Concanavalin A-conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal drug delivery to the cervical lymph nodes.
Concanavalin A (ConA)-conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (ConA-NPs) were prepared for targeted drug delivery to the cervical lymph nodes after intranasal administration. ConA, a lectin specifically binding to α-mannose and α-glucose, was covalently conjugated on NPs without loss of its carbohydrates binding bioactivity. In vitro cellular uptake experiment demonstrated that NPs could be uptaken by Calu-3 cells in a time- and concentration-dependent manner, and conjugation of ConA on NPs could significantly increase the rate and amount of cellular uptake. ConA-NP showed no obvious toxicity to Calu-3 cells in vitro or to the nasal cilia of rats in vivo. Compared with NPs without ConA, ConA-NP is more effective in targeting drugs to the deep cervical lymph nodes, as evidenced by 1.36-2.52 times increase of targeting efficiency, demonstrating that ConA-NP is a potential carrier for targeted drug delivery to the cervical lymph nodes via nasal route.


Effect of Inhibition of Glycosylation on the Appearance of a 60 kD Membrane Glycopolypeptide in Endomembrane Fractions of Soybean Root.
Endomembrane (endoplasmic reticulum, Golgi apparatus, plasma membrane) proteins of soybean (Glycine max) root cells are highly glycosylated. We investigated whether N-linked oligosaccharide moieties are essential for the correct intracellular transport of plant endomembrane glycoproteins. Excised roots were incubated with tunicamycin, to block cotranslational glycosylation of proteins, and dual labeled with [(3)H]glucosamine and [(35)S] (methionine, cysteine). In the presence of tunicamycin, the incorporation of glucosamine into membrane proteins was inhibited by 60 to 90% while amino acid incorporation was only slightly affected. Autoradiograms of two-dimensionally separated polypeptides from each endomembrane fraction revealed the presence of at least one new polypeptide in tunicamycin-treated tissue. The new polypeptide was of the same isoelectric point but lower molecular weight than a preexisting polypeptide. The new polypeptide was unreactive to concanavalin A, as opposed to the preexisting polypeptide, suggesting the absence of the glycan portion. Trifluoromethanesulfonic acid and N-glycanase were used to cleave the carbohydrate from the preexisting concanavalin A binding polypeptide. In each case a deglycosylated polypeptide of the same isoelectric point and molecular weight as the new polypeptide from tunicamycin-treated tissue resulted. Since the absence of carbohydrate from the new endomembrane polypeptide did not prevent its appearance on autoradiograms of Golgi and plasma membrane, intracellular transport and intercalation of newly synthesized glycoproteins into plant cell membranes may not require the presence of polysaccharide moieties.


A structural and functional perspective into the mechanism of Ca2+-sensitizers that target the cardiac troponin complex.
The Ca(2+) dependent interaction between troponin I (cTnI) and troponin C (cTnC) triggers contraction in heart muscle. Heart failure is characterized by a decrease in cardiac output, and compounds that increase the sensitivity of cardiac muscle to Ca(2+) have therapeutic potential. The Ca(2+)-sensitizer, levosimendan, targets cTnC; however, detailed understanding of its mechanism has been obscured by its instability. In order to understand how this class of positive inotropes function, we investigated the mode of action of two fluorine containing novel analogs of levosimendan; 2',4'-difluoro(1,1'-biphenyl)-4-yloxy acetic acid (dfbp-o) and 2',4'-difluoro(1,1'-biphenyl)-4-yl acetic acid (dfbp). The affinities of dfbp and dfbp-o for the regulatory domain of cTnC were measured in the absence and presence of cTnI by NMR spectroscopy, and dfbp-o was found to bind more strongly than dfbp. Dfbp-o also increased the affinity of cTnI for cTnC. Dfbp-o increased the Ca(2+)-sensitivity of demembranated cardiac trabeculae in a manner similar to levosimendan. The high resolution NMR solution structure of the cTnC-cTnI-dfbp-o ternary complex showed that dfbp-o bound at the hydrophobic interface formed by cTnC and cTnI making critical interactions with residues such as Arg147 of cTnI. In the absence of cTnI, docking localized dfbp-o to the same position in the hydrophobic groove of cTnC. The structural and functional data reveal that the levosimendan class of Ca(2+)-sensitizers work by binding to the regulatory domain of cTnC and stabilizing the pivotal cTnC-cTnI regulatory unit via a network of hydrophobic and electrostatic interactions, in contrast to the destabilizing effects of antagonists such as W7 at the same interface.


Progressive myopia and intraocular pressure: what is the linkage? A literature review.
Progressive myopia may result from an inherited biomechanical weakness of the sclera that allows it to stretch (creep) in response to stress. Increased intraocular pressure could be the mediator of stress produced by the inclined head position and the accommodation/convergence aspects of near work. This paper reviews data that relate to this hypothesis including work on sclera, intraocular pressure, animal models of myopia, and attempts at human treatment. Although the weight of evidence appears to support the proposed notion, no firm conclusion can be drawn due to imperfections in the design of prior studies. A future research agenda is proposed, including a controlled clinical trial of pharmacologically sustained ocular hypotension in young progressive myopes.


Evaluation of inspiratory rise time and inspiration termination criteria in new-generation mechanical ventilators: a lung model study.
Inspiratory rise time adjustment during pressure ventilation and inspiration termination criteria adjustment during pressure support ventilation are available on some of the newest mechanical ventilators. Both are designed to improve patient-ventilator synchrony. However, the function of these adjuncts during pressure ventilation on these ventilators has not been evaluated. Three inspiratory rise times (minimum, medium, and maximum) were evaluated in 5 new-generation mechanical ventilators (Hamilton Galileo, Siemens 300A, Puritan Bennett 840, BEAR 1000, and Dräger Evita 4) during pressure support and pressure assist/control. Three inspiration termination criteria settings (minimum, medium, and maximum) were also evaluated in 2 mechanical ventilators (Hamilton Galileo and Puritan Bennett 840) during pressure support. All evaluations were performed with a spontaneous breathing lung model (compliance 50 mL/cm H2O, resistance 8.2 cm H2O/L/s, respiratory rate 12 breaths/min, inspiratory time 1.0 s, and lung model peak inspiratory flow 60 L/min). Throughout the evaluation, inspiratory pressure was set at 15 cm H2O and positive end-expiratory pressure at 5 cm H2O, resulting in a peak airway pressure of 20 cm H2O. Significant (p < 0.05) and important (> 10%) differences were found among the ventilators at similar rise times (minimum, medium, and maximum) and for each ventilator as rise time was varied. Also, significant (p < 0.05) and important (> 10%) differences were observed between ventilators and within each ventilator when inspiration termination criteria were varied. There were significant (p < 0.05) differences between pressure support and pressure assist/control, but most were < 10%, except those associated with expiration. Major differences exist for each ventilator as rise time or inspiration termination criteria are varied and among ventilators at similar settings. Inspiration termination criteria adjustment markedly affects transition to exhalation in the Puritan Bennett 840.


Design of a stable charge transfer complex electrode for a third-generation amperometric glucose sensor.
A novel approach to prepare a stable charge transfer complex (CTC) electrode for the direct oxidation of flavoproteins and the fabrication of a third generation amperometric biosensor (Koopal, C.G.J.; Feiters, M.C.; Nolte, R.J.M. Bioelectrochem. Bioenerg. 1992, 29, 159-175) system is described. Tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ), an organic CTC, is grown at the surface of a shapable electroconductive (SEC) film (a polyanion-doped polypyrrole film) in such a way that it makes a tree-shaped crystal structure standing vertically on the surface. Glucose oxidase (GOx) is adsorbed and cross-linked with glutaraldehyde to fix at the surface of the CTC structure. The space between crystals is filled with cross-linked gelatin to ensure the stability of the treelike crystal structure as well as the stability of the enzyme. Because of the close proximity and the favorable orientation of the enzyme at the CTC surface, the enzyme is directly oxidized at the crystal surface, which leads to a glucose sensor with remarkably improved performance. It works at a potential from 0.0 to 0.25 V (vs Ag/AgCl). The maximum current density at 0.25 V reaches 1.8 mA/cm2, with an extended linear range. The oxygen in the normal buffer solution has little effect on the sensor output. The current caused by interference contained in the physiological fluids is negligible. The working life as well as the shelf life of the sensor is substantially prolonged. The sensor was continuously used in a flow injection system with a continuous polarization at 0.1 V, and the samples (usually 10 mM glucose) were injected at 30 min intervals. After 100 days of continuous use, the current output dropped to 40% of the initial level. No change in the output of the sensor was observed over a year when the sensor was stored dry in a freezer. The electrochemical rate constants and the effective Michaelis constant of the system are reported.


Anti-Inflammatory and antiproliferative activities of trifolirhizin, a flavonoid from Sophora flavescens roots.
Trifolirhizin, a pterocarpan flavonoid, was isolated from the roots of Sophora flavescens, and its chemical structure was confirmed by (1)H and (13)C NMR and MS spectra. Its anti-inflammatory activity was examined in lipopolysaccharide (LPS)-stimulated mouse J774A.1 macrophages. Trifolirhizin not only dose-dependently inhibited LPS-induced expression of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) but also inhibited lipopolysaccharide (LPS)-induced expression of cyclooxygenase-2 (COX-2). In addition, trifolirhizin showed in vitro inhibitory effects on the growth of human A2780 ovarian and H23 lung cancer cells. These results suggest that trifolirhizin possesses potential anti-inflammatory and anticancer activities.


Pancreatic function in amyotrophic lateral sclerosis.
No abnormality of exocrine function of the pancreas was found in 10 patients with amyotrophic lateral sclerosis. Eight patients showed abnormal glucose metabolism, attributed to the effects of age, malnutrition, diminished physical activity, and decreased muscle mass.


Health, SES, and the Timing of Education Among Military Retirees.
The timing of education across the life cycle is differentially associated with older-age health outcomes and socioeconomic status among military retirees, a subpopulation with common levels of adolescent health but variation in educational timing. A year of education obtained before military service lowers the probability of poor health in retirement by 2.5 percentage points, while a year obtained after service reduces poor health by only 0.6 percentage point. By contrast, education raises income and wealth uniformly through vintage. This suggests that education improves health through fostering the lifelong accumulation of healthy behaviors and habits rather than raising income or wealth.


Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis.
The major obstacle to successful discordant xenotransplantation is the phenomenon of hyperacute rejection (HAR). In the pig-to-primate discordant transplant setting, HAR results from the deposition of high-titre anti-alpha-galactosyl antibodies and complement activation leading to endothelial cell destruction and rapid graft failure. To overcome HAR, we developed an enzymatic carbohydrate remodelling strategy designed to replace expression of the Gal alpha-1,3-Gal xenoepitope on the surface of porcine cells with the non-antigenic universal donor human blood group O antigen, the alpha-1,2-fucosyl lactosamine moiety (H-epitope). Xenogenic cells expressing the human alpha-1,2-fucosyltransferase expressed high levels of the H-epitope and significantly reduced Gal alpha-1,3-Gal expression. As a result, these cells were shown to be resistant to human natural antibody binding and complement-mediated cytolysis.


Identification, Expression Analysis, and Target Prediction of Flax Genotroph MicroRNAs Under Normal and Nutrient Stress Conditions.
Cultivated flax (Linum usitatissimum L.) is an important plant valuable for industry. Some flax lines can undergo heritable phenotypic and genotypic changes (LIS-1 insertion being the most common) in response to nutrient stress and are called plastic lines. Offspring of plastic lines, which stably inherit the changes, are called genotrophs. MicroRNAs (miRNAs) are involved in a crucial regulatory mechanism of gene expression. They have previously been assumed to take part in nutrient stress response and can, therefore, participate in genotroph formation. In the present study, we performed high-throughput sequencing of small RNAs (sRNAs) extracted from flax plants grown under normal, phosphate deficient and nutrient excess conditions to identify miRNAs and evaluate their expression. Our analysis revealed expression of 96 conserved miRNAs from 21 families in flax. Moreover, 475 novel potential miRNAs were identified for the first time, and their targets were predicted. However, none of the identified miRNAs were transcribed from LIS-1. Expression of seven miRNAs (miR168, miR169, miR395, miR398, miR399, miR408, and lus-miR-N1) with up- or down-regulation under nutrient stress (on the basis of high-throughput sequencing data) was evaluated on extended sampling using qPCR. Reference gene search identified ETIF3H and ETIF3E genes as most suitable for this purpose. Down-regulation of novel potential lus-miR-N1 and up-regulation of conserved miR399 were revealed under the phosphate deficient conditions. In addition, the negative correlation of expression of lus-miR-N1 and its predicted target, ubiquitin-activating enzyme E1 gene, as well as, miR399 and its predicted target, ubiquitin-conjugating enzyme E2 gene, was observed. Thus, in our study, miRNAs expressed in flax plastic lines and genotrophs were identified and their expression and expression of their targets was evaluated using high-throughput sequencing and qPCR for the first time. These data provide new insights into nutrient stress response regulation in plastic flax cultivars.


Genetic causes of hydrops fetalis.
A series of 1790 fetal and neonatal autopsies performed between 1976 and 1988 were retrospectively investigated for the presence of hydrops. Thirty (5.5%) and 35 (2.8%) cases of hydrops were found in the groups of fetal and neonatal autopsies, respectively. Genetic causes accounted for 35%. A careful search for previously reported genetic causes of fetal hydrops indicated 64 different etiologies. Twenty-one of them were not mentioned in the previous reviews: these include 9 skeletal dysplasias, 5 inborn errors of metabolism, 3 autosomal recessive, 3 autosomal dominant conditions, and 1 chromosomal abnormality.


Profile and severity of the patients of intensive care units: prospective application of the APACHE II index.
This study aimed to understand the profile and severity of patients in physiotherapy treatment after their admission to the intensive care unit (ICU) by applying the APACHE II index. One hundred and forty six subjects, with a mean age of 60.5 +/- 19.2 years, were evaluated. The APACHE II index was applied in the first 24 hours to evaluate the severity and mortality risk score. Patients were monitored until hospital discharge or death. The mean APACHE II score was 20+/-7.3 with an estimated risk of death of 32.4% and observed mortality of 58.2%. The mean hospital stay was 27.8+/-25.2 days. The patients in physiotherapy at the institution studied were predominantly male, elderly, from the emergency service for treatment (non-surgical), and had clear severity, suggested by the APACHE II score and the observed mortality.


Aggressive Ciliary Body Adenocarcinoma with Bilateral Lung Metastases: Histological, Molecular, Genetic and Clinical Aspects.
To describe the clinical and histopathological features of an aggressive ciliary body adenocarcinoma with pulmonary metastases and skull base spread. A 45-year-old female patient presented with a post-traumatic phthisical eye that was eviscerated. This showed an unexpected carcinoma (positive for cytokeratins and melanocytic markers), the histological differential diagnosis for which included a primary ciliary body adenocarcinoma or a metastasis. The patient developed rapid post-surgical localized recurrence that required an orbital exenteration. This showed identical tumour to the evisceration specimen, with vascular invasion in orbital blood vessels and a contaminated orbital soft tissue margin. Staging imaging revealed multiple lung metastases, which were biopsied and shown to be a disseminated ciliary body adenocarcinoma rather than a disseminated primary lung carcinoma. The tumour spread locally to the skull base for which radiotherapy was given. Unfortunately, the patient passed away a few weeks later. To our knowledge, this is the first case of ciliary body adenocarcinoma with bilateral lung metastases. The malignant potential of these tumours should be considered as a possibility, and appropriate screening and staging tests should therefore be considered to guide appropriate management.


The effect of gabapentin on intensity and duration of hot flashes in postmenopausal women: a randomized controlled trial.
Menopause is the stage of time in which the menstruation stops following the loss of ovarian activity. The purpose of this study was to find out the effectiveness of gabapentin on hot flashes in postmenopausal women. A randomized controlled trial from Feb 2010 to 2011 was conducted. Sixty postmenopausal women who were referred to obstetrics and gynecology ward of two educational hospitals were recruited and divided into two groups (intervention and control). Intervention group received 300 mg gabapentin three times a day for three months, while control group received placebo. The Intensity and duration of hot flashes in women scored and recorded using visual analog scale. Independent, Paired t-test and chi-square test were used for analyzing data. Intensity of hot flashes in the beginning of research in the intervention group was significantly different with the first, second and third follow-up visit (P<0.05). Also at the end of intervention a significant difference between intervention and control groups were observed regarding the intensity, frequency and duration of hot flashes (P<0.05 and P=0.01 respectively). According to the findings of this study; it appears that the use of gabapentin could decrease the intensity, duration and frequency of hot flashes in postmenopausal women. For postmenopausal women who hormone therapy is contraindicated, gabapentine could be an acceptable alternative.


Therapeutic options for the treatment of postherpetic neuralgia: a systematic review.
Postherpetic neuralgia (PHN) is a chronic and painful condition that may result in significant disturbances to normal activities and decreases in the quality of life for those affected. Despite the availability of several first- and second-line treatment options, many patients may experience refractory pain. The objectives of this review were to summarize evidence for Food and Drug Administration (FDA)-approved and off-label therapies for the treatment of PHN and to present gaps in the current literature for future research focus. Several agents, including pregabalin, gabapentin, and opioids, have been shown to significantly improve pain when compared with placebo. However, evidence regarding the comparative effectiveness of these treatment alternatives is lacking. In order to choose the optimal treatment, providers should consider issues related to efficacy, safety, and tolerability in conjunction with patient goals, preferences, and adherence issues. Evidence from randomized or observational studies that directly compare agents with each other should help to inform treatment choices.


[Biological characteristics of periodontal ligament stem cells modified by platelet derived growth factor BB].
To investigate the biological characteristics of human periodontal stem cells (hPDLSCs) modified with platelet derived growth factor BB(PDGFBB) gene, and to explore its influence on proliferation, migration and osteogenic induction of hPDLSCs. hPDLSCs were isolated and amplified, and immunofluorescence staining was performed to identify cell surface markers and osteogenic differentiation ability. hPDLSCs were transfected with PDGFBB gene by lentivirus vector, and the effects on cell proliferation and migration were detected by CCK-8 and scratch test after transfection. Real-time PCR was performed to analyze the mRNA expression levels of osteogenic and angiogenic genes in hPDLSCs cells transfected with PDGFBB gene. Statistical analysis was performed using SPSS 22.0 software package. hPDLSCs were successfully obtained by tissue mass culture and finite dilution method. Compared with the blank virus group and non-transfected group, the proliferation and migration ability of the cells in the transfection group were significantly increased, and the mRNA expression levels of OPN, COL-1 and VEGF were significantly up-regulated(P<0.05). Lentiviral vector can transfer PDGFBB gene into hPDLSCs in vitro and obtain continuous and stable expression. PDGFBB can promote proliferation and migration of hPDLSCs cells and up-regulate expression of osteogenic and angiogenic genes.


Interventional neuroradiology.
Interventional neuroradiology is a dynamic subspecialty which is rapidly gaining new applications in the treatment of neurological diseases. The most common therapeutic role is still in the treatment of brain AVMs, aneurysms and fistulae in close association with neurosurgical support. Endovascular treatment of aneurysms with thrombogenic coils is a promising technique which can be performed with low morbidity. The goal of complete aneurysm occlusion, including the neck, has not yet been achieved in all cases and the procedure has not been shown to possess clear advantages over surgical clipping. Pre-operative embolization of tumours and spinal lesions are common procedures in some centres. Angioplasty and papaverine infusion for treatment of cerebral vasospasm are being performed in most neurosurgical teaching centres. Although angiographic results are often impressive, corresponding clinical improvement is not always seen, particularly when treatment is delayed. Thrombolysis for treatment of acute stroke and angioplasty for treatment of cerebrovascular atherosclerosis are new techniques which await scientific validation before being accepted as standard therapies.


Binding and location of dipyridamole derivatives in micelles: the role of drug molecular structure and charge.
Binding and localization of the vasodilator and antitumor drug coactivator dipyridamole (DIP) and of its three derivatives, RA14, RA47 and RA25 (DIPD), to cationic (cetyltrimethylammonium chloride), anionic (sodium dodecylsulfate), zwitterionic (N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate), and neutral (t-octylphenoxypolyethoxyethanol) micelles was studied using fluorescence, optical absorption and 1H NMR spectroscopy. The analysis of NMR, optical absorption and fluorescence data indicates that the depth of localization of the drugs in the micelles from the surface decreased in the order DIP > RA14 > RA47 > RA25. The binding constants for the neutral drug forms change in the same order in the range of 1400-3100 M-1 for DIP to 80-300 M-1 for RA25. This order is identical with the reported biological activity of DIPD. For the protonated drugs in zwitterionic or neutral micelles the binding constants are reduced by a factor of 20-75.


Dyadic effects of marital satisfaction on coparenting in Chinese families: Based on the actor-partner interdependence model.
Based on the actor-partner interdependence model, this study explored the spillover and crossover effects of marital satisfaction on coparenting in Chinese nuclear and extended families. Spillover and crossover effects refer to the transfer of experiences, affects or behaviors, focusing on the intra-personal and inter-personal transfer of a marital subsystem to a coparenting subsystem. The participants comprised 279 couples with children ranging in age from 3 to 7 years old. The marital satisfaction and extent of coparenting of both the fathers and the mothers was tested to examine the dyadic interaction. Structural equation modeling results revealed significant intra-personal and inter-personal correlations between marital satisfaction and coparenting, indicating spillover and crossover effects in nuclear and extended families, and there were no differences between the two family structures. The results indicated that fathers' marital satisfaction influenced both fathers' and mothers' coparenting practices.


Clarifying Role Expectations and Practice Standards Using a Clinical Nurse Leader Professional Practice Model Illustration.
Despite evidence of the positive impact of the clinical nurse leader (CNL) role, implementation of supplemental nursing roles has proven to be challenging due to unclear role explanations and organizational unfamiliarity. Nurses practice in a dynamic environment and need to cope with the rapid pace of change in practice roles. Outside of the preparation of the CNL, many nursing professionals are not educated or prepared on the essential aspects the CNL role. A graphic illustration was developed to facilitate discussion and provide insight into the CNL role, with the aim of creating consensus on the CNL role functions and expectations. Following the implementation of the CNL practice model illustration, participants reported a significant improvement in their understanding and importance of the CNL role. Professional practice model illustrations may be beneficial in developing a consensus of practice.


Professional Organization Membership: The Benefits of Increasing Nursing Participation.
Membership in professional organizations is a way for professionals with similar objectives to join together to have the voice of many, versus the voice of one. Joining an organization can lead to personal growth, enhanced professional prospective and knowledge development, and support for creating change.


Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in Mycobacterium tuberculosis, and its application to assessment of drug targets.
Targeting persistent tubercule bacilli has become an important challenge in the development of anti-tuberculous drugs. As the glyoxylate bypass is essential for persistent bacilli, interference with it holds the potential for designing new antibacterial drugs. We have developed kinetic models of the tricarboxylic acid cycle and glyoxylate bypass in Escherichia coli and Mycobacterium tuberculosis, and studied the effects of inhibition of various enzymes in the M. tuberculosis model. We used E. coli to validate the pathway-modeling protocol and showed that changes in metabolic flux can be estimated from gene expression data. The M. tuberculosis model reproduced the observation that deletion of one of the two isocitrate lyase genes has little effect on bacterial growth in macrophages, but deletion of both genes leads to the elimination of the bacilli from the lungs. It also substantiated the inhibition of isocitrate lyases by 3-nitropropionate. On the basis of our simulation studies, we propose that: (i) fractional inactivation of both isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 is required for a flux through the glyoxylate bypass in persistent mycobacteria; and (ii) increasing the amount of active isocitrate dehydrogenases can stop the flux through the glyoxylate bypass, so the kinase that inactivates isocitrate dehydrogenase 1 and/or the proposed inactivator of isocitrate dehydrogenase 2 is a potential target for drugs against persistent mycobacteria. In addition, competitive inhibition of isocitrate lyases along with a reduction in the inactivation of isocitrate dehydrogenases appears to be a feasible strategy for targeting persistent mycobacteria. We used kinetic modeling of biochemical pathways to assess various potential anti-tuberculous drug targets that interfere with the glyoxylate bypass flux, and indicated the type of inhibition needed to eliminate the pathogen. The advantage of such an approach to the assessment of drug targets is that it facilitates the study of systemic effect(s) of the modulation of the target enzyme(s) in the cellular environment.


Low-frequency repetitive transcranial magnetic stimulation for patients with aphasia after stoke: A meta-analysis.
To perform a meta-analysis of studies investigating the effects of low-frequency repetitive transcranial magnetic stimulation on post-stroke aphasia. Studies were identified by performing a search of electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Knowledge) for articles published until June 2014. Randomized controlled trials (RCTs) reporting treatments with low-frequency repetitive transcranial magnetic stimulation in patients with post-stroke aphasia were included. The outcomes included naming, repetition, comprehension, changes in brain excitability, and adverse events. Two independent reviewers extracted the data. Study quality was evaluated with the PEDro scale. Of the 879 articles identified, 4 RCTs were included in the final analysis. Data synthesis showed that low-frequency repetitive transcranial magnetic stimulation was beneficial for post-stroke patients in terms of naming (standard mean difference (SMD) 0.51; 95% confidence interval (95% CI) 0.16-0.86) and changes in brain excitability (7.6 ± 33.55; 95% CI -10.7-26.20). However, the changes in repetition (SMD 0.31; 95% CI -0.04-0.65) and comprehension (SMD 0.31; 95% CI -0.14-0.75) after stimulation were not significant. No adverse effects were reported. The included studies were of high methodological quality. These findings indicate that low-frequency repetitive transcranial magnetic stimulation is an effective treatment for recovery of naming. In addition, this treatment favours reorganization of the left-hemispheric language networks.


PSMA PET in Imaging Prostate Cancer.
After prostate malignancy diagnosis, precise determination of disease extent are fundamental steps for tailored made therapy. The earlier the diagnosis of the burden of the disease, the longer the survival in many cases. National and international guidelines are based on "classic" imaging technics combining radiological and nuclear medicine scans like CT, MRI and bone scintigraphy (BS). The most recent nuclear medicine development is the prostate specific membrane antigen (PSMA) PET and is emerging as the most promising tool of medical imaging, gaining ground every day. Nevertheless, the different onset among multiple studies fails to establish a worldwide admission and incorporation of this technique in guidelines and its position in workaday medical algorithms. It seems that the medical community agrees not to utilize PSMA PET for low-risk patients; intense debate and research is ongoing for its utility in intermediate risk patients. Contrariwise, in high-risk patients PSMA PET is confirmed outperforming CT and BS combined. Additionally, irrespectively to their castration status, patients with biochemical failure should be referred for PSMA PET. Even though PSMA PET reveals more extended disease than expected or exonerates equivalent lesions, thus impacting treatment optimization. Studies being in progress and future trials with clarify whether PSMA PET will be the new gold standard technic for specific groups of patients.


Plasmon mediated Fe-O in an octahedral site of cuprospinel by Cu NPs for photocatalytic hydrogen evolution.
Cu NPs (copper nanoparticles) were synthesized in situ on the surface of CuFe2O4 (cuprospinel). The enhancement of the separation efficiency of photogenerated e-/h+ and the catalytic quantum efficiency showed that the LSPR (local surface plasmon resonance) of Cu NPs facilitated the photocatalytic reaction activity of CuFe2O4. And due to the fact that CuFe2O4 was constructed with Cu-O in the tetrahedral site and Fe-O in the octahedral site, the results of DTG and Raman spectra after HER (hydrogen evolution reaction) displayed that the phase change of Fe-O in the octahedral site of CuFe2O4 took place during the HER process, and along with the peak of Fe2+ in XPS spectra after HER, which indicated that light activated Fe-O in the octahedral site was responsible for the photocatalytic process.


Comparison of different models for genetic analysis of clinical mastitis in Austrian Fleckvieh dual-purpose cows.
The performance of different models for genetic analyses of clinical mastitis in Austrian Fleckvieh dual-purpose cows was evaluated. The main objective was to compare threshold sire models (probit and logit) with linear sire and linear animal models using REML algorithm. For comparison, data were also analyzed using a Bayesian threshold sire model. The models were evaluated with respect to ranking of sires and their predictive ability in cross-validation. Only minor differences were observed in estimated variance components and heritability from Bayesian and REML probit models. Heritabilities for probit and logit models were 0.06 and 0.08, respectively, whereas heritabilities for linear sire and linear animal models were lower (0.02). Correlations among ranking of sires from threshold and linear sire models were high (>0.99), whereas correlations between any sire model (threshold or linear) and the linear animal model were slightly lower (0.96). The worst sires were ranked very similar across all models, whereas for the best sires some reranking occurred. Further, models were evaluated based on their ability to predict future data, which is one of the main concerns of animal breeders. The predictive ability of each model was determined by using 2 criteria: mean squared error and Pearson correlation between predicted and observed value. Overall, the 5 models did not differ in predictive ability. In contrast to expectations, sire models had the same predictive ability as animal models. Linear models were found to be robust toward departures from normality and performed equally well as threshold models.


[Standardized oculocardiac reflex in ex-premature near full term (93 cases)].
The aim of the study was to present data investigating vagal reactivity in a population of premature infants reaching term, using the oculo-cardiac reflex. Ninety three premature infants, free of any disease, near full term at the moment of testing, were prospectively investigated at a time close to discharge from neonatal unit. After an all-night polygraphic recording, a standardized oculo-cardiac reflex test was performed during quiet sleep. Data were classified in relation to both chronological and postconceptional ages. Simple liner regression analyses were performed on the selected variables. The results showed heterogeneity of the vagal response in this population: longest asystole (1049 ms +/- 540; 95th percentile = 1894 ms); maximal percentage of deviation between two successive RR intervals (88% +/- 90; 95th percentile = 200%); and duration between the beginning of decrease in heart rate and return to mean heart rate (14 s +/- 10; 95th percentile = 30 s). Our healthy premature infants at time of discharge exhibited a wider range of vagal reactivity than previously reported for the full term newborns. Considering our findings, we recommend caution before proceeding with treatment of vagal bradycardia in a similar premature infant population.


Interaction of L-alanyl-L-valine and L-valyl-L-alanine with organic vapors: thermal stability of clathrates, sorption capacity and the change in the morphology of dipeptide films.
The strong effect of the amino acid sequence in L-alanyl-L-valine and L-valyl-L-alanine on their sorption properties toward organic compounds and water, and the thermal stability of the inclusion compounds of these dipeptides have been found. Generally, L-valyl-L-alanine has a greater sorption capacity for the studied compounds, but the thermal stability of the L-alanyl-L-valine clathrates is higher. Unusual selectivity of L-valyl-L-alanine for vapors of few chloroalkanes was observed. The correlation between the change in the surface morphology of thin film of dipeptides and stoichiometry of their clathrates with organic compounds was found. This discovery may be used to predict the influence of vapors on the morphology of films of short-chain oligopeptides.


Characterization of differentially expressed genes in purified Drosophila follicle cells: toward a general strategy for cell type-specific developmental analysis.
Axis formation in Drosophila depends on correct patterning of the follicular epithelium and on signaling between the germ line and soma during oogenesis. We describe a method for identifying genes expressed in the follicle cells with potential roles in axis formation. Follicle cells are purified from whole ovaries by enzymatic digestion, filtration, and fluorescence-activated cell sorting (FACS). Two strategies are used to obtain complementary cell groups. In the first strategy, spatially restricted subpopulations are marked for FACS selection using a green fluorescent protein (GFP) reporter. In the second, cells are purified from animals mutant for the epidermal growth factor receptor ligand gurken (grk) and from their wild-type siblings. cDNA from these samples of spatially restricted or genetically mutant follicle cells is used in differential expression screens employing PCR-based differential display or hybridization to a cDNA microarray. Positives are confirmed by in situ hybridization to whole mounts. These methods are found to be capable of identifying both spatially restricted and grk-dependent transcripts. Results from our pilot screens include (i) the identification of a homologue of the immunophilin FKBP-12 with dorsal anterior expression in egg chambers, (ii) the discovery that the ecdysone-inducible nuclear hormone receptor gene E78 is regulated by grk during oogenesis and is required for proper dorsal appendage formation, and (iii) the identification of a Drosophila homologue of the human SET-binding factor gene SBF1 with elevated transcription in grk mutant egg chambers.


Tetramate Derivatives by Chemoselective Dieckmann Ring Closure of threo-Phenylserines and Their Antibacterial Activity.
A general route, which provides direct access to substituted bicyclic tetramates, making use of Dieckmann cyclization of oxazolidines derived from threo-arylserines, is reported; the latter were found to be available by an efficient aldol-like reaction of glycine with some substituted benzaldehydes under alkaline conditions. The tetramates were found to release chelated metal cations acquired during chromatographic purification by mild acid wash. Some compounds in the library showed good antibacterial activity against Gram-positive bacteria. Cheminformatic analysis demonstrates that the most active compounds were Ro5-compliant and occupy a narrow region of chemical space, distinct from that occupied by other known antibiotics, with the most potent compounds having 399 < Mw < 530 Da; 3.5 < cLogP < 6.6; 594 < MSA <818 Å2; 9.6 < rel. PSA <13.3%. MIC values were shifted to higher concentrations when tested in the presence of HSA or blood, but was not completely abolished, consistent with a plasma protein binding (PPB) effect.


The adequacy of consent forms for informing patients entering oncological clinical trials.
The impact on 100 patients of information and consent forms signed prior to medical oncology clinical trials was evaluated by a survey at a subsequent visit. Only 40 patients believed that the purpose of the form was to explain the treatment. The form was listed as the major source of information by 12 patients while 52 listed a doctor and 26 a nurse. Although 21 patients believed that the form mad them less anxious, 19 patients believed that it made them more anxious. Despite 80 patients reading all of the form, 60 claiming to understand all of it and 68 claiming that in contained adequate information, in tests of recall only 52 patients could name all of their drugs and only 4 all of the side effects. The number of drugs named correlated with how much of the consent form had been read (p = 0.003) and the highest education level achieved by the patient (p = 0.0003). Patients under 55 years had significantly better recall. Patients with a better ECOG performance status were more likely to find the form very helpful. Such forms may not ensure that the requirements for informed consent are satisfied.


SPG20 protein spartin is recruited to midbodies by ESCRT-III protein Ist1 and participates in cytokinesis.
Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. The SPG20 protein spartin localizes to lipid droplets and endosomes, and it interacts with tail interacting protein 47 (TIP47) as well as the ubiquitin E3 ligases atrophin-1-interacting protein (AIP)4 and AIP5. Spartin harbors a domain contained within microtubule-interacting and trafficking molecules (MIT) at its N-terminus, and most proteins with MIT domains interact with specific ESCRT-III proteins. Using yeast two-hybrid and in vitro surface plasmon resonance assays, we demonstrate that the spartin MIT domain binds with micromolar affinity to the endosomal sorting complex required for transport (ESCRT)-III protein increased sodium tolerance (Ist)1 but not to ESCRT-III proteins charged multivesicular body proteins 1-7. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells by small interfering RNA significantly decreases the number of cells where spartin is present at midbodies. Depletion of spartin does not affect Ist1 localization to midbodies but markedly impairs cytokinesis. A structure-based amino acid substitution in the spartin MIT domain (F24D) blocks the spartin-Ist1 interaction. Spartin F24D does not localize to the midbody and acts in a dominant-negative manner to impair cytokinesis. These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis.


A natural marmoset model of genetic generalized epilepsy.
Epilepsy has been extensively studied as a common neurological disease. Efforts have been made on rodent and other animal models to reveal the pathogenic mechanisms of epilepsy and develop new drugs for treatment. However, the features of current epilepsy models cannot fully mimic different types of epilepsy in humans, hence non-human primate models of epilepsy are required. The common marmoset (Callithrix jacchus) is a New World monkey that is widely used to study brain function. Here, we present a natural marmoset model of generalized epilepsy. In this unique marmoset family, generalized epilepsy was successfully induced by handling operations in some individuals. We mapped the marmoset family with handling-sensitive epilepsy and found that the epileptic phenotype can be inherited. These marmosets were more sensitive to the epilepsy inducers pentylenetetrazol. Using electrocorticogram (ECoG) recordings, we detected epileptiform discharge in marmosets with a history of seizures. In summary, we report a family of marmosets with generalized seizures induced by handling operations. This epileptic marmoset family provides insights to better understand the mechanism of generalized epilepsy and helps to develop new therapeutic methods.


Molecular cloning and characterization of a sym plasmid locus that regulates cultivar-specific nodulation of soybean by Rhizobium fredii USDA257.
Rhizobium fredii strain USDA257 produces nitrogen-fixing nodules on primitive soybean cultivars such as Peking but fails to nodulate agronomically improved cultivars such as McCall. Transposon-mutant 257DH4 has two new phenotypes: it nodulates McCall, and its ability to do so is sensitive to the presence of parental strain USDA257, i.e. it is subject to competitive nodulation blocking. We have isolated a cosmid containing DNA that corresponds to the site of transposon insertion in 257DH4 and have localized Tn5 on an 8.0 kb EcoRI fragment. The 5596 bp DNA sequence that surrounds the insertion site contains seven open reading frames. Five of these, designated nolBTU, ORF4, and nolV, are closely spaced and of the same polarity. nolW and nolX are of the opposite polarity. The initiation codon for nolW lies 155 bp upstream from that of nolB, and its is separated from nolX by 281 bp. The predicted NolT and NolW proteins have putative membrane-spanning regions. The N-terminus of the hypothetical NolW protein also has limited homology to NodH of Rhizobium meliloti, but none of the deduced protein sequences has significant homology to known nodulation gene products. Site-directed mutagenesis with mudII1734 confirms that inactivation of nolB, nolT, nolU, nolV, nolW, or nolX extends host range for nodulation to McCall soybean. This phenotype could not be genetically dissected from sensitivity to competitive nodulation blocking. Expression of nolBTU and nolX is induced as much as 30-fold by flavonoid signal molecules, even though these genes lack nod-box promoters. Histochemical staining of McCall roots inoculated with nolB-, nolU-, or nolX-lacZ fusions verifies that these genes are expressed continuously from preinfection to the stage of the functional nodule. Although a nolU-ORF4-nolV clone hybridizes to a single 8.0 kb EcoRI fragment from 10 strains of R. fredii and broad-host-range Rhizobium sp. NGR234, hybridizing sequences are not detectable in other rhizobia.


Long-term costs of inflated self-estimate on academic performance among adolescent students: a case of second-language achievements.
Past studies suggest that the adaptive or maladaptive consequences of inflated self-estimate, one form of positive illusions, require further investigation. 308 freshmen at a junior college (164 women, 144 men; M age = 19.8 yr., SD = 1.1) participated in a longitudinal study during a 2-yr. period. There were three assessments of short- and long-term effects of overly positive self-estimates on second-language achievement. Students' overestimation of subsequent performance appears to be associated with lower achievement. Those students with apparently inflated self-estimates performed marginally better on the first assessment but worse in the second and final assessments. Students with more accurate self-estimates showed improvement on all assessments. The findings suggested that overinflated self-estimates, i.e., positive illusions, among adolescent students might lead to a lower achievement over the long-term.


[Clinical analysis of low grade myofibroblastic sarcoma in head and neck].
To explore the clinical characteristic, the CT, MRI features, diagnosis and treatment of low grade myofibroblastic sarcoma in head and neck. Six cases of low grade myofibroblastic sarcoma in head and neck were diagnosis and reviewed retrospectively. Routine preoperative CT and MRI examination were performed. All cases were operated one case with radiotherapy before operation was given with a total dose of 60 Gy. The patients were follow-up for 6 months to 5 year and no recurrence was found. No complications occurred in 6 cases. It has been confirmed in this research that LGMS is a low-grade malignangt tumor. It was difficult to make early diagnosis through frozen section. The final diagnosis depend on paraffin section and immunohistochemisty. Extended local excision with tumor-free margin is the treatment of choice.


Antihypertensive effect and underlying mechanism of tripeptide NCW on spontaneously hypertensive rats using metabolomics analysis.
Tripeptide NCW identified in our previous study displayed a strong ACE inhibitory activity, but whether it has any antihypertensive effect in vivo remains unknown. Thus, in this study, we aimed to investigate the protective effects of tripeptide NCW in spontaneously hypertensive rats (SHRs) and to further figure out the serum metabolic profiling variations due to its oral administration via UPLC-Q-TOF-MS/MS-based metabolomics analysis to clarify the underlying hypotensive mechanism. After three weeks of oral administration, the tripeptide NCW-treated group (NCW/SHR group, 80 mg per kg BW per d) showed significantly reduced systolic and diastolic blood pressure by 48.08 ± 3.84 mmHg and 48.92 ± 5.77 mmHg, respectively. Additionally, a total of 25 blood pressure-related metabolites were identified as being significantly changed in SHRs given tripeptide NCW after three weeks. These 25 metabolites might be biomarkers that indicated that the tripeptide NCW exhibits antihypertensive activity via regulating bile acid metabolism, lipid metabolism, amino acid metabolism, purinergic signaling, pantothenate and CoA biosynthesis, and the citrate cycle. Collectively, tripeptide NCW has a protective effect on SHRs associated with serum metabolite abnormalities.


Comparison of Single and Combined Effects of Nature Sounds and Foot Sole Reflexology Massage on the Level of Consciousness in Traumatic Comatose Patients: A Randomized Controlled Clinical Trial.
Consciousness disturbances are the most common posttraumatic complications. The purpose of this study was to compare the single and combined effects of nature sounds and foot sole reflexology massage on level of consciousness in traumatic comatose patients. This randomized controlled clinical trial was conducted in 2 teaching hospitals in an urban area of Iran. Samples were 120 traumatic comatose patients who were randomly assigned into control, nature sounds, foot reflexology massage, and nature sounds plus foot sole reflexology massage groups. Patients in all groups received routine care. Interventions were performed twice a day for 2 weeks, each time for 30 minutes. The patients' level of consciousness was assessed using the Glasgow Coma Scale before, 1 week, and 2 weeks after the intervention. The groups had no significant differences in the mean scores of the consciousness level before, 1 week after, and the last day of the intervention. Also, there was a significant difference in the number of patients who regained full consciousness (P = .001) in the intervention groups compared with the control group. Significant differences in the number of days of consciousness were reported in at least one of the groups compared with other groups (P = .001). This difference was significant in the control group compared with the foot reflexology massage group (P = .032), as well as the nature sounds plus foot sole reflexology massage group (P = .001). Single or combined interventions can increase the level of consciousness in comatose patients and reduce the duration of coma.


Assessment of the functional regions of the superantigen staphylococcal enterotoxin B.
The functional activity of superantigens is based on capacity of these microbial proteins to bind to both the β-chain of the T cell receptor (TcR) and the major histocompatibility complex (MHC) class II dimer. We have previously shown that a subset of the bacterial superantigens also binds to a membrane protein, designated p85, which is expressed by renal epithelial cells. This binding activity is a property of SEB, SEC1, 2 and 3, but not SEA, SED, SEE or TSST. The crystal structure of the tri-molecular complex of the superantigen staphylococcal enterotoxin B (SEB) with both the TcR and class II has previously been reported. However, the relative contributions of regions of the superantigen to the overall functional activity of this superantigen remain undefined. In an effort to better define the molecular basis for the interaction of SEB with the TcR β-chain, we report studies here which show the comparative contributions of amino- and carboxy-terminal regions in the superantigen activity of SEB. Recombinant fusion proteins composed of bacterial maltose-binding protein linked to either full-length or truncated toxins in which the 81 N-terminal, or 19 or 34 C-terminal amino acids were deleted, were generated for these studies. This approach provides a determination of the relative strength of the functional activity of the various regions of the superantigen protein.


The ALDH2 rs671 polymorphism affects post-stroke epilepsy susceptibility and plasma 4-HNE levels.
Recent studies have demonstrated the protective effect of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases. Increased levels of the potential ALDH2 substrate 4-hydroxynonenal (4-HNE) are involved in myocardial/cerebral ischemia accompanied by a high level of oxidative stress. In this investigation, we first performed a case-control study to explore the potential association of ALDH2 rs671 polymorphism and post-stroke epilepsy (PSE). Then, we performed an in vitro study to determine whether the overexpression of ALDH2 could decrease the level of oxidative stress and the apoptosis ratio induced by 4-HNE. There was a significant difference in the distribution of the allele and genotype frequencies of the rs671 polymorphism between PSE patients and ischemic stroke (IS) patients. Individuals with the rs671 A allele showed significantly higher levels of plasma 4-HNE. The overexpression of ALDH2 partially blocked the increased levels of malondialdehyde (MDA), reactive oxygen species (ROS) and apoptosis ratio induced by 4-HNE and also partially restored the ALDH2 activity in PC12 cells; these effects were reversed in the presence of εV1-2. Our results suggest that the ALDH2 rs671 polymorphism is associated with PSE susceptibility and affects the 4-HNE levels. Targeting ALDH2 might be a useful strategy for the treatment or prevention of PSE.


STEP sisters, sex, and STDs: a process evaluation of the recruitment of lay health advisors.
Individual interviews, field observations, and group debriefings were used in this qualitative study that assessed the accuracy of the recruitment strategy used to identify natural helpers to assist African American women, aged 18-34, to prevent and seek care for sexually transmitted diseases (STDs). The study indicates that the recruitment strategy is effective when a list of natural helpers is generated by advisory groups from the same geographic community. Screening protocols used to interview potential natural helpers appear to reduce later barriers to advising on sensitive topics like STDs. The data suggest the importance of using community members to identify natural helpers and the importance of addressing sensitive topics early in the recruitment process.


Testicular Nodules Suspected for Malignancy. Does the Pathologist Make the Difference for Organ-Sparing Surgery? .
To evaluate the factors that influence decision-making after frozen section examination (FSE) when a urologist sends a surgical specimen of a testicular nodule to a pathologist. We retrieved, from surgical and pathological files of our center from 2008 to 2014, the clinical information of 15 patients who underwent an explorative inguinal testicular surgery for an intratesticular nodule suspected for malignancy and managed with intention of testicular-sparing surgery. We identify the factors that influenced the correlation between outcome of the FSE and final histopathological report. Mean diameter of the testicular nodules was 8.37 mm. Very small lesions (< 5 mm) were detected in 4 cases (27%), with definitive diagnosis of seminoma in 2 of those (50%). At clinical evaluation 2 nodules were palpable but not malignant at definitive diagnosis. Overall, at definitive histopathological nodule report, a pathologist diagnosed 5 Leydig cell tumors, 4 seminomas, 1 adenomatoid tumor, 1 Sertoli cell tumor, 1 malignant teratoma, and a hemorragic infiltrate in 3 cases. FSE on testicular biopsy reported intratesticular neoplasia only in all cases of definitive diagnosis of seminoma. We observed a concordance between nodule FSE and definitive pathologic report in 11 cases (73%) and in 87% of ancillary testicular biopsies. Discordance was observed in cases lacking the availability of a dedicated pathologist. In cases of small testicular nodule FSE may aid the surgery decision and avoid overtreatment. The close collaboration between urologist and a dedicated pathologist is very useful in reducing diagnostic and therapeutic errors.


Intranasal surfactant protein D as neuroprotective rescue in a neonatal rat model of periventricular leukomalacia.
Periventricular leukomalacia (PVL) is the leading cause of neurocognitive deficits in children with prematurity. We previously hypothesized that surfactant protein D (SPD) with its ability to bind toll-like receptors may have a possible ameliorating effect in PVL. Three groups were defined as: LPS-administered and postnatal intranasal saline administered group, LPS-administered and postnatal intranasal SPD-treated group, and control group. Twenty-eight offspring rats were reared with their dams until their sacrifice for histological evaluation on day 7. A significant loss of brain weight occurred in the LPS group compared with controls. The postnatal intranasal SPD treatment significantly reduced the number of TUNEL-positive cells in the periventricular white matter as compared with the LPS-treated group. Compared with the control group, LPS injection in the rat brain significantly reduced the MBP-positive staining. Postnatal SPD treatment greatly prevented LPS-stimulated loss of MBP staining. Present study demonstrated a neuroprotective effect of SPD in a rat model of PVL. Our results offer future implications towards increasing our understanding about multifactorial mechanisms underlying periventricular leukomalacia and developing plausible therapeutic strategies in order to prevent neurocognitive deficits in preterm infants.


High-speed mosaic imaging using scanner-synchronized stage position sampling.
Two-photon and confocal microscopy can obtain high frame rates; however, mosaic imaging of large tissue specimens remains time-consuming and inefficient, with higher imaging rates leading to a larger fraction of time wasted translating between imaging locations. Strip scanning obtains faster mosaic imaging rates by translating a specimen at constant velocity through a line scanner at the expense of more complex stitching and geometric distortion due to the difficulty of translating at completely constant velocity. We aim to develop an approach to mosaic imaging that can obtain higher accuracy and faster imaging rates while reducing computational complexity. We introduce an approach based on scanner-synchronous position sampling that enables subwavelength accurate imaging of specimens moving at a nonuniform velocity, eliminating distortion. We demonstrate that this approach increases mosaic imaging rates while reducing computational complexity, retaining high SNR, and retaining geometric accuracy. Scanner synchronous strip scanning enables accurate, high-speed mosaic imaging of large specimens by reducing acquisition and processing time.


A Self-Powered Transparent Photodetector Based on Detached Vertical (In,Ga)N Nanowires with 360° Omnidirectional Detection for Underwater Wireless Optical Communication.
Underwater wireless optical communication (UWOC) is a wireless communication technology using visible light to transmit data in an underwater environment, which has wide applications. Based on lift-off (In,Ga)N nanowires, this work has proposed and successfully demonstrated a self-powered photoelectrochemical (PEC) photodetector (PD) with excellent transmissivity. The transparent functionality of the PD is critical for 360° omnidirectional underwater detection, which was realized by detaching the (In,Ga)N nanowires from the opaque epitaxial substrates to the indium tin oxide (ITO)/glass. It was also found that the insulating SiO2 layer can enhance the photocurrent by about 12 times. The core-shell structure of the nanowires is beneficial for generating carriers and contributing to the photocurrent. Furthermore, a communication system with ASCII code is set to demonstrate the PD detection in underwater communication. This work paves an effective way to develop 360° omnidirectional PDs for the wide applications in UWOC system and underwater photodetection.


In vivo imaging of HIV protease activity in amplicon vector-transduced gliomas.
In vivo imaging of endogenously expressed mammalian proteases has been useful for the detection of cancer and preneoplastic lesions, for staging of inflammatory and autoimmune diseases, and for testing the efficacy of novel protease inhibitors. Here we report on the synthesis of a novel imaging probe that is specific for HIV-1 protease (PR). The probe was designed to be biocompatible, i.v. injectable, and detectable by fluorescence imaging. Human Gli36 glioblastoma cells infected with an human simplex virus amplicon vector expressing HIV-1PR showed specific fluorescence activation, an effect that could be inhibited by the HIV-1PR inhibitor, indinavir. The transfer of the HIV-1PR marker gene could be detected in vivo after intratumoral delivery of the human simplex virus-amplicon vector. These results are the first proof of principle that viral proteases can directly be imaged in vivo. These findings may be directly applicable in using viral protease expression as a transgene marker in tumor therapy and may have implications in testing the efficacy of HIV-1PR inhibitors in vivo.


Patient Experience and Satisfaction with an e-Health Care Management Application for Inflammatory Bowel Diseases.
Rising healthcare expenditures have been partially attributed to suboptimal management of inflammatory bowel diseases (IBD). Electronic health interventions may help improve care management for IBD patients, but there is a need to better understand patient perspectives on these emerging technologies. The primary aim was to evaluate patient satisfaction and experience with the UCLA eIBD mobile application, an integrative care management platform with disease activity monitoring tools and educational modules. The secondary objective was to capture patient feedback on how to improve the mobile application. We surveyed IBD patients treated at the UCLA Center for Inflammatory Bowel Diseases. The patient experience survey assessed the patients' overall satisfaction with the application, perception of health outcomes after participation in the program, and feedback on educational modules as well as areas for application improvement. 50 patients were included. The responses indicated that the patients were greatly satisfied with the ease of patient-provider communication within the application and appointment scheduling features (68%). A majority of respondents (54%) also reported that program participation resulted in improved perception of disease control and quality of life. Lastly, a majority of participants (79%) would recommend this application to others. Mobile tools such as UCLA eIBD have promising implications for integration into patients' daily lives. This patient satisfaction study suggests the feasibility of using this mobile application by patients and providers. We further showed that UCLA eIBD and its holistic approach led to improved patient experience and satisfaction, which can provide useful recommendations for future electronic health solutions.


Three Levels of Autonomy and One Long-Term Solution for Native American Health Care.
Native Americans have twice the poverty rate of the general US population, suffer significant health inequity, and are chronically underrepresented, at only 0.08%, in the US physician workforce. The COVID-19 pandemic has illuminated key ethical, clinical, and economic complexities in health decision making among Native patients. This article discusses 3 levels of autonomy relevant to health decisions, including taking care of our own by increasing numbers of Native medical students.


Localization of astrovirus in experimentally infected turkeys as determined by in situ hybridization.
Twenty-one 3-day-old turkey poults from British United Turkeys of America were orally inoculated with a recently characterized astrovirus, TAstV-2, isolated from turkeys with poult enteritis and mortality syndrome. At 1, 2, 3, 4, 5, 7, and 9 days postinfection (dpi), three inoculated birds were euthanatized, and tissues (intestines, spleen, bursa, and thymus) were collected immediately into 10% neutral buffered formalin. Inoculated birds were diarrheic by 3 dpi, and frothy feces persisted throughout the experimental period. Histologically, there was only slight evidence of enteric damage, which was characterized by mild epithelial necrosis, lamina propria infiltrates, minimal villus atrophy, and mild crypt hyperplasia. In situ hybridization, using a negative sense digoxigenin-labeled riboprobe to the capsid gene of TAstV-2, revealed viral RNA in intestinal epithelial cells at the basal margins of the villi, in distal small intestine, and in cecum at 2 dpi, with subsequent extension to epithelium of the large intestine and proximal small intestine (3-5 dpi). Minimal virus remained by 9 dpi.


Optimal interruption time of dabigatran oral administration to ablation (O-A time) in patients with atrial fibrillation: Integrated analysis of 2 randomized controlled clinical trials.
RE-CIRCUIT (NCT02348723) and ABRIDGE-J (UMIN000013129) are recently published randomized clinical trials showing that anticoagulation therapy with dabigatran during the periprocedural period of catheter ablation (CA) for atrial fibrillation (AF) was associated with fewer complications. However, the dabigatran administration protocols were different (uninterrupted in RE-CIRCUIT and minimally interrupted in ABRIDGE-J). The aim of this present study was to clarify the optimal interruption time of dabigatran Oral administration to Ablation (O-A time). We conducted an integrated analysis of the 2 prospective trials. The endpoint of the study was the incidence of major bleeding events during and up to 8 weeks after CA across participants with different O-A times. The 535 patients in the dabigatran groups of the 2 trials were divided into 3 groups based on their O-A times (<8 h, n = 258; 8-24 h, n = 191; >24 h, n = 86). Major bleeding events occurred in 5 patients (1.9%) in the <8 h group, and 3 (3.5%) in the >24 h group; however, no major bleeding events occurred in the 8-24 h group (3 group-comparison, p = 0.026). No thromboembolic complication was observed in any of the 3 O-A time groups. In patients undergoing CA for AF using dabigatran as a periprocedural anticoagulant, an O-A time of 8-24 h was associated with no bleeding complications. These data suggest that an O-A time of 8-24 h may be an appropriate option, especially in a low thromboembolic-risk patient.


Beneficial impact of a clinical care pathway in patients with testicular cancer undergoing retroperitoneal lymph node dissection.
Since 1997, we have used a clinical collaborative care pathway for patients undergoing retroperitoneal lymph node dissection. We examined its impact on perioperative care and outcome. We examined the records of all patients with germ cell carcinoma who underwent retroperitoneal lymph node dissection from July 1990 to July 2001. Variables examined included clinical/pathological stage, hospital stay, postoperative care and the complication rate. A total of 118 patients underwent retroperitoneal lymph node dissection for germ cell carcinoma during this period, including 46 (39%) before pathway implementation in 1997 and 72 patients (61%) after pathway implementation. Of the 118 patients 40 (34%) underwent the procedure after chemotherapy. This rate remained fairly constant in the period before and after pathway initiation (31% and 36%, respectively). After pathway implementation fewer patients received a nasogastric tube (94% versus 5%, p <0.001) and had complications (26% versus 16%, p = 0.036). Mean hospital stay decreased after pathway implementation in all primary and post-chemotherapy retroperitoneal lymph node dissection cases (4.2 versus 6.4 days, p <0.005). Although patients who underwent the procedure after chemotherapy were more likely to have complications than those who underwent a primary procedure, the difference was not statistically significant (p = 0.09). Our collaborative clinical care pathway safely and efficiently outlines routine postoperative care and significantly decreased hospital stay.


[Coagulofibrinolytic response to surgical insult].
During recent years, evidence has accumulated demonstrating bidirectional cross-talk in the classic neuroendocrine response as well as immune-mediated inflammatory response, and newly described coagulofibrinolytic response. This review outlines the influences that these systems exert on each other and discusses the implications of the coagulofibrinolytic response to the multiple-organ dysfunction syndrome (MODS) and patient prognosis. The results of the physiological coagulofibrinolytic response to physical insults such as surgery and trauma are hemostasis and wound healing. We stress that this response is nonspecific and is similar in all types of insult without exception. An abnormal hemostatic response to surgical insult is called disseminated intravascular coagulation (DIC). DIC associated with the sustained systemic inflammatory response syndrome (SIRS) in postsurgical insult leads to the development of MODS, which is the main determinant of patient outcome. To prevent the progression of DIC, new drugs like activated protein C which can control both coagulation and inflammation now appear promising.


MicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1.
MicroRNA-34a (miR-34a), a transcriptional target of p53, is a well-known tumor suppressor gene. Here, we identified Fra-1 as a new target of miR-34a and demonstrated that miR-34a inhibits Fra-1 expression at both protein and messenger RNA levels. In addition, we found that p53 indirectly regulates Fra-1 expression via a miR-34a-dependant manner in colon cancer cells. Overexpression of miR-34a strongly inhibited colon cancer cell migration and invasion, which can be partially rescued by forced expression of the Fra-1 transcript lacking the 3'-untranslated region. The expression of matrix metalloproteinase (MMP)-1 and MMP-9, two enzymes involved in cell migration and invasion, was decreased in miR-34a-transfected cells, and this can be rescued by Fra-1 overexpression. Moreover, we found that miR-34a was downregulated in 25 of 40 (62.5%) colon cancer tissues, as compared with the adjacent normal colon tissues and that the expression of miR-34a was correlated with the DNA-binding activity of p53. Unexpectedly, the DNA-binding activity of p53 was not inversely correlated with Fra-1 expression, and a significant statistical inverse correlation between miR-34a and Fra-1 expression was only observed in 14 of 40 (35%) colon cancer tissues. Taken together, our in vitro data suggest that p53 regulates Fra-1 expression, and eventually cell migration/invasion, via a miR-34a-dependent manner. However, in vivo data indicate that the p53-miR-34a pathway is not the major regulator of Fra-1 expression in human colon cancer tissues.


Spin-adapted open-shell random phase approximation and time-dependent density functional theory. I. Theory.
The spin-adaptation of single-reference quantum chemical methods for excited states of open-shell systems has been nontrivial. The primary reason is that the configuration space, generated by a truncated rank of excitations from only one component of a reference multiplet, is spin-incomplete. Those "missing" configurations are of higher ranks and can, in principle, be recaptured by a particular class of excitation operators. However, the resulting formalisms are then quite involved and there are situations [e.g., time-dependent density functional theory (TD-DFT) under the adiabatic approximation] that prevent one from doing so. To solve this issue, we propose here a tensor-coupling scheme that invokes all the components of a reference multiplet (i.e., a tensor reference) rather than increases the excitation ranks. A minimal spin-adapted n-tuply excited configuration space can readily be constructed by tensor products between the n-tuple tensor excitation operators and the chosen tensor reference. Further combined with the tensor equation-of-motion formalism, very compact expressions for excitation energies can be obtained. As a first application of this general idea, a spin-adapted open-shell random phase approximation is first developed. The so-called "translation rule" is then adopted to formulate a spin-adapted, restricted open-shell Kohn-Sham (ROKS)-based TD-DFT (ROKS-TD-DFT). Here, a particular symmetry structure has to be imposed on the exchange-correlation kernel. While the standard ROKS-TD-DFT can access only excited states due to singlet-coupled single excitations, i.e., only some of the singly excited states of the same spin (S(i)) as the reference, the new scheme can capture all the excited states of spin S(i)-1, S(i), or S(i)+1 due to both singlet- and triplet-coupled single excitations. The actual implementation and computation are very much like the (spin-contaminated) unrestricted Kohn-Sham-based TD-DFT. It is also shown that spin-contaminated spin-flip configuration interaction approaches can easily be spin-adapted via the tensor-coupling scheme.


Bilateral persistence of type 1 proatlantal arteries: report of a case and review of the literature.
Persistent proatlantal artery type 1 is one of the four anastomotic vessels between the carotid and vertebrobasilar arterial systems. Persistence of this embryonic anastomosis is extremely rare. We present such a case with bilateral persistent proatlantal arteries that arose from internal carotid arteries, entered the skull via the foramen magnum and united with the horizontal portions of vertebral arteries. We also mention its embryology, potential clinical implications, and differentiating features between two types of proatlantal arteries.


Cecal colonization of chicks by porcine strains of Campylobacter coli.
Ten genotypically distinct strains of Campylobacter coli were isolated from a swine production facility. These porcine isolates were then orally inoculated into day-of-hatch leghorn chicks and were excellent colonizers of the chick cecum. Campylobacter coli recovered from inoculated chickens were genotypically identical to the challenge strain. The absence of host specificity suggests a possible movement of strains among swine, field animals and birds, and poultry houses.


Physical examination tests for the diagnosis of posterior cruciate ligament rupture: a systematic review.
Systematic literature review. To summarize and evaluate research on the accuracy of physical examination tests for diagnosis of posterior cruciate ligament (PCL) tear. Rupture of the PCL is a severe knee injury that can lead to delayed rehabilitation, instability, or chronic knee pathologies. To our knowledge, there is currently no systematic review of studies on the diagnostic accuracy of clinical examination tests to evaluate the integrity of the PCL. A comprehensive systematic literature search was conducted in MEDLINE from 1946, Embase from 1974, and the Allied and Complementary Medicine Database from 1985 until April 30, 2012. Studies were considered eligible if they compared the results of physical examination tests performed in the context of a PCL physical examination to those of a reference standard (arthroscopy, arthrotomy, magnetic resonance imaging). Methodological quality assessment was performed by 2 independent reviewers using the revised version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The search strategy revealed 1307 articles, of which 11 met the inclusion criteria for this review. In these studies, 11 different physical examination tests were identified. Due to differences in study types, different patient populations, and methodological quality, meta-analysis was not indicated. Presently, most physical examination tests have not been evaluated sufficiently enough to be confident in their ability to either confirm or rule out a PCL tear. The diagnostic accuracy of physical examination tests to assess the integrity of the PCL is largely unknown. There is a strong need for further research in this area. Level of Evidence Diagnosis, level 3a.


Attitudes about cannabis mediate the relationship between cannabis knowledge and use in active adult athletes.
Little is known about how cannabis knowledge and attitudes impact cannabis use behavior. To test the knowledge-attitudes-behavior paradigm in active adult athletes. The Athlete Pain, Exercise, and Cannabis Experience (PEACE) Survey, a cross-sectional survey study, used social media and email blasts to recruit participants and SurveyGizmo to collect data. Self-defined active adult athletes (n = 1161). Knowledge about cannabis was evaluated with four questions. Attitudes toward cannabis was evaluated with 11 questions. The attitudes questions were used in a TwoStep Cluster analysis in SPSS to assign group membership by attitudes. Chi-square was used to determine if there were differences in cluster membership by demographic factors and if knowledge about cannabis differed by cluster membership. Regression analysis was performed to determine if cannabis attitudes mediated the relationship between cannabis knowledge and cannabis use. A three-cluster solution was the best fit to the data. The clusters were named Conservative (n = 374, 32.2%), Unsure (n = 533, 45.9%), and Liberal (n = 254, 21.9). There was a significant difference among the clusters for all 11 attitudes items (all p < 0.001). Attitude cluster membership was significantly different by age (p < 0.001), primary sport (p < 0.05), and knowledge about cannabis (p < 0.001). Athletes in the liberal cluster answered the knowledge questions correctly most often. Attitudes mediated the relationship between cannabis knowledge and cannabis use [Never (32.4%), Past (41.6%), Current (26.0%)] with athletes in the liberal cluster showing more knowledge and greater likelihood to be a current cannabis user (p < 0.001). Among current cannabis users there were differential patterns of cannabis use depending on their attitudes and knowledge; liberal athletes tended to co-use THC and CBD and used cannabis longer. (p < 0.001). Cannabis education needs to consider attitudes about cannabis, especially among those who might benefit from medical cannabis.


Hormone-refractory prostate cancer: a primer for the primary care physician.
To provide a current and evidence-based clinical review of practical value to primary care physicians encountering men with hormone-refractory prostate cancer (HRPC) in their practice. Evidence-based narrative review by two expert clinicians incorporating results of systematic reviews and randomized trials whenever available. HRPC represents the final common pathway to death from prostate adenocarcinoma, the single most prevalent cancer in Canadian men. However, primary care physicians will not encounter these patients with a frequency adequate to develop confidence in their care. HRPC is defined by progressive disease despite castration, and biologically is a characterized by androgen hypersensitivity. It is important to understand that HRPC is a disease spectrum ranging from asymptomatic patients with only a rising prostatic-specific antigen (PSA) level and a prognosis measured in years to extremely symptomatic patients with widespread metastases requiring end-of-life care. Numerous effective management options are now available for HRPC and are selected based on the phase of the disease natural history, and patient comorbidities and preferences. Men with HRPC have therapeutic options that can improve and maintain both the quality and quantity of their lives. A co-management approach including a medical oncologist and the patient's urologist and primary care physician is preferred.


An enhanced mutant of red fluorescent protein DsRed for double labeling and developmental timer of neural fiber bundle formation.
We developed a new variant of coral-derived red fluorescent protein, DsRed S197Y, which is brighter and essentially free from secondary fluorescence peak. This makes it an ideal reporter for double labeling with green fluorescent protein (GFP). Though purified protein shows only 20% stronger fluorescence emission, culture cells that express DsRed S197Y exhibit a 3-3.5 times higher level of fluorescence than the cells that express wild-type DsRed. The much slower fluorescence maturation of DsRed than that of GFP is a beneficial feature for a fluorescent developmental timer application. When GFP and DsRed S197Y are expressed simultaneously, emissions start at different latency. This provides information about the time after the onset of expression. It reflects the order of cell differentiation if the expression is activated upon differentiation of certain types of cells. We applied this system to the developing brain of Drosophila and visualized, for the first time, the formation order of neural fibers within a large bundle. Our results showed that newly extending fibers of the mushroom body neurons mainly run into the core rather than to the periphery of the existing bundle. DsRed-based timer thus presents an indispensable tool for developmental biology and genetics of model organisms.


Microbial volatile organic compounds in intra-kingdom and inter-kingdom interactions.
Microorganisms produce and excrete a versatile array of metabolites with different physico-chemical properties and biological activities. However, the ability of microorganisms to release volatile compounds has only attracted research attention in the past decade. Recent research has revealed that microbial volatiles are chemically very diverse and have important roles in distant interactions and communication. Microbial volatiles can diffuse fast in both gas and water phases, and thus can mediate swift chemical interactions. As well as constitutively emitted volatiles, microorganisms can emit induced volatiles that are triggered by biological interactions or environmental cues. In this Review, we highlight recent discoveries concerning microbial volatile compounds and their roles in intra-kingdom microbial interactions and inter-kingdom interactions with plants and insects. Furthermore, we indicate the potential biotechnological applications of microbial volatiles and discuss challenges and perspectives in this emerging research field.


[A case of disseminated Penicillium marneffei infection in a liver transplant recipient].
Penicillium marneffei is the only dimorphic fungus among Penicillium spp. that can cause a fatal infection in immunocompromised patients. P. marneffei is endemic in Southeast Asia and eastern China. P. marneffei infection is an AIDS-defining illness and the third most common opportunistic infection in the endemic regions. Here, the authors report a case of disseminated P. marneffei infection in a patient who underwent liver transplantation in China. During the hospital stay, the mold form of the fungus that produced a red wine-colored pigment on the agar plate was isolated from the patient's urine, transtracheal aspirate, and blood. The fungus was identified as P. marneffei by direct sequencing of the D1-D2 and ITS regions. Thermal dimorphism was also confirmed by subculturing the colony at 37 degrees C. To the best of our knowledge, this is the first Korean case of disseminated P. marneffei infection in a liver transplant recipient.


The Vogt-Koyanagi-Harada syndrome: association with autoimmune polyglandular syndrome type 1.
We describe a young woman with primary adrenal insufficiency, hypoparathyroidism (autoimmune polyglandular syndrome type 1), Graves disease, vitiligo, and alopecia universalis. Five years after the diagnosis, she presented with recurrent ophthalmological and neurological disorders as features of Vogt-Koyanagi-Harada syndrome. A marked therapeutic response was noted on systemic high-dose corticosteroid treatment. To the best of our knowledge, such a spectre of autoimmune diseases has not been reported previously.


[A view of general practice].
What happens during our consultation and what are the determining factors or specific practice patterns in general practice? Six Swiss general practitioners discuss this questions based on a random sample of 300 descriptions of unbiased consultations. Further information obtained from the patient after the consultation by questionnaire and a recorded semi-structured interview was analysed. In the following article the methods are presented.


Estimation of relative bioavailability of lead in soil and soil-like materials using young Swine.
In this article we summarize the results of a series of studies that measured the relative bioavailability (RBA) of lead in a variety of soil and soil-like test materials. Reference material (Pb acetate) or Pb-contaminated soils were administered orally to juvenile swine twice a day for 15 days. Blood samples were collected from each animal at multiple times during the course of the study, and samples of liver, kidney, and bone were collected at sacrifice. All samples were analyzed for Pb. We estimated the RBA of a test material by fitting mathematical models to the dose-response curves for each measurement end point and finding the ratio of doses that gave equal responses. The final RBA for a test material is the simple average of the four end point-specific RBA values. Results from 19 different test materials reveal a wide range of RBA values across different exposure materials, ranging from 6 to 105%. This variability in RBA between different samples highlights the importance of reliable RBA data to help improve risk assessments for Pb in soil. Although the RBA value for a sample depends on the relative amounts of the different chemical and physical forms of Pb present, data are not yet adequate to allow reliable quantitative predictions of RBA from chemical speciation data alone.


Biochemical bone turnover markers: significance in patients with osteoporosis.
Osteoporosis is a systemic disease, which is characterized by reduced bone mass and microarchitectural deterioration of the bone tissue, resulting in an increased risk of fracture. Since osteoporosis is today a disease with high incidence rate, the aim of this study was to determine a correlation between bone mass density (BMD) and concentration of biochemical bone turnover markers--deoxypyridinoline (DPD) as a marker of bone resorption, and osteocalcin (OC) as a marker of bone formation. The study included 70 women between 33 and 76 years of age. In all women BMD was measured by Dual X-ray Absorptiometry (DXA) as a T-score. T-score was defined as the number of standard deviations of the bone mass density from the maximum bone mass density in young adults. According to T-score, patients were divided into three groups: patients with osteoporosis, patients with osteopenia and control group consisting of patients with normal T-score. DPD in urine and OC in serum were measured by a routine procedure. a negative correlation between BMD and concentration of bone turnover marker was discovered. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < 0.05 being considered significant. Although a negative correlation was discovered, we concluded that both procedures have a significant role in diagnosis and follow-up of patients with osteoporosis.


[Double primary carcinoma of the uterine corpus and ovary].
This article presents 19 patients with double primary carcinoma of the uterine corpus and ovary diagnosed and treated at Queen Mary Hospital, University of Hong Kong in last ten years. 14 patients had typical endometrial adenocarcinoma and endometrioid carcinoma of the ovary (group A), 5 had non-endometrioid carcinoma in the uterine corpus and/or ovary (group B). There is no significant difference in survival rate in group A and B (78.6% and 80%, respectively, mean follow-up 42 months), but the total survival rate in our series is 78%, which is equal to stage I ovarian cancer. The tumor grade and positive abdominal washing were proven to be statistically significant indicators of the poor prognosis (P < 0.05). The result reveals that the prognosis of double primary carcinoma of the uterine corpus and ovary is better and it is necessary to distinguish double primary carcinoma of the uterine corpus and ovary from stage II ovarian cancer and stage III endometrial carcinoma.


Pastoral care, spirituality, and religion in palliative care journals.
With the growth and development of palliative care, interest in pastoral care, spirituality, and religion also seems to be growing. The aim of this article is to review the topic of pastoral care, spirituality, and religion appearing in the journals of palliative care, between January 1984 and January 2002.


Economic and medical significance of sleep-related breathing disorders.
The improvement in outpatient sleep medical care in the Federal Republic of Germany over the last 10 years has been associated with an increase in the costs for diagnosis and therapy of sleep-related breathing disorders. The medical importance of these sleep-related problems consists in their high prevalence, especially in middle-aged men and risk groups, e.g. in patients with cardiovascular conditions. The effect on the performability of patients, which is manifested in the excessive daytime sleepiness at the workplace and in everyday life, are likewise significant. For social insurance agencies, immense costs arise from the sequelae and concomitant illnesses of untreated sleep-related breathing disorders. A comparison of the costs and the benefits of diagnosis, therapy and follow-up of patients with sleep-related breathing disorders over a period of 10 years shows that a mean annual monetary net benefit of DEM 2.3 billion in the Federal Republic of Germany can be assumed. The health economics analysis shows that an appropriate provision of sleep-medical care for the population is of great benefit for the health of the nation and thus for the entire economy.


[Sentinel node biopsy in head and neck cancer. Is there an indication for use of this new surgical technique in the treatment of head and neck cancer?].
Management of the clinically N0 neck in head and neck squamous cell carcinoma remains controversial. Since lymph node metastasis reduces the five-year survival by up till 50%, the need for an accurate diagnostic procedure is necessary. The sentinel node, being the initial lymph node to which the primary tumour drains, is believed to be invaded by early metastasis. Identification of the sentinel node by means of a dye or isotope or a combination, and surgical removal followed by histological examination verifies the involvement of the regional glands. At present few and limited materials on head and neck cancers exist, primarily on oral and oropharyngeal cancers. The techniques used are various and not without difficulties. To evaluate the feasibility of the sentinel node biopsy in head and neck cancer, it is proposed to perform a nationwide cohort study that comprises all minor oral and oropharyngeal cancers (T1, T2, N0).


Flow Behavior of Chain and Star Polymers and Their Mixtures.
Star-shaped polymers show a continuous change of properties from flexible linear chains to soft colloids, as the number of arms is increased. To investigate the effect of macromolecular architecture on the flow properties, we employ computer simulations of single chain and star polymers as well as of their mixtures under Poiseuille flow. Hydrodynamic interactions are incorporated through the multi-particle collision dynamics (MPCD) technique, while a bead-spring model is used to describe the polymers. For the ultradilute systems at rest, the polymers are distributed uniformly in the slit channel, with a weak dependence on their number of arms. Once flow is applied, however, we find that the stars migrate much more strongly towards the channel center as the number of arms is increased. In the star-chain mixtures, we find a flow-induced separation between stars and chains, with the stars located in the channel center and the chains closer to the walls. In order to identify the origin of this flow-induced partitioning, we conduct additional simulations without hydrodynamic interactions, and find that the observed cross-stream migration originates from a combination of wall-induced hydrodynamic lift forces and viscoelastic effects. The results from our study give valuable insights for designing microfluidic devices for separating polymers based on their architecture.


Medical management of AIDS patients. Psychiatric disturbances.
Despite the complexity and magnitude of the psychiatric disturbances associated with HIV illness, a good deal is understood about their clinical presentation. Techniques for psychopharmacologic and psychotherapeutic management have been well established and are readily available. The expertise developed for management of psychiatric disturbances in other medical illnesses applies quite well to HIV-related conditions. Although the HIV epidemic challenges us with new difficulties, our experience with other illnesses provides us with a basis to respond.


Apixaban: first global approval.
Apixaban (Eliquis™), an oral direct factor Xa inhibitor, is being developed by Bristol-Myers Squibb and Pfizer as a therapy for the prevention and/or treatment of thrombotic disorders. Apixaban has been approved in the EU for the prevention of venous thromboembolism (VTE) after hip or knee replacement. A rolling submission for approval of apixaban for the prevention of stroke in patients with atrial fibrillation has also been initiated in the US. Worldwide phase III development of apixaban is underway for the prevention and treatment of VTE, and prevention of stroke in patients with atrial fibrillation. Development for acute coronary syndromes has been stopped following the discontinuation of the phase III APPRAISE-II trial. This article summarizes the milestones in the development of apixaban leading to this first approval for the prevention of VTE after hip or knee replacement.


Possible link between strain ST-T change on the electrocardiogram and subendocardial dysfunction assessed by two-dimensional speckle-tracking echocardiography.
Strain ST-T changes on surface electrocardiogram (ECG) may reflect subendocardial dysfunction. We hypothesized that strain ST-T changes are associated with (i) decrease in longitudinal strain, (ii) decrease in early systolic clockwise twist and early diastolic untwisting, and (iii) augmentation of peak twist due to subendocardial dysfunction. Three levels of left ventricular (LV) short-axis views and three LV apical views were acquired in 46 hypertensive patients with LV hypertrophy and 23 age-matched control subjects using 2D echocardiography. Patients were divided into two groups according to the presence (n = 18) or absence (n = 28) of strain ST-T change on 12-lead ECG. Using 2D strain software, longitudinal, radial, and circumferential strain were measured. Early systolic clockwise twist, end-systolic twist, and untwisting at early diastole were measured from time-domain LV twist curves. No significant intergroup differences in LV ejection fraction were noted. Longitudinal strain was significantly reduced in hypertensive patients with strain ST-T changes compared with those without these changes or control subjects. Although LV twist at end-systole was similar between patients with and without strain ST-T changes, early systolic clockwise twist and untwisting was significantly reduced in strain ST-T change group compared with the no ST-T change group. Multivariate analysis revealed that not LV mass index but strain ST-T change was an independent predictor of global longitudinal strain. The reduction in longitudinal strain, early systolic clockwise twist, and untwisting in hypertensive patients with strain ST-T changes suggests possible link between this ECG abnormality and subendocardial dysfunction, which can be assessed by 2D speckle tracking echocardiography.


Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury.
Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 cells and primary murine RPE cells, obacunone potently inhibited UVR-induced reactive oxygen species accumulation, mitochondrial depolarization, lipid peroxidation and single strand DNA accumulation. UVR-induced RPE cell death and apoptosis were largely alleviated by obacunone. Obacunone activated Nrf2 signaling cascade in RPE cells, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation. It promoted transcription and expression of antioxidant responsive element-dependent genes. Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout almost reversed obacunone-induced RPE cytoprotection against UVR. Forced activation of Nrf2 cascade, by Keap1 knockout, similarly protected RPE cells from UVR. Importantly, obacunone failed to offer further RPE cytoprotection against UVR in Keap1-knockout cells. In vivo, intravitreal injection of obacunone largely inhibited light-induced retinal damage. Collectively, obacunone protects RPE cells from UVR-induced oxidative injury through activation of Nrf2 signaling cascade.