strain background, making it a useful model for identifying and characterizing epilepsy modifier genes. Scn2a(Q54) mice on the [C57BL/6JxSJL/J]F1 background exhibit earlier seizure onset, elevated spontaneous seizure frequency, and decreased survival compared to Scn2a(Q54) mice congenic on the C57BL/6J strain. Genetic mapping and RNA-Seq analysis identified Cacna1g as a candidate modifier gene at the Moe1 locus, which influences Scn2a(Q54) phenotype severity. In this study, we evaluated the modifier potential of Cacna1g, encoding the Cav3.1 voltage-gated calcium channel, by testing whether transgenic alteration of Cacna1g expression modifies severity of the Scn2a(Q54) seizure phenotype. Scn2a(Q54) mice exhibited increased spontaneous seizure frequency with elevated Cacna1g expression and decreased seizure frequency with decreased Cacna1g expression. These results provide support for Cacna1g as an epilepsy modifier gene and suggest that modulation of Cav3.1 may be an effective therapeutic strategy.


Value of information in natural resource management: technical developments and application to pink-footed geese.
The "value of information" (VOI) is a generic term for the increase in value resulting from better information to guide management, or alternatively, the value foregone under uncertainty about the impacts of management (Yokota and Thompson, Medical Decision Making 2004; 24: 287). The value of information can be characterized in terms of several metrics, including the expected value of perfect information and the expected value of partial information. We extend the technical framework for the value of information by further developing the relationship between value metrics for partial and perfect information and describing patterns of their performance. We use two different expressions for the expected value of partial information to highlight its relationship to the expected value of perfect information. We also develop the expected value of partial information for hierarchical uncertainties. We highlight patterns in the value of information for the Svalbard population of the pink-footed goose (Anser brachyrhynchus), a population that is subject to uncertainty in both reproduction and survival functions. The framework for valuing information is seen as having widespread potential in resource decision making, and serves as a motivation for resource monitoring, assessment, and collaboration.


Molecular and cellular biology of interleukin-3.
The cloning and expression of the genes for rat, mouse, and human IL-3 have resulted in major advances in our knowledge of this lymphokine and the biological processes in which it is involved. Such advances include the primary structures of the IL-3 proteins, the nucleotide sequences of the IL-3 genes, and the elucidation of the retroviral insertion that resulted in constitutive synthesis of IL-3 by the leukemic cell line WEHI-3B. These advances have facilitated studies of the control of IL-3 gene expression in normal and malignant cells, which is an ongoing area of interest. The use of the cloned IL-3 gene in a retroviral expression vector has allowed the generation of experimental autocrine leukemias from IL-3-dependent cell lines. The use of recombinant rat, mouse, and human IL-3 has verified that IL-3 is a multilineage hemopoietic regulator in each of these species. Although it is clear that in each of the above species IL-3 promotes the growth of a wide variety of myeloid progenitors, the regulation of stem-cell division and maturation by IL-3 and its synergism with other regulators requires clarification and remains an active area of research. The discovery that hemopoietic stem cells from certain murine strains do not proliferate in response to IL-3 alone has provided a model system in which to analyze the synergistic activities of IL-3. It will be interesting to see whether analogous differences in the responsiveness of stem cells to IL-3 also exist in humans. Our work on the ontogeny of blood cell development in embryonic and fetal mice indicates that in every strain, early hemopoietic progenitor cells respond to IL-3 plus M-CSF, or to IL-3 plus IL-4, rather than to IL-3, M-CSF, or IL-4 alone. The difficulties encountered in acquiring sufficient cells to work with from embryonic sources could possibly be overcome by developing a fetal sheep model in which access to the embryo and fetus can be achieved at several sequential points in development. It may then be possible to determine the molecular events that regulate primitive stem-cell responsiveness to IL-3 as well as other hemopoietic cytokines. Recombinant IL-3 proteins should continue to prove valuable in further biological studies of IL-3, in the generation of monoclonal antibodies against IL-3, and for further studies of the IL-3 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)


Brazilin-7-acetate, a novel potential drug of Parkinson's disease, hinders the formation of α-synuclein fibril, mitigates cytotoxicity, and decreases oxidative stress.
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the accumulation of α-synuclein (α-Syn) aggregates. However, there are currently no effective therapies for PD. Brazilin, an inhibitor of α-Syn aggregation, is unstable and toxic. Therefore, we have developed and synthesized derivatives of brazilin. One of these derivatives, called brazilin-7-acetate (B-7-A), has shown reduced toxicity and a stronger effect on inhibiting α-Syn aggregation. It showed that B-7-A prevented the formation of α-Syn fibers and disrupted existing fibers in a dosage-dependent manner. Additionally, B-7-A significantly reduced the cytotoxicity of α-Syn aggregates and alleviated oxidative stress in PC12 cells. The beneficial effects of B-7-A were also confirmed using the Caenorhabditis elegans model. These effects included preventing the accumulation of α-Syn clumps, improving behavior disorder, increasing lifespan, reducing oxidative stress, and protecting against lipid oxidation and loss. Finally, B-7-A showed good ADMET properties in silico. Based on these findings, B-7-A exhibits potential as a prospective treatment for PD.


Early technical and clinical results with retrievable inferior vena caval filters.
Deep venous thrombosis with or without subsequent pulmonary embolism is a common preventable cause of hospital death. Although anticoagulation is the accepted standard therapy for thromboembolic disease, in situations in which anticoagulation is contraindicated, interruption of the inferior vena cava (IVC) by means of percutaneous placement of a filter has become a widely used alternative. We report our initial experience with two retrievable IVC filters. Between July 2002 and April 2003, 13 patients (mean age 54 +/- 7 years; range 29-75 years) underwent percutaneous placement of either the Gunther Tulip (n = 5; Cook Inc., Bloomington, IN) or OptEase (n = 8; Cordis, Miami Lakes, FL) IVC filter. Five patients had filters placed prophylactically before major surgery. The remaining eight patients had had a contraindication to anticoagulation, and three had experienced a hemorrhagic complication as a result of anticoagulation following either a recently documented deep venous thrombosis (n = 3) or pulmonary embolism (n = 5). Filters were successfully placed in all 13 patients, with a duration of implantation ranging from 2 to 15 days. Retrieval was attempted in 12 patients (in 1 patient, permanent filtration was secondarily requested) and was achieved in 10 (84.6%) patients. In 2 patients, retrieval failure was due to device angulation within the vena cava precluding safe retrieval. In both instances, the device used was the Gunther Tulip filter. No patient developed symptomatic pulmonary embolism or insertion-site thrombosis following either filter deployment or removal. Trapped thrombus in the filters was seen in all patients. Retrieval required a mean of 6.8 minutes (range 5-10.2 minutes) of fluoroscopy time. Neither filter migration nor caval injury was observed. Temporary IVC filters are effective and are associated with a high retrieval success rate. Further study is warranted to determine the maximal duration of implantation and whether retrievable IVC filters should expand the indications for IVC filter placement.


Association of device type, flavours and vaping behaviour with tobacco product transitions among adult electronic cigarette users in the USA.
Few studies assess whether electronic cigarette (e-cigarette) device characteristics or flavours impact longitudinal patterns of cigarette and e-cigarette use. We examined data from waves 2-4 of the Population Assessment of Tobacco and Health Study (2014-2018). Among adult (≥18 years) current e-cigarette users at wave 2 who were current smokers (dual users; n=1759) and former smokers (exclusive e-cigarette users; n=470), we classified participants into four use patterns at wave 3 (~12 months later) and wave 4 (~24 months later): (1) dual use of e-cigarettes and cigarettes; (2) exclusive cigarette smoking; (3) exclusive e-cigarette use; (4) non-use of both products. We used multinomial logistic regression to assess correlates of changing use patterns at 24 months, relative to no change, adjusting for sociodemographic factors. At 24 months, 26.5% of baseline exclusive e-cigarette users, and 9% of baseline dual users, abstained from both vaping and smoking. Participants who vaped non-tobacco flavours (vs tobacco flavours), and used refillable tank or modifiable devices (vs disposable, cartridges and other devices) were less likely to transition to non-use of both products and to exclusive cigarette smoking. Baseline daily vaping (vs non-daily) was positively associated with exclusive e-cigarette use at 24 months for baseline daily cigarette smokers, but negatively associated with exclusive e-cigarette use and non-use of both products at 24 months for baseline non-daily smokers. Non-tobacco flavours, daily vaping and modifiable e-cigarette devices may help some smokers abstain from cigarette smoking via transitioning to exclusive e-cigarette use, but are also associated with ongoing exclusive e-cigarette use.


Obesity in America.
The prevalence of obesity in America continues to grow significantly. Awareness and understanding of the disease of obesity and treatment options for it appear to be lacking among the general US population. This study aimed to identify misperceptions in diagnosis and treatment of obesity, struggles Americans face in obtaining treatment, consequences of obesity, and perceived barriers to weight loss. University hospital, United States. A survey of 1509 adults was completed in September 2016 using AmeriSpeak, a probability-based panel designed to be representative of the US household population. The survey included oversamples of blacks and Hispanics. The study analyzed quantitative data from structured interviews and presents descriptive statistics related to public attitudes toward obesity. Of Americans, 81% consider obesity to be the most serious health problem facing the nation, tying cancer as the top issue and landing ahead of diabetes (72%), heart disease (72%), mental illness (65%), and HIV infection and AIDS (46%). Nearly all Americans (94%) agree that obesity itself, even when no other diseases are present, increases the risk for early death. Most Americans overestimate the effectiveness of some obesity treatments, such as diet and exercise alone. Many overweight and obese Americans do not consult a doctor at all about their issues of excess weight. There is increased awareness about the serious consequences of obesity, but there is still a lack of understanding about the reasons and best treatment modalities for the disease.


Interdisciplinary-Inspired Smart Antibacterial Materials and Their Biomedical Applications.
The discovery of antibiotics has saved millions of lives, but the emergence of antibiotic-resistant bacteria has become another problem in modern medicine. To avoid or reduce the overuse of antibiotics in antibacterial treatments, stimuli-responsive materials, pathogen-targeting nanoparticles, immunogenic nano-toxoids, and biomimetic materials are being developed to make sterilization better and smarter than conventional therapies. The common goal of smart antibacterial materials (SAMs) is to increase the antibiotic efficacy or function via an antibacterial mechanism different from that of antibiotics in order to increase the antibacterial and biological properties while reducing the risk of drug resistance. The research and development of SAMs are increasingly interdisciplinary because new designs require the knowledge of different fields and input/collaboration from scientists in different fields. A good understanding of energy conversion in materials, physiological characteristics in cells and bacteria, and bactericidal structures and components in nature are expected to promote the development of SAMs. In this review, the importance of multidisciplinary insights for SAMs is emphasized, and the latest advances in SAMs are categorized and discussed according to the pertinent disciplines including materials science, physiology, and biomimicry.


Molecular Characterization of, and Antimicrobial Resistance in, Clostridioides difficile from Thailand, 2017-2018.
Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI). Many antimicrobials, such as fluoroquinolones, have been associated with outbreaks of CDI globally. This study characterized AMR among clinical C. difficile strains in Thailand, where antimicrobial use remains inadequately regulated. Stool samples were screened for tcdB and positives were cultured. C. difficile isolates were characterized by toxin profiling and PCR ribotyping. Antimicrobial susceptibility testing was performed by agar incorporation, and whole-genome sequencing and AMR genotyping were performed on a subset of strains. There were 321 C. difficile strains isolated from 326 stool samples. The most common toxigenic ribotype (RT) was RT 017 (18%), followed by RTs 014 (12%) and 020 (7%). Resistance to clindamycin, erythromycin, moxifloxacin, and rifaximin was common, especially among RT 017 strains. AMR genotyping revealed a strong correlation between resistance genotype and phenotype for moxifloxacin and rifaximin. The presence of erm-class genes was associated with high-level clindamycin and erythromycin resistance. Point substitutions in the penicillin-binding proteins were not sufficient to confer meropenem resistance, but a Y721S substitution in PBP3 was associated with a 4.37-fold increase in meropenem minimal inhibitory concentration. No resistance to metronidazole, vancomycin, or fidaxomicin was observed.


Predictors of emotional distress reported by soldiers in the combat zone.
Few studies have examined rates of distress of military personnel during deployment to a war zone. Our study sought to (a) identify rates of self-reported posttraumatic stress disorder (PTSD) and depression symptoms during combat deployment, (b) characterize higher order dimensions of emotional distress experienced by soldiers during deployment, and (c) identify predictors of these dimensions of emotional distress. Participants were 2677 National Guard soldiers deployed as part of Operation Iraqi Freedom in 2006-07. We performed a principal components factor analysis on items of the PTSD Checklist - Military Version and the Beck Depression Inventory to identify dimensions of emotional distress, followed by multiple regression analyses to identify factors that predicted these dimensions of distress. Rates of PTSD and depression in our sample were 7% and 9%, respectively. Five dimensions of emotional distress emerged: negative affect/cognitions, trauma-specific re-experiencing and avoidance, vegetative symptoms, loss of interest/numbing symptoms, and arousal/irritability. Two dimensions, trauma-specific symptoms and arousal/irritability, appeared to be more indicative of trauma sequelae, while the other three dimensions were more indicative of depressive symptoms. Demographic factors, combat exposure (including injury and exposure to explosive blast), and attitudinal variables predicted trauma-specific aspects of distress. Symptoms characteristic of depression or generalized distress were predicted by female gender, recent prior deployment, and attitudinal factors but were not predicted by blast exposure or injury. These findings suggest specific targets for contextual and individual interventions to reduce deployment-related distress and point out the need for longitudinal follow-up to determine long-term implications for post-deployment functioning.


Use of folded vascularized rib graft in anterior fusion after treatment of thoracic and upper lumbar lesions. Technical note.
For lesions involving the anterior and/or middle column of the spine, an anterior approach is adequate for curetting the lesion and restoring spinal stability. Materials such as autogenous bone grafts, cages with bone chips, some artificial materials, or allografts are used as strut materials. Rib material is usually removed when the anterior approach is conducted for thoracic or thoracolumbar lesions. A rib itself is not rigid enough to support the load, and a bone union is not easily obtained. The purpose of this paper is to describe a method of grafting vascularized rib in folded form to fill the defects left after removal of a spinal lesion. The rib, with the artery and vein at two levels cranial to the involved vertebral body, was isolated from surrounding tissues such as the intercostal nerve, muscles, and pleura. After curetting the lesion, the rib was folded into three or four pieces to a length adequate to fill the defect and inserted as a pedicled vascularized graft. A total of 23 cases, including 14 men and nine women, underwent surgery in which this grafting technique was used. The pathological conditions requiring anterior decompression and fusion were spinal trauma in nine cases, spinal infection in six cases, osteoporotic fracture in seven cases, and spinal metastasis in one case. In all cases a solid bone union was obtained and all infections resolved. With vascularized rib graft folded into three to four pieces, solid bone union can be obtained without use of any other grafted materials even in cases of infection and osteoporosis.


Salmonella spp. are cytotoxic for cultured macrophages.
We have shown by a variety of microscopical and biochemical techniques that Salmonella spp. are cytotoxic for cultured J774A.1 and bone marrow-derived murine macrophages. The cytotoxicity is initially manifested by inhibition of membrane ruffling and macropinocytosis in infected macrophages, and is followed by cell death. Macrophages killed by Salmonella spp. exhibited features of apoptosis such as condensation and fragmentation of chromatin, membrane blebbing, and the presence of cytoplasmic nucleosomes and apoptotic bodies. Cytotoxicity does not require bacterial internalization as cytochalasin D, a drug that prevents bacterial uptake, did not prevent Salmonella-induced macrophage cell death. However, the cytotoxic effects are strictly dependent upon the expression of the invasion-associated Type III protein-secretion system encoded at centisome 63 of the Salmonella chromosome. Wild-type Salmonella typhimurium grown under conditions that do not allow optical expression of this system or strains of Salmonella carrying mutations in genes that encode components of this protein-secretion system were devoid of macrophage cytotoxicity. In addition, mutations in invJ, spaO, sipB, sipC and sipD, which encode proteins that are secreted via this secretion apparatus and are required for bacterial entry into non-phagocytic cells, also abolished the toxicity. In contrast, mutations in sipA and sptP, which encode secreted proteins that are not required for bacterial invasion, had no effect on macrophage cytotoxicity. These results indicate a close correlation between the mechanisms of bacterial internalization into non-phagocytic cells and those that lead to macrophage cytotoxicity. Host-adapted serotypes of Salmonella such as S. typhi, S. gallinarum and S. dublin were also toxic for murine macrophages, indicating that this virulence property is probably present in most Salmonella spp. and is not associated with the mechanisms responsible for host range.