MARCKS-like protein is an initiating molecule in axolotl appendage regeneration.
Identifying key molecules that launch regeneration has been a long-sought goal. Multiple regenerative animals show an initial wound-associated proliferative response that transits into sustained proliferation if a considerable portion of the body part has been removed. In the axolotl, appendage amputation initiates a round of wound-associated cell cycle induction followed by continued proliferation that is dependent on nerve-derived signals. A wound-associated molecule that triggers the initial proliferative response to launch regeneration has remained obscure. Here, using an expression cloning strategy followed by in vivo gain- and loss-of-function assays, we identified axolotl MARCKS-like protein (MLP) as an extracellularly released factor that induces the initial cell cycle response during axolotl appendage regeneration. The identification of a regeneration-initiating molecule opens the possibility of understanding how to elicit regeneration in other animals.


Ultrastructure of the human posterior tunica vasculosa lentis during early gestation.
In human embryos with a gestational age of from 7.6 to 14.0/15.0 weeks, the posterior tunica vasculosa lentis (TVL) was examined by both scanning and transmission electron microscopy. Even at the very early age of 7.6 weeks the tunica was found to be fully developed. It consisted of a radiating network of tortuous capillaries. Their walls were composed of a continuous layer of endothelial cells, surrounded by a basement membrane and a discontinuous sheath of pericytes. The thickness of the basement membrane increased with increasing gestational age. As opposed to previous studies, the endothelial cells exhibited transitory fenestrations. In the neighborhood of the posterior TVL macrophages were found.


Genetic bases for protein polymorphism in Fundulus heteroclitus (L.).I. Lactate dehydrogenase (Ldh-B), malate dehydrogenase (Mdh-A), glucosephosphate isomerase (Gpi-B), and phosphoglucomutase (Pgm-A).
Electrophoretic analysis has shown populations of F. heteroclitus to possess variants at four enzyme-coding loci: Ldh-B, Mdh-A, Gpi-B, and Pgm-A. Based on the phenotypic distribution in the F1 generation, each variant segregates as an autosomally inherited codominant allele. A pairwise comparison of the expected phenotypic classes among these loci showed no evidence of strong linkage; however, weak linkage could not be ruled out. Despite the considerable genetic divergence of populations from the geographical extremes of this species, offspring resulting from crosses between individuals from these localities show viabilities similar to those found for crosses of local populations.


Astereognosis as a presenting symptom in cervical meningioma.
Three unusual cases with astereognosis caused by cervical meningioma are presented. Astereognosis of subcortical origin has been reported several times. According to these reports, the causative lesion was confined to the area extending between the lower brain stem and the fourth cervical vertebra, thus suggesting that a sensory centre for stereognosis could be confined within these well defined anatomical limits, and that therefore a lesion in this area could lead to astereognosis. It is assumed in this paper that the lesion involves the sensory system of the Nucleus Cervicalis Lateralis. Fibres from the spinothalamic tract, a specialized sensory pathway, ascend from the palms of the hands to this nucleus. From this nucleus arise fibres which decussate and reach the Ventral Posterolateral Nucleus of the thalamus. It is likely that a lesion of the nucleus itself or its related sensory tracts may cause astereognosis.


A protein with homology to the C-terminal repeat sequence of Octopus rhodopsin and synaptophysin is a member of a multigene family in Dictyostelium discoideum.
Monoclonal antibodies were raised against a protein with a molecular mass of 24 kDa that has been described as a membrane-associated, actin binding protein from Dictyostelium discoideum [( 1985) J. Cell Biol. 100, 727-735]. Using these monoclonal antibodies we isolated from a lambda gt11 expression library cDNA clones coding for this protein. The cDNA deduced amino acid sequence revealed the presence of an unusual carboxy-terminus which has homologies to the C-termini of Octopus rhodopsin and synaptophysin. This part of the protein sequence contains 5 direct repeats with the motif GYP (P)Q(P). Southern and Northern blots showed that this sequence is present in a series of Dictyostelium genes transcribed in all stages of development.


Hemostatic effects of the ticagrelor antidote MEDI2452 in pigs treated with ticagrelor on a background of aspirin.
Essentials MEDI2452 is a specific antidote of the platelet P2Y12 receptor antagonist ticagrelor. Hemostatic effects of MEDI2452 were evaluated in pigs treated with ticagrelor and aspirin. MEDI2452 eliminated free ticagrelor within 5 min and gradually normalized platelet aggregation. Improvements in blood pressure (significant) and in blood-loss and survival (non-significant) were observed. Background Ticagrelor, a P2Y12 antagonist, is approved for the prevention of thromboembolic events. However, antiplatelet therapies carry a risk of bleeding. Objective To explore the hemostatic effects of MEDI2452, an antidote for ticagrelor. Methods Pigs, pre-treated with aspirin, were given an intravenous infusion of ticagrelor or vehicle. At the end of the infusion, a piece of a liver lobe was cut off and a bolus of MEDI2452 or vehicle was administered intravenously. Blood was collected to monitor blood loss, mean arterial blood pressure (MAP) was recorded and survival time was observed over 4 h. Blood samples for drug plasma exposures and platelet aggregation were collected. Results MEDI2452 eliminated the free concentrations of ticagrelor and its active metabolite AR-C124910XX within 5 min. ADP-induced platelet aggregation was close to normal at 60 min, which was not significantly different from aspirin alone. MEDI2452 numerically reduced ticagrelor-mediated effects: body-weight-adjusted blood loss in the 15- to 90-min interval, 12 (confidence interval [CI] 95% 7-28] vs. 17 (CI 95% 5-31) (ticagrelor and aspirin) vs. 5 (CI 95% 3-9) mL kg-1 (aspirin alone), survival 70% (CI 95% 47-100) vs. 45% (CI 95% 21-92) (ticagrelor and aspirin) vs. 100% (CI 95% 100-100) (aspirin alone), and median survival time, 240 (CI 95% 180-240) vs. 169 (CI 95% 64-240) (ticagrelor and aspirin) vs. 240 (CI 95% 240-240) min (aspirin alone). Finally, MEDI2452 significantly attenuated the decline in MAP, 0.08 (CI 95% 0.07-0.09) vs. 0.141 (CI 95% 0.135-0.148) (ticagrelor and aspirin) vs. 0.04 (CI 95% 0.03-0.05) mmHg per min (aspirin alone) and maintained MAP at a significantly higher level, 73 (CI 95% 51-95) vs. 48 (CI 95% 25-70) (ticagrelor and aspirin) vs. 115 (CI 95% 94-136) mmHg (aspirin alone). Conclusion MEDI2452 eliminated free ticagrelor and AR-C124910XX within 5 min. This translated into a gradual normalization of ADP-induced platelet aggregation and significant improvement in blood pressure and numerical but non-significant improvements in blood-loss and survival.


In situ measurements of mitochondrial matrix enzyme activities using plasma and mitochondrial membrane permeabilization agents.
Activities of enzymes localized to the mitochondrial matrix of mammalian cells are often critical regulatory steps in cellular metabolism. As such, measurement of matrix enzyme activities in response to genetic modifications or drug interventions is often desired. However, measurements in intact cells are often hampered by the presence of other isozymes in the cytoplasm as well as the inability to deliver enzyme substrates across cellular membranes. Classic approaches to liberate matrix enzymes utilize harsh treatments that disrupt intracellular architecture or require significant starting material to allow mitochondrial isolation prior to sample extraction. We describe a method using permeabilization reagents for both the plasma and mitochondrial membranes to allow in situ measurement of matrix enzyme activities. It is applied to adherent cell monolayers in 96-well plates treated with perfringolysin O to permeabilize the plasma membrane and alamethicin to permeabilize the mitochondrial inner membrane. We present three examples validated with inhibitor sensitivity: (i) Complex I-mediated oxygen consumption driven by NADH, (ii) ATP hydrolysis by the F1FO complex measuring pH changes in an Agilent Seahorse XF Analyzer, and (iii) Mitochondrial glutaminase (GLS1) activity in a coupled reaction monitoring NADH fluorescence in a plate reader.


A semi-mechanism approach based on MRI and proteomics for prediction of conversion from mild cognitive impairment to Alzheimer's disease.
Mild cognitive impairment (MCI) is a precursor phase of Alzheimer's disease (AD). As current treatments may be effective only at the early stages of AD, it is important to track MCI patients who will convert to AD. The aim of this study is to develop a high performance semi-mechanism based approach to predict the conversion from MCI to AD and improve our understanding of MCI-to-AD conversion mechanism. First, analysis of variance (ANOVA) test and lasso regression are employed to identify the markers related to the conversion. Then the Bayesian network based on selected markers is established to predict MCI-to-AD conversion. The structure of Bayesian network suggests that the conversion may start with fibrin clot formation, verbal memory impairment, eating pattern changing and hyperinsulinemia. The Bayesian network achieves a high 10-fold cross-validated prediction performance with 96% accuracy, 95% sensitivity, 65% specificity, area under the receiver operating characteristic curve of 0.82 on data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The semi-mechanism based approach provides not only high prediction performance but also clues of mechanism for MCI-to-AD conversion.


Powering Amyloid Beta Degrading Enzymes: A Possible Therapy for Alzheimer's Disease.
The accumulation of amyloid beta (Aβ) in the brain is believed to play a central role in the development and progression of Alzheimer's disease. Revisions to the amyloid cascade hypothesis now acknowledge the dynamic equilibrium in which Aβ exists and the importance of enzymes involved in the production and breakdown of Aβ in maintaining healthy Aβ levels. However, while a wealth of pharmacological and immunological therapies are being generated to inhibit the Aβ-producing enzymes, β-site APP cleavage enzyme 1 and γ-secretase, the therapeutic potential of stimulating Aβ-degrading enzymes such as neprilysin, endothelin-converting enzyme-1 and insulin-degrading enzyme remains relatively unexplored. Recent evidence indicates that increasing Aβ degradation as opposed to inhibiting synthesis is a more effective strategy to prevent Aβ build-up. Therefore Aβ degrading enzymes have become valuable targets of therapy. In this review, we discuss the pathway of Aβ synthesis and clearance along with the opportunities they present for therapeutic intervention, the benefits of increasing the expression/activity of Aβ-degrading enzymes, and the untapped therapeutic potential of enzyme activation.


Workforce Needs and Demands in Surgery.
The health care environment in the United States is witnessing major changes. The Halstedian model has produced surgeons who joined the workforce for over a century. While the Halstedian model will continue to be of benefit, we need to be proactive and develop innovative models of graduate medical education that meet the needs of the 21st century. The history of graduate medical education is punctuated by surgical leaders that made great contributions. The time is ripe again for the surgical community to develop innovative models of graduate medical education that will continue to sustain the surgical workforce of the future.


Identifying the causal relationship between sedentary behavior and heart failure: Insights from a Mendelian randomization study and mediation analysis.
Observational studies have revealed that a lack of physical exercise may be linked to a higher risk of heart failure (HF). Here, the causal relationship between sedentary behavior (SB) and HF was investigated using Mendelian randomization (MR). SB was considered as an important risk factor of HF. Single nucleotide polymorphisms with a genome-wide statistical significance threshold of <5 × 10-8 among the SB-proxied phenotypes (TV screen time, computer use, and driving) from genome-wide association study (GWAS) datasets were identified as instrumental variables (IVs). The MR study was performed using the inverse-variance weighting (IVW) model as a primary standard to evaluate causal relationships. Simultaneously, MR-Egger regression, weighted median, and maximum likelihood models were used as supplements. Sensitivity analysis, consisting of a heterogeneity and horizontal pleiotropy test, was performed using Cochran's Q, MR-Egger intercept, and MR-PRESSO tests to ensure the reliability of conclusions. The IVW model results showed that increased TV screen time correlated with a higher genetic susceptibility for HF in both HF-associated GWAS datasets, which was also supported by weighted median and maximum likelihood model results. The odds ratios with 95% confidence intervals were 1.418 (1.182-1.700) and 1.486 (1.136-1.943), respectively. Although the results of Cochran's Q test indicated certain heterogeneity among the IVs. The MR-Egger intercept and MR-PRESSO tests suggested no horizontal pleiotropy and verified the reliability of the conclusion. This MR study identified that increased TV screen time may predispose individuals to the development of HF.


Sesquiterpene lactones and other constituents from a cytotoxic extract of Michelia floribunda.
The pentane and CHCl3 fractions of a crude extract of Michelia floribunda exhibited cytotoxic activity when tested in KB and P388 tumor cell cultures. Repeated chromatography led to the isolation of three cytotoxic sesquiterpene lactones (costunolide, parthenolide, and santamarine) and a cytotoxic isoquinoline alkaloid (liriodenine). Inactive sesquiterpene lactones obtained during the course of this study included dihydroparthenolide and two new glucosides of dihydrotamaulipin A and dihydroreynosin (1 and 2). The structures of these new compounds were determined through interpretation of their spectroscopic data including 2D-NMR spectroscopy. Syringin was also isolated from the extract.


Interstitial fluid and hypoechoic wall: two sonographic signs of breast abscess.
Many mammographic and sonographic features of breast abscess overlap with those of carcinoma. We reviewed the usefulness of interstitial fluid and hypoechoic walls in the sonographic diagnosis of breast abscess. The sonograms and records of 65 patients with breast infection and 60 contemporaneous patients with breast cancer were retrospectively reviewed. Of 49 abscesses identified in patients with breast infection, 14 (29%) had adjacent interstitial fluid that was sonographically visible, and 15 (31%) had a hypoechoic wall. No patients with breast cancer had either sign. The overall sensitivity of the presence of either sign was 55%, and the specificity was 100%. Two sonographic findings, interstitial fluid and a hypoechoic wall, are relatively specific for breast abscess and may aid in the diagnosis of breast disease.


Use of recombinant human follicle-stimulating hormone in the treatment of male factor infertility.
To evaluate the effects of treatment with recombinant human FSH (r-hFSH) on seminal parameters and seminiferous epithelium in idiopathic patients with oligozoospermia with normal FSH plasma levels. Randomized single-blind study. Academic setting. Forty-five subjects with idiopathic oligozoospermia (sperm count <10 x 10(6)/mL) and normal FSH and inhibin B plasma levels. Three months of treatment with r-hFSH 50 IU (15 patients) or with r-hFSH 100 IU on alternate days (15 patients) or no treatment (15 patients); bilateral testicular fine-needle aspiration (FNA) performed before and after therapy; FSH and inhibin B plasma levels evaluated during treatment. Seminal parameters; testicular cytological features evaluated by FNA; plasma levels of FSH, LH, T, and inhibin B. Treatment with r-hFSH at a dose of 50 IU induced no increase in sperm concentration, while treatment with r-hFSH at a dose of 100 IU induced a significant increase in sperm concentration. In particular, in 11/15 patients a doubling of the pretreatment sperm concentration was observed. No significant increase in sperm parameters was observed in the control group. In both groups of patients treated with r-hFSH, the cytological analysis before treatment showed hypospermatogenesis. An increase in the percentage of spermatogonia and spermatocytes was observed only after the treatment with r-hFSH at a dose of 100 IU. The findings of this study demonstrate that r-hFSH at a dose of 100 IU, as previously seen with highly purified FSH, increases the spermatogonial population and sperm production in idiopathic patients with oligozoospermia with normal FSH and inhibin B plasma levels and a cytological picture of hypospermatogenesis.


Lung water assessment in isolated lung perfusion model via reactance monitoring.
The aim of this work was to build up a new monitoring technique for the lung preservation. The medical aside problem is to measure the integrity and functionality of the lung tissue, specifically at cellular preservation level in order to improve the survival time until it is grafted. The Impedance monitoring technique for diagnosis edema development is the key in this new technique. The hypothesis was that lung edema formation is highly correlated with the reactance changes so that a rat lung perfusion model was considered as a good model to produce edema in vitro. To prove that pulmonary edema can be induced increasing the venous pressure and the perfusion time, the reactance and hemodynamic parameters were recorder in 16 pulmonary blocks of Wistar rats as methodology. Results showed statistical changes in each pulmonary block weight as a consequence to apply 7.5 ± 1.2 and 10.2 ± 1.7 mmHg venous pressure (multiple samples, Anova, p<0.05). These edema weights were correlated with the reactance changes giving 0.6 (p<0.05, Pearson). Also, data analysis showed significant differences in reactance with the time of perfusion at 16, 30, and 50 min when venous pressure level were intermittent switched from 7.5 to 10.2 mmHg. The conclusion was this preliminary evidence sustains that reactance measurement is a good technique for monitoring the lung edema level in rats. However, more research should be continuing in bigger animal models in order to prove the validity and application of this monitoring technique in human lungs.


The retinotopic distribution of visual callosal projections in the suprasylvian visual areas compared to the classical visual areas (17, 18, 19) in the cat.
The distribution of the interhemispheric projection from area 17 and 18 was studied using the anterograde degeneration technique. Besides the classical visual areas (17, 18, 19), area 21 and several visual areas in the middle suprasylvian sulcus also received visual callosal input. In the four terminal areas of the middle suprasylvian sulcus the projection was found to be focused on representations of the ventrical meridian including the area centralis, as in the classical visual areas. An increase of the width of visual field represented in the zone of callosal terminations can be seen from area 17 through area 18 to area 19 and possibly this trend continues in the suprasylvian visual areas.


Phase I/II trial with docetaxel and S-1 for patients with advanced or recurrent gastric cancer with consideration to age.
To determine the dose-limiting toxicity (DLT) and activity of combination with docetaxel and S-1 on unresectable gastric cancer. Docetaxel was administered intravenously on day 1 and S-1 was administered orally on days 1-14, every 3 weeks. Doses of each drug in phase I study were docetaxel 60-75 mg/m(2) and S-1 60-80 mg/m(2). A phase II study was conducted with the recommended dose (RD) based on phase I. Sixty-five patients (median age 54 years) were enrolled. The DLTs were neutropenia with fever or stomatitis. The RD was docetaxel 75 mg/m(2) and S-1 60 mg/m(2). Two patients (aged 66 and 64 years) developed septic shock during the initial part of phase II study. A phase I study at lower dose (docetaxel 60 mg/m(2) and S-1 80 mg/m(2)) was conducted for patients older than 60 years, and this dose was determined as the RD for these patients. In the phase II study, frequent grade 3/4 toxicities were neutropenia (47%) and febrile neutropenia (26%). The overall response rate was 50% (95% CI, 35-66%) and median survival was 15.3 months (95% CI, 10.0-20.6 months). Combination with docetaxel and S-1 was active against advanced gastric cancer and gave manageable toxicities.


Testosterone levels of free-ranging resident mantled howler monkey males in relation to the number and density of solitary males: a test of the challenge hypothesis.
The challenge hypothesis asserts that testosterone levels and aggression in male adult animals are closely associated with one another in the context of intense reproductive competition, particularly when males challenge one another for the access to females. For mantled howler monkeys (Alouatta palliata), the presence of a solitary male in the vicinity of a social group can be considered a threat for the reproductive success of the resident males, as group takeovers by solitary males are followed by a reestablishment of the access to females among group males and sometimes by infanticide. Therefore, these episodes should be accompanied by an increase in testosterone secretion according to the challenge hypothesis. In order to test our prediction, we relate different group and subpopulation variables to the testosterone levels measured in feces collected from 10 groups living in 6 forest fragments, at Los Tuxtlas, Mexico. Our results suggest that resident A. palliata males regard solitary individuals as potential contesters for their reproductive success and that they respond to interactions with them with an increase in testosterone levels, that is increasing their aggressiveness. Our results also suggest that in the studied groups all males have at least certain access to mates and that the entrance of a new male would affect their reproductive success negatively. Finally, the negative effects of chronically high testosterone levels may be negatively affecting the fitness of our study groups living in high population densities and small fragments.


The fusion of synaptic vesicle membranes studied by lipid mixing: the R18 fluorescence assay validity.
The various experimental approaches and octadecyl rhodamine B chloride (R18) assay's capability to meet the criteria for examining the Ca²(+)dependent synaptic vesicles (SVs) fusion with target membranes have been investigated. The existence of at least two simultaneous processes one of which attributed to real Ca²(+)-dependent membrane fusion, while another is considered to be non-specific probe transfer has been shown. The differences in response to temperature changes were found for R18 fluorescence dequenching upon stimulation of membrane fusion or nonspecific probe transfer. The temperature dependences of the probe dequenching rate were the same for heterotypic and homotypic membrane systems and increased with the temperature growth. The combination of R18 fluorescence studies with the data obtained by dynamic light scattering (DLS) offers a unique opportunity for the determination of SVs aggregation and the membrane fusion. The cholesterol content of the synaptosomal plasma membrane was modulated by methyl-β-cyclodextrin (MCD). The MCD molecule has proven to bind directly the membrane cholesterol and interact with lipophilic probe R18 that affects its fluorescence. The obvious distinctions in probe dequenching due to the membrane mixing or the MCD effect were observed. The cholesterol depletion from the synaptosomal plasma membranes was found to inhibit the process of Ca²(+)-induced membrane fusion with SVs. Thus, the manipulations with conditions of R18 probe dequenching at the model conditions, specific for the Ca²(+)-triggered fusion steps of regulated exocytosis, allowed us to determine the relative contribution of probe transfer and genuine membrane fusion to the overall fluorescence signal.


Case identification of depression with self-report questionnaires.
Many self-report measures that are used to identify cases of depression are symptom severity measures that are adopted for diagnostic purposes by use of cutoff scores. A troublesome problem with this approach is that optimal cutoff scores often vary across studies, which increases the difficulty of cross-study comparisons. This study evaluated the performance of a DSM-IV based depression screening scale, the Diagnostic Inventory for Depression. We compared the diagnostic performance of two different approaches to scoring the DID: a cutoff scoring approach and a standardized DSM-IV symptom-summation algorithm. Clinical diagnosis based on a semi-structured interview was the standard of comparison. Receiver operating characteristic (ROC) analysis indicated that a DID cutoff score performed comparably to the DID algorithmic approach in identifying cases. This finding is in contrast to prior research which suggested that algorithmic approaches might improve test performance over the cutoff score approach. The manner by which a user might choose the appropriate scale-scoring method for case identification is discussed.


Experimental evaluation of portal venous pulsatile flow synchronized with heartbeat intervals.
The aim of this study was to analyze pulsatile flow in the portal vein, to clarify the origin of pulsatile flow, and to acquire new knowledge about the hepatic circulation. Mini-pigs underwent general anesthesia. Pressure and flow in the portal vein, inferior vena cava, hepatic artery, and mesenteric artery were measured simultaneously. We (1) studied the relationship between changes in pressure and changes in flow and (2) measured heartbeat intervals and the onset times of pressure and flow waves. In the inferior vena cava, pressure and flow showed mirror-image changes. In the hepatic artery and the mesenteric artery, pressure and flow increased simultaneously. In the inferior vena cava, the longer the heartbeat interval, the more delayed were the onset times of pressure and flow waves. The onset time of pressure and flow waves in the hepatic artery and the mesenteric artery was only minimally affected by changes in heartbeat interval. The relationship between pressure and flow in the portal vein was closer to that in the hepatic artery and the mesenteric artery. However, the onset times of pressure and flow waves in the portal vein showed two different patterns: some showed a pattern similar to that of the inferior vena cava, whereas others showed a pattern similar to that of the hepatic artery and the mesenteric artery. Blood flow in the portal vein is pulsatile and influenced by both the inferior vena cava and the arterial system in a complex manner.


Visual Perception: Human Brain Cells Cause a Change of View.
Some images spontaneously change in appearance. A new study has found that these changes are reflected in high-level visual cortical areas before they become apparent in early sensory cortex. This suggests that visual information not only flows towards interpretative areas of our brain, but also in the reverse direction.


The structure of NADH peroxidase from Streptococcus faecalis at 3.3 A resolution.
NADH peroxidase (EC 126.96.36.199) previously isolated from Streptococcus faecalis 10C1 has been crystallized. The crystal structure has been solved by multiple isomorphous replacement and solvent-flattening at 3.3 A (1 A = 0.1 nm) resolution. The enzyme forms a tetramer consisting of 4 crystallographically related subunits. The monomer chain fold is in general similar to those of glutathione reductase and lipoamide dehydrogenase. FAD binds in the same region and in a similar conformation as in glutathione reductase. The unusual cysteine-sulfenic acid participating in catalysis is located at the isoalloxazine of FAD.


The Financial Impact of a Multidisciplinary Preoperative Risk Stratification Program for Joint Arthroplasty.
This study's purpose was to assess the impact of a preoperative risk stratification program on joint arthroplasty outcomes at a single institution. We hypothesized that by using a standardized preoperative risk stratification center we would see better outcomes and decreased costs. The triage cohort (T) included 1498 patients assessed at a standardized risk stratification center, and the non-triage cohort (NT) included 1100 patients who did not utilize the center. The T cohort had significantly higher ASA classification (P<0.0001) and ACCI scores (P=0.028). We found no significant difference in complication rates. The T cohort showed a significant decrease in LOS (P<0.0001) and an increase in average reimbursement (P=0.009). A standardized preoperative risk stratification center can contribute to decreased LOS, increased reimbursement and help prevent complications.


Urinary sodium and calcium in various dog models and relationship to endogenous plasma glucagon.
Clearance studies were performed in 23 dogs undergoing extracellular volume (ECV) expansion by saline in order to evaluate relationship between endogenous glucagon and renal excretion of sodium and calcium. In control animals plasma glucagon (pG1) rose following 120 minutes of ECV expansion and was further increased by additional infusion of arginine. In pancreatectomised dogs ECV expansion failed to increase pG1. Both fractional and absolute urinary excretion of sodium in pancreatectomised dogs were markedly lower compared to control dogs. The difference in renal sodium excretion between control and pancreatectomised animals cannot be explained by the sum of nonhormonal factors influencing sodium excretion. In thyro-parathyroidectomised dogs renal sodium excretion was lower than in control dogs, but significantly higher than in pancreatectomised dogs. The arginine-induced increase of glucagon was associated with an increase of renal sodium and calcium excretion in each group under study without any change in glomerular filtration rate. In control dogs all parameters of renal sodium and calcium excretion investigated in this study were linearly correlated. Thyro-parathyroidectomy did not influence the relationship between renal sodium and calcium excretion. Hyperglucagonaemia therefore might be one factor contributing to the hypercalciuria associated with renal stone formation. In pancreatectomised dogs undergoing ECV expansion there was no significant correlation between renal sodium and calcium excretion. Pancreatic hormones might be involved in the coupling of renal sodium and calcium excretion.


Pupillodynamics and corneal spherical aberrations in a set of Indian cataract patients and its implications for aberrometric customisation of intraocular lenses.
Assessment of pupil diameter in various light conditions and the corresponding corneal spherical aberrations in a cohort of Indian eyes with bilateral senile cataracts and the possible use of this data in aberrometric customization of intraocular lenses (IOLs). In this prospective observational study done at a tertiary eye care centre in India, the selected patients were subjected to measurement of their pupil diameters in scotopic, mesopic, and photopic conditions as well as the corresponding corneal spherical aberrations, using the Sirius Topographer (Costruzione Strumenti Oftalmici, Florence, Italy). Shapiro-Wilk test, Independent t-test, ANOVA with Bonferroni correction on post-hoc testing were used for statistical analysis. 104 eyes of 52 patients were enrolled for the study. The mean age was 53 ± 11.88 years. The mean scotopic, mesopic, and photopic pupil sizes were 4.37 mm (4.11-4.63 mm), 3.92 mm (3.71 mm-4.15 mm), and 3.37 mm (3.18-3.67 mm), respectively. There was a statistically significant difference (P = <0.001) in the mean corneal spherical aberration measured at the 6 mm zone (0.23 ± 0.02 microns) and at the 4 mm zone (0.06 ± 0.01 microns). The mean corneal spherical aberration corresponding to the average mesopic pupil size of our patient population was substantially lower than that of the scotopic pupil size and also less than the amount corrected by most of the negative aspheric IOLs. This perhaps indicates the need for customising IOLs based on the spherical aberrations of cornea at the zone corresponding to the mesopic pupil diameter for optimal residual total postoperative spherical aberrations.


Inhibition of phagocytic activity by the N-acetyl-D-galactosamine-specific lectin from Amaranthus leucocarpus.
Amaranthus leucocarpus lectin (ALL), specific for N-acetyl-D-galactosamine, induces inhibition of the erythrophagocytic activity of resident murine peritoneal macrophages and of the macrophage-like cell line J-774. This effect was observed only in macrophages that were Mac-2 (CD11c/CD18 or CR4) negative, indicating that macrophage activation induces important modification to the glycosylation (mainly O-glycosylation) of the membrane. Receptors for IgM and C3b remain unaltered after lectin treatment. Ultrastructural analysis revealed (a) that ALL induced the formation of pinocytic vacuoles, and (b) a regular distribution over the macrophage membrane as well as endosomal vesicles of the gold labeled ALL. Our results suggest that macrophage membrane glycoproteins with constitutive N-acetyl-D-galactosamine residues participate in the regulation of pinocytic-phagocytic vacuole formation.


Soluble FcgammaRIIIa(Mphi) levels in plasma correlate with carotid maximum intima-media thickness (IMT) in subjects undergoing an annual medical checkup.
Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express FcgammaRIIIa (CD16) identical to that in NK cells, but with a cell type-specific glycosylation, and these soluble forms (sFcgammaRIIIa) are present in plasma. We measured sFcgammaRIIIa(Mphi) derived from macrophages in plasma from subjects undergoing an annual medical checkup. The levels of sFcgammaRIIIa(Mphi) increased with age, and correlated positively with body mass index, blood pressure, LDL cholesterol to HDL cholesterol ratio, triglycerides, hemoglobin A1c, and creatinine, but negatively with HDL-cholesterol levels. The sFcgammaRIIIa(Mphi) levels were related to the number of risk factors for atherosclerosis: such as aging, current smoking, diabetes, hypertension, hyper-LDL-cholesterolemia, hypo-HDL-cholesterolemia, and family history of atherosclerotic diseases. In addition, the sFcgammaRIIIa(Mphi) levels were correlated with carotid maximum intima-media thickness (IMT). These findings indicate the macrophages are activated during the incipient stage of atherosclerosis, and suggest sFcgammaRIIIa(Mphi) may be used as a predictive marker for atherosclerosis.


[Case reports of emergency exeresis for intractable pulmonary hemorrhages].
Five cases of surgically treated unrestrainable pulmonary haemorrhage are described. The satisfactory results obtained show that pulmonary exeresis, in some cases of haemorrhages, is the only effective method for saving the patient's life and removing the anatomic cause of the haemorrhage.


Tanshinone II A attenuates vascular remodeling through klf4 mediated smooth muscle cell phenotypic switching.
The aim of this study is to investigate the therapeutic role of Tanshinone II A, a key integrant from salvia miltiorrhiza, against pathological vascular remodeling. Completed ligation of mouse left common carotid arteries animal model and rat smooth muscle cells used to investigate the role of Tanshinone II A in regulating pathological vascular remodeling through hematoxylin and eosin staining, immunohistochemistry staining, immunofluorescence staining, adenovirus infection, real time PCR and western blotting. Our data demonstrated that Tanshinone II A treatment suppresses vascular injury-induced neointima formation. In vitro studies on rat smooth muscle cell indicated that Tanshinone II A treatment attenuates PDGF-BB induced cell growth, and promotes smooth muscle cell differentiated marker genes expression that induced by rapamycin treatment. Tanshinone II A treatment significant inhibits rat smooth muscle cell proliferation and migration. Tanshinone II A promotes KLF4 expression during smooth muscle phenotypic switching. Overexpression of KLF4 exacerbates Tanshinone II A mediated smooth muscle cell growth inhibition. Tanshinone II A plays a pivotal role in regulating pathological vascular remodeling through KLF4 mediated smooth muscle cell phenotypic switching. This study demonstrated that Tanshinone II A is a potential therapeutic agent for vascular diseases.


Initiation of renal replacement therapy in the intensive care unit in Vicenza (IRRIV) score.
One of the top research priorities in acute kidney injury is related to the timing of renal replacement therapy (RRT) initiation. The purpose was to develop an index that might serve as a standardized concept of timing of initiation of RRT. A previously described database was used. We applied a multivariable Cox regression model with backward selection to characterize parameters present in those patients who received RRT compared with those who did not receive RRT. We studied 590 patients. We identified independent risk factors for RRT and a risk score was devised. The Area Under the Curve of the receiver operating characteristic curve was 0.81 (95% CI 0.74-0.86) for predicting the need for RRT. We have developed a simple Score (IRRIV Score) to identify patients at high risk of requiring RRT. This score may serve as a standardized definition of the timing of initiation of RRT.


Successful fertilization, pregnancy, and birth using epididymal sperm frozen 24 hours after conventional oocyte insemination.
To assess if epididymal sperm cryopreserved 24 hours after exposure to oocytes in conventional IVF can be successfully used for intracytoplasmic sperm injection (ICSI) in a subsequent cycle. Case report. University of California, Irvine, Center for Reproductive Health. Two men with obstructive azoospermia requiring microsurgical epididymal sperm aspiration, IVF, and ICSI. Freezing of epididymal sperm 24 hours after egg exposure in conventional IVF and subsequent use for assisted fertilization in a new cycle. Frozen-thawed epididymal sperm survivability and maintenance of fertilization and pregnancy capacity. At the time of sperm aspiration procedure (cycle I) a total of 30 oocytes were available for insemination. Of these, 15 were used for conventional IVF resulting in 2 embryos (13%) and 15 were used for ICSI, resulting in 3 embryos (20%). Sperm was cryopreserved 24 hours after conventional IVF and thawed 6 months later in a new cycle. Upon thawing, sperm were still found to be motile and at this time (cycle II) only assisted fertilization was used. Of 27 oocytes injected, 12 (44%) produced normal, cleaving embryos. One singleton pregnancy with the birth of a healthy infant girl was achieved after the tubal transfer of 5 embryos. The birth of a normal, healthy infant girl with epididymal sperm frozen 24 hours after exposure to oocytes in conventional IVF emphasizes the value of freezing any aliquot of epididymal sperm, even if the motility is very low, to avoid additional surgery in the male. From a basic science standpoint, this observation may renew interest in the study of sperm cryopreservation after occurrence of acrosome reaction and hyperactivation.


The pTiC58 tzs gene promotes high-efficiency root induction by agropine strain 1855 of Agrobacterium rhizogenes.
Root induction on flax (Linum usitatissimum L.) cotyledon explants by Agrobacterium rhizogenes strain 1855 is markedly increased by co-inoculation with disarmed A. tumefaciens strain LBA 4404 containing a plasmid carrying the tzs gene of pTiC58. Most of the roots (estimated to be more than 90%) were transformed. This effect is most likely due to the secretion of trans-zeatin by A. tumefaciens stimulating the division of plant cells making them more receptive to transformation by A. rhizogenes, although other explanations are possible. This observation supports the idea that the tzs gene, although not essential for transformation, may promote transformation. An obvious application for genetic engineering experiments involving transformation by A. rhizogenes, is to include a vir-induced tzs gene in the transformation system to help maximize transformation efficiency.


Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro.
Transmucosal drug delivery (TMD) system using mucoadhesive polymer has been recently interested due to the rapid onset of action, high blood level, avoidance of the first-pass effect and the exposure of the drug to the gastrointestinal tract. A novel mucoadhesive polymer complex composed of chitosan and poly(acrylic acid) (PAA) was prepared by template polymerization of acrylic acid in the presence of chitosan for the TMD system. Triamcinolone acetonide (TAA) was loaded into the chitosan/PAA polymer complex film. TAA was evenly dispersed in chitosan, PAA polymer complex film without interaction with polymer complex. Release behavior of TAA from the mucoadhesive polymer film was dependent on time, pH, loading content of drug, and chitosan PAA ratio. The analysis of the drug release from the mucoadhesive film showed that TAA might be released from the chitosan/PAA polymer complex film through non-Fickian diffusion mechanism.


Nationwide impact of laparoscopic lysis of adhesions in the management of intestinal obstruction in the US.
Treatment of adhesion-related complications is cost intensive and presents a considerable burden to the health care system. The objective of this study was to compare open (OLA) and laparoscopic lysis of adhesions (LLA) in the treatment of intestinal obstruction, based on a nationwide representative sample. Patients with intestinal obstruction undergoing OLA, LLA, and conversion were identified from the 2002 National Inpatient Sample. After propensity methods were used to adjust for covariates including patient demographics, hospital characteristics, and comorbidities, the impact of OLA and LLA was analyzed concerning in-hospital mortality, postoperative complications, length of stay (LOS), and in-hospital costs. Of 6,165 patients, 88.6% underwent OLA and 11.4% had LLA. Conversion was required in 17.2% of LLA patients. Unadjusted mortality was equal between LLA and conversion (1.7%) and half the rate compared with OLA (3.4%) (p = 0.014). After adjusting with propensity methods, the odds of complications in the LLA group (intention to treat) were 25% less than in the OLA (p = 0.008). The LLA group had a 27% shorter LOS (p = 0.0001) and was 9% less expensive than the OLA group (p = 0.0003). There was no statistical significant difference for LOS, complications, and costs between the conversion and OLA groups. Results from this study suggest that when LLA is applied to selected patients with intestinal obstruction, there are reductions in postoperative complications, LOS, and costs. Prospective studies are needed to confirm these data and better identify the subgroup of patients who have improved outcomes with LLA.


Health-related quality of life measurement in patients admitted with coronary heart disease and heart failure to a cardiology department of a secondary urban hospital in Greece.
The aim of this study was to measure the quality of life in patients with coronary heart disease and heart failure, who make up the majority of admissions to an acute hospital cardiology unit. The study was undertaken in the General Hospital of Agios Nikolaos, Crete, and recruited 153 patients. The SF-36 and EQ-5D questionnaires were administered to evaluate health-related quality of life at hospital admission, discharge and one month after the discharge date. The analysis indicates that the quality of life of coronary disease patients is quite low and improved very marginally between admission and one month post discharge. The same applies for heart failure patients, who are associated with even lower quality of life scores. As illness affects all aspects of life, such as physical functioning, emotional balance, social role and general wellbeing, measurement of quality of life is considered to be an important factor in the assessment of the objective and subjective status of the individual's health. It appears in this context that patients with cardiac conditions suffer a significant deterioration in their quality of life status.


The expression pattern of pyruvate dehydrogenase kinases predicts prognosis and correlates with immune exhaustion in clear cell renal cell carcinoma.
Renal cancer cells constitute a paradigm of tumor cells with a glycolytic reprogramming which drives metabolic alterations favouring cell survival and transformation. We studied the expression and activity of pyruvate dehydrogenase kinases (PDK1-4), key enzymes of the energy metabolism, in renal cancer cells. We analysed the expression, subcellular distribution and clinicopathological correlations of PDK1-4 by immunohistochemistry of tumor tissue microarray samples from a cohort of 96 clear cell renal cell carcinoma (ccRCC) patients. Gene expression analysis was performed on whole tumor tissue sections of a subset of ccRCC samples. PDK2 and PDK3 protein expression in tumor cells correlated with lower patient overall survival, whereas PDK1 protein expression correlated with higher patient survival. Gene expression analysis revealed molecular association of PDK2 and PDK3 expression with PI3K signalling pathway, as well as with T cell infiltration and exhausted CD8 T cells. Inhibition of PDK by dichloroacetate in human renal cancer cell lines resulted in lower cell viability, which was accompanied by an increase in pAKT. Together, our findings suggest a differential role for PDK enzymes in ccRCC progression, and highlight PDK as actionable metabolic proteins in relation with PI3K signalling and exhausted CD8 T cells in ccRCC.


Accuracy of CAD-CAM Surgically Guided Tooth Autotransplantation Using Guided Templates and Custom-designed Osteotomes in Human Cadaver Mandibles.
A major challenge in dentistry is the replacement of teeth lost prematurely due to trauma, caries, or malformations; especially in growing patients. The aim of this study was to assess the accuracy of CAD-CAM surgically guided tooth autotransplantation in cryopreserved cadaver mandibles using guided templates and custom-designed osteotomes. Cryopreserved human cadaver heads were digitized and scanned using an intraoral optical scanner and a large-volume cone beam computed tomography device. First, virtual surgical planning was performed to create a 3D tooth replica, 2 surgical guides, and a custom-made osteotome for each single-rooted tooth autotransplantation procedure/case. Surgical sockets were created in the selected mandibles using guided tooling consisting of an initial guided osteotomy with implant burs and a final guided osteotomy using custom osteotomes. After tooth autotransplantation, second large-volume cone beam computed tomography images of the 5 cadaver mandibles were obtained. The discrepancy in mm within the 3D space (apical and mesiodistal deviations) between the final position of the autotransplanted teeth and their digitally planned 3D initial position was calculated and analyzed statistically (P < .05). All donor teeth were placed without incident within their newly created sockets in the real mandibles. The mean difference between the digitally planned root apex position and the final tooth position was 2.46 ± 1.25 mm. The mesiodistal deviation of the autotransplanted teeth was 1.63 ± 0.96 mm. The autotransplantation of single-rooted teeth with custom-designed and 3D-printed surgical tooling provided promising results. The technique was able to create surgically prepared sockets that could accommodate transplanted teeth in mandibles.


Muscle tension in generalized anxiety disorder: a critical review of the literature.
Generalized anxiety disorder (GAD) is a prevalent, disabling, and often chronic disorder. With a typical recovery rate of only about 40% with current psychological treatments a better understanding of potential psychophysiological mechanisms is vital. Since the most discriminative somatic symptom of GAD compared to other anxiety disorders is muscle tension this review qualitatively examines the literature on muscle tension as it relates to GAD and muscle relaxation therapy for GAD patients. Muscle tension in GAD is poorly understood. Experimental studies refute the often-assumed direct relationship between anxiety and muscle tension. However, muscle relaxation therapies have been as effective as cognitive interventions directly addressing the defining symptom worry. Muscle tension in its objective and subjective representations may play a role in GAD through various pathways that are testable. Future research needs to better examine the different aspects and functions of muscle tension in GAD.


Pre-existing anti-drug antibodies in Fabry disease show less affinity for pegunigalsidase alfa.
We analyzed the cross-reactivity of anti-drug antibodies (ADAs) against agalsidase-alfa and -beta from 49 patients with Fabry disease (FD) against the novel PEGylated enzyme pegunigalsidase-alfa (PRX-102). The affinity of purified anti-AGAL antibodies from pooled patient sera was significantly lower for PRX-102 compared to agalsidase-alfa and -beta (both p < 0.05). Pull-down experiments revealed the presence of masked epitopes on PRX-102, possibly due to PEGylation. ADA titers in serum (μg/mL) and corresponding inhibitory capacities against agalsidase-alfa and -beta were measured in male patients with FD, showing strong correlations (r2 = 0.9978 and 0.4930, both p < 0.001). Affinities of ADAs of individual patients against PRX-102 (Kd: 3.55 ± 2.72 μmol) were significantly lower compared to agalsidase alfa (Kd: 1.99 ± 1.26 μmol) and -beta (Kd: 2.18 ± 1.51 μmol) (both p < 0.0001). Cross-ELISAs supported the presence of masked epitopes on PRX-102. Importantly, inhibition measurements also revealed a 30% reduction in inhibitory capacity of pre-existing ADAs towards PRX-102. Enzyme-uptake experiments in AGAL-deficient EA.hy926 cells demonstrated less effects of ADAs on cellular PRX-102 uptake compared with agalsidase beta. We conclude that due to the reduced affinity of pre-existing ADAs against agalsidase-alfa or -beta, ADA-affected patients might benefit from a therapy switch to PRX-102, which is currently evaluated in clinical trials.


Age-related changes in place learning for adjacent and separate locations.
The effect of spatial interference on place learning was examined in young and old rats. Rats were trained on a radial 8-arm maze to discriminate between a reward arm and a nonreward arm that either were adjacent to each other (high spatial interference) or separated by a distance of 2 arm positions (low spatial interference). Each rat was tested until reaching a criterion of 9 correct choices out of 10 trials across 2 consecutive days. The data revealed that old rats committed significantly more errors than young rats when the arms were adjacent and spatial interference was high. However, no group differences were detected when the arms were separated and spatial interference was low. Group differences also were not detected in the number of trials required to reach the learning criterion in either condition. The results indicate that age-related brain changes result in increased errors during place learning, particularly when spatial interference is high, suggesting that spatial pattern separation might be less efficient in aged animals.


[Real-time optical coherence tomography-assisted high-precision vitreoretinal surgery in the clinical routine].
The complete integration of spectral domain optical coherence tomography (SD-OCT) into an operating microscope now enables targeted, high-resolution imaging-guided vitreoretinal surgery. This provides real-time visualization of retinal layers, vitreous body and instrument-tissue interactions, which can be used for intraoperative decision making. Compared to conventional surgical microscopes, intraoperative OCT enables a greatly enhanced precision of vitreoretinal surgical maneuvers and is an essential prerequisite for the implementation of real-time guided surgical techniques at the micrometer level.


Neuropathy in sporadic inclusion body myositis: A multi-modality neurophysiological study.
Sporadic inclusion body myositis (sIBM) has been associated with neuropathy. This study employs nerve excitability studies to re-examine this association and attempt to understand underlying pathophysiological mechanisms. Twenty patients with sIBM underwent median nerve motor and sensory excitability studies, clinical assessments, conventional nerve conduction testing (NCS) and quantitative thermal threshold studies. These results were compared to established normal controls, or results from a normal cohort of older control individuals. Seven sIBM patients (35%) demonstrated abnormalities in conventional NCS, with ten patients (50%) demonstrating abnormalities in thermal thresholds. Median nerve motor and sensory excitability differed significantly in sIBM patients when compared to normal controls. None of these neurophysiological markers correlated significantly with clinical markers of sIBM severity. A concurrent neuropathy exists in a significant proportion of sIBM patients, with nerve excitability studies revealing changes possibly consistent with axolemmal depolarization or concurrent neuronal adaptation to myopathy. Neuropathy in sIBM does not correlate with muscle disease severity and may reflect a differing tissue response to a common pathogenic factor. This study affirms the presence of a concurrent neuropathy in a large proportion of sIBM patients that appears independent of the severity of myopathy.


Organ culture as a model of studying follicular development and function of postnatal mouse ovaries.
Ovarian organ culture was used to study the influence of various gonadotropin hormones (100 ng FSH, 100 ng LH, 100 ng LH added together with 100 ng FSH; 1 i.u. hCG or 10 i.u. PMSG) on growth and development of follicles as well as on steroid secretion by ovaries of postnatal, 15-day-old mice. Ovaries were aseptically removed and single organs were placed on a piece of lens paper which was supported by a stainless steel grid in the small organ culture dish. The cultures were maintained in medium M199 supplemented with 5% of calf serum in a CO2 incubator at 37 degrees C. The morphological changes and steroid secretion measured by appropriate RIAs were studied. The stages of follicular development and the incidence of particular types of follicles were scored. Progesterone and estradiol were detected in the medium by radioimmunoassay. Differences between control and gonadotropin stimulated ovaries were found in the number of the ovarian follicles in more advanced maturation stages. There was increased number of multilaminar and antral follicles in FSH and FSH plus LH treated cells. The adding of gonadotropin hormones to the culture medium stimulated significantly progesterone secretion. The most significant effect was observed in media of cultures treated with LH and hCG. As to estradiol secretion the highest stimulatory effect was seen in cultures supplemented with FSH alone, together with LH and with PMSG. The organ culture technique applied in the current study could be a suitable model of studying the interaction of various factors as well as its effect on ovarian differentiation and on selection of dominant follicles. This system allows maintaining the structural integrity of the whole ovary, thus in the physiological functional status of the organ.


Lack of effect of morphine and buprenorphine on hypoxic pulmonary vasoconstriction in the isolated perfused cat lung and the perfused lobe of the dog lung.
In an isolated perfused cat lung preparation and a perfused lobe of dog lung preparation a pressor response of the pulmonary circulation was elicited to alveolar hypoxia (5% oxygen). The magnitude of this reponse was not affected by either of the opioid drugs, morphine or buprenorphine.


Functional interaction between -629C/A, -971G/A and -1337C/T polymorphisms in the CETP gene is a major determinant of promoter activity and plasma CETP concentration in the REGRESS Study.
Cholesteryl ester transfer protein (CETP) plays a key role in the determination of high-density lipoprotein (HDL) levels via its action on intravascular HDL metabolism. The TaqIB polymorphism of the CETP gene is associated with plasma CETP and high-density lipoprotein cholesterol (HDL-C) levels and with premature coronary artery disease. Such associations appear to result from linkage disequilibrium between TaqIB and other functional polymorphisms. To date, only one functional promoter variant, which may explain the effects of TaqIB, has been identified at position -629 in the CETP gene. Here we describe a C/T polymorphism located at position -1337 in the human CETP gene (C allele frequency: 0.684), which is significantly associated with plasma HDL-C and CETP levels (P=0.0001 and P<0.0001, respectively). Transient transfection of a reporter gene construct containing the CETP promoter from -1707/+28 in liver cells (HepG2) revealed that the -1337T allele was expressed to a significantly lower degree (-34%, P<0.0001) than the -1337C allele. In addition, we clearly demonstrated that the -971G/A polymorphism is functional and that its functionality is intimately linked to the presence of the -1337 site. In vitro evaluation of potential interaction between -1337C/T and other functional variants of the CETP gene (-971G/A and -629C/A) demonstrated that these three functional CETP promoter polymorphisms can interact together to determine the overall activity of the CETP gene and thus contribute significantly to variation in plasma CETP mass concentration.


Immediate onset of DNA synthesis in remnant rat liver after 90% hepatectomy by an administration of follistatin.
Follistatin is an antagonist of activins and is effective in promoting liver regeneration after 70% hepatectomy. To examine its efficacy under more critical conditions, we studied the effect of follistatin on liver regeneration in 90% hepatectomized rat. Human recombinant follistatin was infused into the portal vein immediately after 90%, hepatectomy in 24-h-starved rats, and changes in the liver regeneration rate and nuclear bromodeoxyuridine labeling were measured. In control rats, nuclear labeling was first detected at 11 h of hepatectomy. In follistatin-treated rats, nuclear labeling was markedly increased at 3 h, and was significantly higher than that in control rats at 24, 72, 96, 120 and 144 h. The liver regeneration rate was significantly higher in follistatin-treated rats at 48, 72, 96, 120, 144 and 168 h. To determine the reason for the accelerated growth in starved rats, we compared the expression of mRNA for c-myc, p53, p21CIP1, p15INK4B, p27KIP1, and subunits of activins in fed and starved rats. mRNA for p21CIP1 and p15INK4B, but not p27KIP1 were decreased in 24 h-starved rats compared to the fed rats. mRNA for betaA subunit of activin was not detected in either fed or 24-h-starved rats, whereas that for betaC subunit was increased in starved rats. These results indicate that follistatin induces immediate onset of DNA synthesis in 90% hepatectomized rats and is quite effective in promoting liver regeneration.


A qualitative study of childbirth fear and preparation among primigravid women: The blind spot of antenatal care in Lilongwe, Malawi.
This study aimed to explore childbirth fear and childbirth preparation among primigravid women in the late pregnancy from 36 to 40 weeks gestation. We purposively recruited 18 primigravid women into in-depth interviews, 21 birth companions, and 13 health workers into focus group discussions. Participants were recruited from two community hospitals' maternity waiting homes in Lilongwe, Malawi. Semi-structured interview guides were used to collect data that were analyzed using content analysis. NVivo11 computer software was used to organize the data. The four categories developed were: "ambivalent pregnancy feelings" , "dependence on traditional childbirth counseling" ,"inadequate prenatal childbirth instruction" and "inconsistent roles of a birth companion" . The findings suggest that primigravid women who were mainly exposed to traditional childbirth mentoring rather than professional care providers, experienced childbirth fear, and lacked proper psychosocial childbirth preparation. Childbirth fear among primigravid women emanate from personal; family; ineffective traditional counseling; and inadequate antenatal childbirth instruction. Birth companions may increase childbirth stress. However, our findings highlight birth companions as readily available psychosocial support resources among primigravid women. We recommend that professional childbirth instruction during antenatal care should be strengthened to surpass traditional childbirth counseling. Appropriateness and effectiveness of birth companions need to be carefully assessed.


Stoichiometrically bound beta-carotene in the cytochrome b6f complex of oxygenic photosynthesis protects against oxygen damage.
The cytochrome b6f complex of oxygenic photosynthesis carries out "dark reactions" of electron transfer that link the light-driven reactions of the reaction centers, and coupled proton transfer that generates part of the electrochemical potential utilized for ATP synthesis. In contrast to the bc1 complex of the respiratory chain, with which there are many structural and functional homologies, the b6f complex contains bound pigment molecules. Along with the specifically bound chlorophyll a previously found to be bound stoichiometrically in the dimeric b6f complex, it was found in the present study that beta-carotene is also present in the b6f complex at stoichiometric levels or nearly so. Chlorophyll and carotenoid pigments were quantitatively extracted from b6f complex purified from (i) the thermophilic cyanobacterium, Mastigocladus laminosus, (ii) spinach chloroplasts, and (iii) the green alga, Chlamydomonas reinhardtii. Visible and mass spectra showed the carotenoid to be a beta-carotene of molecular weight = 536, with a stoichiometry of 1. 0:1 relative to cytochrome f in the highly active M. laminosus complex but somewhat lower stoichiometries, 0.77 and 0.55, in the b6f complex obtained from spinach chloroplasts and C. reinhardtii. A photoprotective function for the beta-carotene was inferred from the findings that the rate of photobleaching of the chlorophyll a bound in the complex was found to vary inversely with beta-carotene content and to decrease markedly in the presence of ambient N2 instead of air. The presence of beta-carotene in the b6f complex, and not in the related bc1 complexes of the mitochondrial respiratory chain and photosynthetic bacteria, suggests that an additional function is to protect the protein complexes in oxygenic photosynthetic membranes against toxic effects of intramembrane singlet O2.


Hypoplastic right-sided heart complex: a cluster of cases with associated congenital birth defects. A new syndrome?
Fourteen infants, all born within the same geographic area in a two-year period, had hypoplastic right-sided heart complex associated with a high incidence of other congenital defects. No common teratogenic exposure or genetic relationships were discovered. Twelve of the 14 infants were conceived in the spring or summer. Significant elevations in serum antibody titers against coxsackie group B virus and echoviruses were noted in the general referral population during those spring and summer quarters. Cardiac defects included a hypoplastic right ventricle in every case; three types were noted. Varying degrees of right-sided valvular lesions and other intracardiac defects accompanied the hypoplastic ventricle. Eleven infants had extracardiac congenital anomalies: 10 had microcephaly, two had micrognathia with posterior cleft palate, four had low-set ears, and one had arrhinencephaly. The high incidence of extracardiac defects in the syndrome (79%) is in distinct contrast to the incidence reported in the New England Regional Infant Cardiac Program in infants who had pulmonic atresia with intact ventricular septum.


Unanswered questions about the structure of cytochrome bc1 complexes.
X-ray crystal structures of bc1 complexes obtained over the last 15 years have provided a firm structural basis for our understanding of the complex. For the most part there is good agreement between structures from different species, different crystal forms, and with different inhibitors bound. In this review we focus on some of the remaining unexplained differences, either between the structures themselves or the interpretations of the structural observations. These include the structural basis for the motion of the Rieske iron-sulfur protein in response to inhibitors, a possible conformational change involving tyrosine132 of cytochrome (cyt) b, the presence of cis-peptides at the beginnings of transmembrane helices C, E, and H, the structural insight into the function of the so-called "Core proteins", different modelings of the retained signal peptide, orientation of the low-potential heme b, and chirality of the Met ligand to heme c1. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.


Measurement of cholinesterases in amniotic fluid using alpha naphthyl acetate as substrate: a possible initial test for prenatal diagnosis of open neural tube defects.
A quantitative method for cholinesterases in amniotic fluid using the non-specific substrate alpha naphthyl acetate and the cholinesterase-specific inhibitor, eserine, is described. This assay was used to test 671 samples of amniotic fluid. The diagnoses for fetal ONTDs, based on the levels of AChE + ChE, were compared with those made for the same samples by the AFP method. Correct diagnoses were made by both methods with amniotic fluid from 35 women carrying fetuses with ONTDs and 631 carrying normal fetuses. There were five false-positive test results for normal fetuses by both methods when the cut-off points were 5 standard deviations above the mean for AFP and above the upper limit of the normal range (7.5 milliunits) for cholinesterase (AChE + ChE). None of the false-positive samples from either method had the acetylcholinesterase band of activity characteristic of ONTDs after gel electrophoresis. In addition to the above 671 samples, 37 pregnancies with serious fetal abnormalities other than ONTDs were tested. Two were identified by both the AFP and AChE + ChE methods, two more by AFP assay and one other by the AChE + ChE assay.


Bioremoval of arsenic species from contaminated waters by sulphate-reducing bacteria.
A mixed culture of sulphate-reducing bacteria was used to study the bioremoval of arsenic species (As(III) or As(V)) from groundwater. During growth of a mixed SRB culture adapted to 0.1mg/L arsenic species through repeated sub-culturing, 1mg/L of either As(III) or As(V) was reduced to 0.3 and 0.13mg/L respectively. Sorption experiments on the precipitate produced by batch cultured sulphate-reducing bacteria (SRB-PP) indicated a removal of about 77 and 55% of As(V) and As(III) respectively under the following conditions: pH 6.9; biomass (2g/L); 24h contact time; initial arsenic concentration, 1mg/L of either species. These results were compared with synthetic iron sulphide as adsorbent. The adsorption data were fitted to Langmuir and Freundlich isotherms. Energy dispersive X-ray analysis showed the SRB-PP contained elements such as sulphur, iron, calcium and phosphorus. Biosorption studies indicated that SRB cell pellets removed about 6.6% of the As(III) and 10.5% of the As(V) from water containing an initial concentration of 1mg/L of either arsenic species after 24h contact.


A community-based asthma program: Study design and methods of RVA Breathes.
Disparities in pediatric asthma morbidity and healthcare utilization exist on the basis of race, ethnicity, environment, and income; interventions are needed to address these inequities. The following protocol describes an evidence-based intervention, RVA Breathes, designed to coordinate pediatric asthma care across family, home, community, and medical sectors. Community stakeholder feedback was utilized to refine the intervention specifically for the Richmond, Virginia community. The aims of this study are to assess the effect of RVA Breathes on asthma-related healthcare utilization, as well as secondary outcomes of asthma control, asthma symptoms, and quality of life. We will enroll 300 elementary school children from the Richmond City Public School system. Participants will be between the ages of 5-11, have a diagnosis of asthma, and have had an asthma exacerbation (as indicated by an asthma-related ED visit, hospitalization, unscheduled PCP visit, or use of systemic steroids) in the last two years. Participants will be randomized to one of three groups: asthma education + home environment remediation + school intervention, asthma education + home environment remediation, or a comparator condition. Data will be collected across one baseline research visit, four intervention sessions, and four follow-up research visits over the course of 18 months. A General Linear Mixed Model (GLMM) will be used to test primary aims. We expect the findings will provide support for coordination of asthma care across sectors. Further, we hope RVA Breathes will serve as a model of community-based pediatric asthma care.


Corneal Repair Models in Mice: Epithelial/Mechanical Versus Stromal/Chemical Injuries.
The tissue response to injury is a complex process. The cornea is an excellent model for studying wound repair processes because of its simple anatomy, easy accessibility, and normal avascular state. Here, we describe two corneal repair models in mice: an epithelial/mechanical injury model and a stromal/chemical injury model. The two models induce different repair responses, and consequently enable the study of independent repair processes. Here, we describe how these two wound models may be used to study basic cellular and molecular mechanisms of corneal repair.


Diagnosis of spine metastases by FDG imaging using a gamma camera in the coincidence mode.
To illustrate the detection of metastatic lung cancer using a conventional dual detector gamma camera modified to operate in the coincidence mode to image the static distribution of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG). A patient with known lung cancer underwent FDG imaging to evaluate the extent of metastatic disease. Twenty-three-minute emission image acquisition at one bed position using a dual detector coincidence gamma camera was performed to evaluate the entire chest and upper abdomen. In addition to detecting the malignant lung nodule, mediastinal lymph node metastases and a rib metastasis, symptomatic metastases to lower thoracic and upper lumbar vertebral bodies, which were not identified on radiographs, CT, or bone scan, were shown clearly by FDG coincidence gamma camera imaging. FDG tumor imaging in the body is feasible using a dual detector gamma camera operating in coincidence mode and may find an important role in a certain subset of FDG tumor imaging.


Thymic involution in aging.
The size of the naive T-cell pool is governed by output from the thymus and not by replication. This pool contributes cells to the activated/memory T-cell pool whose size can be increased through cell multiplication; both pools together constitute the peripheral T-cell pool. Aging is associated with involution of the thymus leading to a reduction in its contribution to the naive T-cell pool; however, despite this diminished thymic output, there is no significant decline in the total number of T cells in the peripheral T-cell pool. There are, however, considerable shifts in the ratios of both pools of cells, with an increase in the number of activated/memory T cells and the accumulation in older individuals of cells that fail to respond to stimuli as efficiently as T cells from younger individuals. Aging is also associated with a greater susceptibility to some infections and some cancers. An understanding of the causal mechanism of thymic involution could lead to the design of a rational therapy to reverse the loss of thymic tissue, renew thymic function, increase thymic output, and potentially improve immune function in aged individuals.


Rehabilitation in dual disability of hemiplegia and upper extremity amputation: two case reports.
Dual disability involving amputation and hemiplegia is relatively rare. The vast majority of these cases involve lower extremity amputations. In this report two patients sustained a right-sided hemiplegia complicating an old left upper extremity amputation. Through the comprehensive rehabilitation program these two patients were able to make gains, especially in some activities of daily living and in lower extremity functions. Since some of the upper extremity activities, such as dressing or bathing, could not be accomplished, it appears that patients with upper extremity amputation who have a contralateral hemiplegia have a poorer prognosis for achieving functional independence than patients with lower extremity amputation and similar neurologic loss.


Micropipette-guided Drug Administration (MDA) as a non-invasive chronic oral administration method in male rats.
In preclinical studies resorting to rodents, the effects of prolonged oral intake of active substances are difficult to evaluate. Indeed, to get closer to clinical reality, oral gavage (OG) is frequently used but the repetition of administrations induces risks of lesions of the digestive tract, and stress for animals which can compromise the quality of the results. This study describes the development of a non-invasive oral administration method in male Sprague Dawley rats, as a safe alternative of OG, more faithful to clinical reality and limiting biases in pharmacokinetics and/or pharmacodynamics interpretation. Micropipette-guided Drug Administration (MDA) is based on the administration by micropipette of a sufficiently palatable vehicle for the animals to voluntarily take its contents. MDA was not demonstrated as less stressful than OG. A pharmacokinetics equivalence between MDA and OG was demonstrated for pregabalin administration but not for aripiprazole. Despite the use of a sweet vehicle, the MDA method does not result in weight gain or significant elevation of blood glucose and fructosamines level. Regarding the time needed to administrate the solution, the MDA method is significantly faster than OG. Contrastingly to procedures using food or water, this method allows for a rigorous control of the time and dose administered and is delivered in discrete administration windows which is therefore closer to the clinical reality. This method appears particularly suitable for pharmacological evaluation of hydrophilic compounds. The MDA procedure represents a respectful and adapted pharmacological administration method to study the effects of chronic oral administration in rats.


Interleukin-10 gene promoter region polymorphisms are not associated with BCG osteitis in vaccinated infants.
Complications arising from bacille Calmette-Guérin (BCG) vaccination were recorded in a national register in Finland until 1988. In the period 1960-1988, 222 patients suffered from BCG osteitis. To evaluate whether single nucleotide polymorphisms (SNPs) in the promoter region of the gene encoding interleukin 10 (IL-10) are associated with BCG osteitis after vaccination in neonates. Blood samples of 132 former BCG osteitis patients now aged 21-49 years were analysed in a controlled study for IL10 rs1800896 (-1082G/A), rs1800871 (-819C/T), rs1800872 (-592C/A) and rs1800890 (-3575T/A) polymorphisms. The frequencies of genotypes of IL10 rs1800896, rs1800871, rs1800872 and rs1800890, the frequencies of variant genotypes and the frequencies of major or minor alleles did not differ between patients and controls. Furthermore, the frequencies of the eight possible combinations of the three IL10 alleles located close to each other (IL10 rs1800896, IL10 rs1800871 and IL10 rs1800872) were surprisingly similar. Our results suggest that polymorphisms of the IL-10 encoding gene do not play a central role in the development of complications due to BCG vaccination, although the IL10 gene, especially IL10 rs1800896 (-1082G/A) polymorphism, is known to be associated with tuberculosis risk in Europeans and North Americans.


Cavopulmonary assist in the neonate: an alternative strategy for single-ventricle palliation.
Cavopulmonary blood flow, rather than a systemic arterial source of pulmonary blood flow, stabilizes Norwood physiology. We hypothesized that pump-assisted cavopulmonary diversion would yield stable pulmonary and systemic hemodynamics in the neonate. This was tested in a newborn animal model of total cavopulmonary diversion and univentricular Fontan circulation. Lambs (n = 13; mean weight, 5.6 +/- 1.5 kg; mean age, 6.8 +/- 4.0 days) were anesthetized and mechanically ventilated. Baseline hemodynamic parameters were measured. Total cavopulmonary diversion was performed with bicaval venous-to-main pulmonary artery cannulation. A miniature centrifugal pump was used to assist cavopulmonary flow. Support was titrated to normal physiologic parameters. Hemodynamic data, arterial blood gases, and lactate values were measured for 8 hours. Baseline, 1-hour, and 8-hour time points were compared by using analysis of variance. All animals remained stable without the use of volume loading, inotropic support, or pulmonary vasodilator therapy. Cardiac index, systemic arterial pressure, left atrial pressure, and lactate values were similar to baseline values 8 hours after surgery. Mean pulmonary arterial pressure and pulmonary vascular resistance were modestly increased 8 hours after surgery. Mean arterial pH, Po(2), and Pco(2) values remained stable throughout the study. Cavopulmonary assist is feasible in a neonatal animal model of total cavopulmonary diversion and univentricular Fontan circulation with acceptable pulmonary arterial pressures and without altering regional volume distribution or cardiac output. Pump-assisted cavopulmonary diversion, in combination with Norwood aortic arch reconstruction, could solve several major problems associated with a systemic shunt-dependent univentricular circulation, including hypoxemia, impaired diastolic coronary perfusion, and ventricular volume overload.


Semi-Automated Volumetric and Morphological Assessment of Glioblastoma Resection with Fluorescence-Guided Surgery.
Glioblastoma (GBM) neurosurgical resection relies on contrast-enhanced MRI-based neuronavigation. However, it is well-known that infiltrating tumor extends beyond contrast enhancement. Fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) was evaluated to improve extent of resection (EOR) of GBMs. Preoperative morphological tumor metrics were also assessed. Thirty patients from a phase II trial evaluating 5-ALA FGS in newly diagnosed GBM were assessed. Tumors were segmented preoperatively to assess morphological features as well as postoperatively to evaluate EOR and residual tumor volume (RTV). Median EOR and RTV were 94.3 % and 0.821 cm(3), respectively. Preoperative surface area to volume ratio and RTV were significantly associated with overall survival, even when controlling for the known survival confounders. This study supports claims that 5-ALA FGS is helpful at decreasing tumor burden and prolonging survival in GBM. Moreover, morphological indices are shown to impact both resection and patient survival.


Obeticholic acid ameliorates severity of Clostridioides difficile infection in high fat diet-induced obese mice.
Severe Clostridiodes difficile infection (CDI) is life-threatening and responds poorly to treatment. Obesity is associated with development of severe CDI. Therefore, to define the mechanisms that exacerbate disease severity, we examined CDI pathogenesis in high-fat diet (HFD)-fed obese mice. Compared to control mice, HFD-fed mice failed to clear C. difficile bacteria which resulted in protracted diarrhea, weight loss and colonic damage. After infection, HFD-induced obese mice had an intestinal bile acid (BA) pool that was dominated by primary BAs which are known promoters of C. difficile spore germination, and lacked secondary BAs that inhibit C. difficile growth. Concurrently, synthesis of primary BAs from liver was significantly increased in C. difficile-infected HFD-fed mice. A key pathway that regulates hepatic BA synthesis is via feedback inhibition from intestinal Farnesoid X receptors (FXRs). Our data reveal that the proportion of FXR agonist BAs to FXR antagonist BAs in the intestinal lumen was significantly reduced in HFD-fed mice after CDI. Treatment of HFD-fed mice with an FXR agonist Obeticholic acid, resulted in decreased primary BA synthesis, fewer C. difficile bacteria and better CDI outcomes. Thus, OCA treatment holds promise as a therapy for severe CDI.


Complete Genome Sequence of Microbacterium sp. Strain Nx66, Isolated from Waters Contaminated with Petrochemicals in El Saf-Saf Valley, Algeria.
Microbacterium sp. strain Nx66 was isolated from waters contaminated by petrochemical effluents collected in Algeria. Its genome was sequenced using Illumina MiSeq (2 × 150-bp read pairs) and Oxford Nanopore (long reads) technologies and was assembled using Unicycler. It is composed of one chromosome of 3.42 Mb and one plasmid of 34.22 kb.


Possible role of PEPT1 in gastrointestinal hormone secretion.
Oligopeptides originating from ingested meal stimulate the secretion of various gastrointestinal hormones, but the mechanism is unknown. In this study, we show that transfection of oligopeptide transporter 1 (PEPT1) in STC-1 cells, a murine enteroendocrine cell line, evokes di-peptide-stimulated hormone secretion in a pH-dependent manner. Measurement of membrane potentials shows that PEPT1- transfected STC-1 cells are depolarized by di-peptide glycyl-glycine but not by glycine monomer. Glycyl-glycine stimulation induces a rise in the intracellular calcium concentration in PEPT1-transfected STC-1 cells. The secretion induced by glycyl-glycine in PEPT1-transfected STC-1 cells was blocked by nifedipine, a Ca(2+) channel blocker, suggesting that the secretion is triggered by Ca(2+) influx through L-type voltage-dependent Ca(2+) channels. These data suggest that PEPT1 mediates oligopeptide-induced hormone secretion in enteroendocrine cells.


Foliage value, apparency and defence investment in birch seedlings and trees.
Two factors determining plant anti-herbivore defence investment fitness loss due to herbivory and the probability of herbivory occurring in the field were quantified for birch seedlings and trees. Fitness loss due to defoliation (assumed to be related to loss of growth increment compared to controls) appeared to be greater in seedlings compared to trees, but the result was equivocal. In contrast, seedling foliage at the field site - a typical habitat for birch - suffered much less natural defoliation than tree foliage, suggesting that seedlings are markedly less apparent to most birch herbivores than trees. This low apparency should result in lower investment in anti-herbivore defences by seedlings compared to trees - and being a strong effect, should outweigh the possibly greater growth loss suffered by seedlings, which in isolation would tend to increase their optimum defence investment compared to trees. This prediction was tested using palatability trials with a wide range of common birch herbivores and by direct quantification of anti-herbivore defences. Problems and assumptions inherent in these approaches are discussed, but it seems that birch seedlings are genuinely unapparent to herbivores, and consequently do not need the degree of defence investment required by trees.


In-capillary probing QDs and HAT tag self-assembly and displacement using Förster resonance energy transfer.
HAT tag, a natural His affinity tag, is one of the most popular fusion tags. However, HAT tag containing three positive charges limited its self-assembly with quantum dots (QDs). Herein, ATTO 590-labeled HAT peptide was synthesized to self-assemble with QDs inside the capillary. QDs and ATTO 590-labeled HAT peptide were sequentially injected into the capillary and probed by fluorescence-coupled CE (CE-FL), showing an obvious Förster resonance energy transfer signal. Online self-assembly, separation, and detection were achieved within 10 min. CE-FL further revealed that imidazole and H6 G6 peptide could partially outcompete with HAT tag on the QDs surface inside the capillary. The displacement intermediates were separated clearly using CE-FL. Our study demonstrates the power of online CE-FL in analyzing the binding interaction between ligands containing positive charges and QDs.


Absolute and relative bioavailability of a slow release theophylline preparation in asthmatic children.
This study was carried out on 14 asthmatic children aged 7-13 years. They all received three preparations (aminophylline by intravenous infusion, lysine theophyllinate orally in solution and slow release theophylline orally as capsules) in a single dose of 100 mg active ingredient in a crossover design. Plasma theophylline concentrations, determined by a fluorescent polarization immunoassay, were evaluated both by compartmental and non-compartmental analysis. After administration of slow release theophylline, its maximum plasma concentration and the time needed to reach this were (+/- SD) 3.19 +/- 0.63 microgram/ml and 8.71 +/- 2.30 h, respectively, compared to 4.51 +/- 0.94 microgram/ml and 1.96 +/- 0.85 h, respectively, for the oral normal release solution. Mean absolute and relative percentage bioavailabilities for slow release theophylline in asthmatic children were (+/- SD) 92.7 +/- 23.2% and 83.14 +/- 14.69%, respectively. These are similar to the values found with other slow release formulations in paediatric patients.


The moderating role of acculturation mode on the relationship between depressive symptoms and health-related quality of life among international students in Korea.
We examined the moderating role of acculturation mode on the relationship between depressive symptoms and health-related quality of life (HRQoL) in international students. This cross-sectional study enrolled a convenience sample of 147 international students at a university in Korea. Participants' overall HRQoL was moderate (mean = 57.2 of 80). The main and interaction effects of depressive symptoms and selected acculturation modes explained 39.9% of the variance in HRQoL. For all acculturation modes except the integration mode, as depressive symptom scores increased, HRQoL decreased. Specifically, at high depressive symptoms levels, participants with the marginalization, separation, and assimilation modes had worse HRQoL than did the integration mode, while HRQoL was similar for all acculturation modes at low depressive symptom levels. These findings suggest that future prospective intervention strategies should be considered for not only depressive symptoms levels, but also for different acculturation modes to enhance HRQoL in this population.


Effects of a novel antimycobacterial compound on the biophysical properties of a pulmonary surfactant model membrane.
In this work, the interactions of a novel rifabutin's analogue (N'-acetyl-rifabutin, RFB2) with two-dimensional (Langmuir monolayers) and three-dimensional (large unilamellar and multilamellar vesicles) membrane models of the pulmonary surfactant (PS) were evaluated. The main purpose of this study is to obtain detailed information at the molecular level between the interactions of RFB2 with the phospholipids of the PS, under physiological conditions. Therefore, the effects of RFB2 in the monolayer phase behaviour at the air-water interface and in the lipid bilayer of membrane models composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) have been systematically compared. In this context, several biophysical techniques were carried out to establish the interactions of RFB2 with the two-dimensional membrane models of the PS: Langmuir isotherms, Brewster angle microscopy (BAM), and polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS); and with three-dimensional membrane models of the PS: derivate spectrophotometry partition coefficient (Kp), dynamic light scattering (DLS), small and wide angle X-ray scattering (SAXS and WAXS). The results gathered by the different biophysical techniques and the PS membrane model used provide detailed information about the strong interactions of RFB2 with the polar head groups of the PS phospholipids and permit to establish the impact of the RFB2-PS membrane interactions, justifying an often unexplored biophysical approach to the drug's pharmacokinetics and toxicological effect.


Orthodontic treatment of anterior open bite: a review article--is surgery always necessary?
Anterior open bite cases are very difficult to treat satisfactorily because of their multifactorial aetiology and their very high relapse rate. Dependent on the origin of the anterior open bite malocclusion and the patient's age, there are several treatment possibilities ranging from deterrent appliances, high-pull headgear, fixed appliances with and without extractions to orthognathic surgery, and skeletal anchorage with miniplates or miniscrews. The gold standard treatment of skeletal anterior open bite cases is the combined approach of orthodontic treatment with fixed appliances and orthognathic surgery. In recent years, temporary anchorage devices (TAD) have been developed to correct anterior open bites orthodontically. With the introduction of TAD as an effective treatment modality, orthognathic surgery may be avoidable in selected anterior open bite cases. This is a relatively new technique and to date there remains a lack of evidence of long-term stability of anterior open bite closure with TAD.


Effect of Chinese medicine treatment based on pattern identification on cellular immunophenotype of myelodysplastic syndrome.
To observe the influence of treatment based on Chinese medicine pattern identification on cellular immunophenotype of the myelodysplastic syndrome (MDS). Sixty patients with MDS were randomly and equally assigned to the treatment group and the control group using a randomized digital table. Thirty patients in each group included 3 risk levels (low, moderate and high risks) with each level 10 patients according to the international prognostic scoring system. The control group was given conventional therapy which was also used in the treatment group. While the treatment group was given Zuogui Pill () and Yougui Pill () for low risk patients; Qingwen Baidu Decoction () and Bazhen Decoction () for moderate risk patients; Gexia Zhuyu Decoction () and Qinghao Biejia Decoction () combined with Shiquan Dabu Decoction () for high risk patients. After the treatment, the differences of overall response rate and immunophenotype (CD13, CD14, CD15, CD33 and CD34) of each group were analyzed. The overall response rate of the treatment group was significantly higher than the control group in low risk and moderate risk patients (P=0.029), there was no statistical differences of overall response rate between the treatment group and the control group in high risk patients (P=0.089). The expressions of CD13, CD14, CD33 and CD34 in all three risk levels of the treatment group were obviously decreased after the treatment, while CD15 in all three risk levels of the treatment group was obviously increased after the treatment (P<0.05 or P<0.01). Meanwhile, the difference values of CD13 and CD33 in low risk level of the treatment group, CD33 and CD34 in moderate risk level of the treatment group as well as CD34 and CD15 in high risk level of the treatment group, were all greater than the control groups and they were statistically significant (P<0.05 or P<0.01). It shows a better therapeutic effect if the MDS patients treated with Chinese medicine pattern identification in addition to conventional therapy. Since the treatment may inhibit the malignant clones and improve the dysmaturity of granulocyte differentiation, it is a feasible option in clinical practice.


Tibio-talocalcaneal arthrodesis as a primary procedure using a retrograde intramedullary nail: a retrospective study of 26 patients with rheumatoid arthritis.
Arthrodesis of the ankle joint using screws or external fixation is often a demanding procedure, notably in patients with rheumatoid arthritis. We investigated whether tibio-talocalcaneal arthrodesis with the use of an intramedullary nail is a safe and simple procedure. We retrospectively reviewed 25 ankles (25 patients) at median 3 (1-7) years after tibio-talocalcaneal arthrodesis because of rheumatoid arthritis. All had been operated on by retrograde insertion of a retrograde nail. 5 types of nail had been used. Complications, functional outcome scores, and patient satisfaction were determined and the radiographs evaluated for healing. All but 1 ankle had a radiographically healed arthrodesis. We recorded 3 deep infections, all healed--in 2 cases after extraction of the nail--and the arthrodesis healed in all 3 patients. The average functional scores at follow-up were high, considering that the patients suffered from rheumatoid arthritis. 23 patients were satisfied with the outcome. We found a correlation between the functional scores and the general activity of the disease expressed as a Health Assessment Questionnaire score. In patients with rheumatoid arthritis, tibio-talocalcaneal arthrodesis with a retrograde intra-medullary nail results in a high rate of healing, a high rate of patient satisfaction, and relatively few complications.


[Not Available].
Rheumatoid Arthritis is a progressive and systemic inflammatory disorder of unknown etiology that frequently leads to joint destruction accompanied by multi-system extra-articular manifestations. No curative therapy is available today. Compared to usual Disease Modifying Antirheumatic Drugs (DMARDs), biologicals such as tumor necrosis factor (TNF) α- and interleukin (IL) 1-inhibitors appear to offer greater efficacy and safety, especially in refractory cases. This article deals with the new agents infliximab, etanercept, and anakinra as well as with additional newly developed cytokine-inhibitors. In order to control their use and possible unknown long-term effects, a network of international and national committees has been installed. The actual recommendations for the treatment of rheumatoid arthritis with biologicals are presented, and the cost-benefit relation is discussed.


Multiple LINEs of retrotransposon silencing mechanisms in the mammalian germline.
Retrotransposons play an important role in genome evolution but pose acute challenges to host genome integrity, particularly in early stage germ cells where epigenetic control is relaxed to permit genome-wide reprogramming. In most species, the inability to silence retrotransposons in the germline is usually associated with sterility. LINE1 is the most abundant retrotransposon type in the mammalian genome. Mammalian germ cells employ multiple mechanisms to suppress retrotransposon activity, including small non-coding piRNAs, DNA methylation, and repressive histone modifications. Novel factors contributing to the epigenetic silencing of retrotransposons in the germline continue to be identified. Recent studies have provided insight into how epigenetic changes associated with retrotransposon activation impact on fertility.


Limnological factors that affect waterbird assemblages in semi-arid reservoirs of Tigray National Regional State, northern Ethiopia.
Published accounts of the conservation of biodiversity indicate that understanding patterns of species distribution and richness is crucial. However, what drives patterns of species composition in a landscape remains debatable. I examined the relationship between limnological characteristics of reservoirs, morpho-edaphic variables, biological variables, and patterns of bird species richness and distribution. Six limnological, three morpho-edaphic variables, and biological variables were recorded for 35 reservoirs and analyzed by multivariate statistical techniques. To investigate the most important explanatory factors influencing avian species richness and their distribution, redundancy analysis (RDA) was used. A total of 85 bird species from 54 genera, with a mean species richness 14.23 ± 6.72 (mean ± standard deviation) per reservoir, were recorded. The RDA analysis identified two significant RDA axes, and 34.4% of the variation in species richness is explained by environmental variation (R2adj = 0.34375; P < 0.001). Bird species richness was positively correlated with the surface area of reservoirs. I showed here that reservoir size and environmental heterogeneity were the important features that affect bird species richness, thus providing an important insight into the ecological relationship between waterbird species richness and the limnological characteristics of reservoirs. The strong positive correlation between species richness and both size and environmental variables underscores the importance of these reservoir features in the management of wildlife conservation. Large, environmentally heterogeneous reservoirs can support more species than small, environmentally homogeneous reservoirs because large, environmentally heterogeneous limnetic ecosystems can provide different resources for nesting, foraging, and roosting habitats for a diversified bird species. The result here also plays a role towards strengthening our knowledge of aquatic bird ecology and the natural history of African-Eurasian Migratory waterbirds.


Modifications of transnasal and transoral stereotactic procedures--technical notes.
Stereotactic transnasal and transoral procedures have been reported by different authors in the past. In this paper, several modifications of these methods are described. The modifications are: transnasal approach to the frontal skull base and suprasellar regions; and transoral approaches to the clivus, the petroclival junction, medial part of the cerebellopontine angle and the lateral mass of C-1. Eleven patients were operated on using these modifications. The procedures were for biopsy and brachytherapy. No complications resulted from the procedures.