Antibodies towards high-density lipoprotein components in patients with psoriasis.
Psoriasis is a chronic inflammatory immune disorder associated with an increased risk of atherosclerosis. This increased risk is not fully understood. High-density lipoproteins (HDL) play an important role in the prevention of atherosclerosis and any factors that may hamper HDL function such as anti-HDL antibodies (aHDL) might be associated with an increased cardiovascular risk. We aimed to determine whether anti-HDL antibodies (aHDL) are present in patients with psoriasis. Sixty-seven patients with psoriasis were compared with a healthy control group. Epidemiologic and clinical data were recorded. IgG and IgM aHDL, IgG anti-apolipoprotein A-I (aApoA-I), anti-apolipoprotein E (aApoE), and anti-paraoxonase 1 (aPON1) antibodies, as well as VCAM-1, IL-6, and TNF-α were assessed by ELISA. Apolipoprotein A-I (ApoA-I) and Apolipoprotein E (ApoE) were measured by immunoturbidimetric immunoassay. Patients with psoriasis had higher titers of IgG aHDL (p < 0.001), IgG aApoA-I (p = 0.001) and aApoE antibodies (p < 0.001). IgG aHDL and aApoE titers were higher in patients with severe psoriasis (p = 0.010 and p = 0.018, respectively). Multiple regression analysis, considering all clinical and biological variables, showed that aApoE, IL-6, and aPON1 are the biological variables that best explain aHDL variability. This is the first report showing the presence of aHDL, aApoA-I, and aApoE antibodies in patients with psoriasis. These antibodies were associated with increased disease severity and may contribute to the pathogenesis of atherosclerosis in psoriasis. They may fulfill the clinical need for biomarkers of cardiovascular risk associated with psoriasis that would help to stratify patients for prevention and therapeutic approaches.


Modulation of the spinal N13 SEP component by high- and low-frequency electrical stimulation. Experimental pain models matter.
The N13 component of somatosensory evoked potential (N13 SEP) represents the segmental response of cervical dorsal horn neurons. Neurophysiological studies in healthy participants showed that capsaicin-induced central sensitization causes an increase of the N13 SEP amplitude. Consequently, in human research, this spinal component may serve as a valuable readout of central sensitization. In this study, we wanted to verify if the sensitivity of the N13 SEP for detecting central sensitization is consistent across different experimental pain models inducing central sensitization and secondary hyperalgesia, namely high and low-frequency electrical stimulation (HFS and LFS). In 18 healthy participants, we recorded SEP after bilateral ulnar nerve stimulation before and after secondary hyperalgesia was induced through HFS and LFS applied on the ulnar nerve territory of the hand of one side. The area of secondary hyperalgesia was mapped with a calibrated 128-mN pinprick probe, and the mechanical pain sensitivity with three calibrated 16-64-256-mN pinprick probes. Although both HFS and LFS successfully induced secondary hyperalgesia only LFS increased the amplitude of the N13 SEP. These findings suggest that the sensitivity of the N13 SEP for detecting dorsal horn excitability changes may critically depend on the different experimental pain models. Our results indicate that LFS and HFS could trigger central sensitization at the dorsal horn level through distinct mechanisms, however this still needs confirmation by replication studies.


Death or survival from invasive pneumococcal disease in Scotland: associations with serogroups and multilocus sequence types.
We describe associations between death from invasive pneumococcal disease (IPD) and particular serogroups and sequence types (STs) determined by multilocus sequence typing (MLST) using data from Scotland. All IPD episodes where blood or cerebrospinal fluid (CSF) culture isolates were referred to the Scottish Haemophilus, Legionella, Meningococcal and Pneumococcal Reference Laboratory (SHLMPRL) from January 1992 to February 2007 were matched to death certification records by the General Register Office for Scotland. This represented 5959 patients. The median number of IPD cases in Scotland each year was 292. Deaths, from any cause, within 30 days of pneumococcal culture from blood or CSF were considered to have IPD as a contributing factor. Eight hundred and thirty-three patients died within 30 days of culture of Streptococcus pneumoniae from blood or CSF [13.95 %; 95 % confidence interval (13.10, 14.80)]. The highest death rates were in patients over the age of 75. Serotyping data exist for all years but MLST data were only available from 2001 onward. The risk ratio of dying from infection due to particular serogroups or STs compared to dying from IPD due to all other serogroups or STs was calculated. Fisher's exact test with Bonferroni adjustment for multiple testing was used. Age adjustment was accomplished using the Cochran-Mantel-Haenszel test and 95 % confidence intervals were reported. Serogroups 3, 11 and 16 have increased probability of causing fatal IPD in Scotland while serogroup 1 IPD has a reduced probability of causing death. None of the 20 most common STs were significantly associated with death within 30 days of pneumococcal culture, after age adjustment. We conclude that there is a stronger association between a fatal outcome and pneumococcal capsular serogroup than there is between a fatal outcome and ST.


Side chain modifications of (indol-3-yl)glyoxamides as antitumor agents.
New series of analogues of N-(pyridin-4-yl)-2-[1-(4-chlorobenzyl)-indol-3-yl]glyoxamide D-24851 were synthesized, characterized and tested for their in vitro anticancer properties. In the first series, an amino acid spacer was introduced in the glyoxamide chain of D-24851. In the second series, the glyoxamide chain was moved to positions 4 and 5 of indole skeleton. These new compounds were tested on four cancer cell lines (KB, SK-OV-3, NCI-H460 and SF-268), with promising activity for the glycine derivative.


Cucumber mosaic virus 2b protein subcellular targets and interactions: their significance to RNA silencing suppressor activity.
The RNA silencing suppressor activity of the 2b protein of Cucumber mosaic virus (CMV) has been variously attributed to its nuclear targeting, its interaction with and inhibition of Argonaute 1 (AGO1), or its ability to bind small RNAs in vitro. In addition, the 2b ortholog of Tomato aspermy virus forms aggregates and binds RNAs in vitro. We have further studied the relationships between CMV 2b protein silencing suppressor activity and its subcellular distribution, protein-protein interactions in vivo, and interactions with small interfering RNAs in vitro. To do this, we tagged the protein with fluorescent markers and showed that it retained suppressor activity. We showed that the 2b protein is present in the nucleolus and that it self-interacts and interacts with AGO1 and AGO4 in vivo. Using a battery of mutants, we showed that the putative nuclear localization signals and phosphorylation motif of the 2b protein are not required for self-interaction or for interaction with AGO proteins. The occurrence of neither of these interactions or of nucleolar targeting was sufficient to provide local silencing-suppression activity. In contrast, the ability of the 2b protein to bind small RNAs appears to be indispensable for silencing suppressor function.


Myosin phosphorylation and regulation of cross-bridge cycle in tracheal smooth muscle.
We have tested the hypothesis that phosphorylation of the 20,000-dalton myosin light chains (LC 20) in rabbit tracheal smooth muscle modulates cross-bridge kinetics and isotonic shortening velocity. The thin muscle [190 +/- 10 (SE) microns] allowed detection of rapid changes in carbachol-induced active stress development, LC 20 phosphorylation, and isotonic shortening velocities. Phosphorylation of the LC 20 in resting muscle was 0.12 +/- 0.04 mol Pi/mol LC 20. Carbachol (10(-5) M) increased the level of phosphorylation to 0.46 +/- 0.03 mol Pi/mol LC 20 within 30 s. Phosphorylation then declined significantly as steady-state active stress was reached. A positive correlation was always found between LC 20 phosphorylation and shortening velocity. This result supports the hypothesis that the level of myosin phosphorylation was related to the mean cross-bridge cycling rate rather than the number of cross bridges contributing to the developed stress. Dephosphorylation of LC 20 occurred at about the same rate as the decline in shortening velocity and stress upon stimulus washout.


Epidemiology of childhood blindness: A community-based study in Bangladesh.
This study aimed to investigate the prevalence and causes of childhood blindness in a rural area of Bangladesh. We adopted a cross-sectional quantitative study design for this study, which was performed in three unions (sub-districts) located in Raiganj Upazila of the Sirajganj district in Bangladesh. Using a validated tool, a screening program was conducted at the household level. After initial screening, a team of ophthalmologists confirmed the diagnoses by clinical examinations. The prevalence of childhood blindness was observed to be 6.3 per 10,000 children, whereas the rate of uniocular blindness was 4.8 per 10,000 children. Congenital problems were the major causes of both uniocular and binocular blindness (uniocular blindness: 84% and binocular blindness: 92%). The whole globe was the site responsible for binocular blindness (28.0%, 95% confidence interval [CI]: 13.1, 47.7), whereas the cornea was responsible for uniocular blindness (57.8%, 95% CI: 35.3, 78.1). Childhood blindness is a public health problem in Bangladesh and is highly prevalent, regardless of sex. The major causes of childhood blindness are congenital.


Multiomics Substrates of Resistance to Emerging Pathogens? Transcriptome and Proteome Profile of a Vancomycin-Resistant Enterococcus faecalis Clinical Strain.
Antibiotic resistance and hospital acquired infections are on the rise worldwide. Vancomycin-resistant enterococci have been reported in clinical settings in recent decades. In this multiomics study, we provide comprehensive proteomic and transcriptomic analyses of a vancomycin-resistant Enterococcus faecalis clinical isolate from a patient with a urinary tract infection. The previous genotypic profile of the strain C2620 indicated the presence of antibiotic resistance genes characteristic of the vanB cluster. To further investigate the transcriptome of this pathogenic strain, we used whole genome sequencing and RNA-sequencing to detect and quantify the genes expressed. In parallel, we used two-dimensional gel electrophoresis followed by MALDI-TOF/MS (Matrix-assisted laser desorption/ionization-Time-of-flight/Mass spectrometry) to identify the proteins in the proteome. We studied the membrane and cytoplasm subproteomes separately. From a total of 207 analysis spots, we identified 118 proteins. The protein list was compared to the results obtained from the full transcriptome assay. Several genes and proteins related to stress and cellular response were identified, as well as some linked to antibiotic and drug responses, which is consistent with the known state of multiresistance. Even though the correlation between transcriptome and proteome data is not yet fully understood, the use of multiomics approaches has proven to be increasingly relevant to achieve deeper insights into the survival ability of pathogenic bacteria found in health care facilities.


Trends in managing COVID-19 from an emerging infectious disease to a common respiratory infectious disease: What are the subsequent impacts on and new challenges for healthcare systems?
Targeting the 9 countries with the highest cumulative number of newly confirmed cases in the past year, we analyzed the case fatality ratio (CFR) among newly confirmed cases and the vaccination rate (two or more doses of vaccine per 100 people) in the United States of America (USA), India, France, Germany, Brazil, the Republic of Korea, Japan, Italy, and the United Kingdom (UK) for the period of 2020-2022. Data reveal a decrease in the CFR among newly confirmed cases since the beginning of 2022, when transmission of the Omicron variant predominates, and an increase in vaccination rates. The Republic of Korea had the lowest CFR among newly confirmed cases (0.093%) in 2022 and the highest vaccination rate (86.27%). Japan had the second highest vaccination rate (83.12%) and a decrease in the CFR among newly confirmed cases of 1.478% in 2020, 1.000% in 2021, and 0.148% in 2022; while the average estimated fatality ratio for seasonal influenza from 2015-2020 was 0.020%. Currently, most countries are now easing COVID-19-related restrictions and are exploring a shift in management of COVID-19 from an emerging infectious disease to a common respiratory infectious disease that can be treated as the equivalent of seasonal or regional influenza. However, compared to influenza, infection with the Omicron variant still has a higher fatality ratio, is more transmissible, and the size of future outbreaks cannot be accurately predicted due to the uncertainty of viral mutation. More importantly, as countries shift their response strategies to COVID-19, there is an urgent need at this time to clarify what the subsequent impacts on healthcare systems and new challenges will be, including the clinical response, the dissemination of scientific information, vaccination campaigns, the creation of future surveillance and response systems, the cost of treatments and vaccinations, and the flexible use of big data in healthcare systems.


Magnetic resonance imaging accurately estimates LV mass in a transgenic mouse model of cardiac hypertrophy.
Transgenic mice with a dysfunctional guanylyl cyclase A gene (GCA -/-) are unable to transduce the signals from atrial naturetic peptide and develop hypertension and cardiac hypertrophy. Magnetic resonance imaging (MRI) was performed to assess cardiac hypertrophy in these animals, using wild-type siblings as controls. Anesthetized mice were studied by gated multislice, multiphase cine MRI at 1.5 T. Simpson's rule was used to estimate left ventricle (LV) mass and volumes from short-axis images. Correlation between LV mass evaluated by MRI and at necropsy was excellent, with LVnecropsy = 1.04 x LVMRI + 4.69 mg (r2 = 0.95). By MRI, GCA -/- LV mass was significantly different when compared with isogenic controls [GCA -/-, 226 +/- 43 mg (n = 14) vs. controls, 156 +/- 14 mg (n = 10); P < 0.0001]. LV volumes and ejection fraction in the two groups were not significantly different. MRI provides an accurate means for the noninvasive assessment of murine cardiac phenotype and may be useful in following the effects of genetic modification.


Imaging of renal cystic diseases.
The improved understanding of hereditary cystic diseases is changing the nomenclature used to describe these diseases. Detailed family studies of the inheritance of these conditions become possible as the genes involved, or their DNA markers, are identified. At the same time, ultrasonography allows cystic disease to be detected very early in life in some patients. The new information necessitates changes in the terminology, which was based previously on the patient's age at clinical presentation. Thus, because ultrasonography now sometimes identifies the cysts of adult polycystic kidney disease in utero or in neonates, the term autosomal dominant polycystic kidney disease is now more appropriate. Similarly, the term autosomal recessive polycystic kidney disease is replacing infantile polycystic kidney disease. Despite the success of ultrasonography in identifying the cysts of these and other inherited conditions very early, it is important to appreciate that precise definition of the type and heredity of the condition concerned requires detailed pathologic and genetic studies. The other renal cystic disease receiving considerable attention in the recent literature is acquired cystic disease, about which more data are accumulating. With increasing numbers of patients on long-term dialysis, the condition and its complications, especially renal adenocarcinoma but also hemorrhage, continue to cause concern. The evidence for an increased incidence of renal cell carcinoma has strengthened over recent years, and the debate on the need for CT screening of patients on long-term dialysis continues.


Mechanical Behaviors of Si/CNT Core/Shell Nanocomposites under Tension: A Molecular Dynamics Analysis.
The silicon/carbon nanotube (core/shell) nanocomposite electrode model is one of the most promising solutions to the problem of electrode pulverization in lithium-ion batteries. The purpose of this study is to analyze the mechanical behaviors of silicon/carbon nanotube nanocomposites via molecular dynamics computations. Fracture behaviors of the silicon/carbon nanotube nanocomposites subjected to tension were compared with those of pure silicon nanowires. Effective Young's modulus values of the silicon/carbon nanotube nanocomposites were obtained from the stress and strain responses and compared with the asymptotic solution of continuum mechanics. The size effect on the failure behaviors of the silicon/carbon nanotube nanocomposites with a fixed longitudinal aspect ratio was further explored, where the carbon nanotube shell was found to influence the brittle-to-ductile transition behavior of silicon nanowires. We show that the mechanical reliability of brittle silicon nanowires can be significantly improved by encapsulating them with carbon nanotubes because the carbon nanotube shell demonstrates high load-bearing capacity under tension.


A comparison between methods of measuring postrual stability: force plates versus accelerometers.
Several methods exist for the assessment of balance. In the clinical setting, they are often assessed through qualitative tests. In the laboratory, instrumentation can quantitatively and more accurately measure balance. To date, force platforms remain one of the most commonly used tools in balance assessment. They are, however, costly and cumbersome, making them impractical in clinical settings and field studies. Utilization of accelerometers in balance assessment has been studied but has not yet become a laboratory standard due to the unknown accuracy of this method. If proven accurate, the use of accelerometers in laboratory and clinical environments would be ideal because they are inexpensive, noninvasive, and easy to transport. The purpose of this study was to compare the use of accelerometers as an inclinometer to the use of a force platform in the assessment of postural stability. A triaxial accelerometer was placed on the trunk of five subjects. The subjects stood barefoot on a force platform under various conditions which affect balance: all sensory systems intact; impaired visual feedback; impaired proprioceptive feedback; and impaired visual and proprioceptive feedback. During each trial, trunk acceleration and ground reaction forces and moments were collected. Force plate data was used to plot the path of the center of pressure and acceleration data was used to plot a projected path of the trunk acceleration. Behavioral similarities were seen in both methods of balance assessment. Therefore, balance assessment via accelerometers is feasible. This method does, however, require further investigation.


Gender Differences in Pragmatic Communication in School-Aged Children with Autism Spectrum Disorder (ASD).
Possible gender differences in manifestations of autism spectrum disorder (ASD) were examined using data on production of narratives. The Expression, Reception and Recall of Narrative Instrument (ERRNI; Bishop, Expression, Reception and Recall of Narrative Instrument, Harcourt assessment, London, 2004) was administered to a sample of matched 8-year-old intellectually able boys and girls with ASD (13M, 13F), who had been selected from a large, longitudinal study. In addition, transcripts of the narratives were analyzed in detail. Significant gender differences were found in narrative production. Girls included more salient story elements than boys. On detailed language analysis, girls were also shown to tell richer stories, including more descriptors of planning or intention. Overall, our findings suggest that subtle differences in social communication may exist between intellectually able boys and girls with ASD. If reliably identifiable in young children, such gender differences may contribute to differential diagnosis of ASD. In addition, such differences may pave the way for differential approaches to intervention when the target is effective communication in sophisticated discourse contexts.


Using the concept of Chou's pseudo amino acid composition to predict apoptosis proteins subcellular location: an approach by approximate entropy.
The function of protein is closely correlated with it subcellular location. Prediction of subcellular location of apoptosis proteins is an important research area in post-genetic era because the knowledge of apoptosis proteins is useful to understand the mechanism of programmed cell death. Compared with the conventional amino acid composition (AAC), the Pseudo Amino Acid composition (PseAA) as originally introduced by Chou can incorporate much more information of a protein sequence so as to remarkably enhance the power of using a discrete model to predict various attributes of a protein. In this study, a novel approach is presented to predict apoptosis protein solely from sequence based on the concept of Chou's PseAA composition. The concept of approximate entropy (ApEn), which is a parameter denoting complexity of time series, is used to construct PseAA composition as additional features. Fuzzy K-nearest neighbor (FKNN) classifier is selected as prediction engine. Particle swarm optimization (PSO) algorithm is adopted for optimizing the weight factors which are important in PseAA composition. Two datasets are used to validate the performance of the proposed approach, which incorporate six subcellular location and four subcellular locations, respectively. The results obtained by jackknife test are quite encouraging. It indicates that the ApEn of protein sequence could represent effectively the information of apoptosis proteins subcellular locations. It can at least play a complimentary role to many of the existing methods, and might become potentially useful tool for protein function prediction. The software in Matlab is available freely by contacting the corresponding author.


Effect of a peer-educational intervention on provider knowledge and reported performance in family planning services: a cluster randomized trial.
Peer education is an interactive method of teaching or learning which is widely used for educating school and college students, in a variety of different forms. However, there are few studies on its effectiveness for in-service education. The aim of this study was to evaluate the effect of an educational programme including peer discussions, based on a needs assessment, on the providers' knowledge and reported performance in family planning services. An educational programme was designed and applied in a random selection of half of in-charges of the 74 family health units (intervention group) in Tabriz at a regular monthly meeting. The other half constituted the control group. The programme included eight pages of written material and a two-hour, face-to-face discussion session with emphasis on the weak areas identified through a needs assessment questionnaire. The educated in-charges were requested to carry out a similar kind of programme with all peers at their health facilities within one month. All in-charges received one self-administered questionnaire containing knowledge questions one month after the in-charge education (follow-up I: 61 responses), and another one containing knowledge and self-reported performance questions 26 months later (follow-up II: 61 responses). Also, such tests were done for the peers facilitated by the in-charges one (105 responses) and 27 months (114 responses) after the peer discussions. Multiple linear regression was used for comparing mean total scores, and Chi square for comparing proportions between control and intervention groups, after defining facility as the unit of randomization. The mean total percentage scores of knowledge (percent of maximal possible score) in the intervention group were significantly higher than in the control group, both at follow-up I (63%) and at follow-up II (57%); with a difference of 16 (95% CI: 11, 22) and 5 (95% CI: 0.4, 11) percentage units, respectively. Only two of the nine reported performance items were significantly different among the non in-charges in the intervention group at follow-up II. The educational programme including peer discussions using existing opportunities with no need for additional absence from the workplace might be a useful complement to formal large group education for the providers.


Kernel density surface modelling as a means to identify significant concentrations of vulnerable marine ecosystem indicators.
The United Nations General Assembly Resolution 61/105, concerning sustainable fisheries in the marine ecosystem, calls for the protection of vulnerable marine ecosystems (VME) from destructive fishing practices. Subsequently, the Food and Agriculture Organization (FAO) produced guidelines for identification of VME indicator species/taxa to assist in the implementation of the resolution, but recommended the development of case-specific operational definitions for their application. We applied kernel density estimation (KDE) to research vessel trawl survey data from inside the fishing footprint of the Northwest Atlantic Fisheries Organization (NAFO) Regulatory Area in the high seas of the northwest Atlantic to create biomass density surfaces for four VME indicator taxa: large-sized sponges, sea pens, small and large gorgonian corals. These VME indicator taxa were identified previously by NAFO using the fragility, life history characteristics and structural complexity criteria presented by FAO, along with an evaluation of their recovery trajectories. KDE, a non-parametric neighbour-based smoothing function, has been used previously in ecology to identify hotspots, that is, areas of relatively high biomass/abundance. We present a novel approach of examining relative changes in area under polygons created from encircling successive biomass categories on the KDE surface to identify "significant concentrations" of biomass, which we equate to VMEs. This allows identification of the VMEs from the broader distribution of the species in the study area. We provide independent assessments of the VMEs so identified using underwater images, benthic sampling with other gear types (dredges, cores), and/or published species distribution models of probability of occurrence, as available. For each VME indicator taxon we provide a brief review of their ecological function which will be important in future assessments of significant adverse impact on these habitats here and elsewhere.


Estimation of metabolic syndrome heritability in three large populations including full pedigree and genomic information.
Metabolic syndrome is a complex human disorder characterized by a cluster of conditions (increased blood pressure, hyperglycemia, excessive body fat around the waist, and abnormal cholesterol or triglyceride levels). Any of these conditions increases the risk of serious disorders such as diabetes or cardiovascular disease. Currently, the degree of genetic regulation of this syndrome is under debate and partially unknown. The principal aim of this study was to estimate the genetic component and the common environmental effects in different populations using full pedigree and genomic information. We used three large populations (Gubbio, ARIC, and Ogliastra cohorts) to estimate the heritability of metabolic syndrome. Due to both pedigree and genotyped data, different approaches were applied to summarize relatedness conditions. Linear mixed models (LLM) using average information restricted maximum likelihood (AIREML) algorithm were applied to partition the variances and estimate heritability (h2) and common sib-household effect (c2). Globally, results obtained from pedigree information showed a significant heritability (h2: 0.286 and 0.271 in Gubbio and Ogliastra, respectively), whereas a lower, but still significant heritability was found using SNPs data ([Formula: see text]: 0.167 and 0.254 in ARIC and Ogliastra). The remaining heritability between h2 and [Formula: see text] ranged between 0.031 and 0.237. Finally, the common environmental c2 in Gubbio and Ogliastra were also significant accounting for about 11% of the phenotypic variance. Availability of different kinds of populations and data helped us to better understand what happened when heritability of metabolic syndrome is estimated and account for different possible confounding. Furthermore, the opportunity of comparing different results provided more precise and less biased estimation of heritability.


Development and validation of reversed phase-high-performance liquid chromatography method for determination of paracetamol and lornoxicam in tablet dosage form.
A simple, precise, reliable, rapid and reproducible reversed phase-high-performance liquid chromatography method was developed and validated for the simultaneous estimation of Paracetamol (PCM) and Lornoxicam (LOX) present in tablet dosage forms. Chromatographic separation achieved isocratically on Luna C18 column (5 μm, 150 × 4.60 mm) and methanol/phosphate buffer (60:40, v/v, pH 7.0) as mobile phase, at a flow rate of 1 ml/min. Detection was carried out at 260 nm. Parameters such as linearity, precision, accuracy, recovery, specificity and ruggedness are studied as reported in the ICH guidelines. The retention times for PCM and LOX was found to be 2.06±0.013and 4.38±0.07 min, respectively. Linearity for PCM and LOX was in the range of 10-50 mg/ml and 8-40 mg/ml, respectively. The mean recoveries obtained for LOX and PCM were 100± 0.16 and 99.50± 0.43%, respectively, and relative standard deviation (RSD) was less than 2. The correlation coefficients for all components are close to 1. The RSDs for three replicate measurements in three concentrations of samples in tablets are always less than 2%. Developed method was found to be accurate, precise, selective and rapid for simultaneous estimation of PCM and LOX in tablets.


Muscarinic receptor M3 mediates human gallbladder contraction through voltage-gated Ca2+ channels and Rho kinase.
Muscarinic receptors mediate contraction of the human gallbladder through unclear receptor subtypes. The aim of the present study was to characterize muscarinic acetylcholine receptors mediating contraction of the human gallbladder. Contraction of human gallbladder muscle strips caused by agonists carbachol and muscarine was measured and the inhibition of carbachol-induced contraction by muscarinic receptor antagonists was evaluated. Reverse transcription polymerase chain reaction was performed to determine the existence of muscarinic receptor subtypes. Carbachol and muscarine caused concentration-dependent contraction of gallbladder strips. Four receptor antagonists, including atropine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), methoctramine, and pirenzepine, inhibited the carbachol-induced contraction. The relative inhibitory potency of these receptor antagonists was atropine > 4-DAMP > methoctramine > pirenzepine. The antagonist affinity estimates (pA(2) values) correlated with the known affinities at M(3), M(4), and M(5) muscarinic receptors. In addition, the M(4)-selective antagonist muscarinic toxin 3 did not inhibit and the M(5)-selective positive allosteric modulator VU0238429 did not potentiate carbachol-induced gallbladder contraction. This suggests that M(3) muscarinic receptors mediate the muscarinic response predominantly. The contractile response of carbachol was attenuated by the voltage-gated Ca(2+) channel inhibitor nifedipine and Rho-kinase inhibitor H-1152, but not affected by protein kinase C inhibitor chelerythrine. This implies the involvement of voltage-gated Ca(2+) channel and Rho kinase but not protein kinase C. These results suggest a major role of M(3) muscarinic receptors mediating the human gallbladder contraction through voltage-gated Ca(2+) channels and Rho kinase. M(3)-selective muscarinic receptor antagonists could be of therapeutic importance in the treatment of biliary motility disorders.


Interidentity memory transfer in dissociative identity disorder.
Controversy surrounding dissociative identity disorder (DID) has focused on conflicting findings regarding the validity and nature of interidentity amnesia, illustrating the need for objective methods of examining amnesia that can discriminate between explicit and implicit memory transfer. In the present study, the authors used a cross-modal manipulation designed to mitigate implicit memory effects. Explicit memory transfer between identities was examined in 7 DID participants and 34 matched control participants. After words were presented to one identity auditorily, the authors tested another identity for memory of those words in the visual modality using an exclusion paradigm. Despite self-reported interidentity amnesia, memory for experimental stimuli transferred between identities. DID patients showed no superior ability to compartmentalize information, as would be expected with interidentity amnesia. The cross-modal nature of the test makes it unlikely that memory transfer was implicit. These findings demonstrate that subjective reports of interidentity amnesia are not necessarily corroborated by objective tests of explicit memory transfer.


Superprecipitation is a model for in vitro contraction superior to ATPase activity.
We investigated which activity of myosin B (natural actomyosin), super-precipitation or ATPase, is better suited as a parameter for measuring in vitro contraction with emphasis on the response of myosin B to Sr2+. The Sr2+ concentration giving half-maximum (KSr2+) binding of Sr2+ to cardiac troponin was not different from that to skeletal troponin, whether the troponins were contained in the actomyosin system or in the isolated state. However, KSr2+ for the ATPase activity of cardiac myosin B is slightly smaller than that of skeletal myosin B. This difference in KSr2+ is more marked when superprecipitation was used as the indication for in vitro contraction. If the above results were compared with those of Kitazawa (1976) using glycerinated fibers of cardiac and skeletal muscle, the differences in KSr2+ between cardiac and skeletal muscle increased in the order: Sr-binding to troponin less than ATPase activity less than superprecipitation less than contraction of glycerinated fibers. The increase in the effect of pH on Ca2+-related properties is also in the order: Ca-binding to troponin less than or equal to ATPase activity less than superprecipitation less than contraction of glycerinated fibers. All the results coincide with one another that the results with super-precipitation are invariably more akin to those with glycerinated fibers than to those with the ATPase activity. It is concluded that superprecipitation is a better parameter for representing in vitro contraction than ATPase activity.


Purification and crystallization of a complex between human interferon gamma receptor (extracellular domain) and human interferon gamma.
X-ray diffraction quality crystals have been obtained from a complex between interferon gamma and the extracellular domain of its high-affinity cell surface receptor. The crystals were obtained from interferon gamma/interferon gamma receptor complexes purified by size exclusion chromatography. Diffraction quality crystals required analyzing these complex samples by isoelectric focusing gels to select purified complex fractions devoid of unbound interferon gamma. These studies used interferon gamma receptor engineered with an eight amino acid N-terminal deletion to eliminate heterogeneity generated due to proteolytic cleavage. In addition, the receptor was expressed in an E. coli secretion cell line which eliminated the need to refold the protein. Hexagonal crystals were grown from 1.6 M ammonium phosphate solutions and belong to a spacegroup of P6(5)22 with unit cell dimensions a = 145.9 A and c = 180.3 A. These crystals diffract to at least 2.9 A resolution when exposed to synchrotron radiation. SDS PAGE analysis of the crystals demonstrated that both interferon gamma and the receptor were present. Analysis of the x-ray diffraction data revealed that the crystals contain complexes with a stoichiometry of 2:1 receptor: ligand within the crystallographic asymmetric unit and consist of approximately 55% solvent.


U.S. hospital care for HIV-infected persons and the role of public, private, and Veterans Administration hospitals.
Hospitals are a major provider of medical care for human immunodeficiency virus (HIV)-infected persons. Although utilization and patterns of care profiles in public and private hospitals have been evaluated for acquired immunodeficiency syndrome (AIDS)-related Pneumocystis carinii pneumonia (PCP), one of the most costly and common severe complications of AIDS, information from Veterans Administration (VA) hospitals has not been reported previously. This article reports on inpatient care for PCP patients by obtaining data from VA, private, and public hospitals. Cost and resource utilization data were obtained from reviews of medical records, claims, and provider bills from 26 non-VA hospitals and 18 VA hospitals in 10 cities in the United States. Data on severity of illness, patterns of care, and outcomes for PCP were obtained from medical record reviews from 2,174 PCP cases treated in 82 non-VA and 14 VA hospitals in five U.S. cities. Estimates were made of the average costs and the rates of use of diagnostic tests, anti-PCP medications, and intensive care units for samples of public hospital, private hospital, and VA patients with PCP. With mean charges for a single PCP episode of $14,500 to $16,060, PCP remains one of thea most costly complications of AIDS. Although the severity of PCP illness at admission was greatest at public hospitals, the intensity of care was lowest: for frequency of cytologic diagnosis (48% at public, 62% at VA, and 66% at private hospitals), bronchoscopy (45% at public, 60% at VA, and 66% at private hospitals), and intensive care unit use (11% at public, 22% at VA, and 19% at private hospitals). In-hospital mortality rates for PCP also differed in the three types of hospitals (20% at public, 24% at VA, and 18% at private hospitals). Patterns of PCP care differ among VA, public, and private hospitals. Future studies on the HIV epidemic should include data collected from uniform data sources from VA hospitals, in addition to public and private hospitals, to provide insight on the processes of care and outcomes for HIV-infected persons.


Immunohistochemical analysis of Na+/I- symporter distribution in human extra-thyroidal tissues.
131Iodine concentration has been described in several extra-thyroidal tissues. Recent evidence has shown that iodine uptake is achieved by the recently cloned human Na(+)/I(-) symporter (hNIS) gene. However, conflicting results were observed in the expression of hNIS transcripts in extra-thyroidal tissues. In order to document further the distribution of hNIS, we investigated its expression using an immunohistochemical method, based on a polyclonal antibody raised against a synthetic peptide. Various extra-thyroidal tissues were examined, particularly from the digestive tract. Our results confirm that the salivary glands and the stomach express hNIS protein significantly. In contrast, hNIS was undetectable in the colon but the rectal mucosa, which has never been examined, exhibited positive immunohistochemical staining. Other digestive tissues, including the oesophagus, small intestine and appendix, were negative. Weak staining was observed in the mammary gland, indicating that hNIS is expressed in this tissue. The pancreas, skin, ovaries, spleen and kidney showed no positive immunostaining.


Depth from shading and disparity in humans and monkeys.
A stimulus display was devised that enabled us to examine how effectively monkeys and humans can process shading and disparity cues for depth perception. The display allowed us to present these cues separately, in concert and in conflict with each other. An oddities discrimination task was used. Humans as well as monkeys were able to utilize both shading and disparity cues but shading cues were more effectively processed by humans. Humans and monkeys performed better and faster when the two cues were presented conjointly rather than singly. Performance was significantly degraded when the two cues were presented in conflict with each other suggesting that these cues are processed interactively at higher levels in the visual system. The fact that monkeys can effectively utilize depth information derived from shading and disparity indicates that they are a good animal model for the study of the neural mechanisms that underlie the processing of these two depth cues.


Diabetes and thyroid cancer risk: literature review.
Diabetic patients have a higher risk of various types of cancer. However, whether diabetes may increase the risk of thyroid cancer has not been extensively studied. This paper reviews and summarizes the current literature studying the relationship between diabetes mellitus and thyroid cancer, and the possible mechanisms linking such an association. Epidemiologic studies showed significant or nonsignificant increases in thyroid cancer risk in diabetic women and nonsignificant increase or no change in thyroid cancer risk in diabetic men. A recent pooled analysis, including 5 prospective studies from the USA, showed that the summary hazard ratio (95% confidence interval) for women was 1.19 (0.84-1.69) and was 0.96 (0.65-1.42) for men. Therefore, the results are controversial and the association between diabetes and thyroid cancer is probably weak. Further studies are necessary to confirm their relationship. Proposed mechanisms for such a possible link between diabetes and thyroid cancer include elevated levels of thyroid-stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D deficiency, and antidiabetic medications such as insulin or sulfonylureas.


Modulation of adenylyl cyclase activity in rat striatal homogenate by dopaminergic receptors.
We have characterized the modulation of adenylyl cyclase (AC) activity by ligands of dopaminergic receptors in rat striatal homogenate and compared the results with receptor-ligand binding affinities. Despite the fact that rat striatum contains high level of both dopamine D(1) and D(2) receptors, only the D(1)-specific AC activation by agonists could be determined. All D(1)-receptor agonists (dopamine, dihydrexidine, and A 77636) used were able to increase cAMP accumulation in a concentration-dependent manner, while D(1)-receptor antagonists (SCH23390, SKF83566, and butaclamol) blocked the effects induced by the aforementioned agonists. At the same time, the D(2)-receptor agonist quinpirole and antagonist sulpiride had no effect on cAMP accumulation in striatal homogenate neither on the basal level nor on the activated level of AC, while inhibited [(3)H]raclopride binding to these membranes. Comparing the ligands of the D(1) receptor in modulating the activity of AC and displacing D(1)-receptor-specific radioligand [(3)H]SCH23390 binding revealed that the ligands modulate both of these processes with similar affinities. It indicates that under given experimental conditions, only dopamine D(1)-receptor-mediated stimulation of AC activity can be measured in membrane homogenate of rat striatum, while dopamine D(2)-receptor effects remain fully hidden.


Patient understanding of the importance of statin use in the perioperative period.
Perioperative hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (statins) have been shown to decrease morbidity and mortality after noncardiac surgery. The objective of this study was to assess patient understanding of the potential benefits of perioperative statins in a select population already on chronic therapy. A secondary aim was to determine the frequency with which patients recalled having a discussion with their provider regarding perioperative statins. Survey. Teaching hospital. Patients taking daily statins presenting to a preoperative medical evaluation clinic were offered a 12-question survey that assessed their understanding of the potential benefit of taking the medication in the perioperative period. None. One hundred thirty-two patients completed the questionnaire. The mean age was 68.3 years (standard deviation, 9.0); 42% were female. The most frequent surgical referral to the clinic was orthopedics, at 36%. The most common statin prescribed was atorvastatin, in 35% of patients. Twenty-seven percent of patients (n = 36) recognized that perioperative statins are beneficial; 44% of these patients (n = 14) cited decreased cholesterol during the procedure as the reason, representing 12% of the total sampled population. Twenty-two percent (n = 8) of those recognizing the benefit of perioperative statins identified a decrease in the risk of heart attack or death as the reason. This represented only 6% of the total sample. One percent of surgeons mentioned statins in relation to the planned surgery; 2% of primary or prescribing physicians mentioned the medication in relation to surgery. This study suggested low patient understanding of the potential importance and reasons for perioperative statins. In addition, this study also suggested that the information regarding the importance of perioperative statins is not being relayed to the patient at the level of the surgeon or primary care physician. All physicians involved in perioperative care can offer improved patient education to promote compliance with statin therapy in hopes of a favorable impact on perioperative outcomes.


[Proliferative potential of nasal septum chondrocytes for in vitro culture of cartilage transplants].
Recent developments in the field of tissue engineering provide novel approaches in tissue repair and reconstructive surgery using the patients own cells. Isolated chondrocytes form new cartilage when seeded in appropriate scaffolds. Usually the number of cells from a cartilage biopsy is not sufficient. The present study investigates the potential of cell amplification of human nasal chondrocytes in monolayer culture. Nasal cartilage cells from seven healthy patients with age between 16 and 60 years were enzymatically isolated with collagenase and hyaluronidase. Subsequently, cells were seeded in 75 cm2 culture flasks. After confluency, cultures were trypsinized, counted, and again seeded at a concentration of 5 x 10(4) cells/ml. Dulbecco's MEM supplemented with 10% FCS was used as culture medium. After enzymatic digest, an average of 5 x 10(5) cells per patient were isolated. At least 85% of the cells were vital. Within four to eight weeks, the cells number was increased 10(3) to 10(5) fold. No correlation between the proliferative activity and the age of the patient was observed in this study. The observed increase in cell number resembles about 10 to 20 cell doublings. Although the doubling time appears to be longer during the second month, no definite limit of proliferative activity was seen during the time of study. Proliferating chondrocytes in monolayer lose their tissue-specific phenotype. For the de novo formation of cartilage transplants, redifferentiation of the expanded cells has to be stimulated. This study shows that human nasal chondrocytes can be expanded sufficiently in monolayer for the engineering of autologous cartilage transplants.


[Primary peritonitis in the newborn: a recently recognised disease].
Neonatal primary peritonitis (or autonomic bacterial peritonitis) is a diffuse peritoneal inflammation without any obvious visceral cause. It is a disease rarely described during the neonatal period. The aim of the current study was to make the surgical community aware of it, in an attempt to help a prompt diagnose and to avoid any unnecessary surgery in patients admitted in Neonatal Intensive Care Unit (NICU). It concerns the description of 7 cases of newborns affected by primary peritonitis during their hospitalization in the NICU, underlining their signs and symptoms along with all additional paraclinical tests and the final outcome. Primary peritonitis was identified in 7 neonates (5 females and 2 males). Despite the severity of their symptoms (e.g., abdominal sensibility, a long standing ileus etc.) none of them had sustained any surgery and the mortality was nil. Neonatal primary peritonitis should always be taken into account in such circumstances. The final outcome, despite the initial clinical severity, is favorable with the appropriate conservative therapy


Muscular Contribution to Adolescent Idiopathic Scoliosis from the Perspective of Stem Cell-Based Regenerative Medicine.
Adolescent idiopathic scoliosis (AIS) is a relatively frequent disease within a range 0.5%-5.0% of population, with higher frequency in females. While a resultant spinal deformity is usually medically benign condition, it produces far going psychosocial consequences, which warrant attention. The etiology of AIS is unknown and current therapeutic approaches are symptomatic only, and frequently inconvenient or invasive. Muscular contribution to AIS is widely recognized, although it did not translate to clinical routine as yet. Muscle asymmetry has been documented by pathological examinations as well as systemic muscle disorders frequently leading to scoliosis. It has been also reported numerous genetic, metabolic and radiological alterations in patients with AIS, which are linked to muscular and neuromuscular aspects. Therefore, muscles might be considered an attractive and still insufficiently exploited therapeutic target for AIS. Stem cell-based regenerative medicine is rapidly gaining momentum based on the tremendous progress in understanding of developmental biology. It comes also with a toolbox of various stem cells such as satellite cells or mesenchymal stem cells, which could be transplanted; also, the knowledge acquired in research on regenerative medicine can be applied to manipulation of endogenous stem cells to obtain desired therapeutic goals. Importantly, paravertebral muscles are located relatively superficially; therefore, they can be an easy target for minimally invasive approaches to treatment of AIS. It comes in pair with a fast progress in image guidance, which allows for precise delivery of therapeutic agents, including stem cells to various organs such as brain, muscles, and others. Summing up, it seems that there is a link between AIS, muscles, and stem cells, which might be worth of further investigations with a long-term goal of setting foundations for eventual bench-to-bedside translation.


Sinorhizobium medicae sp. nov., isolated from annual Medicago spp.
The taxonomic position of isolates of a new genomic species (designated genomic species 2) obtained from several annual Medicago species and originating from different geographical locations was established through the results of phenotypic tests (including the results of auxanographic and biochemical tests and symbiotic properties) and 16S rRNA phylogenetic inferences. A comparison of the complete 16S rRNA sequence of a representative of genomic species 2 (strain A 321T [T = type strain]) with the 16S rRNA sequences of other members of the Rhizobiaceae and closely related taxa showed that genomic species 2 was phylogenetically related to Sinorhizobium meliloti, Sinorhizobium fredii, Sinorhizobium saheli, and Sinorhizobium teranga. The levels of sequence similarity and observed numbers of nucleotide substitutions in Sinorhizobium strains indicated that A 321T and S. meliloti exhibited the highest level of sequence similarity (99.7%), with four nucleotide substitutions and one deletion. The results of a numerical analysis based on data from 63 auxanographic and biochemical tests clearly separated genomic species 2 isolates from S. meliloti. Genomic species 2 isolates nodulated and fixed nitrogen with Medicago polymorpha, whereas S. meliloti isolates were ineffective and formed rudimentary nodules on this host plant. On the basis of phenotypic and 16S sequence analysis data, genomic species 2 isolates cannot be assigned to a previously described species. We propose that these isolates belong to a new species, Sinorhizobium medicae.


Sulfonated diiron complexes as water-soluble models of the [Fe-Fe]-hydrogenase enzyme active site.
A series of diiron complexes developed as fundamental models of the two-iron subsite in the [FeFe]-hydrogenase enzyme active site show water-solubility by virtue of a sulfonate group incorporated into the -SCH(2)NRCH(2)S- dithiolate unit that bridges two Fe(I)(CO)(2)L moieties. The sulfanilic acid group imparts even greater water solubility in the presence of β-cyclodextrin, β-CyD, for which NMR studies suggest aryl-sulfonate inclusion into the cyclodextrin cavity as earlier demonstrated in the X-ray crystal structure of 1Na·2 β-CyD clathrate, where 1Na = Na(+)(μ-SCH(2)N(C(6)H(4)SO(3)(-))CH(2)S-)[Fe(CO)(3)](2), (Singleton et al., J. Am. Chem. Soc.2010, 132, 8870). Electrochemical analysis of the complexes for potential as electrocatalysts for proton reduction to H(2) finds the presence of β-CyD to diminish response, possibly reflecting inhibition of structural rearrangements required of the diiron unit for a facile catalytic cycle. Advantages of the aryl sulfonate approach include entry into a variety of water-soluble derivatives from the well-known (μ-SRS)[Fe(CO)(3)](2) parent biomimetic, that are stable in O(2)-free aqueous solutions.


Quantifying phagocytosis of Mycobacterium avium complex by human monocytes in whole blood.
Studies of phagocytic efficiency in cells of the macrophage lineage have assumed additional importance since the discovery that HIV infection of these cells impairs their immune function. A rapid method has been developed for measuring phagocytosis of the opportunistic pathogen Mycobacterium avium complex by human monocytes. Fluoresceinated M. avium complex (F-MAC) was incubated with whole blood at 37 degrees C and the fluorescence of extracellular F-MAC was quenched using a vital blue stain. Monocytes were then stained with a monoclonal antibody (mAb) to human CD14 conjugated to phycoerythrin (PE) red cells were lysed, and the percentage of monocytes which had phagocytosed F-MAC was measured by flow cytometry. The results were reproducible in samples of blood taken from individual donors over a period of 1 or 2 weeks, and optimum F-MAC concentrations and an optimum incubation time were determined by experiment. This method has the advantages of requiring only a small volume of blood, not necessitating manipulation of cells before testing, and using a phagocytic target relevant to the pathogenesis of HIV infection.


[Diagnosis of mild cranio-cerebral injury].
As many as 143 patients with concussion and 79 with contusion of the brain of the mild degree were examined. In concussion, the oral reflex never occurs. Meanwhile Marinesco-Radovici reflex is positive almost in 90%, appearing, however, not earlier than 6 hours after the injury and lasting up to 7-16 days. It should be mentioned that in 53.5%, the reflex is unilateral. The latter fact indicates that in concussion, over half the patients manifest the signs of cortical focal derangement together with general cerebral disseminated minisymptoms, seen throughout 1-2 weeks. In mild contusion of the brain in the acute stage, the oral reflex is detectable in 27% of cases. Marinesco-Radovici reflex appears only by days 2-4 after the contusion. The data obtained are helpful in defining the level, degree of the involvement of brain structures, and dynamics of their reverse development in patients with craniocerebral injury, thereby contributing to adequate differential diagnosis of concussion and contusion of the brain of the mild degree.


Genetic knowledge and attitudes of parents of children with congenital heart defects.
Clinical genetic testing for specific isolated congenital heart defects (CHD) is becoming standard of care in pediatric cardiology practice. Both genetic knowledge and attitudes toward genetic testing are associated with an increased utilization of genetic testing, but these factors have not been evaluated in parents of children with CHD. We mailed a survey to measure the demographics, genetic knowledge, and attitudes towards genetic testing of parents of children with CHD who previously consented to participate in a separate research study of the genetic etiology of left ventricular outflow tract malformations (LVOT). Of the 378 eligible families, 190 (50%) returned surveys with both parents completing surveys in 97 (51%) families, resulting in 287 participants. Genetic knowledge was assessed on an adapted measure on which the mean percent correct was 73.8%. Educational attainment and household income were directly and significantly associated with genetic knowledge (P < 0.001). Attitudes about the health effects of genetic testing were favorable with at least 57% agreeing that genetic testing would be used for managing health care and finding cures for disease. Conversely, a minority of participants found it likely that genetic testing would be used for insurance (up to 39.9%), employment (15.8%), or racial/social discrimination (up to 11.2%). Parents of younger children were less likely to endorse employment or racial/social discrimination. Genetic knowledge was not correlated with specific attitudes. Among parents of children with CHD, genetic knowledge was directly associated with household income and education, but additional research is necessary to determine what factors influence attitudes towards genetic testing.


Quantifying the effects of neutron dose, dose protraction, age and sex on mouse survival using parametric regression and machine learning on a 21,000-mouse data set.
The biological effects of densely-ionizing radiations such as neutrons and heavy ions encountered in space travel, nuclear incidents, and cancer radiotherapy, significantly differ from those of sparsely-ionizing photons and necessitate a comprehensive understanding for improved protection measures. Data on lifespan studies of laboratory rodents exposed to fission neutrons, accumulated in the Janus archive, afford unique insights into the impact of densely ionizing radiation on mortality from cancers and various organ dysfunction. We extracted and analyzed data for 21,308 individual B6CF1 mice to investigate the effects of neutron dose, fractionation, protraction, age, and sex on mortality. As Cox regression encountered limitations owing to assumption violations, we turned to Random Survival Forests (RSF), a machine learning algorithm adept at modeling nonlinear relationships. RSF interpretation using Shapley Additive Explanations revealed a dose response for mortality risk that curved upwards at low doses < 20 cGy, became nearly-linear over 20-150 cGy, and saturated at high doses. The response was enhanced by fractionation/protraction of irradiation (exhibiting an inverse dose rate effect), and diminished by older age at exposure. Somewhat reduced mortality was predicted for males vs females. This research expands our knowledge on the long-term effects of densely ionizing radiations on mammal mortality.


Evaluation of Health Literacy and Depression Literacy Among Korean Americans.
Low health literacy is closely related to a higher rate of hospitalization and of emergency services usage, leading to billions of dollars in avoidable health care costs and contributing to individuals' poor physical and mental health. While Korean Americans (KAs) have a high prevalence of general health and mental health problems, relatively little is known about their health and mental health literacy, specifically their depression literacy. This study aims to evaluate KAs' health literacy and depression literacy, as related to sociodemographic characteristics. An exploratory study was conducted with 681 community-residing adult KAs using the Center for Epidemiologic Studies Depression (CES-D) Scale, the Depression Literacy Questionnaire (D-Lit), and the One-Question Health Literacy Scale. Data analyses were performed using one-way analysis of variance and ordinal logistic regression of health literacy, a multiple linear regression model of depression literacy. Findings indicate a positive correlation between depression literacy and health literacy. Health literacy was also significantly related to religion, English language proficiency, income, education, and perceived physical health. Additionally, depression literacy was significantly related to age, Korean language preference over English, and education. Health literacy and depression literacy education are warranted to address low health literacy and depression literacy among KAs to reduce their health and mental health disparities.


International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors.
The hormone melatonin (5-methoxy-N-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in several peripheral tissues and organs. In the circulation, the concentration of melatonin follows a circadian rhythm, with high levels at night providing timing cues to target tissues endowed with melatonin receptors. Melatonin receptors receive and translate melatonin's message to influence daily and seasonal rhythms of physiology and behavior. The melatonin message is translated through activation of two G protein-coupled receptors, MT(1) and MT(2), that are potential therapeutic targets in disorders ranging from insomnia and circadian sleep disorders to depression, cardiovascular diseases, and cancer. This review summarizes the steps taken since melatonin's discovery by Aaron Lerner in 1958 to functionally characterize, clone, and localize receptors in mammalian tissues. The pharmacological and molecular properties of the receptors are described as well as current efforts to discover and develop ligands for treatment of a number of illnesses, including sleep disorders, depression, and cancer.


Self-voice perception and its relationship with hallucination predisposition.
Introduction: Auditory verbal hallucinations (AVH) are a core symptom of psychotic disorders such as schizophrenia but are also reported in 10-15% of the general population. Impairments in self-voice recognition are frequently reported in schizophrenia and associated with the severity of AVH, particularly when the self-voice has a negative quality. However, whether self-voice processing is also affected in nonclinical voice hearers remains to be specified. Methods: Thirty-five nonclinical participants varying in hallucination predisposition based on the Launay-Slade Hallucination Scale, listened to prerecorded words and vocalisations differing in identity (self/other) and emotional quality. In Experiment 1, participants indicated whether words were spoken in their own voice, another voice, or whether they were unsure (recognition task). They were also asked whether pairs of words/vocalisations were uttered by the same or by a different speaker (discrimination task). In Experiment 2, participants judged the emotional quality of the words/vocalisations. Results: In Experiment 1, hallucination predisposition affected voice discrimination and recognition, irrespective of stimulus valence. Hallucination predisposition did not affect the evaluation of the emotional valence of words/vocalisations (Experiment 2). Conclusions: These findings suggest that nonclinical participants with high HP experience altered voice identity processing, whereas HP does not affect the perception of vocal emotion. Specific alterations in self-voice perception in clinical and nonclinical voice hearers may establish a core feature of the psychosis continuum.


Development of the Rheumatoid Arthritis Distress Scale (RADS): a new tool to identify disease-specific distress in patients with Rheumatoid Arthritis.
Patients with Rheumatoid Arthritis (RA) may experience psychological distress (depression, anxiety) in addition to their physical symptoms. People with RA may also experience disease-specific distress (DSD), related to the specific burden of living with their life-long condition. DSD is a patient reported outcome in several long-term conditions, including type 1 and 2 diabetes. The aims of this study were to determine whether DSD is experienced by people with RA, and if so, develop a Patient Reported Outcome Measure (PROM) to assess for DSD in people with RA. A five-phased qualitative study was conducted which consisted of a secondary data analysis of 61 interviews of people with rheumatological disease (Phase 1), validation of findings via a Patient and Public Involvement (PPI) group of people with RA (n = 4) (Phase 2), item generation for a PROM (Phase 3) and establishing face and content validity of the PROM via PPI group (n = 4) and individual cognitive interviews (n = 9) of people with RA respectively (Phase 4 and 5). The final PROM was presented at a Patient Education Evening for patients with long-term rheumatological conditions, including RA, and carers. Five themes of rheumatological disease distress emerged from Phase 1, which were validated in the Phase 2 PPI group. After Phases 3-5, the Rheumatoid Arthritis Distress Scale (RADS) was formed of 39 items and 3 supplementary questions. Overall participants reported the content of the RADS to be clear and relevant, and that DSD is a valid concept in RA, distinct from other entities like clinical depression or anxiety. DSD appears to be an important concept in RA. The 39-item RADS demonstrates acceptable face and content validity in this patient group. Further psychometric testing is needed. The RADS may be a useful tool for healthcare professionals to identify RA distress.


Kinetic analysis of F-actin depolymerization in polymorphonuclear leukocyte lysates indicates that chemoattractant stimulation increases actin filament number without altering the filament length distribution.
The rate of filamentous actin (F-actin) depolymerization is proportional to the number of filaments depolarizing and changes in the rate are proportional to changes in filament number. To determine the number and length of actin filaments in polymorphonuclear leukocytes and the change in filament number and length that occurs during the increase in F-actin upon chemoattractant stimulation, the time course of cellular F-actin depolymerization in lysates of control and peptide-stimulated cells was examined. F-actin was quantified by the TRITC-labeled phalloidin staining of pelletable actin. Lysis in 1.2 M KCl and 10 microM DNase I minimized the effects of F-actin binding proteins and G-actin, respectively, on the kinetics of depolymerization. To determine filament number and length from a depolymerization time course, depolymerization kinetics must be limited by the actin monomer dissociation rate. Comparison of time courses of depolymerization in the presence (pointed ends free) or absence (barbed and pointed ends free) of cytochalasin suggested depolymerization occurred from both ends of the filament and that monomer dissociation was rate limiting. Control cells had 1.7 +/- 0.4 x 10(5) filaments with an average length of 0.29 +/- 0.09 microns. Chemo-attractant stimulation for 90 s at room temperature with 0.02 microM N-formylnorleucylleucylphenylalanine caused a twofold increase in F-actin and about a two-fold increase in the total number of actin filaments to 4.0 +/- 0.5 x 10(5) filaments with an average length of 0.27 +/- 0.07 microns. In both cases, most (approximately 80%) of the filaments were quite short (less than or equal to 0.18 micron). The length distributions of actin filaments in stimulated and control cells were similar.


The effect of vagotomy on the distribution of sulphomucin-containing cells in the rat pyloric antrum.
The present histological investigation showed that bilateral truncal vagotomy (with accompanying pyloroplasty) reduced the sulphomucin-containing cell population of the pyloric antral mucosa of the rat stomach. Although this did not reach statistical significance (95% confidence limits), study of the absolute distribution of the sulphomucin-containing cells showed that significantly fewer of these cells were situated in the basal third of the mucosa as a result of the operation. A study of the percentage distribution revealed that a much higher percentage of sulphomucin-containing cells was present in the middle third of the mucosa in vagotomized rats than in the corresponding regions of the control stomachs. Thus, vagotomy and pyloroplasty had effected a redistribution of the sulphomucin-containing cells in the pyloric antrum. The possible explanation and significance of this finding are discussed.


T-box transcription regulator Tbr2 is essential for the formation and maintenance of Opn4/melanopsin-expressing intrinsically photosensitive retinal ganglion cells.
Opsin 4 (Opn4)/melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) play a major role in non-image-forming visual system. Although advances have been made in understanding their morphological features and functions, the molecular mechanisms that regulate their formation and survival remain unknown. Previously, we found that mouse T-box brain 2 (Tbr2) (also known as Eomes), a T-box-containing transcription factor, was expressed in a subset of newborn RGCs, suggesting that it is involved in the formation of specific RGC subtypes. In this in vivo study, we used complex mouse genetics, single-cell dye tracing, and behavioral analyses to determine whether Tbr2 regulates ipRGC formation and survival. Our results show the following: (1) Opn4 is expressed exclusively in Tbr2-positive RGCs; (2) no ipRGCs are detected when Tbr2 is genetically ablated before RGC specification; and (3) most ipRGCs are eliminated when Tbr2 is deleted in established ipRGCs. The few remaining ipRGCs display abnormal dendritic morphological features and functions. In addition, some Tbr2-expressing RGCs can activate Opn4 expression on the loss of native ipRGCs, suggesting that Tbr2-expressing RGCs may serve as a reservoir of ipRGCs to regulate the number of ipRGCs and the expression levels of Opn4.


Efficacy, speed of action and tolerability of almotriptan in the acute treatment of migraine: pooled individual patient data from four randomized, double-blind, placebo-controlled clinical trials.
A meta-analysis of pooled individual patient data from four randomized, placebo-controlled, double-blind trials comparing several doses of almotriptan (n = 1,908) with placebo (n = 386) was used to investigate the efficacy, speed of onset and tolerability of almotriptan in the acute treatment of migraine. As early as 30 min after dosing, almotriptan 12.5 mg was significantly more effective than placebo for pain relief (14.9% vs. 8.2%; P < 0.05) and pain free (2.5% vs. 0.7%; P < 0.05). At 2 h, pain-relief rates were 56.0%, 63.7% and 66.0% for almotriptan 6.25, 12.5 and 25 mg, respectively, compared with 35% for placebo; 2-h pain-free rates were 26.7%, 36.4% and 43.4% compared with 13.9% for placebo. All almotriptan dosages were significantly more effective than placebo in eliminating migraine-associated symptoms (P < 0.05) and in achieving sustained pain relief up to 24 h (P < 0.05). The incidence of adverse events after almotriptan 6.25 mg and 12.5 mg was not significantly different from that of placebo. This meta-analysis confirms the findings of individual clinical trials, while demonstrating for the first time, significant pain-free efficacy at 30 min compared with placebo.


Neuronavigated Cerebellar 50 Hz tACS: Attenuation of Stimulation Effects by Motor Sequence Learning.
Cerebellar transcranial alternating current stimulation (tACS) is an emerging non-invasive technique that induces electric fields to modulate cerebellar function. Although the effect of cortical tACS seems to be state-dependent, the impact of concurrent motor activation and the duration of stimulation on the effects of cerebellar tACS has not yet been examined. In our study, 20 healthy subjects received neuronavigated 50 Hz cerebellar tACS for 40 s or 20 min, each during performance using a motor sequence learning task (MSL) and at rest. We measured the motor evoked potential (MEP) before and at two time points after tACS application to assess corticospinal excitability. Additionally, we investigated the online effect of tACS on MSL. Individual electric field simulations were computed to evaluate the distribution of electric fields, showing a focal electric field in the right cerebellar hemisphere with the highest intensities in lobe VIIb, VIII and IX. Corticospinal excitability was only increased after tACS was applied for 40 s or 20 min at rest, and motor activation during tACS (MSL) cancelled this effect. In addition, performance was better (shorter reaction times) for the learned sequences after 20 min of tACS, indicating more pronounced learning under 20 min of tACS compared to tACS applied only in the first 40 s.


Impaired elastin fiber assembly related to reduced 67-kD elastin-binding protein in fetal lamb ductus arteriosus and in cultured aortic smooth muscle cells treated with chondroitin sulfate.
In the fetal ductus arteriosus (DA) disruption in the assembly of elastin fibers is associated with intimal thickening and we previously reported that fetal lamb DA smooth muscle cells incubated with endothelial conditioned medium produce two-fold more chondroitin sulfate (CS) compared with aorta (Ao) cells (Boudreau, N., and M. Rabinovitch. 1991. Lab. Invest. 64:187-199). We hypothesized that CS or dermatan sulfate (DS), both N-acetylgalactosamine glycosaminoglycans (GAGs), may be similar to free galactosugars in causing release of the 67-kD elastin binding protein (EBP) from the smooth muscle cell surfaces and impaired elastin fiber assembly. Using immunohistochemistry, immunoelectron microscopy, and western immunoblot we demonstrated a reduction in the 67-kD EBP in fetal lamb DA smooth muscle in tissue and in cultured cells. Also, reduced EBP was observed in fetal lamb and neonatal rat Ao smooth muscle cells incubated with N-acetylgalactosamine GAGs, CS, and DS, but not with N-acetylglucosamine containing GAGs, heparan sulfate (HS), or hyaluronan. Reduction in EBP was related to shedding from cell surfaces into the conditioned medium. This was associated with impaired elastin fiber assembly in cultured cells, assessed both morphologically and by a relative increase in tropoelastin and decrease in desmosines. The EBP extracted from smooth muscle cell membranes binds to an elastin affinity gel and can be eluted from it with CS but not with HS. Moreover, the amount of EBP extractable from smooth muscle cell membranes correlated with the morphologic assessment. We propose that increased CS or DS, may impair assembly of newly synthesized elastin in the media of the ductus arteriosus associated with the development of intimal thickening.


[Morphology, ultrastructure and populational features of bacteria francisella].
The morphology, ultrastructure of cells and the structure of microbial populations of various bacteria of the Francisella genus were estimated by electron microscopy. The strain 503 has been found to produce a bacterial population that is most homogeneous in shape and size. It contains microbes of only round and avoid forms, 0.5-0.6 micron in size. In addition of oval and round microbes there are ellipsoid and rod-shaped ones in the strains 15/3M, A. Cole 120, 117, etc. The largest tularemia microbes are typical of the strain Schu. The bacteria of all strains are covered by a capsule-like coat with well-defined borders. A thick capsule (0.12-0.35 micron) is specific for virulent strains whereas a thin capsular coat (0.06-0.12 micron) is encountered in vaccinal and avirulent microbes. The cells of the strain 503 were also shown to have the thickest envelope. All tularemia microbes have an asymmetric structure in the outer and cytoplasmic membranes due to the location of the bulk of intramembrane particles on their inner hydrophobic surfaces. Some F. tularensis microbes are able to produce keel-like protrusions on the outer membrane. The microbial nucleotide occupies 55-65% of the cytoplasmic volume and forms about 20-30 DNA-membrane contacts. Under unfavourable conditions, the microbes are capable of producing cell envelop protrusions and involutional cells, 0.1-0.3 micron in size.


Performance analysis of the ARCHITECT anti-cyclic citrullinated peptide antibody in the diagnosis of rheumatoid arthritis.
Anti-cyclic citrullinated peptide (CCP) antibody is emerging as an important diagnostic marker for rheumatoid arthritis (RA). We evaluated the analytical and diagnostic performance of the ARCHITECT anti-CCP (Abbott Diagnostics), a new fully automated chemiluminescent microparticle immunoassay. Serum samples from 69 patients with RA and 86 non-RA patients were used to evaluate the performance of the ARCHITECT anti-CCP assay, and the results were compared with those of EliA CCP (Phadia). The optimal cut-off value was calculated using receiver operating characteristic (ROC) curve analysis. Within-run and total imprecision (%CV) of the ARCHITECT anti-CCP were <6% and good linearity was observed over the claimed range. The areas under the ROC curves for the ARCHITECT anti-CCP and EliA CCP were 0.90 and 0.89, respectively. The sensitivity and specificity were 76.8% and 95.3% for the ARCHITECT anti-CCP and 78.3% and 95.3% for EliA CCP using the manufacturer's cut-off thresholds. Both assays showed sensitivity of 84.1% and specificity of 94.2% using the optimal cut-off values. The analytical performance of the ARCHITECT anti-CCP was satisfactory and diagnostic performance was comparable to that of EliA CCP. The use of optimal cut-off thresholds can yield higher sensitivity with minimal loss of specificity.


Emerging dysfunctions consequent to combined monoaminergic depletions in Parkinsonism.
The loss of dopamine (DA) neurons has been the pathophysiological focus of the devastating conditions of Parkinson's disease, but depletion of DA alone in animal models has failed to simultaneously elicit both the motor and non-motor deficits of PD. The present study aimed to investigate, in rats, the respective role of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) depletions on motor and non-motor behaviors and on subthalamic (STN) neuronal activity. We show that NA or DA depletion significantly decreased locomotor activity and enhanced the proportion of bursty and irregular STN neurons. Anxiety-like states required DA depletion plus the depletion of 5-HT or NA. Anhedonia and "depressive-like" behavior emerged only from the combined depletion of all three monoamines, an effect paralleled by an increase in the firing rate and the proportion of bursty and irregular STN neurons. Here, we provide evidence for the exacerbation of behavioral deficits when NA and/or 5-HT depletions are combined with DA depletion, bringing new insight into the combined roles of the three monoamines in PD.


Plasma N-terminal fragment of the prohormone B-type natriuretic peptide concentrations in relation to time to treatment and Thrombolysis in Myocardial Infarction (TIMI) flow: a substudy of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial.
We investigated the prognostic significance of plasma N-terminal fragment of the prohormone B-type natriuretic peptide (Nt-proBNP) concentrations in addition to time to reperfusion and Thrombolysis in Myocardial Infarction (TIMI) flow before and after coronary intervention in patients with ST elevation myocardial infarction (STEMI) from the database of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial. Plasma Nt-proBNP was available in 1,037 patients with STEMI. Patients were randomized either to primary (p-PCI) or to full-dose tenecteplase before PCI (f-PCI).The study end point was the composite of death, cardiogenic shock, or congestive heart failure at 90 days. According to classification tree analysis, patients with Nt-proBNP levels >694 pg/mL had the highest primary end point rates (33.8% vs 11%, P < .001). In Cox regression analysis, Nt-proBNP >694 pg/mL strongly predicted 90-day survival even among patients with short treatment delay (f-PCI < or =3 hours: hazard ratio [HR] 2.63, P = .002 and p-PCI < or =3 hours: HR 4.87, P < .001, respectively). Patients with TIMI 3 flow after coronary intervention were at significantly higher risk of the primary end point if admission Nt-proBNP exceeded 694 pg/mL (f-PCI: HR 2.88, P < .001 and p-PCI: HR 3.84, P < .001, respectively). In multivariable analysis, Nt-proBNP >694 pg/mL significantly (P = .001) predicted 90-day survival in addition to age (P < .001), TIMI flow after PCI (P < .001), body mass index (P = .026), anterior wall infarction (P = .035), and systolic blood pressure at randomization (P = .036), respectively. Elevated plasma concentrations of Nt-proBNP in the early phase of STEMI determine in-hospital and 90-day outcome after infarction irrespective of time to treatment and pre- or postinterventional TIMI flow.


Integrated multi-omics identified the novel intratumor microbiome-derived subtypes and signature to predict the outcome, tumor microenvironment heterogeneity, and immunotherapy response for pancreatic cancer patients.
Background: The extremely malignant tumour known as pancreatic cancer (PC) lacks efficient prognostic markers and treatment strategies. The microbiome is crucial to how cancer develops and responds to treatment. Our study was conducted in order to better understand how PC patients' microbiomes influence their outcome, tumour microenvironment, and responsiveness to immunotherapy. Methods: We integrated transcriptome and microbiome data of PC and used univariable Cox regression and Kaplan-Meier method for screening the prognostic microbes. Then intratumor microbiome-derived subtypes were identified using consensus clustering. We utilized LASSO and Cox regression to build the microbe-related model for predicting the prognosis of PC, and utilized eight algorithms to assess the immune microenvironment feature. The OncoPredict package was utilized to predict drug treatment response. We utilized qRT-PCR to verify gene expression and single-cell analysis to reveal the composition of PC tumour microenvironment. Results: We obtained a total of 26 prognostic genera in PC. And PC samples were divided into two microbiome-related subtypes: Mcluster A and B. Compared with Mcluster A, patients in Mcluster B had a worse prognosis and higher TNM stage and pathological grade. Immune analysis revealed that neutrophils, regulatory T cell, CD8+ T cell, macrophages M1 and M2, cancer associated fibroblasts, myeloid dendritic cell, and activated mast cell had remarkably higher infiltrated levels within the tumour microenvironment of Mcluster B. Patients in Mcluster A were more likely to benefit from CTLA-4 blockers and were highly sensitive to 5-fluorouracil, cisplatin, gemcitabine, irinotecan, oxaliplatin, and epirubicin. Moreover, we built a microbe-derived model to assess the outcome. The ROC curves showed that the microbe-related model has good predictive performance. The expression of LAMA3 and LIPH was markedly increased within pancreatic tumour tissues and was linked to advanced stage and poor prognosis. Single-cell analysis indicated that besides cancer cells, the tumour microenvironment of PC was also rich in monocytes/macrophages, endothelial cells, and fibroblasts. LIPH and LAMA3 exhibited relatively higher expression in cancer cells and neutrophils. Conclusion: The intratumor microbiome-derived subtypes and signature in PC were first established, and our study provided novel perspectives on PC prognostic indicators and treatment options.


Biodistribution properties of (111)indium-labeled C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid humanized 3S193 diabody and F(ab')(2) constructs in a breast carcinoma xenograft model.
The humanized complementarity determining region-grafted anti-Lewis Y (Le(y)) monoclonal antibody [humanized 3S193 (hu3S193)] was developed for targeting Le(y)-expressing epithelial tumors such as breast, colon, lung, prostate, and ovarian carcinoma. We are exploring the potential use of smaller molecular size, bivalent analogues of hu3S193, because the faster blood clearance of M(r) approximately 54,000 diabody and M(r) approximately 110,000 F(ab')(2) molecules may be advantageous in achieving optimal and rapid tumor uptake for diagnostic and potential therapeutic applications. The single-chain variable fragment-5 residue linker construct (diabody) was expressed using the bacterial secretion vector pPOW3, and soluble product was purified without refolding processes. The F(ab')(2) fragment was obtained by pepsin digest of parental hu3S193. To facilitate evaluations, the radiometal (111)In was used to label C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid chelated diabody and F(ab')(2). The immunoreactivity of the radiolabeled constructs was 41.3 and 58.6%, and the K(a) was 1.68 x 10(6) M(-1) and 5.33 x 10(6) M(-1) for the diabody and F(ab')(2), respectively. Radioconjugates were injected into mice bearing Le(y)-positive MCF-7 tumors, and biodistribution properties were determined at various time points after injection. The uptake of radiolabeled diabody in xenografts was maximal at 1 h after injection (4.7 +/- 0.6% injected dose/g), whereas the F(ab')(2) peaked at 8 h after injection (14.2 +/- 2.4% injected dose/g). The tumor:blood ratio at 4 h for the diabody and F(ab')(2) was 5:1 and 2:1, which increased to 20:1 and 5:1, respectively, at 8 h and increased further to 40:1 and 130:1, respectively, at 48 h. These results demonstrate that the diabody construct may have applications as a diagnostic imaging reagent, whereas F(ab')(2) displayed effective tumor targeting and may have potential as a therapeutic molecule in patients with Le(y)-expressing tumors.


Systematic analysis of binding of transcription factors to noncoding variants.
Many sequence variants have been linked to complex human traits and diseases1, but deciphering their biological functions remains challenging, as most of them reside in noncoding DNA. Here we have systematically assessed the binding of 270 human transcription factors to 95,886 noncoding variants in the human genome using an ultra-high-throughput multiplex protein-DNA binding assay, termed single-nucleotide polymorphism evaluation by systematic evolution of ligands by exponential enrichment (SNP-SELEX). The resulting 828 million measurements of transcription factor-DNA interactions enable estimation of the relative affinity of these transcription factors to each variant in vitro and evaluation of the current methods to predict the effects of noncoding variants on transcription factor binding. We show that the position weight matrices of most transcription factors lack sufficient predictive power, whereas the support vector machine combined with the gapped k-mer representation show much improved performance, when assessed on results from independent SNP-SELEX experiments involving a new set of 61,020 sequence variants. We report highly predictive models for 94 human transcription factors and demonstrate their utility in genome-wide association studies and understanding of the molecular pathways involved in diverse human traits and diseases.


The prevalence of distal junctional kyphosis following posterior instrumentation and arthrodesis for adolescent idiopathic scoliosis.
Distal junctional kyphosis (DJK) is a radiographic finding in patients that undergo spinal instrumentation and fusion, since there is an abrupt transition between fixed and mobile spinal segments.The true incidence of DJK is variable in literature and seems that has a multifactorial etiology. A consecutive series of 130 patients (mean age 15.6 years) with adolescent idiopathic scoliosis who underwent posterior spinal fusion and instrumentation were evaluated by analyzing coronal and sagittal angulation and balance measurements from standing radiographs obtained pre-operatively, within 6 weeks post-operation, at two years postoperative and at the latest follow-up. There was 35 male and 95 female. The mean time of follow-up was 36 months. The incidence of DJK at latest follow-up was 6.9% (9 patients). In DJK group, distal junctional angle from pre-operative of -12.5° lordosis (-30 to 0) reached to -5.5° (P=0.015) at 6 weeks postoperation and to -1.4° (-20 to 12°) (P=0.000) at 2 years follow-up,with mean of 12.1° kyphotic change (10-20°). In non DJK group, distal junctional angle from pre-operative angle of -7.5° reached -8.1° at 2 years follow-up (P=0.43). The mean age of DJK group at surgery was 17 years and for non-DJK group was 15.4 years (P=0.022). Distal junctional kyphosis was less common in this study than previous reports and stabilized after two years. The magnitude of coronal cobb angles or multiplicity of coronal curves had no effect in developing DJK that may be prevented by incorporation of the first lordotic disc into the fusion construct.


Effect of Gymnema sylvestre Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion.
Gymnema sylvestre is a medicinal plant whose consumption has demonstrated benefits on lipid and glucose levels, blood pressure, and body weight (BWt). The aim of this study was to evaluate the effect of G. sylvestre administration on metabolic syndrome (MetS), insulin secretion, and insulin sensitivity. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (without pharmacological treatment), 30-60 years old, with diagnosis of MetS in accordance with the modified International Diabetes Federation criteria. Patients were randomly assigned to receive G. sylvestre or placebo twice daily before breakfast and dinner in 300 mg capsules for a total of 600 mg per day for 12 weeks. Before and after the intervention, the components of MetS were evaluated as well as BWt, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein (VLDL). Area under the curve of glucose and insulin, phases of insulin secretion, and insulin sensitivity were calculated. Statistical analysis was performed using Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests; P ≤ .05 was considered statistically significant. After G. sylvestre administration, significant decreases in BWt (81.3 ± 10.6 kg vs. 77.9 ± 8.4 kg, P = .02), BMI (31.2 ± 2.5 kg/m2 vs. 30.4 ± 2.2 kg/m2, P = .02), and VLDL levels (0.45 ± 0.15 mmol/dL vs. 0.35 ± 0.15 mmol/dL, P = .05) were observed, without modifying the components of MetS, insulin secretion, and insulin sensitivity. In conclusion, G. sylvestre administration decreased BWt, BMI, and VLDL levels in subjects with MetS, without changes in insulin secretion and insulin sensitivity.


From patient care to research: a validation study examining the factors contributing to data quality in a primary care electronic medical record database.
Electronic Medical Records (EMRs) are increasingly used in the provision of primary care and have been compiled into databases which can be utilized for surveillance, research and informing practice. The primary purpose of these records is for the provision of individual patient care; validation and examination of underlying limitations is crucial for use for research and data quality improvement. This study examines and describes the validity of chronic disease case definition algorithms and factors affecting data quality in a primary care EMR database. A retrospective chart audit of an age stratified random sample was used to validate and examine diagnostic algorithms applied to EMR data from the Manitoba Primary Care Research Network (MaPCReN), part of the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). The presence of diabetes, hypertension, depression, osteoarthritis and chronic obstructive pulmonary disease (COPD) was determined by review of the medical record and compared to algorithm identified cases to identify discrepancies and describe the underlying contributing factors. The algorithm for diabetes had high sensitivity, specificity and positive predictive value (PPV) with all scores being over 90%. Specificities of the algorithms were greater than 90% for all conditions except for hypertension at 79.2%. The largest deficits in algorithm performance included poor PPV for COPD at 36.7% and limited sensitivity for COPD, depression and osteoarthritis at 72.0%, 73.3% and 63.2% respectively. Main sources of discrepancy included missing coding, alternative coding, inappropriate diagnosis detection based on medications used for alternate indications, inappropriate exclusion due to comorbidity and loss of data. Comparison to medical chart review shows that at MaPCReN the CPCSSN case finding algorithms are valid with a few limitations. This study provides the basis for the validated data to be utilized for research and informs users of its limitations. Analysis of underlying discrepancies provides the ability to improve algorithm performance and facilitate improved data quality.


The role of low-molecular-weight heparins in the management of unstable angina and non-ST elevation myocardial infarction.
Non-ST elevation myocardial infarction (NSTEMI) is a subset clinical manifestation of acute coronary syndrome (ACS), which is usually caused by disruption of vulnerable atherosclerotic plaque, followed by thrombosis resulting various degree of occlusions in coronary arteries. The exposure of tissue factors following the plaque rupture causes activation of coagulation cascades and formation of factor Xa. The thrombin formation will cause fibrin deposition, platelet activation and finally lead to the formation of a stable plaque. Given the central role of thrombin in the pathogenesis of ACs, and antithrombotic agent is an important element in therapy ACS. Low-molecular-weight heparin (LMWHs) is one of antithrombotic agents which has been widely studied in various clinical trials and has been proven useful in clinical efficacy, safety and practical characteristics for ACS treatment. They have been found to improve clinical outcomes in acute coronary syndromes and to provide a more predictable therapeutic response, longer and more stable anticoagulation, and a lower incidence of UFH-induced thrombocytopenia. Of the several LMWH agents that have been studied in large clinical trials, including enoxaparin, dalteparin, and nadroparin, not all have shown better efficacy than UFH. Enoxaparin is the only LMWH compound to have demonstrated sustained clinical and economic benefits in comparison with UFH in the management of unstable angina/non-ST-segment elevation myocardial infarction (NSTEMI).


Interaction of gangliosides with fibronectin in the mobilization of capillary endothelium. Possible influence on the growth of metastasis.
Mobilization of the capillary endothelium is one of the first events observed during angiogenesis, and the study of conditions that control or influence the mobilization of the endothelium in vitro has been assumed to offer information relevant to the understanding of angiogenesis in vivo. In vitro mobilization of the bovine capillary endothelium was substantially enhanced by addition of gangliosides to the culture medium. Optimal mobilization was obtained when the endothelium incorporated the gangliosides first and was then seeded on fibronectin anchored to collagen type I. Preincubation of the capillary endothelium with gangliosides, trisialoganglioside in particular, doubled the amount of fibronectin bound to the cells and enhanced the migration about 5-fold. 'Blockage' of ganglioside binding with cholera toxin or gamma-interferon substantially reduced migration. Rabbit corneas, treated in vivo with a variety of angiogenesis effectors to induce neovascularization, consistently showed an increase in sialic acid content just prior to the time the tissue would be penetrated by the capillaries. This finding was interpreted to indicate that an increment of the ganglioside content of the capillary endothelial cell membranes may play a determinant role in the mobilization of the capillary endothelium in vivo as shown here to take place in vitro. Since the formation of a tumor from a micrometastasis requires formation of new capillaries and highly metastasizing tumors very frequently have high levels of sialic acid on the cell surface, it is hypothesized that production and shedding of gangliosides from the surface of neoplastic cells may be a factor in promoting angiogenesis and metastatic growth.