Inhibition of MK801 binding in adult rat brain sections by conantokin-G and conantokin-T.
The functional interactions of conantokins with anatomical sites in rat brain have been assessed through displacement of the non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, dizocilpine (MK801). The binding of (+)-3-[125I]-iodo-MK801 (1 nM) to coronal sections from adult rat brain was inhibited in a dose-dependent manner by conantokin-T (con-T) and conantokin-G (con-G). Quantitative densitometry was used to determine IC50 values for conantokin inhibition of [125I]-MK801 binding in the cortex, thalamus and hippocampus. Con-T completely inhibited [125I]-MK801 specific binding in all brain regions at a saturating concentration of 100 microM. Con-G was able to completely displace [125I]-MK801 in the cortex and thalamus, but only inhibited this same binding up to approximately 90% in the hippocampus. Both peptides maintained their inhibitory properties in the presence of 1 mM EDTA, suggesting that divalent cations are not required for their action in this regard. The added presence of spermine (150 microM) resulted in a two-fold increase in [125I]-MK801 binding and a two-fold decrease in the IC50 values for both peptides. The data obtained in this investigation further demonstrate that [125I]-MK801 is a useful probe for the indirect determination of functional NMDAR ligand binding sites in rat brain sections.


Spatial distribution of canine zoonotic enteroparasites in Bahía Blanca, Argentina.
The objectives of this research were: (1) to determine the occurrence of zoonotic enteroparasites in dog feces from Bahía Blanca, Argentina; (2) to characterize the spatial distribution of the parasites found in association with the quality of life index (QLI) in neighborhoods of Bahía Blanca; and (3) to determine if the presence of a particular parasite genus in a stool sample was facilitated or impeded by the presence of other parasite genera. Samples of dog stools (n=475) were collected between December 2012 and December 2013 in areas with varying QLI. The association between QLI values and the presence of parasites was analyzed using logistic regression. Overall enteroparasite occurrence was 36.6%. Parasitic forms found included nematode larvae, cysts of Blastocystis spp., Giardia spp., and oocysts of Cryptosporidium spp., and eggs of Ancylostoma caninum, Toxocara canis, cestodes and Trichuris spp. For certain enteroparasites, we detected significant associations between their occurrence and QLI. Feces collected in areas with medium and low QLI were 2.46 and 5.43 times more likely, respectively, to contain A. caninum than stools from the high-QLI area. Samples from areas with low QLI were 2.36 times more likely to contain Trichuris spp. than those from the high QLI area. Regarding protozoa, feces from areas with low QLI were 2.4 times more likely to be positive than those from areas with high QLI. We demonstrated that canine zoonotic parasites have a wide distribution in the study area, and that occurrence is higher in neighborhoods with lower QLI.


Chronic consumption of alcohol increases alveolar bone loss.
This study evaluated the effects of the chronic consumption of different concentrations of alcohol on the experimental periodontitis (EP). 160 rats were divided into 4 groups: (EP-NT) rats with EP and no alcohol exposure; (EP-A14) rats with EP exposed to 14% alcohol; (EP-A25) rats with EP exposed to 25% alcohol; (EP-A36) rats with EP exposed to 36% alcohol. The animals from the EP-A14, EP-A25 and EP-A36 groups were subjected to different concentrations of alcohol 30 days before EP induction. The histological characteristics, percentage of bone in the furcation (PBF) and bone metabolism in the furcation region were evaluated. The PBF and tartrate-resistant acid phosphatase (TRAP) data were subjected to statistical analysis. The EP-A14, EP-A25 and EP-A36 groups had lower PBFs compared with the EP-NT group. A more severe inflammatory process and a greater number of TRAP+ cells were also observed. In the EP-A14, EP-A25 and EP-A36 groups, the inflammatory process became more severe as the ingested alcoholic concentration increased. An increase in RANKL immunolabeling and a significantly higher number of TRAP+ cells were also observed. We conclude that chronic alcohol consumption increases the severity of experimental periodontitis in a dose-dependent manner by increasing the magnitude of local inflammatory responses and stimulating alveolar bone resorption.


Condylomata acuminata of the cervix: histopathology and association with cervical neoplasia.
Cervical specimens from 531 consecutive cases were reviewed to determine the frequency of cervical condylomata acuminata (CLA) and their association with cervical intraepithelial neoplasia (CIN). CLA and CIN were subclassified into three groups based on the criteria previously established in the literature. Our data indicate that CLA was present in 103 (19%) cases and that 44 (43%) of these had CIN as well. The total number of cases of CIN in this series was 146 (27%) with 44 of these (30%) having associated CLA. Of the eight CIN cases in women under 20 years of age, seven (99.6%) had associated CLA. The mean age of patients with CIN alone was 31 years; patients with CIN and CLA were younger, with a mean age of 24 years. These findings indicate that cervical CLA is a common lesion affecting young women and that there is a significant association of CLA with CIN. Women with CLA appear to be at significant risk for development of CIN.


Population receptive field estimates for motion-defined stimuli.
The processing of motion changes throughout the visual hierarchy, from spatially restricted 'local motion' in early visual cortex to more complex large-field 'global motion' at later stages. Here we used functional magnetic resonance imaging (fMRI) to examine spatially selective responses in these areas related to the processing of random-dot stimuli defined by differences in motion. We used population receptive field (pRF) analyses to map retinotopic cortex using bar stimuli comprising coherently moving dots. In the first experiment, we used three separate background conditions: no background dots (dot-defined bar-only), dots moving coherently in the opposite direction to the bar (kinetic boundary) and dots moving incoherently in random directions (global motion). Clear retinotopic maps were obtained for the bar-only and kinetic-boundary conditions across visual areas V1-V3 and in higher dorsal areas. For the global-motion condition, retinotopic maps were much weaker in early areas and became clear only in higher areas, consistent with the emergence of global-motion processing throughout the visual hierarchy. However, in a second experiment we demonstrate that this pattern is not specific to motion-defined stimuli, with very similar results for a transparent-motion stimulus and a bar defined by a static low-level property (dot size) that should have driven responses particularly in V1. We further exclude explanations based on stimulus visibility by demonstrating that the observed differences in pRF properties do not follow the ability of observers to localise or attend to these bar elements. Rather, our findings indicate that dorsal extrastriate retinotopic maps may primarily be determined by the visibility of the neural responses to the bar relative to the background response (i.e. neural signal-to-noise ratios) and suggests that claims about stimulus selectivity from pRF experiments must be interpreted with caution.


Temporal adjustment of the juxtaglomerular apparatus during sustained inhibition of proximal reabsorption.
Tubuloglomerular feedback (TGF) stabilizes nephron function by causing changes in single-nephron GFR (SNGFR) to compensate for changes in late proximal flow (VLP). TGF responds within seconds and reacts over a narrow range of VLP that surrounds normal VLP. To accommodate sustained increases in VLP, TGF must reset around the new flow. We studied TGF resetting by inhibiting proximal reabsorption with benzolamide (BNZ; administered repeatedly over a 24-hour period) in Wistar-Froemter rats. BNZ acutely activates TGF, thereby reducing SNGFR. Micropuncture was performed 6-10 hours after the fourth BNZ dose, when diuresis had subsided. BNZ caused glomerular hyperfiltration, which was prevented with inhibitors of macula densa nitric oxide synthase (NOS). Because of hyperfiltration, BNZ increased VLP and distal flow, but did not affect the basal TGF stimulus (early distal salt concentration). BNZ slightly blunted normalized maximum TGF response and the basal state of TGF activation. BNZ sensitized SNGFR to reduction by S-methyl-thiocitrulline (SMTC) and caused the maximum TGF response to be strengthened by SMTC. Sensitization to type I NOS (NOS-I) blockers correlated with increased macula densa NOS-I immunoreactivity. Tubular transport measurements confirmed that BNZ affected TGF within the juxtaglomerular apparatus. During reduced proximal reabsorption, TGF resets to accommodate increased flow and SNGFR through a mechanism involving macula densa NOS.


Ischemic injury induces ADF relocalization to the apical domain of rat proximal tubule cells.
Breakdown of proximal tubule cell apical membrane microvilli is an early-occurring hallmark of ischemic acute renal failure. Intracellular mechanisms responsible for these apical membrane changes remain unknown, but it is known that actin cytoskeleton alterations play a critical role in this cellular process. Our laboratory previously demonstrated that ischemia-induced cell injury resulted in dephosphorylation and activation of the actin-binding protein, actin depolymerizing factor [(ADF); Schwartz, N, Hosford M, Sandoval RM, Wagner MC, Atkinson SJ, Bamburg J, and Molitoris BA. Am J Physiol Renal Fluid Electrolyte Physiol 276: F544-F551, 1999]. Therefore, we postulated that ischemia-induced ADF relocalization from the cytoplasm to the apical microvillar microfilament core was an early event occurring before F-actin alterations. To directly investigate this hypothesis, we examined the intracellular localization of ADF in ischemic rat cortical tissues by immunofluorescence and quantified the concentration of ADF in brush-border membrane vesicles prepared from ischemic rat kidneys by using Western blot techniques. Within 5 min of the induction of ischemia, ADF relocalized to the apical membrane region. The length of ischemia correlated with the time-related increase in ADF in isolated brush-border membrane vesicles. Finally, depolymerization of microvillar F-actin to G-actin was documented by using colocalization studies for G- and F-actin. Collectively, these data indicate that ischemia induces ADF activation and relocalization to the apical domain before microvillar destruction. These data further suggest that ADF plays a critical role in microvillar microfilament destruction and apical membrane damage during ischemia.


Production of high concentrations of H2O2 in a bioelectrochemical reactor fed with real municipal wastewater.
Bioelectrochemical systems can be used to energy-efficiently produce hydrogen peroxide (H2O2) from wastewater. Organic compounds in the wastewater are oxidized by microorganisms using the anode as electron acceptor. H2O2 is produced by reduction of oxygen on the cathode. In this study, we demonstrate for the first time production of high concentrations of H2O2 production from real municipal wastewater. A concentration of 2.26 g/L H2O2 was produced in 9 h at 8.3 kWh/kgH2O2. This concentration could potentially be useful for membrane cleaning at membrane bioreactor wastewater treatment plants. With an acetate-containing nutrient medium as anode feed, a H2O2 concentration of 9.67 g/L was produced in 21 h at an energy cost of 3.0 kWh/kgH2O2. The bioelectrochemical reactor used in this study suffered from a high internal resistance, most likely caused by calcium carbonate deposits on the cathode-facing side of the cation exchange membrane separating the anode and cathode compartments.


The nature and extent of war injuries sustained by combat specialty personnel killed and wounded in Afghanistan and Iraq, 2003-2011.
Previous studies regarding combat wounding have a limited translational capacity due to inclusion of soldiers from all military branches and occupational specialties as well as a lack of information regarding soldiers who died in theater. A search was performed of the Department of Defense Trauma Registry and Armed Forces Medical Examiner data set for the years 2003 to 2011 to identify all injured personnel with the military specialty 19D (cavalry scout). A manual search was conducted for each record identified, and age, rank, location and manner of injury, mechanism of injury, Injury Severity Score (ISS), and extent of wounding were abstracted. The incidence of injuries by body region and rates for specific types of wounds were determined. Statistically significant associations between rank, location of injury, manner of injury, body region involved, and injury mechanism were assessed using χ2 analysis. Associations between ISS, rank, manner of injury, and survival were evaluated by t test with Satterthwaite correction. A total of 701 casualties were identified with 3,189 distinct injuries. Mean (SD) age of injured personnel was 25.9 (6.0) years. Thirty-five percent of the cohort was composed of soldiers who died in theater. Explosions were the most common mechanism of injury (70%), while 18% of wounds occurred owing to gunshot. Extremity wounds and injuries to the head and neck represented 34% of casualty burden. Thoracic trauma occurred in 16%, and abdominal injuries occurred in 17%. Wounds with a frequency exceeding 5% included skin, extremity, facial, brain, and gastrointestinal injuries. Vascular injury occurred in 4%. Gunshot wounds were a greater cause of injury in Afghanistan (p = 0.001) and resulted in a higher percentage of thoracic injuries (p < 0.001). The nature and extent of trauma sustained by combat-specific personnel seems to be different from that experienced by all soldiers deployed to a war zone.


Barriers and Facilitators to Model Replication Within Health Economics.
Model replication is important because it enables researchers to check research integrity and transparency and, potentially, to inform the model conceptualization process when developing a new or updated model. The aim of this study was to evaluate the replicability of published decision analytic models and to identify the barriers and facilitators to replication. Replication attempts of 5 published economic modeling studies were made. The replications were conducted using only publicly available information within the manuscripts and supplementary materials. The replicator attempted to reproduce the key results detailed in the paper, for example, the total cost, total outcomes, and if applicable, incremental cost-effectiveness ratio reported. Although a replication attempt was not explicitly defined as a success or failure, the replicated results were compared for percentage difference to the original results. In conducting the replication attempts, common barriers and facilitators emerged. For most case studies, the replicator needed to make additional assumptions when recreating the model. This was often exacerbated by conflicting information being presented in the text and the tables. Across the case studies, the variation between original and replicated results ranged from -4.54% to 108.00% for costs and -3.81% to 0.40% for outcomes. This study demonstrates that although models may appear to be comprehensively reported, it is often not enough to facilitate a precise replication. Further work is needed to understand how to improve model transparency and in turn increase the chances of replication, thus ensuring future usability.


Strangulated Small Bowel Obstruction After Renal Transplant With No History of Laparotomy: Case Report.
Strangulated small bowel obstruction is a complication after abdominal surgery, which is rare in renal transplant patients. A 61-year-old man with a strangulated small bowel obstruction underwent renal transplant surgery 7 years before the current admission. He was admitted to our hospital for abdominal pain, nausea, and abdominal distention. An abdominal computed tomography and an ultrasound examination showed intestinal expansion and fluid collection without ascites. His disease was diagnosed as a small bowel obstruction and conservative treatment was begun. However, because of increasing abdominal pain and the collection of ascites, he underwent an emergency laparotomy and was diagnosed as having a strangulated small bowel obstruction. A fibrous cord had formed between the peritoneum (beside the transplanted kidney) and the root of the sigmoid mesocolon, strangulating the looped ileum and causing bleeding necrosis and hemorrhagic ascites collection. The cord and the necrotic ileum were resected, followed by an end-to-end anastomosis. He was discharged 17 days after the surgery in good condition. This is the first reported case of a person having a strangulated small bowel obstruction by a fibrous cord, who did not have a history of laparotomy after renal transplant. A strangulated small bowel obstruction after a renal transplant in a patient with no history of a laparotomy is a rare, but possible postoperative complications should be considered when making a differential diagnosis.


Statin therapy--Part II: Clinical considerations for cardiovascular disease.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins, are the medical treatment of choice for hypercholesterolemia. In addition to achieving a therapeutic decrease in serum cholesterol levels, statin therapy appears to promote pleiotropic effects that are independent of changes in serum cholesterol. These cholesterol lowering and pleiotropic effects are beneficial not only for the coronary circulation, but for the myocardium and peripheral arterial system as well. Patients receiving statin therapy must be carefully monitored, however, as statins potentially have harmful side effects and drug interactions. This article is part II of a 2-part review, and it focuses on the clinical aspects of statin therapy in cardiovascular disease.


Lower limb proprioception deficits persist following knee replacement surgery despite improvements in knee extension strength.
Knee pain and disability can persist following knee replacement surgery which may place patients at increased risk of falls. This study investigated the falls risk and the occurrence of falls of people with knee osteoarthritis (OA) before and at 12 months following knee replacement surgery. Thirty-five patients with knee OA were tested prior to undergoing knee replacement surgery and at 12 months following surgery using the short form Physiological Profile Assessment, which incorporates tests of vision, lower limb proprioception, knee extension strength, reaction time and postural sway. Physical activity, number of falls, fear of falling, pain, disability and health-related quality of life were also assessed. No significant differences were found between the number of falls pre- and post-surgery (n.s.), with 48.5 and 40% reporting at least one fall in the 12 months before and following the surgery, respectively. Improvements in knee strength, reaction time and fear of falling were evident following surgery, with no improvement in lower limb proprioception. Self-reported pain, function and stiffness were significantly improved, but health-related quality of life deteriorated following the surgery. The number of falls experienced following knee replacement surgery remained relatively high, which may be attributed to the persistence of impaired lower limb proprioception. Although knee replacement surgery improves function and alleviates pain, people who undergo this procedure may need to engage in rehabilitation following the surgery to reduce the risk of falling. Therapeutic study investigating the result of treatment on patient outcomes, Level IV.


Global snapshot of the effects of the COVID-19 pandemic on the research activities of materials scientists between Spring and Autumn 2020.
We conducted a global survey on the effects of the COVID-19 pandemic on the research activities of materials scientists by distributing a questionnaire on 9 October 2020 with a response deadline of 23 October 2020. The questions covered issues such as access to labs, effectiveness of online conferences, and effects on doctoral students for the period covering the first lockdowns until the relaxation of restrictions in late September 2020 in many countries. The survey also included online interviews with eminent materials scientists who shared their local experiences during this period. The interviews were compiled as a series of audio conversations for The STAM Podcast that is freely available worldwide. Our findings included that the majority of institutes were not prepared for such a crisis; researchers in China, Japan, and Singapore were able to resume research much quicker - for example after approximately one month in Japan - than their counterparts in the US and Europe after the first lockdowns; researchers adapted to using virtual teleconferencing to maintain contact with colleagues; and doctoral students were the hardest hit by the pandemic with deep concerns about completing their research and career prospects. We hope that the analysis from this survey will enable the global materials science community to learn from each other's experiences and move forward from the unprecedented circumstances created by the pandemic.


Cytogenetic and histological studies of testicular biopsies from subfertile men with chromosome anomaly.
Testicular biopsies from eight men with abnormal karyotypes have been examined for histological and cytogenetic evidence of disturbances of meiosis. Quantitative analysis of this material showed one, with a 13;14 Robertsonian translocation, to have apparently normal spermatogenesis. Three patients, one with a 47,XYY and two with 45,XY, inv 9 karyotypes, had an overall depression of spermatogenesis. Four others, all with major chromosomal abnormalities, had apparently normal spermatogenesis until the primary spermatocyte stage. Two of these had sex autosomal translocations. One, 45,Y,t(X;21), had a complete block at MI, the other, 46,X,t(Y;16), had a partial block at spermatid formation. One man with a reciprocal 2;10 translocation showed delay at all stages beyond spermatocyte formation and one man with an inversion of chromosome 3 showed impaired spermatid maturation.


Remission and recovery in schizophrenia: practitioner and patient perspectives.
Schizophrenia remains a complex, dynamic, multi-dimensional, and poorly understood condition. Although the concept of heterogeneity in outcome has conceptually overturned the post Kraepelinian legacy of progressive deterioration, a number of factors appear to contribute to perpetuating a pessimistic attitude toward outcome within the field. These include the limited access people with schizophrenia have to effective interventions and the phenomenon of the "clinician's illusion," which refers to the tendency of practitioners to assume that patients remain seriously ill when outside of the clinical care settings in which they are typically seen. Longitudinal studies, however, continue to point to a large number of people who experience improvements in their condition over time. Pressure from patients and their families, who experience periods of symptomatic relief and enhanced functioning first-hand, has led to the introduction of such concepts as "remission" and being "in" recovery with schizophrenia, in addition to the conventional notion of recovering "from" schizophrenia. These developments are consistent with recent policy initiatives by the U.S. and other governments around the world and aim to re-orient research and clinical practice from a traditional focus on effecting cure to exploring ways to encourage and assist people with schizophrenia to live meaningful lives in the face of an enduring illness.


Lenalidomide in the treatment of young patients with multiple myeloma: from induction to consolidation/maintenance therapy.
Multiple myeloma is the second most common hematologic malignancy. It accounts for 20,580 new cancer cases in the USA in 2009, including 11,680 cases in men, 8,900 cases in women, and 10,580 deaths overall. Although the disease remains still incurable, outcomes have improved substantially over recent years thanks to the use of high-dose therapy and the availability of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib. Various trials have shown the advantages linked to the use of novel agents in the transplant and not-transplant settings. In particular, this paper will present an overview of the results achieved with lenalidomide-containing combinations in patients eligible for high-dose therapies, namely, young patients. The advantages obtained should always be outweighed with the toxicity profile associated with the regimen used. Therefore, here, we will also provide a description of the main adverse events associated with lenalidomide and its combination.


Incidental ostracism emerges from simple learning mechanisms.
Ostracism, or social exclusion, is widespread and associated with a range of detrimental psychological and social outcomes. Ostracism is typically explained as instrumental punishment of free-riders or deviants. However, this instrumental account fails to explain many of the features of real-world ostracism, including its prevalence. Here we hypothesized that ostracism can emerge incidentally (non-instrumentally) when people choose partners in social interactions, and that this process is driven by simple learning mechanisms. We tested this hypothesis in four experiments (n = 456) with economic games in dynamic social networks. Contrary to the instrumental account of ostracism, we find that the targets of ostracism are not primarily free-riders. Instead, incidental initial variability in choosing partners for social interactions predicts later ostracism better than the instrumental account. Using computational modelling, we show that simple reinforcement learning mechanisms explain the incidental emergence of ostracism, and that they do so better than a formalization of the instrumental account. Finally, we leveraged these reinforcement learning mechanisms to experimentally reduce incidental ostracism. Our results demonstrate that ostracism is more incidental than previously assumed and can arise from basic forms of learning. They also show that the same mechanisms that result in incidental ostracism can help to reduce its emergence.


Initial maintenance therapy adherence among older adults with asthma-COPD overlap.
To examine the impact of initial maintenance therapy (IMT) type (inhaled corticosteroid [ICS] vs fixed-dose combination of ICS and long-acting β agonist [ICS/LABA]) on trajectories of adherence among older adults (≥ 65 years) with coexisting asthma and chronic obstructive pulmonary disease (COPD), known as asthma-COPD overlap (ACO). We used a longitudinal, retrospective cohort design. This study used a cohort of older adults with ACO using longitudinal data from a 10% sample of Optum's Deidentified Clinformatics Data Mart. We adopted group-based trajectory modeling to identify medication adherence trajectories over 12 months. Multinomial logistic regressions were used to evaluate the unadjusted and adjusted associations of IMT medication and adherence trajectory categories. All analyses accounted for treatment option selection bias with inverse probability treatment weighting. Of 1555 individuals, 73% of the sample used ICS/LABA for IMT. Four medication adherence trajectories were observed regardless of regimen: (1) persistent high adherence (12.0%), (2) progression to high adherence (20.8%), (3) progression to low adherence (10.5%), and (4) persistent low adherence (56.7%). Those who were initiated on ICS/LABA were less likely to have persistent low adherence (unadjusted odds ratio [OR], 0.44; 95% CI, 0.29-0.67) compared with those initiated on ICS monotherapy when "persistent high adherence" was used as the reference group. The relationship remained significant in adjusted regressions (adjusted OR, 0.38; 95% CI, 0.24-0.59). Real-world evidence suggests that using ICS/LABA for IMT may decrease the likelihood of persistent low adherence over time among older adults with ACO compared with ICS monotherapy.


Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial.
Evidence supporting the effectiveness of aerobic training, specific for fatigue, in severely fatigued patients with multiple sclerosis (MS) is lacking. To estimate the effectiveness of aerobic training on MS-related fatigue and societal participation in ambulant patients with severe MS-related fatigue. Patients ( N = 90) with severe MS-related fatigue were allocated to 16-week aerobic training or control intervention. Primary outcomes were perceived fatigue (Checklist Individual Strength (CIS20r) fatigue subscale) and societal participation. An improvement of ⩾8 points on the CIS20r fatigue subscale was considered clinically relevant. Outcomes were assessed by a blinded observer at baseline, 2, 4, 6 and 12 months. Of the 89 patients that started treatment (median Expanded Disability Status Scale (interquartile range), 3.0 (2.0-3.6); mean CIS20r fatigue subscale (standard deviation (SD)), 42.6 (8.0)), 43 received aerobic training and 46 received the control intervention. A significant post-intervention between-group mean difference (MD) on the CIS20r fatigue subscale of 4.708 (95% confidence interval (CI) = 1.003-8.412; p = 0.014) points was found in favour of aerobic training that, however, was not sustained during follow-up. No effect was found on societal participation. Aerobic training in MS patients with severe fatigue does not lead to a clinically meaningful reduction in fatigue or societal participation when compared to a low-intensity control intervention.


Multimode resonances in silver nanocuboids.
A rich variety of dipolar and higher order plasmon resonances have been predicted for nanoscale cubes and parallopipeds of silver, in contrast to the simple dipolar modes found on silver nanospheres or nanorods. However, in general, these multimode resonances are not readily detected in experimental colloidal ensembles, due primarily to the usual variation of size and shape of the particles obscuring or blending the individual extinction peaks. Recently, methods have been found to prepare silver parallopipeds with unprecedented shape control by nucleating the silver onto a tightly controlled suspension of gold nanorods (Okuno, Y.; Nishioka, K.; Kiya, A.; Nakashima, N.; Ishibashi, A.; Niidome, Y. Uniform and Controllable Preparation of Au-Ag Core-Shell Nanorods Using Anisotropic Silver Shell Formation on Gold Nanorods. Nanoscale 2010, 2, 1489-1493). The optical extinction spectra of suspensions of such monodisperse particles are found to contain multiple extinction peaks, which we show here to be due to the multimode resonances predicted by theoretical studies. Control of the radius of the nanoparticle edges is found to be an effective way to turn some of these modes on or off. These nanoparticles provide a flexible platform for the excitation, manipulation, and exploration of higher order plasmon resonances.


The IL-31/IL-31 receptor axis: general features and role in tumor microenvironment.
IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA+CD45RO+ T cells. Studies in humans have demonstrated a pathogenic role for IL-31 in atopic dermatitis and allergic asthma. The first demonstration of the involvement of the IL-31/IL-31R axis in cancer came from studies in patients with mycosis fungoides/Sézary syndrome, the most frequent, cutaneous T cell lymphoma. Tumor cells were shown to produce IL-31, whose serum levels correlated with pruritus intensity. Follicular lymphoma (FL) B cells and their counterparts-germinal center B cells-produced IL-31 and expressed IL-31R, which signaled in the former, but not the latter, cells. IL-31 released in association with microvesicles promoted tumor growth through autocrine/paracrine loops. Malignant mast cells from patients with mastocytosis or Philadelphia-negative myeloproliferative disorder produced IL-31, which contributed to pruritus pathogenesis. Finally, patients with endometrial carcinoma displayed high serum levels of IL-31 and IL-33, which may represent promising disease biomarkers. Targeting strategies for the IL-31/IL-31R axis have been developed, including the CIMM331 humanized anti-human IL-31RA antibody recently tested in a phase I/Ib study.


Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies.
Gold nanoparticles (GNPs) have been shown to sensitize cancer cells to x-ray radiation, particularly at kV energies where photoelectric interactions dominate and the high atomic number of gold makes a large difference to x-ray absorption. Protons have a high cross-section for gold at a large range of relevant clinical energies, and so potentially could be used with GNPs for increased therapeutic effect.Here, we investigate the contribution of secondary electron emission to cancer cell radiosensitization and investigate how this parameter is affected by proton energy and a free radical scavenger. We simulate the emission from a realistic cell phantom containing GNPs after traversal by protons and x-rays with different energies. We find that with a range of proton energies (1-250 MeV) there is a small increase in secondaries compared to a much larger increase with x-rays. Secondary electrons are known to produce toxic free radicals. Using a cancer cell line in vitro we find that a free radical scavenger has no protective effect on cells containing GNPs irradiated with 3 MeV protons, while it does protect against cells irradiated with x-rays. We conclude that GNP generated free radicals are a major cause of radiosensitization and that there is likely to be much less dose enhancement effect with clinical proton beams compared to x-rays.


A versatile integrating sphere based photoacoustic sensor for trace gas monitoring.
A compact versatile photoacoustic (PA) sensor for trace gas detection is reported. The sensor is based on an integrating sphere as the PA absorption cell with an organ pipe tube attached to increase the sensitivity of the PA sensor. The versatility and enhancement of the sensitivity of the PA signal is investigated by monitoring specific ro-vibrational lines of CO(2) in the 2 μm wavelength region and of NO(2) in the 405 nm region. The measured enhancement factor of the PA signal exceeds 1200, which is due to the acoustic resonance of the tube and the absorption enhancement of the integrating sphere relatively to a non-resonant single pass cell. It is observed that the background absorption signals are highly attenuated due to the thermal conduction and diffusion effects in the polytetrafluoroethylene cell walls. This demonstrates that careful choice of cell wall materials can be highly beneficial to the sensitivity of the PA sensor. These properties makes the sensor suitable for various practical sensor applications in the ultraviolet (UV) to the near infrared (NIR) wavelength region, including climate, environmental and industrial monitoring.


Health care workers and respiratory protection: is the user seal check a surrogate for respirator fit-testing?
Many agencies recommend that health care workers wear N95 filtering facepiece respirators (N95-FFR) to minimize occupational exposure to bioaerosols, such as tuberculosis and pandemic influenza. Published standards outline procedures for the proper selection of an N95-FFR model, including user seal checks and respirator fit-testing. Some health officials have argued that the respirator fit-test step should be eliminated altogether, given its additional time and cost factors, and that only a user seal check be utilized to ensure that an adequate face seal has been achieved. One of the aims of the current study is to examine whether a user seal check is an appropriate surrogate for respirator fit-testing. Subjects were assigned an N95-FFR and asked to perform a user seal check (as per manufacturer's instructions) after which they immediately underwent a respirator fit-test. Successfully passing a respirator fit-test was based on not detecting a leakage through the face seal (either qualitatively with a test agent or quantitatively with a particulate counter). The sample population consisted of 647 subjects who had never been previously fit-tested (naive), while the remaining 137 participants were experienced respirator users. Only four of the 647 naive subjects (0.62%) identified an inadequate seal during their user seal check. Of the 643 remaining naive subjects who indicated that they had an adequate face seal prior to fit-testing, 158 (25%) failed the subsequent quantitative fit-test and 92 (14%) failed the qualitative fit-test. All 137 experienced users indicated that they had an adequate seal after performing the user seal check; however, 41 (30%) failed the subsequent quantitative fit-test, and 30 (22%) failed the qualitative fit-test. These findings contradict the argument to eliminate fit-testing and rely strictly on a user seal check to evaluate face seal.


Baclofen-induced decrease of excitability of primary afferents and depression of monosynaptic transmission in cat spinal cord.
The relationship of the depressant effect of baclofen on spinal monosynaptic transmission and its effect on the excitability of primary afferents was examined in spinal unanesthetized cats. Baclofen (1.0 mg/kg, i.v.) produced a deep and long-lasting depression of spinal reflex responses with a concomitant decrease of terminal excitability. Primary afferent depolarization, as indicated by an increase of terminal excitability, evoked by conditioning of an antagonistic muscle nerve, was greatly reduced by this drug. Depression of monosynaptic transmission induced by baclofen was temporarily reversed by posttetanic potentiation. However, the same high frequency orthodromic stimulation further reduced excitability of terminals. It is therefore unlikely that block of terminal invasion is responsible for baclofen-induced depression of spinal monosynaptic transmission. These results are compatible with the suggestion that baclofen causes a reduction of transmitter release. In the spinal cord, this action is probably limited to the excitatory transmitter of primary afferents.


Severe adult burn survivors. What information about skin allografts?
During the acute phase of a severe burn, surgery is an emergency. In this situation, human skin allografts constitute an effective temporary skin substitute. However, information about the use of human tissue can not be given to the patients because most of the allografted patients are unconscious due to their injury. This study explored the restitution of information on skin donation to patients who have been skin allografted and who have survived their injury. A qualitative study was conducted due to the limited number of patients in ability to be interviewed according to our medical and psychological criteria. 12 patients who had been treated between 2002 and 2008 were interviewed. Our results show that 10 of them ignored that they had received skin allografts. One of the two patients who knew that they had received allografts knew that skin had been harvested from deceased donor. All patients expressed that there is no information that should not be delivered. They also expressed their relief to have had the opportunity to discuss their case and at being informed during their interview. Their own experience impacted their view in favor of organ and tissue donation.


Development of reaching during the first year: role of movement speed.
When infants first learn to reach at about 4 months, their hand paths are jerky and tortuous, but their reaches become smoother and straighter over the first year. Here the authors consider the role of the underlying limb dynamics, which scale with movement speed, on the development of trajectory control. The authors observed 4 infants weekly and then biweekly from reach onset to 1 year. Improvements in trajectories were not linear, but showed plateaus and regressions in straightness and smoothness. When infants' nonreaching movements were fast, their reaches were also fast, and faster reaches were also less straight. This is consistent with an equilibrium trajectory form of control, where development involves the increasing ability to stabilize the trajectory against self-generated movement perturbations.


Effects of polymethylmethacrylate nanoplastics on the polychaete Hediste diversicolor: Behavioural, regenerative, and biochemical responses.
Plastics, particularly microplastics (MPs) and nanoplastics (NPs), have been regarded as pollutants of emerging concern due to their effects on organisms and ecosystems, especially considering marine environments. However, in terms of NPs, there is still a knowledge gap regarding the effects of size and polymer on marine invertebrates, such as benthic organisms. Therefore, this study aimed to understand, regarding behavioural, physiological, and biochemical endpoints (neurotransmission, energy metabolism, antioxidant status, and oxidative damage), the effects of 50 nm waterborne polymethylmethacrylate (PMMA) NPs (0.5 to 500 µg/L) on the marine benthic polychaete Hediste diversicolor, a key species in estuarine and coastal ecosystems. Results demonstrated that worms exposed to PMMA NPs had a shorter burrowing time than control organisms. Nevertheless, worms exposed to PMMA NPs (0.5 and 500 µg/L) decreased cholinesterase activity. Energy metabolism was decreased at 50 and 500 µg/L, and glycogen content decreased at all concentrations of PMMA NPs. Enzymes related to the antioxidant defence system (superoxide dismutase and glutathione peroxidase) displayed increased activities in H. diversicolor specimens exposed to concentrations between 0.5 and 500 µg/L, which led to no damage at the cell membrane and protein levels. In this study, polychaetes also displayed a lower regenerative capacity when exposed to PMMA NPs. Overall, the data obtained in this study emphasize the potential consequences of PMMA NPs to benthic worms, particularly between 0.5 and 50 µg/L, with polychaetes exposed to 50 µg/L being the most impacted by the analysed NPs. However, since sediments are considered to be sinks and sources of plastics, further studies are needed to better understand the impacts of different sizes and polymers on marine organisms, particularly benthic species.


Phosphor informatics based on confirmatory factor analysis.
The theoretical understanding of phosphor luminescence is far from complete. To accomplish a full understanding of phosphor luminescence, the data mining of existing experimental data should receive equal consideration along with theoretical approaches. We mined the crystallographic and luminescence data of 75 reported Eu(2+)-doped phosphors with a single Wyckoff site for Eu(2+) activator accommodation, and 32 descriptors were extracted. A confirmatory factor analysis (CFA) based on a structural equation model (SEM) was employed since it has been helpful in understanding complex problems in social sciences and in bioinformatics. This first attempt at applying CFA to the data mining of engineering materials provided a better understanding of the structural and luminescent-property relationships for LED phosphors than what we have learnt so far from the conventional theoretical approaches.


regQTLs: Single nucleotide polymorphisms that modulate microRNA regulation of gene expression in tumors.
Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with trait diversity and disease susceptibility, yet their functional properties often remain unclear. It has been hypothesized that SNPs in microRNA binding sites may disrupt gene regulation by microRNAs (miRNAs), short non-coding RNAs that bind to mRNA and downregulate the target gene. While several studies have predicted the location of SNPs in miRNA binding sites, to date there has been no comprehensive analysis of their impact on miRNA regulation. Here we investigate the functional properties of genetic variants and their effects on miRNA regulation of gene expression in cancer. Our analysis is motivated by the hypothesis that distinct alleles may cause differential binding (from miRNAs to mRNAs or from transcription factors to DNA) and change the expression of genes. We previously identified pathways-systems of genes conferring specific cell functions-that are dysregulated by miRNAs in cancer, by comparing miRNA-pathway associations between healthy and tumor tissue. We draw on these results as a starting point to assess whether SNPs on dysregulated pathways are responsible for miRNA dysregulation of individual genes in tumors. Using an integrative regression analysis that incorporates miRNA expression, mRNA expression, and SNP genotype data, we identify functional SNPs that we term "regulatory QTLs (regQTLs)": loci whose alleles impact the regulation of genes by miRNAs. We apply the method to breast, liver, lung, and prostate cancer data from The Cancer Genome Atlas, and provide a tool to explore the findings.


Artesunate-atovaquone-proguanil rescue treatment of multidrug-resistant Plasmodium falciparum malaria in pregnancy: a preliminary report.
Pregnant women are particularly vulnerable to malaria infections. Multidrug resistance in Plasmodium falciparum seriously compromises treatment in some endemic areas. Between April 1999 and October 2001, we treated and prospectively followed 27 Karen pregnant women with multiple recrudescent P. falciparum infections who were resistant to all other antimalarials with a triple combination of artesunate-atovaquone-proguanil. The treatment was well tolerated and we found no evidence of toxicity for the mothers and the fetus. All but 1 woman were cured (cure rate 96%, 95% CI 89-100). The triple combination of artesunate (4 mg/kg/d), atovaquone (20 mg/kg/d), and proguanil (8 mg/kg/d) may provide a much needed, albeit expensive, 3-d rescue treatment for pregnant women exposed to multidrug- resistant P. falciparum malaria.


Effects of housing systems and feed additive on growth, carcass traits, liver function, oxidative status, thyroid function, and immune parameters of broilers.
The effects of rearing Cobb500 broiler chickens under 3 different housing systems (floor litter, floor plastic, and batteries) without or with feed additive (Butinov) on broiler performance, blood parameters and carcass traits were evaluated. Three hundred 1-day-old chicks were distributed in a 3 × 2 factorial arrangement (6 treatments each of 5 replicates). The results showed that reared broilers on litter or plastic floors had high values (P ≤ 0.01) of bird's weight (BW), weight gain (WG), and feed intake (FI) throughout the entire study period (1-42 d of age) compared with rearing on batteries. Rearing broilers in the different housing systems and with or without feed additives did not affect (P ≥ 0.05) total feed conversion (FCR). Different rearing systems or feed additives did not influence broiler chicks' carcass traits and some serum blood parameters. The plastic floor system significantly increased (P ≤ 0.05) blood serum corticosterone compared with litter and batteries. Feed additive (Butinov) decreased the level of T4 (P ≤ 0.05) in blood serum. Plastic floors or batteries significantly increased (P ≤ 0.01) the level of antibody titer against avian influenza virus (HIAV) compared to chicken reared on a litter floor. The results suggested that using housing systems of litter or plastic floors could improve broiler growth performance without adversely affecting carcass traits and blood characteristics compared with rearing in batteries. Also, broiler diets' feed additive (Butinov) and their interaction with rearing systems did not improve broiler growth performance.


Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study.
To evaluate the relative risk (RR) of mild cognitive impairment (MCI) associated with cerebrovascular risk factors and cerebrovascular-related brain changes. Mild cognitive impairment was determined for the subjects of the prospective National Heart, Lung, and Blood Institute Twin Study. Quantitative measures of brain, white matter hyperintensity, cerebral infarction, apolipoprotein E genotype, and psychometric testing were obtained. Subjects with MCI were older (73.5 +/- 3.0 vs 72.1 +/- 2.8 years), consumed less alcohol (3.7 +/- 5.8 vs 7.0 +/- 10.7 drinks per week), had greater white matter hyperintensity volumes (0.56% +/- 0.82% vs 0.25% +/- 0.34% of cranial volume), and had an increased prevalence of apolipoprotein E4 genotype (31.4% vs 19.2%) than normal subjects. White matter hyperintensity and the presence of the apolipoprotein E4 genotype were associated with a significantly increased risk for MCI. When all subjects were included in the analysis, alcohol consumption was associated with a reduced risk for MCI (RR = 0.93, P<.05). When subjects with a history of symptomatic cerebrovascular disease were excluded from the analysis, elevated midlife diastolic blood pressure was associated with an increased risk for MCI (RR = 1.70, P<.05). Elevated midlife blood pressures, and the resulting increased white matter hyperintensities, increase the risk for MCI in a group of community-dwelling older men to at least the same degree as apolipoprotein E4 genotype. Given the common occurrence of elevations in midlife blood pressure, early and effective treatment may be warranted to prevent late-life brain abnormalities and MCI. Moreover, since many individuals with MCI progress to clinical dementia, longitudinal evaluations of this cohort will be important.


Indicator-based public health monitoring in old age in OECD member countries: a scoping review.
The scoping review was conducted as part of the project "Improving Health Monitoring in Old Age" (IMOA) which aims at developing a conceptual framework with key indicators for a public health monitoring of the population aged 65 years and older in Germany. We systematically identified indicator-based monitoring systems that focus on health and wellbeing of older populations in member countries of the Organisation for Economic Co-operation and Development (OECD) and analysed them with regard to structure, development and content. A systematic search strategy included searching the websites of national public health institutes, an additional internet search and a MEDLINE search via PubMed. Indicator systems were included if they presented data on a national level, if they were published or updated after 01/01/2007, if they relied on more than one data source and if they were available in English or German. Data on the structure and development of the indicator sets were extracted using a standardized documentation form, and a content analysis of the indicators was conducted using a pre-defined conceptual framework with three health areas and 11 health domains that is based on the Worlds Health Organization's "World Report on Ageing and Health" and on the International Classification of Functioning, Disability and Health (ICF). Ten indicator-based monitoring systems met our inclusion criteria. Of these, six systems focused exclusively on older populations, and four offer a specific subset of indicators for older age. The number of indicators varied between 22 and 53 (median 32.5). Four systems were directly related to national public health or healthy ageing strategies, and two systems had been developed in consensus processes involving multiple stakeholders. The highest numbers of indicators could be assigned to the domains "health care", "nursing and community care", "wealth and poverty" and "physical health". Overall, 47 different concepts could be identified in the monitoring systems. Among indicator-based monitoring systems of health in older age identified in member countries of the OECD, there is considerable variation with regard to structure, development and content. The results will inspire the development of a public health monitoring of the older population in Germany.


Socio-cognitive factors influencing access to HIV prevention services among people who inject drugs in Dar es Salaam, Tanzania: An integrated bio-behavioural survey.
People who inject drugs (PWID) in Sub-Saharan Africa have limited access to comprehensive HIV services. While it is important to inform programming, knowledge about factors influencing access to comprehensive HIV services is scarce. We assessed the proportions of PWID with access to HIV prevention services and associated socio-cognitive factors in Tanzania. A cross-sectional survey was conducted among PWID between October and December 2017 in Dar es Salaam, Tanzania. Data on access to HIV prevention services, demographics and selected socio-cognitive factors were collected through structured face-to-face interviews. Weighted descriptive and forward selection multivariable logistics regression analyses were done to assess independent associations between HIV prevention services and predictors of interest. The results were two tailed and a p-value of less than 0.05 was considered statistically significant. The study included 611 PWID (males: 94.4%) with a median age of 34 years (Interquartile Range (IQR), 29-38). A large majority of participants reported to have access to condoms (87.8%), sterile needles/syringes (72.8%) and ever tested for HIV (66.0%). About half (52.0%) reported to have used condoms in the past one month and about a third (28.5%) accessed a peer educator. The odds of testing for HIV decreased among participants who perceived their HIV risk to be high (aOR = 0.29; 95%CI: 0.17-0.49) and those experienced sexual violence (aOR = 0.60; 95%CI 0.37-0.98). However, the odds of testing for HIV increased among participants with secondary level of education (aOR = 2.16; 95%CI: 1.06-5.55), and those who reported having correct comprehensive HIV knowledge (CCHK) (aOR = 1.63; 95%CI 1.12-2.41). The odds of access to condoms increased among females (aOR = 2.23; 95%CI: 1.04-5.02) but decreased among participants with secondary level of education (aOR = 0.41; 95%CI: 0.19-0.84), an income of >TZS 200,000 (aOR = 0.39; 95%CI: 0.23-0.66) and those who perceived their HIV risk to be high (aOR = 0.13; 95%CI: 0.03-0.36). The odds of access to peer educators was higher among participants with primary (aOR = 1.61; 95%CI: 1.01-2.26), and secondary (aOR = 2.71; 95%CI: 1.39-5.33) levels of education. The odds of access to sterile needle and syringe decreased among participants who perceived their HIV risk to be high (aOR = 0.11;95%CI 0.05-0.22), and low-medium (aOR = 0.25;95%CI 0.11-0.52) but increased among those with primary level of education (aOR = 1.72;95%CI 1.06-2.78). Access to condom, HIV testing, sterile needles and syringes were relatively high among PWID. However, condom use and access to peer educators was relatively low. HIV knowledge and risk perception, gender, education, and sexual violence influenced access to HIV prevention services. There is an urgent need to address the identified socio-cognitive factors and scale up all aspects of HIV prevention services to fast-track attainment of the 2025 UNAIDS goals and ending the HIV epidemic.


Mixed breeding of Aedes aegypti (L.) and Aedes albopictus Skuse in four dengue endemic areas in Kuala Lumpur and Selangor, Malaysia.
Ovitrap surveillance was conducted in four dengue endemic areas in Kuala Lumpur and Selangor, Malaysia to determine the distribution and percentage of mixed breeding of both Aedes aegypti and Aedes albopictus. The percentage of mixed breeding in all study sites both indoors and outdoors accounted for 10 to 32 % from the total ovitraps collected. Ae. aegypti was found at a higher frequency than Ae. albopictus in these ovitraps. This study again indicates that ovitrap is a sensitive tool to attract gravid females of more than one mosquito species to oviposit in the container.


Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates.
Biased left-right asymmetry is a fascinating and medically important phenomenon. We provide molecular genetic and physiological characterization of a novel, conserved, early, biophysical event that is crucial for correct asymmetry: H+ flux. A pharmacological screen implicated the H+-pump H+-V-ATPase in Xenopus asymmetry, where it acts upstream of early asymmetric markers. Immunohistochemistry revealed an actin-dependent asymmetry of H+-V-ATPase subunits during the first three cleavages. H+-flux across plasma membranes is also asymmetric at the four- and eight-cell stages, and this asymmetry requires H+-V-ATPase activity. Abolishing the asymmetry in H+ flux, using a dominant-negative subunit of the H+-V-ATPase or an ectopic H+ pump, randomized embryonic situs without causing any other defects. To understand the mechanism of action of H+-V-ATPase, we isolated its two physiological functions, cytoplasmic pH and membrane voltage (Vmem) regulation. Varying either pH or Vmem, independently of direct manipulation of H+-V-ATPase, caused disruptions of normal asymmetry, suggesting roles for both functions. V-ATPase inhibition also abolished the normal early localization of serotonin, functionally linking these two early asymmetry pathways. The involvement of H+-V-ATPase in asymmetry is conserved to chick and zebrafish. Inhibition of the H+-V-ATPase induces heterotaxia in both species; in chick, H+-V-ATPase activity is upstream of Shh; in fish, it is upstream of Kupffer's vesicle and Spaw expression. Our data implicate H+-V-ATPase activity in patterning the LR axis of vertebrates and reveal mechanisms upstream and downstream of its activity. We propose a pH- and Vmem-dependent model of the early physiology of LR patterning.


A comparison of machine learning classifiers for dementia with Lewy bodies using miRNA expression data.
Dementia with Lewy bodies (DLB) is the second most common subtype of neurodegenerative dementia in humans following Alzheimer's disease (AD). Present clinical diagnosis of DLB has high specificity and low sensitivity and finding potential biomarkers of prodromal DLB is still challenging. MicroRNAs (miRNAs) have recently received a lot of attention as a source of novel biomarkers. In this study, using serum miRNA expression of 478 Japanese individuals, we investigated potential miRNA biomarkers and constructed an optimal risk prediction model based on several machine learning methods: penalized regression, random forest, support vector machine, and gradient boosting decision tree. The final risk prediction model, constructed via a gradient boosting decision tree using 180 miRNAs and two clinical features, achieved an accuracy of 0.829 on an independent test set. We further predicted candidate target genes from the miRNAs. Gene set enrichment analysis of the miRNA target genes revealed 6 functional genes included in the DHA signaling pathway associated with DLB pathology. Two of them were further supported by gene-based association studies using a large number of single nucleotide polymorphism markers (BCL2L1: P = 0.012, PIK3R2: P = 0.021). Our proposed prediction model provides an effective tool for DLB classification. Also, a gene-based association test of rare variants revealed that BCL2L1 and PIK3R2 were statistically significantly associated with DLB.


Incorporating genomics into the toolkit of nematology.
The study of nematode genomes over the last three decades has relied heavily on the model organism Caenorhabditis elegans, which remains the best-assembled and annotated metazoan genome. This is now changing as a rapidly expanding number of nematodes of medical and economic importance have been sequenced in recent years. The advent of sequencing technologies to achieve the equivalent of the $1000 human genome promises that every nematode genome of interest will eventually be sequenced at a reasonable cost. As the sequencing of species spanning the nematode phylum becomes a routine part of characterizing nematodes, the comparative approach and the increasing use of ecological context will help us to further understand the evolution and functional specializations of any given species by comparing its genome to that of other closely and more distantly related nematodes. We review the current state of nematode genomics and discuss some of the highlights that these genomes have revealed and the trend and benefits of ecological genomics, emphasizing the potential for new genomes and the exciting opportunities this provides for nematological studies.


Efficacy and cost-effectiveness of an online mindfulness program (MindOnLine) to reduce fear of recurrence among people with cancer: study protocol for a randomised controlled trial.
Fear of cancer recurrence (FCR) is a common condition among cancer survivors that can lead to significant levels of distress, anxiety and depression. Online mindfulness programmes may provide the mechanism to support cancer survivors manage FCR and distress, and improve people's well-being over the short, medium and long term. The primary aim of this study is to determine the potential efficacy of MindOnLine, a 9 session mindfulness-based programme for survivors of breast, prostate and colorectal cancer. A formal economic programme will also be conducted. A single-blind randomised controlled trial to determine the efficacy and cost-efficacy of a MindOnLine programme for cancer survivors. A total of 400 people living with cancer will be recruited via online advertisements on social media platforms, peak consumer advocacy groups or through outpatient services at healthcare providers across Victoria, Australia. People will be randomly allocated to either the MindOnLine programme (n=200) or waitlist control (n=200). Participant assessments will occur at baseline, at 9 weeks and 9-month follow-up. The primary outcome is change in Fear of Recurrence Index Score total score between baseline and 9 weeks; secondary outcomes are changes in depression and anxiety, quality of life and mindfulness. The economic analysis comprises a cost-consequences analysis where all outcomes will be compared with costs. Ethics approval was obtained from the Peter MacCallum Cancer Centre (20-53) and Deakin University (2020-284). All participants will be required to provide written informed consent. Findings will be disseminated in peer reviewed journals and among key stakeholder organisations including hospitals, cancer and community organisations and Government. If successful the project will be rolled out nationally with a formal implementation plan. Australian New Zealand Clinical Trials Registry (12620000645954); Pre-results. Registered 6 June 2020, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379520&isReview=true.


Effect of mode of polymerization of bonding agent on shear bond strength of autocured resin composite luting cements.
There have been anecdotal reports of low bond strength with autocured resin composite materials, particularly when light-cured bonding agents that combine primer and adhesive in a 1-bottle preparation are used. The objective of this study was to determine if the mode of polymerization of the bonding agent influences the strength of the attachment of autocured resin composite luting cements to dentin. The shear bond strength of 2 resin luting cements, Calibra and RelyX ARC, polymerized by autocuring, in combination with 4 different bonding agents, Scotchbond Multipurpose Plus, Prime & Bond NT, IntegraBond and Single Bond, polymerized to bovine dentin by light-curing, autocuring or dual-curing, was determined. The pH of each bonding agent and its components was measured. Two-way analysis of variance was used to test the effect of cement and adhesive on shear bond strength. For each bonding agent, the adhesive variable combined the factors product brand and mode of polymerization. With significant interaction among the above variables, the least square means of the 16 combinations of resin cement and adhesive were compared. There was no consistent relationship between shear bond strength and mode of polymerization of the bonding agent. Significant differences in bond strength were specific to the proprietary brand of bonding agent. The pH of the bonding agent depends on the manufacturer's formulation, and low pH may contribute to low bond strength. The low in vitro bond strength occurring with some combinations of bonding agent and resin cement could be clinically significant.


Identifying Prevalence and Risk Factors for Intimate Partner Violence in Pregnant Women in Rural Guatemala.
Victims of intimate partner violence (IPV) during pregnancy experience significant physical and mental health consequences and adverse birth outcomes. Our objective was to describe the prevalence of IPV, and risk factors associated with IPV in pregnant, rural Guatemalan women. This retrospective cohort study was completed using quality improvement data gathered during routine prenatal health visits to women of Trifinio, Guatemala, by the Madres Sanas maternal health program from 2018 through 2020. Chi-square and t-tests were used to determine if there were differences in characteristics between women who self-reported experiencing IPV and those who did not. If differences occurred (p < 0.2), those covariates were included in a multivariable logistic regression to determine sociodemographic risk associated with IPV. 583 women were enrolled with Madres Sanas between October 10, 2018, and October 1, 2020, and reported on IPV. Nineteen (3.26%) women reported experiencing IPV. The highest prevalence of IPV (7.6%) occurred in the sub-group of women who experienced food insecurity during the past year. The sole covariate of all sociodemographic and health characteristics which differed significantly between women who reported experiencing and not experiencing IPV was food insecurity. A regression model found that those who had worried about ability to buy food in the past year had a 3.19-fold increase in the odds that they experienced IPV (95% CI 1.072, 9.486, p-value 0.037). Among this convenience sample of women, the prevalence of IPV was 3.26%. Food insecurity was associated with increased odds of experiencing IPV, highlighting an opportunity for interventions.


Cancer-associated fibroblasts are associated with poor prognosis in solid type of lung adenocarcinoma in a machine learning analysis.
Cancer-associated fibroblasts (CAFs) participate in critical processes in the tumor microenvironment, such as extracellular matrix remodeling, reciprocal signaling interactions with cancer cells and crosstalk with infiltrating inflammatory cells. However, the relationships between CAFs and survival are not well known in lung cancer. The aim of this study was to reveal the correlations of CAFs with survival rates, genetic alterations and immune activities. This study reviewed the histological features of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. We performed gene set enrichment analysis (GSEA), network-based analysis and survival analysis based on CAFs in four histological types of lung adenocarcinoma: acinar, papillary, micropapillary and solid. We found four hallmark gene sets, the epithelial-mesenchymal transition, angiogenesis, hypoxia, and inflammatory response gene sets, that were associated with the presence of CAFs. CAFs were associated with tumor proliferation, elevated memory CD4+T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, CAFs were related to blood vessel remodeling, matrix organization, negative regulation of apoptosis and transforming growth factor-β signaling. In the survival analysis of each histological type, CAFs were associated with poor prognosis in the solid type. These results may contribute to the development of therapeutic strategies against lung adenocarcinoma cases in which CAFs are present.


Stroma regulates increased epithelial lateral cell adhesion in 3D culture: a role for actin/cadherin dynamics.
Cell shape and tissue architecture are controlled by changes to junctional proteins and the cytoskeleton. How tissues control the dynamics of adhesion and cytoskeletal tension is unclear. We have studied epithelial tissue architecture using 3D culture models and found that adult primary prostate epithelial cells grow into hollow acinus-like spheroids. Importantly, when co-cultured with stroma the epithelia show increased lateral cell adhesions. To investigate this mechanism further we aimed to: identify a cell line model to allow repeatable and robust experiments; determine whether or not epithelial adhesion molecules were affected by stromal culture; and determine which stromal signalling molecules may influence cell adhesion in 3D epithelial cell cultures. The prostate cell line, BPH-1, showed increased lateral cell adhesion in response to stroma, when grown as 3D spheroids. Electron microscopy showed that 9.4% of lateral membranes were within 20 nm of each other and that this increased to 54% in the presence of stroma, after 7 days in culture. Stromal signalling did not influence E-cadherin or desmosome RNA or protein expression, but increased E-cadherin/actin co-localisation on the basolateral membranes, and decreased paracellular permeability. Microarray analysis identified several growth factors and pathways that were differentially expressed in stroma in response to 3D epithelial culture. The upregulated growth factors TGFβ2, CXCL12 and FGF10 were selected for further analysis because of previous associations with morphology. Small molecule inhibition of TGFβ2 signalling but not of CXCL12 and FGF10 signalling led to a decrease in actin and E-cadherin co-localisation and increased paracellular permeability. In 3D culture models, paracrine stromal signals increase epithelial cell adhesion via adhesion/cytoskeleton interactions and TGFβ2-dependent mechanisms may play a key role. These findings indicate a role for stroma in maintaining adult epithelial tissue morphology and integrity.


Tempo and mode of morphological evolution are decoupled from latitude in birds.
The latitudinal diversity gradient is one of the most striking patterns in nature, yet its implications for morphological evolution are poorly understood. In particular, it has been proposed that an increased intensity of species interactions in tropical biota may either promote or constrain trait evolution, but which of these outcomes predominates remains uncertain. Here, we develop tools for fitting phylogenetic models of phenotypic evolution in which the impact of species interactions-namely, competition-can vary across lineages. Deploying these models on a global avian trait dataset to explore differences in trait divergence between tropical and temperate lineages, we find that the effect of latitude on the mode and tempo of morphological evolution is weak and clade- or trait dependent. Our results indicate that species interactions do not disproportionately impact morphological evolution in tropical bird families and question the validity of previously reported patterns of slower trait evolution in the tropics.


Performance Comparison of Systematic Methods for Rigorous Definition of Coarse-Grained Sites of Large Biomolecules.
Construction of coarse-grained (CG) models for large biomolecules used for multiscale simulations demands a rigorous definition of CG sites for them. Several coarse-graining methods such as the simulated annealing and steepest descent (SASD) based on the essential dynamics coarse-graining (ED-CG) or the stepwise local iterative optimization (SLIO) based on the fluctuation maximization coarse-graining (FM-CG), were developed to do it. However, the practical applications of these methods such as SASD based on ED-CG are subject to limitations because they are too expensive. In this work, we extend the applicability of ED-CG by combining it with the SLIO algorithm. A comprehensive comparison of optimized results and accuracy of various algorithms based on ED-CG show that SLIO is the fastest as well as the most accurate algorithm among them. ED-CG combined with SLIO could give converged results as the number of CG sites increases, which demonstrates that it is another efficient method for coarse-graining large biomolecules. The construction of CG sites for Ras protein by using MD fluctuations demonstrates that the CG sites derived from FM-CG can reflect the fluctuation properties of secondary structures in Ras accurately.


[Classification and principles of treatment of acute purulent peritonitis].
State of immune-secretory system of intestinal mucosa, bacterial contamination of the small intestine, peritoneal exudate, portal and systemic venous blood, ultrastructural changes in the liver (electron microscopy) were studied in 167 patients with general acute purulent peritonitis (APP) and clinical-laboratory symptoms of endotoxicosis. It is demonstrated that the main links of APP pathogenesis are disorders of small intestine barrier function, massive bacterial translocation from intestinal lumen to abdominal cavity and portal circulation, damage of reticuloendothelial hepatic barrier manifested as fulminant macrophagal hepatic failure, "bursting" of infectious-toxic agents into systemic circulation with resultant toxico-septic shock and visceral insufficiency. This approach permits to classify three clinical stages of APP and to propose differential surgical policy and detoxication treatment for these patients.


Advances in nanopore sensing promises to transform healthcare.
International Conference on Nanopore Technology (Shenzhen), 30 March-1 April 2017, Shenzhen, China The International Conference on Nanopore Technology (Shenzhen) was held from 30 March to 1 April 2017 in Shenzhen, China. The goal of the meeting was threefold: leverage the unique properties of nanopore technology to promote transformative advances in medicine, encourage cross-disciplinary collaborations in the research community within China and abroad; and discuss critical challenges that need to be addressed to rapidly advance the field. The meeting was chaired by Peixuan Guo, Endowed chair professor and Director of The Center for RNA Nanobiotechnology & Nanomedicine at The Ohio State University, USA and co-chaired by Xian-En Zhang, distinguished professor of the Institute of Biophysics, Chinese Academy of Sciences, China. The conference was attended by more than 300 academic researchers, hospital administrators, government leaders and scientists from many disciplines across the country from both academic institutions and industry.


Low-parameter supervised learning models can discriminate pseudoprogression and true progression in non-perfusion-based MRI.
Discrimination of pseudoprogression and true progression is one challenge to the treatment of malignant gliomas. Although some techniques such as circulating tumor DNA (ctDNA) and perfusion-weighted imaging (PWI) demonstrate promise in distinguishing PsP from TP, we investigate robust and replicable alternatives to distinguish the two entities based on more widely-available media. In this study, we use low-parametric supervised learning techniques based on geographically-weighted regression (GWR) to investigate the utility of both conventional MRI sequences as well as a diffusion-weighted sequence (apparent diffusion coefficient or ADC) in the discrimination of PsP v TP. GWR applied to MRI modality pairs is a unique approach for small sample sizes and is a novel approach in this arena. From our analysis, all modality pairs involving ADC maps, and those involving post-contrast T1 regressed onto T2 showed potential promise. This work on ADC data adds to a growing body of research suggesting the predictive benefits of ADC, and suggests further research on the relationships between post-contrast T1 and T2.Clinical relevance- Few studies have investigated predictive potential of conventional MRI and ADC to detect PsP. Our study adds to the growing research on the topic and presents a new perspective to research by exploiting the utility of ADC in PsP v TP distinction. In addition, our GWR methodology for low-parametric supervised computer vision models demonstrates a unique approach for image processing of small sample sizes.


Effects of fluoride-modified titanium surfaces with the similar roughness on RUNX2 gene expression of osteoblast-like MG63 cells.
Chemical modification of titanium surfaces by hydrofluoric acid (HF) is an effective method to improve bone responses on titanium implant surfaces. In this study, titanium disks were sandblasted with titanium oxide grits and modified with 0.2% and 0.4% of diluted HF under different exposure times of 40 and 60 s. Surface characteristics, such as surface chemical composition, surface topography, and surface wettability, were investigated. To examine MG63 osteoblast-like cell responses to fluoride-modified titanium surfaces with roughness similar to that of nonmodified surfaces, a cell proliferation assay was performed and gene expression levels of Runx2 were evaluated using real-time PCR. Fluoride-modified titanium surfaces revealed no significant roughness difference but with hydrophilic properties than control group SB. Moreover, the relative atomic concentration percentages of fluoride were 0.7, 1.5, and 2.8. As fluoride concentrations increased, surface wettability increased and cell proliferation began earlier. However, the gene expression levels of Runx2 increased earlier on surfaces with 1.5% fluoride, with significantly high surface skewness. There seems to be an optimal fluoride concentration percentage when gene expression levels of Runx2 were taken into consideration. In addition, surface parameters, such as surface wettability and surface skewness, seem to be important factors in the enhancement of osteoblast differentiation by HF. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3102-3109, 2017.


Perception of bronchoconstriction and bronchial hyper-responsiveness in asthma.
The inter-relationship between the perception of bronchoconstriction, bronchial hyper-responsiveness and temporal adaptation in asthma is still a matter of debate. In a total of 52 stable asthmatic patients, 32 without airway obstruction ¿forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) 84.1% (S.D. 7.9%), and 20 with airway obstruction [FEV(1)/VC 60% (4%)], we assessed the perception of bronchoconstriction during methacholine inhalation by using: (i) the slope and intercept of the Borg and VAS (Visual Analog Scale) scores against the decrease in FEV(1), expressed as a percentage of the predicted value; and (ii) the Borg and VAS scores at a 20% decrease in FEV(1) from the lowest post-saline level (PB(20)). Bronchial hyper-responsiveness was assessed as the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)FEV(1)). The reduction in FEV(1) was significantly related to the Borg and VAS scores, with values for the group mean slope and intercept of this relationship of 0.13 (S.D. 0.08) and -1.1 (3.02) for Borg, and 1.5 (1.19) and -12.01 (35) for VAS. PB(20) was 3 (1.75) with Borg scores and 34.6 (20.5) with VAS scores. Compared with the subgroup without airway obstruction, the obstructed subgroup exhibited similar slopes, but lower Borg and VAS intercepts. For similar decreases in FEV(1) (5-20% decreases from the lowest post-saline values), the Borg and VAS scores were lower in the non-obstructed than in the obstructed subgroup. PC(20)FEV(1) was significantly related to both Borg PB(20) and VAS PB(20) when considering all patients. When assessing the subgroups, PC(20)FEV(1) was related to Borg PB(20) and VAS PB(20) in the non-obstructed subjects, but not in the obstructed subjects. In neither subgroup was the log of the cumulative dose related to the Borg and VAS scores at the end of the test. We conclude that, unlike in previous studies, the ability to perceive acute bronchoconstriction may be reduced as background airflow obstruction increases in asthma. Bronchial hyper-responsiveness did not play a major role in perceived breathlessness in patients without airway obstruction, and even less of a role in patients with obstruction. The cumulative dose of agonist did not appear to influence the perception of bronchoconstriction.


A neuro-inspired spike-based PID motor controller for multi-motor robots with low cost FPGAs.
In this paper we present a neuro-inspired spike-based close-loop controller written in VHDL and implemented for FPGAs. This controller has been focused on controlling a DC motor speed, but only using spikes for information representation, processing and DC motor driving. It could be applied to other motors with proper driver adaptation. This controller architecture represents one of the latest layers in a Spiking Neural Network (SNN), which implements a bridge between robotics actuators and spike-based processing layers and sensors. The presented control system fuses actuation and sensors information as spikes streams, processing these spikes in hard real-time, implementing a massively parallel information processing system, through specialized spike-based circuits. This spike-based close-loop controller has been implemented into an AER platform, designed in our labs, that allows direct control of DC motors: the AER-Robot. Experimental results evidence the viability of the implementation of spike-based controllers, and hardware synthesis denotes low hardware requirements that allow replicating this controller in a high number of parallel controllers working together to allow a real-time robot control.


The Piracicaba River basin: isotope hydrology of a tropical river basin under anthropogenic stress.
The stable isotope content of samples of precipitation and of the river water throughout the Piracicaba basin in Brazil was measured over a two-year period. The isotope values of precipitation follow a consistent pattern of relatively depleted values of both deuterium and oxygen 18 during the rainy summers and enriched ones during the dry winters, with all values aligned slightly above the Global Meteoric Water Line. The isotopic composition of the river water throughout the basin shows a remarkable spatial coherence and much smaller scatter of data than those of the precipitation. The isotope composition of river water is close to that of the precipitation in the rainy season, however, with a consistent lower d-excess value by 1/1000-2/1000. This is attributed to evaporative water loss in the basin, in part an expression of the recycling of water due to the anthropogenic activity in the region. The more divergent values are recorded during high-water stages in the rivers. In many cases, the floods during the beginning of the rainy season are characterized by an enrichment of the heavy isotopes and lower d-excess values when compared to the precipitation, with the opposite situation later in the rainy season. This is interpreted as resulting from the watershed/riverflow interaction pattern, and it thus suggests that the isotope composition can monitor the hydrologic situation in the basin and its changes.


[Marketizing of the State, erosion of democracy and impoverishment of citizenship: global tendencies?].
This article analyses the advance of the neo-liberal regime, in order to contextualise the international formulation of policies focussed on poverty reduction. In recent debates, terms such as 'citizenship' and 'democracy' have been subject to critical scrutiny, revealing changes in the relations between citizens and the State which accompany the hegemony of economic criteria that put financial considerations at the centre of national states. We argue that analyses of such global processes require an ample political economy perspective, capable of illuminating how the substance of democracy and the legitimacy of state authority have been conditioned by the advance of new global entities that represent the interests of capital, favouring the concentration of wealth and the increase of poverty, inequality and exclusion, and installing a state of vital insecurity that affects the majority of the world's population.


Risk assessments and recidivism among a population-based group of Swedish offenders sentenced to life in prison.
In Sweden, the number of people serving life sentences has steadily increased. To date, few studies have examined the recidivism rate or the predictive validity of different risk assessment instruments in this group. Our aim was to test the predictive validity among inmates serving life sentences of two different instruments used for assessing risk--the Historical, Clinical and Risk Management-20 (HCR-20), most widely used in clinical populations, and the Psychopathy Checklist-Revised (PCL-R), commonly applied in both penal and clinical settings. Ninety-eight life-sentenced prisoners were included, 26 of whom were released during the study period. Data on risk assessments and dates for release were collected from administrative records, while recidivism data were retrieved from a national database on criminal convictions. Sex offenders obtained the highest scores and inmates charged with domestic violent offences obtained the lowest scores on both instruments. The released prisoners were followed for a mean period of 33 months. During this time five prisoners (19%) reoffended, four of them violently, with an average time to recidivism of 10 months. Only PCL-R Facet 4, which reflects antisocial features, was significantly associated with recidivism. This small, but population-based, study demonstrates that antisocial behaviour shows incremental predictive validity for reoffending among life-sentenced offenders, but other measures have little to add for this specific task. The fact that those life sentenced prisoners who reoffended did so so soon after release should prompt allocation of earlier interventions towards preventing this.


Correction of coarse-graining errors by a two-level method: Application to the Asakura-Oosawa model.
We present a method that exploits self-consistent simulation of coarse-grained and fine-grained models in order to analyze properties of physical systems. The method uses the coarse-grained model to obtain a first estimate of the quantity of interest, before computing a correction by analyzing properties of the fine system. We illustrate the method by applying it to the Asakura-Oosawa model of colloid-polymer mixtures. We show that the liquid-vapor critical point in that system is affected by three-body interactions which are neglected in the corresponding coarse-grained model. We analyze the size of this effect and the nature of the three-body interactions. We also analyze the accuracy of the method as a function of the associated computational effort.


Prevention of diabetes in family medicine.
none declared. The incidence of diabetes type 2 (diabetes mellitus type 2 - DM 2) is rapidly increasing worldwide. Physical inactivity and obesity are the major determinants of the disease. Primary prevention of DM 2 entails health monitoring of people at risk category. People with impaired glycemic control are at high risk for development of DM 2 and enter the intensive supervision program for primary and secondary prevention. To evaluate the impact of metformin and lifestyle modification on glycemia and obesity in patients with prediabetes. The study was conducted on three groups of 20 patients each (total of 60 patients) aged from 45 to 80, with an abnormal glycoregulation and prediabetes. The study did not include patients who already met the diagnostic criteria for the diagnosis of diabetes. During the study period of 6 months, one group was extensively educated on changing lifestyle (healthy nutrition and increased physical activity), the second group was treated with 500 mg metformin twice a day, while the control group was advised about diet and physical activities but different from the first two groups. At beginning of the study, all patients were measured initial levels of blood glucose, HbA1C, BMI (Body Mass Index), body weight and height and waist size. Also the same measurements were taken at the end of the conducted research, 6 months later. For the assessment of diabetes control was conducted fasting plasma glucose (FPG) test and 2 hours after a glucose load, and HbA1C. At the beginning of the study the average HbA1C (%) values in three different groups according to the type of intervention (lifestyle changes, metformin, control group) were as follows: (6.4 ± 0.5 mmol / l), (6.5 ± 1.2 mmol / l), (6.7 ± 0.5 mmol / l). At the end of the research, the average HbA1C values were: 6.2 ± 0.3 mmol / l, 6.33 ± 0.5 mmol / l and 6.7 ± 1.4 mmol / l. In the group of patients who received intensive training on changing lifestyle or group that was treated with metformin, the average reduction in blood glucose and HbA1C remained within the reference range and there were no criteria for the diagnosis of diabetes. Unlike the control group, a group that was well educated on changing habits decreased average body weight by 4.25 kg, BMI by 1.3 and waist size by 2.5 cm. Metformin therapy led to a reduction in the average weight of 3.83 kg, BMI of 1.33 and 3.27 for waist size. Changing lifestyle (healthy diet and increased physical activity) has led to a reduction in total body weight in 60% of patients, BMI in 65% of patients, whereas metformin therapy led to a reduction of the total body weight in 50%, BMI in 45% of patients. In the control group, the overall reduction in body weight was observed in 25%, and BMI in 15% of patients. Modification of lifestyle, such as diet and increased physical activity or use of metformin may improve glycemic regulation, reduce obesity and prevent or delay the onset of developing DM 2.


Lost Earnings and Nonmedical Expenses of Pediatric Hospitalizations.
Hospitalization-related nonmedical costs, including lost earnings and expenses such as transportation, meals, and child care, can lead to challenges in prioritizing postdischarge decisions. In this study, we quantify such costs and evaluate their relationship with sociodemographic factors, including family-reported financial and social hardships. This was a cross-sectional analysis of data collected during the Hospital-to-Home Outcomes Study, a randomized trial designed to determine the effects of a nurse home visit after standard pediatric discharge. Parents completed an in-person survey during the child's hospitalization. The survey included sociodemographic characteristics of the parent and child, measures of financial and social hardship, household income and also evaluated the family's total nonmedical cost burden, which was defined as all lost earnings plus expenses. A daily cost burden (DCB) standardized it for a 24-hour period. The daily cost burden as a percentage of daily household income (DCBi) was also calculated. Median total cost burden for the 1372 households was $113, the median DCB was $51, and the median DCBi was 45%. DCB and DCBi varied across many sociodemographic characteristics. In particular, single-parent households (those with less work flexibility and more financial hardships experienced significantly higher DCB and DCBi. Those who reported ≥3 financial hardships lost or spent 6-times more of their daily income on nonmedical costs than those without hardships. Those with ≥1 social hardships lost or spent double their daily income compared with those without social hardships. Nonmedical costs place burdens on families of children who are hospitalized, disproportionately affecting those with competing socioeconomic challenges.


Green fluorescence protein driven by the Na,K-ATPase α4 isoform promoter is expressed only in male germ cells of mouse testis.
Expression of the Na,K-ATPase α4 isoform is required for sperm motility and fertility and is controlled by the Atp1a4 promoter. Here, we have investigated the specific tissue, cell type and developmental regulation of expression mediated by the Atp1a4 promoter. We have inserted the green fluorescent protein (GFP), downstream of the endogenous Atp1a4 promoter, in place of the Na,K-ATPase α4 gene, and used it as a marker for α4 expression in mice (Atp1a4 ( null(GFP) ) mice). Replacement of α4 by GFP completely disrupted α4 expression and activity, produced sperm morphological and functional abnormalities, and caused infertility of Atp1a4 ( null(GFP) ) male mice. Immunoblot analysis of Atp1a4 ( null(GFP) ) mouse tissues showed GFP expression in testis. This particular expression pattern was found in adult, but not in mouse embryos or in 7, 18 day old mice. In agreement with expression of GFP, adult Atp1a4 ( null(GFP) ) mouse testis displayed the typical fluorescence of GFP. Immunocytochemistry of testis identified GFP in more differentiated male germ cells, but not in spermatogonia, Leydig or Sertoli cells. Further analysis, using immunoblot of fluorescently sorted testis cells with cell specific markers, detected GFP only in spermatocytes, spermatids and spermatozoa. While epididymis showed GFP expression, this was confined to the spermatozoa within the epididymal tubules. Our results show that the Atp1a4 promoter drives GFP expression exclusively in male germ cells of the testis, where it restricts it to post-meiotic stages of spermatogenesis. These findings highlight the exquisite spatial and temporal control of expression exerted by the Atp1a4 promoter on Na,K-ATPase α4, which is particularly well suited to fulfill the special functions of spermatozoa.


Measurement of stresses in optical fiber and preform.
A method of measuring the stresses, residual or applied, in an optical fiber or preform is presented. It is shown that the stress profiles can be obtained from the Abel transform of the derivative of the retardation. The axial stress profile is shown to bear the same shape as the refractive-index profile. Measurement results indicate that the applied tension during the fiber drawing process is frozen into the fiber, consequently affecting the intrinsic strength of the fiber. The method of estimating the fiber drawing tension from the fiber stress profile is also given.


Factors associated with adolescent school girl's pregnancy in Kumbo East Health District North West region Cameroon.
Teenage pregnancy is a social problem in Cameroon in general and in Kumbo East in particular. This results in physical, psychological and socio-economic consequences on the teenage mother, family and the society as a whole. In spite of studies and interventions that have been and are being implemented, the prevalence of unplanned teenage pregnancy in Kumbo East Health District is still high, suggesting that more efforts are required to achieve effective preventive measures. The aim of this study was to determine factors associated with adolescent school girl's pregnancy in Kumbo East health district. A cross-sectional descriptive study design was used and a simple random sampling technique was used to select 293 respondents aged 15 to 19year. The district hospital antenatal clinics and the Health Centres were selected. Data was obtained from 292 participants under the age of 20 years who were willing using a questionnaire administered through face-to-face interviews. The study show a high prevalence (60.75%) of teenage pregnancy in the sampled antenatal clinics of Kumbo East Health District attributable to inadequate considerations given to factors associated with school girl's pregnancy. This study has indicated that the age of teenager at first pregnancy, low contraceptive use, socio-economic status and physical violence are factors that are greatly associated with teenage pregnancy. Among the reasons contributing to the low use of contraceptives are: sexually activity, lack of knowledge, fear of side effects, including sterility, condoms disappearing in the womb and inequality of power with sexual partners. This study shows that teenagers obtain information mainly from school (53%) and relatives (20%). The use of contraceptive alone may not reduce teenage pregnancy, however double method is very effective but addressing the impact of poverty on teenagers, empowering them on their rights and information in order to make right choices is very important.


Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals.
High-density lipoprotein (HDL) function rather than absolute level may be a more accurate indicator for cardiovascular disease (CVD). Novel methods can measure HDL function using patient samples. The objective of this study is to identify factors that may contribute to HDL dysfunction in chronic treated HIV-1 infection. Retrospective study of HDL function measured in 2 ways in HIV-1-infected men with low overall CVD risk and healthy men with no known CVD risk matched by race to the HIV-1-infected participants. We examined patient-level factors associated with 2 different measures of HDL dysfunction: reduced antioxidant function (oxidized HDL, HDLox) and reduced HDL-apoA-I exchange (HAE), a measure of HDL remodeling, in the HIV infected and control men. Multivariable-adjusted linear regression analyses were used adjusting for false discovery rate, age, race, body mass index (BMI), CD4 count, viremia, CVD risk, smoking, lipids, apoA-I, and albumin. In multivariate analysis among HIV-1-infected men (n = 166) (median age 45 years, CD4 T-cell count 505 cells/mm, 30.1% were viremic), higher BMI, lower apoA-I, and lower albumin were among the most notable correlates of higher HDLox and lower HAE (P < 0.05). In HIV-1 uninfected participants, lower albumin and higher BMI were associated with lower HAE and higher HDLox, respectively (P ≤ 0.05). HDLox was inversely related to HAE in HIV-1-infected individuals (P < 0.001). Increased HDLox correlates with reduced HAE in chronic HIV-1 infection. Higher BMI, lower apoA-I, and albumin were identified as factors associated with HDL dysfunction in chronic HIV-1 infection using 2 independent methods.