Impediments to comprehensive treatment models for substance-dependent women: treatment and research questions.
A number of factors need to be addressed in order to provide efficacious treatment for drug-dependent women, particularly those who are opioid dependent. If left unaddressed, these factors may reduce the effectiveness of treatment. In addition, evaluation research frequently overlooks the impact of these factors in methodological approaches examining treatment outcomes. This article discusses several of the problems brought to treatment settings by women, considers how these problems impact on current treatment models, examines alternative research approaches to evaluating treatment for women, and focuses on three critical factors regularly overlooked in treatment provision and in research related to women: (1) broader issues of dependency in women; (2) the impact of chaotic early interpersonal relationships on developmental levels; and (3) diagnostic criteria and treatment goals appropriate for women. It attempts to provide an understanding of the impact of these three elements on treatment and on research methodologies in order to provide and evaluate comprehensive and effective treatment for drug-dependent women.


[A fistule of the anus in the Crohn's disease].
A fistule is defined as a canal or a cavity, created by necrotic degradation of the tissue, which may, (but not necessarily has to) communicate directly with the digestive tract via an internal orifice. In case of the Crohn's disease, the abscesi and fistules result from the same pathological process and are caused by penetration of the inflammatory process through the wall of the digestive tube and to its outer side. The authors, having initially described the types and the pathogenesis of the anal fistules in the Crohn's disease, present a brief examination algorithm including examination of the whole digestive tract, based on the pan-entero-colitic character of the disorder. Sound diagnostics and establishment of the disease activity is very important, beacuse the treatment strategy differs from that of other perianal inflammatory affections. Furthermore, options for both the surgical and conservative treatment are listed in this work, including experience with use of the advancement flap. According to some authors, the success-rate of this treatment reaches up to 80%.


Identification of the Main Phenolic Markers in Turkish Pine Honeys and Their Biological Functions.
The purpose of this research was to identify the biological activity of Turkish pine honeys and the most abundant phenolic compound(s) to guide future studies to be done about this type of honey. Moreover, this will provide the chance to introduce Turkish pine honeys by elucidating a distinct parameter compared to other forms of honey reported in the literature. To this end, microscopic examination based on the number of honeydew elements (NHE) and the number of total pollen (NTP) grains was performed on 17 samples of pine honeys from the Aegean region of Turkey. Then 18 commonly-occurring phenolic standards were used in high-performance liquid chromatography (HPLC) to examine the samples. Each sample was tested for individual phenolic compounds, as well as total phenolic content (TPC), total flavonoid content (TFC), and ferric reducing antioxidant power (FRAP). As shown by the numerical data, the values for NHE and NTP were 6600-144000 and 3000-75000, respectively. In addition, the general means of TPC, TFC, and FRAP values for the samples were 53.000 mg GAE/100 g fresh sample, 1.944 mg QE/100 g fresh sample, and 3.455 μmol FeSO4 /g fresh sample, respectively. Protocatechuic acid predominated with a range of 197.841-780.227 μg phenolic /100 g sample in all samples. According to the general mean for values detected in the samples, p-hydroxybenzoic acid and benzoic acid were the second and third markers for Turkish pine honey samples. It is believed that these results will help efforts to set standards for pine honey on a national and global scale.


Anti-cancer activity of sustained release capsaicin formulations.
Capsaicin (trans-8-methyl-N-vanillyl-6-noneamide) is a hydrophobic, lipophilic vanilloid phytochemical abundantly found in chili peppers and pepper extracts. Several convergent studies show that capsaicin displays robust cancer activity, suppressing the growth, angiogenesis and metastasis of several human cancers. Despite its potent cancer-suppressing activity, the clinical applications of capsaicin as a viable anti-cancer drug have remained problematic due to its poor bioavailability and aqueous solubility properties. In addition, the administration of capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, nausea and diarrhea and vomiting. All these hurdles may be circumvented by encapsulation of capsaicin in sustained release drug delivery systems. Most of the capsaicin-based the sustained release drugs have been tested for their pain-relieving activity. Only a few of these formulations have been investigated as anti-cancer agents. The present review describes the physicochemical properties, bioavailability, and anti-cancer activity of capsaicin-sustained release agents. The asset of such continuous release capsaicin formulations is that they display better solubility, stability, bioavailability, and growth-suppressive activity than the free drug. The encapsulation of capsaicin in sustained release carriers minimizes the adverse side effects of capsaicin. In summary, these capsaicin-based sustained release drug delivery systems have the potential to function as novel chemotherapies, unique diagnostic imaging probes and innovative chemosensitization agents in human cancers.


Local Observability Analysis of Star Sensor Installation Errors in a SINS/CNS Integration System for Near-Earth Flight Vehicles.
Strapdown inertial navigation system/celestial navigation system (SINS/CNS) integrated navigation is a fully autonomous and high precision method, which has been widely used to improve the hitting accuracy and quick reaction capability of near-Earth flight vehicles. The installation errors between SINS and star sensors have been one of the main factors that restrict the actual accuracy of SINS/CNS. In this paper, an integration algorithm based on the star vector observations is derived considering the star sensor installation error. Then, the star sensor installation error is accurately estimated based on Kalman Filtering (KF). Meanwhile, a local observability analysis is performed on the rank of observability matrix obtained via linearization observation equation, and the observable conditions are presented and validated. The number of star vectors should be greater than or equal to 2, and the times of posture adjustment also should be greater than or equal to 2. Simulations indicate that the star sensor installation error could be readily observable based on the maneuvering condition; moreover, the attitude errors of SINS are less than 7 arc-seconds. This analysis method and conclusion are useful in the ballistic trajectory design of near-Earth flight vehicles.


The influence of bacterial vaginosis on gestational week of the completion of delivery and biochemical markers of inflammation in the serum.
Preterm delivery is one of the most common complications in pregnancy, and it is the major cause (75-80%) of all neonatal deaths. Bacterial vaginosis predisposes to an increased risk of preterm delivery, premature rupture of membrane and miscarriage. In this syndrome normal vaginal lactobacilli, which produce protective H2O2, are reduced and replaced with anaerobic, gram-negative bacteria and others. The aim of this study was to evaluate the influence of bacterial vaginosis on the week of delivery and biochemical markers of inflammation in the serum. A total of 186 pregnant women were included into this study, between the week 16 and 19 of pregnancy. In the study group there were 76 pregnant women with diagnosed bacterial vaginosis by the criteria based on vaginal Gram-stain Nugent score and Amsel criteria. In the control group there were 110 healthy women with normal vaginal flora. Ultrasound examination was performed in both groups. Vaginal fluid and blood samples were taken to determine biochemical markers with colorimetric methods. The week of delivery was statistically significantly shorter in the study group and the levels of biochemical markers of inflammation (C-reactive protein and fibrinogen in the serum) were statistically significantly higher in women with bacterial vaginosis comparing to the control group. Also the levels of uric acid and white blood cells in the serum were higher in the study group compared to the control one. Our study indicates that the pregnancy complicated with bacterial vaginosis ends much earlier than the pregnancy without it. Also, higher levels of biochemical markers of inflammation in the serum in the study group, similarly to results of other studies, suggest that pathophysiological processes responsible for preterm delivery can begin very early in pregnancy.


Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models.
Brain microvascular endothelial cells (BEC) constitute the blood-brain barrier (BBB) which forms a dynamic interface between the blood and the central nervous system (CNS). This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local surroundings of BEC within the neurovascular unit are presented and discussed.


Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.
Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.


Psychophysiological dysfunctions in the developmental course of schizophrenic disorders.
Psychophysiological anomalies in symptomatic schizophrenic patients, remitted schizophrenic patients, and individuals at heightened risk for a schizophrenic disorder are reviewed with an emphasis on electrodermal anomalies. Two electrodermal anomalies are identified in different subgroups of symptomatic patients: (1) an abnormally high sympathetic arousal and (2) an abnormal absence of skin conductance orienting responses to innocuous environmental stimuli. The same two electrodermal anomalies also have been observed in remitted schizophrenic patients. Among high-risk individuals, the offspring of schizophrenic patients display abnormally high electrodermal responsiveness to aversive stimulation, whereas a substantial proportion of college students who score high on physical anhedonia (a putative risk factor for schizophrenia) exhibit skin conductance nonresponsiveness. Thus, heightened sensitivity to aversive stimulation appears to be associated with a genetic vulnerability to schizophrenia, while tonic hyperarousal , which occurs in subgroups of symptomatic and remitted schizophrenic patients, may reflect a later developmental consequence of the underlying vulnerability. Skin conductance nonresponsivity may represent a different developmental consequence associated with the same underlying vulnerability or it may represent a different type of vulnerability. Other psychophysiological anomalies also are promising indicators of the vulnerability to schizophrenia (e.g., deviant smooth pursuit eye movements, attenuated P300 component of the event-related brain potential, reduced electroencephalic (EEG) alpha activity, and heightened EEG delta activity).


t(11;18)(q21;q21)-positive advanced-stage MALT lymphoma associated with monoclonal gammopathy: resistance to rituximab or rituximab-containing chemotherapy.
Here we describe two cases of mucosa-associated lymphoid tissue (MALT) lymphoma with monoclonal immunoglobulins (Igs). The first case was a 77-year-old man with primary lymphoma of the lung. Immunoelectrophoresis detected IgM-kappa in serum and kappa light chain excretion into urine. Three months after treatment with single-agent rituximab, a large amount of pleural fluid was found to have accumulated. The fluid contained CD5(-), CD10(-), CD19(+), CD38(+) and CD138(-/+) lymphoma cells with lymphoplasmacytoid appearance. Although a small fraction of the cells were CD20(+), the majority of the lymphoma cells were negative and expressed surface-membrane IgM-kappa at low levels. The cells possessed a karyotype of 46, XY, t(11;18)(q21;q21). The second case was a 55-year-old man who underwent total gastrectomy due to gastric perforation. Surgical specimens demonstrated the histopathological features of MALT lymphoma associated with plasma cell differentiation. The lymphoma cells had a 46, XY, t(11;18)(q21;q21) karyotype. Monoclonal Igs detected were serum IgA (M)-kappa and urinary kappa light chain. The patient was subsequently treated with six cycles of R-CVP (rituximab, cyclophosphamide, vincristine and prednisolone) ; however, serum monoclonal Ig levels were not affected. The lymphoma cells in both cases may have contained two populations, a rituximab-sensitive CD20(+) population and a rituximab-resistant population that had differentiated into the Ig-secreting plasma cell stage.


Immuno-phenotypes and prognosis of acute leukemia in elderly patients.
This study is to provide reliable experimental treatment options for the diagnosis of acute leukemia, prognosis analysis and the detection of minimal residual disease. We observed the bone marrow CD123/CD117/CD34/HLA-DR antigen expression in 64 elderly patients with acute leukemia (AL). The immune phenotypes of 64 elderly AL patients were detected and the correlations of CD123, HLA-DR, CD34 and CD117 expression with the leukemia cell morphology were analyzed. The cell genetics, molecular biology and the prognostic stratification were compared based on flow cytometry. In CDl23-positive patients, the complete remission (CR) rate was 21.5%. In CDl23-negative patients, the CR rate was 59.1%. The CR rate was 21.9% in HLA-DR-positive patients and 43.8% in HLA-DR-negative patients. The CR rate was 24.0% in CD34-positive patients and 41.1% in CD34-negative patients. The CR rate was 29.0% in CD117-positive patients and 42.3% in CD117-negative patients. The CR rate was 34.4% in CD38-positive patients and 0.00% in CD38-negative patients. These results suggest that CD123(+), CD117(+), CD34(+), and HLA-DR(+) are the factors related with the poor prognosis of elderly patients with acute leukemia.


Autoimmunity after allogeneic bone marrow transplantation. A study of 53 long-term-surviving patients.
Various autoantibodies were screened in 53 long-term survivors after allogeneic bone marrow transplantation. Among them, 40 displayed chronic graft-versus-host disease, with clinical features reminiscent of collagen diseases, especially scleroderma, Sjögren's syndrome, and autoimmune hepatitis. Antinuclear, anti-smooth muscle, antimitochondria, anti-liver kidney microsome, and antiepidermal antibodies were found at a frequency of 62.2%, 49.0%, 11.3%, 5.6%, and 11.3%, respectively. The screening for native anti-DNA, anti-extractable nuclear antigen, anticentromere, and anti-salivary gland duct antibodies was negative. The presence or absence of acute GVHD made no difference in the frequency of autoantibodies. No correlation between cutaneous hepatic involvement, sicca syndrome, scleroderma status, and autoantibodies could be established. Despite clinical features mimicking collagen vascular diseases, the biological autoimmune profile of GVHD was different. The precise role of autoimmunity in chronic GVHD remains to be defined.


A randomized, double-blind, crossover comparison of iloprost with dextran in patients with peripheral arterial occlusive disease.
Iloprost, a stable carbaprostacyclin analog, was infused (up to 2-4 ng/kg/min) for 12 h daily on 5 consecutive days into the forearm vein of 13 patients with peripheral arterial occlusive disease (PAOD) of legs (stages IIb-III). All vasodilatory and antiplatelet drugs were stopped three weeks earlier. For comparison, dextran was infused in a randomized, crossover, double-blind manner with an average interval of 3 months. Iloprost increased significantly ankle systolic pressure and ankle/arm pressure ratio for the follow-up period of one month. Foot skin temperature increased insignificantly. Pain-free walking distance was prolonged up to 1.51 times by iloprost and 1.14 times by dextran (p less than 0.05). Venous occlusion plethysmography showed no improvement in the blood flow of legs. Eight patients experienced a subjective improvement in their clinical status with iloprost. Ten patients suffered from mild to severe headache, nausea, transient rest pain of legs, and hypotension. One patient with gastric ulcer history was withdrawn because of mild hematemesis, not definitely drug-related. No significant changes occurred in standard laboratory safety control or in hemostasis. The results suggest that a 5-day iloprost infusion exerts a mild favourable effect on patients with PAOD.


Domino liver transplantation for familial amyloid polyneuropathy.
Familial amyloid polyneuropathy is an autosomal dominant disorder in which the liver produces a variant prealbumin that is deposited along nerves, leading to a progressive and fatal polyneuropathy that begins in the third decade of life. Liver transplantation has been the only successful treatment to date. Apart from the production of the variant protein, there are no other abnormalities in these amyloid livers. We describe two cases in which, at the time of transplantation, the amyloid livers were subsequently used for transplantation in another patient, and we discuss the implications.


Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain.
This study presents data from a prospective study of adult patients with community-acquired pneumonia (CAP). Of 493 patients included in the study, 223 (45.2%) were aged > or = 65 years, and 265 (53.7%) had one or more underlying diseases, mostly chronic obstructive pulmonary disease, diabetes mellitus or dementia. In total, 281 microorganisms were identified in 250 (50.7%) patients, with two or more pathogens detected in 28 (5.7%) cases. Microbial diagnosis varied according to age, severity, co-morbidity and site-of-care, but there was much overlap among groups. Streptococcus pneumoniae was the single most prevalent organism in outpatients, patients admitted to hospital, and patients who died, either as a single pathogen or combined with another organism. Infections caused by 'atypical' pathogens were seen across all groups, including the elderly and patients with co-morbidities. Mortality varied according to the pneumonia severity index (PSI) of the pneumonia patient outcomes research team. Shock (OR 34.48), an age of > 65 years (OR 25) and altered mental status (OR 9.92) were factors associated independently with 30-day mortality. Key findings from this study were the advanced age of the population with CAP, and the high prevalence of dementia as an underlying disease. The study also revealed that microbiological diagnosis of CAP remains problematic. Although certain epidemiological features may help to predict the microbial aetiology, the overlap among groups reduces the usefulness of this information in guiding therapeutic decisions. Greater effort should be made to improve identification methods for microbial pathogens causing CAP.


Study of the H+O2 reaction by means of quantum mechanical and statistical approaches: the dynamics on two different potential energy surfaces.
The possible existence of a complex-forming pathway for the H+O(2) reaction has been investigated by means of both quantum mechanical and statistical techniques. Reaction probabilities, integral cross sections, and differential cross sections have been obtained with a statistical quantum method and the mean potential phase space theory. The statistical predictions are compared to exact results calculated by means of time dependent wave packet methods and a previously reported time independent exact quantum mechanical approach using the double many-body expansion (DMBE IV) potential energy surface (PES) [Pastrana et al., J. Phys. Chem. 94, 8073 (1990)] and the recently developed surface (denoted XXZLG) by Xu et al. [J. Chem. Phys. 122, 244305 (2005)]. The statistical approaches are found to reproduce only some of the exact total reaction probabilities for low total angular momenta obtained with the DMBE IV PES and some of the cross sections calculated at energy values close to the reaction threshold for the XXZLG surface. Serious discrepancies with the exact integral cross sections at higher energy put into question the possible statistical nature of the title reaction. However, at a collision energy of 1.6 eV, statistical rotationally resolved cross sections managed to reproduce the experimental cross sections for the H+O(2)(v=0,j=1)-->OH(v(')=1,j('))+O process reasonably well.


Influences of background noise on infants and children.
The goal of this review is to provide a high-level, selected overview of the consequences of background noise on health, perception, cognition, and learning during early development, with a specific focus on how noise may impair speech comprehension and language learning (e.g., via masking). Although much of the existing literature has focused on adults, research shows that infants and young children are relatively disadvantaged at listening in noise. Consequently, a major goal is to consider how background noise may affect young children, who must learn and develop language in noisy environments despite being simultaneously less equipped to do so.


Isolation of new CHO cell mutants defective in CMP-sialic acid biosynthesis and transport.
Sialic acid is a sugar typically found at the N-glycan termini of glycoproteins in mammalian cells. Lec3 CHO cell mutants are deficient in epimerase activity, due to a defect in the gene that encodes a bifunctional UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Sialic acid modification on the cell surface is partially affected in these cells. We have mutagenized Lec3 CHO cells and isolated six mutants (termed C2m) deficient in the cell surface expression of polysialic acid (PSA). Mutant C2m9 was partially defective in expression of cell-surface PSA and wheat germ agglutinin (WGA) binding, while in the other five mutants, both cell-surface PSA and WGA binding were undetectable. PSA expression was restored by complementation with the gene encoding the CMP-sialic acid transporter (CST), indicating that CST mutations were responsible for the phenotypes of the C2m cells. We characterized the CST mutations in these cells by Northern blotting and RT-PCR. C2m9 and C2m45 carried missense mutations resulting in glycine to glutamate substitutions at amino acids 217 (G217E) and 256 (G256E), respectively. C2m13, C2m39 and C2m31 had nonsense mutations that resulted in decreased CST mRNA stability, and C2m34 carried a putative splice site mutation. PSA and CD15s expression in CST-deficient Lec2 cells were partially rescued by G217E CST, but not by G256E CST, although both proteins were expressed at similar levels, and localized to the Golgi. These results indicate that the novel missense mutations isolated in this study affect CST activity.


Application of avidin-biotin technology for the characterization of a model hapten-protein conjugate.
A simple method was developed for the rapid characterization of the covalent binding of haptens to proteins such as enzymes, bovine serum albumin (BSA), and other carrier-proteins and antibodies. In the present study, a commercially available fentanyl-BSA conjugate was characterized by a 4'-hydroxyazobenzene-2-carboxylic acid (HABA) dye assay that followed a biotinylation reaction. This protocol allowed the indirect observation of the average hapten number per BSA molecule. Such measurement is useful for optimizing reaction conditions to yield a more precisely defined product for immunological applications. The obtained result was within the limits suggested by the manufacturer of the conjugate.


Gene expression profiles in mouse cumulus cells derived from in vitro matured oocytes with and without blastocyst formation.
Cumulus cells (CCs) are considered as an important source to predict oocyte quality. Despite numerous candidate genes in CCs have been identified for embryonic developmental competence, the results are inconsistent. The next generation RNA-sequencing was used to investigate the transcriptomic differences in CCs from in vitro matured oocytes did or did not develop to blastocyst stage following in vitro fertilization (IVF). In our study, the corresponding mouse oocytes were traced using a single-cell tracking system, and CCs were pooled into groups based on the embryonic developmental outcomes. In vivo matured oocytes with blastocyst development were set as a reference group. The transcriptomic differences in mouse CCs from in vitro maturated oocytes with or without blastocyst formation were tested by RNA-sequencing. Real-time PCR was used to verify the expression levels of those candidate genes. A total of 103 transcripts were significantly up-regulated, and 97 down-regulated, in the CCs with the oocytes developed to blastocyst stage. The bioinformatics study showed that those genes were involved in tube morphogenesis, cell-cell signaling and cell projection formation. Nine genes were selected from the most significantly changed transcripts after comparison with the reference group: Arrb1, Atp2c1, Cdh5, Cntnap1, Mkln1, Lgr4, Rhobtb1, Smc2 and Six2, as the candidate target genes. They were associated with the regulation of G-protein coupled receptors, Wnt and MAPK signaling, actin filaments and cell adhesion. Real-time PCR verified the up-regulation of all 9 genes, and significantly increased of Rhobtb1, Mkln1, Smc2, Arrb1, Atp2c1, Cdh5 and Lgr4. Based on RNA-sequencing, we found the changes in gene transcription of mouse CCs that were critical for the communication between CCs and oocytes. The results could provide novel insights on non-invasively predicting the oocyte quality and improving developmental competence.


Cytotoxic effect of lymphocyte-antigen interaction in delayed hypersensitivity.
Lymph node cells from inbred rats having delayed sensitivity to soluble proteins inhibit growth of syngeneic or allogeneic fibroblasts in the presence of specific antigen. A relation is suggested between this in vitro phenomenon and other systems believed to be specific manifestations of delayed hypersensitivity.


Static properties of a simulated supercooled polymer melt: structure factors, monomer distributions relative to the center of mass, and triple correlation functions.
We analyze structural and conformational properties in a simulated bead-spring model of a nonentangled, supercooled polymer melt. We explore the statics of the model via various structure factors, involving not only the monomers, but also the center of mass (CM). We find that the conformation of the chains and the CM-CM structure factor, which is well described by a recently proposed approximation [Europhys. Lett. 58, 53 (2002)]], remain essentially unchanged on cooling toward the critical glass transition temperature T(c) of mode-coupling theory. Spatial correlations between monomers on different chains, however, depend on temperature, albeit smoothly. This implies that the glassy behavior of our model cannot result from static intrachain or CM-CM correlations. It must be related to interchain correlations at the monomer level. Additionally, we study the dependence of interchain correlation functions on the position of the monomer along the chain backbone. We find that this site dependence can be well accounted for by a theory based on the polymer reference interaction site model. We also analyze triple correlations by means of the three-monomer structure factors for the melt and for the chains. These structure factors are compared with the convolution approximation that factorizes them into a product of two-monomer structure factors. For the chains this factorization works very well, indicating that chain connectivity does not introduce special triple correlations in our model. For the melt deviations are more pronounced, particularly at wave vectors close to the maximum of the static structure factor.


[Impact of maternal weight gain during pregnancy on the risk of infant obesity].
To study the impact of maternal weight gain during pregnancy on the risk of infant obesity within 1 year old. A total of 785 infants who were born in Hefei and participated children medical care in one district health center and their mothers were chosen as the research subjects from September 2010 to September 2011. Three groups were classified by weight gain during pregnancy according to the percentiles: excessive pregnancy weight gain group of 126 pairs, adequate pregnancy weight gain group of 542 pairs and inadequate pregnancy weight gain group of 117 pairs. Mother's general demographic information was collected. The height and weight were measured when the infant was 42 days, 3, 6, 9, and 12 months of physical examination. Z score was calculated. The differences of Z score in different groups were compared and the RR values of different weight gain during pregnancy on infant obesity were computed. The weight-for-age Z score (WAZ) of infant at 42 days 3, 6, 9 and 12 months in excessive pregnancy weight gain group were 0.23 ± 0.93, 0.25 ± 1.03, 0.23 ± 0.99, 0.28 ± 1.09, 0.26 ± 1.14, respectively, all higher than that of the corresponding age in adequate pregnancy weight gain group (-0.04 ± 1.02, -0.07 ± 0.99, -0.05 ± 0.98, -0.06 ± 0.97, -0.07 ± 0.95, respectively). The differences were statistically significant (all P values < 0.05). In excessive pregnancy weight gain group, infant body mass index (BMI) at 9 months ((18.01 ± 0.15) kg/m(2)) and 12 months ((17.66 ± 0.15) kg/m(2)) were higher than that of adequate pregnancy weight gain group ((17.63 ± 0.13) and (17.22 ± 0.15) kg/m(2), respectively). The differences were statistically significant (all P values < 0.05). Differences of infant Height-for-age Z score (HAZ) among three groups were not statistically significant (all P values > 0.05). Compared to adequate pregnancy weight gain group, RR (95%CI) value of infant obesity in excessive pregnancy weight gain group was 1.86 (1.14 - 3.03). Excessive maternal weight gain during pregnancy increased the risk of infant obesity within 1 year old.


Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells.
Skeletal muscle has high energy requirement and alterations in metabolism are associated with pathological conditions causing muscle wasting and impaired regeneration. Congenital muscular dystrophy type 1A (MDC1A) is a severe muscle disorder caused by mutations in the LAMA2 gene. Leigh syndrome (LS) is a neurometabolic disease caused by mutations in genes related to mitochondrial function. Skeletal muscle is severely affected in both diseases and a common feature is muscle weakness that leads to hypotonia and respiratory problems. Here, we have investigated the bioenergetic profile in myogenic cells from MDC1A and LS patients. We found dysregulated expression of genes related to energy production, apoptosis and proteasome in myoblasts and myotubes. Moreover, impaired mitochondrial function and a compensatory upregulation of glycolysis were observed when monitored in real-time. Also, alterations in cell cycle populations in myoblasts and enhanced caspase-3 activity in myotubes were observed. Thus, we have for the first time demonstrated an impairment of the bioenergetic status in human MDC1A and LS muscle cells, which could contribute to cell cycle disturbance and increased apoptosis. Our findings suggest that skeletal muscle metabolism might be a promising pharmacological target in order to improve muscle function, energy efficiency and tissue maintenance of MDC1A and LS patients.


Clinical trials on placement of implants in existing bone.
The use of dental implants has become a predictable and frequently used treatment modality in partially and fully edentulous patients. In 1987, the United States Food and Drug Administration (FDA) classified dental implants as class III medical devices. In 1989, a proposed rule was published by the FDA calling for a Premarket Approval Application (PMA) for dental implants. A PMA requires the demonstration of safety and effectiveness through clinical trials. Although the effective date for Premarket Approvals and detailed information on study requirements have not been announced, many implant manufacturers have already initiated multi-center clinical trials. Despite these initiatives, several aspects regarding appropriate study designs, outcome criteria, and success or failure analysis still need clarification. Trials should be designed to minimize bias and variability. The cornerstone of the experimental design is set by the study objective. It will determine which of many possible clinical trial parameters are essential to enable the presentation of data to a regulatory body on which basis the safety and effectiveness of a device can be judged. With the multiplicity of patient characteristics, implant types, supported prostheses, study designs, evaluation parameters, and statistical analyses, it is a difficult task to design an optimal trial. It is the purpose of this paper to propose designs and components for implant clinical trials with various objectives.


Attentional bias to threat in the general population is contingent on target competition, not on attentional control settings.
Dot-probe studies usually find an attentional bias towards threatening stimuli only in anxious participants. Here, we investigated under what conditions such a bias occurs in unselected samples. According to contingent-capture theory, an irrelevant cue only captures attention if it matches an attentional control setting. Therefore, we first tested the hypothesis that an attentional control setting tuned to threat must be activated in (non-anxious) individuals. In Experiment 1, we used a dot-probe task with a manipulation of attentional control settings ('threat' - set vs. control set). Surprisingly, we found an (anxiety-independent) attentional bias to angry faces that was not moderated by attentional control settings. Since we presented two stimuli (i.e., a target and a distractor) on the target screen in Experiment 1 (a necessity to realise the test of contingent capture), but most dot-probe studies only employ a single target, we conducted Experiment 2 to test the hypothesis that attentional bias in the general population is contingent on target competition. Participants performed a dot-probe task, involving presentation of a stand-alone target or a target competing with a distractor. We found an (anxiety-independent) attentional bias towards angry faces in the latter but not the former condition. This suggests that attentional bias towards angry faces in unselected samples is not contingent on attentional control settings but on target competition.


Recognition and consequences of obstructive sleep apnea hypopnea syndrome.
There is a growing recognition of sleep-disordered breathing (SDB) in patient groups and in the general population. This article reviews issues related to recognizing the disorder, including the problems of relying on narrowly defined polysomnographic data for case findings and for assessment of disease severity. The distributions of symptoms and physiologic measurements of SDB in the population and their inter-relationships are reviewed. The epidemiological data that address risk factors and consequences of sleep apnea hypopnea syndrome (SAHS) also are discussed, with recommendations regarding recognition priorities.


Intimacy in nursing.
There are many definitions of intimacy in nursing but what they all have in common is the need for communicated empathy, for nursing that is not just caring for but also caring about.


Students' Perspectives of the Economic, Financial, and Psychological Effects of Online Learning and Its Gender Association: A Cross-Sectional Study in Jordanian Universities.
Jordan declared a quarantine in March 2020 and shut down all educational institutions in response to the COVID-19 outbreak. E-learning was a novel way to continue the educational process in the wake of the pandemic. The study evaluates online learning (OL), aiming to examine the economic, financial, and psychological effects of OL on students, as well as their concentration, university instructors' efficiency, and satisfaction with OL. This research also explores the gender association of OL effects in Jordanian universities. This is a cross-sectional study. A self-filled questionnaire was generated using an online form and distributed to students at public and private universities through social media. The questionnaire utilized a five-point Likert scale to assess various aspects related to OL. The main evaluation involved a Chi-square test and posthoc test to examine gender-based differences in the factors associated with OL. The reliability of the questionnaire was assessed using a Kaiser-Meyer-Olkin (KMO) value of 0.721 and a Cronbach's Alpha of 0.7. A total of 720 responses were collected and analyzed. The results revealed a significant gender association with the economic/financial (P=0.001) and psychological (P=0.002) effects of OL. It was observed that 65.3% of students reported feeling depressed due to online learning. Moreover, a significant correlation was found between students' concentration and university instructors' efficiency (P=0.00). Interestingly, only 14.72% of students believed university instructors were 100% efficient in teaching theoretical and practical subjects. Additionally, 55% of the students expressed their desire for university instructors to record lectures for ease of access. The study concludes that OL's poor economic/financial effects disproportionately affect female students. On the other hand, male students were more likely to strongly disagree with the poor psychological effects of OL. Moreover, female students were more inclined to strongly disagree with the notion that OL has no psychological effect. Lastly, significant findings indicate that both students and university instructors share equal responsibility for the success of OL in Jordanian universities.


Vagus nerve inflammation contributes to dysautonomia in COVID-19.
Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.


Screening for intrauterine growth retardation using ratio of mid-arm circumference to occipitofrontal circumference.
Uncritical application of standard weight percentile charts, derived from white infants, to infants from different ethnic groups may result in an overestimate of the incidence of intrauterine growth retardation in those groups. The ratio of mid-arm circumference to occipitofrontal circumference was studied in 194 babies (49 Asian, 58 black, and 87 white). In contrast with birth weight the ratio did not vary among the ethnic groups; it was also independent of sex. In a prospective study of 64 neonates whose weight was below the 10th percentile on standard charts the ratio of mid-arm circumference to occipitofrontal circumference was a more accurate predictor than weight of those infants who would develop symptoms associated with intrauterine growth retardation. The ratio of mid-arm circumference to occipitofrontal circumference therefore provides a simple, accurate, and cheap way of assessing intrauterine growth retardation in areas with a large multiethnic population, where birth weight varies greatly.


A new membrane-bound cytochrome c works as an electron donor to the photosynthetic reaction center complex in the purple bacterium, Rhodovulum sulfidophilum.
A new type of membrane-bound cytochrome c was found in a marine purple photosynthetic bacterium, Rhodovulum sulfidophilum. This cytochrome c was significantly accumulated in cells growing under anaerobic photosynthetic conditions and showed an apparent molecular mass of approximately 100 kDa when purified and analyzed by SDS-PAGE. The midpoint potential of this cytochrome c was 369 mV. Flash-induced kinetic measurements showed that this new cytochrome c can work as an electron donor to the photosynthetic reaction center. The gene coding for this cytochrome c was cloned and analyzed. The deduced molecular mass was nearly equal to 50 kDa. Its C-terminal heme-containing region showed the highest sequence identity to the water-soluble cytochrome c(2), although its predicted secondary structure resembles that of cytochrome c(y). Phylogenetic analyses suggested that this new cytochrome c has evolved from cytochrome c(2). We, thus, propose its designation as cytochrome c(2m). Mutants lacking this cytochrome or cytochrome c(2) showed the same growth rate as the wild type. However, a double mutant lacking both cytochrome c(2) and c(2m) showed no growth under photosynthetic conditions. It was concluded that either the membrane-bound cytochrome c(2m) or the water-soluble cytochrome c(2) work as a physiological electron carrier in the photosynthetic electron transfer pathway of Rvu. sulfidophilum.


Biohydrogen production by purple non-sulfur bacteria Rhodobacter sphaeroides: Effect of low-intensity electromagnetic irradiation.
The present work was focused on the effects of low-intensity (the flux capacity was of 0.06mWcm(-2)) electromagnetic irradiation (EMI) of extremely high frequencies or millimeter waves on the growth and hydrogen (H2) photoproduction by purple non-sulfur bacteria Rhodobacter sphaeroides MDC6521 (from Armenian mineral springs). After exposure of R. sphaeroides, grown under anaerobic conditions upon illumination, to EMI (51.8GHz and 53.0GHz) for 15min an increase of specific growth rate by ~1.2-fold, in comparison with control (non-irradiated cells), was obtained. However, the effect of EMI depends on the duration of irradiation: the exposure elongation up to 60min caused the delay of the growth lag phase and the decrease specific growth rate by ~1.3-fold, indicating the bactericidal effect of EMI. H2 yield of the culture, irradiated by EMI for 15min, determined during 72h growth, was ~1.2-fold higher than H2 yield of control cells, whereas H2 production by cultures, irradiated by EMI for 60min was not observed during 72h growth. This difference in the effects of extremely high frequency EMI indicates a direct effect of radiation on the membrane transfer and the enzymes of these bacteria. Moreover, EMI increased DCCD-inhibited H(+) fluxes across the bacterial membrane and DCCD-sensitive ATPase activity of membrane vesicles, indicating that the proton FoF1-ATPase is presumably a basic target for extremely high frequency EMI related to H2 production by cultures.


Antisocial behavioral syndromes in cocaine and cannabis dependence.
Antisocial personality disorder (ASPD) is highly associated with substance use disorders (SUD). In addition to the full ASPD syndrome, which requires both childhood conduct disorder and the adult features, other antisocial behavioral syndromes, including conduct disorder (CD) alone without the adult syndrome, and the adult antisocial behavioral syndrome without childhood CD (AABS) are also frequently diagnosed in patients with SUD. The aim of this study was to compare the rates of these various ASPD syndromes between cocaine- and cannabis-dependent individuals seeking treatment. A structured interview for ASPD excluding symptoms that occurred solely in the context of substance use was conducted in 241 outpatients (cocaine dependence, n = 111; cannabis dependence, n = 130). Overall, the proportion of substance-dependent individuals in this study with AABS was significantly larger than the proportion with ASPD (30.9% vs. 17.3%). A diagnosis of CD-only, where CD did not progress to ASPD, was uncommon. No significant differences in the prevalence of antisocial behavioral syndrome diagnoses were found between cocaine- and cannabis-dependent patients. Antisocial behavioral syndrome diagnosis did not influence treatment retention. Antisocial behavioral syndromes are commonly diagnosed in patients with SUD and future research should evaluate prognostic implications of AABS compared to ASPD in a variety of clinical treatment settings.


Ketamine Within Clinically Effective Range Inhibits Glutamate Transmission From Astrocytes to Neurons and Disrupts Synchronization of Astrocytic SICs.
Astrocytes are now considered as crucial modulators of neuronal synaptic transmission. General anesthetics have been found to inhibit astrocytic activities, but it is not clear whether general anesthetics within the clinical concentration range affects the astrocyte-mediated synaptic regulation. The effects of propofol, dexmedetomidine, and ketamine within clinically effective ranges on the slow inward currents (SICs) were tested by using the whole-cell recording in acute prefrontal cortex (PFC) slice preparations of rats. Astrocytes culture and HPLC were used to measure the effects of different anesthetics on the glutamate release of astrocytes. Propofol and dexmedetomidine showed no significant effect on the amplitude or frequency of SICs. Ketamine was found to inhibit the frequency of SICs in a concentration-dependent manner. The SICs synchronization rate of paired neurons was inhibited by 30 μM ketamine (from 42.5 ± 1.4% to 9.6 ± 0.8%) and was abolished by 300 μM ketamine. The astrocytic glutamate release induced by DHPG, an agonist of astrocytic type I metabotropic glutamate receptors, was not affected by ketamine, and ifenprodil, a selective antagonist of GluN1/GluN2B receptor, blocked all SICs and enhanced the inhibitory effect of 30 μM ketamine on the frequency of SICs. Ketamine at low concentration (3 μM) could inhibit the frequency of SICs, not the miniature excitatory postsynaptic currents (mEPSCs), and the inhibition rate of SICs was significantly higher than mEPSCs with 30 μM ketamine (44.5 ± 3% inhibition vs. 28.3 ± 6% inhibition). Our data indicated that ketamine, not propofol and dexmedetomidine, within clinical concentration range inhibits glutamatergic transmission from astrocytes to neurons, which is likely mediated by the extrasynaptic GluN1/GluN2B receptor activation.


[Antitumor activity of tumor necrosis factor (TNF) in vitro and in vivo].
The antitumor activity of highly purified tumor necrosis factor (TNF) was tested. TNF had direct cytotoxic activity on all cancer cells examined in vitro, and no species specificity. Normal cells showed no damage on addition of TNF. TNF showed excellent curative effects against all types of murine and human tumors tested in vivo. A great difference in curative effects of TNF was observed between Meth A sarcoma transplanted into Balb/c nu/+ and Balb/c nu/nu mice with a single intravenous administration. This experiment suggested that in addition to direct cytotoxicity against tumor cells, TNF-induced host-mediated factor which contributed to the antitumor effects Murine TNF has on inhibitory effect against multiple pulmonary metastasis of Lewis Lung-tumor. Very few references to this field could be found in the literature and the present paper mainly presented our own research.


Advances toward LSD1 inhibitors for cancer therapy.
LSD1 has become an important biologically validated epigenetic target for cancer therapy since its identification in 2004. LSD1 mediates many cellular signaling pathways and is involved in the initiation and development of cancers. Aberrant overexpression of LSD1 has been observed in different types of cancers, and inactivation by small molecules suppresses cancer cell differentiation, proliferation, invasion and migration. To date, a large number of LSD1 inhibitors have been reported, RG6016, GSK-2879552, INCB059872, IMG-7289 and CC-90011 are currently undergoing clinical assessment for the treatment of acute myeloid leukemia, small-cell lung cancer, etc. In this review, we briefly highlight recent advances of LSD1 inhibitors mainly covering the literatures from 2015 to 2017 and tentatively propose our perspectives on the design of new LSD1 inhibitors for cancer therapy.


The effects of rosiglitazione on renal artery endothelium in diabetic rats.
Macrovascular disease is a common complication of Diabetes Mellitus (DM). Study of renal artery endothelium may serve as a surrogate for cardiovascular and renal vascular disease. This study is to elucidate (1) how about the changes of renal endothelial ultrastructures it is in different time of diabetes animals (2) Whether PPARgamma ligand (such as rosiglitazone: ROS) could improve endothelium destruction in diabetes. Streptozoticin (STZ) induced diabetic rats were stratified by age groups from 6 to 10 weeks of age and were paired with age-matched control non-diabetic rats. Further, another group of diabetic rats were treated with ROS and matched with non-treated diabetic rats. The renal artery endothelium of diabetic rats was partially coarse, distended, cracked and destroyed. The Vascular Endothelial Structure Score (VESS) was 34.5 in diabetic rats compared with non-diabetic control male rats (P=0.001). The older rats demonstrated more endothelial wall damage, more pronounced in male rats. Compared with non-treated control diabetic rats, ROS prevented diabetic endothelial damage (VESS=4.6, P=0.001). Renal artery endothelium damage in STZ induced diabetic rats was significantly attenuated by rosiglitazone.


Sulfonated polybenzophenone/poly(arylene ether) block copolymer membranes for fuel cell applications.
Sulfonated polybenzophenone/poly(arylene ether) block copolymers were designed and synthesized via Ni-mediated coupling polymerization. The block copolymers were obtained as high-molecular-weight (Mn = 70-110 kDa, Mw = 150-230 kDa) with low polydispersity index (Mw/Mn = 2.0-2.3). The block copolymer membranes showed well-developed hydrophilic/hydrophobic phase separation and high proton conductivity and low gas permeability. The membrane showed better fuel cell performance and durability compared with those with Nafion, state-of-the-art proton conducting membrane.


Comparative shell buffering properties correlate with anoxia tolerance in freshwater turtles.
Freshwater turtles as a group are more resistant to anoxia than other vertebrates, but some species, such as painted turtles, for reasons not fully understood, can remain anoxic at winter temperatures far longer than others. Because buffering of lactic acid by the shell of the painted turtle is crucial to its long-term anoxic survival, we have tested the hypothesis that previously described differences in anoxia tolerance of five species of North American freshwater turtles may be explained at least in part by differences in their shell composition and buffering capacity. All species tested have large mineralized shells. Shell comparisons included 1) total shell CO2 concentration, 2) volume of titrated acid required to hold incubating shell powder at pH 7.0 for 3 h (an indication of buffer release from shell), and 3) lactate concentration of shell samples incubated to equilibrium in a standard lactate solution. For each measurement, the more anoxia-tolerant species (painted turtle, Chrysemys picta; snapping turtle, Chelydra serpentina) had higher values than the less anoxia-tolerant species (musk turtle, Sternotherus odoratus; map turtle, Graptemys geographica; red-eared slider, Trachemys scripta). We suggest that greater concentrations of accessible CO2 (as carbonate or bicarbonate) in the more tolerant species enable these species, when acidotic, to release more buffer into the extracellular fluid and to take up more lactic acid into their shells. We conclude that the interspecific differences in shell composition and buffering can contribute to, but cannot explain fully, the variations observed in anoxia tolerance among freshwater turtles.


Casein kinase II stimulates Xenopus laevis DNA topoisomerase I by physical association.
A Xenopus laevis casein kinase II-like activity copurified with X. laevis DNA topoisomerase I activity during chromatography on DEAE-cellulose, phosphocellulose, and hydroxylapatite, but the two activities were resolved by chromatography on DNA-agarose [Kaiserman, H. B., Ingebritsen, T. S., & Benbow, R. M. (1988) Biochemistry 27, 3216-3222]. Phosphorylation of the catalytic polypeptides of dephosphorylated X. laevis DNA topoisomerase I by the endogenous X. laevis casein kinase II-like activity apparently resulted in a severalfold increase in catalytic activity. In this study, we show that incubation of purified X. laevis DNA topoisomerase I with electrophoretically homogeneous bovine brain casein kinase II and ATP strongly stimulated catalytic activity. Surprisingly, purified bovine casein kinase II stimulated X. laevis DNA topoisomerase I activity by more than an order of magnitude in the absence of ATP, although ATP resulted in additional stimulation. Other basic proteins, such as histone H1 and HMG proteins, also stimulated X. laevis DNA topoisomerase I catalytic activity 2-3-fold in the absence of ATP. Modulation of catalytic activity by direct physical association (protein-protein interactions) must, therefore, be considered in addition to phosphorylation in assessing the physiological role of casein kinase II and other basic proteins during regulation of X. laevis DNA topoisomerase I activity in vivo.


The progression and evaluation of hetatologic and serum biochemical values in the chimpanzee.
Summary statistics of various hematologic and serum biochemical measures are presented for a colony of 74 chimpanzees (Pan troglodytes). Covariance analysis of longitudinal values revealed a progression of some measures with maturity. Equations for evaluating these measures as they relate to the health of individual colony members and new additions to the colony were formulated. From these equations, confidence bounds (95%), which can be regarded as normative ranges, were established for each of the measures. The literature on hematologic and serum biochemical values in the chimpanzee, especially as they pertain to the evaluation and progression of values, is reviewed.


Subtyping of avian influenza viruses H1 to H15 on the basis of hemagglutinin genes by PCR assay and molecular determination of pathogenic potential.
Serious concern about the worldwide transmission of the Asian H5N1 highly pathogenic (HP) avian influenza (AI) virus by migratory birds surrounds the importance of the AI global surveillance in wild aquatic birds and underscores the requirement for a reliable subtyping method of AI viruses. PCR is advantageous due to its simplicity, lower cross-reactivity, and unlimited reagent supply. Currently, the only available hemagglutinin (HA) subtyping primer set that can subtype H1 through H15 is not fully evaluated and, since it only targets HA1, is unavailable for molecular pathotyping of AI viruses. Our preliminary experiments found that these primer sets were cross-reactive and missed some recent AI viruses. In this study, we developed new primer sets against HA cleavage sites for subtyping H1 to H15 genes and for molecular pathotyping. Our primer sets were subtype specific and detected 99% of previously identified HA genes (115/116, 1949 to March 2006), and the correct amplifications of HA genes were confirmed by sequence analyses of all 115 PCR products. The primer sets successfully subtyped most of the recent AI viruses isolated in Japan (96% [101/105], October 2006 to March 2007). Taken together, our primer sets could efficiently detect HA genes (98% [216/221]) of both previously and recently identified HA genes or of both American (29/29) and Eurasian (187/192) lineages. All 38 H5 and 13 H7 viruses were molecularly pathotyped by sequencing analyses of the HA cleavage site. In contrast, despite efficient detection of previously identified strains (98% [114/116]), the published primer sets exhibited lower specificity and lower detection efficiency against recent AI viruses (80% [84 of 105]). These results indicate that our primers are useful not only for HA subtyping but also for molecular pathotyping of both previous and recent AI viruses. These advancements will enable general diagnostic laboratories to subtype AI viruses for the surveillance in wild aquatic birds.


Anthocyanins from black soybean seed coat prevent radiation-induced skin fibrosis by downregulating TGF-β and Smad3 expression.
The aim of this study was to evaluate the protective effects of anthocyanins from the black soybean seed coat against radiation injury in dermal fibroblasts and mouse skin. Dermal fibroblasts treated with 50 and 100 µg/mL anthocyanins were irradiated with single doses of 20 Gy. Cell viability, intracellular reactive oxygen species (ROS) production, and mRNA expression were measured. A total of 60 mice were used for an in vivo study. A dose of 100 µg/mL anthocyanins was administered daily for 5 days before or after radiation therapy. Following irradiation (45 Gy), mice were inspected for gross pathology twice per wk for 8 weeks. At 4 and 8 weeks post-irradiation, dorsal skin was harvested for histopathologic examination and protein isolation. In dermal fibroblasts, treatment with 50 and 100 µg/mL anthocyanins significantly reduced radiation-induced apoptosis at 72 h and intracellular reactive oxygen species generation at 48 h. Furthermore, 100 µg/mL anthocyanins markedly decreased Smad3 mRNA expression and increased Smad7 mRNA expression at 72 h post-irradiation. In mice, treatment with 100 µg/mL anthocyanins resulted in a significant reduction in the level of skin injury, epidermal thickness, and collagen deposition after irradiation. Treatment with 100 µg/mL anthocyanins significantly decreased the number of α-SMA-, TGF-β-, and Smad3-positive cells after irradiation. Our study demonstrated that black soybean anthocyanins inhibited radiation-induced fibrosis by downregulating TGF-β and Smad3 expression. Therefore, anthocyanins may be a safe and effective candidate for the prevention of radiation-induced skin fibrosis.


Pneumatic displacement of submacular hemorrhage due to age-related macular degeneration.
Subretinal hemorrhage is one of the most serious complications of exudative age-related macular degeneration (AMD). Treatment with vitreous surgery with or without plasminogen activator, fluid-gas exchange, or perfluorocarbon yields only a small improvement in visual acuity. The files of 24 patients with submacular hemorrhage secondary to AMD who were treated by injection of perfluoropropane gas (C(3)F(8)) (11 patients) or sulfur hexafluoride (SF(6)) (13 patients) were reviewed for visual acuity before and after the procedure and time of treatment from onset of symptoms. For the whole sample, pneumatic displacement led to a statistically significant improvement in mean visual acuity (p = 0.015). A significant difference between pre- and postoperative visual acuity was found for the patients treated with SF(6) (p = 0.034), but not for the patients treated with C(3)F(8) (p = 0.245). The use of gas injection to displace submacular hemorrhage can significantly improve visual acuity.


Transvalvular mitral regurgitation following mitral valve replacement a diagnostic dilemma.
After mitral valve replacement with a prosthetic valve, the valve should be competent and there should not be any residual prosthetic valve regurgitation. Transvalvular residual prosthetic valve regurgitation are difficult to diagnose and quantify. we are reporting interesting TEE images as a diagnostic dilemma in a case of transvalvular mitral regurgitation following mitral valve replacement secondary to entrapment of sub-valvular apparatus in a Chitra mechanical heart valve.


Autonomic involvement in Guillain-Barré syndrome: a review.
Autonomic neuropathy is an important and common complication of Guillain-Barré syndrome (GBS). Manifestations be present in cardiovascular, sudomotor, gastrointestinal and other systems involving both sympathetic and parasympathetic fibers. Some apparently selective acute autonomic neuropathies may be subvarieties of GBS. Experimental work in animal models, pathological studies of GBS patients, and autonomic function studies have provided some help in the understanding of this complication. In managing GBS patients with autonomic dysfunction there are important practical considerations that can improve their care. In this article we review the literature on autonomic neuropathy in GBS and propose a management scheme to accommodate it in the overall treatment of the neuropathy.


Cardiogel: a nano-matrix scaffold with potential application in cardiac regeneration using mesenchymal stem cells.
3-Dimensional conditions for the culture of Bone Marrow-derived Stromal/Stem Cells (BMSCs) can be generated with scaffolds of biological origin. Cardiogel, a cardiac fibroblast-derived Extracellular Matrix (ECM) has been previously shown to promote cardiomyogenic differentiation of BMSCs and provide protection against oxidative stress. To determine the matrix composition and identify significant proteins in cardiogel, we investigated the differences in the composition of this nanomatrix and a BMSC-derived ECM scaffold, termed as 'mesogel'. An optimized protocol was developed that resulted in efficient decellularization while providing the maximum yield of ECM. The proteins were sequentially solubilized using acetic acid, Sodium Dodecyl Sulfate (SDS) and Dithiothreitol (DTT). These proteins were then analyzed using surfactant-assisted in-solution digestion followed by nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). The results of these analyses revealed significant differences in their respective compositions and 17 significant ECM/matricellular proteins were differentially identified between cardiogel and mesogel. We observed that cardiogel also promoted cell proliferation, adhesion and migration while enhancing cardiomyogenic differentiation and angiogenesis. In conclusion, we developed a reproducible method for efficient extraction and solubilization of in vitro cultured cell-derived extracellular matrix. We report several important proteins differentially identified between cardiogel and mesogel, which can explain the biological properties of cardiogel. We also demonstrated the cardiomyogenic differentiation and angiogenic potential of cardiogel even in the absence of any external growth factors. The transplantation of Bone Marrow derived Stromal/Stem Cells (BMSCs) cultured on such a nanomatrix has potential applications in regenerative therapy for Myocardial Infarction (MI).


Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index in Patients With Renal Cell Carcinoma Undergoing Laparoscopic Nephrectomy: A Multi-Institutional, Propensity Score Matching Cohort Study.
We conducted a multi-institutional clinical study to assess the prognostic value of the advanced lung cancer inflammatory index (ALI) and modified ALI (mALI) in patients with renal cell carcinoma (RCC). We collected 440 patients who underwent laparoscopic nephrectomy at three centers from 2014 to 2019. ALI was defined as body mass index (BMI) × serum albumin (ALB)/neutrophil-to-lymphocyte ratio (NLR) and mALI as L3 muscle index × ALB/NLR. Kaplan-Meier curves, receiver operating characteristic (ROC) curves and Cox survival analysis were used to assess the effect of ALI and mALI on overall survival (OS). In addition, we performed 1:1 propensity score matching (PSM) for the high mALI and low mALI groups to further explore the impact of mALI on survival in RCC patients. The optimal cut-off values for ALI and mALI were 40.6 and 83.0, respectively. Based on the cut-off values, we divided the patients into high ALI and low ALI groups, high mALI and low mALI groups. ALI and mALI were significantly associated with the AJCC stage, Fuhrman grade, T stage, and M stage. Low ALI (p = 0.002) or low mALI (p < 0.001) was associated with poorer prognosis. ROC curves showed that mALI was a better predictor of OS than ALI. Multivariate Cox regression analysis showed that low mALI (aHR = 2.22; 95% CI 1.19-4.13, p = 0.012) was an independent risk factor for OS in RCC patients who underwent nephrectomy, while ALI (aHR = 1.40; 95% CI 0.73-2.66, p = 0.309) was not significantly associated. Furthermore, after PSM analysis, we found that mALI remained an independent risk factor for OS (aHR = 2.88; 95% CI 1.33-6.26, p = 0.007) in patients with RCC. For RCC patients undergoing laparoscopic nephrectomy, low ALI and low mALI were associated with poor prognosis, and preoperative mALI can be used as a potential independent prognostic indicator for RCC patients.


Synergistic effect triggered by Fe2O3 and oxygen-induced hydroxyl radical enhances formation of amino-phenolic humic-like substance.
Metal oxides play a promising role in the transformation of polyphenols and amino acids involved in naturally occurring humification. The objective of this study was to explore the synergistic interactions between Fe2O3 and O2 in the formation of humic substances under a controlled O2 atmosphere (0%, 21% and 40% O2 levels). The results indicate that an O2 level of 21% with Fe2O3 was optimal for humic acid (HA) production. Hydroxyl radicals (∙OH) formed and promoted the formation of HA in the presence of O2, and O2 improved the enhancing capacity of Fe2O3 by oxidizing Fe(II) to Fe(III). Moreover, the combination of these processes resulted in a synergistic improvement in humification. The evolution of functional groups in HA suggested that O2 promoted the formation of oxygen-containing groups such as lipids, and Fe2O3 was conducive to the formation of dark-coloured polymers during the darkening process of humification. Furthermore, the O2 level of 40% inhibited the formation of HA by reducing the transformation from Fe(III) to Fe(II). The XRD results showed few changes in the composition of Fe2O3 before and after humification, which indicated that Fe2O3 was a catalyst and an oxidant. The heterospectral UV-Vis/FTIR results suggested that ∙OH attacked phenolic rings to form the aromatic ring skeleton of HA and benefit the ring-opening copolymerization of humic precursors. In addition, structural equation modelling demonstrated that dissolved Fe was the key parameter affecting the HA yield. These findings provide new insights into the synergism of O2-mediated ∙OH production associated with metal oxide-facilitated humification.


Towards efficient, ecological assessment of interaction: A scoping review of co-constructed communication.
The complexity of communication presents challenges for clinical assessment, outcome measurement and intervention for people with acquired brain injury. For the purposes of assessment or treatment, this complexity is usually managed by isolating specific linguistic functions or speech acts from the interactional context. Separating linguistic functions from their interactional context can lead to discourse being viewed as a static entity comprised of discrete features, rather than as a dynamic process of co-constructing meaning. The ecological validity of discourse assessments which rely on the deconstruction of linguistic functions is unclear. Previous studies have reported assessment tasks that preserve some of the dialogic features of communication, but as yet, these tasks have not been identified as a distinct genre of assessment. We suggest the term 'co-constructed communication' to describe tasks which are specifically designed to capture the dynamic, jointly produced nature of communication within a replicable assessment task. To identify and summarize how co-constructed communication has been assessed with individuals with non-progressive acquired communication disability regarding task design, measures and psychometric robustness. A scoping review methodology was used to identity relevant studies. Systematic database searches were conducted on studies published before July 2021. Studies in the yield were assessed against eligibility criteria, with 37 studies identified as eligible for inclusion. This is the first time that co-constructed communication has been defined as a genre of discourse assessment for stroke and traumatic brain injury populations. Co-constructed communication has been assessed for 144 individuals with aphasia and 111 with cognitive-communication disability. Five categories of co-constructed communication tasks were identified, ranging in complexity. Variability exists in how these assessment tasks are labelled and measured. Assessment measures require further psychometric profiling, specifically regarding test-retest reliability and validity. Co-constructed communication is a discourse genre which offers researchers and clinicians a replicable method to assess language and communication in an experimentally rigorous way, within an ecologically valid context, bridging the gap between experimental and ecological assessment approaches. What is already known on this subject Standardized assessments of language skills and monologue offer reliable, replicable ways to measure language. However, isolating language from an interactional context fundamentally changes the behaviour under study. This raises questions about the ecological validity of the measures we routinely use to determine diagnoses, guide treatment planning and measure the success of treatment. What this study adds to the existing knowledge This review highlights studies that conceptualize, and often quantify, interaction by combining experimental rigour and aspects of everyday dialogue. This is the first time this genre of discourse assessment has been identified. We propose the term 'co-constructed communication' to describe this genre and provide an operational definition for the term. What are the practical and clinical implications of this study? Co-constructed communication assessment tasks require refinement, particularly regarding aspects of psychometric robustness. In the future, these tasks offer pragmatic, meaningful ways to capture the effect and impact of aphasia and cognitive-communication disability within interaction.


RNase9, an androgen-dependent member of the RNase A family, is specifically expressed in the rat epididymis.
Members of the RNase superfamily participate in a diverse array of biological processes, including RNA degradation, antipathogen activities, angiogenesis, and digestion. In the present study, we cloned the rat RNase9 gene by in silico methods and genome walking based on homology to the Macaca mulatta (rhesus monkey) epididymal RNase9. The gene is located on chromosome 15p14, spanning two exons, and is clustered with other members of the RNase A superfamily. It contains 1279 bp and encodes 182 amino acids, including a 24-amino acid signal peptide, and it has unique features known from other RNases. Unlike those other members, the rat RNase9 mRNA was specifically expressed in the epididymis, especially in the caput and corpus, and exhibited an androgen-dependent expression pattern but was downregulated in an epididymitis animal model. The RNASE9 was expressed in a principal cell-specific pattern. Interestingly, most of the principal cells in the caput expressed the RNASE9; however, in the distal caput, the principal cells showed a checkerboard-like pattern of immunoreactivity. We also observed that the RNASE9 was bound on the acrosomal domain of sperm. Its potential roles in sperm maturation are discussed.


Autophagy induced by suberoylanilide hydroxamic acid in Hela S3 cells involves inhibition of protein kinase B and up-regulation of Beclin 1.
Histone deacetylase inhibitors are promising chemotherapeutic agents and some are in clinical trials. Several molecular mechanisms have been invoked to describe their effects on cancer cells in vivo and in vitro. Autophagy has been observed in response to several anticancer reagents and has been demonstrated to be responsible for cell death. However, the exact mechanism of this phenomenon is still not clear. Here we demonstrated that suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, induces nonapoptotic cell death with several specific features characteristic of autophagy in Hela S3 cells. Suberoylanilide hydroxamic acid inhibits the activity of the mammalian target of rapamycin, a negative regulator of macroautophagy which induces the formation of autophagosomes in a Beclin 1- and autophagy-related 7-dependent manner. This process is mediated by Akt and tuberous sclerosis 2 as is demonstrated by inhibition by continuous active Akt plasmid transfection and RNA interference of tuberous sclerosis 2. Our data provide the first evidence that suberoylanilide hydroxamic acid induces autophagy in Hela S3 cells through interference with the mammalian target of rapamycin signaling pathway. These findings suggest that suberoylanilide hydroxamic acid may induce autophagic cancer cell death via its specific pathway, and invite further investigation into the detailed mechanism of this pathway to explore this compound's full potential as a chemotherapeutic agent.


Differential dispersal and the Allee effect create power-law behaviour: Distribution of spot infestations during mountain pine beetle outbreaks.
Mountain pine beetles (MPB, Dendroctonus ponderosae Hopkins) are aggressive insects attacking Pinus host trees. Pines use defensive resin to overwhelm attackers, creating an Allee effect requiring beetles to attack en masse to successfully reproduce. MPB kill hosts, leaving observable, dying trees with red needles. Landscape patterns of infestation depend on MPB dispersal, which decreases with host density. Away from contiguously impacted patches (low beetle densities), infestations are characterized by apparently random spots (of 1-10 trees). It remains unclear whether the new spots are spatially random eruptions of a locally endemic population or a mode of MPB spread, with spatial distribution determined by beetle motility and the need to overcome the Allee effect. To discriminate between the hypothesis of population spread versus independent eruption, a model of spot formation by dispersing beetles facing a local Allee effect is derived. The model gives rise to an inverse power distribution of travel times from existing outbreaks. Using landscape-level host density maps in three study areas, an independently calibrated model of landscape resistance depending on host density, and aerial detection surveys, we calculated yearly maps of travel time to previous beetle impact. Isolated beetle spots were sorted by travel time and compared with predictions. Random eruption of locally endemic populations was tested using artificially seeded spots. We also evaluated the relationship between number of new spots and length of the perimeter of previously infested areas. Spot distributions conformed strongly to predicted power-law behaviour. The spatially random eruption hypothesis was found to be highly improbable. Spot numbers grew consistently with perimeter of previously infested area, suggesting that MPB spread long distances from infestation boundaries via spots following an inverse power distribution. The Allee effect in MPB therefore accelerates, rather than limits, invasion rates, contributing to recent widespread landscape-scale mortality in western North America.


Recovery of Claw Size and Function Following Autotomy in Cancer productus (Decapoda: Brachyura).
We examined recovery of claw size and function following autotomy in red rock crabs Cancer productus. We also tested for costs of regeneration to growth and documented the frequency of claw injury in C. productus populations in Barkley Sound, Canada. Field and laboratory results indicated that crabs required at least three molts to recover a full-length cheliped. For injured crabs, regenerating claws were significantly less powerful than contralateral, normal (i.e., uninjured) claws even two instars after autotomy. Greater mechanical advantage in normal claws of injured (versus uninjured) crabs, however, suggests some morphological response by the remaining normal claw to increased exercise. Despite this compensatory response, our experiments indicate that injured crabs remain at a significant disadvantage while foraging. After adjusting for differences in propodus length, both regenerating and normal claws of injured crabs delivered significantly lower crushing forces than did claws of intact crabs. Energetic costs, in the form of reduced body size increase at the molt, were detected only for crabs regenerating both claws. High incidences of single claw loss in C. productus in Barkley Sound, together with our experimental data, suggest that much of the population experiences a prolonged foraging handicap following injury.


The influence of evaluation protocol on time spent exercising at a high level of oxygen uptake during continuous cycling.
This study evaluated the effects of protocol variation on the time spent exercising at ≥95% V̇O2max during cycle ergometer trials performed at the exercise intensity associated with V̇O2max (iV̇O2max). Nine male triathletes (age: 32±10 years; body mass: 73.3±6.1 kg; stature: 1.79±0.07 m; V̇O2max: 3.58±0.45 L.min(-1)) performed four exercise tests. During tests 1 and 2, participants performed a maximal incremental cycle ergometer test using different stage durations (1 min and 3 min) for the determination of iV̇O2max (1 min) and iV̇O2max (3 min). During tests 3 and 4, participants performed a continuous bout of exhaustive cycling at iV̇O2max (1 min) (CONT1) and iV̇O2max (3 min) (CONT3). iV̇O2max (1 min) was significantly greater (P<0.001) than iV̇O2max (3 min) (340±31 W vs. 299±44 W). Time to exhaustion (TTE) measured during CONT3 was significantly longer (P<0.001) than CONT1 (529±140 s vs. 214±65 s). Time spent at V̇O2max was significantly longer (P=0.036) during CONT3 than CONT1 (146±158 s vs. 11±20 s), and time spent at ≥95% V̇O2max was significantly longer (P=0.005) during CONT3 than CONT1 (326±211 s vs. 57±51 s). These results show that when exercising continuously at iV̇O2max, time spent at ≥95% V̇O2max is influenced by the initial measurement of iV̇O2max.


Strategies for providing healthcare services to street-dwellers in Dhaka city: evidence from an operations research.
In almost every major urban city, thousands of people live in overcrowded slums, streets, or other public places without any health services. Bangladesh has experienced one of the highest rates of urban population growth in the last three decades compared to the national population growth rate. The numbers of the urban poor and street-dwellers are likely to increase at least in proportion to the overall population growth of the country. The street-dwellers in Bangladesh are extremely vulnerable in terms of their health needs and healthcare-seeking behaviours. In Bangladesh, there is no health service-delivery mechanism targeting this marginalized group of people. This study, therefore, assessed the effectiveness of two models to provide primary healthcare (PHC) services to street-dwellers. This study of experimental pre-post design tested two models, such as static clinic and satellite clinics, for providing PHC services to street-dwellers in the evening through paramedics in Dhaka city during May 2009-April 2010. Both quantitative and qualitative techniques were used for collecting data. Data were analyzed comparing before and after the implementation of the clinics for the assessment of selected health and family-planning indicators using the statistical t-test. Services received from the model l and model 2 clinics were also compared by calculating the absolute difference to determine the relative effectiveness of one model over another. The use of healthcare services by the street-dwellers increased at endline compared to baseline in both the model clinic areas, and the difference was highly significant (p < 0.001). Institutional delivery among the female street-dwellers increased at endline compared to baseline in both the clinic areas. The use of family-planning methods among females also significantly (p < 0.001) increased at endline compared to baseline in both the areas. As the findings of the study showed the promise of this approach, the strategies could be implemented in all other cities of Bangladesh and in other countries which encounter similar problems.


Dental phobic patients' view of dental anxiety and experiences in dental care: a qualitative study.
Dental phobic patients' view of dental anxiety and experiences in dental care: a qualitative study The aim of this study was to explore and describe dental phobic patients' perceptions of their dental fear and experiences in dental care. The study sample consisted of 18 participants (12 women), with a mean age of 39.4 years, selected consecutively from patients applying for treatment at a specialized dental fear clinic in Göteborg, Sweden. Dental fear, assessed by the Dental Anxiety Scale, showed score levels well over established levels for severe dental fear. The method for sampling and analysis was inspired by the constant comparative method for Grounded Theory (GT). The thematized in-depth interviews took place outside the clinic and lasted for 1-1.5 h. All the interviews were conducted by the first author (KHA), audiotaped and transcribed verbatim. Three higher-order categories were developed and labelled existential threat, vulnerability and unsupportive dentist. Existential threat was identified as the core category, describing the central meaning of the subjects' experiences in dental care. The core category included two dimensions, labelled threat of violation and threat of loss of autonomy and independence. The core category and the descriptive categories are integrated in a model framing the process of dental fear, as described by the informants. In conclusion, the onset of dental fear was commonly related to individual vulnerability and to traumatic dental care experiences, where perceived negative dentist behaviour played a significant role. The patient was caught in a 'vicious circle' that was difficult to break, and where fear and anxiety were maintained by negative expectations about treatment and about patient's own ability to cope in dental care situations.


[Preparation and characterization of Ad-ERα-36-Fc-GFP].
ERα-36 is a novel subtype of estrogen receptor α which promotes tumor cell proliferation, invasion and drug resistance, and it serves as a therapeutic target. However, only small-molecule compounds targeting ERα-36 are under development as anticancer drugs at present. Gene therapy approach targeting ERα-36 can be explored using recombinant adenovirus armed with decoy receptor. The recombinant shuttle plasmid pDC316-Ig κ-ERα-36-Fc-GFP was constructed via genetic engineering to express an Ig κ-signaling peptide-leading secretory recombinant fusion protein ERα-36-Fc. The recombinant adenovirus Ad-ERα-36-Fc-GFP was subsequently packaged, characterized and amplified using AdMaxTM adenovirus packaging system. The expression of fusion protein and functional outcome of Ad-ERα-36-Fc-GFP transduction were further analyzed with triple-negative breast cancer MDA-MB-231 cells. Results showed that the recombinant adenovirus Ad-ERα-36-Fc-GFP was successfully generated. The virus effectively infected MDA-MB-231 cells which resulted in expression and secretion of the recombinant fusion protein ERα-36-Fc, leading to significant inhibition of EGFR/ERK signaling pathway. Preparation of the recombinant adenovirus Ad-ERα-36-Fc-GFP provides a basis for further investigation on cancer gene therapy targeting ERα-36.


Trichome regulator SlMIXTA-like directly manipulates primary metabolism in tomato fruit.
Trichomes are storage compartments for specialized metabolites in many plant species. In trichome, plant primary metabolism is significantly changed, providing substrates for downstream secondary metabolism. However, little is known of how plants coordinate trichome formation and primary metabolism regulation. In this report, tomato (Solanum lycopersicum) trichome regulator SlMIXTA-like is indicated as a metabolic regulation gene by mGWAS analysis. Overexpression of SlMIXTA-like in tomato fruit enhances trichome formation. In addition, SlMIXTA-like can directly bind to the promoter region of gene encoding 3-deoxy-7-phosphoheptulonate synthase (SlDAHPS) to activate its expression. Induction of SlDAHPS expression enhances shikimate pathway activities and provides substrates for downstream secondary metabolism. Our data provide direct evidence that trichome regulator can directly manipulate primary metabolism, in which way plants can coordinate metabolic regulation and the formation of storage compartments for specialized metabolites. The newly identified SlMIXTA-like can be used for future metabolic engineering.


Winning matches in Grand Slam men's singles: an analysis of player performance-related variables from 1991 to 2008.
This study examines factors that lead to winning matches in men's singles Grand Slam tennis, and proposes guidelines for coaches and professional tennis players both in training and preparation for Grand Slam competitions. Using longitudinal data between 1991 and 2008 retrieved from the official website of the Association of Tennis Professionals, we analysed player performance over 9,144 matches in men's singles Grand Slam tournaments. To predict match outcome, 16 variables were classified into one of three categories: player skills and performance, player characteristics and match characteristics. The three categories were entered sequentially into a logistic regression model to predict the dependent variable: the chance of winning a men's singles Grand Slam match. The final altered model explains 79.4% of the variance (Nagelkerke's pseudo R (2)) in match outcomes and correctly predicted 90.6% of cases. The importance of serving, receiving, and break points is further confirmed. The positive effect of stature diminishes when players are taller than 186 cm. We recommend more training in returning skills; to avoid overestimation of the positive impact of stature, left hand and professional experience; and that a male player begins his professional tennis career by participating in the US Open or Wimbledon.


Characterization of an intracellular receptor for activated protein kinase C (RACK) from the mollusc Biomphalaria glabrata, the intermediate host for Schistosoma mansoni.
A receptor for activated protein kinase C (RACK) was characterized from the mollusc Biomphalaria glabrata, the intermediate host for the human parasite Schistosoma mansoni. This protein was shown to possess structural and functional characteristics of other RACK proteins from various cells and organisms. Its ability to bind mammalian PKCs also confirmed the conservation of PKC and RACK interactive domains throughout evolution. Results of immunolocalization indicated the presence of Bg RACK in the cytoplasm of mollusc hemocytes and B. glabrata embryonic (Bge) cells with a more intense staining around the nucleus. These results are in agreement with the association of RACK proteins with cytoskeletal elements.


Effect of adjacent chiral tertiary and quaternary centers on the metal-catalyzed allylic substitution reaction.
The metal-catalyzed allylic substitution reaction of 5a,b and 6a was examined. Reaction with stabilized nucleophiles led to exclusive attack at the less-hindered allylic terminus, and the stereoselectivity varied with the bidentate ligand used but favored retention. The yields and reaction times were improved with the use of microwaves. Alkylation via transmetalation was only observed with phenyl- and vinylstannatranes and gave regio- and stereoselectivity opposite those observed with the stabilized anions. The epimeric carbonates 5a and 5b displayed very different reactivities. Catalysts containing metals other than palladium were completely unreactive and led to recovered starting material.


Time-Resolved Linear Dichroism Measurements of Carbonmonoxy Myoglobin as a Probe of the Microviscosity in Crowded Environments.
The distribution of viscosities in living cells is heterogeneous because of the different sizes and natures of macromolecular components. When thinking about protein folding/function processes in such an environment, the relevant (micro)viscosity at the micrometer length scale is necessarily distinguished from the bulk (macro)viscosity. The concentration dependencies of microviscosities are determined by a number of factors, such as electrostatic interactions, van der Waals forces, and excluded volume effects. To explore such factors, the rotational diffusion time of myoglobin in the presence of varying concentrations of macromolecules that differ in molecular weight (dextran 6000, 10 000, and 70 000), shape (dextran versus Ficoll), size, and surface charge is measured with time-resolved linear dichroism spectroscopy. The results of these studies offer simple empirically determined linear and exponential functions useful for predicting microviscosities as a function of concentration for these macromolecular crowders that are typically used to study crowding effects on protein folding. To understand how relevant these microviscosity measurements are to intracellular environments, the TRLD results are discussed in the context of studies that measure viscosity in cells.


Immunoreactive LHRH in cerebrospinal fluid: the clinical significance in intracranial diseases.
Cerebrospinal fluid (CSF) and plasma levels of luteinizing hormone-releasing hormone (LHRH) were measured by RIA in 46 patients with acute intracranial diseases, ie, cerebral bleeding (group A), cerebral thrombosis (B), head injury (C) and meningitis (D), and the results were compared to those obtained in 21 patients with non-intracranial diseases (group E; control). Immunoreactive LHRH concentrations in CSF (CSF IR-LHRH) of 8 postmenopausal women in group E ranged 1.3 to 6.1 (mean +/- SE: 3.1 +/- 0.6) pg/ml, and those of 5 other women and 8 men with group E ranged 1.0 to 5.6 (3.6 +/- 0.4)pg/ml. In 7 out of 15 patients in group A(7/15), CSF IR-LHRH were above the levels seen in group E. In group B, C and D, CSF IR-LHRH were above the control levels in 9/15, 1/9, 3/7, respectively. The changes in plasma LHRH were not clear in postmenopausal patients in groups A and B. Plasma IR-LHRH in other women and men in group A were above the control levels in 2 out of 9 patients (2/9). Those in groups B, C and D were above the control levels in 3/8, 1/9, 2/7, respectively. Moreover, both plasma and CSF IR-LHRH of 13 patients in group A or B in chronic stage were within the control ranges. In cases observed following the time course, the occasionally increased IR-LHRH in plasma and CSF tended to decrease following the abatement of the diseases.(ABSTRACT TRUNCATED AT 250 WORDS)


Benchmarking Intrinsic Promoters and Terminators for Plant Synthetic Biology Research.
The emerging plant synthetic metabolic engineering has been exhibiting great promise to produce either value-added metabolites or therapeutic proteins. However, promoters for plant pathway engineering are generally selected empirically. The quantitative characterization of plant-based promoters is essential for optimal control of gene expression in plant chassis. Here, we used N. benthamiana leaves and BY2 suspension cells to quantitatively characterize a library of plant promoters by transient expression of firefly/Renilla luciferase. We validated the dual-luciferase reporter system by examining the correlation between reporter protein and mRNA levels. In addition, we investigated the effects of terminator-promoter combinations on gene expression and found that the combinations of promoters and terminators resulted in a 326-fold difference between the strongest and weakest performance, as reflected in reporter gene expression. As a proof of concept, we used the quantitatively characterized promoters to engineer the betalain pathway in N. benthamiana. Seven selected plant promoters with different expression strengths were used orthogonally to express CYP76AD1 and DODA, resulting in a final betalain production range of 6.0-362.4 μg/g fresh weight. Our systematic approach not only demonstrates the various intensities of multiple promoter sequences in N. benthamiana and BY2 cells but also adds to the toolbox of plant promoters for plant engineering.


The human immunodeficiency virus type 2 (HIV-2) contains a novel gene encoding a 16 kD protein associated with mature virions.
The HIV-2 genome contains an open reading frame (designated X-orf) that does not have a counterpart in HIV-1. To establish whether X-orf is a gene, we studied its expression in HIV-2-infected individuals and in infected cells in vitro. An HIV-2 proviral DNA fragment containing the X-orf was expressed in E. coli, and the recombinant protein was used in an immunoblot assay. The X-orf protein was recognized specifically by the sera of HIV-2-infected people but not by the sera of SIV-infected monkeys or HIV-1-infected humans. A rabbit antiserum raised against the recombinant X-orf protein recognized a 16 kD protein in HIV-2-infected cells. The native X-orf protein was not glycosylated or phosphorylated, was localized in the cytoplasm of HIV-2-infected cells, and appeared to be associated with mature virions.