Search

Anomalous self-experiences (ASEs) are disturbances in the subjective experience of the self and are common in people with schizophrenia. Theorists have suggested that ASEs may underlie the neurocognitive deficits that are also common in people with schizophrenia; however, few studies have empirically investigated the relationship between these variables. Thus, the current study aimed to determine whether self-reported ASEs, particularly disturbances in cognitive or mental experiences, are meaningfully related to neurocognitive performance in individuals with schizophrenia.48 individuals with schizophrenia and 34 healthy comparison participants completed the Inventory of Psychotic-Like Anomalous Experiences (IPASE), which is composed of five subscales including disturbances in cognition, and the MATRICS Consensus Cognitive Battery (MCCB).Participants with schizophrenia performed worse than controls on each MCCB domain and had higher ASE scores on the total IPASE and all five subscales. Only the IPASE-Cognition subscale was associated with cognitive performance. Specifically, IPASE-Cognition was negatively correlated with scores in attention, visual learning, reasoning, and working memory.These results suggest that self-reported subjective disturbances in cognition may be meaningfully associated with several objectively-measured domains of neurocognition. Severity of ASEs may therefore be an important consideration when analysing the extent of cognitive deficits in schizophrenia.

INTRODUCTION The contribution of coagulation activation to the pathogenesis of sickle cell disease (SCD) remains incompletely defined. We evaluated the efficacy and safety of rivaroxaban, an oral direct factor Xa inhibitor, in subjects with sickle cell anemia. MATERIALS AND METHODS In this pilot, single-center, randomized, double-blind, placebo-controlled, crossover study, eligible subjects with sickle cell anemia received rivaroxaban or placebo. The effect of rivaroxaban on coagulation activation, endothelial activation, inflammation, and microvascular blood flow was evaluated. RESULTS Fourteen patients (HbSS - 14; females - 9) with mean age of 38 ± 10.6 years were randomized to receive rivaroxaban 20 mg daily or placebo for 4 weeks and, following a 2-week washout phase, were "crossed-over" to the treatment arm opposite to which they were initially assigned. Mean adherence to treatment with rivaroxaban, assessed by pill counts, was 85.6% in the first treatment period and 93.6% in the second period. Treatment with rivaroxaban resulted in a decrease from baseline of thrombin-antithrombin complex versus placebo (-34.4 ug/L [95% CI: -69.4, 0.53] vs. 0.35 ug/L [95% CI: -3.8, 4.5], p = .08), but the difference was not statistically significant. No significant differences were observed in changes from baseline of D-dimer, inflammatory, and endothelial activation markers or measures of microvascular blood flow. Rivaroxaban was well tolerated. CONCLUSIONS Rivaroxaban was safe but did not significantly decrease coagulation activation, endothelial activation, or inflammation. Rivaroxaban did not improve microvascular blood flow. Adequately powered studies are required to further evaluate the efficacy of rivaroxaban in SCD. Clinicaltrials.gov Identifier: NCT02072668.

A stabilized cartilage construct without signs of hypertrophy in chondrocytes is still a challenge. Suspensions of adipose stem/stromal cells (ASCs) and cartilage progenitor cells (CPCs) were seeded into micromolded nonadhesive hydrogel to produce spheroids (scaffold- and serum-free method) characterized by size, immunohistochemistry, fusion, and biomechanical properties. After cell dissociation, they were characterized for mesenchymal cell surface markers, cell viability, and quantitative real-time polymerase chain reaction. Both targeted and nontargeted (shotgun mass spectrometry) analyses were conducted on the culture supernatants. Induced ASC spheroids (ø = 350 μm) showed high cell viability and CD73 downregulation contrasting to CD90. The transforming growth factor (TGF)-β3/TGF-β1 ratio and

Бурштинопрояви і родовища бурштину в Україні представлені еоцен-олігоценовими розсипами прибережно-морського і лагунно-дельтового генезису. Дані поклади мають невисокий промисловий вміст бурштину – від 5–10 до 250 г/м3. Більшість родовищ розвідано на північно-західному схилі Українського щита, в Прип’ятському басейні. Порівняно мало вивченими на бурштиноносність залишаються східні і південно-західні схили Українського щита на стику з Дніпровсько-Донецькою та Причорноморською западинами. Незважаючи на велику кількість праць, присвячених дослідженню бурштину України, необхідно констатувати, що у науковій літературі так і не сформовано єдиного підходу до вивчення генезису бурштину та інших викопних смол. У зв'язку із зазначеним мета цієї роботи полягає в визначенні підходів до прогнозування промислових розсипів бурштину-сукциніту в Україні. У статті розглянуто геологічні закономірності розповсюдження та умови накопичення первинних біогенно-осадових покладів – корінних першоджерел розсипів самоцвіту. Наведено результати геолого-стратиграфічних досліджень, проведених для уточнення генезису розсипів перших колекторів і їх віку. Коротко подано геологічний і палеогеографічний аналіз поширення древніх розсипів у межах Українського щита і басейнів седиментації в еоцені–ранньому олігоцені. Для досліджуваного виду розсипів проведено аналіз накопичення і захоронення корисного компонента в відкладах глауконітових пісків середнього еоцену–раннього олігоцену. Наведена схема демонструє області потенційного накопичення покладів бурштину-сукциніту і викопних смол, закономірності територіальної диференціації. Результати досліджень дали змогу обґрунтувати виявлення нового типу похованих розсипів бурштину-сукциніту в Україні, пов'язаних з віддаленою частиною шельфу. Вони цілком визначають практичну і наукову цінність проведених авторами досліджень, які в остаточному підсумку спрямовані на підвищення якості пошуково-розвідувальних робіт на бурштин. Окреслено можливості практичного використання результатів дослідження для прогнозування та пошуку родовищ цінної корисної копалини

Postinflammatory hyperpigmentation (PIH) is a common, acquired pigmentary disorder of the skin associated with significant quality-of-life impairment, especially in individuals with skin of colour. Current treatment for PIH is limited, largely due to a poor understanding of disease pathogenesis and the lack of a representative disease model.This study is intended to further develop, update and validate our previously designed in vivo model of acne-induced PIH/postinflammatory erythema (PIE) using different concentrations of trichloroacetic acid (TCA), a medium-depth chemical peel.Twenty-nine patients with skin types II-VI and clinician-confirmed presence of two or more truncal acne pustules and PIH/PIE were included. On the basis of Investigator's Global Assessment (IGA), clinical polarized photography (CPP), colorimetry and Skindex, we experimentally determined an optimum TCA concentration and assessed our model's ability to exhibit a dose-response relationship between degree of inciting insult and severity of resulting pigmentation. We also performed differential microRNA profiling and pathway analysis to explore the potential of microRNAs as molecular adjuncts to our model.Application of TCA 30% produced lesions indistinguishable from acne-induced PIH and PIE lesions on the basis of colorimetry data without causing epidermal necrosis. Application of progressively increasing TCA doses from 20% to 30% resulted in concentration-dependent increases in CPP, IGA and colorimetry scores at all timepoints during the study. miRNA-31 and miRNA-23b may play a role in PIH pathogenesis, although further validation is required.Our TCA-based in vivo model, using TCA concentrations between 20% and 30% with an optimum of 30%, enables the quantitative assessment of the pigmentary response to varying degrees of cutaneous inflammation in a fashion that mirrors natural acne-induced PIH and PIE.

Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a >30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.gov as #NCT01960413.

Background: Both physical inactivity and sedentary behavior (too much sitting) can contribute to renal dysfunction. However, the potential benefits of behavior change (e.g., replacing sedentary behavior with physical activity) on renal function are not fully understood. We used isotemporal substitution to model potential impacts on renal function of replacing time from one behavior to another in middle-aged and older adults. Methods: For 174 Japanese adults (aged 50 – 83 years; 76 % women), the time spent in sedentary behavior, light-intensity physical activity (LPA), and moderate to vigorous-intensity physical activity (MVPA) were assessed using uniaxial accelerometers. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C levels. Results: In univariate analyses, eGFR was significantly, albeit weakly, correlated with time spent in sedentary behavior ( r s = – 0.229), LPA ( r s = 0.265) and with MVPA ( r s = 0.353). In the isotemporal substitution models, replacement of 30 min/day of sedentary behavior with equivalent LPA time was not significantly associated with eGFR ( β = 2.25, p = 0.111); however, replacement with the same amount of MVPA was beneficially associated with eGFR ( β = 5.51, p < 0.05). Conclusions: These cross-sectional findings suggest that both sedentary behavior (detrimentally) and physical activity (beneficially) may be contributors to maintaining renal function and that replacing sedentary behavior with MVPA may benefit renal health in middle-aged and older adults.

RESUMEN. El objetivo del presente trabajo de investigación fue evaluar la condición corporal (CC) de vacas en lactación y comparar la CC de vacas con buen desempeño reproductivo (alta tasa de preñez) con vacas que tuvieron menor tasa de preñez en la Región Oriental del Paraguay. Fueron evaluadas 116 vacas de 13 diferentes establecimientos. Los datos obtenidos fueron analizados usando el programa SAS Enterprise Guide versión 4.3. A pesar de la gran variación en la CC durante el periodo evaluado, la CC fue menor en la fase temprana y media de la lactación que en la fase tardía (p

Summary Background The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. Methods We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. Findings On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4–31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8–44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2–59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02–2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37–0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9–351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. Interpretation The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the burden of sepsis in resource-limited settings, highlighting the need to establish programmes aiming for sepsis prevention, early diagnosis, and adequate treatment. Funding Fundacao de Apoio a Pesquisa do Estado de Sao Paulo (FAPESP).

Background and Objective Tissue engineering by using recombinant human (rh) growth factor technology may offer a promising therapeutic approach for treatment of gingival recession. Fibroblast growth factor-2 (FGF-2) has shown the ability to promote periodontal regeneration. Gelatin/beta-tricalcium phosphate (gelatin/β-TCP) sponges have been developed to control the release of growth factors. The present study evaluated the periodontal regenerative efficacy of rhFGF-2 by comparing gelatin/β-TCP sponges incorporated with rhFGF-2 to the scaffolds alone in artificially created recession-type defects in dogs. Material and methods Critically sized buccal gingival recession defects were surgically created on maxillary canine teeth of five dogs. In each animal, defects were randomized to receive either a gelatin/β-TCP sponge soaked with rhFGF-2 (gelatin/β-TCP/rhFGF-2) or phosphate-buffered saline (gelatin/β-TCP). Eight weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography and histological analyses. Results Complete root coverage was achieved in both groups. Microcomputed tomography revealed significantly greater new bone volume in the gelatin/β-TCP/rhFGF-2 group. Histologically, both groups achieved periodontal regeneration; however, gelatin/β-TCP/rhFGF-2 sites exhibited more tissue regeneration, characterized by significantly larger amounts of new cementum and new bone. Gelatin/β-TCP sites featured increased long junctional epithelium and connective tissue attachment. In the gelatin/β-TCP/rhFGF-2 sites, new bone exhibited many haversian canals and circumferential lamellae as well as remarkably thick periosteum with blood vascularization and hypercellularity. Conclusion Within the limitations of this study, rhFGF-2 in gelatin/β-TCP sponges exhibits an increased potential to support periodontal wound healing/regeneration in canine recession-type defects.

A sample return mission from Jupiter trojans is proposed in JAXA. Reentry velocity in this mission is estimated at 14 km/s. It is reported that there is a discrepancy between predictions and experimental results with regard to the electron number density in the shock layer. Precursor photoionization is one candidate to cause the discrepancy. To clarify the phenomenon, it is necessary to measure the electron density ne distribution from across a strong shock wave. Then, we are developing a heterodyne interferometer whose measurement range and time resolution is ne = 1019–1022 m−3, above 1 μs, respectively. In this study, the limit of phase shift was evaluated by the variation of ZnSe window thickness. Measured value is in agreement with theoretical curve. However the error is 5.8 × 1019 m−3. Variability of phase is 5.35°, it is equivalent to ne of 4.4 × 1019 m−3 with l = 70 mm and λ = 10.6 μm, and it is found out that phase stability of laser is a major factor of phase variability. It is required for the enhancement of sensitivity. It is required for the enhancement of phase stability of laser beam.

Our previous numerical study (Katsurayama et al. AIAA Paper 2008-4016) has predicted that an insulating boundary in a flow is necessary to activate electrodynamic braking in a rarefied flow: the insulating boundary can prevent the Hall effect from dissipating the current which is necessary for the electrodynamic braking. In order to validate this numerical prediction, the present study measures the total drag on a test model in a rarefied arc flow whose insulating boundary (that is an arc plume boundary) location is variable and compares the measured electrodynamic increases of the total drag with the computed values. As a result, the measured and computed total drags increase by applying the magnetic field, but contrary to the computational prediction, the measured electrodynamic increase of the total drag is insensitive to the insulating boundary location.

Dasatinib treatment markedly increases the number of large granular lymphocytes (LGLs) in a proportion of Ph+ leukemia patients, which associates with a better prognosis. The lymphocytosis is predominantly observed in cytomegalovirus (CMV)-seropositive patients, yet detectable CMV reactivation exists only in a small fraction of patients. Thus, etiology of the lymphocytosis still remains unclear. Here, we identified NK cells as the dominant LGLs expanding in dasatinib-treated patients, and applied principal component analysis (PCA) to an extensive panel of NK cell markers to explore underlying factors in NK cell activation. PCA displayed phenotypic divergence of NK cells that reflects CMV-associated differentiation and genetic differences, and the divergence was markedly augmented in CMV-seropositive dasatinib-treated patients. Notably, the CMV-associated highly differentiated status of NK cells was already observed at leukemia diagnosis, and was further enhanced after starting dasatinib in virtually all CMV-seropositive patients. Thus, the extensive characterization of NK cells by PCA strongly suggests that CMV is an essential factor in the NK cell activation, which progresses stepwise during leukemia and subsequent dasatinib treatment most likely by subclinical CMV reactivation. This study provides a rationale for the exploitation of CMV-associated NK cell activation for treatment of leukemias.

Although bone morphogenetic protein 2 (BMP-2) is known to stimulate osteogenesis, there is evidence that high doses of BMP-2 can lead to side effects, including inflammation and carcinogenesis. The supplementation of other bone-augmenting agents is considered helpful in preventing such side effects by reducing the amount of BMP-2 required to obtain a sufficient amount of bone. We recently showed that a receptor activator of nuclear factor κB ligand (RANKL)–binding peptide promotes osteoblast differentiation. In the present study, we aimed to investigate whether OP3-4, a RANKL-binding peptide, promotes BMP-2–induced bone formation in the murine maxilla using an injectable gelatin hydrogel (GH) carrier. A GH carrier containing OP3-4 with BMP-2 was subperiosteally injected into the murine maxillary right diastema between the incisor and the first molar. The mice were sacrificed 28 d after the injections. The local bone formation in the OP3-4-BMP-2–injected group was analyzed in comparison to the carrier-injected, BMP-2–injected, and control-peptide-BMP-2–injected groups. The GH carrier containing OP3-4 with BMP-2 enlarged the radio-opaque area and increased the bone mineral content and density in the radiological analyses in comparison to the other experimental groups. Interestingly, fluorescence-based histological analyses revealed that the mineralization had started from the outside, then proceeded inward, suggesting that the size of the newly formed bone had already been set before calcification started and that the effects of OP3-4 might be involved in accelerating the early steps of osteogenesis. Actually, OP3-4 enhanced the BMP-2–induced 5-bromo-2′-deoxyuridine (BrdU)–positive cell numbers at the injected site on day 7 and the expression of Runx2 and Col1a1, which are early osteogenic cell markers, on day 10 after the subperiosteal injections. In summary, we demonstrated, for the first time, that the application of OP3-4 by subperiosteal injection promoted BMP-2–induced bone formation, which could lead to the development of an easy and noninvasive means of promoting alveolar ridge formation.

An indoline dye having both α-cyanoacrylic acid and rhodanine acetic acid anchor groups at the acceptor moiety exhibited improved stability under fluorescence light irradiation.

In cattle, human chorionic gonadotrophin (hCG) is administered at Day 5 post-ovulation to improve fertility. This treatment can induce ovulation of the first-wave dominant follicle (W1DF), from which an accessory corpus luteum (CL) is generated. In addition, hCG has the effect of promoting CL development. It is possible that the locational relationship between the original and accessary CLs influences the effect of hCG on CL development, because the locational relationship of the CLs affects intraovarian blood flow. The present study aimed to clarify whether the locational relationship between the original and accessory CLs influences the effect of hCG on their development. Cross-bred beef heifers (Holstein×Japanese Black, n=56) were used for the present study. The oestrus cycle was synchronized using oestradiol benzoate (EB) and a controlled internal drug release (CIDR)-based program. Briefly, an administration of EB (2mg) with 9-day CIDR insertion was followed by administration of prostaglandin F2a analogue (PGF2a) on the day of CIDR removal, EB (1mg) 1 day after a PGF2a injection, and GnRH 12h after the second EB injection. At Day 5 post-ovulation, the locational relationship between the original CL and the W1DF was confirmed using transrectal ultrasonography (USG), and two groups were defined: ipsilateral group (IG; n=30), in which the CL and the W1DF are in the same ovary, and contralateral group (CG; n=26), in which the CL and the W1DF are in separate ovaries. Moreover, IG and CG were respectively subdivided into two groups, with or without hCG (1500IU) treatment (IG/hCG, n=15; IG without hCG, n=15, and CG/hCG, n=14; CG without hCG, n=12). The diameter and luteal tissue area (i.e. minus the cavity area) of the original CL and the accessory CL were examined at Days 5, 7, and 14, using USG. Two-way repeated-measures ANOVA was used to compare the diameter and luteal tissue area between IG/hCG and IG without hCG, and between CG/hCG and CG without hCG. In CG, the diameter (P

Hypotension induced by spinal anesthesia for cesarean section causes a decrease in maternal regional cerebral blood volume and oxygenation. We used near-infrared spectroscopy to determine whether prophylactic infusion of phenylephrine attenuates these decreases.Sixty patients undergoing bupivacaine spinal anesthesia for cesarean section were randomly divided into one of three intravenous infusion groups: saline (P0), phenylephrine 25 (P25) or 50 µg/min (P50). Mean arterial pressure, heart rate and near-infrared spectroscopy measurements were made at one-minute intervals for 20 minutes, and oxyhemoglobin, deoxy-hemoglobin and total-hemoglobin concentrations and tissue oxygenation index were determined. Mean changes in the values between baseline and each measurement time after intrathecal injection were compared.Significant decreases in mean arterial pressure were seen in group P0 compared to P25 and P50 (P 0.01). Heart rate decreased in a dose-dependent manner during phenylephrine infusion (P0 vs. P25 and P50, P25 vs. P50; P 0.05). Significantly higher total-hemoglobin levels were observed in the phenylephrine groups versus the P0 group (P 0.01). The largest decrease in tissue oxygenation index was found in the P50, followed by P0 and P25 groups (P0 vs. P25 and P50, P25 vs. P50; P 0.05).Prophylactic infusion of phenylephrine, especially at 25 µg/min, can effectively suppress decreases in regional cerebral blood volume and regional cerebral blood oxygenation after induction of spinal anesthesia for cesarean section.

The fluorescence intensity of indolenium carbocyanine dyes in the solid state depended on both the alkyl group on the nitrogen atoms in the indolenium rings and the kind of counter anions. The N-propyl derivative having a bis(trifluoromethylsulfonyl)imide anion, whose fluorescence maximum was observed at 657 nm with shoulder peaks, exhibited the highest fluorescence quantum yield of 0.31. The wave deconvolution of fluorescence spectrum indicated three components assigned to the S1,0→S0,0, S1,0→S0,1, and S1,0→S0,2 transitions. The X-ray structure of this compound indicates an isolated monomer-type packing, whereas the other derivatives shows the isolated dimer-type packing or consequent π/π stacking. The cyanine dye having the least π/π interactions among adjacent cationic fluorophores could exhibit the most intense fluorescence in the solid state.

To make a molecular design of efficient indoline dyes, fluorescence lifetimes should be longer than ca. 0.8 ns in chloroform, in addition to suitable HOMO and LUMO levels and bathochromic UV-vis absorption bands.

The scaffold-free tissue engineering using spheroids is pointed out as an approach for optimizing the delivery system of cartilage construct. In this study, we aimed to evaluate the micromolded nonadhesive hydrogel (MicroTissues®) for spheroid compaction (2-day culture) and spontaneous chondrogenesis (21-day culture) using cartilage progenitors cells (CPCs) from human nasal septum without chondrogenic stimulus. CPC spheroids showed diameter stability (486 μm ± 65), high percentage of viable cells (88.1 ± 2.1), and low percentage of apoptotic cells (2.3%). After spheroid compaction, the synthesis of TGF-β1, TGF-β2, and TGF-β3 was significantly higher compared to monolayer (p<0.005). Biomechanical assay revealed that the maximum forces applied to spheroids after chondrogenesis were 2.6 times higher than for those cultured for 2 days. After spontaneous chondrogenesis, CPC spheroids were entirely positive for N-cadherin, collagen type II and type VI, and aggrecan and chondroitin sulfate. Comparing to monolayer, the expression of SOX5 and SOX6 genes analyzed by qPCR was significantly upregulated (p<0.01). Finally, we observed the capacity of CPC spheroids starting to fuse. To the best of our knowledge, this is the first time in the scientific literature that human CPC spheroids were formed by micromolded nonadhesive hydrogel, achieving a successful scaffold-free cartilage engineering without chondrogenic stimulus (low cost).

Purpose: Chronic Obstructive Pulmonary Disease (COPD) is one of the few causes of mortality and COPD patients are increasing especially aged 75 years and older in Japan. Advance care planning (ACP), which involves patients-provider communication about end-of-life care, is important for COPD patients to promote end-of-life discussion. This study reviewed completion rates of advance directives (AD) and related factors to ACP discussion in COPD patients. Methods: A systematic review was conducted searching of PubMed and CINAHL from 1992 to 30 June 2016. Keywords such as “Chronic Obstructive Pulmonary Disease (COPD)”, “advance care planning”, “advance directives”, “completion”, “factors”, and “predictors” were used to select the articles. Abstracts of the search results were reviewed according to inclusion criteria which described completion rates of AD and factors related to ACP process. Results: Ten articles were included for the review regarding the study purpose. Qualitative research design was used 5 studies of 10. Completion rates of AD were from 17% to 61%. A study of outpatient palliative care program for COPD reported that documented advance care plan at the initial appointment 0% changed 61% at follow-up. A multicenter, prospective, longitudinal study showed preferences regarding CPR or MV changed in 38.3% of the patients during the follow-up period, and related factors were generic health status, mobility, symptoms of anxiety and depression. Conclusion: AD Completion rates and factors related to ACP process were well-not examined in COPD. Professional support to COPD patients is important, therefore, respiratory practitioners must choose the right time to promote ACP discussion.

Purpose: Elderly heart failure (HF) patients are increasing, they have a significant symptom burden and palliative care needs including advance care planning (ACP). End-of-life discussion is needed to improve quality of life among elderly HF patients, little is known about factors related to promoting ACP and completion of advance directives (AD) in HF patients. This study examined completion rates of AD and predictors of ACP process in HF patients by conducting a systematic review.

Contains fulltext : 170312.pdf (Publisher’s version ) (Open Access) Acinetobacter baumannii is an important cause of multidrug-resistant hospital acquired infections in the world. Here, we investigate the presence of NDM-1 and other carbapenemases among carbapenem-resistant A. baumannii isolated between August 2010 and December 2014 from three large hospitals in Hanoi, Vietnam. We identified 23/582 isolates (4 %) (11 from hospital A, five from hospital B, and seven from hospital C) that were NDM-1 positive, and among them 18 carried additional carbapenemase genes, including seven isolates carrying NDM-1, IMP-1, and OXA-58 with high MICs for carbapenems. Genotyping indicated that NDM-1 carrying A. baumannii have expanded clonally in these hospitals. Five new STs (ST1135, ST1136, ST1137, ST1138, and ST1139) were identified. One isolate carried NDM-1 on a plasmid belonging to the N-repA replicon type; no NDM-1-positive plasmids were identified in the other isolates. We have shown the extent of the carbapenem resistance and the local clonal spread of A. baumannii carrying NDM-1 in these hospitals; coexistence of NDM-1 and IMP-1 is reported for the first time from Vietnam here, and this will further seriously limit future therapeutic options.

Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma.

Previous studies have identified several residues lining the groove of the HLA-A2.1 molecule that are critical for Ag presentation. However, it is not clear whether these residues are critical for binding of the peptide epitope per se or for determining the appropriate conformation of bound peptide. To distinguish between these possibilities, mutations at eight of these residues have been tested for their effects on the ability of the molecule to bind and present two known peptide epitopes--one derived from the influenza A matrix protein, the other from HIV pol. With only one exception, the mutations were found to affect the binding of the two peptides similarly. Most of the mutations resulted in intermediate deleterious effects on binding, with the B pocket mutant F9Y having the most dramatic negative effect on binding for both peptides. Two of the mutations significantly enhanced binding of both peptides and a peptide-specific effect on binding was seen with the substitution, Y99H, which enhanced binding of the matrix peptide yet diminished binding of the pol peptide. In contrast to the effects on binding, the effects of the mutations on presentation differed considerably for the two peptides. The most striking difference was seen with two alpha 2 alpha helix mutants that are fully recognized by pol peptide-specific CTL but not recognized by matrix peptide-specific CTL even though levels of binding were comparably diminished for the two peptides. These results suggest that some interactions, although not critical for binding per se, are critical for functional binding and the importance of these interactions differs among peptide epitopes.

Dasatinib treatment markedly increases the number of large granular lymphocytes (LGLs) in a proportion of Ph

Human astroviruses (HAstVs) are a major cause of gastroenteritis. HAstV assembles from the structural protein VP90 and undergoes a cascade of proteolytic cleavages. Cleavage to VP70 is required for release of immature particles from cells, and subsequent cleavage by trypsin confers infectivity. We used electron cryomicroscopy and icosahedral image analysis to determine the first experimentally derived, three-dimensional structures of an immature VP70 virion and a fully proteolyzed, infectious virion. Both particles display T = 3 icosahedral symmetry and nearly identical solid capsid shells with diameters of ~ 350 Å. Globular spikes emanate from the capsid surface, yielding an overall diameter of ~ 440 Å. While the immature particles display 90 dimeric spikes, the mature capsid only displays 30 spikes, located on the icosahedral 2-fold axes. Loss of the 60 peripentonal spikes likely plays an important role in viral infectivity. In addition, immature HAstV bears a striking resemblance to the structure of hepatitis E virus (HEV)-like particles, as previously predicted from structural similarity of the crystal structure of the astrovirus spike domain with the HEV P-domain [Dong, J., Dong, L., Méndez, E. & Tao, Y. (2011). Crystal structure of the human astrovirus capsid spike. Proc. Natl. Acad. Sci. USA108, 12681–12686]. Similarities between their capsid shells and dimeric spikes and between the sequences of their capsid proteins suggest that these viral families are phylogenetically related and may share common assembly and activation mechanisms., Graphical Abstract Highlights ► Three‐dimensional electron cryomicroscopy density maps of immature and mature HAstV. ► Mature virions only display 30 of 90 spikes after proteolytic cleavage. ► Immature virions are remarkably similar to HEV.

Abnormal blood flow accounts for most of the clinical morbidity of sickle cell disease (SCD) [1,2]. Most notably, occlusion of flow in the microvasculature causes the acute pain crises [3] that are the commonest cause for patients with SCD to seek medical attention [4] and major determinants of their quality of life [5]. Based on evidence that endothelial P-selectin is central to the abnormal blood flow in SCD we provide results from four of our studies that are germane to microvascular blood flow in SCD. A proof-of-principle study established that doses of heparin lower than what are used for anticoagulation but sufficient to block P-selectin improved microvascular blood flow inpatients with SCD. An in vitro study showed that Pentosan Polysulfate Sodium (PPS) had greater P-selectin blocking activity than heparin. A Phase I clinical study demonstrated that a single oral dose of PPS increased microvascular blood flow in patients with SCD. A Phase II clinical study that was not completed documented that daily oral doses of PPS administered for 8 weeks lowered plasma levels of sVCAM-1 and tended to improve microvascular blood flow in patients with SCD. These data support the concept that P-selectin on the microvascular endothelium is critical to both acute vascular occlusion and chronically impaired microvascular blood flow in SCD. They also demonstrate that oral PPS is beneficial to microvascular sickle cell blood flow and has potential as an efficacious agent for long-term prophylactic therapy of SCD.